Sample records for generation cephalosporin antibiotic

  1. Resistance to Third-Generation Cephalosporins and Other Antibiotics by Enterobacteriaceae in Western Nigeria

    Microsoft Academic Search

    A. O. Okesola; O. Makanjuola

    2009-01-01

    Problem statement: The emergence and spread of resistance to third-gen eration cephalosporins are threatening to create species re sistant to all currently available agents. The most common cause of bacterial resistance to beta-lactam antibiotics is the production of beta-lactamases and many of the 2nd and 3rd-generation penicillins and cephalosporins were specifically designed to resist the hydrolytic action of major ?-lactamases.

  2. Transport of cefodizime, a novel third generation cephalosporin antibiotic, in isolated rat choroid plexus

    SciTech Connect

    Nohjoh, T.; Suzuki, H.; Sawada, Y.; Sugiyama, Y.; Iga, T.; Hanano, M.

    1989-07-01

    To characterize the transport system by which cephalosporin antibiotics are accumulated by the choroid plexus, kinetic analysis of cefodizime transport was performed. Accumulation of cefodizime was against an electrochemical potential gradient via a saturable process (Km = 470 microM, Vmax = 174 nmol/ml of tissue per min) that was inhibited by metabolic inhibitors (KCN and 2,4-dinitrophenol), hypothermia, a sulfhydryl reagent (p-hydroxymer-curibenzoic acid) and anion transport inhibitors (probenecid and 4,4'-diisothiocyanostilbene -2,2'-disulfonic acid). Accumulation of cefodizime was inhibited competitively by benzylpenicillin with an inhibition constant of aproximately 100 microM. Cefodizime inhibited competitively the accumulation of benzylpenicillin with an inhibition constant of approximately 500 microM. Kinetic analysis using 16 kinds of beta-lactam antibiotics also supported the view (1) that the transport system of cefodizime is shared by benzylpenicillin and (2) that these beta-lactam antibiotics are transported via a common transport system. These findings indicate that the major transport system of cephalosporin antibiotics in the rat choroid plexus is via a carrier-mediated active anion transport process. The affinity of beta-lactam antibiotics for this transport system in the choroid plexus may be a major factor in determining their pharmacokinetics in the cerebrospinal fluid.

  3. Community-acquired pneumonia: impact of empirical antibiotic therapy without respiratory fluoroquinolones nor third-generation cephalosporins.

    PubMed

    Pradelli, J; Risso, K; de Salvador, F G; Cua, E; Ruimy, R; Roger, P-M

    2015-03-01

    Guidelines for inpatients with community-acquired pneumonia (CAP) propose to use respiratory fluoroquinolone (RFQ) and/or third-generation cephalosporins (Ceph-3). However, broad-spectrum antibiotic therapy is associated with the emergence of drug-resistant bacteria. We established a guideline in which RFQ and Ceph-3 were excluded as a first course. Our aim was to evaluate the impact of our therapeutic choices for CAP on the length of hospital stay (LOS) and patient outcome. This was a cohort study of patients with CAP from July 2005 to June 2014. We compared patients benefiting from our guideline established in 2008 to those receiving non-consensual antibiotics. Disease severity was evaluated through the Pneumonia Severity Index (PSI). The empirical treatment for PSI III to V was a combination therapy of amoxicillin-clavulanic acid (AMX-C)?+?roxithromycin (RX) or AMX?+?ofloxacin. Adherence to guidelines was defined by the prescription of one of these antibiotic agents. Requirement for intensive care or death defined unfavorable outcome. Among 1,370 patients, 847 were treated according to our guideline (61.8 %, group 1) and 523 without concordant therapy (38.2 %, group 2). The mean PSI was similar: 82 vs. 83, p?>?0.5. The mean LOS was lower in group 1: 7.6 days vs. 9.1 days, p?

  4. Third generation cephalosporin use in a tertiary hospital in Port of Spain, Trinidad: need for an antibiotic policy

    Microsoft Academic Search

    Lexley M Pinto Pereira; Marjorie Phillips; Hema Ramlal; Karen Teemul; P Prabhakar

    2004-01-01

    BACKGROUND: Tertiary care hospitals are a potential source for development and spread of bacterial resistance being in the loop to receive outpatients and referrals from community nursing homes and hospitals. The liberal use of third-generation cephalosporins (3GCs) in these hospitals has been associated with the emergence of extended-spectrum beta- lactamases (ESBLs) presenting concerns for bacterial resistance in therapeutics. We studied

  5. Dramatic increase of third-generation cephalosporin-resistant E. coli in German intensive care units: secular trends in antibiotic drug use and bacterial resistance, 2001 to 2008

    PubMed Central

    2010-01-01

    Introduction The objective of the present study was to analyse secular trends in antibiotic consumption and resistance data from a network of 53 intensive care units (ICUs). Methods The study involved prospective unit and laboratory-based surveillance in 53 German ICUs from 2001 through 2008. Data were calculated on the basis of proportions of nonduplicate resistant isolates, resistance densities (that is, the number of resistant isolates of a species per 1,000 patient-days) and an antimicrobial usage density (AD) expressed as daily defined doses (DDD) and normalised per 1,000 patient-days. Results Total mean antibiotic use remained stable over time and amounted to 1,172 DDD/1,000 patient-days (range 531 to 2,471). Carbapenem use almost doubled to an AD of 151 in 2008. Significant increases were also calculated for quinolone (AD of 163 in 2008) and third-generation and fourth-generation cephalosporin use (AD of 117 in 2008). Aminoglycoside consumption decreased substantially (AD of 86 in 2001 and 24 in 2008). Resistance proportions were as follows in 2001 and 2008, respectively: methicillin-resistant Staphylococcus aureus (MRSA) 26% and 20% (P = 0.006; trend test showed a significant decrease), vancomycin-resistant enterococcus (VRE) faecium 2.3% and 8.2% (P = 0.008), third-generation cephalosporin (3GC)-resistant Escherichia. coli 1.2% and 19.7% (P < 0.001), 3GC-resistant Klebsiella pneumoniae 3.8% and 25.5% (P < 0.001), imipenem-resistant Acinetobacter baumannii 1.1% and 4.5% (P = 0.002), and imipenem-resistant K. pneumoniae 0.4% and 1.1%. The resistance densities did not change for MRSA but increased significantly for VRE faecium and 3GC-resistant E. coli and K. pneumoniae. In 2008, the resistance density for MRSA was 3.73, 0.48 for VRE, 1.39 for 3GC-resistant E. coli and 0.82 for K. pneumoniae. Conclusions Although total antibiotic use did not change over time in German ICUs, carbapenem use doubled. This is probably due to the rise in 3GC-resistant E. coli and K. pneumoniae. Increased carbapenem consumption was associated with carbapenem-resistant K. pneumoniae carbapenemase-producing bacteria and imipenem-resistant A. baumannii. PMID:20546564

  6. Influence of Cephalosporin Antibiotics on Blood Coagulation and Platelet Function

    PubMed Central

    Natelson, Ethan A.; Brown, Clarence H.; Bradshaw, Major W.; Alfrey, Clarence P.; Williams, Temple W.

    1976-01-01

    Administration of cephalothin to normal volunteers in maximal doses of 300 mg/kg per day resulted in a combined defect of platelet function and blood coagulation. No such abnormalities were evident after infusion of cefazolin or cephapirin at a maximal dosage of 200 mg/kg per day. The observed thrombocytopathy was similar to but less severe than that induced by carbenicillin or ticarcillin and was not reflected by a prolonged bleeding time test or impaired prothrombin consumption. Moreover, it was not a consistent finding in those persons receiving cephalothin. A separate defect involving blood coagulation appeared to result from delayed fibrinogen-fibrin polymerization and was evidenced by extended values of the activated partial thromboplastin and thrombin time tests. It remains uncertain whether the abnormalities described may constitute clinically important hemostatic disorders in patients with normal renal function receiving large doses of cephalosporin antibiotics. PMID:1259395

  7. Metabolism of [14C]Cefaclor, a Cephalosporin Antibiotic, in Three Species of Laboratory Animals

    PubMed Central

    Sullivan, Hugh R.; Due, Susan L.; Kau, Donald L. K.; Quay, John F.; Miller, Warren M.

    1976-01-01

    The metabolic fate of the orally effective cephalosporin antibiotic cefaclor (Lilly 99638) has been studied in rats, mice, and dogs. Cefaclor is efficiently absorbed from the gastrointestinal tract as the intact antibiotic. In rats and mice, cefaclor, for the most part, escapes metabolism in the body and is eliminated unchanged as unaltered antibiotic, primarily by renal excretion. In dogs, however, cefaclor is more labile to metabolism and only a portion of the administered antibiotic is eliminated unchanged via the kidney. PMID:984800

  8. Dramatic increase of third-generation cephalosporin-resistant E. coli in German intensive care units: secular trends in antibiotic drug use and bacterial resistance, 2001 to 2008

    Microsoft Academic Search

    Elisabeth Meyer; Frank Schwab; Barbara Schroeren-Boersch; Petra Gastmeier

    2010-01-01

    INTRODUCTION: The objective of the present study was to analyse secular trends in antibiotic consumption and resistance data from a network of 53 intensive care units (ICUs). METHODS: The study involved prospective unit and laboratory-based surveillance in 53 German ICUs from 2001 through 2008. Data were calculated on the basis of proportions of nonduplicate resistant isolates, resistance densities (that is,

  9. Third generation cephalosporin resistant Enterobacteriaceae and multidrug resistant gram-negative bacteria causing bacteremia in febrile neutropenia adult cancer patients in Lebanon, broad spectrum antibiotics use as a major risk factor, and correlation with poor prognosis

    PubMed Central

    Moghnieh, Rima; Estaitieh, Nour; Mugharbil, Anas; Jisr, Tamima; Abdallah, Dania I.; Ziade, Fouad; Sinno, Loubna; Ibrahim, Ahmad

    2015-01-01

    Introduction: Bacteremia remains a major cause of life-threatening complications in patients receiving anticancer chemotherapy. The spectrum and susceptibility profiles of causative microorganisms differ with time and place. Data from Lebanon are scarce. We aim at evaluating the epidemiology of bacteremia in cancer patients in a university hospital in Lebanon, emphasizing antibiotic resistance and risk factors of multi-drug resistant organism (MDRO)-associated bacteremia. Materials and Methods: This is a retrospective study of 75 episodes of bacteremia occurring in febrile neutropenic patients admitted to the hematology-oncology unit at Makassed General Hospital, Lebanon, from October 2009-January 2012. It corresponds to epidemiological data on bacteremia episodes in febrile neutropenic cancer patients including antimicrobial resistance and identification of risk factors associated with third generation cephalosporin resistance (3GCR) and MDRO-associated bacteremia. Results: Out of 75 bacteremias, 42.7% were gram-positive (GP), and 57.3% were gram-negative (GN). GP bacteremias were mostly due to methicillin-resistant coagulase negative staphylococci (28% of total bacteremias and 66% of GP bacteremias). Among the GN bacteremias, Escherichia coli (22.7% of total, 39.5% of GN organisms) and Klebsiella pneumoniae(13.3% of total, 23.3% of GN organisms) were the most important causative agents. GN bacteremia due to 3GC sensitive (3GCS) bacteria represented 28% of total bacteremias, while 29% were due to 3GCR bacteria and 9% were due to carbapenem-resistant organisms. There was a significant correlation between bacteremia with MDRO and subsequent intubation, sepsis and mortality. Among potential risk factors, only broad spectrum antibiotic intake >4 days before bacteremia was found to be statistically significant for acquisition of 3GCR bacteria. Using carbapenems or piperacillin/tazobactam>4 days before bacteremia was significantly associated with the emergence of MDRO (p < 0.05). Conclusion: Our findings have major implications for the management of febrile neutropenia, especially in breakthrough bacteremia and fever when patients are already on broadspectrum antibiotics. Emergence of resistance to 3GCs and, to a lesser extent, to carbapenems in GN isolates has to be considered seriously in our local guidelines for empiric treatment of febrile neutropenia, especially given that their occurrence was proven to be associated with poorer outcomes. PMID:25729741

  10. Genome Sequence and Annotation of Acremonium chrysogenum, Producer of the ?-Lactam Antibiotic Cephalosporin C

    PubMed Central

    Terfehr, Dominik; Dahlmann, Tim A.; Specht, Thomas; Zadra, Ivo; Kürnsteiner, Hubert

    2014-01-01

    The filamentous fungus Acremonium chrysogenum is the industrial producer of the ?-lactam antibiotic cephalosporin C. Here, we present the genome sequence of strain ATCC 11550, which contains genes for 8,901 proteins, 127 tRNAs, and 22 rRNAs. Genome annotation led to the prediction of 42 gene clusters for secondary metabolites. PMID:25291769

  11. Metabolic Fate of [14C]Cefamandole, a Parenteral Cephalosporin Antibiotic, in Rats and Dogs

    PubMed Central

    Sullivan, H. R.; Due, S. L.; Kau, D. L. K.; Quay, J. F.; Miller, W. M.

    1977-01-01

    The biotransformation of the parenterally effective cephalosporin antibiotic cefamandole nafate (I) has been studied in rats and dogs. After rapid in vivo hydrolysis of the nafate pharmaceutical form to cefamandole (II), the antibiotic was found to be very resistant to metabolic degradation in both species. In dogs, cefamandole escaped metabolism and was eliminated as unaltered antibiotic almost exclusively by renal excretion. In rats, cefamandole was somewhat labile to metabolism; however, a major portion of the administered antibiotic was eliminated unchanged principally by renal excretion. PMID:883820

  12. Impact of restriction of third generation cephalosporins on the burden of third generation cephalosporin resistant K. pneumoniae and E. coli in an ICU

    Microsoft Academic Search

    Elisabeth Meyer; Matthias Lapatschek; Andreas Bechtold; Gerhard Schwarzkopf; Petra Gastmeier; Frank Schwab

    2009-01-01

    Objective  To test whether a reduction of third generation cephalosporin (3GC) use has a sustainable positive impact on the high endemic\\u000a prevalence of 3GC resistant K. pneumoniae and E. coli.\\u000a \\u000a \\u000a \\u000a Design  Segmented regression analysis of interrupted time series was used to analyse antibiotic consumption and resistance data 30 months\\u000a before and 30 after the intervention.\\u000a \\u000a \\u000a \\u000a Setting  Surgical intensive care unit (ICU) with 16-bed unit

  13. Clinical experience with the fourth generation cephalosporins.

    PubMed

    Giamarellou, H

    1996-02-01

    The author reviews the comparative and non-comparative studies of cefepime and cefpirome, from which it is evident that both cephalosporins are extremely effective both clinically and bacteriologically. Success rates of about 90% have been reported for both drugs as therapy for complicated urinary tract infections, lower respiratory tract infections of the community as well as of nosocomial origin, including a large number of penicillin-resistant Streptococcus pneumoniae infections, skin and soft-tissue infections, surgical infections, as well as therapy for infections in neutropenic hosts. Cure rates are similar to or better than those obtained with ceftazidime, cefotaxime and ceftriaxone. The author also points out the various precautions necessary in utilizing these two antimicrobial agents. PMID:8738851

  14. Feasibility and impact of an intensified antibiotic stewardship programme targeting cephalosporin and fluoroquinolone use in a tertiary care university medical center

    PubMed Central

    2014-01-01

    Background Restricted use of third-generation cephalosporins and fluoroquinolones has been linked to a reduced incidence of hospital-acquired infections with multidrug-resistant bacteria. We implemented an intensified antibiotic stewardship (ABS) programme in the medical service of a university hospital center aiming at a reduction by at least 30% in the use of these two drug classes. Methods The ABS programme was focused on the 300-bed medical service. Prescription of third-generation cephalosporins was discouraged, whereas the use of penicillins was encouraged. Monthly drug use density was measured in WHO-ATC defined and locally recommended daily doses (DDD and RDD) per 100 patient days, to evaluate trends before (01/2008 to 10/2011) and after starting the intervention (1/2012 to 3/2013). The effect was analysed using interrupted time-series analysis with six non-intervention departments as controls. Results Following initiation of the ABS intervention, overall antibiotic use in the medical service declined (p?cephalosporins and fluoroquinolones (p?cephalosporin use reductions (p?cephalosporins from 16.3 to 10.3 (?37%) and for fluoroquinolones from 17.7 to 10.1 (?43%), respectively. During the same period, the use of penicillins increased (15.4 to 18.2; 18%). The changes in expenditures for antibiotics in the medical service compared to control services minus programme costs indicated initial net cost savings likely to be associated with the programme. Conclusion An intensified ABS programme targeting cephalosporin und fluoroquinolone use in the setting of a large academic hospital is feasible and effective. The intervention may serve as a model for other services and hospitals with a similar structure and baseline situation. PMID:24731220

  15. Clindamycin vs. first-generation cephalosporins for acute osteoarticular infections of childhood--a prospective quasi-randomized controlled trial.

    PubMed

    Peltola, H; Pääkkönen, M; Kallio, P; Kallio, M J T

    2012-06-01

    No sufficiently powered trial has examined two antimicrobials in acute osteoarticular infections of childhood. We conducted a prospective, multicentre, quasi-randomized trial in Finland, comparing clindamycin with first-generation cephalosporins. The age of patients ranged between 3 months and 15 years, and all cases were culture-positive. We assigned antibiotic treatment intravenously for the first 2-4 days, and continued oral treatment with clindamycin 40 mg/kg/24 h or first-generation cephalosporin 150 mg/kg/24 h in four doses. Surgery was kept to a minimum. Subsiding symptoms and signs and normalization of C-reactive protein (CRP) level were preconditions for the discontinuation of antimicrobials. The main outcome was full recovery without further antimicrobials because of an osteoarticular indication during 12 months after therapy. The intention-to-treat analysis comprised 252 children, 169 of whom were analysed per-protocol: 82 cases of osteomyelitis, 80 of septic arthritis, and seven of osteomyelitis-arthritis. Staphylococcus aureus strains (all methicillin-sensitive) caused 84% of the cases. Except for one non-serious sequela during convalescence in both groups, and two late infections caused by dissimilar agents in one child, all patients recovered. The entire courses (medians) of clindamycin and cephalosporin lasted for 23 and 24 days, respectively. CRP normalized in both groups in 9 days. The patients were discharged, on average, on day 10. Loose stools were reported less often (1%) in the clindamycin group than in the cephalosporin group (7%), but two clindamycin recipients developed rash. Clindamycin or a first-generation cephalosporin, administered mostly orally, perform equally well in childhood osteoarticular infections, provided that high doses and administration four times daily are used. As most methicillin-resistant staphylococci remain clindamycin-sensitive, clindamycin remains an option instead of costly alternatives. PMID:22011265

  16. Outbreak of cephalosporin resistant Enterobacter cloacae infection in a neonatal intensive care unit

    Microsoft Academic Search

    N Modi; V Damjanovic; R W Cooke

    1987-01-01

    Enterobacter cloacae resistant to third generation cephalosporins emerged rapidly during an outbreak of serious infections due to this organism in a neonatal intensive care unit where ampicillin and gentamicin were used as first line antibiotic treatment. Organisms resistant to cephalosporins were isolated from 12 infants, six of whom developed systemic infection. Two infants died. Isolates of E. cloacae from four

  17. Third-generation cephalosporin resistance of community-onset Escherichia coli and Klebsiella pneumoniae bacteremia in a secondary hospital

    PubMed Central

    Lee, Shinwon; Han, Seung Woo; Kim, Kun Woo; Song, Do Young

    2014-01-01

    Background/Aims To enable appropriate antimicrobial treatment for community-onset infections in emergency departments (EDs), data are needed on the resistance profiles of Escherichia coli and Klebsiella pneumoniae, which are the main pathogens of community-onset bacteremia. Methods Records were reviewed of 734 patients with E. coli and K. pneumoniae bacteremia who visited the Daegu Fatima Hospital ED, Daegu, Korea between 2003 and 2009. We investigated the demographic data, clinical findings, and antimicrobial susceptibility patterns of the organisms. Results Of 1,208 cases of community-onset bacteremia, 62.8% were caused by E. coli or K. pneumoniae in an ED of a secondary care hospital. Five hundred and forty-eight cases of E. coli (75%) and 183 cases of K. pneumoniae (25%) were analyzed. Urinary tract infection (43.1%) was most common, followed by intra-abdominal infection (39%) and pneumonia (7.2%). Trimethoprim/sulfamethoxazole, fluoroquinolone, third-generation cephalosporin (3GC) and amikacin resistance rates among E. coli and K. pneumoniae were 22.8%, 19.6%, 6.2%, and 1.3%, respectively. In 2009, the rate of 3GC resistance (10.6%) was significantly higher, compared to the annual averages of 2003 to 2008 (6.1%; p = 0.03). Previous exposure to antibiotics was an independent risk factor for 3GC resistance in multivariate logistic regression analysis. Conclusions The rate of 3GC resistance increased in community-onset infections, and previous exposure to antibiotics was an independent risk factor. Despite the increased 3GC resistance in community-onset infections, an amikacin combination therapy could provide an option for treatment of bacteremic patients with previous antibiotic exposure in an ED. PMID:24574833

  18. Evaluation of the ?Lacta test, a rapid test detecting resistance to third-generation cephalosporins in clinical strains of Enterobacteriaceae.

    PubMed

    Renvoisé, Aurélie; Decré, Dominique; Amarsy-Guerle, Rishma; Huang, Te-Din; Jost, Christelle; Podglajen, Isabelle; Raskine, Laurent; Genel, Nathalie; Bogaerts, Pierre; Jarlier, Vincent; Arlet, Guillaume

    2013-12-01

    For decades, third-generation cephalosporins (3GC) have been major drugs used to treat infections due to Enterobacteriaceae; growing resistance to these antibiotics makes the rapid detection of such resistance important. The ?Lacta test is a chromogenic test developed for detecting 3GC-resistant isolates from cultures on solid media within 15 min. A multicenter prospective study conducted in 5 French and Belgian hospitals evaluated the performance of this test on clinical isolates. Based on antibiotic susceptibility testing, strains resistant or intermediate to cefotaxime or ceftazidime were classified as 3GC resistant, and molecular characterization of this resistance was performed. The rates of 3GC resistance were 13.9% (332/2,387) globally, 9.4% in Escherichia coli (132/1,403), 25.6% in Klebsiella pneumoniae (84/328), 30.3% in species naturally producing inducible AmpC beta-lactamases (109/360), and 5.6% in Klebsiella oxytoca and Citrobacter koseri (7/124). The sensitivities and specificities of the ?Lacta test were, respectively, 87.7% and 99.6% overall, 96% and 100% for E. coli and K. pneumoniae, and 67.4% and 99.6% for species naturally producing inducible AmpC beta-lactamase. False-negative results were mainly related to 3GC-resistant strains producing AmpC beta-lactamase. Interestingly, the test was positive for all 3GC-resistant extended-spectrum beta-lactamase-producing isolates (n = 241). The positive predictive value was 97% and remained at ?96% for prevalences of 3GC resistance ranging between 10 and 30%. The negative predictive values were 99% for E. coli and K. pneumoniae and 89% for the species producing inducible AmpC beta-lactamase. In conclusion, the ?Lacta test was found to be easy to use and efficient for the prediction of resistance to third-generation cephalosporins, particularly in extended-spectrum beta-lactamase-producing strains. PMID:24068012

  19. Evaluation of the ?Lacta Test, a Rapid Test Detecting Resistance to Third-Generation Cephalosporins in Clinical Strains of Enterobacteriaceae

    PubMed Central

    Renvoisé, Aurélie; Decré, Dominique; Amarsy-Guerle, Rishma; Huang, Te-Din; Jost, Christelle; Podglajen, Isabelle; Raskine, Laurent; Genel, Nathalie; Bogaerts, Pierre; Jarlier, Vincent

    2013-01-01

    For decades, third-generation cephalosporins (3GC) have been major drugs used to treat infections due to Enterobacteriaceae; growing resistance to these antibiotics makes the rapid detection of such resistance important. The ?Lacta test is a chromogenic test developed for detecting 3GC-resistant isolates from cultures on solid media within 15 min. A multicenter prospective study conducted in 5 French and Belgian hospitals evaluated the performance of this test on clinical isolates. Based on antibiotic susceptibility testing, strains resistant or intermediate to cefotaxime or ceftazidime were classified as 3GC resistant, and molecular characterization of this resistance was performed. The rates of 3GC resistance were 13.9% (332/2,387) globally, 9.4% in Escherichia coli (132/1,403), 25.6% in Klebsiella pneumoniae (84/328), 30.3% in species naturally producing inducible AmpC beta-lactamases (109/360), and 5.6% in Klebsiella oxytoca and Citrobacter koseri (7/124). The sensitivities and specificities of the ?Lacta test were, respectively, 87.7% and 99.6% overall, 96% and 100% for E. coli and K. pneumoniae, and 67.4% and 99.6% for species naturally producing inducible AmpC beta-lactamase. False-negative results were mainly related to 3GC-resistant strains producing AmpC beta-lactamase. Interestingly, the test was positive for all 3GC-resistant extended-spectrum beta-lactamase-producing isolates (n = 241). The positive predictive value was 97% and remained at ?96% for prevalences of 3GC resistance ranging between 10 and 30%. The negative predictive values were 99% for E. coli and K. pneumoniae and 89% for the species producing inducible AmpC beta-lactamase. In conclusion, the ?Lacta test was found to be easy to use and efficient for the prediction of resistance to third-generation cephalosporins, particularly in extended-spectrum beta-lactamase-producing strains. PMID:24068012

  20. Case-case-control study of patients with carbapenem-resistant and third-generation-cephalosporin-resistant Klebsiella pneumoniae bloodstream infections.

    PubMed

    Gallagher, Jason C; Kuriakose, Safia; Haynes, Kevin; Axelrod, Peter

    2014-10-01

    Strains of third-generation-cephalosporin-resistant Klebsiella pneumoniae (3GCRKP) and carbapenem-resistant K. pneumoniae (CRKP) are rapidly spreading. Evidence is needed to establish whether differences exist between patients at risk for 3GCRKP and those at risk for CRKP bloodstream infections (BSIs); thus, this retrospective case-case-control study was conducted to determine if the risk factors for these two infections differ. The inclusion criteria for cases were positive blood cultures for K. pneumoniae, first episode of BSI, age of ?18 years, and susceptibility results indicating resistance to either third-generation cephalosporins (3GCRKP group) or carbapenems and cephalosporins (CRKP group). Controls were patients admitted for ?72 h and were matched to cases by month/year and medical unit. Variables of interest were analyzed by univariate analysis, and those of significance were analyzed by logistic regression. In total, 111 patients with 3GCRKP BSIs and 43 patients with CRKP BSIs were matched to 154 controls. Multivariate analyses of 3GCRKP case and control groups demonstrated that a length of stay (LOS) of >40 days (odds ratio [OR], 17.7; 95% confidence interval [CI], 3.7 to 84.3), the use of antibiotics in the past 90 days (OR, 4.3; 95% CI, 1.5 to 11.9), and the presence of a central venous catheter (OR, 4.1; 95% CI, 1.3 to 13.4) were independent risk factors. Multivariate analyses of the CRKP case and control groups demonstrated that a LOS of >40 days (OR, 13.5; 95% CI, 2.9 to 62.8) and the use of antibiotics in the past 90 days (OR, 5.9; 95% CI, 1.3 to 26.5) were independent risk factors. Similar factors put patients at risk for these two types of K. pneumoniae BSIs. PMID:25022587

  1. Microbial production of 7-amino-cephalosporanic acid and new generation cephalosporins (cephalothin) by different processing strategies.

    PubMed

    Gaurav, Kumar; Kundu, Kanika; Kundu, Subir

    2007-01-01

    The development of beta-lactam antibiotics has been a continuous battle of the design of new compounds to withstand inactivation by the ever-increasing diversity of beta-lactamases. Semisynthetic cephalosporins like cephalothin were synthesized from 7-amino-cephalosporanic acid (7-ACA), and thiophene-2-acetic acid using cephalosporin-C acylase enzyme was studied. The production of cephalosporin-C acylase by Pseudomonas diminuta was used and the growth kinetics studied. The optimum condition of enzyme activity was determined by using response surface methodology. A 2(3) full-factorial composite design was employed for experimental design and the result analyzed. The pH value and temperature for optimum activity were 6.5 and 32 degrees C, respectively. The structural analog compound similar to the side-chain of semisynthetic cephalosporins, e.g., thiophene-2-acetic acid, was added. HPLC data analysis indicate that the concentration of cephalothin was 1.6 mg/mL. PMID:17701482

  2. Cephalosporins in veterinary medicine - ceftiofur use in food animals.

    PubMed

    Hornish, Rex E; Kotarski, Susan F

    2002-07-01

    Cephalosporins are an important class of antibacterial agents in use today for both humans and animals. Four generations of cephalosporins have evolved, all of which contain the beta-lactam sub-structure first found in penicillin. The range of cephalosporins available for use in food-producing animals, which is the subject of this review, is limited compared to humans. A few first- and second-generation cephalosporins are approved worldwide strictly for treatment of mastitis infections in dairy cattle. A third-generation cephalosporin, ceftiofur, and a fourth-generation cephalosporin, cefquinome, have been developed strictly for veterinary use. Cefquinome has been approved in several countries for the treatment of respiratory disease in cattle and swine, foot rot in cattle and for mastitis in dairy cattle. Ceftiofur has worldwide approvals for respiratory disease in swine, ruminants (cattle, sheep and goats) and horses and has also been approved for foot rot and metritis infections in cattle. Ceftiofur has also been approved in various countries for early mortality infections in day-old chicks and turkey poults. This review summarizes cephalosporin use in general terms, and provides an overview of ceftiofur, in terms of its spectrum of activity, indications, metabolism, and degradation in the environment. The safety of ceftiofur is also reviewed, with respect to food-animal residues, rapid metabolism and degradation, and non-persistence of ceftiofur in the environment. The environmental fragility of cephalosporins have not been explored generally, but may be an important characteristic of this antibiotic class with respect to safety of use in animals. PMID:12052187

  3. Bacteraemia caused by third-generation cephalosporin-resistant Escherichia coli in France: prevalence, molecular epidemiology and clinical features.

    PubMed

    Courpon-Claudinon, A; Lefort, A; Panhard, X; Clermont, O; Dornic, Q; Fantin, B; Mentré, F; Wolff, M; Denamur, E; Branger, C

    2011-04-01

    Escherichia coli is one of the major pathogens responsible for bactaeremia. Empirical antibiotherapy of these infections usually relies on third-generation cephalosporins (3GCs). Thus, the occurrence and epidemiology of 3GC-resistant strains have to be monitored. The French prospective multicentre study COLIBAFI collected 1081 strains of E. coli responsible for bacteraemia in 2005. In the present work, the prevalence of resistance to 3GCs was evaluated, and the implicated molecular mechanisms were characterized by specific PCR and sequencing. Phylogenetic grouping, O-typing, pulsed-field gel electrophoresis and virulence factor analysis were used to investigate the genetic background of the 3GC-resistant (3GC-R) strains. Clinical features of the patients with documented data (n = 1051) were analysed. Decreased susceptibility to 3GCs was observed in 41 strains (3.8%): 19, 18 and four had extended-spectrum ?-lactamase (ESBL), AmpC cephalosporinase and OXA-type penicillinase phenotypes, respectively. Pulsed-field gel electrophoresis revealed that the 3GC-R strains constitute a diverse population. All but one of the strains with an ESBL phenotype produced a CTX-M-type enzyme, and six of them belonged to the widespread intercontinental clone O25b:H4-ST131. AmpC phenotype strains harboured various chromosomal ampC promoter and coding region mutations and/or the bla(CMY-2) plasmidic gene. 3GC-R strains carried fewer virulence factors and were more co-resistant to other antibiotics than 3GC-susceptible (3GC-S) strains. Infections with 3GC-R strains were mostly community-acquired and, as compared with those caused by their 3GC-S counterparts, were more severe. Underlying chronic disease and prior use of antibiotics were independent risk factors for development of a 3GC-R strain bacteraemia. The fact that the molecular support of 3GC resistance is mainly plasmid-mediated represents a potentially epidemic threat. PMID:20649802

  4. Association of Veterinary Third-Generation Cephalosporin Use with the Risk of Emergence of Extended-Spectrum-Cephalosporin Resistance in Escherichia coli from Dairy Cattle in Japan

    PubMed Central

    Sato, Toyotaka; Okubo, Torahiko; Usui, Masaru; Yokota, Shin-ichi; Izumiyama, Satoshi; Tamura, Yutaka

    2014-01-01

    The use of extended-spectrum cephalosporins in food animals has been suggested to increase the risk of spread of Enterobacteriaceae carrying extended-spectrum ?-lactamases to humans. However, evidence that selection of extended-spectrum cephalosporin–resistant bacteria owing to the actual veterinary use of these drugs according to criteria established in cattle has not been demonstrated. In this study, we investigated the natural occurrence of cephalosporin-resistant Escherichia coli in dairy cattle following clinical application of ceftiofur. E. coli isolates were obtained from rectal samples of treated and untreated cattle (n?=?20/group) cultured on deoxycholate-hydrogen sulfide-lactose agar in the presence or absence of ceftiofur. Eleven cefazoline-resistant isolates were obtained from two of the ceftiofur-treated cattle; no cefazoline-resistant isolates were found in untreated cattle. The cefazoline-resistant isolates had mutations in the chromosomal ampC promoter region and remained susceptible to ceftiofur. Eighteen extended-spectrum cephalosporin–resistant isolates from two ceftiofur-treated cows were obtained on ceftiofur-supplemented agar; no extended-spectrum cephalosporin–resistant isolates were obtained from untreated cattle. These extended-spectrum cephalosporin–resistant isolates possessed plasmid-mediated ?-lactamase genes, including blaCTX-M-2 (9 isolates), blaCTX-M-14 (8 isolates), or blaCMY-2 (1 isolate); isolates possessing blaCTX-M-2 and blaCTX-M-14 were clonally related. These genes were located on self-transmissible plasmids. Our results suggest that appropriate veterinary use of ceftiofur did not trigger growth extended-spectrum cephalosporin–resistant E. coli in the bovine rectal flora; however, ceftiofur selection in vitro suggested that additional ceftiofur exposure enhanced selection for specific extended-spectrum cephalosporin–resistant ?-lactamase-expressing E. coli clones PMID:24755996

  5. [Role of parenteral cephalosporins for outpatients treatment of infections].

    PubMed

    Esposito, S; Mazzei, T; Novelli, A

    2001-12-01

    OPAT (Outpatient Parenteral Antibiotic Therapy) arose in the early 1980s in the USA and later in many other countries from the primary consideration that outpatient treatment is more cost-effective than hospitalisation. Currently, several thousand patients undergo OPAT programmes all over the world and several different bacterial infections are included in the list of treatable diseases, especially those requiring long-term parenteral treatment such as osteomyelitis and soft tissue infections. All injectable antibiotics are suitable for OPAT according to their microbiological spectrum, although clearly some pharmacological properties make one antibiotic more preferable than another. Beta-lactams represent more than half of the antibiotic world market and two-thirds of them are cephalosporins. Such a widespread use of cephalosporins is certainly due to their wide antibacterial spectrum and good tolerability. Among third-generation cephalosporins, covering the majority of micro-organisms responsible for community-acquired infections, ceftriaxone is the only one with an 8-hour half-life, thereby permitting a single daily dose, which represents a great advantage when undertaking an OPAT programme. Analysis of antibiotic consumption used for OPAT therapies, based on data collected from the International OPAT Registry project, with the participation of many countries (USA, Canada, Britain, Argentina, etc.) including Italy, shows that ceftriaxone is the most widely used antibiotic for home therapy, clearly due to the above-mentioned properties. PMID:12087207

  6. Limited diversity in the gene pool allows prediction of third-generation cephalosporin and aminoglycoside resistance in Escherichia coli and Klebsiella pneumoniae.

    PubMed

    Ginn, Andrew N; Zong, Zhiyong; Wiklendt, Agnieszka M; Thomas, Lee C; Merlino, John; Gottlieb, Thomas; van Hal, Sebastiaan; Harkness, Jock; Macleod, Colin; Bell, Sydney M; Leroi, Marcel J; Partridge, Sally R; Iredell, Jonathan R

    2013-07-01

    Early appropriate antibiotic treatment reduces mortality in severe sepsis, but current methods to identify antibiotic resistance still generally rely on bacterial culture. Modern diagnostics promise rapid gene detection, but the apparent diversity of relevant resistance genes in Enterobacteriaceae is a problem. Local surveys and analysis of publicly available data sets suggested that the resistance gene pool is dominated by a relatively small subset of genes, with a very high positive predictive value for phenotype. In this study, 152 Escherichia coli and 115 Klebsiella pneumoniae consecutive isolates with a cefotaxime, ceftriaxone and/or ceftazidime minimum inhibitory concentration (MIC) of ? 2 ?g/mL were collected from seven major hospitals in Sydney (Australia) in 2008-2009. Nearly all of those with a MIC in excess of European Committee on Antimicrobial Susceptibility Testing (EUCAST) resistance breakpoints contained one or more representatives of only seven gene types capable of explaining this phenotype, and this included 96% of those with a MIC ? 2 ?g/mL to any one of these drugs. Similarly, 97% of associated gentamicin-non-susceptibility (MIC ? 8 ?g/mL) could be explained by three gene types. In a country like Australia, with a background prevalence of resistance to third-generation cephalosporins of 5-10%, this equates to a negative predictive value of >99.5% for non-susceptibility and is therefore suitable for diagnostic application. This is an important proof-of-principle that should be tested in other geographic locations. PMID:23706544

  7. Impact of third-generation-cephalosporin administration in hatcheries on fecal Escherichia coli antimicrobial resistance in broilers and layers.

    PubMed

    Baron, Sandrine; Jouy, Eric; Larvor, Emeline; Eono, Florent; Bougeard, Stéphanie; Kempf, Isabelle

    2014-09-01

    We investigated the impact of the hatchery practice of administering third-generation cephalosporin (3GC) on the selection and persistence of 3GC-resistant Escherichia coli in poultry. We studied 15 3GC-treated (TB) and 15 non-3GC-treated (NTB) broiler flocks and 12 3GC-treated (TL) and 10 non-3GC-treated (NTL) future layer flocks. Fecal samples from each flock were sampled before arrival on the farm (day 0), on day 2, on day 7, and then twice more. E. coli isolates were isolated on MacConkey agar without antibiotics and screened for 3GC resistance, and any 3GC-resistant E. coli isolates were further analyzed. 3GC-resistant E. coli isolates were found in all 3GC-treated flocks on at least one sampling date. The percentages of 3GC-resistant E. coli isolates were significantly higher in TB (41.5%) than in NTB (19.5%) flocks and in TL (49.5%) than in NTL (24.5%) flocks. In the day 2 samples, more than 80% of the E. coli strains isolated were 3GC resistant. 3GC-resistant E. coli strains were still detected at the end of the follow-up period in 6 out of 27 3GC-treated and 5 out of 25 non-3GC-treated flocks. Many 3GC-resistant E. coli strains were resistant to tetracycline, and there were significant differences in the percentages of resistance to sulfamethoxazole-trimethoprim, streptomycin, or gentamicin between treated and nontreated flocks. blaCTX-M and blaCMY-2 were the most frequently detected genes. These results clearly demonstrated that 3GC-resistant strains are introduced early in flocks and that the use of 3GC in hatcheries promotes the selection of 3GC-resistant E. coli. Measures must be implemented to avoid the spread and selection of 3GC-resistant strains. PMID:24982086

  8. Cephalosporins are scavengers of hypochlorous acid

    Microsoft Academic Search

    Domenico Lapenna; Luigina Cellini; Sergio De Gioia; Andrea Mezzetti; Giuliano Ciofani; Davide Festi; Franco Cuccurullo

    1995-01-01

    Potential scavenging properties of cephalosporins (i.e. cefamandole, cefotaxime and ceftriaxone) towards hypochlorous acid (HOCl) as well as the antibacterial activity of control and HOCl-reacted antibiotics were investigated. We found that these drugs, at therapeutically relevant concentrations, are indeed scavengers of HOCl, with ceftriaxone showing the highest anti-HOCl capacity. However, the efficiency of cephalosporins in protecting biological molecules is also related

  9. Analysis of Salmonella enterica with reduced susceptibility to the third-generation cephalosporin ceftriaxone isolated from U.S. cattle during 2000-2004.

    PubMed

    Frye, Jonathan G; Fedorka-Cray, Paula J; Jackson, Charlene R; Rose, Markus

    2008-12-01

    Over the past decade enteric bacteria in Europe, Africa, and Asia have become increasingly resistant to cephalosporin antimicrobial agents. This is largely due to the spread of genes encoding extended-spectrum beta-lactamase (ESBL) enzymes that can inactivate many cephalosporins. Recently, these resistance mechanisms have been identified in Salmonella isolated from humans in the United States. Due to the potential for transmission of resistant bacteria to humans via food animals, Salmonella animal isolates were monitored for ESBL production. During 2000-2004, Salmonella cattle slaughter isolates (n = 3,984) were tested, and 97 (2.4%) of these were found to have decreased susceptibility (minimum inhibitory concentration [MIC] >32 microg/ml) to the third-generation cephalosporin ceftriaxone. The majority of these were serotypes Newport (58) and Agona (14), some of which were genetically indistinguishable by pulsed field gel electrophoresis (PFGE) analysis. None of the isolates had an ESBL phenotype; all were susceptible to the fourth-generation cephalosporins cefepime and cefquinome. PCR and sequence analysis for resistance genes detected the bla(CMY-2) gene in 93 isolates and the bla(TEM-1) gene in 12 isolates; however, neither gene encodes an ESBL. These data indicate that bovine Salmonella isolates from the United States with decreased susceptibility or resistance to ceftriaxone do not exhibit an ESBL phenotype and most contain the bla(CMY-2) gene. PMID:19025468

  10. Kirby-Bauer disc approximation to detect inducible third-generation cephalosporin resistance in Enterobacteriaceae

    Microsoft Academic Search

    Xuan Qin; Scott J Weissman; Mary Frances Chesnut; Bei Zhang; Lisong Shen

    2004-01-01

    Resistance to ?-lactam antibiotics in enteric Gram-negative bacilli may be difficult to detect using standard methods of either Kirby-Bauer disc diffusion (KBDD) or broth dilution for minimal inhibitory concentration (MIC). This difficulty is due to genetic differences in resistance determinants, differences in levels of gene expression, and variation in spectra of enzymatic activity against the substrate ?-lactams used for susceptibility

  11. Diagnosis and Management of Immediate Hypersensitivity Reactions to Cephalosporins

    PubMed Central

    Kim, Min-Hye

    2014-01-01

    Cephalosporins can cause a range of hypersensitivity reactions, including IgE-mediated, immediate reactions. Cephalosporin allergy has been reported with use of a specific cephalosporin, as a cross-reaction between different cephalosporins or as a cross-reaction to other ?-lactam antibiotics. Unlike penicillins, the exact allergenic determinants of cephalosporins are less well understood and thus, standardized diagnostic skin testing is not available. Nevertheless, skin testing with diluted solutions of cephalosporins can be valuable in confirming IgE-mediated hypersensitivity reactions. In vitro tests are in development using recent technological advances and can be used as complementary tests. However, they are not commonly used because of their reduced sensitivity and limited availability. In selected cases of inconclusive results in both skin tests and IgE assays, a graded challenge or induction of drug tolerance with the implicated cephalosporin should be performed. PMID:25374747

  12. Resistance to cephalosporins and carbapenems in Gram-negative bacterial pathogens

    Microsoft Academic Search

    Yvonne Pfeifer; Angela Cullik; Wolfgang Witte

    2010-01-01

    During the past 15 years, emergence and dissemination of ?-lactam resistance in nosocomial Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii, became a serious problem worldwide. Especially the increasing resistance to 3rd and 4th generation cephalosporins and carbapenems is of particular concern. Gram-negative bacteria pursue various molecular strategies for development of resistance to these antibiotics: (a) generation of extended-spectrum ?-lactamases (ESBL) according

  13. Reciprocal Regulation of Cephalosporin Resistance in Enterococcus faecalis

    PubMed Central

    Kristich, Christopher J.; Little, Jaime L.; Hall, Cherisse L.; Hoff, Jessica S.

    2011-01-01

    ABSTRACT Antibiotic-resistant enterococci are major causes of hospital-acquired infections and therefore represent a serious public health problem. One well-known risk factor for the acquisition of hospital-acquired enterococcal infections is prior therapy with broad-spectrum cephalosporin antibiotics. Enterococci can proliferate in patients undergoing cephalosporin therapy due to intrinsic cephalosporin resistance, a characteristic of the genus Enterococcus. However, the molecular basis for cephalosporin resistance in E. faecalis has yet to be adequately elucidated. Previously we determined that a putative Ser/Thr kinase, IreK (formerly PrkC), is required for intrinsic cephalosporin resistance in E. faecalis. Here we show that kinase activity is required for cephalosporin resistance and, further, that resistance in E. faecalis is reciprocally regulated by IreK and IreP, a PP2C-type protein phosphatase encoded immediately upstream of IreK. Mutants of two divergent lineages of E. faecalis lacking IreP exhibit remarkable hyperresistance to cephalosporins but not to antibiotics targeting other cellular processes. Further genetic analyses indicate that hyperresistance of the IreP mutant is mediated by the IreK kinase. Additionally, competition experiments reveal that hyperresistant ?ireP mutants exhibit a substantial fitness defect in the absence of antibiotics, providing an evolutionary rationale for the use of a complex signaling system to control intrinsic cephalosporin resistance. These results support a model in which IreK and IreP act antagonistically via protein phosphorylation and dephosphorylation as part of a signal transduction circuit to regulate cellular adaptation to cephalosporin-induced stress. PMID:22045988

  14. Tissue concentrations of third-generation cephalosporins (ceftazidime and ceftriaxone) in lower extremity tissues using a tourniquet

    Microsoft Academic Search

    N. Papaioannou; L. Kalivas; J. Kalavritinos; S. Tsourvakas

    1994-01-01

    Prophylactic antibiotic administration for selected major orthopaedic procedures is feasible with wide-spectrum antibiotics that can achieve high tissue levels. We studied the influence of tourniquet on the in vivo concentrations of ceftazidime and ceftriaxone in soft tissue and bone. Our study group consisted of 47 patients undergoing reconstructive operations of lower extremities. The effect of different time intervals between antibiotic

  15. In vitro synergistic effect of curcumin in combination with third generation cephalosporins against bacteria associated with infectious diarrhea.

    PubMed

    Sasidharan, Nishanth Kumar; Sreekala, Sreerag Ravikumar; Jacob, Jubi; Nambisan, Bala

    2014-01-01

    Diarrhea is one of the leading causes of morbidity and mortality in humans in developed and developing countries. Furthermore, increased resistance to antibiotics has resulted in serious challenges in the treatment of this infectious disease worldwide. Therefore, there exists a need to develop alternative natural or combination drug therapies. The aim of the present study was to investigate the synergistic effect of curcumin-1 in combination with three antibiotics against five diarrhea causing bacteria. The antibacterial activity of curcumin-1 and antibiotics was assessed by the broth microdilution method, checkerboard dilution test, and time-kill assay. Antimicrobial activity of curcumin-1 was observed against all tested strains. The MICs of curcumin-1 against test bacteria ranged from 125 to 1000 ? g/mL. In the checkerboard test, curcumin-1 markedly reduced the MICs of the antibiotics cefaclor, cefodizime, and cefotaxime. Significant synergistic effect was recorded by curcumin-1 in combination with cefotaxime. The toxicity of curcumin-1 with and without antibiotics was tested against foreskin (FS) normal fibroblast and no significant cytotoxicity was observed. From our result it is evident that curcumin-1 enhances the antibiotic potentials against diarrhea causing bacteria in in vitro condition. This study suggested that curcumin-1 in combination with antibiotics could lead to the development of new combination of antibiotics against diarrhea causing bacteria. PMID:24949457

  16. Dual-Action Cephalosporin Utilizing a Novel Therapeutic Principle

    PubMed Central

    Greenwood, D.; O'Grady, F.

    1976-01-01

    A new cephalosporin is described that overcomes, in a novel way, the general susceptibility of this group of agents to enterobacterial ?-lactamases. The new compound carries a substituent that is released on cleavage of the ?-lactam ring and then exhibits antibacterial activity in its own right. The possible therapeutic benefits of such an antibiotic are discussed. PMID:791095

  17. Degradation kinetics and mechanism of antibiotic ceftiofur in recycled water derived from beef farm

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ceftiofur is a third-generation cephalosporin antibiotic that has been widely used to treat bacterial infections in concentrated animal feeding operations (CAFOs). Land application of CAFO waste may lead to the loading of ceftiofur residues and its metabolites to the environment. To mitigate the pot...

  18. Dissemination of cephalosporin resistance genes between Escherichia coli strains from farm animals and humans by specific plasmid lineages.

    PubMed

    de Been, Mark; Lanza, Val F; de Toro, María; Scharringa, Jelle; Dohmen, Wietske; Du, Yu; Hu, Juan; Lei, Ying; Li, Ning; Tooming-Klunderud, Ave; Heederik, Dick J J; Fluit, Ad C; Bonten, Marc J M; Willems, Rob J L; de la Cruz, Fernando; van Schaik, Willem

    2014-12-01

    Third-generation cephalosporins are a class of ?-lactam antibiotics that are often used for the treatment of human infections caused by Gram-negative bacteria, especially Escherichia coli. Worryingly, the incidence of human infections caused by third-generation cephalosporin-resistant E. coli is increasing worldwide. Recent studies have suggested that these E. coli strains, and their antibiotic resistance genes, can spread from food-producing animals, via the food-chain, to humans. However, these studies used traditional typing methods, which may not have provided sufficient resolution to reliably assess the relatedness of these strains. We therefore used whole-genome sequencing (WGS) to study the relatedness of cephalosporin-resistant E. coli from humans, chicken meat, poultry and pigs. One strain collection included pairs of human and poultry-associated strains that had previously been considered to be identical based on Multi-Locus Sequence Typing, plasmid typing and antibiotic resistance gene sequencing. The second collection included isolates from farmers and their pigs. WGS analysis revealed considerable heterogeneity between human and poultry-associated isolates. The most closely related pairs of strains from both sources carried 1263 Single-Nucleotide Polymorphisms (SNPs) per Mbp core genome. In contrast, epidemiologically linked strains from humans and pigs differed by only 1.8 SNPs per Mbp core genome. WGS-based plasmid reconstructions revealed three distinct plasmid lineages (IncI1- and IncK-type) that carried cephalosporin resistance genes of the Extended-Spectrum Beta-Lactamase (ESBL)- and AmpC-types. The plasmid backbones within each lineage were virtually identical and were shared by genetically unrelated human and animal isolates. Plasmid reconstructions from short-read sequencing data were validated by long-read DNA sequencing for two strains. Our findings failed to demonstrate evidence for recent clonal transmission of cephalosporin-resistant E. coli strains from poultry to humans, as has been suggested based on traditional, low-resolution typing methods. Instead, our data suggest that cephalosporin resistance genes are mainly disseminated in animals and humans via distinct plasmids. PMID:25522320

  19. Impact of a Change in Antibiotic Prophylaxis on Total Antibiotic Use in a Surgical Intensive Care Unit

    Microsoft Academic Search

    E. Meyer; F. Schwab; A. Pollitt; W. Bettolo; B. Schroeren-Boersch; M. Trautmann

    2010-01-01

    \\u000a Abstract\\u000a \\u000a \\u000a Objective:\\u000a   The aim of this study was to evaluate the impactof reducing the length of antibiotic prophylaxis for cerebrospinalshunts on\\u000a total antibiotic use and key resistantpathogens.\\u000a \\u000a \\u000a \\u000a \\u000a \\u000a Methods:\\u000a   In January 2004, the use of antibiotic prophylaxiswas reduced to a single shot dose with cefuroxime in anintensive care unit\\u000a (ICU). Prior to this intervention, prophylaxiswith second-generation cephalosporins wasadministered during the entire

  20. A moderate amplification of the mec B gene encoding cystathionine-?-lyase stimulates cephalosporin biosynthesis in Acremonium chrysogenum

    Microsoft Academic Search

    K Kosalkova ´; A T Marcos; J F Martín

    2001-01-01

    L  -cysteine is a precursor of the penicillin, cephalosporin and cephamycin families of ?-lactam antibiotics. Cystathionine-?-lyase\\u000a (encoded by the mecB gene), an enzyme that splits cystathionine releasing cysteine, is required for high-level cephalosporin production in methionine-supplemented\\u000a medium. By amplification of the mecB gene in Acremonium chrysogenum C10, several transformants were obtained that produced 10-40% higher levels of cephalosporin. All selected transformants

  1. Mutations in the ? Subunit of RNA Polymerase Alter Intrinsic Cephalosporin Resistance in Enterococci

    PubMed Central

    Little, Jaime L.

    2012-01-01

    As major causes of hospital-acquired infections, antibiotic-resistant enterococci are a serious public health concern. Enterococci are intrinsically resistant to many cephalosporin antibiotics, a trait that enables proliferation in patients undergoing cephalosporin therapy. Although a few genetic determinants of cephalosporin resistance in enterococci have been described, overall, many questions remain about the underlying genetic and biochemical basis for cephalosporin resistance. Here we describe an unexpected effect of specific mutations in the ? subunit of RNA polymerase (RNAP) on intrinsic cephalosporin resistance in enterococci. We found that RNAP mutants, selected initially on the basis of their ability to provide resistance to rifampin, resulted in allele-specific alterations of the intrinsic resistance of enterococci toward expanded- and broad-spectrum cephalosporins. These mutations did not affect resistance toward a diverse collection of other antibiotics that target a range of alternative cellular processes. We propose that the RNAP mutations identified here lead to alterations in transcription of as-yet-unknown genes that are critical for cellular adaption to cephalosporin stress. PMID:22290974

  2. Chromatographic studies of some cephalosporins on thin layers of silica gel G-zinc ferrocyanide.

    PubMed

    Singh, Dhruv K; Maheshwari, Gunjan

    2010-10-01

    A simple, selective and precise thin-layer chromatographic method has been developed for the analysis of eight cephalosporin antibiotics, namely cephadroxil, cephalexin, cefixime, cefaclor, cefpodoxime proxetil, cefuroxime axetil, cefotaxime sodium and ceftriaxone sodium. The hR(F) values of these cephalosporins were investigated on silica gel G-zinc ferrocyanide layers. Mixing of zinc ferrocyanide with silica gel G resulted in a decrease in hR(F) values, removal of tailing and better resolutions. The influence of silica gel G-zinc ferrocyanide ratio and mobile phases on the chromatographic behavior of cephalosporins on thin layers was investigated. Cephalosporins were selectively separated in their binary and ternary synthetic mixtures and pharmaceutical formulations. Quantitative separations of cephalosporins from their synthetic mixtures were also achieved with good recoveries (97.8-100.3%). PMID:20853462

  3. Genetic characterization of the mechanisms of resistance to amoxicillin/clavulanate and third-generation cephalosporins in Salmonella enterica from three Spanish hospitals.

    PubMed

    de Toro, María; Sáenz, Yolanda; Cercenado, Emilia; Rojo-Bezares, Beatriz; García-Campello, Marta; Undabeitia, Esther; Torres, Carmen

    2011-09-01

    The mechanisms of antimicrobial resistance were characterized in 90 Salmonella enterica isolates either resistant or with intermediate resistance to amoxicillin/clavulanate (AMC(R/I)) or resistant to third-generation cephalosporins (C3G(R)). These isolates were recovered in three Spanish hospitals during 2007-2009. The C3G(R) phenotype was expressed by three isolates that carried the following extended-spectrum ?-lactamase genes: phage-associated bla(CTX M-10) in S. Virchow, bla(CTX-M-14a) surrounded by ISEcp1 and IS903 in S. Enteritidis, and bla(CTX-M-15) linked to ISEcp1 and orf477 in S. Gnesta (first description in this serotype). The AMC(R/I) phenotype was found in 87 isolates (79 S. Typhimurim, 7 S. Enteritidis, and one S. Thompson). The bla(PSE-1) gene, followed by bla(OXA-1) was mostly found among S. Typhimurim, and the bla(TEM-1) gene among S. Enteritidis. Three different gene combinations [bla(PSE-1) +floR+aadA2+sul+tet(G); bla(OXA-1) +catA+aadA1/strA-strB+sul+tet(B) and bla(TEM-1) + cmlA1+aadA/strA-strB+sul+tet(A)/tet(B) genes] were associated with the ampicillin-chloramphenicol-streptomycin-sulfonamides-tetracycline phenotype in 68 AMC(R/I) S. enterica isolates. Class 1 integrons were observed in 79% of the isolates and in most of them (45 isolates) two integrons including the aadA2 and bla(PSE-1) gene cassettes, respectively, were detected. The bla(OXA-1) +aadA1 arrangement was detected in 23 isolates, and the aac(6')-Ib-cr+bla(OXA-1) +catB3+arr3 in another one. Non-classic class 1 integrons were found in three isolates: dfrA12+orfF+aadA2+cmlA1+aadA1 (1 isolate), dfrA12+orfF+aadA2+ cmlA1+aadA1+qacH+IS440+sul3 (1 isolate) and dfrA12+orfF+aadA2+cmlA1+aadA1+qacH+IS440+ sul3+orf1+mef(B)?-IS26 (1 isolate). Taken together, these results underline the need for clinical concern regarding ?-lactam resistance in Salmonella and thus for continuous monitoring. PMID:22101415

  4. Expanded-spectrum cephalosporin resistance in non-typhoid Salmonella

    Microsoft Academic Search

    V Miriagou; P. T Tassios; N. J Legakis; L. S Tzouvelekis

    2004-01-01

    Expanded-spectrum cephalosporins (ESCs) such as ceftriaxone, together with fluorinated quinolones, are the choice antibiotics in the treatment of invasive salmonella infections. Resistance to ESCs among non-typhoid salmonella has been recognised since the late 1980s. Currently, ESC-resistant salmonella strains are reported world-wide and in some areas their incidence is significant. Resistance is mainly due to acquisition of multi-resistant plasmids encoding a

  5. Review of the use of cephalosporins in children with anaphylactic reactions from penicillins

    PubMed Central

    Hameed, Tahir K; Robinson, Joan L

    2002-01-01

    OBJECTIVE: It is a widely accepted practice that children with anaphylaxis from penicillins should avoid cephalosporins. The purpose of the present study was to determine whether there is evidence in the literature to support this practice. DATA SOURCES: MEDLINE, EMBASE, Toxline, International Pharmaceutical Abstracts and PubMed were used to search the literature published from 1966 to 2001. The Canadian Medical Protective Association, Health Canada and the Boston Collaborative Drug Surveillance Program were also contacted to determine whether there were any unpublished cases of cross-reactivity between penicillins and cephalosporins. DATA EXTRACTION: Cases describing the use of cephalosporins in adults and children with positive penicillin skin tests or anaphylaxis from penicillin were evaluated. Case reports of anaphylaxis from cephalosporins in paediatric patients were identified. DATA SYNTHESIS: There have been five reported cases of serious reactions from cephalosporins in patients with a history of anaphylaxis from penicillins. All cases occurred in adults; three developed anaphylaxis from the older, first-generation cephalosporins, cephalothin and cephaloridine; one developed anaphylaxis from cefamandole; and one developed anaphylaxis from cefaclor. There have been 12 other published reports of anaphylaxis from cephalosporins in adults with a history of penicillin allergy or a positive penicillin skin test, but with no history of anaphylaxis from penicillin. In seven studies, in which a total of 158 patients with positive penicillin skin tests were administered cephalosporins, seven had apparent immunoglobulin E-mediated reactions when they were given a cephalosporin. When the class of cephalosporin was able to be determined, none of the reports of reactions from cephalosporins in patients with allergies to penicillin involved third-generation cephalosporins. There have been 13 case reports of anaphylaxis from cephalosporins in paediatric patients. CONCLUSION: There are no published case reports of anaphylaxis from cephalosporins in children with anaphylaxis from penicillin, and there are only a small number of such reports in adults. Anaphylaxis from cephalosporins appears to be incredibly rare in children. There is minimal evidence in the literature to support the avoidance of cephalosporins in children with anaphylaxis from penicillins. PMID:18159398

  6. Outcome of Cephalosporin Treatment for Serious Infections Due to Apparently Susceptible Organisms Producing Extended-Spectrum b-Lactamases: Implications for the Clinical Microbiology Laboratory

    Microsoft Academic Search

    DAVID L. PATERSON; WEN-CHIEN KO; ANNE VON GOTTBERG; JOSE MARIA CASELLAS; LUTFIYE MULAZIMOGLU; KEITH P. KLUGMAN; ROBERT A. BONOMO; LOUIS B. RICE; JOSEPH G. MCCORMACK; VICTOR L. YU

    Although extended-spectrum beta-lactamases (ESBLs) hydrolyze cephalosporin antibiotics, some ESBL- producing organisms are not resistant to all cephalosporins when tested in vitro. Some authors have suggested that screening klebsiellae or Escherichia coli for ESBL production is not clinically necessary, and when most recently surveyed the majority of American clinical microbiology laboratories did not make efforts to detect ESBLs. We performed a

  7. Outcome of Cephalosporin Treatment for Serious Infections Due to Apparently Susceptible Organisms Producing Extended-Spectrum  -Lactamases: Implications for the Clinical Microbiology Laboratory

    Microsoft Academic Search

    DAVID L. PATERSON; WEN-CHIEN KO; ANNE VON GOTTBERG; JOSE MARIA CASELLAS; LUTFIYE MULAZIMOGLU; KEITH P. KLUGMAN; ROBERT A. BONOMO; LOUIS B. RICE; JOSEPH G. MCCORMACK; VICTOR L. YU

    2001-01-01

    Although extended-spectrum beta-lactamases (ESBLs) hydrolyze cephalosporin antibiotics, some ESBL- producing organisms are not resistant to all cephalosporins when tested in vitro. Some authors have suggested that screening klebsiellae or Escherichia coli for ESBL production is not clinically necessary, and when most recently surveyed the majority of American clinical microbiology laboratories did not make efforts to detect ESBLs. We performed a

  8. Comparative activity of ampicillin and seven cephalosporins against group D streptococci

    PubMed Central

    Hamilton-Miller, J. M. T.

    1974-01-01

    Minimum inhibitory concentrations have been determined for ampicillin and seven cephalosporins against 93 strains of group D streptococci isolated recently from clinical material. Ampicillin was much the most active compound (modal MIC = 1·6 ?g/ml); cephaloridine, cephacetrile, and cefazolin had a modal MIC of 25 ?g/ml, while corresponding figures for cephalothin, cephradine, cephalexin, and cefoxitin were 50, 100, 200, and 800 ?g/ml, respectively. Thus, none of the newer cephalosporins is an improvement in respect to activity against enterococci over existing compounds, and ampicillin remains overwhelmingly the ?-lactam antibiotic of choice for the treatment of infections by such organisms. Pharmacokinetic considerations, however, indicate that certain cephalosporins, for instance, cephaloridine, cefazolin, and cephanone, may be worthy of further study in view of possible synergy with aminoglycoside antibiotics. PMID:4214839

  9. Effect of Peritoneal Dialysis Solution on the Antimicrobial Activity of Cephalosporins

    Microsoft Academic Search

    Daryl H. Appleby

    1982-01-01

    We studied the effect of peritoneal dialysis solution (PDS) on the antibacterial activity of seven cephalosporins, gentamicin, tobramycin and amikacin. The six bacterial species employed in the study survived in a wide range of concentrations of PDS, however, Staphylococcus aureus did not survive beyond 24 h in PDS. There were no physical incompatibilities between any of the antibiotics and PDS.

  10. Azithromycin Resistance Is Coevolving with Reduced Susceptibility to Cephalosporins in Neisseria gonorrhoeae in Ontario, Canada

    PubMed Central

    Allen, Vanessa G.; Seah, Christine; Martin, Irene

    2014-01-01

    Azithromycin (AZM) is routinely recommended as a component of dual therapy for gonorrhea in combination with third-generation cephalosporins (3GC). In this study, we examined the prevalence of AZM-resistant (AZMr) Neisseria gonorrhoeae from July 2010 to February 2013, assessed the rate of concurrent cephalosporin resistance under the current treatment recommendations, and analyzed the clonal distribution of AZMr isolates in Ontario, Canada. Nineteen AZMr clinical isolates (one per patient; MIC, ?2 ?g/ml) were included in the study. Susceptibility profiles of these isolates to 11 antibiotics, molecular typing, characterization of macrolide resistance mechanisms, and penicillin-binding protein 2 (PBP2) patterns were determined for all the isolates. Two groups were defined based on AZMr level; group A isolates displayed high-level resistance (MIC, ?2,048 ?g/ml) due to mutations (A2143G) in the four copies of the 23S rRNA rrl gene, and group B isolates had moderate resistance to AZM (MICs, 2 to 8 ?g/ml, C2599T mutation in the rrl gene), with a subgroup belonging to sequence type 3158 (ST3158) (n = 8), which also showed reduced susceptibility to 3GC (MICs, 0.12 to 0.25 ?g/ml, PBP2 pattern XXXIV). This AZMr phenotype was not observed in previous provincial surveillance in 2008 (the ST3158 clone was found, with AZM MICs of 0.25 to 0.5 ?g/ml associated with mtrR mutations). We hypothesized that the AZM mutant prevention concentration (MPC) in the ST3158 subpopulation we found in 2008 was higher than the MPC in wild-type isolates (AZM MIC, ?0.031 ?g/ml), increasing the chances of additional selection of AZMr mutations. Full AZM resistance is now emerging in this clone together with reduced susceptibility to 3GC, threatening the future efficacy of these antibiotics as therapeutic options for treatment of gonorrhea. PMID:24514092

  11. A chromogenic cephalosporin for ?-lactamase inhibitor screening assays.

    PubMed

    Yu, Sophia; Vosbeek, Amy; Corbella, Katherine; Severson, Jonathan; Schesser, Jacob; Sutton, Larry D

    2012-09-15

    Production of ?-lactamases is the primary mechanism of antibiotic resistance employed by gram-negative pathogens. Chromogenic ?-lactams are important reagents for detection and assay of ?-lactamases, but limited commercial availability and exorbitant pricing of these compounds are prohibitive. Here we describe a straightforward synthesis of a chromogenic cephalosporin for ?-lactamase assay that gives an overall yield of 74%. On hydrolysis, its ?(max) undergoes a bathochromic shift that is easy to see and measure spectrophotometrically with a ??(442 nm) of 14,500 cm?¹ M?¹. This compound was shown to be a substrate for a variety of ?-lactamases. PMID:22709853

  12. Laboratory Evaluation of FR10024, a New Cephalosporin Derivative

    PubMed Central

    Nishida, Minoru; Murakawa, Takeo; Kamimura, Toshiaki; Okada, Naohiko; Fukada, Shigemi; Sakamoto, Hiroshi; Nakamoto, Shoji; Yokota, Yoshiko; Kono, Yoko

    1977-01-01

    FR10024 is a broad-spectrum antibiotic. The in vitro antibacterial activity of FR10024 against clinical isolates of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis is greater than that of any of the cephalosporins developed to date. Indole-positive Proteus, Enterobacter, and Citrobacter are resistant to FR10024, as is true for the other cephalosporins. However, more than half of the strains of Enterobacter and Citrobacter tested were susceptible to FR10024 at an inoculum of 106 cells/ml. A single subcutaneous injection of FR10024 to mice with peritoneal infections due to S. aureus and several species of gram-negative bacilli gave a protective effect inferior to that of cefazolin but appeared to be superior to that of cephalothin. When given in two divided doses, however, the protective effect of FR10024 was enhanced and almost equaled that of cefazolin. The serum levels and rates of urinary recovery of FR10024 varied in different animal species. The mean peak serum level of FR10024 in humans after a single intramuscular injection of 500 mg was two times higher than that of cephalothin. The serum half-life after intramuscular injections of 250 and 500 mg was slightly shorter than that of cephalothin. After receiving 250 mg of FR10024 intramuscularly the urinary recovery rate was 87.7% in healthy volunteers. The biliary excretion rate of FR10024 was particularly high. The 24-h excretion of FR10024 in rats was 63.3%, this being six to seven times higher than that for cefazolin, which has the highest biliary excretion of the other known cephalosporins. When FR10024 was injected intramuscularly (20 mg/kg), it was found that the hepatic levels of FR10024 in rats were the highest of all the cephalosporins, including cefazolin, but the levels of FR10024 in other tissues were not as high as those of cefazolin. PMID:836014

  13. Vol 441|18 May 2006 A promising new antibiotic is generating both

    E-print Network

    Cai, Long

    several of the major drug-resistant bacteria that plague hospitals. Among them are methicillin-resistant Staphy- loccocus aureus (MRSA) and bacteria resistant to vancomycin, one of the last lines of antiVol 441|18 May 2006 260 NEWS A promising new antibiotic is generating both excitement

  14. Diverse modulation of spa transcription by cell wall active antibiotics in Staphylococcus aureus

    PubMed Central

    2012-01-01

    Background The aim of this study was to investigate the effect of various classes of clinically relevant antibiotics at sub-lethal concentrations on virulence gene expression and biofilm formation in Staphylococcus aureus. Findings LacZ promoter fusions of genes related to staphylococcal virulence were used to monitor the effects of antibiotics on gene expression in a disc diffusion assay. The selected genes were hla and spa encoding ?-hemolysin and Protein A, respectively and RNAIII, the effector molecule of the agr quorum sensing system. The results were confirmed by quantitative real-time PCR. Additionally, we monitored the effect of subinhibitory concentrations of antibiotics on the ability of S. aureus to form biofilm in a microtiter plate assay. The results show that sub-lethal antibiotic concentrations diversely modulate expression of RNAIII, hla and spa. Consistently, expression of all three genes were repressed by aminoglycosides and induced by fluoroquinolones and penicillins. In contrast, the ?-lactam sub-group cephalosporins enhanced expression of RNAIII and hla but diversely affected expression of spa. The compounds cefalotin, cefamandole, cefoxitin, ceftazidime and cefixine were found to up-regulate spa, while down-regulation was observed for cefuroxime, cefotaxime and cefepime. Interestingly, biofilm assays demonstrated that the spa-inducing cefalotin resulted in less biofilm formation compared to the spa-repressing cefotaxime. Conclusions We find that independently of the cephalosporin generation, cephalosporins oppositely regulate spa expression and biofilm formation. Repression of spa expression correlates with the presence of a distinct methyloxime group while induction correlates with an acidic substituted oxime group. As cephalosporines target the cell wall penicillin binding proteins we speculate that subtle differences in this interaction fine-tunes spa expression independently of agr. PMID:22920188

  15. Evaluating the need, timing and best choice of antibiotic therapy for acute otitis media and tonsillopharyngitis infections in children.

    PubMed

    Pichichero, M E

    2000-12-01

    Deciding whether an antibiotic is necessary, when to begin therapy and selecting an optimal drug is an everyday challenge in clinical practice. In vitro susceptibility testing which determines the minimum concentration necessary for a particular antibiotic to inhibit or kill most strains of a bacterial species and pharmacodynamic modeling are useful but have limitations. The need for antibiotic therapy for acute otitis media (AOM) has been recently questioned. However, explanations for uniformly positive results with many antibiotic and placebo comparative trials include overdiagnosis of AOM at study entry, inclusion of patients with mild or uncomplicated AOM and broad criteria for the definition of clinical success. Recurrent and persistent AOM does not have as favorable a natural history as uncomplicated AOM; children below 2 years of age benefit most from antibiotic therapy. Selecting the best choice among the many antibiotics that can be used to treat AOM has become more complex over the last decade due to escalating antibiotic resistance among the pathogens that cause this infection. Broader spectrum antibiotics such as cefdinir, the newly introduced third generation cephalosporin, have their most prominent use in the treatment of persistent and recurrent AOM. In the early 1950s and 1960s penicillin clearly was the best available agent for the treatment of group A streptococcal (GAS) infections. In the 1970s the situation began to change as cephalosporin antibiotics became available. Superior eradication rates with cephalosporins such as cefdinir have now been well-documented. The leading hypothesis to explain the widening gap in efficacy between penicillin and cephalosporins relates to two major concepts: the presence of copathogens and differential alteration of the normal microbial ecology in the throat as a consequence of the selected therapy. There are positive and negative consequences to early initiation of antibiotic therapy for GAS tonsillopharyngitis. Penicillin has persisting good efficacy in patients older than the age of 12 years and in those who have been ill for >2 days. Shortening therapy for GAS tonsillopharyngitis offers a therapeutic advantage. Cefpodoxime proxetil and cefdinir have a 5-day indication for the treatment of GAS tonsillopharyngitis. Antibiotics with lower side effect profile, infrequent dosing, good palatability in suspension formulation and efficacy with short duration of treatment may lead to better outcomes because noncompliance often results in failed therapy, persistence of infection and morbidity. PMID:11144394

  16. MurAA Is Required for Intrinsic Cephalosporin Resistance of Enterococcus faecalis

    PubMed Central

    Vesi?, Dušanka

    2012-01-01

    Enterococcus faecalis is a low-GC Gram-positive bacterium that is intrinsically resistant to cephalosporins, antibiotics that target cell wall biosynthesis. To probe the mechanistic basis for intrinsic resistance, a library of transposon mutants was screened to identify E. faecalis strains that are highly susceptible to ceftriaxone, revealing a transposon mutant with a disruption in murAA. murAA is predicted to encode a UDP-N-acetylglucosamine 1-carboxyvinyl transferase that catalyzes the first committed step in peptidoglycan synthesis: phosphoenolpyruvate (PEP)-dependent conversion of UDP-N-acetylglucosamine to UDP-N-acetylglucosamine-enolpyruvate. In-frame deletion of murAA, but not its homolog in the E. faecalis genome (murAB), led to increased susceptibility of E. faecalis to cephalosporins. Furthermore, expression of murAA enhanced cephalosporin resistance in an E. faecalis mutant lacking IreK (formerly PrkC), a key kinase required for cephalosporin resistance. Further genetic analysis revealed that MurAA catalytic activity is necessary but not sufficient for this role. Collectively, our data indicate that MurAA and MurAB have distinct roles in E. faecalis physiology and suggest that MurAA possesses a unique property or activity that enables it to enhance intrinsic resistance of E. faecalis to cephalosporins. PMID:22290954

  17. AN INHIBITION TEST INTENDED TO DETECT AND TO DIFFERENTIATE BETWEEN PENICILLINS, CEPHALOSPORINS, TETRACYCLINES AND QUINOLONES, FOR USE IN MUSCLE TISSUE FROM DIFFERENT ANIMAL SPECIES

    Microsoft Academic Search

    Lieve Okerman; Katia De Wasch; Jan Van Hoof

    A combination of three plates, seeded with resp. Micrococcus luteus, Bacillus cereus and Escherichia coli, can be used for detection of beta-lactam antibiotics, cephalosporins, tetracyclines and quinolones in pork, veal, beef, poultry and fish muscle tissue. The sensitivity of each plate is optimal for one or two antibiotic families, resulting in detection limits lower than the corresponding maximal residue limits

  18. Response of ampicillin resistant Escherichia coli to cephalosporins in an in vitro model simulating conditions of bacterial growth in the urinary bladder.

    PubMed Central

    Greenwood, D.; O'Grady, F.

    1975-01-01

    Five ampicillin resistant strains of Escherichia coli were exposed to cephalosporins in an in vitro model which simulates the hydrokinetic features of the urinary bladder. Although the strains showed substantial zones of inhibition when tested against cephalosporins by the disc diffusion method, the results in the bladder model suggest that, in conditions where the antibiotic concentration is being reduced by dilution and micturition as well as enzymic hydrolysis by the organism, activity of this group of agents may be insufficient to eradicate infection. It is suggested that the results warrant a closer investigation into the efficacy of cephalosporins against ampicillin resistant Gram negative bacilli in vivo. PMID:1106751

  19. Response of ampicillin resistant Escherichia coli to cephalosporins in an in vitro model simulating conditions of bacterial growth in the urinary bladder.

    PubMed

    Greenwood, D; O'Grady, F

    1975-04-01

    Five ampicillin resistant strains of Escherichia coli were exposed to cephalosporins in an in vitro model which simulates the hydrokinetic features of the urinary bladder. Although the strains showed substantial zones of inhibition when tested against cephalosporins by the disc diffusion method, the results in the bladder model suggest that, in conditions where the antibiotic concentration is being reduced by dilution and micturition as well as enzymic hydrolysis by the organism, activity of this group of agents may be insufficient to eradicate infection. It is suggested that the results warrant a closer investigation into the efficacy of cephalosporins against ampicillin resistant Gram negative bacilli in vivo. PMID:1106751

  20. Antibiotic Susceptibilities of Bacteria Isolated within the Oral Flora of Florida Blacktip Sharks: Guidance for Empiric Antibiotic Therapy

    PubMed Central

    Unger, Nathan R.; Ritter, Erich; Borrego, Robert; Goodman, Jay; Osiyemi, Olayemi O.

    2014-01-01

    Sharks possess a variety of pathogenic bacteria in their oral cavity that may potentially be transferred into humans during a bite. The aim of the presented study focused on the identification of the bacteria present in the mouths of live blacktip sharks, Carcharhinus limbatus, and the extent that these bacteria possess multi-drug resistance. Swabs were taken from the oral cavity of nineteen live blacktip sharks, which were subsequently released. The average fork length was 146 cm (±11), suggesting the blacktip sharks were mature adults at least 8 years old. All swabs underwent standard microbiological work-up with identification of organisms and reporting of antibiotic susceptibilities using an automated microbiology system. The oral samples revealed an average of 2.72 (±1.4) bacterial isolates per shark. Gram-negative bacteria, making up 61% of all bacterial isolates, were significantly (p<0.001) more common than gram-positive bacteria (39%). The most common organisms were Vibrio spp. (28%), various coagulase-negative Staphylococcus spp. (16%), and Pasteurella spp. (12%). The overall resistance rate was 12% for all antibiotics tested with nearly 43% of bacteria resistant to at least one antibiotic. Multi-drug resistance was seen in 4% of bacteria. No association between shark gender or fork length with bacterial density or antibiotic resistance was observed. Antibiotics with the highest overall susceptibility rates included fluoroquinolones, 3rd generation cephalosporins and sulfamethoxazole/trimethoprim. Recommended empiric antimicrobial therapy for adult blacktip shark bites should encompass either a fluoroquinolone or combination of a 3rd generation cephalosporin plus doxycycline. PMID:25110948

  1. Strategic alliance between the infectious diseases specialist and intensive care unit physician for change in antibiotic use.

    PubMed

    Curcio, D; Belloni, R

    2005-02-01

    There is a general consensus that antimicrobial use in intensive care units (ICU) is greater than that in general wards. By implementing a strategy of systematic infectious disease consultations in agreement with the ICU chief, we have modified the antibiotic prescription habits of the ICU physician. A reduction was observed in the use of selected antibiotics (third-generation cephalosporins, vancomycin, carbapenems and piperacillin-tazobactam), with a significant reduction in the length of hospital stay for ICU patients and lower antibiotic costs without negative impact on patient mortality. Leadership by the infectious diseases consultant in combination with commitment by ICU physicians is a simple and effective method to change antibiotic prescription habits in the ICU. PMID:15828447

  2. [Antibiotic treatment of complicated urinary tract infections].

    PubMed

    Peters, H J

    1995-06-01

    The diagnosis of an urinary tract infection (UTI) is proved by the identification of a significant leucocyturia and bacteriuria of the mid-stream urine analysis in men and catheter urine in women. A diagnostical localisation is possible by the case history as well as clinical, sonographical and laboratory tests (leucocytes, CRP) to classify into a cystitis and infection of the parenchyma, respectively an uncomplicated or complicated UTI. Untreated complicated urinary tract infections have a bad prognosis. The therapy consists of bed rest, normalization of the urinary flow, a specific antibiotic therapy corresponding to the antibiotic sensitivity pattern and the administration of a prostaglandin-synthesis-inhibitor. Every physician should choose one of the many antibiotics and must get acquainted with the pharmacokinetics and side-effects. In severe acute infections, a calculated antibiotic therapy in certain combinations is necessary until the bacteriological findings are known. Corresponding to the spectrum of bacteria in complicated UTI, one should select a fluoro-chinolone, a broad-spectrum penicilline in combination with a beta-lactamase-inhibitor, a cephalosporine of the second and third generation with a relative stability against beta-lactamase as well as an aminoglycoside. Reserve-antibiotics for special indications are for example, cefsulodine. Less effective than the drugs mentioned above is cotrimoxazole, which was favourized before. In complicated UTI, the older gyrase-inhibitors like nalidixic acid, pipemidic acid, cinoxacin and nitrofurantoin are not longer indicated. There is only one indication for the application of doxycyclin: the treatment of bacterial prostatitis. A lower dosage of antibiotics and a drug therapy of 7-10 days are sufficient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7668016

  3. Decrease of methicillin resistant Staphylococcus aureus prevalence after introduction of a surgical antibiotic prophylaxis protocol in an Italian hospital.

    PubMed

    Nicastri, Emanuele; Leone, Sebastiano; Petrosillo, Nicola; Ballardini, Milva; Pisanelli, Claudio; Magrini, Patrizia; Cerquetani, Franco; Ippolito, Giuseppe; Comandini, Emma; Narciso, Pasquale; Meledandri, Marcello

    2008-10-01

    The use of antimicrobials is an important factor contributing to the emergence of antibiotic resistance. The goal of our study was to evaluate the impact of the introduction of an antibiotic surgical prophylaxis protocol on the prevalence of methicillin resistant Staphylococcus aureus (MRSA) infections in a tertiary care hospital. The protocol of surgical antibiotic prophylaxis was designed by a multidisciplinary team and was implemented in December 2001. Between January 2002 and December 2002, pharmacy, laboratory and active surveillance-records were prospectively reviewed to calculate prevalence rates of defined daily doses (DDD), microorganism isolation and health-care related infections. A progressive decrease from 1.58 to 0.56 of MRSA isolations per 1000 patient-days and from 76.4% to 29.4% MRSA prevalence rate was reported (p<0.001). Monthly prevalence rates of MRSA showed a significant linear correlation with the reduction of the DDD of the 3rd generation cephalosporins (r=0.90; p<0.001). MRSA surgical site and blood stream infections decreased from 78% to 38% and from 89% to 38%, respectively (p=0.017 and p=0.026). In our experience, the reduction of 3rd generation cephalosporin use was an effective strategy to reduce the MRSA infection rate and was associated with the reduction of the overall expenditure for antibiotics in the hospital. PMID:19123308

  4. Studies on 3?-quaternary ammonium cephalosporins—III. Synthesis and antibacterial activity of 3?-(3-aminopyrazolium)cephalosporins

    Microsoft Academic Search

    Hidenori Ohki; Kohji Kawabata; Yoshiko Inamoto; Shinya Okuda; Toshiaki Kamimura; Kazuo Sakane

    1997-01-01

    The synthesis and in vitro antibacterial activity of 7?-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]cephalosporins bearing N-mono or dialkyl and carbamoyl aminopyrazolium, and five- or six-membered rings fused to the 3-aminopyrazolium methyl groups at the 3-position, are described. Aminopyrazolium methyl cephalosporins (23e, f, i), with fused saturated and unsaturated rings were especially effective against Staphylococcus strains compared to 3-amino-2-methylpyrazolium methyl cephalosporin (1). Among the cephalosporins prepared

  5. evaluation of Eigh different Cephalosporins for Detection of Cephalosporin Resistance in Salmonella enterica and Escherichia coli

    Microsoft Academic Search

    Frank M. Aarestrup; Henrik Hasman; Kees Veldman; Dik Mevius

    2010-01-01

    This study evaluates the efficacy of eight different cephalosporins for detection of cephalosporin resistance mediated by extended spectrum beta-lactamases (ESBL) and plasmidic AmpC beta-lactamases in Salmonella and Escherichia coli. A total of 138 E. coli and 86 Salmonella isolates with known beta-lactamase genes were tested for susceptibility toward cefoperazone, cefotaxime, cefpodoxime, cefquinome, ceftazidime, ceftiofur, ceftriaxone, and cefuroxime using minimum inhibitory

  6. Laboratory antibiotic susceptibility reporting and antibiotic prescribing in general practice.

    PubMed

    Tan, Thean Yen; McNulty, Cliodna; Charlett, Andre; Nessa, Nazma; Kelly, Clare; Beswick, Trevor

    2003-02-01

    This study set out to investigate whether there was an association between antibiotic susceptibility reporting from microbiology laboratories and antibiotic prescribing for urinary tract infections in the community. Data were collected over a 3 month period using a prospective questionnaire survey of general practitioners, who submitted and received a mid-stream urine (MSU) result from selected microbiology laboratories in England and Wales. In addition, prescribing analyses and cost (PACT) data were requested from the Prescription Prescribing Authority. The study demonstrated an association between laboratory reporting of antibiotic susceptibilities and antibiotic prescribing for treatment of urinary tract infections. The reporting of susceptibilities to oral cephalosporins and nitrofurantoin from microbiology laboratories was associated with increased prescribing of each antibiotic. This association was demonstrated for the choice of empirical antibiotic therapy and the choice of antibiotic prescribed for each studied episode of urinary tract infection. PACT data demonstrated a consistently greater use of antibiotics that were reported by the servicing laboratory, although this was only statistically significant for nitrofurantoin. This study demonstrates that there is an association between antibiotic susceptibility reporting from microbiology laboratories and antibiotic prescribing for the treatment of urinary tract infections. PMID:12562706

  7. IN-VITRO SUSCEPTIBILITY OF ESCHERICHIA COLI ISOLATED FROM FECES OF US DAIRY CATTLE TO CEPHALOSPORINS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: The objective of this study was to obtain baseline antimicrobial susceptibility data on E. coli isolated from feces of US dairy cows to the 4th generation cephalosporins (4-GC) cefquinome and cefepime. Cefquinome is licensed for therapeutic use in cattle and swine in Europe, and cefepime...

  8. Efficient and reproducible generation of high-expressing, stable human cell lines without need for antibiotic selection

    Microsoft Academic Search

    Gudrun Schiedner; Sabine Hertel; Corinna Bialek; Helmut Kewes; Gero Waschütza; Christoph Volpers

    2008-01-01

    BACKGROUND: Human cell lines are the most innovative choice of host cell for production of biopharmaceuticals since they allow for authentic posttranslational modification of therapeutic proteins. We present a new method for generating high and stable protein expressing cell lines based on human amniocytes without the requirement of antibiotic selection. RESULTS: Primary amniocytes from routine amniocentesis samples can be efficiently

  9. Hypersensitivity Pneumonitis Caused by Cephalosporins With Identical R1 Side Chains.

    PubMed

    Lee, Sang Hee; Kim, Mi Hyun; Lee, Kwangha; Jo, Eun Jung; Park, Hye Kyung

    2015-09-01

    Drug-induced hypersensitivity pneumonitis results from interactions between pharmacologic agents and the human immune system. We describe a 54-year-old man with hypersensitivity pneumonitis caused by cephalosporins with identical R1 side chains. The patient, who complained of cough with sputum, was prescribed ceftriaxone and clarithromycin at a local clinic. The following day, he complained of dyspnea, and chest X-ray revealed worsening of inflammation. Upon admission to our hospital, antibiotics were changed to cefepime with levofloxacin, but his pneumonia appeared to progress. Changing antibiotics to meropenem with ciprofloxacin improved his symptoms and radiologic findings. Antibiotics were de-escalated to ceftazidime with levofloxacin, and his condition improved. During later treatment, he was mistakenly prescribed cefotaxime, which led to nausea, vomiting, dyspnea and fever, and indications of pneumonitis on chest X-ray. We performed bronchoalveolar lavage, and the findings included lymphocytosis (23%), eosinophilia (17%), and a low cluster of differentiation (CD) 4 to CD8 ratio (0.1), informing a diagnosis of drug-induced pneumonitis. After a medication change, his symptoms improved and he was discharged. One year later, he was hospitalized for acute respiratory distress syndrome following treatment with ceftriaxone and aminoglycosides for an upper respiratory tract infection. After steroid therapy, he recovered completely. In this patient, hypersensitivity reaction in the lungs was caused by ceftriaxone, cefotaxime, and cefepime, but not by ceftazidime, indicating that the patient's hypersensitivity pneumonitis was to the common R1 side chain of the cephalosporins. PMID:25749765

  10. Surveillance of Antibiotic Consumption Using the “Focus of Infection” Approach in 2 Hospitals in Ujjain, India

    PubMed Central

    Pathak, Ashish; Mahadik, Kalpana; Dhaneria, Surya Prakesh; Sharma, Ashish; Eriksson, Bo; Lundborg, Cecilia Stålsby

    2012-01-01

    Antibiotic surveillance initiatives are limited in resource-constrained settings. In the present study, a quantitative comparison of antibiotic use rates for suspected infections in 2 hospitals in India was performed using the “focus of infection” approach to identify targets for quality improvement in antibiotic prescription patterns in hospitalized patients. Methods This observational study was carried out in one teaching and one nonteaching hospital. All the patients with suspected bacterial etiology were included. Data on the prescribed antibiotics and the focus of infection were prospectively collected using a structured questionnaire. Each diagnosis was further reviewed and confirmed by an independent consultant. The prescribed antibiotics were coded according to the World Health Organization Anatomic Therapeutic Classification (ATC) index with the defined daily dose (DDD) methodology. Focus-specific DDDs were calculated per hundred patient days (DDD/HPD). Results A total of 6026 patients were included from 72 participating physicians out of available 75 physicians. Overall antibiotic prescribing was higher by 5 percentage points in the teaching hospital (95%) than in the nonteaching hospital (90%). Quinolones (ciprofloxacin constituting 86% of DDD/HPD) were the highest prescribed class in the teaching hospital, and third-generation cephalosporins (with ceftriaxone and ceftriaxone/sulbactam constituting 40% and 28% of the DDD/HPD, respectively), in the nonteaching hospital. The targets identified for improvement were the following: longer than recommended duration of prophylaxis and lack of distinction between prophylaxis and therapy among surgical patients; irrational antibiotic prescribing in gastroenteritis; overuse of quinolones and lack of use of penicillin in pneumonia; overuse of quinolones and lack of use of doxycycline and macrolides in genital infections; and overreliance on antibiotics for treating skin and soft tissue infections. Conclusions Providing a quantitative comparison of antibiotic use rates for suspected infections, using the “focus of infection” approach along with the ATC/DDD methodology, appears appropriate for identifying targets for quality improvement with regards to antibiotic prescribing. PMID:22715402

  11. Application of a capillary-assembled microfluidic system for separation of cephalosporins.

    PubMed

    Koczka, Peter I; Gaspar, Attila

    2014-09-01

    This paper demonstrates a simple and easy setting up of a fused-silica capillary-assembled microfluidic system (?CE). This system incorporates a split-flow pressure injection of the sample into a microfluidic system made from PDMS and a short (?20 cm) length of fused-silica capillary as a separation unit. The on-capillary detection was carried out by fiber optic spectrometry. A mixture of six cephalosporin antibiotics was separated in the ?CE system and the obtained results were compared to those achievable by conventional CE. The six components could be separated within 8.5 min with the number of theoretical plates around 10?000. PMID:24789628

  12. The eradication of bacterial persisters with antibiotic-generated hydroxyl radical

    E-print Network

    Haseley, Nathan Scott

    During Mycobacterium tuberculosis infection, a population of bacteria likely becomes refractory to antibiotic killing in the absence of genotypic resistance, making treatment challenging. We describe an in vitro model ...

  13. Detection of Favorable Oral Cephalosporin-Clavulanate Interactions by In Vitro Disk Approximation Susceptibility Testing of Extended-Spectrum-Beta-Lactamase-Producing Members of the Enterobacteriaceae

    PubMed Central

    Campbell, Jennifer D.; Lewis, James S.; McElmeel, M. Leticia; Fulcher, Letitia C.

    2012-01-01

    Extended-spectrum-beta-lactamase (ESBL)-producing members of the Enterobacteriaceae are often resistant to multiple drug classes, making therapy of urinary infections with oral antibiotics difficult. Previously it was shown that amoxicillin-clavulanate can provide clavulanate inhibition of ESBLs and protect an oral cephalosporin present in combination when tested by broth microdilution. This study has shown that disk approximation testing could detect favorable cephalosporin-clavulanate interactions among a group of 101 previously characterized members of the Enterobacteriaceae with CTX-M, SHV, or TEM ESBLs. PMID:22170910

  14. [Reduced incidence of Staphylococcus isolation in nosocomial setting after introducing preoperative antibiotic prophylaxis guidelines].

    PubMed

    Gattuso, Gianni; Berra, Davide; Palvarini, Loredana; Tomasoni, Donatella; Chiarelli, Cristina; Stradoni, Raffaello; Scalzini, Alfredo

    2007-12-01

    We compare epidemiological data from two twelve-month periods, before and after the introduction of preoperative antibiotic prophylaxis guidelines at Carlo Poma hospital in Mantova, Italy, in June 2003. Considering the results from the microbiology laboratory and the data from the pharmacy, concerning the consumption of some antimicrobials, we noted a significant decrease in the incidence of methicillin-resistant Staphylococcus aureus (MRSA) in surgical wards, where the incidence of MRSA had previously exceeded that in medical wards. At the same time, analysis of antibiotic consumption revealed a considerable decrease in third and fourth-generation cephalosporins and an increasing use of cephazolin, in compliance with prophylaxis protocol rules. This trend was confirmed by analysis of the same data regarding the first six months of 2006. PMID:18162735

  15. Evaluation of eight different cephalosporins for detection of cephalosporin resistance in Salmonella enterica and Escherichia coli.

    PubMed

    Aarestrup, Frank M; Hasman, Henrik; Veldman, Kees; Mevius, Dik

    2010-12-01

    This study evaluates the efficacy of eight different cephalosporins for detection of cephalosporin resistance mediated by extended spectrum beta-lactamases (ESBL) and plasmidic AmpC beta-lactamases in Salmonella and Escherichia coli. A total of 138 E. coli and 86 Salmonella isolates with known beta-lactamase genes were tested for susceptibility toward cefoperazone, cefotaxime, cefpodoxime, cefquinome, ceftazidime, ceftiofur, ceftriaxone, and cefuroxime using minimum inhibitory concentration determinations and disc diffusion. The collection consisted of 84 ampicillin-susceptible, 57 ampicillin-resistant but cephalosporin-susceptible, 56 ESBL isolates and 19 isolates with plasmidic AmpC, as well as 10 ampC hyper-producing E. coli. The minimum inhibitory concentration distributions and zone inhibitions varied with the tested compound. Ampicillin-resistant isolates showed reduced susceptibility to the cephalosporins compared to ampicillin-susceptible isolates. Cefoperazone, cefquinome, and cefuroxime were not useful in detecting isolates with ESBL or plasmidic AmpC. The best substances for detection were cefotaxime, cefpodoxime, and ceftriaxone, whereas ceftazidime and ceftiofur were not as efficient. Ceftriaxone may be the recommended substance for monitoring because of some ability in separating ampC hyper-producing E. coli from ESBL and plasmidic AmpC isolates. PMID:20624078

  16. Genetic Basis for Vancomycin-Enhanced Cephalosporin Susceptibility in Vancomycin-Resistant Enterococci Revealed Using Counterselection with Dominant-Negative Thymidylate Synthase

    PubMed Central

    Djori?, Dušanka; Little, Jaime L.

    2014-01-01

    Antibiotic-resistant enterococci are major causes of hospital-acquired infections. All enterococci are intrinsically resistant to most cephalosporins, antibiotics in the beta-lactam family that impair peptidoglycan synthesis by inactivating the transpeptidases responsible for cross-linking. In addition, clinical isolates of enterococci often possess acquired resistance to vancomycin, a glycopeptide antibiotic that impairs peptidoglycan biosynthesis by a mechanism distinct from that of the beta-lactams, namely, by binding to the d-Ala-d-Ala termini found in peptidoglycan precursors to prevent their utilization by biosynthetic transglycosylases. Antimicrobial synergism between vancomycin and beta-lactams against vancomycin-resistant enterococci was originally described decades ago, but the genetic basis for synergy has remained unknown. Because a complete understanding of the mechanism underlying synergy between vancomycin and beta-lactams might suggest new targets or strategies for therapeutic intervention against antibiotic-resistant enterococci, we explored the genetic basis for synergy between vancomycin and cephalosporins in Enterococcus faecalis. To do so, we developed a counterselection strategy based on a dominant-negative mutant of thymidylate synthase and implemented this approach to create a panel of mutants in vancomycin-resistant E. faecalis. Our results confirm that vancomycin promotes synergy by inducing expression of the van resistance genes, as a mutant in which the van genes are expressed in the absence of vancomycin exhibits susceptibility to cephalosporins. Further, we show that peptidoglycan precursors substituted with d-Ala-d-Lac are not required for vancomycin-enhanced cephalosporin sensitivity. Instead, production of the d,d-carboxypeptidase VanYB is both necessary and sufficient to dramatically sensitize E. faecalis to cephalosporins. PMID:24366749

  17. Cephalosporin and aminoglycoside utilization in different parts of the world.

    PubMed

    Kumana, C R; Li, K Y; Kou, M; Chan, S C

    1989-12-01

    Cephalosporin and aminoglycoside utilization in Hong Kong during 1984, 1985 and 1986, were evaluated from wholesale data and compared with corresponding Swedish statistics and with UK data from a survey of non-hospital prescriptions. Details regarding each drug and category were collated, adjusted for population and if appropriate expressed as defined daily doses (DDDs)/1000 inhabitants/day. With respect to cephalosporins: (a) overall sales (especially those of the newer and more expensive parenteral drugs) were increasing; (b) parenteral sales were much larger in Hong Kong hospitals than in the community (up to about 106 versus 16 kg/million inhabitants/year respectively), but in Sweden they were comparable (up to about 38 and 41 kg/million inhabitants/year respectively); (c) non-hospital oral utilization appeared greater in the UK than in Sweden and Hong Kong (up to about 0.7, 0.4 and 0.4 DDDs/1000 inhabitants/day respectively); (d) oral sales to hospitals were greater in Hong Kong than Sweden (up to 0.3 compared to 0.1 DDDs/1000 inhabitants/day respectively) and (e) oral paediatric formulations (liquids) were most popular in Hong Kong, a higher proportion of children in Hong Kong being one possible reason. Non-hospital sales of gentamicin and kanamycin in Hong Kong were much greater than in Sweden (up to about 0.20 and 0.06 vs. 0.01 and 0.00 DDDs/1000 inhabitants/day respectively), whereas UK utilization appeared almost non-existent. Topical neomycin sales in Hong Kong were much more popular than in Sweden (up to about 60 vs. 9 g/million inhabitants/day). These regional differences in antibiotic utilization may be related to respective health care systems (and thus the affordability and availability of drugs) and prescribing preferences (cultural and/or promoted by drug companies), quite apart from possible differences in drug efficacy, drug tolerance and the prevalence and severity of various infections. PMID:2621172

  18. Antibiotic Resistance

    MedlinePLUS

    ... lives. But there is a growing problem of antibiotic resistance. It happens when bacteria change and become able ... resistant to several common antibiotics. To help prevent antibiotic resistance Don't use antibiotics for viruses like colds ...

  19. Evolution of an Antibiotic Resistance Enzyme Constrained by Stability and Activity Trade-offs

    Microsoft Academic Search

    Xiaojun Wang; George Minasov; Brian K. Shoichet

    2002-01-01

    Pressured by antibiotic use, resistance enzymes have been evolving new activities. Does such evolution have a cost? To investigate this question at the molecular level, clinically isolated mutants of the ?-lactamase TEM-1 were studied. When purified, mutant enzymes had increased activity against cephalosporin antibiotics but lost both thermodynamic stability and kinetic activity against their ancestral targets, penicillins. The X-ray crystallographic

  20. Industrial production of beta-lactam antibiotics.

    PubMed

    Elander, R P

    2003-06-01

    The industrial production of beta-lactam antibiotics by fermentation over the past 50 years is one of the outstanding examples of biotechnology. Today, the beta-lactam antibiotics, particularly penicillins and cephalosporins, represent the world's major biotechnology products with worldwide dosage form sales of approximately 15 billion US dollars or approximately 65% of the total world market for antibiotics. Over the past five decades, major improvements in the productivity of the producer organisms, Penicillium chrysogenum and Acremonium chrysogenum (syn. Cephalosporium acremonium) and improved fermentation technology have culminated in enhanced productivity and substantial cost reduction. Major fermentation producers are now estimated to record harvest titers of 40-50 g/l for penicillin and 20-25 g/l for cephalosporin C. Recovery yields for penicillin G or penicillin V are now >90%. Chemical and enzymatic hydrolysis process technology for 6-aminopenicillanic acid or 7-aminocephalosporanic acid is also highly efficient (approximately 80-90%) with new enzyme technology leading to major cost reductions over the past decade. Europe remains the dominant manufacturing area for both penicillins and cephalosporins. However, due to ever increasing labor, energy and raw material costs, more bulk manufacturing is moving to the Far East, with China, Korea and India becoming major production countries with dosage form filling becoming more dominant in Puerto Rico and in Ireland. PMID:12679848

  1. Comparative Serum Levels and Protective Activity of Parenterally Administered Cephalosporins in Experimental Animals

    PubMed Central

    Fare, Louis R.; Actor, Paul; Sachs, Carl; Phillips, Lillian; Joloza, MacDonald; Pauls, John F.; Weisbach, Jerry A.

    1974-01-01

    Six cephalosporin antibiotics were administered subcutaneously to mice at a level of 20 mg/kg. The serum levels of each were determined at five time intervals ranging from 5 to 120 min after dosing. Urinary recovery and the presence of active metabolites in mouse urine were determined. The peak serum levels and serum half-lives in mice were found to be positively correlated with the mean effective dose values obtained after lethal challenge with Escherichia coli. The administration of cefazolin and cephanone resulted in the highest serum level and the best protection. Good protection was obtained with cephaloridine despite somewhat lower serum levels. The cephalosporins with the acetoxy side chain (cephalothin, cephapirin, and cephacetrile) showed lower serum levels and the poorest protection. Cefazolin, cephaloridine, and cephalothin serum levels were also determined in dogs, squirrel monkeys, and rabbits. A mixed response was obtained in these species, with cefazolin peak serum levels being highest in rabbits and cephaloridine peak highest in dogs. PMID:15828185

  2. Effect of Variants of Penicillin-Binding Protein 2 on Cephalosporin and Carbapenem Susceptibilities in Neisseria gonorrhoeae.

    PubMed

    Bharat, Amrita; Demczuk, Walter; Martin, Irene; Mulvey, Michael R

    2015-08-01

    To characterize the relationship between penicillin-binding protein 2 (PBP2/penA) and susceptibility to extended-spectrum cephalosporins (ESCs) and carbapenem antibiotics, we compared 17 PBP2 variants in Neisseria gonorrhoeae. Nonmosaic and mosaic variants of PBP2 caused decreased susceptibility to ESCs and, to a lesser extent, to carbapenems. An A501P substitution in mosaic XXXIV_A501P conferred decreased susceptibility to ESCs but restored carbapenem susceptibility to wild-type levels. These results could aid the molecular surveillance of antimicrobial resistance to these agents. PMID:25987627

  3. Efficient and reproducible generation of high-expressing, stable human cell lines without need for antibiotic selection

    PubMed Central

    Schiedner, Gudrun; Hertel, Sabine; Bialek, Corinna; Kewes, Helmut; Waschütza, Gero; Volpers, Christoph

    2008-01-01

    Background Human cell lines are the most innovative choice of host cell for production of biopharmaceuticals since they allow for authentic posttranslational modification of therapeutic proteins. We present a new method for generating high and stable protein expressing cell lines based on human amniocytes without the requirement of antibiotic selection. Results Primary amniocytes from routine amniocentesis samples can be efficiently transformed with adenoviral functions resulting in stable human cell lines. Cotransfection of the primary human amniocytes with a plasmid expressing adenoviral E1 functions plus a second plasmid containing a gene of interest resulted in permanent cell lines expressing up to 30 pg/cell/day of a fully glycosylated and sialylated protein. Expression of the gene of interest is very stable for more than 90 passages and, importantly, was achieved in the absence of any antibiotic selection. Conclusion We describe an improved method for developing high protein expressing stable human cell lines. These cell lines are of non-tumor origin, they are immortalized by a function not oncogenic in human and they are from an ethically accepted and easily accessible cell source. Since the cell can be easily adapted to growth in serum-free and chemically defined medium they fulfill the requirements of biopharmaceutical production processes. PMID:18269738

  4. New antibiotics for bad bugs: where are we?

    PubMed Central

    2013-01-01

    Bacterial resistance to antibiotics is growing up day by day in both community and hospital setting, with a significant impact on the mortality and morbidity rates and the financial burden that is associated. In the last two decades multi drug resistant microorganisms (both hospital- and community-acquired) challenged the scientific groups into developing new antimicrobial compounds that can provide safety in use according to the new regulation, good efficacy patterns, and low resistance profile. In this review we made an evaluation of present data regarding the new classes and the new molecules from already existing classes of antibiotics and the ongoing trends in antimicrobial development. Infectious Diseases Society of America (IDSA) supported a proGram, called “the ?10?×?´20? initiative”, to develop ten new systemic antibacterial drugs within 2020. The microorganisms mainly involved in the resistance process, so called the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and enterobacteriaceae) were the main targets. In the era of antimicrobial resistance the new antimicrobial agents like fifth generation cephalosporins, carbapenems, monobactams, ?-lactamases inhibitors, aminoglycosides, quinolones, oxazolidones, glycopeptides, and tetracyclines active against Gram-positive pathogens, like vancomycin-resistant S. aureus (VRSA) and MRSA, penicillin-resistant streptococci, and vancomycin resistant Enterococcus (VRE) but also against highly resistant Gram-negative organisms are more than welcome. Of these compounds some are already approved by official agencies, some are still in study, but the need of new antibiotics still does not cover the increasing prevalence of antibiotic-resistant bacterial infections. Therefore the management of antimicrobial resistance should also include fostering coordinated actions by all stakeholders, creating policy guidance, support for surveillance and technical assistance. PMID:23984642

  5. A broadly applicable approach to prepare monoclonal anti-cephalosporin antibodies for immunochemical residue determination in milk.

    PubMed

    Bremus, Anna; Dietrich, Richard; Dettmar, Lars; Usleber, Ewald; Märtlbauer, Erwin

    2012-04-01

    A simple, efficient and rapid method for the synthesis of cephalosporin-protein conjugates was established. These conjugates were used as immunogens to produce monoclonal antibodies (mAbs) and as solid phase antigens in competitive indirect enzyme immunoassays (EIAs). With this generic approach, a novel set of monoclonal antibodies for cephalosporins was prepared, including ceftiofur and cephalexin as well as, reported here for the first time, cefoperazone, cefquinome and cephapirin. All 5 EIAs were highly sensitive, with standard curve IC(50) values of 0.7 (ceftiofur), 1.1 (cefquinome), 5.2 (cephalexin), 13.8 (cefoperazone) and 40.3 ng mL(-1) (cephapirin). Detection limits (IC(30)) ranged from 0.3 (ceftiofur mAb 1D7) to 17.2 ng mL(-1) (cephapirin mAb 2F10). Specificity studies revealed that cephalosporin-antibody binding was strongly determined by the side chain residues of the cephem nucleus. Therefore all mAbs, to some extent, recognized other beta-lactam antibiotics with similar side chain residues. Within the group of cephalosporins approved for use in veterinary medicine, however, the final EIAs were highly selective for their respective antigen, except for the ceftiofur EIA which showed cross-reactions with cefquinome. The applicability of the five assays for drug residue testing in milk was demonstrated. In each EIA the target drug could be determined in milk with high accuracy and precision at concentrations far below the European Union maximum residue limits. PMID:22362272

  6. Minimum requirements of hydrophobic and hydrophilic features in cationic peptide antibiotics (CPAs): pharmacophore generation and validation with cationic steroid antibiotics (CSAs)

    Microsoft Academic Search

    Sandeep Sundriyal; Rohit K. Sharma; Rahul Jain; Prasad V. Bharatam

    2008-01-01

    Cationic peptide antibiotics (CPAs) are known to possess amphiphilic structure, by virtue of which they display lytic activity\\u000a against bacterial cell membranes. Naturally occurring antimicrobial peptides contain a large number of amino acid residues,\\u000a which limits their clinical applicability. Recent studies indicate that it is possible to decrease the chain-length of these\\u000a peptides without loss of activity, and suggest that

  7. Animal and Human Multidrug-Resistant, Cephalosporin-Resistant Salmonella Isolates Expressing a Plasmid-Mediated CMY-2 AmpC ?-Lactamase

    PubMed Central

    Winokur, P. L.; Brueggemann, A.; DeSalvo, D. L.; Hoffmann, L.; Apley, M. D.; Uhlenhopp, E. K.; Pfaller, M. A.; Doern, G. V.

    2000-01-01

    Salmonella spp. are important food-borne pathogens that are demonstrating increasing antimicrobial resistance rates in isolates obtained from food animals and humans. In this study, 10 multidrug-resistant, cephalosporin-resistant Salmonella isolates from bovine, porcine, and human sources from a single geographic region were identified. All isolates demonstrated resistance to cephamycins and extended-spectrum cephalosporins as well as tetracycline, chloramphenicol, streptomycin, and sulfisoxazole. Molecular epidemiological analyses revealed eight distinct chromosomal DNA patterns, suggesting that clonal spread could not entirely explain the distribution of this antimicrobial resistance phenotype. However, all isolates encoded an AmpC-like ?-lactamase, CMY-2. Eight isolates contained a large nonconjugative plasmid that could transform Escherichia coli. Transformants coexpressed cephalosporin, tetracycline, chloramphenicol, streptomycin, and sulfisoxazole resistances. Plasmid DNA revealed highly related restriction fragments though plasmids appeared to have undergone some evolution over time. Multidrug-resistant, cephalosporin-resistant Salmonella spp. present significant therapeutic problems in animal and human health care and raise further questions about the association between antimicrobial resistance, antibiotic use in animals, and transfer of multidrug-resistant Salmonella spp. between animals and man. PMID:10991860

  8. Persistence of antibiotic resistant bacteria

    Microsoft Academic Search

    Dan I Andersson

    2003-01-01

    Bacterial adaptation to antibiotics has been very successful and over the past decade the increase in antibiotic resistance has generated considerable medical problems. Even though many drug resistances confer a fitness cost, suggesting that they might disappear by reducing the volume of antibiotic use, increasing evidence obtained from laboratory and epidemiological studies indicate that several processes will act to cause

  9. Stenotrophomonas maltophilia endogenous endophthalmitis: clinical presentation, antibiotic susceptibility, and outcomes

    PubMed Central

    Chhablani, Jay; Sudhalkar, Aditya; Jindal, Animesh; Das, Taraprasad; Motukupally, Swapna R; Sharma, Savitri; Pathengay, Avinash; Flynn, Harry W

    2014-01-01

    Objective To describe clinical presentation, antibiotic susceptibility, and outcomes in patients with Stenotrophomonas maltophilia endogenous endophthalmitis. Design Retrospective case series. Participants Four eyes of four patients with S. maltophilia endogenous endophthalmitis. Methods Retrospective chart review of culture-positive S. maltophilia endogenous endophthalmitis treated at L V Prasad Eye Institute, Hyderabad, India, between January 2007 and December 2012, was done. Collected information included demographic, clinical, and microbiology data. Results These four patients with S. maltophilia endogenous endophthalmitis cases accounted for 0.47% (4/836) of total bacterial endophthalmitis cases treated in this period. All patients were from a rural setting and younger than 40 years. Two of the four patients had a history of immune compromise or hospitalization. The visual acuity at presentation was less than 20/320 in all patients. Common presenting features were severe anterior and posterior segment inflammation and hypopyon. All patients underwent vitrectomy with injection of intravitreal antibiotics and dexamethasone. Direct microscopy of the vitreous sample was positive in all cases. All isolates were sensitive to fluoroquinolones and chloramphenicol; sensitivity to aminoglycosides and third-generation cephalosporins was highly variable. The final visual acuity was 20/80 or more in three patients. The time to presentation did not seem to influence the visual or anatomical outcome. Conclusion S. maltophilia is a rare cause of endogenous endophthalmitis and usually occurs in young and apparently healthy individuals. Clinical presentation is moderate to severe, and recovery is variable. Fourth-generation fluoroquinolones and chloramphenicol were the most sensitive antibiotics against S. maltophilia in this series of patients. PMID:25170244

  10. Synthesis and in vitro antibacterial activity of quaternary ammonium cephalosporin derivatives bearing oxazolidinone moiety

    Microsoft Academic Search

    In Hwa Chung; Choong Sup Kim; Jae Hong Seo; Bong Young Chung

    1999-01-01

    Several oxazolidinones having amine moiety were prepared to form a quaternary ammonium salt with cephalosporin nucleus, and\\u000a antibacterial activity of the quaternary ammonium cephalosporin derivatives bearing oxazolidinone moiety were examined particularly\\u000a with expectation of dual activity. However, the cephalosporin-oxazolidinone compounds revealed rather weaker antibacterial\\u000a activityin vitro than their parent exazolidinone and cephalosporin without showing any characteristic activity as expected.

  11. Bio-inspired synthesis yields a tricyclic indoline that selectively resensitizes methicillin-resistant Staphylococcus aureus (MRSA) to ?-lactam antibiotics

    PubMed Central

    Podoll, Jessica D.; Liu, Yongxiang; Chang, Le; Walls, Shane; Wang, Wei; Wang, Xiang

    2013-01-01

    The continuous emergence of resistant bacteria has become a major worldwide health threat. The current development of new antibacterials has lagged far behind. To discover reagents to fight against resistant bacteria, we initiated a chemical approach by synthesizing and screening a small molecule library, reminiscent of the polycyclic indole alkaloids. Indole alkaloids are a class of structurally diverse natural products, many of which were isolated from plants that have been used as traditional medicine for millennia. Specifically, we adapted an evolutionarily conserved biosynthetic strategy and developed a concise and unified diversity synthesis pathway. Using this pathway, we synthesized 120 polycyclic indolines that contain 26 distinct skeletons and a wide variety of functional groups. A tricyclic indoline, Of1, was discovered to selectively potentiate the activity of ?-lactam antibiotics in multidrug-resistant methicillin-resistant Staphylococcus aureus (MRSA), but not in methicillin-sensitive S. aureus. In addition, we found that Of1 itself does not have antiproliferative activity but can resensitize several MRSA strains to the ?-lactam antibiotics that are widely used in the clinic, such as an extended-spectrum ?-lactam antibiotic amoxicillin/clavulanic acid and a first-generation cephalosporin cefazolin. These data suggest that Of1 is a unique selective resistance-modifying agent for ?-lactam antibiotics, and it may be further developed to fight against resistant bacteria in the clinic. PMID:24019472

  12. Bio-inspired synthesis yields a tricyclic indoline that selectively resensitizes methicillin-resistant Staphylococcus aureus (MRSA) to ?-lactam antibiotics.

    PubMed

    Podoll, Jessica D; Liu, Yongxiang; Chang, Le; Walls, Shane; Wang, Wei; Wang, Xiang

    2013-09-24

    The continuous emergence of resistant bacteria has become a major worldwide health threat. The current development of new antibacterials has lagged far behind. To discover reagents to fight against resistant bacteria, we initiated a chemical approach by synthesizing and screening a small molecule library, reminiscent of the polycyclic indole alkaloids. Indole alkaloids are a class of structurally diverse natural products, many of which were isolated from plants that have been used as traditional medicine for millennia. Specifically, we adapted an evolutionarily conserved biosynthetic strategy and developed a concise and unified diversity synthesis pathway. Using this pathway, we synthesized 120 polycyclic indolines that contain 26 distinct skeletons and a wide variety of functional groups. A tricyclic indoline, Of1, was discovered to selectively potentiate the activity of ?-lactam antibiotics in multidrug-resistant methicillin-resistant Staphylococcus aureus (MRSA), but not in methicillin-sensitive S. aureus. In addition, we found that Of1 itself does not have antiproliferative activity but can resensitize several MRSA strains to the ?-lactam antibiotics that are widely used in the clinic, such as an extended-spectrum ?-lactam antibiotic amoxicillin/clavulanic acid and a first-generation cephalosporin cefazolin. These data suggest that Of1 is a unique selective resistance-modifying agent for ?-lactam antibiotics, and it may be further developed to fight against resistant bacteria in the clinic. PMID:24019472

  13. Hernia, Mesh, and Topical Antibiotics, Especially Gentamycin: Seeking the Evidence for the Perfect Outcome…

    PubMed Central

    Kulacoglu, Hakan

    2015-01-01

    Inguinal hernia repair is a clean surgical procedure and surgical site infection (SSI) rate is generally below 2%. Antibiotic prophylaxis is not routinely recommended, but it may be a good choice for institutions with high rates of wound infection (>5%). Typical prophylaxis is the intravenous application of first or second-generation cephalosporins before the skin incision. However, SSI rate remains more than 2% in many centers in spite of intravenous antibiotic prophylaxis. Even a 1% SSI rate may be unacceptable for the surgeons who specifically deal with hernia surgery. A hernia center targets to be a center of excellence not only in respect of recurrence rate but also for other postoperative outcomes, therefore a further measure is required for an excellent result regarding infection control. Topical gentamycin application in combination with preoperative single-dose intravenous antibiotic may be a useful to obtain this perfect outcome. Data about this subject are not complete and high-grade evidence has not been cumulated yet. Prospective randomized controlled trials can make our knowledge more solid about this subject and help the surgeons who seek perfect outcome regarding infection control in inguinal hernia surgery. PMID:25699259

  14. Minimum requirements of hydrophobic and hydrophilic features in cationic peptide antibiotics (CPAs): pharmacophore generation and validation with cationic steroid antibiotics (CSAs).

    PubMed

    Sundriyal, Sandeep; Sharma, Rohit K; Jain, Rahul; Bharatam, Prasad V

    2008-04-01

    Cationic peptide antibiotics (CPAs) are known to possess amphiphilic structure, by virtue of which they display lytic activity against bacterial cell membranes. Naturally occurring antimicrobial peptides contain a large number of amino acid residues, which limits their clinical applicability. Recent studies indicate that it is possible to decrease the chain-length of these peptides without loss of activity, and suggest that a minimum of two positive ionizable (hydrophilic) and two bulky groups (hydrophobic) are required for antimicrobial activity. By employing the HipHop module of the software package CATALYST, we have translated these experimental findings into 3-D pharmacophore models by finding common features among active peptides. Positively ionizable (PI) and hydrophobic (HYD) features are the important characteristics of compounds used for pharmacophore model development. Based on the highest score and the presence of amphiphilic structure, two separate hypothesis, Ec-2 and Sa-6 for Escherichia coli and Staphylococcus aureus, respectively, were selected for mapping analysis of active and inactive peptides against these organisms. The resulting models not only provided information on the minimum requirement of PI and HYD features but also indicated the importance of their relative arrangement in space. The minimum requirement for PI features was two in both cases but the number of HYD features required in the case of E. coli was four while for S. aureus it was found to be three. These hypotheses were able to differentiate between active and inactive CPAs against both organisms and were able to explain the experimental results. The hypotheses were further validated using cationic steroid antibiotics (CSAs), a different class of facial amphiphiles with same mechanism of antimicrobial action as that of CPAs. The results showed that CSAs also require similar minimum features to be active against both E. coli and S. aureus. These studies also indicate that the minimum feature requirements may be conserved for different strains of the same organism. Figure shows the mapping of an active cationic peptide antibiotic (CPA) mapped to the most acceptable hypothesis Sa6 against S. aureus. PMID:18270757

  15. Cephamycins, a New Family of ?-Lactam Antibiotics I. Production by Actinomycetes, Including Streptomyces lactamdurans sp. n1

    PubMed Central

    Stapley, E. O.; Jackson, M.; Hernandez, S.; Zimmerman, S. B.; Currie, S. A.; Mochales, S.; Mata, J. M.; Woodruff, H. B.; Hendlin, D.

    1972-01-01

    A number of actinomycetes isolated from soil were found to produce one or more members of a new family of antibiotics, the cephamycins, which are structurally related to cephalosporin C. The cephamycins were produced in submerged fermentation in a wide variety of media by one or more of eight different species of Streptomyces, including a newly described species, S. lactamdurans. These antibiotics exhibit antibacterial activity against a broad spectrum of bacteria which includes many that are resistant to the cephalosporins and penicillins. PMID:4790552

  16. Do antibiotics maintain antibiotic resistance?

    Microsoft Academic Search

    Jack A. Heinemann; Robert G. Ankenbauer; Carlos F. Amábile-Cuevas

    2000-01-01

    Important human pathogens resistant to antibiotics result from the human use of antibiotics. Does this imply that reducing their usage or removing antibiotics from medicine and agriculture will restore the effectiveness of these drugs? The authors argue that resistance evolution and susceptibility evolution are not, in a sense, just different sides of the same coin. Resistance genes acquire new functions

  17. Antibiotic Attack

    NSDL National Science Digital Library

    2012-06-26

    In this online simulation, learners use antibiotics to cure patients with bacterial infections. When learners use an antibiotic to treat the infection, sometimes the bacteria mutates so stronger antibiotics are needed. Learners are dissuaded from using the strongest antibiotic since it causes the greatest side effects. When learners set up a free account at Kinetic City, they can answer bonus questions at the end of the activity as a quick assessment. As a larger assessment, learners can complete the Smart Attack game after they've completed several activities.

  18. Two-Year Surveillance of Antibiotic Resistance in Streptococcus pneumoniae in Four African Cities

    PubMed Central

    Benbachir, Mohamed; Benredjeb, Saida; Boye, Cheick Saadbouh; Dosso, Mireille; Belabbes, Houria; Kamoun, Aouatef; Kaire, Omar; Elmdaghri, Naima

    2001-01-01

    Worldwide spread of antibiotic resistance in Streptococcus pneumoniae is a major problem. However, data from West and North African countries are scarce. To study the level of resistance and compare the situations in different cities, a prospective study was conducted in Abidjan (Ivory Coast), Casablanca (Morocco), Dakar (Senegal), and Tunis (Tunisia), from 1996 to 1997. The resistances to eight antibiotics of 375 isolates were studied by E test, and the results were interpreted using the breakpoints recommended by the National Committee for Clinical Laboratory Standards. Overall, 30.4% of the isolates were nonsusceptible to penicillin G (25.6% were intermediate and 4.8% were resistant). Amoxicillin (96.3% were susceptible) and parenteral third-generation cephalosporins (92.7%) were highly active. Resistance to chloramphenicol was detected in 8.6% of the isolates. High levels of resistance were noted for erythromycin (28%), tetracycline (38.3%), and cotrimoxazole (36.4%). Resistance to rifampin was rare (2.1%). There were significant differences in resistance rates between individual countries. Multiple resistance was more frequent in penicillin-nonsusceptible isolates than in penicillin-susceptible isolates. Recommendations for treatment could be generated from these results in each participating country. PMID:11158769

  19. Selective Densitometric Analysis of Cephalosporins Using Dragendorff’s Reagent

    Microsoft Academic Search

    Fardous A. Mohamed; Gamal A. Saleh; Salwa R. El-Shaboury; Azza H. Rageh

    2008-01-01

    A simple, selective, precise, and stability-indicating thin-layer chromatographic method has been developed and validated\\u000a for analysis of the cephalosporins cefpodoxime proxetil, ceftriaxone sodium, ceftazidime pentahydrate, cefotaxime sodium,\\u000a cefoperazone sodium, cefazolin sodium, and cefixime in the bulk drug and in pharmaceutical formulations. TLC was performed\\u000a on aluminium sheets precoated with silica gel G 60F254 as stationary phase. The mobile phases chosen

  20. Antibiotic prescribing in women during and after delivery in a non-teaching, tertiary care hospital in Ujjain, India: a prospective cross-sectional study

    PubMed Central

    2013-01-01

    Objectives Antibacterial drugs (hereafter referred to as antibiotics) are crucial to treat infections during delivery and postpartum period to reduce maternal mortality. Institutional deliveries have the potential to save lives of many women but extensive use of antibiotics, add to the development and spread of antibiotic resistance. The aim of this study was to present antibiotic prescribing among inpatients during and after delivery in a non-teaching, tertiary care hospital in the city of Ujjain, Madhya Pradesh, India. Methods A prospective cross-sectional study was conducted including women having had either a vaginal delivery or a cesarean section in the hospital. Trained nursing staff collected the data on daily bases, using a specific form attached to each patient file. Statistical analysis, including bivariate and multivariable logistic regression was conducted. Results Of the total 1077 women, 566 (53%) had a vaginal delivery and 511 (47%) had a cesarean section. Eighty-seven percent of the women that had a vaginal delivery and 98% of the women having a cesarean section were prescribed antibiotics. The mean number of days on antibiotics in hospital for the women with a vaginal delivery was 3.1 (±1.7) and for the women with cesarean section was 6.0 (±2.5). Twenty-eight percent of both the women with vaginal deliveries and the women with cesarean sections were prescribed antibiotics at discharge. The most commonly prescribed antibiotic group in the hospital for both the women that had a vaginal delivery and the women that had a cesarean section were third-generation cephalosporins (J01DD). The total number of defined daily doses (DDD) per100 bed days for women that had a vaginal delivery was 101, and 127 for women that had a cesarean section. Conclusions The high percentage of women having had a vaginal delivery that received antibiotics and the deviation from recommendation for cesarean section in the hospital is a cause of concern. Improved maternal health and rational use of antibiotics are intertwined. Specific policy and guidelines on how to prescribe antibiotics during delivery at health care facilities are needed. Additionally, monitoring system of antibiotic prescribing and resistance needs to be developed and implemented. PMID:25848538

  1. Assessing the Contributions of the LiaS Histidine Kinase to the Innate Resistance of Listeria monocytogenes to Nisin, Cephalosporins, and Disinfectants

    PubMed Central

    Collins, Barry; Guinane, Caitriona M.; Ross, R. Paul

    2012-01-01

    The Listeria monocytogenes LiaSR two-component system (2CS) encoded by lmo1021 and lmo1022 plays an important role in resistance to the food preservative nisin. A nonpolar deletion in the histidine kinase-encoding component (?liaS) resulted in a 4-fold increase in nisin resistance. In contrast, the ?liaS strain exhibited increased sensitivity to a number of cephalosporin antibiotics (and was also altered with respect to its response to a variety of other antimicrobials, including the active agents of a number of disinfectants). This pattern of increased nisin resistance and reduced cephalosporin resistance in L. monocytogenes has previously been associated with mutation of a second histidine kinase, LisK, which is a predicted regulator of liaS and a penicillin binding protein encoded by lmo2229. We noted that lmo2229 transcription is increased in the ?liaS mutant and in a ?liaS ?lisK double mutant and that disruption of lmo2229 in the ?liaS ?lisK mutant resulted in a dramatic sensitization to nisin but had a relatively minor impact on cephalosporin resistance. We anticipate that further efforts to unravel the complex mechanisms by which LiaSR impacts on the antimicrobial resistance of L. monocytogenes could facilitate the development of strategies to increase the susceptibility of the pathogen to these agents. PMID:22327581

  2. 77 FR 735 - New Animal Drugs; Cephalosporin Drugs; Extralabel Animal Drug Use; Order of Prohibition

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-06

    ...Streptococcus agalactiae and Staphylococcus aureus. C. Mechanism of Cephalosporin...2) inadequate animal identification systems for monitoring treated...27. Zhao, S. et al. Identification and expression of...

  3. Assessment of copper and zinc salts as selectors of antibiotic resistance in Gram-negative bacteria.

    PubMed

    Becerra-Castro, Cristina; Machado, Rita A; Vaz-Moreira, Ivone; Manaia, Célia M

    2015-10-15

    Some metals are nowadays considered environmental pollutants. Although some, like Cu and Zn, are essential for microorganisms, at high concentrations they can be toxic or exert selective pressures on bacteria. This study aimed to assess the potential of Cu or Zn as selectors of specific bacterial populations thriving in wastewater. Populations of Escherichia coli recovered on metal-free and metal-supplemented culture medium were compared based on antibiotic resistance phenotype and other traits. In addition, the bacterial groups enriched after successive transfers in metal-supplemented culture medium were identified. At a concentration of 1mM, Zn produced a stronger inhibitory effect than Cu on the culturability of Enterobacteriaceae. It was suggested that Zn selected populations with increased resistance prevalence to sulfamethoxazole or ciprofloxacin. In non-selective culture media, Zn or Cu selected for mono-species populations of ubiquitous Betaproteobacteria and Flavobacteriia, such as Ralstonia pickettii or Elizabethkingia anophelis, yielding multidrug resistance profiles including resistance against carbapenems and third generation cephalosporins, confirming the potential of Cu or Zn as selectors of antibiotic resistant bacteria. PMID:26057541

  4. Retrospective analysis of antibiotic resistance pattern to urinary pathogens in a Tertiary Care Hospital in South India

    PubMed Central

    Somashekara, Saligrama Chikkannasetty; Deepalaxmi, Salmani; Jagannath, Narumalla; Ramesh, Bannaravuri; Laveesh, Madathil Ravindran; Govindadas, Damodaram

    2014-01-01

    Context: The distribution of uropathogens and their susceptibility pattern to antibiotics vary regionally and even in the same region, they change over time. Therefore, the knowledge on the frequency of the causative microorganisms and their susceptibility to various antibiotics are necessary for a better therapeutic outcome. Aim: The aim was to study the frequency and distribution of uropathogens and their resistance pattern to antibiotics in a tertiary care hospital. Settings and Design: Retrospective study for a period of 1 year from January 2011 to December 2011 in a tertiary care hospital. Materials and Methods: The culture and sensitivity data of the uropathogens from suspected cases of UTI were collected from the records of Microbiology Department for study period. Midstream urine samples were processed for microscopy and culture, and the organisms were identified by standard methods. Antibiotic susceptibility was carried out by Kirby-Bauer disk diffusion method according to Clinical and Laboratory Standards Institute guidelines. Descriptive statistics were used to analyze the data. Results: Of 896 urine samples, 348 (38.84%) samples were positive for urine culture. Escherichia coli (52.59%) was the most common organism followed by Klebsiella. E. coli was least resistant to imipenem (8%) and amikacin (16%) and was highly resistant to co-trimoxazole (69%) and ampicillin (86%). Klebsiella species were least resistant to amikacin (26%) and were highly resistant to ampicillin (92%). The overall resistance pattern of antibiotics to uropathogens was the highest to nalidixic acid (79%) followed by co-trimoxazole (75%) and ampicillin (72%). Good susceptibility was seen with imipenem and cephalosporins. Conclusion: E. coli is still the most common uropathogen. Nalidixic acid, ampicillin, co-trimoxazole, and first-generation fluoroquinolones have limited value for the treatment of UTI. Sensitivity to imipenem and amikacin are still retained and may be prescribed for complicated UTI. Routine monitoring of drug resistance pattern will help to identify the resistance trends regionally. This will help in the empirical treatment of UTIs to the clinicians. PMID:25316990

  5. Antibiotics Quiz

    MedlinePLUS

    ... Viruses b) Bacteria c) Viruses and Bacteria 2. Bacteria are germs that cause colds and flu. a) ... The Flu c) Cold d) Strep Throat 4. Bacteria that cause infections can become resistant to antibiotics. ...

  6. In vitro activities of ureidopenicillins alone and in combination with amikacin and three cephalosporin antibiotics.

    PubMed

    Moody, J A; Peterson, L R; Gerding, D N

    1984-08-01

    The MIC and MBC activity of mezlocillin alone and in combination with two concentrations of ceftizoxime, moxalactam, and amikacin and a single concentration of cefoxitin was studied in a broth microdilution partial checkerboard against 472 strains of aerobic gram-negative and gram-positive bacteria. Azlocillin was tested alone and in the same combinations against Pseudomonas aeruginosa. Of the gram-negative bacilli tested, 38% were gentamicin resistant. Antagonism (less than or equal to a fourfold ureidopenicillin MIC increase) was observed frequently with combinations of ureidopenicillins plus cefoxitin and sporadically with ureidopenicillins plus ceftizoxime or moxalactam. Partial synergism (less than or equal to a fourfold ureidopenicillin MIC decrease) was evident with both combinations of ureidopenicillins plus amikacin and ureidopenicillins plus ceftizoxime or moxalactam, the percentage being dependent upon the individual species and combinations. PMID:6435516

  7. Thin Layer Chromatographic Analysis of Beta-Lactam Antibiotics

    PubMed Central

    Hancu, Gabriel; Simon, Brigitta; Kelemen, Hajnal; Rusu, Aura; Mircia, Eleonora; Gyéresi, Árpád

    2013-01-01

    Purpose: The paper describes some thin layer chromatographic procedures that allow simple and rapid separation and identification of penicillins and cephalosporins from complex mixtures. Methods: Using silicagel GF254 as stationary phase and selecting different mobile phases we succeeded in the separation of the studied beta-lactamins. Our aim was not only to develop a simple, rapid and efficient method for their separation but also the optimization of the analytical conditions. Results: No system will separate all the beta-lactams, but they could be identified when supplementary information is used from color reactions and/or by using additional chromatographic systems. Conclusion: The right combination of solvent system and detection method allows the identification of the studied penicillins and cephalosporins and can be successfully used in the preliminary analysis beta-lactam antibiotics. PMID:24312862

  8. The Beta Lactam Antibiotics as an Empirical Therapy in a Developing Country: An Update on Their Current Status and Recommendations to Counter the Resistance against Them

    PubMed Central

    Thakuria, Bhaskar; Lahon, Kingshuk

    2013-01-01

    In a developing country like India, where the patients have to bear the cost of their healthcare, the microbiological culture and the sensitivity testing of each and every infection is not feasible. Moreover, there are lacunae in the data storage, management and the sharing of knowledge with respect to the microorganisms which are prevalent in the local geographical area and with respect to the antibiotics which are effective against them. Thus, an empirical therapy for treating infections is imperative in such a setting. The beta lactam antibiotics have been widely used for the empirical treatment of infections since the the discovery of penicillin. Many generations of beta lactams have been launched with, the claims of a higher sensitivity and less resistance, but their sensitivity has drastically decreased over time. Thus, the preference for beta lactams, especially the cephalosporins, as an empirical therapy, among the prescribers was justified initially, but the current sensitivity patterns do not support their empirical use in hospital and community acquired infections. There is a need for increasing the awareness and the attitudinal change among the prescribers, screening of the antibiotic prescriptions, the strict implementation of antibiotic policies in hospital settings, restricting the hospital supplies and avoiding the prescriptions of beta lactams, a regular census of the local sensitivity patterns to formulate and update the antibiotic policies, upgradation of the laboratory facilities for a better and faster detection of the isolates, proper collection, analyses and sharing of the data and the encouragement of the research and development of newer antibiotics with novel mechanisms of action. PMID:23905143

  9. New spectrofluorimetric method for determination of cephalosporins in pharmaceutical formulations.

    PubMed

    Ali Ahmed, Shazalia M; Elbashir, Abdalla A; Suliman, Fakhr Eldin O; Aboul-Enein, Hassan Y

    2013-01-01

    A simple, accurate, precise spectrofluorimetric method has been proposed for the determination of three cephalosporins, namely, cefixime (cefi), cephalexine (ceph), and cefotaxime sodium (cefo) in pharmaceutical formulations. This method is based on a reaction between cephalosporins with 8-hydroxy-1,3,6-pyrenetrisulfonic acid trisodium salt (HPTS) in alkaline medium, at pH 12.0 for cefi and 13.0 for ceph and cefo to give highly fluorescent derivatives extracted with chloroform and subsequent measurements of the formed fluorescent products at 520, 500 and 510?nm after excitation at 480, 470 and 480?nm for cefi, ceph and cefo respectively. The optimum experimental conditions have been studied. Beer's law is obeyed over concentrations of 10-60?ng/mL, 5-35?ng/mL and 10-60?ng/mL for cefi, ceph and cefo, respectively. The detection limits were 4.20?ng/mL, 2.54?ng/mL and 4.09?ng/mL for cefi, ceph and cefo, respectively, with a linear regression correlation coefficient of 0.99783, 0.99705 and 0.9978 and recoveries in ranges 96.96-105.77, 96.13-102.55 and 95.45-105.39% for cefi, ceph and cefo, respectively. This method is simple and can be applied for the determination of cefi, ceph and cefo in pharmaceutical formulations in quality control laboratories. PMID:22991324

  10. Combating Antibiotic Resistance

    NSDL National Science Digital Library

    In the past few years, there have been more reports of bacteria that are increasingly resilient to antibiotics. Understandably, this antibiotic resistance is of great concern to the medical community in terms of public health, and is due largely to the increased use of antibiotics. With this in mind, the United States Food and Drug Administration has developed this Web site to inform the general public about this phenomenon, as well as to provide a number of documents generated by different government agencies about this problem and strategies for combating it. For those unacquainted with the situation, there are several helpful general fact sheets and overviews provided online from the Center for Disease Control and the University of Wisconsin. Additionally, the site contains several papers outlining some general recommendations about how the problem can be contained with the cooperation of doctors, hospitals, and increased awareness of the populace.

  11. Antibiotic interference with oral contraceptive steroid efficacy.

    PubMed

    Siew, C; Gruninger, S E; Burrell, K H

    1991-01-01

    Dentists prescribing antibiotics to women of childbearing age should be aware that current lower dosage oral contraceptives may fail and cause pregnancy, putting the practitioner at risk for damage claims. The most common antibiotics used in dental practice that may compromise oral contraceptive efficacy are penicillins, such as penicillin V, penicillin G, ampicillin, flucloxacillin, tolampicillin, amoxycillin and cloxacillin, and tetracyclines, such as tetracycline, oxytetracycline, doxycycline and chlortetracycline. Other common antibiotics include sulfonamides, erythromycin, metronidazole, griseofulvin and cephalosporins. The physiological basis for failure of the combined pill is loss of gut bacteria, and decreased enteric recycling of estrogen metabolites. The reason why progesterone-only pills may fail is unknown, and probably not related to drug interaction. Studies on blood levels of estrogens are conflicting; furthermore, it is impossible to predict which woman is at risk. Dentists should inform all women of childbearing age of possible failure of oral contraceptives. They should attempt to get an accurate drug history from female patients, and insert a signed copy in patients' record. It would be helpful to remind the pharmacist to label oral contraceptive prescription bottles with warnings about concurrent antibiotic usage. PMID:1886418

  12. A multivalent approach to drug discovery for novel antibiotics.

    PubMed

    Long, Daniel D; Aggen, James B; Christensen, Burton G; Judice, J Kevin; Hegde, Sharath S; Kaniga, Koné; Krause, Kevin M; Linsell, Martin S; Moran, Edmund J; Pace, John L

    2008-10-01

    The design, synthesis and antibacterial activity of novel glycopeptide/beta-lactam heterodimers is reported. Employing a multivalent approach to drug discovery, vancomycin and cephalosporin synthons, A and B respectively, were chemically linked to yield heterodimer antibiotics. These novel compounds were designed to inhibit Gram-positive bacterial cell wall biosynthesis by simultaneously targeting the principal cellular targets of both glycopeptides and beta-lactams. The antibiotics 8a-f displayed remarkable potency against a wide range of Gram-positive organisms including methicillin-resistant Staphylococcus aureus (MRSA). Compound 8e demonstrated excellent bactericidal activity against MRSA (ATCC 33591) and initial evidence supports a multivalent mechanism of action for this important new class of antibiotic. PMID:19168973

  13. Antibiotic / Antimicrobial Resistance Glossary

    MedlinePLUS

    ... What Everyone Should Know What You Can Do Antibiotic Resistance Q&As Fast Facts Antibiotics Quiz Glossary For ... Pharmacists Continuing Education & Curriculum Opportunities Weighing in on Antibiotic Resistance Improving Prescribing Outpatient Antibiotic Stewardship Interventions That Work ...

  14. Antibiotic resistance

    Microsoft Academic Search

    Geoff Scott

    2005-01-01

    If there were no antibiotic resistance, there would little need for microbiology laboratories. Faced with a patient who has a community-acquired or hospital-acquired infection, the doctor must guess the diagnosis, the likely organisms and the likely sensitivity of these bacteria. If Staphylococcus is grown from a blood culture, there is now a likelihood of more than 50% that it will

  15. TCA Cycle-Mediated Generation of ROS Is a Key Mediator for HeR-MRSA Survival under ?-Lactam Antibiotic Exposure

    PubMed Central

    Rosato, Roberto R.; Fernandez, Regina; Paz, Liliana I.; Singh, Christopher R.; Rosato, Adriana E.

    2014-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) is a major multidrug resistant pathogen responsible for several difficult-to-treat infections in humans. Clinical Hetero-resistant (HeR) MRSA strains, mostly associated with persistent infections, are composed of mixed cell populations that contain organisms with low levels of resistance (hetero-resistant HeR) and those that display high levels of drug resistance (homo-resistant HoR). However, the full understanding of ?-lactam-mediated HeR/HoR selection remains to be completed. In previous studies we demonstrated that acquisition of the HoR phenotype during exposure to ?-lactam antibiotics depended on two key elements: (1) activation of the SOS response, a conserved regulatory network in bacteria that is induced in response to DNA damage, resulting in increased mutation rates, and (2) adaptive metabolic changes redirecting HeR-MRSA metabolism to the tricarboxylic acid (TCA) cycle in order to increase the energy supply for cell-wall synthesis. In the present work, we identified that both main mechanistic components are associated through TCA cycle-mediated reactive oxygen species (ROS) production, which temporally affects DNA integrity and triggers activation of the SOS response resulting in enhanced mutagenesis. The present work brings new insights into a role of ROS generation on the development of resistance to ?-lactam antibiotics in a model of natural occurrence, emphasizing the cytoprotective role in HeR-MRSA survival mechanism. PMID:24932751

  16. [Antibiotic treatment of child empyema: lessons from published studies and therapeutic options].

    PubMed

    Gaudelus, J; Dubos, F; Dommergues, M-A; Vu Thien, H; Bingen, E; Cohen, R

    2008-10-01

    Children empyema pose therapeutic problems for reasons that are not clearly established. The pneumococcus is by far the bacteria most often responsible. There is no clinical study demonstrating the superiority of an antibiotic regimen over another. Even though these studies exist, they would be challenged by the evolution of bacterial resistance that may vary depending on different parameters: antibiotic pressure, vaccination etc. Therefore, it is on the microorganism suspected, the data of bacterial resistance and pharmacokinetics-pharmacodynamic (Pk / Pd) parameters that lead to antibiotic choice. An analysis of these elements can lead to the following proposals. For pneumococcal empyema, intravenous 3rd generation cephalosporin at dose of 100mg/kg/day divided 4 injections IV for cefotaxime or 50mg/kg/day in once a day for ceftriaxone. These doses are likely to be doubled in case of pneumococcus resistant to penicillin. Neither fosfomycine or aminoglycosides have a sufficient activity against pneumococcus to be offered in combination. If an association seems useful, the two best candidates are vancomycin and rifampin. For group A streptococcus empyema, clindamycin in association with is certainly the best choice. The recent evolution of resistance to macrolides should lead to check the susceptibility of the bacteria implicated. If S. aureus is susceptible to meticilline (most often), a M penicillin by parenteral route associated with an aminoglycoside is proposed. Fosfomycine can be an alternative to the aminoglycoside. If S. aureus is meticilline resistant, the association vancomycin and rifampicin seems best suited. When no bacteria has been isolated, the choice against pneumococcus resistant seems most appropriate. PMID:19000861

  17. Improving known classes of antibiotics: an optimistic approach for the future.

    PubMed

    Bush, Karen

    2012-10-01

    New antibiotic agents are desperately needed to treat the multidrug-resistant pathogens that continue to emerge at alarming rates. Many of the agents that have entered full clinical development since 1995 have been members of previously accepted classes of antibiotics. Among these are a new aminoglycoside (plazomicin), anti-MRSA cephalosporins (ceftobiprole and ceftaroline), a monocyclic ?-lactam (BAL30072), the ?-lactamase inhibitor combination of tazobactam with the anti-pseudomonal cephalosporin ceftolozane, ?-lactam combinations with new non-?-lactam inhibitors (MK-7655 with imipenem, and avibactam with ceftazidime and ceftaroline), new macrolides (cethromycin and solithromycin), oxazolidinones (tedizolid phosphate and radezolid), and quinolones (delafloxacin, nemonoxacin and JNJ-Q2). Resistance and safety issues have been circumvented by some of these new agents that have well-established mechanisms of action and defined pathways leading toward regulatory approval. PMID:22748801

  18. Evidence for Induction of Integron-Based Antibiotic Resistance by the SOS Response in a Clinical Setting

    PubMed Central

    Hocquet, Didier; Llanes, Catherine; Thouverez, Michelle; Kulasekara, Hemantha D.; Bertrand, Xavier; Plésiat, Patrick; Mazel, Didier; Miller, Samuel I.

    2012-01-01

    Bacterial resistance to ?-lactams may rely on acquired ?-lactamases encoded by class 1 integron-borne genes. Rearrangement of integron cassette arrays is mediated by the integrase IntI1. It has been previously established that integrase expression can be activated by the SOS response in vitro, leading to speculation that this is an important clinical mechanism of acquiring resistance. Here we report the first in vivo evidence of the impact of SOS response activated by the antibiotic treatment given to a patient and its output in terms of resistance development. We identified a new mechanism of modulation of antibiotic resistance in integrons, based on the insertion of a genetic element, the gcuF1 cassette, upstream of the integron-borne cassette blaOXA-28 encoding an extended spectrum ?-lactamase. This insertion creates the fused protein GCUF1-OXA-28 and modulates the transcription, the translation, and the secretion of the ?-lactamase in a Pseudomonas aeruginosa isolate (S-Pae) susceptible to the third generation cephalosporin ceftazidime. We found that the metronidazole, not an anti-pseudomonal antibiotic given to the first patient infected with S-Pae, triggered the SOS response that subsequently activated the integrase IntI1 expression. This resulted in the rearrangement of the integron gene cassette array, through excision of the gcuF1 cassette, and the full expression the ?-lactamase in an isolate (R-Pae) highly resistant to ceftazidime, which further spread to other patients within our hospital. Our results demonstrate that in human hosts, the antibiotic-induced SOS response in pathogens could play a pivotal role in adaptation process of the bacteria. PMID:22719259

  19. Asexual Cephalosporin C Producer Acremonium chrysogenum Carries a Functional Mating Type Locus?

    PubMed Central

    Pöggeler, Stefanie; Hoff, Birgit; Kück, Ulrich

    2008-01-01

    Acremonium chrysogenum, the fungal producer of the pharmaceutically relevant ?-lactam antibiotic cephalosporin C, is classified as asexual because no direct observation of mating or meiosis has yet been reported. To assess the potential of A. chrysogenum for sexual reproduction, we screened an expressed sequence tag library from A. chrysogenum for the expression of mating type (MAT) genes, which are the key regulators of sexual reproduction. We identified two putative mating type genes that are homologues of the ?-box domain gene, MAT1-1-1 and MAT1-1-2, encoding an HPG domain protein defined by the presence of the three invariant amino acids histidine, proline, and glycine. In addition, cDNAs encoding a putative pheromone receptor and pheromone-processing enzymes, as well as components of a pheromone response pathway, were found. Moreover, the entire A. chrysogenum MAT1-1 (AcMAT1-1) gene and regions flanking the MAT region were obtained from a genomic cosmid library, and sequence analysis revealed that in addition to AcMAT1-1-1 and AcMAT1-1-2, the AcMAT1-1 locus comprises a third mating type gene, AcMAT1-1-3, encoding a high-mobility-group domain protein. The ?-box domain sequence of AcMAT1-1-1 was used to determine the phylogenetic relationships of A. chrysogenum to other ascomycetes. To determine the functionality of the AcMAT1-1 locus, the entire MAT locus was transferred into a MAT deletion strain of the heterothallic ascomycete Podospora anserina (the Pa?MAT strain). After fertilization with a P. anserina MAT1-2 (MAT+) strain, the corresponding transformants developed fruiting bodies with mature ascospores. Thus, the results of our functional analysis of the AcMAT1-1 locus provide strong evidence to hypothesize a sexual cycle in A. chrysogenum. PMID:18689517

  20. Antibiotic-Resistant Fecal Bacteria, Antibiotics, and Mercury in Surface Waters of Oakland County, Michigan, 2005-2006

    USGS Publications Warehouse

    Fogarty, Lisa R.; Duris, Joseph W.; Crowley, Suzanne L.; Hardigan, Nicole

    2007-01-01

    Water samples collected from 20 stream sites in Oakland and Macomb Counties, Mich., were analyzed to learn more about the occurrence of cephalosporin-resistant Escherichia coli (E. coli) and vancomycin-resistant enterococci (VRE) and the co-occurrence of antibiotics and mercury in area streams. Fecal indicator bacteria concentrations exceeded the Michigan recreational water-quality standard of 300 E. coli colony-forming units (CFU) per 100 milliliters of water in 19 of 35 stream-water samples collected in Oakland County. A gene commonly associated with enterococci from humans was detected in samples from Paint Creek at Rochester and Evans Ditch at Southfield, indicating that human fecal waste is a possible source of fecal contamination at these sites. E. coli resistant to the cephalosporin antibiotics (cefoxitin and/or ceftriaxone) were found at all sites on at least one occasion. The highest percentages of E. coli isolates resistant to cefoxitin and ceftriaxone were 71 percent (Clinton River at Auburn Hills) and 19 percent (Sashabaw Creek near Drayton Plains), respectively. Cephalosporin-resistant E. coli was detected more frequently in samples from intensively urbanized or industrialized areas than in samples from less urbanized areas. VRE were not detected in any sample collected in this study. Multiple antibiotics (azithromycin, erythromycin, ofloxacin, sulfamethoxazole, and trimethoprim) were detected in water samples from the Clinton River at Auburn Hills, and tylosin (an antibiotic used in veterinary medicine and livestock production that belongs to the macrolide group, along with erythromycin) was detected in one water sample from Paint Creek at Rochester. Concentrations of total mercury were as high as 19.8 nanograms per liter (Evans Ditch at Southfield). There was no relation among percentage of antibiotic-resistant bacteria and measured concentrations of antibiotics or mercury in the water. Genetic elements capable of exchanging multiple antibiotic-resistance genes (class I integrons) were detected in several samples, indicating that the resistance carried by these organisms may be transferable to other bacteria, including disease-causing bacteria.

  1. Total Synthesis of the Antitumor Antibiotic (±)-Streptonigrin: First- and Second-Generation Routes for de Novo Pyridine Formation Using Ring-Closing Metathesis

    PubMed Central

    2013-01-01

    The total synthesis of (±)-streptonigrin, a potent tetracyclic aminoquinoline-5,8-dione antitumor antibiotic that reached phase II clinical trials in the 1970s, is described. Two routes to construct a key pentasubstituted pyridine fragment are depicted, both relying on ring-closing metathesis but differing in the substitution and complexity of the precursor to cyclization. Both routes are short and high yielding, with the second-generation approach ultimately furnishing (±)-streptonigrin in 14 linear steps and 11% overall yield from inexpensive ethyl glyoxalate. This synthesis will allow for the design and creation of druglike late-stage natural product analogues to address pharmacological limitations. Furthermore, assessment of a number of chiral ligands in a challenging asymmetric Suzuki–Miyaura cross-coupling reaction has enabled enantioenriched (up to 42% ee) synthetic streptonigrin intermediates to be prepared for the first time. PMID:24328139

  2. Characterization of Novel Mycobacterium tuberculosis and Mycobacterium smegmatis Mutants Hypersusceptible to  Lactam Antibiotics

    Microsoft Academic Search

    Anthony R. Flores; Linda M. Parsons; Martin S. Pavelka

    2005-01-01

    with deletions in the genes for their major -lactamases, BlaC and BlaS, respectively, and showed that the mutants have increased susceptibilities to most -lactam antibiotics, particularly the penicillins. However, there is still a basal level of resistance in the mutants to certain penicillins, and the susceptibilities of the mutants to some cephalosporin-based -lactams are essentially the same as those of

  3. How Antibiotics Work

    NSDL National Science Digital Library

    VU Bioengineering RET Program,

    Students are introduced to a challenge question. Towards answering the question, they generate ideas for what they need to know about medicines and how they move through our bodies, watch a few short videos to gain multiple perspectives, and then learn lecture material to obtain a basic understanding of how antibiotics kill bacteria in the human body. They learn why different forms of medicine (pill, liquid or shot) get into the blood stream at different speeds.

  4. Nutritional Control of Antibiotic Resistance via an Interface between the Phosphotransferase System and a Two-Component Signaling System

    PubMed Central

    Snyder, Holly; Kellogg, Stephanie L.; Skarda, Laura M.; Little, Jaime L.

    2014-01-01

    Enterococci are ubiquitous inhabitants of the gastrointestinal (GI) tract. However, antibiotic-resistant enterococci are also major causes of hospital-acquired infections. Enterococci are intrinsically resistant to cephalosporins, enabling growth to abnormally high densities in the GI tract in patients during cephalosporin therapy, thereby promoting dissemination to other sites where they cause infection. Despite its importance, many questions about the underlying basis for cephalosporin resistance remain. A specific two-component signaling system, composed of the CroS sensor kinase and its cognate response regulator (CroR), is required for cephalosporin resistance in Enterococcus faecalis, but little is known about the factors that control this signaling system to modulate resistance. To explore the signaling network in which CroR participates to influence cephalosporin resistance, we employed a protein fragment complementation assay to detect protein-protein interactions in E. faecalis cells, revealing a previously unknown association of CroR with the HPr protein of the phosphotransferase system (PTS) responsible for carbohydrate uptake and catabolite control of gene expression. Genetic and physiological analyses indicate that association with HPr restricts the ability of CroR to promote cephalosporin resistance and gene expression in a nutrient-dependent manner. Mutational analysis suggests that the interface used by HPr to associate with CroR is distinct from the interface used to associate with other cellular partners. Our results define a physical and functional connection between a critical nutrient-responsive signaling system (the PTS) and a two-component signaling system that drives antibiotic resistance in E. faecalis, and they suggest a general strategy by which bacteria can integrate their nutritional status with diverse environmental stimuli. PMID:24277024

  5. Synthesis and structure–activity relationships of quaternary ammonium cephalosporins with 3-pyrazolylpyridinium derivatives

    Microsoft Academic Search

    Kwan Young Chang; Sung Hoon Kim; Ghilsoo Nam; Jae Hong Seo; Joong Hyup Kim; Deok-Chan Ha

    2000-01-01

    Cephalosporins with 3-pyazolylpyridinium at C-3 position, which is supposed to exhibit synergic activity of ceftazidime and cefoselis, were synthesized and their antibacterial activity against Gram-positive and Gram-negative was inspected.

  6. Antibiotic prescribing for adults with acute cough/lower respiratory tract infection: congruence with guidelines.

    PubMed

    Wood, J; Butler, C C; Hood, K; Kelly, M J; Verheij, T; Little, P; Torres, A; Blasi, F; Schaberg, T; Goossens, H; Nuttall, J; Coenen, S

    2011-07-01

    European guidelines for treating acute cough/lower respiratory tract infection (LRTI) aim to reduce nonevidence-based variation in prescribing, and better target and increase the use of first-line antibiotics. However, their application in primary care is unknown. We explored congruence of both antibiotic prescribing and antibiotic choice with European Respiratory Society (ERS)/European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines for managing LRTI. The present study was an analysis of prospective observational data from patients presenting to primary care with acute cough/LRTI. Clinicians recorded symptoms on presentation, and their examination and management. Patients were followed up with self-complete diaries. 1,776 (52.7%) patients were prescribed antibiotics. Given patients' clinical presentation, clinicians could have justified an antibiotic prescription for 1,915 (71.2%) patients according to the ERS/ESCMID guidelines. 761 (42.8%) of those who were prescribed antibiotics received a first-choice antibiotic (i.e. tetracycline or amoxicillin). Ciprofloxacin was prescribed for 37 (2.1%) and cephalosporins for 117 (6.6%). A lack of specificity in definitions in the ERS/ESCMID guidelines could have enabled clinicians to justify a higher rate of antibiotic prescription. More studies are needed to produce specific clinical definitions and indications for treatment. First-choice antibiotics were prescribed to the minority of patients who received an antibiotic prescription. PMID:21233267

  7. Studies on 3?-quaternary ammonium cephalosporins—IV. Synthesis and antibacterial activity of 3?-(2-alkyl-3-aminopyrazolium)cephalosporins related to FK037

    Microsoft Academic Search

    Hidenori Ohki; Kohji Kawabata; Yoshiko Inamoto; Shinya Okuda; Toshiaki Kamimura; Kazuo Sakane

    1997-01-01

    The synthesis and in vitro antibacterial activity of 7?-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido] cephalosporins bearing various 2-alkyl-3-aminopyrazolium groups at the 3-position are described. Antibacterial activity against MRSA was affected by the nature of the substituent at the 2-position on the 3?-aminopyrazolium groups. Among the cephalosporins prepared in this study, 7?-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-[3-amino-2-(2-hydroxyethyl)-pyrazolio]methyl-3-cephem-4-carboxylate sulfate (23e, FK037) showed extremely potent broad-spectrum activity against both Gram-positive bacteria including MRSA,

  8. Facts about Antibiotic Resistance

    MedlinePLUS

    ... and Cost Español: Datos breves Facts about Antibiotic Resistance Antibiotic resistance has been called one of the world’s most ... antibiotic use is a key strategy to control antibiotic resistance. Antibiotic resistance in children is of particular concern ...

  9. Five-year assessment of causative agents and antibiotic resistances in urinary tract infections

    PubMed Central

    Çoban, Bayram; Ülkü, Nesrin; Kaplan, Halit; Topal, Burhan; Erdo?an, Haluk; Bask?n, Esra

    2014-01-01

    Aim: To show the distribution and changes of causative agents of urinary tract infections in children and resistance rates by years and select the most appropriate antibiotics. Material and Methods: In this study, the Ba?kent University Alanya Research and Application Hospital automation system microbiology recording book was screened retrospectively. Growth of a single microorganism above 105 colonies (cfu/mL) was included in the assessment. Throughout the study, 10 691 urinary cultures were studies and growth was found in 392 (3.7%). Results: Three hundred and nine (78.8%) of the samples with growth belonged to girls. Growth was found in the neonatal period in 32 patients (8.2%). The most commonly isolated microorganism was Escherichia coli (E. coli) which was found in 68.4% of the patients. Klebsiella spp. were found with a rate of 12.0%; Enterobacter spp. were found with a rate of 10.7% and proteus spp. were found with a rate of 5.1%. Resistance to cefalotin (62.1%), trimethoprim-sulfamethoxasole (43.1%), amoxycillin-clavulanate (34.8%), ampicillin (30.4%), cefixim (26.3%) and nitrofurantoin (3.6%) was found in E. coli species. The antibiotic which had the highest resistance rate was ampicillin with a rate of 93.2% for klebsiella and 83.4% for enterobacter. Klebsiella spp. were the most commonly grown pathogens in newborns (40.6%). In a follow-up period of 5 years, the resistance of E. coli to amoxycillin-clavulanate regressed from 40.3% to 31.3%, while the resistance to trimethoprim-sulfamethoxasole (TMP-SMX) regressed from 45.6% to 34.7%. Conclusions: A high resistance against first-generation cephalosporins, ampicillin, amoxycillin-clavulanate and TMP-SMX which are the first-line antibiotics in childhood urinary tract infections was found. Carbapenem (meropenem, imipenem) resistance was not found in our center. Nitrofurantoin, aminoglycosides and cefixime can be recommended for empirical treatment in our hospital because of low resistance. Antibiotic treatment should be redecided according to in vitro antibiotic sensitivity results.

  10. Human recreational exposure to antibiotic resistant bacteria in coastal bathing waters.

    PubMed

    Leonard, Anne F C; Zhang, Lihong; Balfour, Andrew J; Garside, Ruth; Gaze, William H

    2015-09-01

    Infections caused by antibiotic resistant bacteria (ARB) are associated with poor health outcomes and are recognised globally as a serious health problem. Much research has been conducted on the transmission of ARB to humans. Yet the role the natural environment plays in the spread of ARB and antibiotic resistance genes is not well understood. Antibiotic resistant bacteria have been detected in natural aquatic environments, and ingestion of seawater during water sports is one route by which many people could be directly exposed. The aim was to estimate the prevalence of resistance to one clinically important class of antibiotics (third-generation cephalosporins (3GCs)) amongst Escherichia coli in coastal surface waters in England and Wales. Prevalence data was used to quantify ingestion of 3GC-resistant E. coli (3GCREC) by people participating in water sports in designated coastal bathing waters. A further aim was to use this value to derive a population-level estimate of exposure to these bacteria during recreational use of coastal waters in 2012. The prevalence of 3GC-resistance amongst E. coli isolated from coastal surface waters was estimated using culture-based methods. This was combined with the density of E. coli reported in designated coastal bathing waters along with estimations of the volumes of water ingested during various water sports reported in the literature to calculate the mean number of 3GCREC ingested during different water sports. 0.12% of E. coli isolated from surface waters were resistant to 3GCs. This value was used to estimate that in England and Wales over 6.3 million water sport sessions occurred in 2012 that resulted in the ingestion of at least one 3GCREC. Despite the low prevalence of resistance to 3GCs amongst E. coli in surface waters, there is an identifiable human exposure risk for water users, which varies with the type of water sport undertaken. The relative importance of this exposure is likely to be greater in areas where a large proportion of the population enjoys water sports. Millions of water sport sessions occurred in 2012 that were likely to have resulted in people ingesting E. coli resistant to a single class of antibiotics (3GCs). However, this is expected to be a significant underestimate of recreational exposure to all ARB in seawater. This is the first study to use volumes of water ingested during different water sports to estimate human exposure to ARB. Further work needs to be done to elucidate the health implications and clinical relevance of exposure to ARB in both marine and fresh waters in order to fully understand the risk to public health. PMID:25832996

  11. Comparative study of the susceptibilities of major epidemic clones of methicillin-resistant Staphylococcus aureus to oxacillin and to the new broad-spectrum cephalosporin ceftobiprole.

    PubMed

    Chung, Marilyn; Antignac, Aude; Kim, Choonkeun; Tomasz, Alexander

    2008-08-01

    Multidrug-resistant strains of Staphylococcus aureus continue to increase in frequency worldwide, both in hospitals and in the community, raising serious problems for the chemotherapy of staphylococcal disease. Ceftobiprole (BPR; BAL9141), the active constituent of the prodrug ceftobiprole medocaril (BAL5788), is a new cephalosporin which was already shown to have powerful activity against a number of bacterial pathogens, including S. aureus. In an effort to test possible limits to the antibacterial spectrum and efficacy of BPR, we examined the susceptibilities of the relatively few pandemic methicillin-resistant S. aureus (MRSA) clones that are responsible for the great majority of cases of staphylococcal disease worldwide. We also included in the tests the highly oxacillin-resistant subpopulations that are present with low frequencies in the cultures of these clones. Such subpopulations may represent a natural reservoir from which MRSA strains with decreased susceptibility to BPR may emerge in the future. We also tested the efficacy of BPR against MRSA strains with reduced susceptibility to vancomycin and against MRSA strains carrying the enterococcal vancomycin resistance gene complex. BPR was shown to be uniformly effective against all these resistant MRSA strains, and the mechanism of superb antimicrobial activity correlated with the strikingly increased affinity of the cephalosporin against penicillin-binding protein 2A, the protein product of the antibiotic resistance determinant mecA. PMID:18505853

  12. Non-Phenotypic Tests to Detect and Characterize Antibiotic Resistance Mechanisms in Enterobacteriaceae

    PubMed Central

    Lupo, Agnese; Papp-Wallace, Krisztina M.; Sendi, Parham; Bonomo, Robert A.; Endimiani, Andrea

    2014-01-01

    In the past two decades, we have observed a rapid increase of infections due to multidrug-resistant Enterobacteriaceae. Regrettably, these isolates possess genes encoding for extended-spectrum ?-lactamases (e.g., blaCTX-M, blaTEM, blaSHV) or plasmid-mediated AmpCs (e.g., blaCMY) that confer resistance to last-generation cephalosporins. Furthermore, other resistance traits against quinolones (e.g., mutations in gyrA and parC, qnr elements) and aminoglycosides (e.g., aminoglycosides modifying enzymes and 16S rRNA methylases) are also frequently co-associated. Even more concerning is the rapid increase of Enterobacteriaceae carrying genes conferring resistance to carbapenems (e.g., blaKPC, blaNDM). Therefore, the spread of these pathogens puts in peril our antibiotic options. Unfortunately, standard microbiological procedures require several days to isolate the responsible pathogen and to provide correct antimicrobial susceptibility test results. This delay impacts the rapid implementation of adequate antimicrobial treatment and infection control countermeasures. Thus, there is emerging interest in the early and more sensitive detection of resistance mechanisms. Modern non-phenotypic tests are promising in this respect, and hence, can influence both clinical outcome and healthcare costs. In this review, we present a summary of the most advanced methods (e.g., next-generation DNA sequencing, multiplex PCRs, real-time PCRs, microarrays, MALDITOF MS, and PCR/ESI MS) presently available for the rapid detection of antibiotic resistance genes in Enterobacteriaceae. Taking into account speed, manageability, accuracy, versatility, and costs, the possible settings of application (research, clinic, and epidemiology) of these methods and their superiority against standard phenotypic methods are discussed. PMID:24091103

  13. [Looking for the new preparations for antibacterial therapy. I. New antibiotics and chemotherapeutics on the market].

    PubMed

    Karpiuk, Izabela; Tyski, Stefan

    2012-01-01

    Development of new mechanisms of resistance and relatively easy and fast transferring of resistance genes between cells have resulted in emergence of large number of multi-drug resistant bacteria in recent years. Therefore, it is important to intensively search for new, effective compounds possessing antibacterial potential and apply them as active ingredients of medicinal products. This procedure may lead to eradication of clinically relevant, dangerous bacteria. In the twentyfirst century, three new classes of antibacterial agents: oxazolidinones, lipopeptides and pleuromutilins were introduced into the therapy. Compounds from the last group, such as tiamulin, were used previously, but only in veterinary. New 18 antimicrobial compounds, belonging to known therapeutic groups, have been registered since 2000. The largest group among antibacterial chemotherapeutics is quinolones. Group of natural compounds includes: new carbapenems, cephalosporins of V generation and other agents, like telithromycin, tigecycline, telavancin and fidaxomicin. This article is a part of the series associated with searching for new antibacterial agents and it relates to new antibiotics and antibacterial chemotherapeutics approved for the world-wide market since 2000. The next parts of this cycle will be devoted to compounds ongoing the clinical trials. PMID:23484382

  14. Molecular and structural analysis of mosaic variants of penicillin-binding protein 2 conferring decreased susceptibility to expanded-spectrum cephalosporins in Neisseria gonorrhoeae: role of epistatic mutations†

    PubMed Central

    Tomberg, Joshua; Unemo, Magnus; Davies, Christopher; Nicholas, Robert A

    2010-01-01

    Mutations in penicillin-binding protein 2 (PBP 2) encoded by mosaic penA alleles are critical for intermediate resistance to the expanded-spectrum cephalosporins ceftriaxone and cefixime in Neisseria gonorrhoeae. Three of the ~60 mutations present in mosaic alleles of penA, G545S, I312M, and V316T, have been reported to be responsible for increased resistance, especially to cefixime (Takahata et al. 2006. Antimicrob Agents Chemother 50:3638-45). However, we observed that the minimum inhibitory concentrations (MICs) of penicillin, ceftriaxone, and cefixime for a wild type strain (FA19) containing a penA gene with these three mutations increased only 1.5-, 1.5-, and 3.5-fold, respectively. In contrast, when these three mutations in a mosaic penA allele (penA35) were reverted back to wild type and the gene transformed into FA19, the MICs of the three antibiotics were reduced to near wild type levels. Thus, these three mutations display epistasis, in that their capacity to increase resistance to ?-lactam antibiotics is dependent on the presence of other mutations in the mosaic alleles. We also identified an additional mutation, N512Y, that contributes to decreased susceptibility to expanded-spectrum cephalosporins. Finally, we investigated the effects of a mutation (A501V) currently found only in non-mosaic penA alleles on decreased susceptibility to ceftriaxone and cefixime, under the expectation that this mutation may arise in mosaic alleles. Transfer of the mosaic penA35 allele containing an A501V mutation into FA6140, a chromosomally mediated penicillin-resistant isolate, increased the MICs of ceftriaxone (0.4 ?g/ml) and cefixime (1.2?g/ml) to levels above their respective breakpoints. The proposed structural mechanisms of these mutations are discussed in light of the recently published structure of PBP 2. PMID:20704258

  15. Sample preservation for the analysis of antibiotics in water.

    PubMed

    Llorca, Marta; Gros, Meritxell; Rodríguez-Mozaz, Sara; Barceló, Damià

    2014-11-21

    This paper describes a stability study performed for 56 antibiotics belonging to 9 different groups--macrolides, tetracyclines, fluoroquinolones, quinolones, penicillins, cephalosporines, lincosamides, sulfonamides and nitroimidazole antibiotics--in purified water samples fortified with the selected compounds at 10 ng/ml. For this purpose, three different sample preservation modes were tested with the aim of avoiding biotic and abiotic degradation: (i) storage at -20°C, (ii) storage at -20°C with 0.1% of EDTA and (iii) pre-concentration in a solid phase extraction cartridge (SPE), which was afterwards stored at -20°C. Concentrations of antibiotics in the samples preserved using the different protocols were monitored after 0, 1, 2 and 12 weeks. The results showed that, for the accurate determination of all compounds they should be analyzed right after sampling. However, if this is not possible, most of the antibiotics can be analyzed within the 1st week after sampling and preservation at -20°C (with or without EDTA) or in a SPE cartridges at -20°C. Nonetheless, some antibiotics found extensively in the environment, such as sulfamethoxazole, ciprofloxacin, ofloxacin, erythromycin, azithromycin and clarithromycin exhibited low stability after 1 week preservation and, therefore, they should be analyzed within this time. PMID:25441070

  16. Prescription auditing and antimicrobial resistance at a tertiary care hospital in New Delhi, India.

    PubMed

    Wattal, C; Joshi, S; Sharma, A; Oberoi, J K; Prasad, K J

    2005-02-01

    This paper reports the antibiotic consumption data of Sir Ganga Ram Hospital, New Delhi and bacterial resistance over a seven-year period. Cephalosporins, penicillins and fluoroquinolones were the most widely prescribed antibiotics. A correlation was seen between Escherichia coli resistance to third-generation cephalosporins and increased cephalosporin use, as well as resistance to co-amoxyclav and its use. PMID:15620451

  17. Antibiotic resistance in the southeastern Mediterranean--preliminary results from the ARMed project.

    PubMed

    Borg, M A; Scicluna, E; de Kraker, M; van de Sande-Bruinsma, N; Tiemersma, E; Gür, D; Ben Redjeb, S; Rasslan, O; Elnassar, Z; Benbachir, M; Pieridou Bagatzouni, D; Rahal, K; Daoud, Z; Grundmann, H; Monen, J

    2006-07-01

    Sporadic reports from centres in the south and east of the Mediterranean have suggested that the prevalence of antibiotic resistance in this region appears to be considerable, yet pan-regional studies using comparable methodology have been lacking in the past. Susceptibility test results from invasive isolates of Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Enterococcus faecium and faecalis routinely recovered from clinical samples of blood and cerebrospinal fluid within participating laboratories situated in Algeria, Cyprus, Egypt, Jordan, Lebanon, Malta, Morocco, Tunisia and Turkey were collected as part of the ARMed project. Preliminary data from the first two years of the project showed the prevalence of penicillin non-susceptibility in S. pneumoniae to range from 0% (Malta) to 36% (Algeria) [median: 29%] whilst methicillin resistance in Staphylococcus aureus varied from 10% in Lebanon to 65% in Jordan [median: 43%]. Significant country specific resistance in E. coli was also seen, with 72% of isolates from Egyptian hospitals reported to be resistant to third generation cephalosporins and 40% non-susceptible to fluoroquinolones in Turkey. Vancomycin non-susceptibility was only reported in 0.9% of E. faecalis isolates from Turkey and in 3.8% of E. faecium isolates from Cyprus. The preliminary results from the ARMed project appear to support previous sporadic reports suggesting high antibiotic resistance in the Mediterranean region. They suggest that this is particularly the case in the eastern Mediterranean region where resistance in S. aureus and E. coli seems to be higher than that reported in the other countries of the Mediterranean. PMID:16966796

  18. Phenotypic and Genome-Wide Analysis of an Antibiotic-Resistant Small Colony Variant (SCV) of Pseudomonas aeruginosa

    Microsoft Academic Search

    Qing Wei; Saeed Tarighi; Andreas Dötsch; Susanne Häussler; Mathias Müsken; Victoria J. Wright; Miguel Cámara; Paul Williams; Steven Haenen; Bart Boerjan; Annelies Bogaerts; Evy Vierstraete; Peter Verleyen; Liliane Schoofs; Ronnie Willaert; Valérie N. De Groote; Jan Michiels; Ken Vercammen; Aurélie Crabbé; Pierre Cornelis

    2011-01-01

    BackgroundSmall colony variants (SCVs) are slow-growing bacteria, which often show increased resistance to antibiotics and cause latent or recurrent infections. It is therefore important to understand the mechanisms at the basis of this phenotypic switch.Methodology\\/Principal FindingsOne SCV (termed PAO-SCV) was isolated, showing high resistance to gentamicin and to the cephalosporine cefotaxime. PAO-SCV was prone to reversion as evidenced by emergence

  19. Microbial resistance to antibiotics

    Microsoft Academic Search

    IBEZIM EMMANUEL CHINEDUM

    Organisms that are normally sensitive to the action of an antibiotic may sometimes develop resistance or insensitivity to it. This, they may do through destroying the antibiotic or by retaining their growth even in the presence of the drug. Microbial resistance to antibiotics is now widespread and poses a serious clinical threat. Microorganisms develop resistance to antibiotics by any of

  20. Effect of incubation temperature and time on the precision of data generated by antibiotic disc diffusion assays.

    PubMed

    Smith, P; Kronvall, G

    2015-07-01

    The influence on the precision of disc diffusion data of the conditions under which the tests were performed was examined by analysing multilaboratory data sets generated after incubation at 35 °C for 18 h, at 28 °C for 24 h and 22 °C for 24 h and 48 h. Analyses of these data sets demonstrated that precision was significantly and progressively decreased as the test temperature was reduced from 35 to 22 °C. Analysis of the data obtained at 22 °C also showed the precision was inversely related to the time of incubation. Temperature and time related decreases in precision were not related to differences in the mean zone sizes of the data sets obtained under these test conditions. Analysis of the zone data obtained at 28 and 22 °C as single laboratory sets demonstrated that reductions of incubation temperature resulted in significant increases in both intralaboratory and interlaboratory variation. Increases in incubation time at 22 °C were, however, associated with statistically significant increases in interlaboratory variation but not with any significant increase in intralaboratory variation. The significance of these observations for the establishment of the acceptable limits of precision of data sets that can be used for the setting of valid epidemiological cut-off values is discussed. PMID:25074782

  1. Susceptibility of Clinical Isolates of Enterobacteriaceae to BL-S640, a New Oral Cephalosporin

    PubMed Central

    Watanakunakorn, Chatrchai; Bannister, Thomas; Glotzbecker, Cheryl

    1975-01-01

    The in vitro activity of BL-S640, a 7-(2-aryl-2-aminoacetamido)-3-(heterocyclic-thiomethyl) cephalosporin, was evaluated against 338 clinical isolates of Enterobacteriaceae in comparison with ampicillin, cephalothin, cefazolin, and cephalexin. Against Escherichia coli, BL-S640 was as active as cefazolin and more active than ampicillin, cephalothin, and cephalexin. BL-S640 was as effective as the other cephalosporins tested and far more active than ampicillin against Klebsiella and was more active than cephalexin against Proteus mirabilis and the indole-positive Proteus. The majority of Enterobacter, Serratia, and Citrobacter were resistant to ampicillin and all the cephalosporins tested. With rare exceptions, the zone of inhibition by the BL-S640 30-?g disk was either larger or the same as the zone obtained by the cephalothin 30-?g disk in the Kirby-Bauer disk susceptibility test. PMID:1137392

  2. Single-step conversion of cephalosporin-C to 7-aminocephalosporanic acid by free and immobilized cells of Pseudomonas diminuta.

    PubMed

    Nigam, V K; Kundu, S; Ghosh, P

    2005-07-01

    7-Aminocephalosporanic acid (7-ACA), the starting material for the production of a number of clinically used semisynthetic cephalosporins, is produced by deacylation of cephalosporin-C. The production of 7-ACA was studied in various modes, at the optimal conditions using free and immobilized whole cells of Pseudomonas diminuta. PMID:16014995

  3. Porin Involvement in Cephalosporin and Carbapenem Resistance of Burkholderia pseudomallei

    PubMed Central

    Aunkham, Anuwat; Schulte, Albert; Winterhalter, Mathias; Suginta, Wipa

    2014-01-01

    Background Burkholderia pseudomallei (Bps) is a Gram-negative bacterium that causes frequently lethal melioidosis, with a particularly high prevalence in the north and northeast of Thailand. Bps is highly resistant to many antimicrobial agents and this resistance may result from the low drug permeability of outer membrane proteins, known as porins. Principal Findings Microbiological assays showed that the clinical Bps strain was resistant to most antimicrobial agents and sensitive only to ceftazidime and meropenem. An E. coli strain defective in most porins, but expressing BpsOmp38, exhibited considerably lower antimicrobial susceptibility than the control strain. In addition, mutation of Tyr119, the most prominent pore-lining residue in BpsOmp38, markedly altered membrane permeability, substitution with Ala (mutant BpsOmp38Y119A) enhanced uptake of the antimicrobial agents, while substitution with Phe (mutant BpsOmp38Y119F) inhibited uptake. Channel recordings of BpsOmp38 reconstituted in a planar black lipid membrane (BLM) suggested that the higher permeability of BpsOmp38Y119A was caused by widening of the pore interior through removal of the bulky side chain. In contrast, the lower permeability of BpsOmp38Y119F was caused by introduction of the hydrophobic side chain (Phe), increasing the ‘greasiness’ of the pore lumen. Significantly, liposome swelling assays showed no permeation through the BpsOmp38 channel by antimicrobial agents to which Bps is resistant (cefoxitin, cefepime, and doripenem). In contrast, high permeability to ceftazidime and meropenem was observed, these being agents to which Bps is sensitive. Conclusion/Significance Our results, from both in vivo and in vitro studies, demonstrate that membrane permeability associated with BpsOmp38 expression correlates well with the antimicrobial susceptibility of the virulent bacterium B. pseudomallei, especially to carbapenems and cephalosporins. In addition, substitution of the residue Tyr119 affects the permeability of the BpsOmp38 channel to neutral sugars and antimicrobial agents. PMID:24788109

  4. Antibiotic resistance in the opportunistic pathogen Stenotrophomonas maltophilia

    PubMed Central

    Sánchez, María B.

    2015-01-01

    Stenotrophomonas maltophilia is an environmental bacterium found in the soil, associated with plants and animals, and in aquatic environments. It is also an opportunistic pathogen now causing an increasing number of nosocomial infections. The treatment of S. maltophilia is quite difficult given its intrinsic resistance to a number of antibiotics, and because it is able to acquire new resistances via horizontal gene transfer and mutations. Certainly, strains resistant to quinolones, cotrimoxale and/or cephalosporins—antibiotics commonly used to treat S. maltophilia infections—have emerged. The increasing number of available S. maltophilia genomes has allowed the identification and annotation of a large number of antimicrobial resistance genes. Most encode inactivating enzymes and efflux pumps, but information on their role in intrinsic and acquired resistance is limited. Non-typical antibiotic resistance mechanisms that also form part of the intrinsic resistome have been identified via mutant library screening. These include non-typical antibiotic resistance genes, such as bacterial metabolism genes, and non-inheritable resistant phenotypes, such as biofilm formation and persistence. Their relationships with resistance are complex and require further study.

  5. Study of Antibiotic Resistance Pattern in Methicillin Resistant Staphylococcus Aureus with Special Reference to Newer Antibiotic

    PubMed Central

    Kaur, Dardi Charan; Chate, Sadhana Sanjay

    2015-01-01

    The worldwide epidemic of antibiotic resistance is in danger of ending the golden age of antibiotic therapy. Resistance impacts on all areas of medicine, and is making successful empirical therapy much more difficult to achieve. Staphylococcus aureus demonstrates a unique ability to quickly respond to each new antibiotic with the development of a resistance mechanism, starting with penicillin, until the most recent, linezolid and daptomycin. Methicillin resistant S. aureus (MRSA) has become endemic today in hospitals worldwide. Resistance to the newer antimicrobial-agents — linezolid, vancomycin, teicoplanin, and daptomycin are been reported and also the fear of pandrug-resistance. This study was carried out to know the antimicrobial resistant pattern of MRSA to newer antibiotic, to know any isolates are extensively-drug resistant (XDR)/pandrug resistant (PDR), inducible macrolide-lincosamide streptogramin B (iMLSB), and mupirocin resistance. Thirty-six MRSA isolates resistant to the routinely tested antibiotic were further tested for list of antibiotic by a group of international experts. Isolates were tested for iMLSB and mupirocin resistance by the disk diffusion method. Of 385 MRSA, 36 (9.35%) isolates of MRSA were resistant to the routinely tested antibiotic. Among these 36 MRSA isolates, none of our isolates were XDR/PDR or showed resistant to anti-MRSA cephalosporins (ceftaroline), phosphonic acids, glycopeptides, glycylcyclines, and fucidanes. Lower resistance was seen in oxazolidinones (2.78%), streptogramins (5.56%), lipopeptide (5.56%). Thirty-four (94.44%) isolates showed constitutive MLSB (cMLSB) resistance and two (5.56%) iMLSB phenotypes. High- and low-level mupirocin resistance were seen in 13 (36.11%) and six (16.67%), respectively. In our study, none of our isolates were XDR or PDR. No resistance was observed to ceftaroline, telavancin, teicoplanin, and vancomycin; but the presence of linezolid resistance (1, 2.28%) and daptomycin resistance (2, 5.56%) in our rural set-up is a cause of concern.

  6. EXPANDED-SPECTRUM CEPHALOSPORIN RESISTANCE AND MULTI-DRUG RESISTANCE IN SALMONELLA ISOLATES FROM SWINE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We examined a group of cephalosporin resistant isolates from various swine sources submitted to the National Antimicrobial Resistance Monitoring System (NARMS). A total of 50 isolates were obtained between the years 1997 and 1999. Each of the isolates had MIC's to Ceftriaxone, Ceftiofur, and Cephalo...

  7. Lack of relevance of kinetic parameters for exocellular DD-peptidases to cephalosporin MICs.

    PubMed Central

    Boyd, D B; Ott, J L

    1986-01-01

    MICs of a set of cephalosporins against a variety of gram-positive and gram-negative pathogens showed no strong correlations with the rate at which these inhibitors acylate or are deacylated by beta-lactam-sensitive DD-peptidases excreted by Streptomyces sp. strain R61 and Actinomadura sp. strain R39. PMID:3729340

  8. Occupational Asthma in Antibiotic Manufacturing Workers: Case Reports and Systematic Review

    PubMed Central

    Díaz Angulo, Sara; Szram, Joanna; Welch, Jenny; Cannon, Julie; Cullinan, Paul

    2011-01-01

    Background. The risks of occupational asthma (OA) from antibiotics are uncertain. We report 4 new cases and a systematic review of the literature. Methods. Cases were identified through a specialist clinic, each underwent specific provocation testing (SPT). We subsequently reviewed the published literature. Results. The patients were employed in the manufacture of antibiotics; penicillins were implicated in three cases, in the fourth erythromycin, not previously reported to cause OA. In two, there was evidence of specific IgE sensitisation. At SPT each developed a late asthmatic reaction and increased bronchial hyperresponsiveness. 36 case reports have been previously published, 26 (citing penicillins or cephalosporins). Seven cross-sectional workplace-based surveys found prevalences of 5–8%. Conclusions. OA in antibiotic manufacturers may be more common than is generally recognised. Its pathogenesis remains unclear; immunological tests are of uncertain value and potential cases require confirmation with SPT. Further study of its frequency, mechanisms, and diagnosis is required. PMID:21603168

  9. Anaerobic digestion of antibiotic residue in combination with hydrothermal pretreatment for biogas.

    PubMed

    Zhang, Guangyi; Li, Chunxing; Ma, Dachao; Zhang, Zhikai; Xu, Guangwen

    2015-09-01

    Antibiotic residues are difficult to be treated or utilized because of their high water content and residual antibiotics. This article is devoted to investigating the possibility of biogas production from cephalosporin C residue (CPCAR), one typical type of antibiotic residues, via anaerobic digestion in combination with hydrothermal pretreatment (HTPT). The results from the bench-scale experiments showed that the combination of HTPT and anaerobic digestion can provide a viable way to convert CPCAR into biogas, and the biogas and methane yields reached 290 and 200ml(gTS)(-1), respectively. This article further evaluated the proposed technology in terms of energy balance and technical feasibility based on theoretical calculation using the data from a pilot HTPT test. It was shown that the process is totally self-sufficient in energy and its main challenging problem of ammonia inhibition can be solved via ammonia stripping. PMID:26038331

  10. Antibiotics and Resistance: Glossary

    MedlinePLUS

    ... a protein; a unit of heredity. Generic vs. trade name (non-generic) antibiotics Commercially available antibiotics may ... identification provided by chemists, for example "Amoxicillin." The trade name is given to it by the manufacturer ...

  11. Factors affecting cure when treating bovine clinical mastitis with cephalosporin-based intramammary preparations

    PubMed Central

    Bradley, A. J.; Green, M. J.

    2009-01-01

    Data were collated for an independent scientific analysis from 2 international, multicenter studies that had compared the efficacy of 3 different cephalosporin-containing intramammary preparations in the treatment of clinical mastitis in dairy cattle [cefalexin (first generation) in combination with kanamycin; cefquinome (fourth generation); and cefoperazone (third generation)]. Quarters were assessed using standard bacteriological techniques before treatment and at 16 and 25 d posttreatment. Additional data were also available on individual cows and study farms, including parity, breed, and cow somatic cell count histories, herd bulk milk somatic cell counts, and farm management regimens. Sufficient data for analysis were available from a total of 491 cases on 192 farms in 3 countries (United Kingdom, France, and Germany) with up to 16 cases being recruited from any one farm. Clinical cases were of diverse etiology, representing both contagious and environmental pathogens. Univariable analysis demonstrated that quarters in the cefalexin + kanamycin and cefquinome treatment groups were not significantly different from each other, but were both significantly more likely to be pathogen free posttreatment than quarters in the cefoperazone group. Multivariable analysis was undertaken using conventional random effects models. Two models were built, with the first incorporating only information available to the practitioner at the time of treatment and the second including all information collected during the study. These models indicated that country, pretreatment rectal temperature (above-normal temperature associated with an increased chance of being pathogen free posttreatment), individual cow somatic cell count (increased somatic cell count associated with a decreased chance of being pathogen free posttreatment), and pathogen (Staphylococcus aureus isolation associated with a decreased chance of being pathogen free posttreatment) were useful predictors of pathogen free status; parity, yield, bulk milk somatic cell counts, and other farm management factors were not. The importance of country in the analysis demonstrates the need to generate local data when assessing treatment regimens. In addition, these results suggest that the factors important in predicting the outcome of treatment of clinical mastitis cases may be dissimilar to those reported to affect the likelihood of cure when treating subclinical intramammary infections. PMID:19389951

  12. Factors affecting cure when treating bovine clinical mastitis with cephalosporin-based intramammary preparations.

    PubMed

    Bradley, A J; Green, M J

    2009-05-01

    Data were collated for an independent scientific analysis from 2 international, multicenter studies that had compared the efficacy of 3 different cephalosporin-containing intramammary preparations in the treatment of clinical mastitis in dairy cattle [cefalexin (first generation) in combination with kanamycin; cefquinome (fourth generation); and cefoperazone (third generation)]. Quarters were assessed using standard bacteriological techniques before treatment and at 16 and 25 d posttreatment. Additional data were also available on individual cows and study farms, including parity, breed, and cow somatic cell count histories, herd bulk milk somatic cell counts, and farm management regimens. Sufficient data for analysis were available from a total of 491 cases on 192 farms in 3 countries (United Kingdom, France, and Germany) with up to 16 cases being recruited from any one farm. Clinical cases were of diverse etiology, representing both contagious and environmental pathogens. Univariable analysis demonstrated that quarters in the cefalexin + kanamycin and cefquinome treatment groups were not significantly different from each other, but were both significantly more likely to be pathogen free posttreatment than quarters in the cefoperazone group. Multivariable analysis was undertaken using conventional random effects models. Two models were built, with the first incorporating only information available to the practitioner at the time of treatment and the second including all information collected during the study. These models indicated that country, pretreatment rectal temperature (above-normal temperature associated with an increased chance of being pathogen free posttreatment), individual cow somatic cell count (increased somatic cell count associated with a decreased chance of being pathogen free posttreatment), and pathogen (Staphylococcus aureus isolation associated with a decreased chance of being pathogen free posttreatment) were useful predictors of pathogen free status; parity, yield, bulk milk somatic cell counts, and other farm management factors were not. The importance of country in the analysis demonstrates the need to generate local data when assessing treatment regimens. In addition, these results suggest that the factors important in predicting the outcome of treatment of clinical mastitis cases may be dissimilar to those reported to affect the likelihood of cure when treating subclinical intramammary infections. PMID:19389951

  13. Multiple antibiotic allergies.

    PubMed

    Harris, R J; Harris, R L

    1978-12-01

    A case of an 18-year-old woman with postoperative infectious complications and multiple antibiotic allergies is discussed. The case poses several problems: the selection of an appropriate antibiotic to combat the infection, the persistence of the infection, and the treatment of multiple allergic responses to each of the antibiotic agents chosen. PMID:281442

  14. Ion-paired extraction of cephalosporins in acetone prior to their analysis by capillary liquid chromatography in environmental water and meat samples.

    PubMed

    Quesada-Molina, Carolina; García-Campaña, Ana M; del Olmo-Iruela, Monsalud

    2013-10-15

    Ion-pair extraction of cephalosporins from aqueous solution into acetone by the addition of ammonium sulfate to a 1:2 (v/v) acetone-water solvent was carried out followed by their determination using reversed-phase capillary liquid chromatography. The analytes included are cephoperazone, cefquinome, cephalexin, cephapirin, cephaloniun, cephamandole, cephazolin and cephadroxile. In order to form the ion-pair, hexadecyltrimethylammonium bromide (CTAB) was selected as cationic ion-pairing agent at a concentration of 0.9 mM using 10mM phosphate buffer at pH 8 as the optimum condition for the aqueous solution. The applied methodology, named salting-out assisted liquid/liquid extraction (SALLE) involves the use of 1.25 g of ammonium sulfate as salting-out agent. The separation of cephalosporins using a Luna C18 (150 mm × 0.3mm, 5 µm, 100 Å) column was achieved under the following conditions: a gradient program combining solvent A (0.1% formic acid in water, pH 4) and solvent B (acetonitrile-methanol (50:50, v/v)), at a flow rate of 20 µl min(-1), column temperature 35°C and injection volume 7 µl with UV detection at 250 nm. The limits of quantification for the studied compounds were between 4.3 and 22.7 ?g/L for water samples and 4.1 and 73.3 ?g/kg in the case of beef samples, lower than the maximum residue limits permitted by the EU for this kind of food. The developed methodology has demonstrated its suitability for the analysis of these widely applied antibiotics in environmental water and meat samples, including beef and pork muscle, with high sensitivity, precision and satisfactory recoveries. PMID:24054686

  15. Prophylactic use of antibiotic-loaded bone cement in primary total knee arthroplasty: Justified or not?

    PubMed Central

    Srivastav, Amit K; Nadkarni, Biren; Srivastav, Shekhar; Mittal, Vivek; Agarwal, Shekhar

    2009-01-01

    Background: The routine use of antibiotic-loaded bone cement (ABLC) during primary or uninfected revision arthroplasty remains controversial. Many studies quote the total joint arthroplasty (TJA) infection rate to be less than 1%. Total knee arthroplasty (TKA) has a higher infection rate than total hip arthroplasty (THA). Based on both animal and human studies in the past, ABLC has been found effective in reducing the risk of infection in primary TJA. We are presenting retrospective analysis of results in terms of infection rate in 659 TKA performed by a single surgeon under similar conditions during 2004–2007 using CMW1 (Depuy, Leeds, UK) with premixed 1 g of gentamicin. Patients and Methods: We did primary TKA in 659 knees of 379 patients during 2004–2007 using CMW1 (Depuy, Leeds, UK) cement containing 1 g of gentamicin in 40 g of cement in a premixed form. Standard OT conditions were maintained using laminar air flow, isolation suits for the operating team, pulse lavage and disposable drapes in each patients. Midvastus approach was used in all the patients to expose the knee joint. A systemic antibiotic (third-generation cephalosporin and aminoglycoside) was used preoperatively and 48 h postoperatively. We observed the patients in terms of infection in the high-risk and low-risk group till the recent follow-up with a mean of 20.6 months (9–38 months). Results: We had deep infection in six knees in six patients and all of them required two-stage revision surgery later in the high-risk group. Infection occurred at a mean of 20.5 months after surgery earliest at 9 months and latest at 36 months after surgery. The infection rate in our study was 0.91% which is comparatively less than the reported incidence of 1–2% in reported studies. Conclusion: We conclude that the use of antibiotic loaded bone cement is one of the effective means in preventing infection in primary TJA. PMID:19838348

  16. Finding alternatives to antibiotics.

    PubMed

    Allen, Heather K; Trachsel, Julian; Looft, Torey; Casey, Thomas A

    2014-09-01

    The spread of antibiotic-resistant pathogens requires new treatments. As the rate of development of new antibiotics has severely declined, alternatives to antibiotics must be considered in both animal agriculture and human medicine. Products for disease prevention are different from those for disease treatment, and examples of both are discussed here. For example, modulating the gut microbial community, either through feed additives or fecal transplantation, could be a promising way to prevent certain diseases; for disease treatment, non-antibiotic approaches include phage therapy, phage lysins, bacteriocins, and predatory bacteria. Interestingly, several of these methods augment antibiotic efficacy by improving bacterial killing and decreasing antibiotic resistance selection. Because bacteria can ultimately evolve resistance to almost any therapeutic agent, it is important to continue to use both antibiotics and their alternatives judiciously. PMID:24953233

  17. [Sensitivity to various antibiotics of coagulase-negative staphylococci isolated from samples of milk from Dutch dairy cattle].

    PubMed

    Sampimon, O C; Vernooij, J C A; Mevius, D J; Sol, J

    2007-03-15

    During recent years the prevalence of coagulase-negative staphylococci in milk samples from Dutch dairy cows has increased. In 1999 16.2% of the bacteria isolated from milk collected from cows with subclinical mastitis were coagulase-negative staphylococci. In 2004 this proportion was 42.2%. The proportion of coagulase-negative staphylococci of the bacteria isolated from milk samples from cows with clinical mastitis was 7.3% in 1999 and 14.1% in 2004. In this study, the susceptibility of 108 coagulase-negative staphylococci to oxacillin, cefquinome, streptomycin, neomycin, penicillin, and the combination of nafcillin, penicillin, and streptomycin was tested. The isolates were cultured from milk collected from cows with mastitis and typed using the Api-Staph system. Eight species were identified. Staphylococcus chromogenes was the predominant species (41.7%), followed by Staphylococcus xylosus (15.7%) and Staphylococcus simulans (10.2%). With the agar dilution method all strains proved to be sensitive to cefquinome and 90% to oxacillin. Three isolates (2.8%) were mecA-positive. Despite the agar dilution results, these three isolates should be considered resistant to all beta-lactam antibiotics (penicillins, penicillins combined with a beta-lactamase inhibitor and all generations of cephalosporins). In the agar diffusion test, all isolates proved to be sensitive to the combination of nafcillin-penicillin-streptomycin, 99% were sensitive to neomycin and 1% intermediate sensitive, and 95% were sensitive to streptomycin, 4% resistant, and 1% intermediate sensitive. The coagulase-negative staphylococci were highly resistant to penicillin (37.4%), although the level of resistance varied between species, from 0% for Staphylococcus simulans to 100% for Staphylococcus saprophyticus. Because coagulase-negative staphylococci are resistant to several antibiotics, sensitivity testing is important for targeted treatment of mastitis. PMID:17436810

  18. Development of an enzyme immunoassay for the antibiotic cefquinome and its application for residue determination in cow's milk after therapeutical mastitis treatment

    Microsoft Academic Search

    Johannes Thal; Monika Steffen; Bianca Meier; Elisabeth Schneider; Ansgar Adriany; Ewald Usleber

    2011-01-01

    The aim of this study was to develop and evaluate an enzyme immunoassay (EIA) for the cephalosporin antibiotic in milk, in\\u000a combination with a new microbiological test system (brilliant black reduction test, BRT-P). Polyclonal antibodies against\\u000a cefquinome were produced in rabbits, using cefquinome-keyhole limpet hemocyanine as the immunogen. These antibodies and a\\u000a cefquinome-glucose oxidase conjugate were used in a competitive

  19. High hepatic excretion in humans of cefpiramide, a new cephalosporin.

    PubMed Central

    Brogard, J M; Jehl, F; Adloff, M; Blickle, J F; Monteil, H

    1988-01-01

    After intravenous administration of 1 g of cefpiramide, the biliary elimination of the drug was studied by using high-performance liquid chromatography. In five healthy volunteers, a mean peak concentration of 339 +/- 107 (standard error of the mean) micrograms/ml was measured in aspirated duodenal fluid during h 2 after administration, and 1.2% of the dose given was recovered over a 4-h period. A maximal concentration of 1,161 +/- 392 micrograms/ml was reached during h 2 in T-tube bile from 10 recently cholecystectomized patients, with a 24-h biliary recovery of 23.1%; urinary recovery over the same period averaged 49.4%. In 10 patients undergoing cholecystectomy, the concentrations in serum, choledochal bile, gallbladder bile, and gallbladder wall 1 h after cefpiramide administration were 157 +/- 21, 1,726 +/- 501, and 84 +/- 33 micrograms/ml and 23 +/- 4 micrograms/g, respectively. These figures represent the highest biliary concentrations attained so far with a beta-lactam antibiotic and are therefore a good prerequisite for treatment of biliary tract infections with cefpiramide. PMID:3195998

  20. Developing New Antibiotics with Combinatorial Biosynthesis

    NASA Astrophysics Data System (ADS)

    Pohl, Nicola L.

    2000-11-01

    Polyketide synthases (PKSs), a class of enzymes found in soil bacteria that produce antibiotics such as erythromycin, string together acetate units using basic organic reactions. The manipulation of the sequence of these reactions at the genetic level has resulted in an alteration of the corresponding chemical structure of the antibiotic produced by the bacteria. This process, called combinatorial biosynthesis, allows the generation of many presently unknown complex structures that can be tested for antibacterial activity, thereby contributing to the race against antibiotic-resistant infectious bacteria.

  1. In vitro activity of Ro 23-9424, a dual-action cephalosporin, compared with activities of other antibiotics.

    PubMed Central

    Gu, J W; Neu, H C

    1990-01-01

    The in vitro activity of Ro 23-9424, which is desacetyl-cefotaxime linked to fleroxacin, was compared with the activities of cefotaxime, desacetyl-cefotaxime, fleroxacin, ofloxacin, and ciprofloxacin. It inhibited the majority of members of the family Enterobacteriaceae, except for some Serratia marcescens, Citrobacter freundii, and Enterobacter cloacae strains, at less than or equal to 0.25 microgram/ml and had an MIC for 90% of strains tested (MIC90) of 8 micrograms/ml against Pseudomonas aeruginosa. Most group A, B, C, and G streptococci and Streptococcus pneumoniae were inhibited at less than or equal to 0.25 microgram/ml. Ninety percent of the staphylococci were inhibited at less than or equal to 4 micrograms/ml, except for some methicillin-resistant Staphylococcus aureus isolates. The MIC90S of Ro 23-9424 for Enterococcus faecalis and Listeria monocytogenes were greater than or equal to 16 micrograms/ml. Ninety percent of Clostridium perfringens isolates were inhibited by less than or equal to 2 micrograms/ml, whereas Bacteroides fragilis had an MIC90 of 32 micrograms/ml. There was a minimal inoculum size effect. The MICs and MBCs were either identical or within a twofold dilution. The MICs of Ro 23-9424 for Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, Enterobacter cloacae, Citrobacter freundii, Pseudomonas aeruginosa, and Staphylococcus aureus increased 16- to 128-fold after 2 weeks of transfer in the presence of Ro 23-9424, showing that the presence of two agents does not prevent resistance. PMID:2327765

  2. Surveillance of antibiotic resistance in South East Asia.

    PubMed

    Williams, J D; Moosdeen, F; Teoh-Chan, C H; Lim, V K; Jayanetra, P

    1989-06-01

    Antibiotic resistance in Gram-negative bacteria, particularly Salmonella and Shigella, requires surveillance worldwide. This study describes results of surveys in Hong Kong, Bangkok and Kuala Lumpur. All strains were isolated in hospitals which have large community catchment areas in addition to specialised hospital units. The prevalence of resistant strains was high in all areas. Gram-negative bacteria such as Enterobacter associated with hospital infections were resistant to penicillins and cephalosporins, with gentamicin resistance ranging from about 20% in Kuala Lumpur and Hong Kong, to 35% in Bangkok. Ninety-seven percent of Shigella isolated in Thailand were resistant to ampicillin. About 10% of Salmonella were resistant to chloramphenicol in all three centres. PMID:2504618

  3. Cephalosporin binding sites to human serum albumin and the relation with the N-B transition of this protein.

    PubMed

    Nerli, B; García, F; Ballán, C; Picó, G

    1995-05-01

    The binding of some cephalosporins to human serum albumin was studied using probes for the so-called I, II, bilirubin and fatty acids binding sites. The results showed that cephradine and cefsulodin bind to site II, cefaclor, cefamandole, cefsulodin, cephaloglycin and cefadroxil bind to the bilirubin binding site, while cefaclor does it to the fatty acid binding site. No binding of these cephalosporins to site I of albumin was found. The binding produced a perturbation on the N-B equilibrium of albumin, stabilizing the N conformational form, which suggests that the N form of albumin has more affinity with the cephalosporins than the B form. This finding gives support to the assumption that the binding of cephalosporins to site II, bilirubin and fatty acids binding sites affects the N-B transition of albumin. PMID:7663413

  4. Antibiotics in the environment.

    PubMed

    Larsson, D G Joakim

    2014-05-01

    Molecules with antibiotic properties, produced by various microbes, have been around long before mankind recognized their usefulness in preventing and treating bacterial infections. Bacteria have therefore been exposed to selection pressures from antibiotics for very long times, however, generally only on a micro-scale within the immediate vicinity of the antibiotic-producing organisms. In the twentieth century we began mass-producing antibiotics, mainly synthetic derivatives of naturally produced antibiotic molecules, but also a few entirely synthetic compounds. As a consequence, entire bacterial communities became exposed to unprecedented antibiotic selection pressures, which in turn led to the rapid resistance development we are facing today among many pathogens. We are, rightly, concerned about the direct selection pressures of antibiotics on the microbial communities that reside in or on our bodies. However, other environments, outside of our bodies, may also be exposed to antibiotics through different routes, most often unintentionally. There are concerns that increased selection pressures from antibiotics in the environment can contribute to the recruitment of resistance factors from the environmental resistome to human pathogens. This paper attempts to 1) provide a brief overview of environmental exposure routes of antibiotics, 2) provide some thoughts about our current knowledge of the associated risks for humans as well as ecosystems, and 3) indicate management options to reduce risks. PMID:24646081

  5. Simultaneous determination of different antibiotic residues in bovine and in porcine kidneys by solid-phase fluorescence immunoassay.

    PubMed

    Okerman, Lieve; De Wasch, Katia; Van Hoof, Jan; Smedts, Walter

    2003-01-01

    Parallux, a solid-phase fluorescence immunoassay (SPFIA) developed for antibiotic residue detection in milk, was used for analysis of bovine and porcine kidney tissue. Four tetracyclines, 2 broad-spectrum cephalosporins, 3 beta-lactam antibiotics, and cephapirin were detected in one run after minimal sample preparation. This commercially available test system is designed as cartridges, each with a combination of 1-4 tests. One cartridge can be used to detect 4 analytes in the same sample, or 1 or 2 analytes in different samples. The cartridge with the combination tetracyclines-ceftiofur-penicillin-cephapirin was selected because tetracyclines, beta-lactam antibiotics as well as cephalosporins, are registered for oral or parenteral use in bovines and pigs in Europe. The test is qualitative and is recommended only for screening. Tetracycline, oxytetracycline, chlortetracycline, and doxycycline were easily detected at 300 ppb with the tetracyclines channel; ceftiofur at 1000 ppb and cefquinome at 200 ppb with the ceftiofur channel; penicillin G, ampicillin, and amoxicillin at 50 ppb with the penicillin channel; and cephapirin at 100 ppb with the cephapirin channel. These levels are equal to or lower than the corresponding maximal residue limits in kidney tissue. Cephalexin was not detected. The SPFIA test can be used as an alternative to classical inhibition tests and for post-screening inhibitor- positive kidneys, because it detects 3 specific groups of antibiotics, which enables selection of specific confirmatory methods for identification and quantification. PMID:12723911

  6. Resistance to extended-spectrum cephalosporins, caused by PER1  -lactamase, in M Salmonella typhimurium from Istanbul, Turkey

    Microsoft Academic Search

    H. Vahaboglu; L. M. C. Hall; L. Mulazimoglu; S. Dodanli; I. Yildirim; D. M. Livermore

    1995-01-01

    Summary. Two Salmonellu typhimurium isolates were studied, one as a representative from a series of neonatal meningitis cases treated at an Istanbul teaching hospital, the other from a gastro-enteritis case seen at a different Istanbul hospital. Both isolates were resistant to extended-spectrum cephalosporins, as well as penicillins, aminoglycosides and chlor- amphenicol. Cephalosporin resistance depended on production of PER- 1 p-lactamase,

  7. The interaction and transport of beta-lactam antibiotics with the cloned rat renal organic anion transporter 1.

    PubMed

    Jariyawat, S; Sekine, T; Takeda, M; Apiwattanakul, N; Kanai, Y; Sophasan, S; Endou, H

    1999-08-01

    In the present study, we investigated the interactions between antibiotics, especially beta-lactam antibiotics, and rat renal organic anion transporter 1 (OAT1). [(14)C]p-Aminohippurate (PAH) uptake via OAT1 expressed in Xenopus laevis oocytes was inhibited by all of the penicillins and cephalosporins tested. Penicillin G, carbenicillin, cephaloridine, cephalothin, cefazolin, and cephalexin inhibited [(14)C]PAH uptake via OAT1 in a competitive manner (K(i) = 0.29-2.33 mM). Cinoxacin, a quinolone gyrase inhibitor, also inhibited PAH uptake via OAT1. Other antibiotics, such as gentamicin, streptomycin, and vancomycin, which do not contain anionic moieties, did not interact with OAT1. [(3)H]Penicillin G and [(14)C]cephaloridine were demonstrated to be transported via OAT1. Using the cells that stably expressed OAT1, we analyzed the cytotoxicity of several beta-lactam antibiotics. Cells expressing OAT1 showed higher susceptibility to cephaloridine (a potentially nephrotoxic beta-lactam antibiotic) toxicity than did control cells. The present study suggests that OAT1 is the major organic anion transporter in the kidney that is responsible for the renal secretion of antibiotics, especially that of beta-lactam antibiotics. Furthermore, the culture cell system expressing OAT1 was revealed to be useful for the prediction of the nephrotoxicity of beta-lactam antibiotics. PMID:10411577

  8. Competing Doctors, Antibiotic Use, and Antibiotic Resistance in Taiwan

    Microsoft Academic Search

    Daniel Bennett; Tsai-Ling Lauderdalez Che-Lun Hung; Che-Lun Hung

    Antibiotics are a cornerstone of modern medicine, but antibiotic resistance increas- ingly threatens to erode their efiectiveness. The emergence of drug-resistant pathogens is a negative externality associated with antibiotic use. Many patients, who do not in- ternalize this social cost, prefer physicians who casually prescribe antibiotics. If ofiering these drugs increases demand, physicians may respond to competition by prescribing antibiotics

  9. Environmental risk assessment of antibiotics including synergistic and antagonistic combination effects.

    PubMed

    Marx, Conrad; Mühlbauer, Viktoria; Krebs, Peter; Kuehn, Volker

    2015-08-15

    The interaction-based hazard index (HIint) allows a prediction of mixture effects different from linear additivity by including information on binary mixtures between the chemicals. The aim of this study is to make a solid estimate on the possible synergistic potential of combined antibiotics and to quantify the subsequent effect for the case of the receiving river Elbe, Germany. Pieces of information on binary interactions between antibiotic groups were used from literature and from knowledge on human antibiotic combination therapy. Applying a moderate and a worst-case scenario, in terms of the interaction magnitude, resulted in 50 to 200% higher environmental risks, compared to the classical assessment approach applying simple concentration addition. A subsequent sensitivity analysis revealed that the data strength for some binary antibiotic combinations is too low to be considered for a solid estimate of synergistic effects. This led to the definition of certain preconditions in order to decide whether or not to include certain interaction information (e.g. the necessary number of interaction studies). The exclusion of information with low data strength resulted in an attenuated risk increase of 20 to 50%, based on the currently available scientific information on binary antibiotic mixtures. In order to include antibiotics with the highest share in the overall risk (macrolides, quinolones, and cephalosporins) as well as their corresponding metabolites, investigations should focus on binary interactions between them. PMID:25897732

  10. Precursor structure of cephalosporin acylase. Insights into autoproteolytic activation in a new N-terminal hydrolase family.

    PubMed

    Kim, Youngsoo; Kim, Sanggu; Earnest, Thomas N; Hol, Wim G J

    2002-01-25

    Autocatalytic proteolytic cleavage is a frequently observed post-translational modification in proteins. Cephalosporin acylase (CA) is a recently identified member of the N-terminal hydrolase family that is activated from an inactive precursor by autoproteolytic processing, generating a new N-terminal residue, which is either a Ser or a Thr. The N-terminal Ser or Thr becomes a nucleophilic catalytic center for intramolecular and intermolecular amide cleavages. The gene structure of the open reading frame of CAs generally consists of a signal peptide followed by the alpha-subunit, a spacer sequence, and the beta-subunit, which are all translated into a single polypeptide chain, the CA precursor. The precursor is post-translationally modified into an active heterodimeric enzyme with alpha- and beta-subunits, first by intramolecular cleavage and second by intermolecular cleavage. We solved the first CA precursor structure (code 1KEH) from a class I CA from Pseudomonas diminuta at a 2.5-A resolution that provides insight into the mechanism of intramolecular cleavage. A conserved water molecule, stabilized by four hydrogen bonds in unusual pseudotetrahedral geometry, plays a key role to assist the OG atom of Ser(1beta) to generate a strong nucleophile. In addition, the site of the secondary intermolecular cleavage of CA is proposed to be the carbonyl carbon of Gly(158alpha) (Kim, S., and Kim, Y., (2001) J. Biol. Chem., 276, 48376-48381), which is different from the situation in two other class I CAs. PMID:11706000

  11. Quantitative determination of some thiazole cephalosporins through complexation with palladium (II) chloride.

    PubMed

    Fattah, A; El-Walily, M; Gazy, A A; Belal, S F; Khamis, E F

    2000-03-01

    A simple and sensitive spectrophotometric method has been developed for the determination of five cephalosporins namely cefpodoxime (CFPD), ceftizoxime (CTIZ), ceftazidime (CZD), ceftriaxone (CTRX), and cefixime (CXIM). This method is based on the formation of yellow to yellowish brown complex between palladium (II) chloride and the investigated cephalosporins in the presence of sodium lauryl sulphate (SLS) as surfactant. The reaction conditions were studied and optimized. The procedure was validated. For each drug, the composition of this complex as well as its stability constant were also investigated. The proposed method was used for the determination of the above-mentioned drugs in their commercial preparations. The results were compared statistically with either official or published methods and showed no significant difference between the two methods. PMID:10719922

  12. Biotic acts of antibiotics

    PubMed Central

    Aminov, Rustam I.

    2013-01-01

    Biological functions of antibiotics are not limited to killing. The most likely function of antibiotics in natural microbial ecosystems is signaling. Does this signaling function of antibiotics also extend to the eukaryotic – in particular mammalian – cells? In this review, the host modulating properties of three classes of antibiotics (macrolides, tetracyclines, and ?-lactams) will be briefly discussed. Antibiotics can be effective in treatment of a broad spectrum of diseases and pathological conditions other than those of infectious etiology and, in this capacity, may find widespread applications beyond the intended antimicrobial use. This use, however, should not compromise the primary function antibiotics are used for. The biological background for this inter-kingdom signaling is also discussed. PMID:23966991

  13. Clinical Studies ofCefazolin andComparison withOtherCephalosporins

    Microsoft Academic Search

    T. MADHAVAN; EDWARD L. QUINN; FRANK COX; KEITH BURCH; DONALD POHLOD

    1973-01-01

    Cefazolin, a new cephalosporin derivative, was studied inthetreatment of105 hospitalized patients witha variety ofinfections including endocarditis, pneu- monia, andurinary andsoft tissue infections, andwas found tobeeffective in104 patients. Cefazolin was alsotested invitro andshowntobeeffective against staphylococci, pneumococci, Escherichia coli, Klebsiella sp., andProteus mirabilis byagar dilution method. Itwas showntoproduce highserum levels whenadministered ina 250-to1,000-mg intramuscular doseandwas well tolerated andfreefromrenal toxicity. Comparison oftheresults ofthisstudy

  14. Multicentre comparative study on the antibacterial activity of FK-037, a new parenteral cephalosporin

    Microsoft Academic Search

    J. Martínez-Beltrán; R. Cantón; J. Liñares; J. García de Lomas; C. Gimeno; F. Tubau; F. Baquero

    1995-01-01

    The in vitro antibacterial activity of FK-037, a new parenteral cephalosporin structurally related to cefpirome and cefepime, was compared with that of cefotaxime, ceftazidime, aztreonam, cefpirome, cefepime, imipenem and meropenem against 1,837 clinical isolates obtained from three Spanish hospitals. FK-037 inhibited 90 % ofEnterobacteriaceae isolates at 0.25 µg\\/ml, with the exception ofEnterobacter aerogenes (MIC90 1 µg\\/ml),Enterobacter cloacae andCitrobacter freundii (MIC90

  15. Determination of cephalosporins in raw bovine milk by high-performance liquid chromatography

    Microsoft Academic Search

    Lambert K Sørensen; Lena K Snor

    2000-01-01

    A high-performance liquid chromatographic (HPLC) method based on solid-phase extraction was developed for the determination of cefazolin, cefoperazone, cefquinome and ceftiofur in raw bovine milk. The milk fat was removed by centrifugation and the cephalosporins were extracted in acetonitrile. The extract was cleaned up by solid-phase extraction on an octadecyl sorbent. The compounds were separated by ion-paired gradient HPLC on

  16. In Vitro Activities of Cephalosporins and Quinolones against Escherichia coli Strains Isolated from Diarrheic Dairy Calves

    Microsoft Academic Search

    JOSEANTONIO ORDEN; JOSEANTONIO RUIZ-SANTA-QUITERIA; SILVIA GARCIA; DOLORES CID; RICARDO DE LA FUENTE

    1999-01-01

    The in vitro activities of several cephalosporins and quinolones against 195 strains of Escherichia coli isolated from dairy calves affected by neonatal diarrhea were determined. One hundred thirty-seven of these strains produced one or more potential virulence factors (F5, F41, F17, cytotoxic necrotizing factor, verotoxin, and the eae gene), but the remaining 58 strains did not produce any of these

  17. SCE-129, Antipseudomonal Cephalosporin: In Vitro and In Vivo Antibacterial Activities

    PubMed Central

    Tsuchiya, Kanji; Kondo, Masahiro; Nagatomo, Hiroshi

    1978-01-01

    SCE-129 [3-(4-carbamoyl-1-pyridiniomethyl)-7?-(d-?-sulfophenylacetamido)-ceph-3-em-4-carboxylate monosodium salt], a new semisynthetic cephalosporin, shows potent in vitro antibacterial activities against Pseudomonas aeruginosa and some gram-positive bacteria, whereas it shows lower activity against many gram-negative rods. Against clinical isolates of P. aeruginosa this cephalosporin exhibited higher activity than did carbenicillin, and against the strains of Staphylococcus aureus, SCE-129 had similar activity to carbenicillin. Variations in pH, addition of horse serum, and type of growth medium had no significant effects on the activity of the cephalosporin; however, the inoculum size had some effect on the activity. SCE-129 is an effective bactericidal agent against P. aeruginosa and S. aureus. The protective effects of SCE-129 in mice infected with P. aeruginosa and S. aureus were more potent than those of carbenicillin. The protective effects of SCE-129 on Pseudomonas infection in mice varied according to the dosage schedule and the challenge dose. In a multiple dose schedule, a smaller amount of SCE-129 was necessary than that in a single dose schedule. The effects of SCE-129 after subcutaneous or intraperitoneal administration were more potent than were those by intravenous administration. No protective effect was observed by oral administration. PMID:417670

  18. Genetic profiles of fluoroquinolone-nonsusceptible Klebsiella pneumoniae among cephalosporin-resistant K. pneumoniae.

    PubMed

    Nagasaka, Yukiko; Kimura, Kouji; Yamada, Keiko; Wachino, Jun-Ichi; Jin, Wanchun; Notake, Shigeyuki; Yanagisawa, Hideji; Arakawa, Yoshichika

    2015-04-01

    The rate of fluoroquinolone (FQ) resistance among the cephalosporin-resistant Klebsiella pneumoniae is considerably high, however, their genetic profiles have not been well investigated. We selected 61 ciprofloxacin-nonsusceptible isolates from 102 K. pneumoniae isolates judged to be "resistant" to some cephalosporins during 2009 and 2012 throughout Japan. Pulsed-field gel electrophoresis excluded clonal isolates, and 29 isolates were subjected to multilocus sequence typing (MLST), detection of the amino acid substitutions in the quinolone resistance determining regions (QRDRs) of GyrA and ParC, ?-lactamase typing, and identification of plasmid-mediated quinolone resistance (PMQR) genes. PCR-based replicon typing was performed, after PMQR gene transfer. Four major sequence types (STs) or clonal complexes (CCs), that is, ST37, CC17 (consisting of ST17 and ST20), ST11, and CC528 (consisting of ST528 and ST1130), were found, and they accounted for 48.2% of the isolates tested. Amino acid substitutions in the QRDRs and the presence of PMQR genes were identified in 20 (68.9%) and 18 (62.0%) isolates, respectively. The replicon type of three PMQR-carrying plasmids was IncN, but others were nontypable. Fifteen (83.3%) of the 18 PMQR-harboring isolates coharbored blaCTX-M and/or blaDHA-1. Ciprofloxacin-nonsusceptible K. pneumoniae clinical isolates demonstrating cephalosporin resistance often belong to the global epidemic lineages and possess PMQR and/or QRDR substitutions. PMID:25419619

  19. The Comparative Performance of Beta-lactam Antibiotics against Ampicillin Sensitive Escherichia Coli in Conditions Simulating those of the Infected Urinary Bladder

    PubMed Central

    Greenwood, D.; O'Grady, F.

    1974-01-01

    The response of an ampicillin sensitive strain of Escherichia coli to 6 beta-lactam antibiotics was compared in a mechanical model which simulates the hydrokinetic features of the urinary bladder. The performance of the antibiotics was found to differ in a way that could not be predicted by more conventional in vitro techniques. For example, benzylpenicillin was found to be at least as effective as any cephalosporin. Possible reasons for these findings and the relevance of the results to therapeutic practice are discussed. PMID:4607731

  20. The Real Practice of Antibiotic Prophylaxis for Prostate Biopsy in Korea Where the Prevalence of Quinolone-Resistant Escherichia coli Is High

    PubMed Central

    Kim, Dae Hyun; Bae, Sang Rak; Choi, Woo Suk; Paick, Sung Hyun; Kim, Hyeong Gon; Loh, Yong Soo

    2014-01-01

    Purpose Transrectal ultrasonography-guided prostate biopsy (TRUS-Bx) is an essential procedure for diagnosing prostate cancer. The American Urological Association (AUA) Guideline recommends fluoroquinolone alone for 1 day during TRUS-Bx. However, this recommendation may not be appropriate in regions where the prevalence of quinolone-resistant Escherichia coli is high. We investigated the real practice of antibiotic prophylaxis for TRUS-Bx in Korea. Materials and Methods A total of 77 hospitals performing TRUS-Bx were identified and an e-mail was sent to the Urology Department of those hospitals. The questions in the e-mail included the choice of antibiotics before and after the procedure and the duration of antibiotic therapy after TRUS-Bx. Results A total of 54 hospitals (70.0%) responded to the e-mail. Before TRUS-Bx, all hospitals administered intravenous antibiotic prophylaxis. The percentage of hospitals that used quinolone, cephalosporin, and aminoglycoside alone was 48.1%, 20.4%, and 9.3%, respectively. The percentage of hospitals that used two or more antibiotics was 22.2%. After biopsy, all 54 hospitals prescribed oral antibiotics. The percentage of hospitals that prescribed quinolone alone, cephalosporin alone, or a combination of two or more antibiotics was 77.8%, 20.4%, and 1.8%, respectively. The duration of antibiotic use was more than 3 days in most hospitals (79.6%). Only four hospitals (7.4%) followed the AUA recommendation of a 1-day regimen. Conclusions The AUA recommendation was not followed by most hospitals in Korea. This clinical behavior might reflect the high quinolone resistance rate in Korea, and further studies on the most efficient prophylactic antibiotics after TRUS-Bx in Korea are warranted. PMID:25237461

  1. Generation of broad specificity antibodies for sulfonamide antibiotics and development of an enzyme-linked immunosorbent assay (ELISA) for the analysis of milk samples.

    PubMed

    Adrian, Javier; Font, Héctor; Diserens, Jean-Marc; Sánchez-Baeza, Francisco; Marco, M-Pilar

    2009-01-28

    Immunoreagents appropriately produced to detect a wide range of sulfonamide antibiotic congeners have been used to develop a highly sensitive enzyme-linked immunosorbent assay (ELISA). The selectivity has been achieved by combining antibodies raised against 5-[6-(4-aminobenzenesulfonylamino)pyridin-3-yl]-2-methylpentanoic acid (SA1), covalently coupled to horseshoe crab hemocyanin (HCH), and 5-[4-(amino)phenylsulfonamide]-5-oxopentanoic acid (SA2), coupled to ovalbumin (OVA), on an indirect ELISA format. The immunizing hapten has been designed to address selectivity against the common aminobenzenesulfonylamino moieties, using theoretical calculations and molecular modeling tools. Hapten SA1 has been synthesized in four steps from methyl 5-(4-amino-3-pyridinyl)-2-methyl-4-pentenoate through a Heck reaction, under Jeffery conditions, to avoid introduction of additional epitopes in the linker. The microplate immunoassay developed is able to reach the necessary detectability for the determination of the sulfonamide antibiotics most frequently used in the veterinary field, in compliance with the EC Regulation 2377/90. As an example, the IC(50) and LOD values accomplished for sulfapyridine are 2.86 +/- 0.24 and 0.13 +/- 0.03 microg L(-1), respectively. Studies performed with different types of milk samples demonstrate that direct and accurate measurements can be performed in this type of matrix without any previous sample cleanup method. PMID:19154159

  2. The future of antibiotics

    PubMed Central

    2014-01-01

    Antibiotic resistance continues to spread even as society is experiencing a market failure of new antibiotic research and development (R&D). Scientific, economic, and regulatory barriers all contribute to the antibiotic market failure. Scientific solutions to rekindle R&D include finding new screening strategies to identify novel antibiotic scaffolds and transforming the way we think about treating infections, such that the goal is to disarm the pathogen without killing it or modulate the host response to the organism without targeting the organism for destruction. Future economic strategies are likely to focus on ‘push’ incentives offered by public-private partnerships as well as increasing pricing by focusing development on areas of high unmet need. Such strategies can also help protect new antibiotics from overuse after marketing. Regulatory reform is needed to re-establish feasible and meaningful traditional antibiotic pathways, to create novel limited-use pathways that focus on highly resistant infections, and to harmonize regulatory standards across nations. We need new antibiotics with which to treat our patients. But we also need to protect those new antibiotics from misuse when they become available. If we want to break the cycle of resistance and change the current landscape, disruptive approaches that challenge long-standing dogma will be needed. PMID:25043962

  3. Selective pharmacologic inhibition of a PASTA kinase increases Listeria monocytogenes susceptibility to ?-lactam antibiotics.

    PubMed

    Pensinger, Daniel A; Aliota, Matthew T; Schaenzer, Adam J; Boldon, Kyle M; Ansari, Israr-ul H; Vincent, William J B; Knight, Benjamin; Reniere, Michelle L; Striker, Rob; Sauer, John-Demian

    2014-08-01

    While ?-lactam antibiotics are a critical part of the antimicrobial arsenal, they are frequently compromised by various resistance mechanisms, including changes in penicillin binding proteins of the bacterial cell wall. Genetic deletion of the penicillin binding protein and serine/threonine kinase-associated protein (PASTA) kinase in methicillin-resistant Staphylococcus aureus (MRSA) has been shown to restore ?-lactam susceptibility. However, the mechanism remains unclear, and whether pharmacologic inhibition would have the same effect is unknown. In this study, we found that deletion or pharmacologic inhibition of the PASTA kinase in Listeria monocytogenes by the nonselective kinase inhibitor staurosporine results in enhanced susceptibility to both aminopenicillin and cephalosporin antibiotics. Resistance to vancomycin, another class of cell wall synthesis inhibitors, or antibiotics that inhibit protein synthesis was unaffected by staurosporine treatment. Phosphorylation assays with purified kinases revealed that staurosporine selectively inhibited the PASTA kinase of L. monocytogenes (PrkA). Importantly, staurosporine did not inhibit a L. monocytogenes kinase without a PASTA domain (Lmo0618) or the PASTA kinase from MRSA (Stk1). Finally, inhibition of PrkA with a more selective kinase inhibitor, AZD5438, similarly led to sensitization of L. monocytogenes to ?-lactam antibiotics. Overall, these results suggest that pharmacologic targeting of PASTA kinases can increase the efficacy of ?-lactam antibiotics. PMID:24867981

  4. Biosensors, antibiotics and food.

    PubMed

    Virolainen, Nina; Karp, Matti

    2014-01-01

    Antibiotics are medicine's leading asset for fighting microbial infection, which is one of the leading causes of death worldwide. However, the misuse of antibiotics has led to the rapid spread of antibiotic resistance among bacteria and the development of multiple resistant pathogens. Therefore, antibiotics are rapidly losing their antimicrobial value. The use of antibiotics in food production animals is strictly controlled by the European Union (EU). Veterinary use is regulated to prevent the spread of resistance. EU legislation establishes maximum residue limits for veterinary medicinal products in foodstuffs of animal origin and enforces the establishment and execution of national monitoring plans. Among samples selected for monitoring, suspected noncompliant samples are screened and then subjected to confirmatory analysis to establish the identity and concentration of the contaminant. Screening methods for antibiotic residues are typically based on microbiological growth inhibition, whereas physico-chemical methods are used for confirmatory analysis. This chapter discusses biosensors, especially whole-cell based biosensors, as emerging screening methods for antibiotic residues. Whole-cell biosensors can offer highly sensitive and specific detection of residues. Applications demonstrating quantitative analysis and specific analyte identification further improve their potential as screening methods. PMID:25216955

  5. Biodegradable implants for potential use in bone infection. An in vitro study of antibiotic-loaded calcium sulphate.

    PubMed

    Mousset, B; Benoit, M A; Delloye, C; Bouillet, R; Gillard, J

    1995-01-01

    Local antibiotic therapy by diffusion from plaster of Paris beads has proved promising in bone surgery. Sustained local delivery depends on thermostability, so we tested the antibacterial activity of 11 antibiotic solutions after storage at 37 degrees C using a microbiological method. Cephalosporins and penicillins were unstable, but aminoglycosides remained fully stable with 100% activity after 2 weeks. About 60% of the initial bactericidal activity of quinolone, glycopeptides and sodium fusidate were still detectable after 2 weeks. Release of these antibiotics from plaster of Paris beads was evaluated in vitro. Even those in the same family differed in their release rate. Plaster beads with sodium fusidate were the most effective association. A therapeutic level of glycopeptides, aminoglycosides and amoxicillin was leached for about 3 weeks. Cephalosporins and sodium amoxicillin were released in 2 to 3 days, and quinolone beads were too brittle to be used. Plaster of Paris, which is cheap, biocompatible and biodegradable, is an excellent carrier for sodium fusidate, aminoglycosides and glycopeptides. PMID:7558491

  6. Reacting to antibiotic allergies.

    PubMed

    Apter, Andrea J; Strom, Brian L

    2006-01-01

    About 10-15% of all adults report that they are allergic penicillin or other antibiotics, although the accuracy and significance these reports remain unclear. In the outpatient setting, clinicians face a dilemma in prescribing for patients with a history of an allergic reaction to antibiotics. Which drugs should these patients avoid? Are these patients at increased risk for an allergic reaction to related drugs? This Issue Brief summarizes several large studies that can help guide improve the management of patients with antibiotic allergies. PMID:16964636

  7. Fighting antibiotic resistance in the intensive care unit using antibiotics.

    PubMed

    Plantinga, Nienke L; Wittekamp, Bastiaan H J; van Duijn, Pleun J; Bonten, Marc J M

    2015-01-01

    Antibiotic resistance is a global and increasing problem that is not counterbalanced by the development of new therapeutic agents. The prevalence of antibiotic resistance is especially high in intensive care units with frequently reported outbreaks of multidrug-resistant organisms. In addition to classical infection prevention protocols and surveillance programs, counterintuitive interventions, such as selective decontamination with antibiotics and antibiotic rotation have been applied and investigated to control the emergence of antibiotic resistance. This review provides an overview of selective oropharyngeal and digestive tract decontamination, decolonization of methicillin-resistant Staphylococcus aureus and antibiotic rotation as strategies to modulate antibiotic resistance in the intensive care unit. PMID:25812462

  8. Eight More Ways To Deal with Antibiotic Resistance

    PubMed Central

    Shlaes, David M.

    2014-01-01

    The fight against antibiotic resistance must be strengthened. We propose actions that U.S. government agencies and private sector entities can take to build a more comprehensive effort. These actions can increase the viability of investing in new antibiotics, ensure the quality and stewardship of all antibiotics, and make responses to emerging resistance more informed. Success requires the thoughtful exercise of federal authority and a firm commitment to share data and reward developers for the value generated with new, life-saving antibiotics. PMID:24867992

  9. Antibiotic resistance: the perfect storm

    Microsoft Academic Search

    I. M. Gould

    2009-01-01

    The worldwide epidemic of antibiotic resistance is in danger of ending the golden age of antibiotic therapy. Resistance impacts on all areas of medicine, and is making successful empirical therapy much more difficult to achieve. Antibiotic choices are often severely restricted, and the pipeline of new antibiotics is almost dry. Resistance cannot be prevented, but its development and spread can

  10. The future of new oral antibiotics including the quinolones.

    PubMed

    Bergeron, M G

    1988-01-01

    It is estimated that more than 110 million dollars' worth of oral antibiotics will have been sold in Canada in 1987. In the next few years several new oral antimicrobial agents will reach the market, including beta-lactamase inhibitors, cephalosporins, monobactams, erythromycins and quinolones. Most of these new agents have a broader spectrum of antibacterial activity than the presently available oral antibiotics. A few have a longer half-life and can be administered once a day. The new oral drugs, especially the quinolones and possibly beta-lactams, will now be used to treat infections that in the past could be treated only parenterally. Exacerbations of pulmonary infections due to Pseudomonas aeruginosa in cystic fibrosis can now be successfully treated at home with the new quinolones. Osteomyelitis, arthritis, pneumonia and pyelonephritis will most likely be treated at home in the future. In severe infections patients will be admitted to hospital for short courses of parenteral therapy, followed by oral treatment. If used appropriately the new oral agents may lead to new approaches to the treatment of infectious diseases. PMID:3275479

  11. Partial antibiotic decontamination.

    PubMed Central

    Guiot, H F; Furth, R

    1977-01-01

    Partial antibiotic decontamination and reverse isolation were carried out in nine patients undergoing bone marrow transplantation. The aim of this approach was to eradicate the patient's endogenous potentially pathogenic bacteria while preserving the anaerobic flora of the gut, which help to prevent recolonisation. No exogenous infections developed, and only one patient developed an infection associated with endogenous recolonisation. Colonisation resistance seemed normal in patients during partial antibiotic decontamination. This form of decontamination deserves further study in patients with immunodepression. PMID:322798

  12. [The history of antibiotics].

    PubMed

    Yazdankhah, Siamak; Lassen, Jørgen; Midtvedt, Tore; Solberg, Claus Ola

    2013-12-10

    The development of chemical compounds for the treatment of infectious diseases may be divided into three phases: a) the discovery in the 1600s in South America of alkaloid extracts from the bark of the cinchona tree and from the dried root of the ipecacuanha bush, which proved effective against, respectively, malaria (quinine) and amoebic dysentery (emetine); b) the development of synthetic drugs, which mostly took place in Germany, starting with Paul Ehrlich's (1854-1915) discovery of salvarsan (1909), and crowned with Gerhard Domagk's (1895-1964) discovery of the sulfonamides (1930s); and c) the discovery of antibiotics. The prime example of the latter is the development of penicillin in the late 1920s following a discovery by a solitary research scientist who never worked in a team and never as part of a research programme. It took another ten years or so before drug-quality penicillin was produced, with research now dependent on being conducted in large collaborative teams, frequently between universities and wealthy industrial companies. The search for new antibiotics began in earnest in the latter half of the 1940s and was mostly based on soil microorganisms. Many new antibiotics were discovered in this period, which may be termed «the golden age of antibiotics». Over the past three decades, the development of new antibiotics has largely stalled, while antibiotic resistance has increased. This situation may require new strategies for the treatment of infectious diseases. PMID:24326504

  13. Stability-indicating spectrofluorometric method for the determination of some cephalosporin drugs via their degradation products.

    PubMed

    Mostafa, Nadia M; Abdel-Fattah, Laila; Weshahy, Soheir A; Hassan, Nagiba Y; Boltia, Shereen A

    2015-01-01

    A stability-indicating spectrofluorometric method was investigated for the determination of three cephalosporin drugs, namely, cefpodoxime proxetil (CPD), cefixime trihydrate (CFX), and cefepime hydrochloride (CPM), via their acid and alkali degradation products. The three drugs were determined via their acid degradation at 432, 422, and 435 nm using an excitation wavelength of 310, 330, and 307 nm for CPD, CFX, and CPM determination, respectively, and via their alkali degradation at 407, 411, and 405 nm using an excitation wavelength of 310, 305, and 297 nm for CPD, CFX, and CPM determination, respectively. Linearity was achieved in the ranges of 0.35-3.50, 0.4-4.0, and 0.3-3.0 ?g/mL for the acid degradation products of CPD, CFX, and CPM, respectively, and in ranges of 0.05-0.5, 0.1-1.0, and 0.08-0.80 ?g/mL for the alkali degradation products of CPD, CFX, and CPM, respectively. The method was validated for various parameters according to International Conference on Harmonization guidelines. The method was successfully applied for the determination of these cephalosporin drugs in pharmaceutical dosage forms with good accuracy and precision. The results obtained by the proposed spectrofluorometric method were compared with good agreement to the official HPLC method. PMID:25905742

  14. Antibiotic use, resistance development and environmental factors: a qualitative study among healthcare professionals in Orissa, India

    Microsoft Academic Search

    Krushna Chandra Sahoo; A J Tamhankar; Eva Johansson; Cecilia Stålsby Lundborg

    2010-01-01

    BACKGROUND: Antibiotic resistance is a major public health problem affecting both current and future generations. The influence of environmental factors on antibiotic use and resistance development in bacteria is largely unknown. This study explored the perceptions of healthcare providers on antibiotic use and resistance development in relation to environmental factors i.e. physical, natural, social and behavioural factors. METHODS: A qualitative

  15. Prevalence, antibiotic resistance, and molecular characterization of Salmonella serovars in retail meat products.

    PubMed

    Hyeon, Ji-Yeon; Chon, Jung-Whan; Hwang, In-Gyun; Kwak, Hyo-Sun; Kim, Moo-Sang; Kim, Soo-Ki; Choi, In-Soo; Song, Chang-Seon; Park, Chankyu; Seo, Kun-Ho

    2011-01-01

    The prevalence of Salmonella was determined in chicken meat (n = 26), beef (n = 49), and pork (n = 56) collected from wholesale markets, retail stores, and traditional markets in Seoul, South Korea, in 2009. Antibiotic resistance was assessed, and the molecular subtypes of Salmonella isolates were ascertained using an automated repetitive sequence-based PCR (rep-PCR) system (DiversiLab). A total of 18 Salmonella strains were isolated from 17 of 131 samples: 16 strains from each of 16 samples and 2 strains from the same pork sample. The prevalence of Salmonella from the retail meats was 2.0% in beef, 8.9% in pork, and 42.3% in chicken meat. Among 10 different serotypes, Salmonella enterica Panama was recovered from a beef sample, and Salmonella London and Salmonella Montevideo were the predominant serotypes from pork and chicken meat, respectively. The highest antibiotic resistance observed was to erythromycin (100%) followed by streptomycin (22.2%) and tetracycline and chloramphenicol (16.7%). Of the 18 isolates, 5 (27.8%) were resistant to two or more antibiotics, and 1 isolate from chicken meat was resistant to eight antibiotics, including cephalosporins. Differentiation between all of the Salmonella isolates except between Salmonella Montevideo and Salmonella London was successfully performed with the automated rep-PCR system, indicating that it can be added to the toolbox for source tracking of foodborne pathogens associated with outbreaks. PMID:21219782

  16. Bile tolerance and its effect on antibiotic susceptibility of probiotic Lactobacillus candidates.

    PubMed

    Hyacinta, Májeková; Hana, Ki?ová Sepová; Andrea, Bilková; Barbora, ?isárová

    2015-05-01

    Before use in practice, it is necessary to precisely identify and characterize a new probiotic candidate. Eight animal lactobacilli and collection strain Lactobacillus reuteri CCM 3625 were studied from the point of saccharide fermentation profiles, bile salt resistance, antibiogram profiles, and influence of bile on sensitivity to antibiotics. Studied lactobacilli differed in their sugar fermentation ability determined by API 50CHL and their identification based on these profiles did not correspond with molecular-biological one in most cases. Survival of strains Lactobacillus murinus C and L. reuteri KO4b was not affected by presence of bile. The resistance of genus Lactobacillus to vancomycin and quinolones (ofloxacin, ciprofloxacin) was confirmed in all strains tested. This study provides the new information about oxgall (0.5 and 1 %) effect on the lactobacilli antibiotic susceptibility. Antibiotic profiles were not noticeably affected, and both bile concentrations tested had comparable impact on the lactobacilli antibiotic sensitivity. Interesting change was noticed in L. murinus C, where the resistance to cephalosporins was reverted to susceptibility. Similarly, susceptibility of L. reuteri E to ceftazidime arose after incubation in both concentration of bile. After influence of 1 % bile, Lactobacillus mucosae D lost its resistance to gentamicin. On the base of gained outcomes, the best probiotic properties manifested L. reuteri KO4b, Lactobacillus plantarum KG4, and L. reuteri E due to their survival in the presence of bile. PMID:25413644

  17. History and epidemiology of antibiotic susceptibilities of Neisseria gonorrhoeae.

    PubMed

    Shigemura, Katsumi; Fujisawa, Masato

    2015-01-01

    Neisseria gonorrhoeae is a common causative microorganism of male urethritis. The most important problem with this infectious disease is antibiotic resistance. For instance, in the 1980's-1990's, most studies showed almost 100% susceptibility of N. gonorrhoeae to the representative cephalosporins, cefixime and cefpodoxime. By the late 1990s, the reported susceptibility decreased to 93.3-100% and further decreased to 82.9-100% in the early 2000's. However, reported susceptibility was revived to 95.8-100% in the late 2000's to 2010's. The susceptibility of N. gonorrhoeae to penicillins varied in different countries and regions. A 2002 Japanese study showed a resistance ratio of about 30% and while Laos, China and Korea showed 80-100% resistance. Fluoroquinolones have shown a dramatic change in their effect on N. gonorrhoeae. In the early 1990's, 0.3-1.3% of N. gonorrhoeae showed low susceptibility or resistance to ciprofloxacin in the US but this figure jumped to 9.5% by 1999. In Asia, N. gonorrhoeae ciprofloxacin resistance or lower susceptibility was about 80-90% in the early 2000's and this trend continues to the present day. Azithromycin is currently the possible last weapon for N. gonorrhoeae treatment per oral administration. The susceptibility of N. gonorrhoeae to azithromycin was 100% in Indonesia in 2004 and the latest study from Germany showed 6% resistance in strains from 2010-2011. This review summarizes the history and epidemiology of N. gonorrhoeae antibiotic susceptibilities, for which the most frequently used antibiotics vary between countries or regions. PMID:25410409

  18. Ultrasound-assisted matrix solid phase dispersive extraction for the simultaneous analysis of ?-lactams (four penicillins and eight cephalosporins) in milk by high performance liquid chromatography with photodiode array detection.

    PubMed

    Karageorgou, Eftichia G; Samanidou, Victoria F; Papadoyannis, Ioannis N

    2012-10-01

    The application of ultrasound-assisted matrix solid phase dispersive extraction for the confirmatory analysis of 12 ?-lactam antibiotics in milk by high performance liquid chromatography with photodiode array detection has been proposed herein. Four penicillins (cloxacillin, dicloxacillin, oxacillin, and amoxicillin) and eight cephalosporins (cefaclor, cefadroxil, ceftiofur, cefuroxime, cefoperazone, cefazolin, cephalexin, and cefotaxime) are effectively extracted using a mixed sorbent of Quick Easy Cheap Effective Rugged Safe technique and OASIS HLB providing a matrix free from any endogenous interference. Examined analytes were well resolved on an Inertsil ODS-3 analytical column with a mobile phase of CH(3)COONH(4) (0.05 M) and acetonitrile delivered under a gradient program. 1,7-Dimethyl-xanthine was used as internal standard. The method was validated meeting the European Legislation determining linearity, selectivity, stability, decision limit, detection capability, accuracy, precision, and ruggedness according to the Youden approach. Recoveries of all antibiotics rated from 85.0 to 115.7%, while RSD values were <12.7%. Finally, the method was successfully applied to milk samples purchased from local market. PMID:22941669

  19. Cephalosporin Resistance among Non-Typhi Salmonella from Humans, Retail Meats and Food Animals in the United States

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: The National Antimicrobial Resistance Monitoring System (NARMS) is a collaboration among the Food and Drug Administration (FDA), U.S. Department of Agriculture (USDA), and the Centers for Disease Control and Prevention (CDC). Here we report on decreased susceptibility to cephalosporins ...

  20. Antibiotic resistant ?-hemolytic streptococci

    Microsoft Academic Search

    Charmaine A. C. Lloyd; Swarna E. Jacob; Thangam Menon

    2007-01-01

    Objective  An antibiotic-sensitivity study was conducted on 117 strains of group A streptococcus (GAS), 60 strains of group G streptococcus\\u000a (GGS) and 20 strains of group C streptococcus (GCS) in order to understand current resistance trends.\\u000a \\u000a \\u000a \\u000a Methods  All strains were tested by the Kirby Bauer disc diffusion method to 15 antibiotics. Resistant strains were confirmed by testing\\u000a the minimum inhibitory concentration (MIC)

  1. Tackling antibiotic resistance

    PubMed Central

    Bush, Karen; Courvalin, Patrice; Dantas, Gautam; Davies, Julian; Eisenstein, Barry; Huovinen, Pentti; Jacoby, George A.; Kishony, Roy; Kreiswirth, Barry N.; Kutter, Elizabeth; Lerner, Stephen A.; Levy, Stuart; Lewis, Kim; Lomovskaya, Olga; Miller, Jeffrey H.; Mobashery, Shahriar; Piddock, Laura J. V.; Projan, Steven; Thomas, Christopher M.; Tomasz, Alexander; Tulkens, Paul M.; Walsh, Timothy R.; Watson, James D.; Witkowski, Jan; Witte, Wolfgang; Wright, Gerry; Yeh, Pamela; Zgurskaya, Helen I.

    2014-01-01

    The development and spread of antibiotic resistance in bacteria is a universal threat to both humans and animals that is generally not preventable, but can nevertheless be controlled and must be tackled in the most effective ways possible. To explore how the problem of antibiotic resistance might best be addressed, a group of thirty scientists from academia and industry gathered at the Banbury Conference Centre in Cold Spring Harbor, New York, May 16-18, 2011. From these discussions emerged a priority list of steps that need to be taken to resolve this global crisis. PMID:22048738

  2. Mission Critical: Preventing Antibiotic Resistance

    MedlinePLUS

    ... Button Past Emails CDC Features Mission Critical: Preventing Antibiotic Resistance Recommend on Facebook Tweet Share Compartir Can you ... spp. So, what can we do to prevent antibiotic resistance in healthcare settings? Patients, healthcare providers, healthcare facility ...

  3. Best antibiotics for buccal delivery

    E-print Network

    Goldberg, Manijeh Nazari

    2011-01-01

    The purpose of the research was to identify the clinical and commercial benefits of switching from intravenous (IV) to buccal delivery of antibiotics. then, the research continued to select 3-5 antibiotics that best met ...

  4. What Can Be Done about Antibiotic Resistance?

    MedlinePLUS

    ... antibiotics for treating human disease. (See Antibiotics in agriculture .) Is there any international action on the antibiotic ... and reducing antibiotic use in animal farming and agriculture. Experts agree that a global system for tracking ...

  5. Antibiotic use for common cold

    Microsoft Academic Search

    Timothy W. Kenealy; Bruce Arroll

    Antibiotics do not help patients with an uncomplicated common cold. Antibiotics can have side effects for the individual taking\\u000a them that range from unpleasant to serious, even lethal. Antibiotic use also contributes to communal harm by encouraging antibiotic\\u000a resistance. If there can be no benefit, but there can be harm, why is the common cold the commonest reason for doctors

  6. Global Perspectives of Antibiotic Resistance

    Microsoft Academic Search

    Carlos F. Amábile-Cuevas

    \\u000a The threat of antibiotic resistance is growing at an alarming pace, perhaps more rapidly in developing countries. Aside from\\u000a the abuse of antibiotics, a number of circumstances converge to this rapid growth and spread, ranging from the biological\\u000a traits that bacteria deploy to face antibiotics, which we are still trying to understand, to regulatory and financial issues\\u000a behind antibiotic abuse.

  7. [Cefuroxime axetil, a new oral cephalosporin for treating infections of the ORL field: clinical synthesis].

    PubMed

    Westphal, J F

    1990-01-01

    Cefuroxime axetil (C.A.E.) is a broad spectrum cephalosporin, suitable for oral route. Its antibacterial activity includes all the pathogens usually responsible for E.N.T. infection, with low M.I.C.'s: H. influenzae, S. pneumoniae, S. aureus, S. pyogene. The stability of the drug against betalactamases, especially those produced by H. influenzae, associated with good bio availability (50%) and tissue penetration (30%) account for the potent in vivo bactericidal activity and clinical efficacy of cefuroxime axetil. More than 1,000 patients had been enrolled in controlled clinical trials: the success rates yielded by C.A.E. were 98%, 96% and 91%, respectively for pharingitis/tonsilitis, otitis media and acute sinusitis. C.A.E. is at least as effective as amoxycillin/clavulanic acid and safety appears to be better. PMID:2087617

  8. In Vitro and Clinical Studies of Cefatrizine, a New Semisynthetic Cephalosporin

    PubMed Central

    Busto, Ramon Del; Haas, Erwin; Madhavan, Tom; Burch, Keith; Cox, Frank; Fisher, Evelyn; Quinn, Edward; Pohlod, Donald

    1976-01-01

    Cefatrizine, a new oral semisynthetic cephalosporin, was evaluated in vitro and in the treatment of 18 patients with acute urinary tract infection, pneumonia, and soft tissue infection. In vitro, it was more active than cephalexin for gram-positive and gram-negative bacteria. It was also more active than cephalothin, cefazolin, and cephapirin against most of the gram-negative bacteria but less active against the gram-positive bacteria. Of the patients treated with cefatrizine, only one failed to respond. This patient had pneumococcal conjunctivitis and hypogammaglobulinemia and neutropenia. The mean peak serum level after multiple 6-hourly doses of 500 mg was 6.2 ?g/ml. The serum levels of cefatrizine necessary for inhibition of most susceptible organisms were well within the achievable range. The drug was well tolerated, and no renal, hepatic, or hematological toxicity was detected. PMID:1259399

  9. [Effectiveness and disposition of the newly developed cephalosporin cefquinome in puerperal septicemia and toxemia in gilts].

    PubMed

    Heinritzi, K; Hagn, J

    1999-04-01

    Epizootiological, clinical, bacteriological and haematological studies were carried out to assess the effectiveness of the recently developed cephalosporin preparation Cefquinome in the treatment of the puerperal septicaemia and toxaemia syndrome. Cefquinome was administered at three different doses (1, 2 and 4 mg/kg BW) to 188 sows with feverish puerperal illness. Amoxicillin (7 mg/kg BW) was used as a control drug. In 41% of cases endometritis was a monoinfection whereas in 70% of mammary infections mixed infections were diagnosed. Results showed that for therapy of puerperal septicaemia and toxaemia Cefquinome at doses of 2 mg/kg BW and 4 mg/kg BW is clearly more effective than the control drug Amoxicillin and Cefquinome at its lowest dose of 1 mg/kg BW. PMID:10326238

  10. Determination of cephalosporins in raw bovine milk by high-performance liquid chromatography.

    PubMed

    Sørensen, L K; Snor, L K

    2000-06-16

    A high-performance liquid chromatographic (HPLC) method based on solid-phase extraction was developed for the determination of cefazolin, cefoperazone, cefquinome and ceftiofur in raw bovine milk. The milk fat was removed by centrifugation and the cephalosporins were extracted in acetonitrile. The extract was cleaned up by solid-phase extraction on an octadecyl sorbent. The compounds were separated by ion-paired gradient HPLC on a phenyl column with ultraviolet detection at 270 nm. The limits of detection estimated by a conservative model were 11 microg/kg for cefazolin and cefoperazone and 7 microg/kg for cequinome and ceftiofur. The mean recoveries were 86-88% for cefazolin, 91-93% for cefoperazone, 69-72% for cefquinome and 84-88% for ceftiofur in the concentration range 20-200 microg/kg. PMID:10895940

  11. Minocycline: far beyond an antibiotic

    PubMed Central

    Garrido-Mesa, N; Zarzuelo, A; Gálvez, J

    2013-01-01

    Minocycline is a second-generation, semi-synthetic tetracycline that has been in therapeutic use for over 30 years because of its antibiotic properties against both gram-positive and gram-negative bacteria. It is mainly used in the treatment of acne vulgaris and some sexually transmitted diseases. Recently, it has been reported that tetracyclines can exert a variety of biological actions that are independent of their anti-microbial activity, including anti-inflammatory and anti-apoptotic activities, and inhibition of proteolysis, angiogenesis and tumour metastasis. These findings specifically concern to minocycline as it has recently been found to have multiple non-antibiotic biological effects that are beneficial in experimental models of various diseases with an inflammatory basis, including dermatitis, periodontitis, atherosclerosis and autoimmune disorders such as rheumatoid arthritis and inflammatory bowel disease. Of note, minocycline has also emerged as the most effective tetracycline derivative at providing neuroprotection. This effect has been confirmed in experimental models of ischaemia, traumatic brain injury and neuropathic pain, and of several neurodegenerative conditions including Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Alzheimer's disease, multiple sclerosis and spinal cord injury. Moreover, other pre-clinical studies have shown its ability to inhibit malignant cell growth and activation and replication of human immunodeficiency virus, and to prevent bone resorption. Considering the above-mentioned findings, this review will cover the most important topics in the pharmacology of minocycline to date, supporting its evaluation as a new therapeutic approach for many of the diseases described herein. PMID:23441623

  12. Molecular Assay for Detection of Genetic Markers Associated with Decreased Susceptibility to Cephalosporins in Neisseria gonorrhoeae.

    PubMed

    Peterson, S W; Martin, I; Demczuk, W; Bharat, A; Hoang, L; Wylie, J; Allen, V; Lefebvre, B; Tyrrell, G; Horsman, G; Haldane, D; Garceau, R; Wong, T; Mulvey, M R

    2015-07-01

    The incidence of antimicrobial-resistant Neisseria gonorrhoeae continues to rise in Canada; however, antimicrobial resistance data are lacking for approximately 70% of gonorrhea infections that are diagnosed directly from clinical specimens by nucleic acid amplification tests (NAATs). We developed a molecular assay for surveillance use to detect mutations in genes associated with decreased susceptibility to cephalosporins that can be applied to both culture isolates and clinical samples. Real-time PCR assays were developed to detect single nucleotide polymorphisms (SNPs) in ponA, mtrR, penA, porB, and one N. gonorrhoeae-specific marker (porA). We tested the real-time PCR assay with 252 gonococcal isolates, 50 nongonococcal isolates, 24 N. gonorrhoeae-negative NAAT specimens, and 34 N. gonorrhoeae-positive NAAT specimens. Twenty-four of the N. gonorrhoeae-positive NAAT specimens had matched culture isolates. Assay results were confirmed by comparison with whole-genome sequencing data. For 252 N. gonorrhoeae strains, the agreement between the DNA sequence and real-time PCR was 100% for porA, ponA, and penA, 99.6% for mtrR, and 95.2% for porB. The presence of ?2 SNPs correlated with decreased susceptibility to ceftriaxone (sensitivities of >98%) and cefixime (sensitivities of >96%). Of 24 NAAT specimens with matched cultures, the agreement between the DNA sequence and real-time PCR was 100% for porB, 95.8% for ponA and mtrR, and 91.7% for penA. We demonstrated the utility of a real-time PCR assay for sensitive detection of known markers for the decreased susceptibility to cephalosporins in N. gonorrhoeae. Preliminary results with clinical NAAT specimens were also promising, as they correlated well with bacterial culture results. PMID:25878350

  13. Survey of plasmid-associated genetic markers in enterobacteriaceae with reduced susceptibilities to cephalosporins.

    PubMed

    Preston, Karen E; Graffunder, Eileen M; Evans, Ann M; Venezia, Richard A

    2003-07-01

    Clinical isolates of Enterobacteriaceae with reduced susceptibilities to cephalosporins were collected from 1993 to 2000. The organisms were screened for the extended-spectrum beta-lactamase (ESBL) phenotype, and plasmid extracts were screened for genetic markers by hybridization. A bla(TEM) probe was derived from pUC19; other probes were derived from pACM1, the plasmid responsible for the first known appearance of an ESBL in our institution. These probes included bla(SHV), int, aac(3)-Ia, dfrA1, IS6100, tetA, IncM markers, and Anon 13, a marker for the Klebsiella pneumoniae chromosomal sequences that flank bla(SHV-5). There were 42 hybridization patterns among 237 isolates. Patterns designated pACM1-like occurred in 44% of the isolates (eight species) and were always associated with the clavulanic acid (CA)-susceptible ESBL phenotype. The TEM marker was not predictive of the ESBL phenotype. Mapping indicated the presence of an SHV marker and up to 7.5 kb of its flanking chromosomal sequences in three non-IncM plasmids obtained in transformation experiments. We theorize that this DNA segment spread to other plasmids from pACM1-like sources. CA insensitivity became more frequent with time and was usually associated with either the TEM marker or the absence of both bla markers. One plasmid-encoded enzyme with characteristics of an AmpC beta-lactamase was observed in a transformant lacking both TEM and SHV markers. Although SHV type ESBLs were a continuing source of reduced susceptibility to cephalosporins in our institution, organisms with different resistance mechanisms were added to the hospital microflora in later years. These changes might be related, in part, to ESBL control strategies implemented in 1995. PMID:12821465

  14. Reservoirs of Antibiotic Resistance Genes

    Microsoft Academic Search

    Abigail Salyers; Nadja B. Shoemaker

    2006-01-01

    A potential concern about the use of antibiotics in animal husbundary is that, as antibiotic resistant bacteria move from the farm into the human diet, they may pass antibiotic resistance genes to bacteria that normally reside in a the human intestinal tract and from there to bacteria that cause human disease (reservoir hypothesis). In this article various approaches to evaluating

  15. Identification of amino acids conferring high-level resistance to expanded-spectrum cephalosporins in the penA gene from Neisseria gonorrhoeae strain H041.

    PubMed

    Tomberg, Joshua; Unemo, Magnus; Ohnishi, Makoto; Davies, Christopher; Nicholas, Robert A

    2013-07-01

    The recent identification of a high-level-ceftriaxone-resistant (MIC = 2 to 4 ?g/ml) isolate of Neisseria gonorrhoeae from Japan (H041) portends the loss of ceftriaxone as an effective treatment for gonococcal infections. This is of grave concern because ceftriaxone is the last remaining option for first-line empirical antimicrobial monotherapy. The penA gene from H041 (penA41) is a mosaic penA allele similar to mosaic alleles conferring intermediate-level cephalosporin resistance (Ceph(i)) worldwide but has 13 additional mutations compared to the mosaic penA gene from the previously studied Ceph(i) strain 35/02 (penA35). When transformed into the wild-type strain FA19, the penA41 allele confers 300- and 570-fold increases in the MICs for ceftriaxone and cefixime, respectively. In order to understand the mechanisms involved in high-level ceftriaxone resistance and to improve surveillance and epidemiology during the potential emergence of ceftriaxone resistance, we sought to identify the minimum number of amino acid alterations above those in penA35 that confer high-level resistance to ceftriaxone. Using restriction fragment exchange and site-directed mutagenesis, we identified three mutations, A311V, T316P, and T483S, that, when incorporated into the mosaic penA35 allele, confer essentially all of the increased resistance of penA41. A311V and T316P are close to the active-site nucleophile Ser310 that forms the acyl-enzyme complex, while Thr483 is predicted to interact with the carboxylate of the ?-lactam antibiotic. These three mutations have thus far been described only for penA41, but dissemination of these mutations in other mosaic alleles would spell the end of ceftriaxone as an effective treatment for gonococcal infections. PMID:23587946

  16. Concurrent Use of Warfarin and Antibiotics and the Risk of Bleeding in Older Adults

    PubMed Central

    Baillargeon, Jacques; Holmes, Holly M.; Lin, Yu-li; Raji, Mukaila A.; Sharma, Gulshan; Kuo, Yong-Fang

    2011-01-01

    Background Antibiotic medications are associated with an increased risk of bleeding among patients receiving warfarin. The recent availability of data from the Medicare Part D prescription drug program provides an opportunity to assess the association of antibiotic medications and the risk of bleeding in a national population of older adults receiving warfarin. Methods We conducted a case-control study nested within a cohort of 38,762 patients aged 65 years and older who were continuous warfarin users, using enrollment and claims data for a 5% national sample of Medicare beneficiaries with Part D benefits. Cases were defined as persons hospitalized for a primary diagnosis of bleeding and were matched with three control subjects on age, race, gender, and indication for warfarin. Logistic regression analysis was used to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the risk of bleeding associated with prior exposure to antibiotic medications. Results Exposure to any antibiotic agent within the 15 days of the event/index date was associated with an increased risk of bleeding (aOR 2.01; 95% CI, 1.62-2.50). All six specific antibiotic drug classes examined [azole antifungals (aOR, 4.57; 95% CI, 1.90-11.03), macrolides (aOR, 1.86; 95% CI, 1.08-3.21), quinolones (aOR, 1.69; 95% CI, 1.09-2.62), cotrimoxazole (aOR, 2.70; 95% CI, 1.46-5.05), penicillins (aOR, 1.92; 95% CI, 1.21-2.07) and cephalosporins (aOR, 2.45; 95% CI, 1.52-3.95) were associated with an increased risk of bleeding. Conclusion Among older continuous warfarin users, exposure to antibiotic agents—particularly azole antifungals—was associated with an increased risk of bleeding. PMID:22269622

  17. Reversing resistance: The next generation antibacterials.

    PubMed

    Shah, Neel Jayesh

    2015-01-01

    Irrational antibiotic usage has led to vast spread resistance to available antibiotics, but we refuse to slide back to "preantibiotic era." The threat is serious with the "Enterococcus, Staphylococcous, Klebsiella, Acinetobacter, Pseudomonas and Enterobacter" organisms causing nosocomial infections that are difficult to treat because of the production of extended spectrum ?-lactamases, carbapenamases and metallo-?-lactamases. Facing us is a situation where soon multidrug resistance would have spread across the globe with no antibiotics to withstand it. The infectious disease society of America and Food and Drug Administration have taken initiatives like the 10 × '20 where they plan to develop 10 new antibiotics by the year 2020. Existing classes of antibiotics against resistant bacteria include the carbapenems, oxazolidinones, glycopeptides, monobactams, streptogramins and daptomycin. Newer drugs in existing classes of antibiotics such as cephalosporins, aminoglycosides, tetracyclines, glycopeptides and ?-lactamase inhibitors continue to get synthesized. The situation demands newer targets against bacterial machinery. Some of them include the peptidoglycantransferase, outer membrane protein of Pseudomonas, tRNA synthase, fatty acid synthase and mycobacterial ATP synthase. To curb the irrational and excessive usage of presently available antibiotics should be a priority if they are still to be kept in usage for the future. PMID:26069360

  18. Reversing resistance: The next generation antibacterials

    PubMed Central

    Shah, Neel Jayesh

    2015-01-01

    Irrational antibiotic usage has led to vast spread resistance to available antibiotics, but we refuse to slide back to “preantibiotic era.” The threat is serious with the “Enterococcus, Staphylococcous, Klebsiella, Acinetobacter, Pseudomonas and Enterobacter” organisms causing nosocomial infections that are difficult to treat because of the production of extended spectrum ?-lactamases, carbapenamases and metallo-?-lactamases. Facing us is a situation where soon multidrug resistance would have spread across the globe with no antibiotics to withstand it. The infectious disease society of America and Food and Drug Administration have taken initiatives like the 10 × ‘20 where they plan to develop 10 new antibiotics by the year 2020. Existing classes of antibiotics against resistant bacteria include the carbapenems, oxazolidinones, glycopeptides, monobactams, streptogramins and daptomycin. Newer drugs in existing classes of antibiotics such as cephalosporins, aminoglycosides, tetracyclines, glycopeptides and ?-lactamase inhibitors continue to get synthesized. The situation demands newer targets against bacterial machinery. Some of them include the peptidoglycantransferase, outer membrane protein of Pseudomonas, tRNA synthase, fatty acid synthase and mycobacterial ATP synthase. To curb the irrational and excessive usage of presently available antibiotics should be a priority if they are still to be kept in usage for the future. PMID:26069360

  19. The abundance of antibiotic resistance genes in human guts has correlation to the consumption of antibiotics in animal

    PubMed Central

    Hu, Yongfei; Yang, Xi; Lu, Na; Zhu, Baoli

    2014-01-01

    Increasing evidence has accumulated to support that the human gut is a reservoir for antibiotic resistance genes. We previously identified more than 1000 genes displaying high similarity with known antibiotic resistance genes in the human gut gene set generated from the Chinese, Danish, and Spanish populations. Here, first, we add our new understanding of antibiotic resistance genes in the US and the Japanese populations; next, we describe the structure of a vancomycin-resistant operon in a Danish sample; and finally, we provide discussions on the correlation of the abundance of resistance genes in human gut with the antibiotic consumption in human medicine and in animal husbandry. These results, combined with those we published previously, provide comprehensive insights into the antibiotic resistance genes in the human gut microbiota at a population level. PMID:24637798

  20. Generic antibiotics in Japan.

    PubMed

    Fujimura, Shigeru; Watanabe, Akira

    2012-08-01

    Generic drugs have been used extensively in many developed countries, although their use in Japan has been limited. Generic drugs reduce drug expenses and thereby national medical expenditure. Because generic drugs provide advantages for both public administration and consumers, it is expected that they will be more widely used in the future. However, the diffusion rate of generic drugs in Japan is quite low compared with that of other developed countries. An investigation on generic drugs conducted by the Ministry of Health, Labour and Welfare in Japan revealed that 17.2 % of doctors and 37.2 % of patients had not used generic drugs. The major reasons for this low use rate included distrust of off-patent products and lower drug price margin compared with the brand name drug. The generic drugs available in the market include external drugs such as wet packs, antihypertensive agents, analgesics, anticancer drugs, and antibiotics. Among them, antibiotics are frequently used in cases of acute infectious diseases. When the treatment of these infections is delayed, the infection might be aggravated rapidly. The pharmacokinetics-pharmacodynamics (PK-PD) theory has been adopted in recent chemotherapy, and in many cases, the most appropriate dosage and administration of antibiotics are determined for individual patients considering renal function; high-dosage antibiotics are used preferably for a short duration. Therefore, a highly detailed antimicrobial agent is necessary. However, some of the generic antibiotics have less antibacterial potency or solubility than the brand name products. We showed that the potency of the generic products of vancomycin and teicoplanin is lower than that of the branded drugs by 14.6 % and 17.3 %, respectively. Furthermore, we confirmed that a generic meropenem drug for injection required about 82 s to solubilize in saline, whereas the brand product required only about 21 s. It was thought that the cause may be the difference in size of bulk particle and amount of solubilizer. The Japanese government hopes to increase the diffusion rate of generic drugs (in terms of quantity) from 20.2 % in 2010 to 30 % or more in 2012, and therefore it will be necessary to clarify the advantages of generic antibiotics in terms of expenditure and equivalency with the branded drugs. PMID:22684334

  1. The Comprehensive Antibiotic Resistance Database

    PubMed Central

    McArthur, Andrew G.; Waglechner, Nicholas; Nizam, Fazmin; Yan, Austin; Azad, Marisa A.; Baylay, Alison J.; Bhullar, Kirandeep; Canova, Marc J.; De Pascale, Gianfranco; Ejim, Linda; Kalan, Lindsay; King, Andrew M.; Koteva, Kalinka; Morar, Mariya; Mulvey, Michael R.; O'Brien, Jonathan S.; Pawlowski, Andrew C.; Piddock, Laura J. V.; Spanogiannopoulos, Peter; Sutherland, Arlene D.; Tang, Irene; Taylor, Patricia L.; Thaker, Maulik; Wang, Wenliang; Yan, Marie; Yu, Tennison

    2013-01-01

    The field of antibiotic drug discovery and the monitoring of new antibiotic resistance elements have yet to fully exploit the power of the genome revolution. Despite the fact that the first genomes sequenced of free living organisms were those of bacteria, there have been few specialized bioinformatic tools developed to mine the growing amount of genomic data associated with pathogens. In particular, there are few tools to study the genetics and genomics of antibiotic resistance and how it impacts bacterial populations, ecology, and the clinic. We have initiated development of such tools in the form of the Comprehensive Antibiotic Research Database (CARD; http://arpcard.mcmaster.ca). The CARD integrates disparate molecular and sequence data, provides a unique organizing principle in the form of the Antibiotic Resistance Ontology (ARO), and can quickly identify putative antibiotic resistance genes in new unannotated genome sequences. This unique platform provides an informatic tool that bridges antibiotic resistance concerns in health care, agriculture, and the environment. PMID:23650175

  2. The comprehensive antibiotic resistance database.

    PubMed

    McArthur, Andrew G; Waglechner, Nicholas; Nizam, Fazmin; Yan, Austin; Azad, Marisa A; Baylay, Alison J; Bhullar, Kirandeep; Canova, Marc J; De Pascale, Gianfranco; Ejim, Linda; Kalan, Lindsay; King, Andrew M; Koteva, Kalinka; Morar, Mariya; Mulvey, Michael R; O'Brien, Jonathan S; Pawlowski, Andrew C; Piddock, Laura J V; Spanogiannopoulos, Peter; Sutherland, Arlene D; Tang, Irene; Taylor, Patricia L; Thaker, Maulik; Wang, Wenliang; Yan, Marie; Yu, Tennison; Wright, Gerard D

    2013-07-01

    The field of antibiotic drug discovery and the monitoring of new antibiotic resistance elements have yet to fully exploit the power of the genome revolution. Despite the fact that the first genomes sequenced of free living organisms were those of bacteria, there have been few specialized bioinformatic tools developed to mine the growing amount of genomic data associated with pathogens. In particular, there are few tools to study the genetics and genomics of antibiotic resistance and how it impacts bacterial populations, ecology, and the clinic. We have initiated development of such tools in the form of the Comprehensive Antibiotic Research Database (CARD; http://arpcard.mcmaster.ca). The CARD integrates disparate molecular and sequence data, provides a unique organizing principle in the form of the Antibiotic Resistance Ontology (ARO), and can quickly identify putative antibiotic resistance genes in new unannotated genome sequences. This unique platform provides an informatic tool that bridges antibiotic resistance concerns in health care, agriculture, and the environment. PMID:23650175

  3. Reviving old antibiotics.

    PubMed

    Theuretzbacher, Ursula; Van Bambeke, Françoise; Cantón, Rafael; Giske, Christian G; Mouton, Johan W; Nation, Roger L; Paul, Mical; Turnidge, John D; Kahlmeter, Gunnar

    2015-08-01

    In the face of increasing antimicrobial resistance and the paucity of new antimicrobial agents it has become clear that new antimicrobial strategies are urgently needed. One of these is to revisit old antibiotics to ensure that they are used correctly and to their full potential, as well as to determine whether one or several of them can help alleviate the pressure on more recent agents. Strategies are urgently needed to 're-develop' these drugs using modern standards, integrating new knowledge into regulatory frameworks and communicating the knowledge from the research bench to the bedside. Without a systematic approach to re-developing these old drugs and rigorously testing them according to today's standards, there is a significant risk of doing harm to patients and further increasing multidrug resistance. This paper describes factors to be considered and outlines steps and actions needed to re-develop old antibiotics so that they can be used effectively for the treatment of infections. PMID:26063727

  4. Pneumococcal resistance to antibiotics.

    PubMed Central

    Klugman, K P

    1990-01-01

    The geographic distribution of pneumococci resistant to one or more of the antibiotics penicillin, erythromycin, trimethoprim-sulfamethoxazole, and tetracycline appears to be expanding, and there exist foci of resistance to chloramphenicol and rifampin. Multiply resistant pneumococci are being encountered more commonly and are more often community acquired. Factors associated with infection caused by resistant pneumococci include young age, duration of hospitalization, infection with a pneumococcus of serogroup 6, 19, or 23 or serotype 14, and exposure to antibiotics to which the strain is resistant. At present, the most useful drugs for the management of resistant pneumococcal infections are cefotaxime, ceftriaxone, vancomycin, and rifampin. If the strains are susceptible, chloramphenicol may be useful as an alternative, less expensive agent. Appropriate interventions for the control of resistant pneumococcal outbreaks include investigation of the prevalence of resistant strains, isolation of patients, possible treatment of carriers, and reduction of usage of antibiotics to which the strain is resistant. The molecular mechanisms of penicillin resistance are related to the structure and function of penicillin-binding proteins, and the mechanisms of resistance to other agents involved in multiple resistance are being elucidated. Recognition is increasing of the standard screening procedure for penicillin resistance, using a 1-microgram oxacillin disk. PMID:2187594

  5. Rationalizing antibiotic use to limit antibiotic resistance in India.

    PubMed

    Ganguly, Nirmal K; Arora, N K; Chandy, Sujith J; Fairoze, Mohamed Nadeem; Gill, J P S; Gupta, Usha; Hossain, Shah; Joglekar, Sadhna; Joshi, P C; Kakkar, Manish; Kotwani, Anita; Rattan, Ashok; Sudarshan, H; Thomas, Kurien; Wattal, Chand; Easton, Alice; Laxminarayan, Ramanan

    2011-09-01

    Antibiotic resistance, a global concern, is particularly pressing in developing nations, including India, where the burden of infectious disease is high and healthcare spending is low. The Global Antibiotic Resistance Partnership (GARP) was established to develop actionable policy recommendations specifically relevant to low- and middle-income countries where suboptimal access to antibiotics - not a major concern in high-income countries - is possibly as severe a problem as is the spread of resistant organisms. This report summarizes the situation as it is known regarding antibiotic use and growing resistance in India and recommends short and long term actions. Recommendations aim at (i) reducing the need for antibiotics; (ii) lowering resistance-enhancing drug pressure through improved antibiotic targeting, and (iii) eliminating antibiotic use for growth promotion in agriculture. The highest priority needs to be given to (i) national surveillance of antibiotic resistance and antibiotic use - better information to underpin decisions on standard treatment guidelines, education and other actions, as well as to monitor changes over time; (ii) increasing the use of diagnostic tests, which necessitates behavioural changes and improvements in microbiology laboratory capacity; (iii) setting up and/or strengthening infection control committees in hospitals; and (iv) restricting the use of antibiotics for non-therapeutic uses in agriculture. These interventions should help to reduce the spread of antibiotic resistance, improve public health directly, benefit the populace and reduce pressure on the healthcare system. Finally, increasing the types and coverage of childhood vaccines offered by the government would reduce the disease burden enormously and spare antibiotics. PMID:21985810

  6. Chromatography as an analytical tool for selected antibiotic classes: a reappraisal addressed to pharmacokinetic applications.

    PubMed

    Marzo, A; Dal Bo, L

    1998-07-01

    The first antibiotic discovered, penicillin, appeared on the market just after the Second World War. Intensive research in subsequent years led to the discovery and development of cephalosporins, aminoglycosides, tetracyclines and rifamycin. The chemotherapeutic quinolones and the more recently discovered fluoroquinolones have added promising new therapeutic weapons to fight the microbial challenge. The major role pharmacokinetics has played in developing these compounds should be highlighted. Plasma concentration-time profiles and the therapeutic activity evoked by these compounds allow the therapeutic window, doses and dose turnovers to be appropriately defined as well as possible dose adjustment to be made in renal failure. The pharmacokinetics of antimicrobial agents were initially explored by using microbiological methods, but these lack specificity. The HPLC technique with UV, fluorometric, electrochemical and, in some cases, mass spectrometry detection has satisfactory solved the problem of antimicrobial agent assay for pharmacokinetic, bioavailability and bioequivalence purposes alike. Indeed, in these studies, plasma concentrations of the given analyte must be followed up for a period > or = 3 times the half-life, which calls for specific sensitive assays. In the review, the authors have described the analytical methods employed in the pharmacokinetics of antibiotics, including some chemotherapeutic agents which are used in medical practice as alternatives to antibiotics. The pharmacokinetic characteristics of each class of drugs are also briefly described, and some historical and chemical notes on the various classes are given. PMID:9691307

  7. Comparison between experimental and theoretical values of effectiveness factor in cephalosporin C production process with immobilized cells

    Microsoft Academic Search

    M. Lucia G. C. Araujo; Roberto C. Giordano; Carlos O. Hokka

    1998-01-01

    Cells ofCephalosporium acretnonium ATCC 48272 immobilized in calcium alginate beads were utilized for cephalosporin C production and the results were compared\\u000a with those obtained with free cells. The experiments were performed with synthetic medium containing glucose and sucrose as\\u000a carbon and energy sources. Experimental effectiveness factor values were obtained at various cell and dissolved-oxygen concentrations,\\u000a considering Monod kinetics for the

  8. Residue analysis of 15 penicillins and cephalosporins in bovine muscle, kidney and milk by liquid chromatography–tandem mass spectrometry

    Microsoft Academic Search

    Matthias Becker; Erhard Zittlau; Michael Petz

    2004-01-01

    A sensitive and specific liquid chromatographic–tandem mass spectrometric (LC–MS–MS) method for most of those penicillins and cephalosporins for which EU maximum residue limits (MRL) were set in Council regulation (EEC) 2377\\/90 was developed and validated in bovine muscle, kidney and milk. The analytes were extracted with acetonitrile\\/water and cleaned-up by a single reversed-phase solid-phase extraction step. Highest sensitivity for the

  9. Glutamate Dehydrogenase Specific Activity and Cephalosporin C Synthesis in the M8650 Series of Cephalosporium acremonium Mutants

    PubMed Central

    Queener, S. W.; McDermott, J.; Radue, A. B.

    1975-01-01

    Conditions for the accurate measure of glutamic dehydrogenase (GDH) from Cephalosporium acremonium were determined. Km values for ?-ketoglutarate and ammonium ion were 7 and 15 mM, respectively. The half-saturation for reduced nicotinamide adenine dinucleotide phosphate was 5 ?M. Reduced nicotinamide adenine dinucleotide did not serve as a cofactor for the enzyme. The specific activity of GDH was measured in six mutants of C. acremonium which varied in their ability to synthesize cephalosporin C. The mutants represented two separately derived lines, A and B. The four mutants in line B were characterized by a derepression of the GDH upon entry into stationary phase. The two mutants in line A were characterized by repressed levels of GDH during the same period. Both lines exhibited high GDH activity early in their fermentations, but activity decreased during the period of active cell growth. Cytochrome c concentrations followed the same pattern as total soluble intracellular protein. Line A mutants were low in cephalosporin C productivity and line B encompassed low, intermediate, and high productivity mutants. The relative frequency of yield improvements in line A and B indicate that the altered regulation pattern for GDH in line B may have removed a nitrogen limitation for cephalosporin C synthesis. PMID:1170808

  10. Antibiotic resistance in pediatric urology

    PubMed Central

    Copp, Hillary L.

    2014-01-01

    Antibiotics are a mainstay in the treatment of bacterial infections, though their use is a primary risk factor for the development of antibiotic resistance. Antibiotic resistance is a growing problem in pediatric urology as demonstrated by increased uropathogen resistance. Lack of urine testing, nonselective use of prophylaxis, and poor empiric prescribing practices exacerbate this problem. This article reviews antibiotic utilization in pediatric urology with emphasis on modifiable practice patterns to potentially help mitigate the growing rates of antibiotic resistance. This includes urine testing to only treat when indicated and tailor broad-spectrum therapy as able; selective application of antibiotic prophylaxis to patients with high-grade vesicoureteral reflux and hydronephrosis with counseling regarding the importance of compliance; and using local antiobiograms, particularly pediatric-specific antiobiograms, with inpatient versus outpatient data. PMID:24688601

  11. The Role of Antibiotic Prophylaxis in Prevention of Wound Infection After Lichtenstein Open Mesh Repair of Primary Inguinal Hernia

    PubMed Central

    Aufenacker, Theo J.; van Geldere, Dirk; van Mesdag, Taco; Bossers, Astrid N.; Dekker, Benno; Scheijde, Edo; van Nieuwenhuizen, Roos; Hiemstra, Esther; Maduro, John H.; Juttmann, Jan-Willem; Hofstede, Diederik; van Der Linden, Cunera T. M.; Gouma, Dirk J.; Simons, Maarten P.

    2004-01-01

    Objective: To determine whether the use of prophylactic antibiotics is effective in the prevention of postoperative wound infection after Lichtenstein open mesh inguinal hernia repair. Summary Background Data: A recent Cochrane meta-analysis (2003) concluded that “antibiotic prophylaxis for elective inguinal hernia repair cannot be firmly recommended or discarded.” Methods: Patients with a primary inguinal hernia scheduled for Lichtenstein repair were randomized to a preoperative single dose of 1.5 g intravenous cephalosporin or a placebo. Patients with recurrent hernias, immunosuppressive diseases, or allergies for the given antibiotic were excluded. Infection was defined using the Centers for Disease Control and Prevention criteria. Results: We included 1040 patients in the study between November 1998 and May 2003. According to the intention-to-treat principle, 1008 patients were analyzed. There were 8 infections (1.6%) in the antibiotic prophylaxis group and 9 (1.8%) in the placebo group (P = 0.82). There was 1 deep infection in the antibiotic prophylaxis group and 2 in the placebo group (P = 0.57). Statistical analysis showed an absolute risk reduction of 0.19% (95% confidence interval, ?1.78%–1.40%) and a number needed to treat of 520 for the total number of infections. For deep infection, the absolute risk reduction is 0.20% (95% confidence interval, ?0.87%–0.48%) with a number needed to treat of 508. Conclusions: A low percentage (1.7%) of wound infection after Lichtenstein open mesh inguinal (primary) hernia repair was found, and there was no difference between the antibiotic prophylaxis or placebo group. The results show that, in Lichtenstein inguinal primary hernia repair, antibiotic prophylaxis is not indicated in low-risk patients. PMID:15570201

  12. Liquid antibiotics in bone cement

    PubMed Central

    Chang, Y. H.; Tai, C. L.; Hsu, H. Y.; Hsieh, P. H.; Lee, M. S.; Ueng, S. W. N.

    2014-01-01

    Objectives The objective of this study was to compare the elution characteristics, antimicrobial activity and mechanical properties of antibiotic-loaded bone cement (ALBC) loaded with powdered antibiotic, powdered antibiotic with inert filler (xylitol), or liquid antibiotic, particularly focusing on vancomycin and amphotericin B. Methods Cement specimens loaded with 2 g of vancomycin or amphotericin B powder (powder group), 2 g of antibiotic powder and 2 g of xylitol (xylitol group) or 12 ml of antibiotic solution containing 2 g of antibiotic (liquid group) were tested. Results Vancomycin elution was enhanced by 234% in the liquid group and by 12% in the xylitol group compared with the powder group. Amphotericin B elution was enhanced by 265% in the liquid group and by 65% in the xylitol group compared with the powder group. Based on the disk-diffusion assay, the eluate samples of vancomycin-loaded ALBC of the liquid group exhibited a significantly larger inhibitory zone than samples of the powder or the xylitol group. Regarding the ALBCs loaded with amphotericin B, only the eluate samples of the liquid group exhibited a clear inhibitory zone, which was not observed in either the xylitol or the powder groups. The ultimate compressive strength was significantly reduced in specimens containing liquid antibiotics. Conclusions Adding vancomycin or amphotericin B antibiotic powder in distilled water before mixing with bone cement can significantly improve the efficiency of antibiotic release than can loading ALBC with the same dose of antibiotic powder. This simple and effective method for preparation of ALBCs can significantly improve the efficiency of antibiotic release in ALBCs. Cite this article: Bone Joint Res 2014;3:246–51. PMID:25104836

  13. Counteraction of antibiotic production and degradation stabilizes microbial communities.

    PubMed

    Kelsic, Eric D; Zhao, Jeffrey; Vetsigian, Kalin; Kishony, Roy

    2015-05-28

    A major challenge in theoretical ecology is understanding how natural microbial communities support species diversity, and in particular how antibiotic-producing, -sensitive and -resistant species coexist. While cyclic ‘rock–paper–scissors’ interactions can stabilize communities in spatial environments, coexistence in unstructured environments remains unexplained. Here, using simulations and analytical models, we show that the opposing actions of antibiotic production and degradation enable coexistence even in well-mixed environments. Coexistence depends on three-way interactions in which an antibiotic-degrading species attenuates the inhibitory interactions between two other species. These interactions enable coexistence that is robust to substantial differences in inherent species growth rates and to invasion by ‘cheating’ species that cease to produce or degrade antibiotics. At least two antibiotics are required for stability, with greater numbers of antibiotics enabling more complex communities and diverse dynamic behaviours ranging from stable fixed points to limit cycles and chaos. Together, these results show how multi-species antibiotic interactions can generate ecological stability in both spatially structured and mixed microbial communities, suggesting strategies for engineering synthetic ecosystems and highlighting the importance of toxin production and degradation for microbial biodiversity. PMID:25992546

  14. In Vitro Activities of Cephalosporins and Quinolones against Escherichia coli Strains Isolated from Diarrheic Dairy Calves

    PubMed Central

    Orden, José Antonio; Ruiz-Santa-Quiteria, José Antonio; García, Silvia; Cid, Dolores; de la Fuente, Ricardo

    1999-01-01

    The in vitro activities of several cephalosporins and quinolones against 195 strains of Escherichia coli isolated from dairy calves affected by neonatal diarrhea were determined. One hundred thirty-seven of these strains produced one or more potential virulence factors (F5, F41, F17, cytotoxic necrotizing factor, verotoxin, and the eae gene), but the remaining 58 strains did not produce any of these factors. From 11 to 18% of the E. coli strains were resistant to cephalothin, nalidixic acid, enoxacin, and enrofloxacin. However, cefuroxime, cefotaxime, and cefquinome were highly effective against the E. coli isolates tested. Some significant differences (P < 0.05) in resistance to quinolones between the strains producing potential virulence factors and nonfimbriated, nontoxigenic, eae-negative strains were found. Thus, eae-positive, necrotoxigenic, and verotoxigenic (except for nalidixic acid) E. coli strains were significantly more sensitive to nalidixic acid, enoxacin, and enrofloxacin than nonfimbriated, nontoxigenic, eae-negative strains. Moreover, eae-positive strains were significantly more sensitive to enoxacin and enrofloxacin than F5-positive strains. Thus, the results of this study suggest that the bovine E. coli strains that produce some potential virulence factors are more sensitive to quinolones than those that do not express these factors. PMID:10049259

  15. In vitro activities of cephalosporins and quinolones against Escherichia coli strains isolated from diarrheic dairy calves.

    PubMed

    Orden, J A; Ruiz-Santa-Quiteria, J A; García, S; Cid, D; De La Fuente, R

    1999-03-01

    The in vitro activities of several cephalosporins and quinolones against 195 strains of Escherichia coli isolated from diary calves affected by neonatal diarrhea were determined. One hundred thirty-seven of these strains produced one or more potential virulence factors (F5, F41, F17, cytotoxic necrotizing factor, verotoxin, and the eae gene), but the remaining 58 strains did not produce any of these factors. From 11 to 18% of the E. coli strains were resistant to cephalothin, nalidixic acid, enoxacin, and enrofloxacin. However, cefuroxime, cefotaxime, and cefquinome were highly effective against the E. coli isolates tested. Some significant differences (P < 0.05) in resistance to quinolones between the strains producing potential virulence factors and nonfimbriated, nontoxigenic, eae-negative strains were found. Thus, eae-positive, necrotoxigenic, and verotoxigenic (except for nalidixic acid) E. coli strains were significantly more sensitive to nalidixic acid, enoxacin, and enrofloxacin than nonfimbriated, nontoxigenic, eae-negative strains. Moreover, eae-positive strains were significantly more sensitive to enoxacin and enrofloxacin than F5-positive strains. Thus, the result of this study suggest that the bovine E. coli strains that produce some potential virulence factors are more sensitive to quinolones than those that do not express these factors. PMID:10049259

  16. Cephalosporin-resistant Escherichia coli among Summer Camp Attendees with Salmonellosis

    PubMed Central

    Mirelis, Beatriz; Miró, Elisenda; Navarro, Ferran; Llovet, Teresa; Johnson, James R.; Camps, Neus; Domínguez, Ángela; Salleras, Lluis

    2003-01-01

    Investigation of an acute gastroenteritis outbreak involving >100 persons at a summer camp in Girona, Spain, in June 2002 led to the detection of Salmonella and extended-spectrum cephalosporin-resistant Escherichia coli (ESCREC). Stool cultures were performed for 22 symptomatic campers, three asymptomatic food handlers, and 10 healthy household members. Of the 22 campers, 19 had Salmonella enterica, 9 had an ESCREC strain carrying an extended-spectrum ?-lactamase, and 2 had a second ESCREC strain carrying a plasmidic cephamycinase. Related ESCREC were detected in two (salmonella-negative) asymptomatic food handlers and in none of the healthy household members. Fecal ESCREC and its ?-lactamases and plasmids were extensively characterized. Three of the five ESCREC clones were recovered from multiple hosts. The apparent dissemination of ESCREC suggests a food or water vehicle. The observed distribution of resistance plasmids and ?-lactamase genes in several clones indicates a high degree of horizontal transfer. Heightened vigilance and increased efforts must be made to discover the reservoirs and vehicles for community dissemination of ESCREC. PMID:14609463

  17. Affinity of the New Cephalosporin CXA-101 to Penicillin-Binding Proteins of Pseudomonas aeruginosa?

    PubMed Central

    Moyá, Bartolomé; Zamorano, Laura; Juan, Carlos; Ge, Yigong; Oliver, Antonio

    2010-01-01

    CXA-101, previously designated FR264205, is a new antipseudomonal cephalosporin. The objective of this study was to determine the penicillin-binding protein (PBP) inhibition profile of CXA-101 compared to that of ceftazidime (PBP3 inhibitor) and imipenem (PBP2 inhibitor). Killing kinetics, the induction of AmpC expression, and associated changes on cell morphology were also investigated. The MICs for CXA-101, ceftazidime, and imipenem were 0.5, 1, and 1 ?g/ml, respectively. Killing curves revealed that CXA-101 shows a concentration-independent bactericidal activity, with concentrations of 1× the MIC (0.5 ?g/ml) producing a >3-log reduction in bacterial load after 8 h of incubation. Live-dead staining showed that concentrations of CXA-101 as low as 0.5× the MIC stopped bacterial septation and induced an intense filamentation, which is consistent with the documented high affinity of PBP3. CXA-101 was found to be a potent PBP3 inhibitor and showed affinities ?2-fold higher than those of ceftazidime for all of the essential PBPs (1b, 1c, 2, and 3). Compared to imipenem, in addition to the obvious inverse PBP2/PBP3 affinities, CXA-101 showed a significantly higher affinity for PBP1b but a lower affinity for PBP1c. Furthermore, CXA-101, like ceftazidime and in contrast to imipenem, was found to be a very weak inducer of AmpC expression, consistent with the low PBP4 affinity documented. PMID:20547785

  18. Low or high doses of cefquinome targeting low or high bacterial inocula cure Klebsiella pneumoniae lung infections but differentially impact the levels of antibiotic resistance in fecal flora.

    PubMed

    Vasseur, Maleck V; Laurentie, Michel; Rolland, Jean-Guy; Perrin-Guyomard, Agnès; Henri, Jérôme; Ferran, Aude A; Toutain, Pierre-Louis; Bousquet-Mélou, Alain

    2014-01-01

    The combination of efficacious treatment against bacterial infections and mitigation of antibiotic resistance amplification in gut microbiota is a major challenge for antimicrobial therapy in food-producing animals. In rats, we evaluated the impact of cefquinome, a fourth-generation cephalosporin, on both Klebsiella pneumoniae lung infection and intestinal flora harboring CTX-M-producing Enterobacteriaceae. Germfree rats received a fecal flora specimen from specific-pathogen-free pigs, to which a CTX-M-producing Escherichia coli strain had been added. K. pneumoniae cells were inoculated in the lungs of these gnotobiotic rats by using either a low (10(5) CFU) or a high (10(9) CFU) inoculum. Without treatment, all animals infected with the low or high K. pneumoniae inoculum developed pneumonia and died before 120 h postchallenge. In the treated groups, the low-inoculum rats received a 4-day treatment of 5 mg/kg of body weight cefquinome beginning at 24 h postchallenge (prepatent phase of the disease), and the high-inoculum rats received a 4-day treatment of 50 mg/kg cefquinome beginning when the animals expressed clinical signs of infection (patent phase of the disease). The dose of 50 mg/kg targeting the high K. pneumoniae inoculum cured all the treated rats and resulted in a massive amplification of CTX-M-producing Enterobacteriaceae. A dose of 5 mg/kg targeting the low K. pneumoniae inoculum cured all the rats and averted an outbreak of clinical disease, all without any amplification of CTX-M-producing Enterobacteriaceae. These findings might have implications for the development of new antimicrobial treatment strategies that ensure a cure for bacterial infections while avoiding the amplification of resistance genes of human concern in the gut microbiota of food-producing animals. PMID:24395228

  19. Low or High Doses of Cefquinome Targeting Low or High Bacterial Inocula Cure Klebsiella pneumoniae Lung Infections but Differentially Impact the Levels of Antibiotic Resistance in Fecal Flora

    PubMed Central

    Vasseur, Maleck V.; Laurentie, Michel; Rolland, Jean-Guy; Perrin-Guyomard, Agnès; Henri, Jérôme; Ferran, Aude A.; Toutain, Pierre-Louis

    2014-01-01

    The combination of efficacious treatment against bacterial infections and mitigation of antibiotic resistance amplification in gut microbiota is a major challenge for antimicrobial therapy in food-producing animals. In rats, we evaluated the impact of cefquinome, a fourth-generation cephalosporin, on both Klebsiella pneumoniae lung infection and intestinal flora harboring CTX-M-producing Enterobacteriaceae. Germfree rats received a fecal flora specimen from specific-pathogen-free pigs, to which a CTX-M-producing Escherichia coli strain had been added. K. pneumoniae cells were inoculated in the lungs of these gnotobiotic rats by using either a low (105 CFU) or a high (109 CFU) inoculum. Without treatment, all animals infected with the low or high K. pneumoniae inoculum developed pneumonia and died before 120 h postchallenge. In the treated groups, the low-inoculum rats received a 4-day treatment of 5 mg/kg of body weight cefquinome beginning at 24 h postchallenge (prepatent phase of the disease), and the high-inoculum rats received a 4-day treatment of 50 mg/kg cefquinome beginning when the animals expressed clinical signs of infection (patent phase of the disease). The dose of 50 mg/kg targeting the high K. pneumoniae inoculum cured all the treated rats and resulted in a massive amplification of CTX-M-producing Enterobacteriaceae. A dose of 5 mg/kg targeting the low K. pneumoniae inoculum cured all the rats and averted an outbreak of clinical disease, all without any amplification of CTX-M-producing Enterobacteriaceae. These findings might have implications for the development of new antimicrobial treatment strategies that ensure a cure for bacterial infections while avoiding the amplification of resistance genes of human concern in the gut microbiota of food-producing animals. PMID:24395228

  20. Asexual Cephalosporin C Producer Acremonium chrysogenum Carries a Functional Mating Type Locus

    Microsoft Academic Search

    Stefanie Poggeler; Birgit Hoff; Ulrich Kuck

    2008-01-01

    Acremonium chrysogenum, the fungal producer of the pharmaceutically relevant -lactam antibiotic cepha- losporin C, is classified as asexual because no direct observation of mating or meiosis has yet been reported. To assess the potential of A. chrysogenum for sexual reproduction, we screened an expressed sequence tag library from A. chrysogenum for the expression of mating type (MAT) genes, which are

  1. Antibiotic-resistant bacteria: a challenge for the food industry.

    PubMed

    Capita, Rosa; Alonso-Calleja, Carlos

    2013-01-01

    Antibiotic-resistant bacteria were first described in the 1940s, but whereas new antibiotics were being discovered at a steady rate, the consequences of this phenomenon were slow to be appreciated. At present, the paucity of new antimicrobials coming into the market has led to the problem of antibiotic resistance fast escalating into a global health crisis. Although the selective pressure exerted by the use of antibiotics (particularly overuse or misuse) has been deemed the major factor in the emergence of bacterial resistance to these antimicrobials, concerns about the role of the food industry have been growing in recent years and have been raised at both national and international levels. The selective pressure exerted by the use of antibiotics (primary production) and biocides (e.g., disinfectants, food and feed preservatives, or decontaminants) is the main driving force behind the selection and spread of antimicrobial resistance throughout the food chain. Genetically modified (GM) crops with antibiotic resistance marker genes, microorganisms added intentionally to the food chain (probiotic or technological) with potentially transferable antimicrobial resistance genes, and food processing technologies used at sub-lethal doses (e.g., alternative non-thermal treatments) are also issues for concern. This paper presents the main trends in antibiotic resistance and antibiotic development in recent decades, as well as their economic and health consequences, current knowledge concerning the generation, dissemination, and mechanisms of antibacterial resistance, progress to date on the possible routes for emergence of resistance throughout the food chain and the role of foods as a vehicle for antibiotic-resistant bacteria. The main approaches to prevention and control of the development, selection, and spread of antibacterial resistance in the food industry are also addressed. PMID:23035919

  2. Antibiotic use during major head and neck surgery.

    PubMed Central

    Johnson, J T; Yu, V L

    1988-01-01

    The appropriate use of prophylactic antimicrobial therapy in patients undergoing major contaminated surgery is an important issue for the head and neck surgeon. A series of five sequential, prospective, randomized, double-blind clinical trials of antibiotics for patients undergoing major contaminated oncologic head and neck surgery are reviewed and summarized. The information generated from the study of these 547 patients indicates that a number of drugs or drug combinations have similar efficacy when employed in adequate dosage. The bacteriologic spectrum of the prophylactic drug should include oral microflora, especially anaerobic bacteria. The administration of antibiotics effective against gram-negative aerobic bacteria may be unnecessary. Perioperative antibiotic administration should be initiated prior to surgery. To date, no evidence exists to support prolonged administration of antibiotics beyond the first 24 hours following surgery. PMID:3276271

  3. Biotherapeutics as alternatives to antibiotics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Increasing pressure to limit antibiotic use in agriculture is heightening the need for alternative methods to reduce the adverse effects of clinical and subclinical disease on livestock performance that are currently managed by in-feed antibiotic usage. Immunomodulators have long been sought as such...

  4. The Antibiotic Resistance Problem Revisited

    ERIC Educational Resources Information Center

    Lawson, Michael A.

    2008-01-01

    The term "antibiotic" was first proposed by Vuillemin in 1889 but was first used in the current sense by Walksman in 1941. An antibiotic is defined as a "derivative produced by the metabolism of microorganisms that possess antibacterial activity at low concentrations and is not toxic to the host." In this article, the author describes how…

  5. Microbes: Too Smart for Antibiotics?

    NSDL National Science Digital Library

    Peggy Deichstetter (St. Edward High School; )

    2002-12-01

    This lesson focuses on examining why microbes become resistant to antibiotics, as well as their roles in human health and the environment. Students can produce public-awareness campaigns on antibiotic use, create yogurt recipe cards, develop a commercial bioremediation product, experiment with simulated germs and more!

  6. Veterinary use and antibiotic resistance

    Microsoft Academic Search

    Michael Teuber

    2001-01-01

    Globally, an estimated 50% of all antimicrobials serve veterinary purposes. Bacteria that inevitably develop antibiotic resistance in animals comprise food-borne pathogens, opportunistic pathogens and commensal bacteria. The same antibiotic resistance genes and gene transfer mechanisms can be found in the microfloras of animals and humans. Direct contact, food and water link animal and human habitats. The accumulation of resistant bacteria

  7. Commonly Used Antibiotics on Dairies

    Microsoft Academic Search

    John H. Kirk; Extension Veterinarian

    A recent survey 1 of dairymen in Minnesota, Michigan, Wisconsin and New York studied the antibiotic use strategies used on nearly 100 conventional and 30 organic dairies. They found that 71% of the dairies kept antibiotic treatment records for lactating dairy cows. Slightly over half of the dairies kept records of treatment of dry-cows and only a third kept records

  8. Multiple antibiotic resistance and efflux

    Microsoft Academic Search

    Hiroshi Nikaido

    1998-01-01

    Multiple antibiotic resistance in bacteria was at first thought to be caused exclusively by the combination of several resistance genes, each coding for resistance to a single drug. More recently, it became clear that such phenotypes are often achieved by the activity of drug efflux pumps. Some of these efflux pumps exhibit an extremely wide specificity covering practically all antibiotics,

  9. Putrescine Reduces Antibiotic-Induced Oxidative Stress as a Mechanism of Modulation of Antibiotic Resistance in Burkholderia cenocepacia

    PubMed Central

    El-Halfawy, Omar M.

    2014-01-01

    Communication of antibiotic resistance among bacteria via small molecules is implicated in transient reduction of bacterial susceptibility to antibiotics, which could lead to therapeutic failures aggravating the problem of antibiotic resistance. Released putrescine from the extremely antibiotic-resistant bacterium Burkholderia cenocepacia protects less-resistant cells from different species against the antimicrobial peptide polymyxin B (PmB). Exposure of B. cenocepacia to sublethal concentrations of PmB and other bactericidal antibiotics induces reactive oxygen species (ROS) production and expression of the oxidative stress response regulator OxyR. We evaluated whether putrescine alleviates antibiotic-induced oxidative stress. The accumulation of intracellular ROS, such as superoxide ion and hydrogen peroxide, was assessed fluorometrically with dichlorofluorescein diacetate, while the expression of OxyR and putrescine synthesis enzymes was determined in luciferase assays using chromosomal promoter-lux reporter system fusions. We evaluated wild-type and isogenic deletion mutant strains with defects in putrescine biosynthesis after exposure to sublethal concentrations of PmB and other bactericidal antibiotics. Exogenous putrescine protected against oxidative stress induced by PmB and other antibiotics, whereas reduced putrescine synthesis resulted in increased ROS generation and a parallel increased sensitivity to PmB. Of the 3 B. cenocepacia putrescine-synthesizing enzymes, PmB induced only BCAL2641, an ornithine decarboxylase. This study reveals BCAL2641 as a critical component of the putrescine-mediated communication of antibiotic resistance and as a plausible target for designing inhibitors that would block the communication of such resistance among different bacteria, ultimately reducing the window of therapeutic failure in treating bacterial infections. PMID:24820075

  10. [Monitoring antibiotic resistance in Argentina. The WHONET program, 1995-1996].

    PubMed

    Rossi, A; Tokumoto, M; Galas, M; Soloaga, R; Corso, A

    1999-10-01

    The World Health Organization has implemented a surveillance program for antimicrobial resistance that is known as WHONET. In Argentina the program was developed through a network of 23 public and private hospitals that participate in national and international quality-control programs. Between January 1995 and December 1996, the antimicrobial susceptibility of 16,073 consecutive clinical isolates was determined, using the recommended standards of the National Committee for Clinical Laboratory Standards of the United States of America. More than half of the Escherichia coli urinary isolates were resistant to ampicillin and more than 30% to trimethoprim/sulfamethoxazole (SXT). When the percentage of resistant isolates from outpatients (OPs) was compared to that observed in hospitalized patients (HPs), a marked difference in antimicrobial activity was noted in the case of gentamicin (2% from OPs resistant vs. 8% from HPs resistant), norfloxacin (2% vs. 6%), and third-generation cephalosporins (7% vs. 15%). Of the Klebsiella pneumoniae isolates recovered from blood cultures, 71% and 60% showed resistance to third-generation cephalosporins and to gentamicin, respectively. The overall rate of oxacillin resistance in Staphylococcus aureus was 39%. Around half of the Enterococcus spp. isolates showed high resistance to aminoglycosides, but resistance to glycopeptides was not found. In Argentina, ampicillin and SXT were not suitable for treating diarrhea. Shigella flexneri had a higher number of isolates resistant to both of those drugs (87% and 74%, respectively) than Sh. sonnei did (47% and 71%, respectively). About 40% of the Salmonella spp. isolated in pediatric hospitals were resistant to third-generation cephalosporins. When microorganisms causing bacterial meningitis were examined, Streptococcus pneumoniae showed a resistance rate of 18% to penicillin and Haemophilus influenzae a resistance rate of 19% to ampicillin. These rates are within the intermediate range reported for other countries of the Americas and for Europe. PMID:10572473

  11. Public Knowledge, Attitudes, and Experience Regarding the Use of Antibiotics in Italy

    PubMed Central

    Napolitano, Francesco; Izzo, Maria Teresa; Di Giuseppe, Gabriella; Angelillo, Italo F.

    2013-01-01

    Background The objectives of the study were to investigate the level of knowledge, attitudes, and behaviors regarding antibiotics of the general population in Italy, and to assess the correlates of these outcomes of interest. Methods A cross-sectional survey was conducted on a random sample of 630 parents of students attending nine randomly selected public primary and secondary schools. A self-administered questionnaire included questions on demographic characteristics, knowledge about antibiotic use and resistance, attitudes and behaviors towards antibiotic use, and sources of information. Results A total of 419 parents participated. Only 9.8% knew the definition of antibiotic resistance and 21.2% knew when it was appropriate to use antibiotics. Respondents with higher education, employed, with a family member working in the health care sector, and with no need for additional information on antibiotics were more likely to know the definition of antibiotic resistance. One third (32.7%) self-classified them as users of self-medication with antibiotics and those with a lower self-rated health status, who did not use the physician as source of information on antibiotics, and who have attended a physician in the last year were more likely to use self-medication. One-fourth (22.7%) of those who had never been self-medicated would be willing to take an antibiotic without a prescription of a physician. Respondents were more likely to be willing to take antibiotics without a prescription if they were under 40 years of age, if they had a lower self-rated health status, if they did not know that antibiotics are not indicated for treating flu and sore throat, and if they knew that antibiotics are not indicated for treating colds. Conclusions The survey has generated information about knowledge, attitudes, and behaviors regarding antibiotics in the general population and effective public education initiative should provide practical and appropriate means to change their behavior. PMID:24376793

  12. Resistance to selected beta-lactam antibiotics.

    PubMed

    Nedbalcova, K; Nechvatalova, K; Pokludova, L; Bures, J; Kucerova, Z; Koutecka, L; Hera, A

    2014-07-16

    Susceptibility in vitro and trends in resistance to antimicrobials were determined by a dilution micromethod in a group of Actinobacillus pleuropneumoniae, Pasteurella multocida, Mannheimia haemolytica and Escherichia coli isolates from clinical cases of cattle and swine diseases in the Czech Republic from 2007 to 2011. A high susceptibility of pig and cattle respiratory pathogens to antimicrobials was found, with the exception of the moderate prevalence of M. haemolytica resistance to ampicillin. In contrast to respiratory pathogens, low susceptibility of E. coli of pig and cattle isolates to ampicillin and amoxicillin/clavulanic acid was noted. Regarding resistance trends, an increase in levels of resistance among E. coli isolates to ampicillin and amoxicillin/clavulanic acid was identified, but the resistance of respiratory isolates was low, with the exception of M. haemolytica. For the period of 2007-2011, there was a significant and almost continuous increase in sales (compared with population correction unit) of ceftiofur, cefquinome and other beta lactams for pigs. Consumption peaked in 2010. In the case of amoxicillin in combination with clavulanic acid, data showed a significant decrease in sales from 2007 to 2008, followed by a period of fluctuation. In cattle, within the groups of 3rd and 4th generation cephalosporins and for the whole group of other betalactams for the period of 2007-2011, there was a significant and almost continuous increase in sales (compared with population correction unit). Consumption peaked in 2010. In the case of ceftiofur, there was a huge increase noted from 2010. In the case of amoxicillin in combination with betalactamase inhibitor (clavulanic acid) data shows a significant decrease from 2007 to 2008, followed by a period of fluctuation in sales. PMID:24612952

  13. Improvement of Water-Soluble Cephalosporin Derivatives Having Antibacterial Activity against Methicillin-Resistant Staphylococcus aureus

    Microsoft Academic Search

    Hideaki Hanaki; Shuichi Nomura; Hiroshi Akagi; Keiichi Hiramatsu

    2001-01-01

    We evaluated a series of novel cephem antibiotics, N-alkylpyridinium (alkyl group), N-carboxyethylpyridinium (carboxylic group), N-sulfoethylpyridinium (sulfonic group) and N-alkylquaternary ammonium salts (ammonioethyl group), N-alkyl-aromatic-quaternary ammonium salts and N-alkyl-heterocyclic quaternary ammonium salts (cyclic group) as vinylthio pyridinium derivatives at the C-3 position and hydroxyiminoaminothiazol at the C-7 position, for their activity against methicillin-resistant Staphylococcus aureus (MRSA) and their solubility, by measuring

  14. Bacterial evolution of antibiotic hypersensitivity

    PubMed Central

    Lázár, Viktória; Pal Singh, Gajinder; Spohn, Réka; Nagy, István; Horváth, Balázs; Hrtyan, Mónika; Busa-Fekete, Róbert; Bogos, Balázs; Méhi, Orsolya; Csörg?, Bálint; Pósfai, György; Fekete, Gergely; Szappanos, Balázs; Kégl, Balázs; Papp, Balázs; Pál, Csaba

    2013-01-01

    The evolution of resistance to a single antibiotic is frequently accompanied by increased resistance to multiple other antimicrobial agents. In sharp contrast, very little is known about the frequency and mechanisms underlying collateral sensitivity. In this case, genetic adaptation under antibiotic stress yields enhanced sensitivity to other antibiotics. Using large-scale laboratory evolutionary experiments with Escherichia coli, we demonstrate that collateral sensitivity occurs frequently during the evolution of antibiotic resistance. Specifically, populations adapted to aminoglycosides have an especially low fitness in the presence of several other antibiotics. Whole-genome sequencing of laboratory-evolved strains revealed multiple mechanisms underlying aminoglycoside resistance, including a reduction in the proton-motive force (PMF) across the inner membrane. We propose that as a side effect, these mutations diminish the activity of PMF-dependent major efflux pumps (including the AcrAB transporter), leading to hypersensitivity to several other antibiotics. More generally, our work offers an insight into the mechanisms that drive the evolution of negative trade-offs under antibiotic selection. PMID:24169403

  15. In vitro activity and beta-lactamase stability of GR69153, a new long-acting cephalosporin.

    PubMed Central

    Chin, N X; Gu, J W; Fang, W; Neu, H C

    1991-01-01

    GR69153, a new parenteral cephalosporin, inhibited 90% of Escherichia coli, Klebsiella oxytoca, Proteus mirabilis, Citrobacter diversus, shigellae, and salmonellae at less than 0.25 micrograms/ml (MIC90). It had activity comparable to those of ceftazidime, cefpirome, cefepime, and E-1040. Against cephalosporinase-producing Enterobacter cloacae, Citrobacter freundii, and Serratia marcescens, MICs ranged from 0.12 to greater than 32 micrograms/ml, and cefpirome and cefepime were the most active agents against these species. Pseudomonas aeruginosa was highly susceptible to GR69153, and for this organism the MIC90 was less than or equal to 2 micrograms/ml, which was similar to the E-1040 MIC90, but most Pseudomonas cepacia and Xanthomonas maltophilia isolates were resistant. GR69153 inhibited Haemophilus influenzae and Moraxella branhamella at less than or equal to 0.5 micrograms/ml. For Staphylococcus aureus GR69153 MICs were similar to those of ceftazidime and E-1040. Enterococci and listeriae were resistant to GR69153, but Streptococcus pyogenes and Streptococcus pneumoniae were inhibited by 0.5 micrograms/ml. The activity of GR69153 was not affected by serum. GR69153 was not inactivated by the beta-lactamases of Staphylococcus aureus, TEM-1, TEM-2, SHV-1, and BRO-1, but it was hydrolyzed by TEM-3, TEM-9, and morganellae. GR69153 had overall activity comparable to those of commercially available parenteral cephalosporins or those found in clinical investigations. It is more active against bacteroides than most available aminothiazolyl parenteral cephalosporins are. GR69153 is hydrolyzed by the new plasmid beta-lactamases, and thus, its primary value may be related to its pharmacological properties. PMID:2024959

  16. Cephalosporin MIC Distribution of Extended-Spectrum-?-Lactamase- and pAmpC-Producing Escherichia coli and Klebsiella Species?

    PubMed Central

    Kohner, Peggy C.; Robberts, Frans J. L.; Cockerill, Franklin R.; Patel, Robin

    2009-01-01

    The acquisition of ?-lactamases in members of the Enterobacteriaceae family poses a challenge to antimicrobial susceptibility testing in the clinical laboratory. We correlated the distribution of the MICs for Klebsiella spp. and Escherichia coli with the presence of extended-spectrum ?-lactamase (ESBL) and plasmid-mediated AmpC ?-lactamase (pAmpC) genes. A total of 264 isolates were subjected to cefazolin, ceftriaxone, cefotaxime, ceftazidime, cefepime, and aztreonam agar dilution MIC determination; ESBL screening and confirmatory testing by the methods of the Clinical and Laboratory Standards Institute (CLSI); and for isolates for which the MICs of extended-spectrum cephalosporins were ?1 ?g/ml or the MICs of cefpodoxime were >4 ?g/ml, PCR amplification and sequencing of the ESBL and pAmpC genes. PCR was positive for 73/81 isolates (45 isolates with an ESBL gene alone, 24 isolates with a pAmpC gene alone, with 4 isolates with both genes). Compared to PCR, confirmatory testing by the CLSI method yielded a sensitivity and a specificity of 98.0 and 96.3%, respectively; there were six false-positive results and one false-negative result. No distinction in the MIC distribution was apparent between isolates with the ESBL gene and isolates with the pAmpC gene. A substantial percentage of the isolates with PCR-confirmed ESBL and/or pAmpC genes fell within the current CLSI susceptible category. For a ceftazidime, ceftriaxone, or cefotaxime MIC of ?2 ?g/ml, a dichotomy existed between isolates with and without ESBL and pAmpC genes in most cases. This suggests that the presence of the ESBL and the pAmpC enzymes may yield similar MICs of extended-spectrum cephalosporins, many of which fall within the current nonresistant categories. Lowering of the current CLSI breakpoints for cephalosporins appears to be warranted. PMID:19494061

  17. A longitudinal field trial assesing the impact of feeding waste milk containing antibiotic residues on the prevalence of ESBL-producing Escherichia coli in calves.

    PubMed

    Brunton, L A; Reeves, H E; Snow, L C; Jones, J R

    2014-11-15

    A longitudinal field trial was carried out on a farm known to harbour cefotaximase (CTX-M)-positive Escherichia coli, in order to assess the impact of feeding waste milk containing antibiotic residues (WM+AR) on the prevalence of these bacteria in the faeces of calves. Fifty calves were alternately assigned to one of two groups at birth and fed either milk replacer (control group) or WM+AR (treatment group). Faecal samples were collected from all calves daily for the first week after enrolment, twice weekly until weaning, then weekly for a further six weeks. Environmental samples from the calf housing were collected weekly. WM+AR and powdered milk samples were examined for antibiotic residues and CTX-M-positive E. coli. Total E. coli and CTX-M-positive E. coli in faecal samples were enumerated using selective media. Regression analyses were performed on the bacterial count data using a population-averaged approach based on generalised estimating equations (GEE) to account for repeated measurements on individual calves over time. Cefquinome, a fourth generation cephalosporin, was detected in 87% of WM+AR samples at a mean concentration of 0.746 mg/l. All environmental sampling locations yielded CTX-M-positive E. coli. Significantly more pen floor samples were positive in the treatment group. Calves in the treatment group shed greater numbers of CTX-M-positive E. coli than calves in the control group throughout the study, and shedding decreased at a slower rate in the treatment group. CTX-M-positive E. coli persisted in a larger number of calves fed WM+AR compared with calves fed milk replacer where the prevalence in the treatment group declined significantly slower over time. There was no difference between calves fed WM+AR or calves fed milk replacer in the proportion of E. coli isolates that were CTX-M-positive. These findings indicate that feeding WM+AR increased the amount of resistant bacteria shed in the faeces. Shedding of CTX-M-positive E. coli persisted for longer in calves fed WM+AR, and persisted after weaning. PMID:25172121

  18. Diverse Antibiotic Resistance Genes in Dairy Cow Manure

    PubMed Central

    Wichmann, Fabienne; Udikovic-Kolic, Nikolina; Andrew, Sheila; Handelsman, Jo

    2014-01-01

    ABSTRACT Application of manure from antibiotic-treated animals to crops facilitates the dissemination of antibiotic resistance determinants into the environment. However, our knowledge of the identity, diversity, and patterns of distribution of these antibiotic resistance determinants remains limited. We used a new combination of methods to examine the resistome of dairy cow manure, a common soil amendment. Metagenomic libraries constructed with DNA extracted from manure were screened for resistance to beta-lactams, phenicols, aminoglycosides, and tetracyclines. Functional screening of fosmid and small-insert libraries identified 80 different antibiotic resistance genes whose deduced protein sequences were on average 50 to 60% identical to sequences deposited in GenBank. The resistance genes were frequently found in clusters and originated from a taxonomically diverse set of species, suggesting that some microorganisms in manure harbor multiple resistance genes. Furthermore, amid the great genetic diversity in manure, we discovered a novel clade of chloramphenicol acetyltransferases. Our study combined functional metagenomics with third-generation PacBio sequencing to significantly extend the roster of functional antibiotic resistance genes found in animal gut bacteria, providing a particularly broad resource for understanding the origins and dispersal of antibiotic resistance genes in agriculture and clinical settings. PMID:24757214

  19. Canadian Multicenter Susceptibility Study, with a focus on cephalosporins, from 15 Canadian medical centers. The Canadian Multicenter Study Group.

    PubMed Central

    Blondeau, J M; Yaschuk, Y

    1997-01-01

    We have previously reported on the in vitro susceptibilities of 4,482 microorganisms to 10 antimicrobial agents tested as part of a Canadian multicenter study. We now report on the remaining 10 agents tested in that study. Of the cephalosporins reported here, ceftriaxone had the greatest activity (82 to 100% susceptible isolates) against Enterobacteriaceae, compared to ceftizoxime (78 to 100%) and cefoperazone (78 to 100%). Cefoperazone activity against Pseudomonas aeruginosa was 87%, compared to 92% for ticarcillin-clavulanate. All agents had 97% or greater activity against Staphylococcus aureus. PMID:9420058

  20. The determinants of the antibiotic resistance process

    PubMed Central

    Franco, Beatriz Espinosa; Altagracia Martínez, Marina; Sánchez Rodríguez, Martha A; Wertheimer, Albert I

    2009-01-01

    Background: The use of antibiotic drugs triggers a complex interaction involving many biological, sociological, and psychological determinants. Resistance to antibiotics is a serious worldwide problem which is increasing and has implications for morbidity, mortality, and health care both in hospitals and in the community. Objectives: To analyze current research on the determinants of antibiotic resistance and comprehensively review the main factors in the process of resistance in order to aid our understanding and assessment of this problem. Methods: We conducted a MedLine search using the key words “determinants”, “antibiotic”, and “antibiotic resistance” to identify publications between 1995 and 2007 on the determinants of antibiotic resistance. Publications that did not address the determinants of antibiotic resistance were excluded. Results: The process and determinants of antibiotic resistance are described, beginning with the development of antibiotics, resistance and the mechanisms of resistance, sociocultural determinants of resistance, the consequences of antibiotic resistance, and alternative measures proposed to combat antibiotic resistance. Conclusions: Analysis of the published literature identified the main determinants of antibiotic resistance as irrational use of antibiotics in humans and animal species, insufficient patient education when antibiotics are prescribed, lack of guidelines for treatment and control of infections, lack of scientific information for physicians on the rational use of antibiotics, and lack of official government policy on the rational use of antibiotics in public and private hospitals. PMID:21694883

  1. Synergy and duality in peptide antibiotic mechanisms

    Microsoft Academic Search

    Dewey G McCafferty; Predrag Cudic; Michael K Yu; Douglas C Behenna; Ryan Kruger

    1999-01-01

    The molecular mechanisms by which peptide antibiotics disrupt bacterial DNA synthesis, protein biosynthesis, cell wall biosynthesis, and membrane integrity are diverse, yet historically have been understood to follow a theme of one antibiotic, one inhibitory mechanism. In the past year, mechanistic and structural studies have shown a rich diversity in peptide antibiotic mechanism. Novel secondary targeting mechanisms for peptide antibiotics

  2. Multiscale Models of Antibiotic Probiotics.

    PubMed

    Kaznessis, Yiannis N

    2014-11-01

    The discovery of antibiotics is one of the most important advances in the history of humankind. For eighty years human life expectancy and standards of living improved greatly thanks to antibiotics. But bacteria have been fighting back, developing resistance to our most potent molecules. New, alternative strategies must be explored as antibiotic therapies become obsolete because of bacterial resistance. Mathematical models and simulations guide the development of complex technologies, such as aircrafts, bridges, communication systems and transportation systems. Herein, models are discussed that guide the development of new antibiotic technologies. These models span multiple molecular and cellular scales, and facilitate the development of a technology that addresses a significant societal challenge. We argue that simulations can be a creative source of knowledge. PMID:25313349

  3. [Use and limitations of antibiotics].

    PubMed

    van Sluijs, F J

    1984-01-01

    Antibiotics may be successful in the treatment of infections, but may also cause these because of their antibacterial activity. These infections are known as superinfections and are preceded by colonization with resistant micro-organisms. Broad-spectrum antibiotics enjoy a worse reputation in this regard than do narrow-spectrum antibiotics, which are preferable in therapeutic indications. Adequate diffusion to the focus of infection and effective local action are essential in obtaining satisfactory results. For this reason kennel cough should not be treated with systemic antibiotics, and the urinary pH should be taken into account in the treatment of urinary tract infections. In antibacterial prophylaxis in surgery, the risk of colonization can be reduced by limiting administration to 24 hours. Tissue levels should be adequate at the time of surgery, which implies that administration should be started prior to surgery. PMID:6691192

  4. Potent combinations of beta-lactam antibiotics using the beta-lactamase inhibition principle.

    PubMed

    Greenwood, D; O'Grady, F

    1975-01-01

    Several penicillins known to be stable to enterobacterial beta-lactamases were tested in combination with beta-lactamase-sensitive penicillins and cephalosporins in a turbidimetric system. Nafcillin was found to be the best beta-lactamase inhibitor amongst agents presently available commercially, but the related, new semi-synthetic penicillin BRL 1437 (2-isopropoxy-1-naphthylpenicillin) was consistently found to be superior. Using 103 ampicillin-resistant coliform bacilli and antibiotic levels achievable in urine, cephalothin or cephaloridine alone achieved long-term suppression of growth (greater than 20 h) of 16 and 13% of strains, respectively, while the additional presence of BRL 1437 suppressed growth for longer than 20 h of 81% of the remaining strains. Even where 'success' was not achieved according to these stringent criteria, regrowth was significantly delayed by the presence of BRL 1437. Suppression of growth for longer than 20 h by BRL 1437 plus cephalothin was achieved with all of the 46 Escherichia coli strains tested. Antibiotic combinations were also studied in an in vitro model which stimulates the hydrokinetic features of the urinary bladder. Suppression of the growth of two highly resistant E. coli strains was achieved in this system, for therapeutically acceptable periods of time, with combinations of cephalothin or cephaloridine with BRL 1437, but not nafcillin. PMID:1102266

  5. Molecular Characteristics of Extended-Spectrum Cephalosporin-Resistant Enterobacteriaceae from Humans in the Community

    PubMed Central

    van Hoek, Angela H. A. M.; Schouls, Leo; van Santen, Marga G.; Florijn, Alice; de Greeff, Sabine C.; van Duijkeren, Engeline

    2015-01-01

    Objective To investigate the molecular characteristics of extended-spectrum cephalosporin (ESC)-resistant Enterobacteriaceae collected during a cross-sectional study examining the prevalence and risk factors for faecal carriage of extended-spectrum ?-lactamase (ESBL)-producing Enterobacteriaceae in humans living in areas with high or low broiler density. Methods ESC-resistant Enterobacteriaceae were identified by combination disc-diffusion test. ESBL/AmpC/carbapenemase genes were analysed using PCR and sequencing. For E. coli, phylogenetic groups and MLST were determined. Plasmids were characterized by transformation and PCR-based replicon typing. Subtyping of plasmids was done by plasmid multilocus sequence typing. Results 175 ESC-resistant Enterobacteriaceae were cultured from 165/1,033 individuals. The isolates were Escherichia coli(n=65), Citrobacter freundii (n=52), Enterobacter cloacae (n=38), Morganella morganii (n=5), Enterobacter aerogenes (n=4), Klebsiella pneumoniae (n=3), Hafnia alvei (n=2), Shigella spp. (n=2), Citrobacter amalonaticus (n=1), Escherichia hermannii (n=1), Kluyvera cryocrescens (n=1), and Pantoea agglomerans (n=1). The following ESBL genes were recovered in 55 isolates originating from 49 of 1,033 (4.7 %) persons: blaCTX-M-1 (n=17), blaCTX-M-15 (n=16), blaCTX-M-14 (n=9), blaCTX-M-2 (n=3), blaCTX-M-3 (n=2), blaCTX-M-24 (n=2), blaCTX-M-27 (n=1), blaCTX-M-32 (n=1), blaSHV-12 (n=2), blaSHV-65 (n=1) and blaTEM-52 (n=1). Plasmidic AmpC (pAmpC) genes were discovered in 6 out of 1,033 (0.6 %) persons. One person carried two different E. coli isolates, one with blaCTX-M-1 and the other with blaCMY-2 and therefore the prevalence of persons carrying Enterobacteriaceae harboring ESBL and/or pAmpC genes was 5.2 %. In eight E. coli isolates the AmpC phenotype was caused by mutations in the AmpC promoter region. No carbapenemase genes were identified. A large variety of E. coli genotypes was found, ST131 and ST10 being most common. Conclusions ESBL/pAmpC genes resembled those from patients in Dutch hospitals, indicating that healthy humans form a reservoir for transmission of these determinants to vulnerable people. The role of poultry in the transmission to humans in the community remains to be elucidated. PMID:26029910

  6. Sorption of antibiotics to biofilm.

    PubMed

    Wunder, David B; Bosscher, Valerie A; Cok, Rhiana C; Hozalski, Raymond M

    2011-03-01

    Using a continuous-flow rotating annular bioreactor, sorption of three selected antibiotics (sulfamethoxazole (SMX), ciprofloxacin (CIP), and erythromycin (ERY)) to bacterial biofilm was investigated. CIP had the greatest biofilm partition coefficient (K(oc) = 92,000 ± 10,000 L/kg) followed by ERY (K(oc) = 6000 ± 1000 L/kg) and then SMX (K(oc) = 4000 ± 1000 L/kg). Antibiotic sorption to biofilm did not correlate with experimentally-determined K(ow) values (CIP: -0.4; ERY: 0.98; SMX: <-0.59 at pH 7), suggesting that hydrophobic interactions do not drive the sorption of these relatively hydrophilic compounds to the biofilm. It appears that speciation (i.e. charge) and molecular size of the antibiotics are important in explaining their sorption to typically negatively charged biofilm. SMX is neutral to negatively charged at circumneutral pH while CIP and ERY are both positively charged. The decreased extent of sorption of ERY relative to CIP is likely due to the larger molecular size of ERY that results in a decreased rate of mass transfer (i.e. diffusion) to and through the biofilm. In conclusion, the results of this research suggest that hydrophobic interactions (predicted by K(ow)) do not control sorption of relatively hydrophilic antibiotics to biofilm and that antibiotic speciation and molecular size are important factors affecting the interactions between antibiotics and biofilm. PMID:21334040

  7. Ferrate(VI) oxidation of ?-lactam antibiotics: reaction kinetics, antibacterial activity changes, and transformation products.

    PubMed

    Karlesa, Anggita; De Vera, Glen Andrew D; Dodd, Michael C; Park, Jihye; Espino, Maria Pythias B; Lee, Yunho

    2014-09-01

    Oxidation of ?-lactam antibiotics by aqueous ferrate(VI) was investigated to determine reaction kinetics, reaction sites, antibacterial activity changes, and transformation products. Apparent second-order rate constants (kapp) were determined in the pH range 6.0-9.5 for the reaction of ferrate(VI) with penicillins (amoxicillin, ampicillin, cloxacillin, and penicillin G), a cephalosporin (cephalexin), and several model compounds. Ferrate(VI) shows an appreciable reactivity toward the selected ?-lactams (kapp for pH 7 = 110-770 M(-1) s(-1)). The pH-dependent kapp could be well explained by considering species-specific reactions between ferrate(VI) and the ?-lactams (with reactions occurring at thioether, amine, and/or phenol groups). On the basis of the kinetic results, the thioether is the main reaction site for cloxacillin and penicillin G. In addition to the thioether, the amine is a reaction site for ampicillin and cephalexin, and amine and phenol are reaction sites for amoxicillin. HPLC/MS analysis showed that the thioether of ?-lactams was transformed to stereoisomeric (R)- and (S)-sulfoxides and then to a sulfone. Quantitative microbiological assay of ferrate(VI)-treated ?-lactam solutions indicated that transformation products resulting from the oxidation of cephalexin exhibited diminished, but non-negligible residual activity (i.e., ?24% as potent as the parent compound). For the other ?-lactams, the transformation products showed much lower (<5%) antibacterial potencies compared to the parent compounds. Overall, ferrate(VI) oxidation appears to be effective as a means of lowering the antibacterial activities of ?-lactams, although alternative approaches may be necessary to achieve complete elimination of cephalosporin activities. PMID:25073066

  8. [Antibacterial activity of carumonam and cefpirome on hospital strains resistant to gentamicin and cephalothin: comparison with other beta-lactam antibiotics, new fluoroquinolones, aminoglycosides and other antibiotics].

    PubMed

    Vanhoof, R; Nyssen, H J; Nulens, E; Roebben, E; Hubrechts, J M

    1990-06-01

    The antibacterial in vitro activity of carumonam, a new monobactam, and cefpirome, a new cephalosporin, was studied on 483 hospital strains resistant to gentamicin and cephalothin, in comparison with amikacin, azlocillin, aztreonam, cefmenoxim, cefoperazone, cefotaxim, cefsulodin (for Pseudomonas), ceftazidime, ceftriaxone, cefuroxim, chloramphenicol, ciprofloxacin, doxycycline, enoxacin, netilmicin, norfloxacin, pefloxacin, piperacillin, rifampicin, tobramycin and trimethoprim. In general the two compounds have a very good in vito activity on Enterobacteriaceae but are less active on non-fermenting microorganisms. For the Enterobacteriaceae the minimal inhibitory concentrations 90% for carumonam was less than or equal to 1.1 mg/l excepted for Enterobacter spp. (43,6 mg/l) and M. morganii (56.8 mg/l) . All the Enterobacteriaceae are susceptible to cefpirome (minimal inhibitory concentrations 90% less than or equal to 5.3 mg/l). The activity of carumonam and cefpirome on Enterobacteriaceae is comparable with that of the third generation cephalosporins. Carumonam is more active than cefpirome and other beta-lactams, ceftazidime excepted, on Pseudomonas aeruginosa and Pseudomonas spp. On the other hand, both compounds reveal to have only a low activity on the other non-fermenters which minimal inhibitory concentrations 90% values of 115.4 mg/l for carumonam and 32.0 mg/l for cefpirome. PMID:2165238

  9. Heat inactivation of beta-lactam antibiotics in milk.

    PubMed

    Zorraquino, M A; Roca, M; Fernandez, N; Molina, M P; Althaus, R

    2008-06-01

    The presence of residues of antimicrobial substances in milk is one of the main concerns of the milk industry, as it poses a risk of toxicity to public health, and can seriously influence the technological properties of milk and dairy products. Moreover, the information available on the thermostability characteristics of these residues, particularly regarding the heat treatments used in control laboratories and the dairy industry, is very scarce. The aim of the study was, therefore, to analyze the effect of different heat treatments (40 degrees C for 10 min, 60 degrees C for 30 min, 83 degrees C for 10 min, 120 degrees C for 20 min, and 140 degrees C for 10 s) on milk samples fortified with three concentrations of nine beta-lactam antibiotics (penicillin G: 3, 6, and 12 microg/liter; ampicillin: 4, 8, and 16 microg/liter; amoxicillin: 4, 8, and 16 microg/liter; cloxacillin: 60, 120, and 240 microg/liter; cefoperazone: 55, 110, and 220 microg/liter; cefquinome: 100, 200, and 400 microg/liter; cefuroxime: 65, 130, and 260 microg/liter; cephalexin: 80, 160, and 220 microg/ liter; and cephalonium: 15, 30, and 60 microg/liter). The method used was a bioassay based on the inhibition of Geobacillus stearothermophilus var. calidolactis. The results showed that heating milk samples at 40 degrees C for 10 min hardly produced any heat inactivation at all, while the treatment at 83 degrees C for 10 min caused a 20% loss in penicillin G, 27% in cephalexin, and 35% in cefuroxime. Of the three dairy industry heat treatments studied in this work, low pasteurization (60 degrees C for 30 min) and treatment at 140 degrees C for 10 s only caused a small loss of antimicrobial activity, whereas classic sterilization (120 degrees C for 20 min) showed a high level of heat inactivation of over 65% for penicillins and 90% for cephalosporins. PMID:18592745

  10. Can vegetative filter strips mitigate veterinary antibiotic loss from agroecosystems?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Veterinary antibiotic (VA) presence in the environment, often associated with land application of manure, has generated significant interest in VA pollutant fate and transport in soil. These compounds have been subject to reconnaissance, column, macroscopic, and spectroscopic studies to elucidate VA...

  11. Biotransformations of lipoglycopeptides to obtain novel antibiotics.

    PubMed

    Gandolfi, Raffaella; Jovetic, Srdjan; Marinelli, Flavia; Molinari, Francesco

    2007-04-01

    The emergence of resistance among Gram-positive pathogens towards glycopeptide antibiotics has stimulated the research of second-generation molecules with improved activity and expanded antimicrobial spectrum. In this paper we investigate biotransformations as a way to generate novel teicoplanin- and A40926-like molecules. A range of commercial enzymes, fungi and actinomycetes were tested on A40926 and on its semi-synthetic derivatives (MDL 63,246 and dalbavancin). Oxidation of dalbavancin to MDL 63,246 was achieved by Nonomuraea sp. ATCC 39727 and Actinomadura parvosata ATCC 53463, while Actinoplanes sp. NRRL 3884, Actinoplanes missouriensis ATCC 23342 and Actinoplanes teichomyceticus ATCC 31121 deacylated MDL 63,246, dalbavancin and A40926. It is worth noting that the actinomycetes able to catalyze the deacylation of lipoglycopeptides are themselves producers of microbiologically active glycopeptides. Structurally related antibiotics (mideplanin and teicoplanin) were not transformed. Biotransformation conditions were optimised and scaled-up for the use of Actinoplanes sp. NRRL 3884 in the production of novel deacylated derivatives. PMID:17456978

  12. WAAR (World Alliance against Antibiotic Resistance): Safeguarding antibiotics

    PubMed Central

    2012-01-01

    Summary Resistance to antibiotics has increased recently to a dramatic extend, and the pipeline of new antibiotics is almost dry for the five next years. Failures happen already for trivial community acquired infections, like pyelonephritis, or peritonitis, and this is likely to increase. Difficult surgical procedures, transplants, and other immunosuppressive therapies will become far more risky. Resistance is mainly due to an excessive usage of antibiotics, in all sectors, including the animal one. Action is urgently needed. Therefore, an alliance against MDRO has been recently created, which includes health care professionals, consumers, health managers, and politicians. The document highlights the different proposed measures, and represents a strong consensus between the different professionals, including general practicionners, and veterinarians. PMID:22958542

  13. In vitro susceptibility of gram-negative bacilli from pediatric patients to moxalactam, cefotaxime, Ro 13-9904, and other cephalosporins.

    PubMed Central

    Shelton, S; Nelson, J D; McCracken, G H

    1980-01-01

    Moxalactam, Ro 13-9904, cefotaxime, cefoperazone, older cephalosporins, and four aminoglycosides were tested in vitro against 432 strains of gram-negative bacteria isolated from pediatric patients. The new drugs were uniformly active against coliform bacilli obtained from patients with meningitis and against aminoglycoside-resistant coliform bacilli. PMID:6252837

  14. Mode of Action of Antibiotic U-24,544

    PubMed Central

    Reusser, Fritz

    1967-01-01

    Antibiotic U-24,544, a new antibacterial agent, was found to be an effective uncoupler of phosphorylation associated with the oxidation of glutamate and succinate in rat liver mitochondria. Respiration was inhibited during glutamate oxidation but not during succinate oxidation. In a medium deficient in inorganic phosphate, the agent showed slight stimulation of mitochondrial glutamate oxidation. Mitochondrial swelling induced by inorganic phosphate was suppressed. The antibiotic inhibited protein, nucleic acid, and cell wall synthesis in Mycobacterium avium cells nearly equally without a predominant inhibition of any one of these macromolecular biosynthetic processes. Nucleic acid and polypeptide synthesis remained unaffected, but respiration was inhibited in cell-free bacterial systems. It was thus concluded that the antibiotic interfered primarily with the cellular energy-generating processes. PMID:6069281

  15. H2S: a universal defense against antibiotics in bacteria.

    PubMed

    Shatalin, Konstantin; Shatalina, Elena; Mironov, Alexander; Nudler, Evgeny

    2011-11-18

    Many prokaryotic species generate hydrogen sulfide (H(2)S) in their natural environments. However, the biochemistry and physiological role of this gas in nonsulfur bacteria remain largely unknown. Here we demonstrate that inactivation of putative cystathionine ?-synthase, cystathionine ?-lyase, or 3-mercaptopyruvate sulfurtransferase in Bacillus anthracis, Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli suppresses H(2)S production, rendering these pathogens highly sensitive to a multitude of antibiotics. Exogenous H(2)S suppresses this effect. Moreover, in bacteria that normally produce H(2)S and nitric oxide, these two gases act synergistically to sustain growth. The mechanism of gas-mediated antibiotic resistance relies on mitigation of oxidative stress imposed by antibiotics. PMID:22096201

  16. Organic or antibiotic-free labeling does not impact the recovery of enteric pathogens and antimicrobial-resistant Escherichia coli from fresh retail chicken.

    PubMed

    Mollenkopf, Dixie F; Cenera, Johana K; Bryant, Erin M; King, Christy A; Kashoma, Isaac; Kumar, Anand; Funk, Julie A; Rajashekara, Gireesh; Wittum, Thomas E

    2014-12-01

    We investigated the implied health benefits of retail chicken breast labeled as "organic" or "antibiotic-free" when compared to conventional products based on frequency of contamination by Salmonella spp., Campylobacter spp., and coliform bacteria resistant to fluoroquinolones, extended-spectrum cephalosporins, or carbapenems. We purchased 231 prepackaged chicken breasts from 99 grocery stores representing 17 retail chains in Ohio, Michigan, and Pennsylvania from June to September 2012. Ninety-six (41.5%) packages were labeled "antibiotic free" and 40 (17.3%) were labeled "organic," with the remaining 95 (41.1%) making neither label claim. Salmonella were recovered from 56 (24.2%) packages, and the recovery rate was not different between product types. Five percent of packages contained Salmonella carrying the extended-spectrum cephalosporin resistance gene bla(CMY-2), representing 21.4% of Salmonella isolates. Campylobacter spp. were recovered from 10.8% of packages, with observed recovery rates similar for the three product types. Using selective media, we recovered Escherichia coli harboring bla(CMY-2) from over half (53.7%) of packages, with similar recovery rates for all product types. In addition, we recovered E. coli carrying bla(CTX-M) from 6.9% of packages, and E. coli with QRDR mutations from 8.2% of packages. Fluoroquinolone-resistant E. coli recovered using selective media were more common (p<0.05) in conventional (18.9%) compared to organic (0) and antibiotic-free (2.1%) packages. Our results indicate that, regardless of product type, fresh retail chicken breast is commonly contaminated with enteric pathogens associated with foodborne illness and commensal bacteria harboring genes conferring resistance to critically important antimicrobial drugs. PMID:25405393

  17. Novel water soluble neutral vanadium(IV)-antibiotic complex: Antioxidant, immunomodulatory and molecular docking studies.

    PubMed

    Datta, Chitraniva; Das, Dharitri; Mondal, Paritosh; Chakraborty, Biswajit; Sengupta, Mahuya; Bhattacharjee, Chira R

    2015-06-01

    A novel water soluble five coordinate oxovanadium(IV) complex, [VO(C16H15N4O8S)HSO4] incorporating cefuroxime, a cephalosporin group of antibiotic have been prepared from an interaction of vanadyl sulfate and cefuroxime in aqueous solution. The compound was characterized by Fourier transform infrared spectroscopy (FTIR), CHN microanalyses, ultraviolet-visible spectroscopy (UV-Vis), fast atom bombardment (FAB) mass spectrometry and thermogravimetric analysis (TGA). Density Functional Theory (DFT) computation using Gaussian 09 program at B3LYP level revealed a distorted square pyramidal energy optimized geometry for the vanadyl(IV) complex. The molecular docking studies show that the interaction between the vanadium complex and protein receptor, clathrin is dominated by hydrophobic forces. The experimental (1)H nuclear magnetic resonance (NMR) features of the analogous Zn(II) complex matched well with the theoretically computed values further affirming the distorted square pyramidal geometry for the vanadyl(IV) complex. Cyclic voltammetry revealed a metal centered single-electron oxidation-reduction response for VO(IV)/VO(V) couple. The antioxidant activity of the vanadium(IV)-complex vis-à-vis the antibiotic has been assessed by 1,1-diphenyl-2-picrylhydrazyl (DPPH) method. The vanadium complex showed comparatively better radical scavenging ability compared to the antibiotic cefuroxime. The antimicrobial activity of the compound has been assayed for five different microbial strains using minimum inhibitory concentration (MIC) method. Immunomodulatory studies carried out using phagocytosis index, myeloperoxidase release and cytokine assay indicated the vanadium(IV)-complex to be immunosuppressant. The cytotoxicity of the compound was evaluated by MTT (3-(4, 5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) reduction assay. PMID:25982330

  18. Transport of sulfonamide antibiotics in small fields during monsoon season

    NASA Astrophysics Data System (ADS)

    Park, J. Y.; Huwe, B.; Kolb, A.; Tenhunen, J.

    2012-04-01

    Transport and fate of 3 sulfonamide antibiotics (sulfamethoxazole, sulfadimethoxine and sulfamethazine) were studied in small agricultural land during monsoon period. The experiment has been conducted in 2 typical sandy loam potato fields of South Korea after application of the veterinary antibiotics and bromide. Precipitation was measured by AWS (Automatic Weather Station) near the fields during the whole monsoon season. Runoff generation was estimated by multislot divisors in combination with pressure sensor. Concentration of the target antibiotics and the conservative tracer in runoff, soil-water and soil was determined using HPLC-MS-MS and Br selected electrode. Transport simulation has been performed with Hydrus-2D program which can consider soil characteristics, climate condition, adsorption/desorption and degradation. Results from the measurements and modeling focus on the role of heavy rainfall, of related the ratio of runoff and infiltration in terms of the selected antibiotics distribution and fate. Bromide on topsoil was moved into soil as increasing rainfall loading. On the contrary, the sulfonamides were relatively retarded in upper soil layer owing to adsorption onto soil particles. Different patterns of runoff were observed, and slope and rain intensity was representative factor in this study. Distribution of target pharmaceuticals was strongly dependent on constitution of furrow and ridge in the agricultural fields. Modeling results positively matched with background studies that describe physico-chemical properties of the sulfonamides, interaction between soil and the antibiotic group, solute transport through vadose zone and runoff induction by storm events.

  19. Combination antibiotic therapy in pediatrics.

    PubMed

    Chadwick, E G; Yogev, R; Shulman, S T

    1986-06-30

    Combinations of beta-lactam and aminoglycoside antibiotics are frequently used in the treatment of pediatric infections. At our institution, amikacin has been the sole aminoglycoside utilized for the past five years. Such regimens are used empirically in specific patient populations to treat the pathogens most likely to be responsible for a symptom complex, e.g., sepsis in the immunocompromised host, pneumonitis in patients with cystic fibrosis, neonatal infections such as sepsis or meningitis, and infections in patients with intestinal perforations. Beta-lactam and aminoglycoside combinations are employed as definitive therapy when synergistic interactions can be predicted, such as in systemic Pseudomonas infections, viridans streptococcal endocarditis, or enterococcal infections. In all of these circumstances, we have utilized amikacin extensively as the sole aminoglycoside, with highly satisfactory results. In vitro antibiotic synergy studies, including those employing aminoglycosides such as amikacin, may be used to predict in vivo antibiotic interactions. However, definitions of in vitro synergy vary with the laboratory method used to evaluate synergy. Furthermore, recent data from our laboratory suggest that the absence of demonstrated in vitro synergy between amikacin and imipenem may not correlate with improved survival of neutropenic rats with gram-negative sepsis that are treated with both agents. Thus, in vitro studies of synergy may underestimate the frequency of improved outcomes with combination antibiotics, especially with amikacin and imipenem. There are potential risks associated with the use of multiple, broad-spectrum antibiotics, including fungal or bacterial superinfection and increased drug toxicity. Although the former is common in pediatric patients, aminoglycoside (amikacin) toxicity has rarely been a problem. Combination antibiotic regimens that include an aminoglycoside such as amikacin continue to have an important role in pediatrics and should be used empirically or definitively for the specific indications discussed. PMID:3728528

  20. Effects of intramammary antibiotic therapy during the dry period on the performance of Lacaune dairy sheep under intensive management.

    PubMed

    Hernandez, Fernando; Elvira, Laura; Fernández, Beatriz; Egea, Marta; Gonzalez-Bulnes, Antonio; Gonzalez-Martin, Juan V; Astiz, Susana

    2015-02-01

    Often the only way to ensure profitability of Lacaune dairy sheep is intensive management, which requires appropriate dry-period treatment to ensure animal productivity and health. The present study aimed to investigate the effects of intramammary antibiotic dry therapy on the performance and health of Lacaune sheep under intensive management. We recorded data for 5981 complete lactation periods that followed a dry period. A total of 2402 lactation periods were preceded by a dry period involving intramammary administration of 300 mg of cephapirin benzathine (antibiotic group) and 3579 lactation periods were preceded by dry periods with no treatment (control group). The following on-farm yield data were collected for individual lactation periods: length of the subsequent lactation period; total milk yield per lactation period; daily milk yield and length of the subsequent dry period. Data on confounding factors that might affect productivity were also recorded, including the individual ewe, number of lactation periods and length of the previous dry period. Milk quality was assessed using data on somatic cell count (SCC) and content of protein and fat taken from the Spanish National Official Milk Yield Recording System. Antibiotic dry therapy significantly improved total yield per lactation period, which was 429±151·1 l in the antibiotic group and 412±165·5 l in the control group, as well as the daily milk yield, which was 1986±497·0 and 1851±543·2 ml/d, respectively (both P<0·0001). The initial dry period was significantly longer in the antibiotic group than in the control group, and dry period length correlated inversely with yield variables such us total yield per lactation period (r=-0·055; P<0·0001) and yield per day in milk (r=-0·039; P<0·0001). As a result, milk yield records systematically underestimated the positive effects of antibiotic dry therapy. Antibiotic dry therapy also significantly improved milk quality. Milk from the antibiotic group showed 50% lower SCC (573±1326 vs. 1022±2126 cells/ml; P<0·0001) and slightly higher content in fat (7·33±0·91 vs. 7·15±0·87%) and protein (5·63±0·44 vs. 5·44±0·4%). The results of this study suggest that cephalosporin dry therapy of Lacaune dairy sheep increases milk production and improves milk quality during subsequent lactation periods. PMID:25467529

  1. MICROBIOLOGY: Noninherited Resistance to Antibiotics

    NSDL National Science Digital Library

    Bruce R. Levin (Emory University; Department of Biology)

    2004-09-10

    Access to the article is free, however registration and sign-in are required. Why is it that the rate of mortality of bacteria exposed to bactericidal antibiotics declines with time but sensitive cells survive for hours or even days of exposure? The mechanisms responsible for this persistence have perplexed microbiologists for decades. In his Perspective, Levin discusses a pair of recent studies (Balaban et al., Miller et al.) that shed light on the mechanisms responsible for this phenomenon and the way in which these bacterial persisters emerge. Levin also considers the potential clinical implications of this non-inherited form of resistance to antibiotics.

  2. Influence of the treatment of Listeria monocytogenes and Salmonella enterica serovar Typhimurium with citral on the efficacy of various antibiotics.

    PubMed

    Zanini, Surama F; Silva-Angulo, Angela B; Rosenthal, Amauri; Aliaga, Dolores Rodrigo; Martínez, Antonio

    2014-04-01

    The main goal of this work was to study the bacterial adaptive responses to antibiotics induced by sublethal concentration of citral on first-and second-generation cells of Listeria monocytogenes serovar 4b (CECT 4032) and Salmonella enterica serovar Typhimurium (CECT 443). The first-generation cells were not pretreated with citral, while the second-generation cells were obtained from cells previously exposed to citral during 5?h. The trials were conducted at 37°C. The presence of citral in the culture medium and the antibiotic strips resulted in a reduced minimum inhibitory concentration (MIC) for the first-generation cells of Listeria monocytogenes serovar 4b and Salmonella Typhimurium. This result was observed for almost all the antibiotics, compared with the same microorganisms of the control group (without citral), which could represent an additive effect. For Listeria serovar 4b, the second-generation cells of the test group maintained the same susceptibility to antibiotics compared with cells in the control group and in the test group of the first generation. The second-generation cells of the control group indicated that the Salmonella Typhimurium maintained the same sensitivity to the antibiotics tested compared with the first generation of this group, except in the case of erythromycin, which exhibited an increased MIC value. With respect to the second-generation cells of Salmonella Typhimurium, the presence of citral determined a decrease in the antibiotic susceptibility for almost all of the antibiotics, except colistin, compared with the first-generation of the test group, which can be seen by increase of MIC values. In conclusion, the presence of citral in the culture medium of Listeria 4b and Salmonella Typhimurium increased the antibiotic susceptibility of the first generations, while we observed an increase in antibiotic resistance in the second generation of Salmonella Typhimurium. PMID:24494856

  3. Immobilization and stabilization of cephalosporin C acylase on aminated support by crosslinking with glutaraldehyde and further modifying with aminated macromolecules.

    PubMed

    He, Hua; Wei, Yanmei; Luo, Hui; Li, Xi; Wang, Xiaona; Liang, Chen; Chang, Yanhong; Yu, Huimin; Shen, Zhongyao

    2015-03-01

    In this work, cephalosporin C acylase (CA), a heterodimeric enzyme of industrial potential in direct hydrolysis of cephalosporin C (CPC) to 7-aminocephalosporanic acid (7-ACA), was covalently immobilized on the aminated support LX1000-HA (HA) with two different protocols. The stability of CA adsorbed onto the HA support followed by crosslinking with glutaraldehyde (HA-CA-glut) was better than that of the CA covalently immobilized on the glutaraldehyde preactivated HA support (HA-glut-CA). The thermostabilization factors (compared with the free enzyme) of these two immobilized enzymes were 11.2-fold and 2.2-fold, respectively. In order to improve the stability of HA-CA-glut, a novel strategy based on postimmobilization modifying with aminated molecules was developed to take advantage of the glutaraldehyde moieties left on the enzyme and support. The macromolecules, such as polyethyleneimine (PEI) and chitosan, had larger effects than small molecules on the thermal stability of the immobilized enzyme perhaps due to crosslinking of the enzymes and support with each other. The quaternary structure of the CA could be much stabilized by this novel approach including physical adsorption on aminated support, glutaraldehyde treatment, and macromolecule modification. The HA-CA-glut-PEI20000 (the HA-CA-glut postmodified with PEI Mw = 20,000) had a thermostabilization factor of 20-fold, and its substrate affinity (Km = 14.3 mM) was better than that of HA-CA-glut (Km = 33.4 mM). The half-life of the immobilized enzymes HA-CA-glut-PEI20000 under the CPC-catalyzing conditions could reach 28 cycles, a higher value than that of HA-CA-glut (21 cycles). © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 31:387-395, 2015. PMID:25641630

  4. Whole-genome phylogenomic heterogeneity of Neisseria gonorrhoeae isolates with decreased cephalosporin susceptibility collected in Canada between 1989 and 2013.

    PubMed

    Demczuk, Walter; Lynch, Tarah; Martin, Irene; Van Domselaar, Gary; Graham, Morag; Bharat, Amrita; Allen, Vanessa; Hoang, Linda; Lefebvre, Brigitte; Tyrrell, Greg; Horsman, Greg; Haldane, David; Garceau, Richard; Wylie, John; Wong, Tom; Mulvey, Michael R

    2015-01-01

    A large-scale, whole-genome comparison of Canadian Neisseria gonorrhoeae isolates with high-level cephalosporin MICs was used to demonstrate a genomic epidemiology approach to investigate strain relatedness and dynamics. Although current typing methods have been very successful in tracing short-chain transmission of gonorrheal disease, investigating the temporal evolutionary relationships and geographical dissemination of highly clonal lineages requires enhanced resolution only available through whole-genome sequencing (WGS). Phylogenomic cluster analysis grouped 169 Canadian strains into 12 distinct clades. While some N. gonorrhoeae multiantigen sequence types (NG-MAST) agreed with specific phylogenomic clades or subclades, other sequence types (ST) and closely related groups of ST were widely distributed among clades. Decreased susceptibility to extended-spectrum cephalosporins (ESC-DS) emerged among a group of diverse strains in Canada during the 1990s with a variety of nonmosaic penA alleles, followed in 2000/2001 with the penA mosaic X allele and then in 2007 with ST1407 strains with the penA mosaic XXXIV allele. Five genetically distinct ESC-DS lineages were associated with penA mosaic X, XXXV, and XXXIV alleles and nonmosaic XII and XIII alleles. ESC-DS with coresistance to azithromycin was observed in 5 strains with 23S rRNA C2599T or A2143G mutations. As the costs associated with WGS decline and analysis tools are streamlined, WGS can provide a more thorough understanding of strain dynamics, facilitate epidemiological studies to better resolve social networks, and improve surveillance to optimize treatment for gonorrheal infections. PMID:25378573

  5. Origins and Evolution of Antibiotic Resistance

    PubMed Central

    Davies, Julian; Davies, Dorothy

    2010-01-01

    Summary: Antibiotics have always been considered one of the wonder discoveries of the 20th century. This is true, but the real wonder is the rise of antibiotic resistance in hospitals, communities, and the environment concomitant with their use. The extraordinary genetic capacities of microbes have benefitted from man's overuse of antibiotics to exploit every source of resistance genes and every means of horizontal gene transmission to develop multiple mechanisms of resistance for each and every antibiotic introduced into practice clinically, agriculturally, or otherwise. This review presents the salient aspects of antibiotic resistance development over the past half-century, with the oft-restated conclusion that it is time to act. To achieve complete restitution of therapeutic applications of antibiotics, there is a need for more information on the role of environmental microbiomes in the rise of antibiotic resistance. In particular, creative approaches to the discovery of novel antibiotics and their expedited and controlled introduction to therapy are obligatory. PMID:20805405

  6. When and How to Take Antibiotics

    MedlinePLUS

    ... Prudent use includes taking antibiotics only for diagnosed bacterial infections and following the precise directions on the prescription. ( ... caused by bacteria. If you do have another bacterial infection, a complete dose of the appropriate antibiotic is ...

  7. Get Smart: Know When Antibiotics Work - What You Can Do

    MedlinePLUS

    ... What Everyone Should Know What You Can Do Antibiotic Resistance Q&As Fast Facts Antibiotics Quiz Glossary For ... Pharmacists Continuing Education & Curriculum Opportunities Weighing in on Antibiotic Resistance Improving Prescribing Outpatient Antibiotic Stewardship Interventions That Work ...

  8. Get Smart: Know When Antibiotics Work - What Everyone Should Know

    MedlinePLUS

    ... What Everyone Should Know What You Can Do Antibiotic Resistance Q&As Fast Facts Antibiotics Quiz Glossary For ... Pharmacists Continuing Education & Curriculum Opportunities Weighing in on Antibiotic Resistance Improving Prescribing Outpatient Antibiotic Stewardship Interventions That Work ...

  9. Influence of Therapeutic Ceftiofur Treatments of Feedlot Cattle on Fecal and Hide Prevalences of Commensal Escherichia coli Resistant to Expanded-Spectrum Cephalosporins, and Molecular Characterization of Resistant Isolates

    PubMed Central

    Griffin, Dee; Kuehn, Larry A.; Brichta-Harhay, Dayna M.

    2013-01-01

    In the United States, the blaCMY-2 gene contained within incompatibility type A/C (IncA/C) plasmids is frequently identified in extended-spectrum-cephalosporin-resistant (ESCr) Escherichia coli strains from both human and cattle sources. Concerns have been raised that therapeutic use of ceftiofur in cattle may increase the prevalence of ESCr E. coli. We report that herd ESCr E. coli fecal and hide prevalences throughout the residency of cattle at a feedlot, including during the period of greatest ceftiofur use at the feedlot, were either not significantly different (P ? 0.05) or significantly less (P < 0.05) than the respective prevalences at arrival. Longitudinal sampling of cattle treated with ceftiofur demonstrated that once the transient increase of ESCr E. coli shedding that follows ceftiofur injection abated, ceftiofur-injected cattle were no more likely than untreated members of the same herd to shed ESCr E. coli. Pulsed-field gel electrophoresis (PFGE) genotyping, antibiotic resistance phenotyping, screening for presence of the blaCMY-2 gene, and plasmid replicon typing were performed on 312 ESCr E. coli isolates obtained during six sampling periods spanning the 10-month residence of cattle at the feedlot. The identification of only 26 unique PFGE genotypes, 12 of which were isolated during multiple sampling periods, suggests that clonal expansion of feedlot-adapted blaCMY-2 E. coli strains contributed more to the persistence of blaCMY-2 than horizontal transfer of IncA/C plasmids between E. coli strains at this feedlot. We conclude that therapeutic use of ceftiofur at this cattle feedlot did not significantly increase the herd prevalence of ESCr E. coli. PMID:23354706

  10. Antibiotic cost reduction by providing cost information

    Microsoft Academic Search

    E. Rubinstein; A. Barzilai; S. Segev; Y. Samra; M. Modan; O. Dickerman; C. Haklai

    1988-01-01

    Antibiotic cost information was added to the computerized print-out for each patient of microbiology culture results, next to the antibiotic susceptibility list. During the first six months of this addition, the average monthly cost of antibiotics decreased by 16.5% ($ 7636) compared to the 12 months period preceding the study period. The average antibiotic cost per admission decreased by 15.7%

  11. Agricultural use of antibiotics and the evolution and transfer of antibiotic-resistant bacteria

    Microsoft Academic Search

    George G. Khachatourians

    1998-01-01

    MICROBIAL RESISTANCE TO ANTIBIOTICS IS ON THE RISE, in part because of inappropriate use of antibiotics in human medicine but also because of practices in the agricul- tural industry. Intensive animal production involves giving livestock animals large quantities of antibiotics to promote growth and prevent infection. These uses pro- mote the selection of antibiotic resistance in bacterial populations. The resistant

  12. New Antibiotic Approved by FDA

    NSDL National Science Digital Library

    Ramanujan, Krishna.

    Last week, the FDA approved Zyvox (known generically as linezolid), the first in a new class of synthetic antibacterial drugs -- called oxazolidinones -- designed to treat a number of drug-resistant infections. Zyvox has proven effective in treatment of infections associated with vancomycin-resistant Enterococcus faecium (VREF) as well as hospital-acquired pneumonia and complicated skin and skin structure infections, including cases caused by methicillin-resistant Staphylococcus aureus (MRSA). This is the first drug to be approved in over 40 years for fighting hospital-acquired infections that are resistant to antibiotics. "It comes at a time when we were literally running out of antibiotics," said Dr. Robert C. Moellering Jr., physician-in-chief of Boston's Beth Israel-Deaconness Hospital, in a recent AP news article. In an attempt to preserve the long-term effectiveness of Zyvox and discourage microbes from developing renewed resistance, some doctors are calling for cautious use of the drug for only the worst antibiotic-resistant infections. This week's In The News takes a look at this new development and its consequences for antibiotic resistant bacteria.

  13. SURGICAL PERSONNEL' ADHERENCE TO ANTIBIOTIC POLICIES

    Microsoft Academic Search

    Emma Keuleyan; G. Kirov; M. Kondarev; I. Lozev; D. Vezeva; S. Toujarov

    2010-01-01

    SUMMARY - Objectives. This work aimed at studying the adherence of personnel of the Surgery clinic of our institute to antibiotic policies in place. - Methods. Antimicrobial resistance surveillance of the alert resistant microorganisms (Staphylococcus aureus (MRSA), Enterobacteriaceae (ESBL-producing), Pseudomonas aeruginosa, MDR); Antibiotic consumption calculation (ABC calc, D. Monnet); Audits of antibiotic prescriptions, and Inquiries - were performed. - Results.

  14. Timing of Antibiotic Prophylaxis in Tourniquet Surgery

    Microsoft Academic Search

    Akinyele L. Akinyoola; Olayinka O. Adegbehingbe; Afolabi Odunsi

    2011-01-01

    It is customary to administer prophylactic antibiotics before exsanguination of the limb and inflation of a tourniquet in extremity surgery. To compare the clinical outcome in lower limb operations when prophylactic antibiotics were administered before versus after limb exsanguination and tourniquet inflation, we randomized patients to the administration of prophylactic antibiotics 5 minutes before exsanguination and inflation of the tourniquet

  15. Genetic Architecture of Intrinsic Antibiotic Susceptibility

    Microsoft Academic Search

    Hany S. Girgis; Alison K. Hottes; Saeed Tavazoie

    2009-01-01

    Background: Antibiotic exposure rapidly selects for more resistant bacterial strains, and both a drug's chemical structure and a bacterium's cellular network affect the types of mutations acquired. Methodology\\/Principal Findings: To better characterize the genetic determinants of antibiotic susceptibility, we exposed a transposon-mutagenized library of Escherichia coli to each of 17 antibiotics that encompass a wide range of drug classes and

  16. ANTIBIOTIC TRANSPORT VIA RUNOFF AND SOIL LOSS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Research has verified the occurrence of veterinary antibiotics in manure, agricultural fields, and surface waters, yet no research has evaluated transport of antibiotics from agricultural fields. We quantified the transportability of antibiotics from agricultural fields where manure or effluent is a...

  17. New business models for antibiotic innovation

    PubMed Central

    Shah, Tejen A.

    2014-01-01

    The increase in antibiotic resistance and the dearth of novel antibiotics have become a growing concern among policy-makers. A combination of financial, scientific, and regulatory challenges poses barriers to antibiotic innovation. However, each of these three challenges provides an opportunity to develop pathways for new business models to bring novel antibiotics to market. Pull-incentives that pay for the outputs of research and development (R&D) and push-incentives that pay for the inputs of R&D can be used to increase innovation for antibiotics. Financial incentives might be structured to promote delinkage of a company’s return on investment from revenues of antibiotics. This delinkage strategy might not only increase innovation, but also reinforce rational use of antibiotics. Regulatory approval, however, should not and need not compromise safety and efficacy standards to bring antibiotics with novel mechanisms of action to market. Instead regulatory agencies could encourage development of companion diagnostics, test antibiotic combinations in parallel, and pool and make transparent clinical trial data to lower R&D costs. A tax on non-human use of antibiotics might also create a disincentive for non-therapeutic use of these drugs. Finally, the new business model for antibiotic innovation should apply the 3Rs strategy for encouraging collaborative approaches to R&D in innovating novel antibiotics: sharing resources, risks, and rewards. PMID:24646116

  18. New business models for antibiotic innovation.

    PubMed

    So, Anthony D; Shah, Tejen A

    2014-05-01

    The increase in antibiotic resistance and the dearth of novel antibiotics have become a growing concern among policy-makers. A combination of financial, scientific, and regulatory challenges poses barriers to antibiotic innovation. However, each of these three challenges provides an opportunity to develop pathways for new business models to bring novel antibiotics to market. Pull-incentives that pay for the outputs of research and development (R&D) and push-incentives that pay for the inputs of R&D can be used to increase innovation for antibiotics. Financial incentives might be structured to promote delinkage of a company's return on investment from revenues of antibiotics. This delinkage strategy might not only increase innovation, but also reinforce rational use of antibiotics. Regulatory approval, however, should not and need not compromise safety and efficacy standards to bring antibiotics with novel mechanisms of action to market. Instead regulatory agencies could encourage development of companion diagnostics, test antibiotic combinations in parallel, and pool and make transparent clinical trial data to lower R&D costs. A tax on non-human use of antibiotics might also create a disincentive for non-therapeutic use of these drugs. Finally, the new business model for antibiotic innovation should apply the 3Rs strategy for encouraging collaborative approaches to R&D in innovating novel antibiotics: sharing resources, risks, and rewards. PMID:24646116

  19. Selective pressure by antibiotic use in livestock

    Microsoft Academic Search

    Wolfgang Witte

    2000-01-01

    Selective pressure exerted by the use of antibiotics as growth promoters in food animals appears to have created large reservoirs of transferable antibiotic resistance in these ecosystems. This first became evident for oxytetracycline and later for the streptothricin antibiotic nurseothricin, for which a transfer of relevant resistance determinants (sat genes) to bacterial pathogens of humans was demonstrated. With the emergence

  20. A call for antibiotic alternatives research.

    PubMed

    Stanton, Thaddeus B

    2013-03-01

    The persistence and spread of antibiotic resistance, in conjunction with decreased profitability of new antibiotics, have created the dangerous prospect of ineffective therapies against bacterial diseases. National strategies aimed at discovery, development, and definition of the mechanisms of effective antibiotic alternatives, especially for agricultural applications, should be encouraged. PMID:23473628

  1. The epidemiology of antibiotic resistance in Campylobacter

    Microsoft Academic Search

    John E. Moore; Mary D. Barton; Iain S. Blair; Deborah Corcoran; James S. G. Dooley; Séamus Fanning; Isabelle Kempf; Albert J. Lastovica; Colm J. Lowery; Motoo Matsuda; David A. McDowell; Ann McMahon; B. Cherie Millar; Juluri R. Rao; Paul J. Rooney; Bruce S. Seal; William J. Snelling; Ola Tolba

    2006-01-01

    Antibiotic resistance, particularly with the fluoroquinolones and macrolide antibiotics, has now emerged globally with thermophilic campylobacters, including Campylobacter jejuni and C. coli, giving rise to concerns about how these organisms have acquired such resistance characteristics, as well as consequences for human and animal treatment. This review examines (i) the clinical epidemiology of antibiotic resistance in human and animal thermophilic campylobacters,

  2. Methicillin-resistant Staphylococcus aureus-induced thrombo-inflammatory response is reduced with timely antibiotic administration

    PubMed Central

    Franks, Zechariah; Campbell, Robert A.; de Abreu, Adriana Vieira; Holloway, Jeffrey T.; Marvin, James E.; Kraemer, Bjoern F.; Zimmerman, Guy A.; Weyrich, Andrew S.; Rondina, Matthew T.

    2013-01-01

    Summary Methicillin-resistant Staphylococcus aureus (MRSA) induces a pro-thrombotic and pro-inflammatory milieu. Although timely antibiotic administration in MRSA sepsis may improve outcomes by arresting bacterial growth, the effects of antibiotics on mitigating injurious thrombo-inflammatory cellular responses remains unexplored. Using a newly developed human whole blood model and an in vivo mouse model of MRSA infection, we examined how antibiotics inhibit MRSA induced thrombo-inflammatory pathways. Human whole blood was inoculated with MRSA. Thrombin generation and inflammatory cytokine synthesis was measured in the presence or absence of linezolid and vancomycin. C57BL/6 mice were injected with MRSA and the effect of vancomycin administration was examined. MRSA accelerated thrombin generation in a time- and concentration-dependent manner and induced the release of cytokines, including interleukin (IL)-6, IL-8, and monocyte chemotactic protein (MCP)-1. The increase in thrombin generation and inflammatory responses was mediated through the synthesis of tissue factor and cytokines, respectively, and the release of microparticles. The early administration of antibiotics restored normal thrombin generation patterns and significantly reduced the synthesis of cytokines. In contrast, when antibiotic administration was delayed, thrombin generation and cytokine synthesis were not significantly reduced. In mice infected with MRSA, early antibiotic administration reduced thrombin anti-thrombin complexes and cytokine synthesis, whereas delayed antibiotic administration did not. These data provide novel mechanistic evidence of the importance of prompt antibiotic administration in infectious syndromes. PMID:23348831

  3. Choice of antibiotics for serious infections in children

    Microsoft Academic Search

    A. N. Prasad; R. K. Marwaha

    1984-01-01

    Effective rational antibiotic therapy is based on the knowledge of drug kinetics and microbial susceptibility to antibiotics. Penetration of antibiotics and achievement of inhibitory concentrations at infection sites constitutes an important criterion for selection of antibiotics. In this communication an attempt is being made to examine antibiotic penetrability into various body fluids and to suggest effective antibiotic regimens for treatment

  4. Antibiotic Resistance: A Concern to Veterinary and Human Medicine

    Microsoft Academic Search

    Sitaram Aryal

    Bacterial resistance to antibiotics occurs even without the use of antibiotics. Antibiotic use exerts a selective pressure to the bacterial flora that help in the emergence and development of antibiotic resistance. Antibiotics are used worldwide both in veterinary and human medicine. The wide spread use of antibiotics in human and animal has raised the concern about the development of resistant

  5. Studies on the synergism of sulbactam and beta-lactam antibiotics under in vitro conditions and in healthy volunteers after intravenous administration. Antibacterial activity in vitro, compatibility and pharmacokinetics of the drugs in combination.

    PubMed

    Wildfeuer, A; Schmalreck, A; Räder, K; Eibel, G; Pfaff, G

    1989-01-01

    Sulbactam, a new beta-lactam inhibitor, increased the in vitro activity of cefotaxime, mezlocillin and piperacillin against 803 clinical bacterial isolates. The synergism of sulbactam and these antibiotics was particular marked against 467 beta-lactamase positive strains, both aerobic and anaerobic. In the presence of sulbactam the mean minimal inhibitory concentrations (MICs) of the antibiotics against beta-lactamase positive bacteria were greatly reduced: with cefotaxime by 58%, with mezlocillin by 64% and with piperacillin by 70%. Sulbactam alone at low concentrations inhibited the growth of only a few strains (Neisseria spp., Acinetobacter spp.). The inhibitor proved to be very stable in infusion media under a variety of conditions and was compatible in vitro with 14 different beta-lactam antibiotics. The pharmacokinetics profiles of sulbactam and the antibiotics cefotaxime, mezlocillin and piperacillin were similar after infusion to healthy volunteers. The relevant pharmacokinetic parameters of the single substances were essentially unchanged when administered in combination. The general similarity between the pharmacokinetics of sulbactam and of the beta-lactam antibiotics appears to be an essential precondition for the therapeutic success of such a synergistic combination. Thus the physicochemical and pharmacological properties of sulbactam apparently permit flexible dosage in combination with different penicillins or cephalosporins and sulbactam can be administered as non-fixed combination in the clinical treatment of bacterial infections. PMID:2785802

  6. Antibiotic susceptibility and molecular epidemiology of Acinetobacter calcoaceticus–baumannii complex strains isolated from a referral hospital in northern Vietnam

    PubMed Central

    Van, Trang Dinh; Dinh, Quynh-Dao; Vu, Phu Dinh; Nguyen, Trung Vu; Pham, Ca Van; Dao, Trinh Tuyet; Phung, Cam Dac; Hoang, Ha Thu Thi; Tang, Nga Thi; Do, Nga Thuy; Nguyen, Kinh Van; Wertheim, Heiman

    2014-01-01

    Acinetobacter calcoaceticus–baumannii complex is a common cause of hospital-acquired infections (HAIs) globally, remarkable for its high rate of antibiotic resistance, including to carbapenems. There are few data on the resistance of A. baumannii in Vietnam, which are essential for developing evidence-based treatment guidelines for HAIs. Antibiotic susceptibility testing was conducted by VITEK®2, and pulsed-field gel electrophoresis (PFGE) was performed on 66 clinical A. baumannii complex isolates recovered during 2009 at the National Hospital of Tropical Diseases (NHTD), a referral hospital in Hanoi, Vietnam. Basic demographic and clinical data were collected and analysed using descriptive statistics. Most isolates came from lower respiratory tract specimens (59; 89.4%) from intensive care unit (ICU) patients [64/65 (98.5%) with available data] who had been admitted to NHTD for ?2 days [42/46 (91.3%) with available data]. More than 90% of the isolates were resistant to the tested ?-lactamase/?-lactamase inhibitors, cephalosporins, carbapenems, fluoroquinolones and trimethoprim/sulfamethoxazole. Moreover, 25.4% (16/63) were resistant to all tested ?-lactams, quinolones and aminoglycosides. All isolates remained sensitive to colistin and 58.7% were susceptible to tigecycline. Of the 66 isolates, 49 could be classified into eight PFGE types (A–H). Every PFGE type, except D, had cluster(s) of three or more isolates with a temporal relationship. In conclusion, these data suggest a significant rise in A. baumannii antibiotic resistance in Vietnam. Clustering within PFGE types supports cross-transmission of A. baumannii within the ICU at NHTD. Increased research and resources in optimising treatment, infection control and antibiotic stewardship are needed. PMID:25540720

  7. Occurrence and Distribution of Antibiotic-resistant Bacteria and Transfer of Resistance Genes in Lake Taihu

    PubMed Central

    Yin, Qian; Yue, Dongmei; Peng, Yuke; Liu, Ying; Xiao, Lin

    2013-01-01

    The overuse of antibiotics has accelerated antibiotic resistance in the natural environment, especially fresh water, generating a potential risk for public health around the world. In this study, antibiotic resistance in Lake Taihu was investigated and this was the first thorough data obtained through culture-dependent methods. High percentages of resistance to streptomycin and ampicillin among bacterial isolates were detected, followed by tetracycline and chloramphenicol. Especially high levels of ampicillin resistance in the western and northern regions were illustrated. Bacterial identification of the isolates selected for further study indicated the prevalence of some opportunistic pathogens and 62.0% of the 78 isolates exhibited multiple antibiotic resistance. The presence of ESBLs genes was in the following sequence: blaTEM > blaSHV > blaCTMX and 38.5% of the isolates had a class I integrase gene. Of all tested strains, 80.8% were able to transfer antibiotic resistance through conjugation. We also concluded that some new families of human-associated ESBLs and AmpC genes can be found in natural environmental isolates. The prevalence of antibiotic resistance and the dissemination of transferable antibiotic resistance in bacterial isolates (especially in opportunistic pathogens) was alarming and clearly indicated the urgency of realizing the health risks of antibiotic resistance to human and animal populations who are dependent on Lake Taihu for water consumption. PMID:24240317

  8. A Mutation of the RNA Polymerase ?? Subunit (rpoC) Confers Cephalosporin Resistance in Bacillus subtilis

    PubMed Central

    Lee, Yong Heon; Nam, Ki Hyun

    2013-01-01

    In bacteria, mutations affecting the major catalytic subunits of RNA polymerase (encoded by rpoB and rpoC) emerge in response to a variety of selective pressures. Here we isolated a Bacillus subtilis strain with high-level resistance to cefuroxime (CEF). Whole-genome resequencing revealed only one missense mutation affecting an invariant residue in close proximity to the C-terminal DNA-binding domain of RpoC (G1122D). Genetic reconstruction experiments demonstrate that this substitution is sufficient to confer CEF resistance. The G1122D mutation leads to elevated expression of stress-responsive regulons, including those of extracytoplasmic function (ECF) ? factors (?M, ?W, and ?X) and the general stress ? factor (?B). The increased CEF resistance of the rpoCG1122D strain is lost in the sigM rpoCG1122D double mutant, consistent with a major role for ?M in CEF resistance. However, a sigM mutant is very sensitive to CEF, and this sensitivity is still reduced by the G1122D mutation, suggesting that other regulatory effects are also important. Indeed, the ability of the G1122D mutation to increase CEF resistance is further reduced in a triple mutant strain lacking three ECF ? factors (?M, ?W, and ?X), which are known from prior studies to control overlapping sets of genes. Collectively, our findings highlight the ability of mutations in RNA polymerase to confer antibiotic resistance by affecting the activity of alternative ? factors that control cell envelope stress-responsive regulons. PMID:23070162

  9. [Antimicrobial spectrum of antibiotic batumin].

    PubMed

    Klochko, V V; Kiprianova, E A; Churkina, L N; Avdeeva, L V

    2008-01-01

    Antibacterial activity of antibiotic batumin, isolated from Pseudomonas genus has been studied using CLSI standard methods. Batumin was highly active against all studied strains belonging to 10 species of Staphylococcus genus (minimal inhibitory concentration (MIC)--0.25-0.5 microg/ml); it has shown a moderate activity against enterobacteria of genera Salmonella, Bordetella, Escherichia, Klebsiella (MIC 8-64 microg/ml) and practically did not inhibit strains ofmicrococci, streptococci, sporeforming bacteria including Clostridium sporogenes (MIC 256 microg/ml or above). Strains of yeasts and microscopic fungi Candida tropicalis, C. utilis, C. albicans, Saccharomyces cerevisiae u Aspergillus niger were resistant to batumin. Antibiotic activity depended on test-culture cells concentration and medium pH and was greatest at pH 5.5 characteristic of human skin. PMID:19140420

  10. Fluoroquinolone Antibiotics in the Environment

    Microsoft Academic Search

    Premasis Sukul; Michael Spiteller

    The occurrence of human and veterinary pharmaceuticals in soil and water (Thiele-Bruhn 2003; Snyder et al. 2003; Hamscher et al. 2004; Kay et al. 2004) has led to increased research activities among environmental scientists to find out their possible environmental threats.\\u000a As antibiotics are used for human and animal medical care, there is a possibility for these drugs to reach

  11. High-dose methylprednisolone influences the physiology and virulence of Candida albicans ambiguously and enhances the candidacidal activity of the polyene antibiotic amphotericin B and the superoxide-generating agent menadione.

    PubMed

    Gyetvai, Agnes; Emri, Tamás; Fekete, Andrea; Varga, Zsuzsa; Gazdag, Zoltán; Pesti, Miklós; Belágyi, József; Emõdy, Levente; Pócsi, István; Lenkey, Béla

    2007-03-01

    Although exposure of Candida albicans cells to high-dose (4 mM) methylprednisolone stimulated microbial growth, germination rate in serum and phospholipase release, it also promoted the recognition of C. albicans cells by polymorphonuclear leukocytes. Pretreatment of C. albicans cells with methylprednisolone did not result in any increase in the pathogenicity of the fungus in intraperitoneal and intravenous mouse assays. Therefore, the virulence of C. albicans is unlikely to increase in patients treated with comparably high-dose methylprednisolone on skin and mucosal membranes. Methylprednisolone treatments also increased the production of conjugated dienes and thiobarbituric acid-reactive substances, and the menadione sensitivity of C. albicans cells, which can be explained by a significant decrease in the specific activities of several antioxidant enzymes. The combination of methylprednisolone with oxidants, e.g. in topical applications, may be of clinical importance when the predisposition to candidiasis is high. Methylprednisolone treatments negatively affected membrane fluidity and decreased the antifungal effects of both the polyene antibiotic nystatin and the ergosterol biosynthesis inhibitor lovastatin, and also enhanced the deleterious effects of the polyene antimycotic amphotericin B on C. albicans cells. These corticosteroid-polyene drug interactions should be considered in the treatment of C. albicans infections in patients with prolonged topical application of corticosteroids. PMID:17266730

  12. In Vitro Activities of Various b-Lactam Antimicrobial Agents against Clinical Isolates ofEscherichia coliandKlebsiellaspp. Resistant to Oxyimino Cephalosporins

    Microsoft Academic Search

    BRADLEY D. JETT; DAVID J. RITCHIE; RICHARD REICHLEY; THOMAS C. BAILEY; ANDDANIEL F. SAHM

    1995-01-01

    Broth microdilution testing was used to study the activity of several beta-lactam antimicrobial agents, includingpiperacillin-tazobactamandcefepime,against108clinicallyderivedEscherichiacoliandKlebsiellasp. strains resistant to oxyimino cephalosporins (i.e., putative extended-spectrum b-lactamase producers). On the basis of the percentage of susceptible strains, imipenem (100%), cefotetan ($92%), and piperacillin-tazobac- tam ($86%) were the most active agents. Cefepime activity (52 to 64% susceptible) was comparable to that of cefotaxime (40

  13. Emergence, spread and characteristics of Neisseria gonorrhoeae isolates with in vitro decreased susceptibility and resistance to extended-spectrum cephalosporins in Sweden

    Microsoft Academic Search

    Daniel Golparian; Bengt Hellmark; Hans Fredlund; Magnus Unemo

    2010-01-01

    BackgroundNeisseria gonorrhoeae has developed resistance to most antimicrobials used for treatment. Worryingly, treatment failures with oral extended-spectrum cephalosporins (ESCs) have been reported, especially in the WHO Western Pacific Region, and susceptibility to all ESCs (oral and injectable), the last remaining treatment options in many settings, is decreasing globally.ObjectivesTo examine the emergence, spread and characteristics of Neisseria gonorrhoeae isolates with decreased

  14. Cephalosporin C production by a highly productive Cephalosporium acremonium strain in an airlift tower loop reactor with static mixers.

    PubMed

    Zhou, W; Holzhauer-Rieger, K; Bayer, T; Schügerl, K

    1993-04-01

    The production of cephalosporin C (CPC) and its precursors penicillin N (PEN N), deacetoxycephalosporin C (DAOC) and deacetylcephalosporin C (DAC), with a highly productive strain of Cephalosporin acremonium, was investigated in an 80-1 airlift tower loop reactor with four static mixer modules (Type SMV, Sulzer) (ATLRM) on a complex medium containing 50 g l-1 peanut flour (PF). The most important key parameters such as glucose concentration and cell mass concentration were monitored during a fed-batch cultivation process. The concentrations of products CPC, PEN N, DAOC an DAC were determined on line by HPLC. The influences of four motionless mixers on the dissolved oxygen concentration (DOC), oxygen transfer rate, the cell growth and the CPC production, as well as the reactor performance, were evaluated. The results were compared with the performance of an airlift tower loop reactor (ATLR) without static mixers as well as with a stirred tank reactor (STR). A comparison of cultivations in the ATLRM and ATLR with 50 g l-1 PF indicates that the obtained maximal CPC concentration and the (CPC + DAC + DAOC) concentration were 7% and 22% higher in the ATLRM (4.96 and 7.46 g l-1) than in the ATLR (4.63 and 6.13 g l-1) respectively. The maximal CPC volumetric productivity in the ATLRM (55.1 mg l-1 h-1) was also considerably higher than that in the ATLR (48.5 mg l-1 h-1). The specific power input was reduced from 2.36 to 1.5 kW m-3, the specific productivity pertaining to the power input was improved from 1.96 to 3.31 g W-1. On the other hand, cultivation in the ATLRM had a lower maximum CPC concentration and volumetric productivity than those in STR (7.2 g l-1 and 71.2 mg l-1 h-1) with the same medium due to the lower shear stress levels and the lower specific power input (1.5 vs. 3.0 kW m-3); but the specific power imput-based yield coefficient was in the ATLRM (3.31 g W-1) higher than in the STR (2.40 g W-1). By increasing the amount of PF, it was possible to enhance the CPC concentration and volumetric productivity in the STR. However, the performance of the ATLRM was limited to using a medium containing maximal 50 g l-1 PF because of the high viscosity of the medium, the limited energy input and thus the limited oxygen supply. PMID:7763560

  15. Optimizing antibiotic selection in treating COPD exacerbations

    PubMed Central

    Siddiqi, Attiya; Sethi, Sanjay

    2008-01-01

    Our understanding of the etiology, pathogenesis and consequences of acute exacerbations of chronic obstructive pulmonary disease (COPD) has increased substantially in the last decade. Several new lines of evidence demonstrate that bacterial isolation from sputum during acute exacerbation in many instances reflects a cause-effect relationship. Placebo-controlled antibiotic trials in exacerbations of COPD demonstrate significant clinical benefits of antibiotic treatment in moderate and severe episodes. However, in the multitude of antibiotic comparison trials, the choice of antibiotics does not appear to affect the clinical outcome, which can be explained by several methodological limitations of these trials. Recently, comparison trials with nontraditional end-points have shown differences among antibiotics in the treatment of exacerbations of COPD. Observational studies that have examined clinical outcome of exacerbations have repeatedly demonstrated certain clinical characteristics to be associated with treatment failure or early relapse. Optimal antibiotic selection for exacerbations has therefore incorporated quantifying the risk for a poor outcome of the exacerbation and choosing antibiotics differently for low risk and high risk patients, reserving the broader spectrum drugs for the high risk patients. Though improved outcomes in exacerbations with antibiotic choice based on such risk stratification has not yet been demonstrated in prospective controlled trials, this approach takes into account concerns of disease heterogeneity, antibiotic resistance and judicious antibiotic use in exacerbations. PMID:18488427

  16. Evaluating antibiotic stewardship programs in patients with bacteremia using administrative data: a cohort study.

    PubMed

    Boel, J; Søgaard, M; Andreasen, V; Jarløv, J O; Arpi, M

    2015-07-01

    When introducing new antibiotic guidelines for empirical treatment of bacteremia, it is imperative to evaluate the performance of the new guideline. We examined the utility of administrative data to evaluate the effect of new antibiotic guidelines and the prognostic impact of appropriate empirical treatment. We categorized 2,008 adult patients diagnosed with bacteremia between 2010 and 2012 according to whether they received cephalosporins or fluoroquinolones (old regimen) or not (new regimen). We used administrative data to extract individual level data on mortality, readmission, and appropriateness of treatment, and computed adjusted hazard ratios (HRs) and 95 % confidence intervals (CIs) for 30-day mortality and post-discharge readmission by regimen and appropriateness of treatment. In total, 945 (47.1 %) were treated by the old regimen and 1,063 (52.9 %) by the new. The median length of stay (8 days) did not differ by regimen and neither did the proportion of those receiving appropriate empirical treatment (84.1 % vs. 85.5 %). However, fewer patients with the new regimen were admitted to the intensive care unit (ICU; 3.8 % vs. 12.0 %) and they had lower 30-day mortality (16.4 % vs. 23.4 %). The adjusted 30-day mortality HR for appropriate versus inappropriate treatment was 0.79 (95 % CI 0.62-1.01) and 0.83 (95 % CI 0.66-1.05) for the new versus the old regimen. The HR for 30-day readmission for appropriate versus inappropriate treatment was 0.91 (95 % CI 0.73-1.13) and 1.05 (95 % CI 0.87-1.25) for the new versus the old regimen. This study demonstrates that administrative data can be useful for evaluating the effect and quality of new bacteremia treatment guidelines. PMID:25894986

  17. Desire for Antibiotics and Antibiotic Prescribing for Adults with Upper Respiratory Tract Infections

    PubMed Central

    Linder, Jeffrey A; Singer, Daniel E

    2003-01-01

    OBJECTIVE Prior studies have shown that 60% to 75% of adults with upper respiratory tract infections want antibiotics. More recent research indicates declines in antibiotic prescribing for upper respiratory tract infections. To investigate whether there has been a comparable decrease in patients’ desire for antibiotics, we measured the proportion of adults with upper respiratory tract infections who wanted antibiotics in the winter of 2001–2002. We also sought to identify factors independently associated with wanting antibiotics and antibiotic prescribing. DESIGN Prospective survey of adults with upper respiratory tract infections prior to visiting an acute care clinic from November 2001 to February 2002. MEASUREMENTS AND MAIN RESULTS Thirty-nine percent of 310 patients wanted antibiotics. Many patients wanted relief from symptoms (43%) or pain (24%) and many patients expected to receive a diagnosis (49%) or reassurance during the visit (13%). In multivariable modeling, independent predictors of wanting antibiotics were prior antibiotic use (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.3 to 4.7) and current smoking (OR, 3.1; 95% CI, 1.3 to 7.3). Physicians prescribed antibiotics to 46% of patients who wanted antibiotics and 29% of patients who did not want antibiotics (P= .01). In multivariable modeling, wanting antibiotics was an independent predictor of antibiotic prescribing (OR, 2.1; 95% CI, 1.1 to 4.4). CONCLUSIONS Only 39% of adults seeking care for upper respiratory tract infections wanted antibiotics, less than in previous studies. In continuing efforts to break the cycle of inappropriate antibiotic use, physicians should not assume that most patients with upper respiratory tract infections want antibiotics. PMID:14521641

  18. [New antibiotics produced by Bacillus subtilis strains].

    PubMed

    Malanicheva, I A; Kozlov, D G; Efimenko, T A; Zenkova, V A; Kastrukha, G S; Reznikova, M I; Korolev, A M; Borshchevskaia, L N; Tarasova, O D; Sineoki?, S P; Efremenkova, O V

    2014-01-01

    Two Bacillus subtilis strains isolated from the fruiting body of a basidiomycete fungus Pholiota squarrosa exhibited a broad range of antibacterial activity, including those against methicillin-resistant Staphylococcus aureus INA 00761 (MRSA) and Leuconostoc mes6nteroides VKPM B-4177 resistant to glycopep-> tide antibiotics, as well as antifungal activity. The strains were identified as belonging to the "B. subtilis" com- plex based on their morphological and physiological characteristics, as well as by sequencing of the 16S rRNA gene fragments. Both strains (INA 01085 and INA 01086) produced insignificant amounts of polyene antibiotics (hexaen and pentaen, respectively). Strain INA 01086 produced also a cyclic polypeptide antibiotic containing Asp, Gly, Leu, Pro, Tyr, Thr, Trp, and Phe, while the antibiotic of strain INA 01085 contained, apart from these, two unidentified nonproteinaceous amino acids. Both polypeptide antibiotics were new compounds efficient against gram-positive bacteria and able to override the natural bacterial antibiotic resistance. PMID:25844455

  19. Probiotics or antibiotics: future challenges in medicine.

    PubMed

    Nami, Yousef; Haghshenas, Babak; Abdullah, Norhafizah; Barzegari, Abolfazl; Radiah, Dayang; Rosli, Rozita; Khosroushahi, Ahmad Yari

    2015-02-01

    Genetic and environmental factors can affect the intestinal microbiome and microbial metabolome. Among these environmental factors, the consumption of antibiotics can significantly change the intestinal microbiome of individuals and consequently affect the corresponding metagenome. The term 'probiotics' is related to preventive medicine rather than therapeutic procedures and is, thus, considered the opposite of antibiotics. This review discusses the challenges between these opposing treatments in terms of the following points: (i) antibiotic resistance, the relationship between antibiotic consumption and microbiome diversity reduction, antibiotic effect on the metagenome, and disease associated with antibiotics; and (ii) probiotics as living drugs, probiotic effect on epigenetic alterations, and gut microbiome relevance to hygiene indulgence. The intestinal microbiome is more specific for individuals and may be affected by environmental alterations and the occurrence of diseases. PMID:25525206

  20. Synthesis, optimization, and characterization of silver nanoparticles from Acinetobacter calcoaceticus and their enhanced antibacterial activity when combined with antibiotics

    PubMed Central

    Singh, Richa; Wagh, Priyanka; Wadhwani, Sweety; Gaidhani, Sharvari; Kumbhar, Avinash; Bellare, Jayesh; Chopade, Balu Ananda

    2013-01-01

    Background The development of nontoxic methods of synthesizing nanoparticles is a major step in nanotechnology to allow their application in nanomedicine. The present study aims to biosynthesize silver nanoparticles (AgNPs) using a cell-free extract of Acinetobacter spp. and evaluate their antibacterial activity. Methods Eighteen strains of Acinetobacter were screened for AgNP synthesis. AgNPs were characterized using various techniques. Reaction parameters were optimized, and their effect on the morphology of AgNPs was studied. The synergistic potential of AgNPs on 14 antibiotics against seven pathogens was determined by disc-diffusion, broth-microdilution, and minimum bactericidal concentration assays. The efficacy of AgNPs was evaluated as per the minimum inhibitory concentration (MIC) breakpoints of the Clinical and Laboratory Standards Institute (CLSI) guidelines. Results Only A. calcoaceticus LRVP54 produced AgNPs within 24 hours. Monodisperse spherical nanoparticles of 8–12 nm were obtained with 0.7 mM silver nitrate at 70°C. During optimization, a blue-shift in ultraviolet-visible spectra was seen. X-ray diffraction data and lattice fringes (d =0.23 nm) observed under high-resolution transmission electron microscope confirmed the crystallinity of AgNPs. These AgNPs were found to be more effective against Gram-negative compared with Gram-positive microorganisms. Overall, AgNPs showed the highest synergy with vancomycin in the disc-diffusion assay. For Enterobacter aerogenes, a 3.8-fold increase in inhibition zone area was observed after the addition of AgNPs with vancomycin. Reduction in MIC and minimum bactericidal concentration was observed on exposure of AgNPs with antibiotics. Interestingly, multidrug-resistant A. baumannii was highly sensitized in the presence of AgNPs and became susceptible to antibiotics except cephalosporins. Similarly, the vancomycin-resistant strain of Streptococcus mutans was also found to be susceptible to antibiotic treatment when AgNPs were added. These biogenic AgNPs showed significant synergistic activity on the ?-lactam class of antibiotics. Conclusion This is the first report of synthesis of AgNPs using A. calcoaceticus LRVP54 and their significant synergistic activity with antibiotics resulting in increased susceptibility of multidrug-resistant bacteria evaluated as per MIC breakpoints of the CLSI standard. PMID:24235826

  1. High-throughput system for screening of Cephalosporin C high-yield strain by 48-deep-well microtiter plates.

    PubMed

    Tan, Jun; Chu, Ju; Hao, Yuyou; Guo, Yuanxin; Zhuang, Yingping; Zhang, Siliang

    2013-03-01

    Improvement of microbial strains for the high-production of industrial products has been the hallmark of all commercial fermentation processes. Strain improvement has been conventionally achieved through mutation and selection. However, most of the screenings were performed in shake flasks, which made the screening procedure very complex, time-consuming, and inefficient. Most mutant spore suspension had no chance to be screened due to the low-throughput of shake flasks and had to be sacrificed. In this paper, in order to get a Cephalosporin C (CPC) high-yield stain, traditional mutagenesis was employed to obtain the mutant library and gave them the equal screening chance by a novel mixture culture method combined with high-throughput screening method. The good correlation of fermentation results between differing-scale cultivations confirmed the feasibility of utilizing the 48-deep microtiter plates as a scale-down tool instead of shake flasks for culturing high-aerobic microbes with long cultivation period. The microbioassay based on the antibacterial activity of CPC against Alcaligenes faecalis was used to select mutants. As a result, the high-yield strain W-6 was successfully screened out and the CPC titer was nearly 50 % higher than that of the parental strain in the shake flask. The CPC production of strain W-6 was further validated in 50 l bioreactor, and the CPC production reached 32.0 g/l, twofold higher than that of the wild strain. PMID:23334835

  2. Acquisition of extended-spectrum cephalosporin- and colistin-resistant Salmonella enterica subsp. enterica serotype Newport by pilgrims during Hajj.

    PubMed

    Olaitan, Abiola Olumuyiwa; Dia, Ndèye Méry; Gautret, Philippe; Benkouiten, Samir; Belhouchat, Khadidja; Drali, Tassadit; Parola, Philippe; Brouqui, Philippe; Memish, Ziad; Raoult, Didier; Rolain, Jean-Marc

    2015-06-01

    Gatherings like the Hajj involving many people who travel from different parts of the world represent a risk for the acquisition and dissemination of infectious diseases. In this study, acquisition of multidrug-resistant (MDR) Salmonella spp. in 2013 Hajj pilgrims from Marseille, France, was investigated. In total, 267 rectal swabs were collected from 129 participants before their departure and after their return from the pilgrimage as well as during the pilgrimage from patients with diarrhoea. Samples were screened for the presence of Salmonella using quantitative real-time PCR and culture. Whole-genome sequencing was performed to characterise one of the isolates, and the mechanism leading to colistin resistance was investigated. Six post-Hajj samples and one sample collected during a diarrhoea episode in Hajj were positive for Salmonella by real-time PCR, with five Salmonella enterica belonging to several serotypes recovered by culture, whereas no pre-Hajj sample was positive. Two of the isolates belonged to the epidemic Newport serotype, were resistant to cephalosporins, gentamicin and colistin, and harboured the blaCTX-M-2 gene and a 12-nucleotide deletion in the pmrB gene leading to colistin resistance. This study shows that pilgrims acquired Salmonella bacteria, including a novel MDR clone, during the Hajj pilgrimage. This calls for more improved public health surveillance during Hajj because Salmonella is one of the most common diarrhoea-causing bacteria worldwide. Therefore, returning pilgrims could disseminate MDR bacteria worldwide upon returning to their home countries. PMID:25769786

  3. Antibacterial activities in vitro and in vivo and pharmacokinetics of cefquinome (HR 111V), a new broad-spectrum cephalosporin.

    PubMed Central

    Limbert, M; Isert, D; Klesel, N; Markus, A; Seeger, K; Seibert, G; Schrinner, E

    1991-01-01

    Cefquinome is a new injectable aminothiazolyl cephalosporin derivative. It is stable against chromosomally and plasmid-encoded beta-lactamases and has a broad antibacterial spectrum. Staphylococcus aureus, streptococci, Pseudomonas aeruginosa, and members of the family Enterobacteriaceae (Escherichia coli, Salmonella spp., Klebsiella spp., Enterobacter spp., Citrobacter spp., and Serratia marcescens) are inhibited at low concentrations. Cefquinome is also active against many strains of methicillin-resistant staphylococci and enterococci. Its in vitro activity against gram-negative anaerobes is very limited. The high in vitro activity of cefquinome is reflected by its high in vivo efficacy against experimental septicemia due to different gram-positive and gram-negative bacteria. We studied the pharmacokinetic properties of cefquinome in mice, dogs, pigs, and calves. After single parenteral administrations, cefquinome displayed high peak levels, declining with half-lives of about 0.5, 0.9, 1.2, and 1.3 h, respectively. The areas under the concentration-time curve determined for dogs and mice showed linear correlations to the given doses. In dogs the urinary recovery was more than 70% within 24 h of dosing. Images PMID:2014969

  4. Antibiotic Resistance in Oral\\/Respiratory Bacteria

    Microsoft Academic Search

    M. C. Roberts

    1998-01-01

    In the last 20 years, changes in world technology have occurred which have allowed for the rapid transport of people, food, and goods. Unfortunately, antibiotic residues and antibiotic-resistant bacteria have been transported as well. Over the past 20 years, the rise in antibiotic-resistant gene carriage in virtually every species of bacteria, not just oral\\/respiratory bacteria, has been documented. In this

  5. Coping with antibiotic resistance: contributions from genomics

    Microsoft Academic Search

    Gian Maria Rossolini; Maria Cristina Thaller

    2010-01-01

    Antibiotic resistance is a public health issue of global dimensions with a significant impact on morbidity, mortality and\\u000a healthcare-associated costs. The problem has recently been worsened by the steady increase in multiresistant strains and by\\u000a the restriction of antibiotic discovery and development programs. Recent advances in the field of bacterial genomics will\\u000a further current knowledge on antibiotic resistance and help

  6. Genome Sequencing of a Neisseria gonorrhoeae Isolate of a Successful International Clone with Decreased Susceptibility and Resistance to Extended-Spectrum Cephalosporins

    PubMed Central

    Wu, Abel; Golparian, Daniel; Esmaili, Sarah; Pandori, Will; Sena, Emilee; Klausner, Jeffrey D.; Barry, Pennan; Unemo, Magnus; Pandori, Mark

    2012-01-01

    The recent emergence of Neisseria gonorrhoeae strains with decreased susceptibility to extended-spectrum cephalosporins is a major concern globally. We sequenced the genome of an N. gonorrhoeae multiantigen sequence typing (NG-MAST) ST1407 isolate (SM-3) with decreased susceptibility and resistance to oral extended-spectrum cephalosporins. The isolate was cultured in 2008 in San Francisco, CA, and possessed mosaic penA allele XXXIV, which is associated with an international clone that possesses decreased susceptibility as well as resistance to oral extended-spectrum cephalosporins globally. The genome sequence of strain NCCP11945 was used as a scaffold, and our assembly resulted in 91 contigs covering 2,029,064 bp (91%; >150× coverage) of the genome. Numerous instances of suspected horizontal genetic transfer events with other Neisseria species were identified, and two genes, opa and txf, acquired from nongonococcal Neisseria species, were identified. Strains possessing mosaic penA alleles (n = 108) and nonmosaic penA alleles (n = 169) from the United States and Europe (15 countries), cultured in 2002 to 2009, were screened for the presence of these genes. The opa gene was detected in most (82%) penA mosaic-containing isolates (mainly from 2007 to 2009) but not in any penA nonmosaic isolates. The txf gene was found in all strains containing opa but also in several (18%) penA nonmosaic strains. Using opa and txf as genetic markers, we identified a strain that possesses mosaic penA allele XXXIV, but the majority of its genome is not genetically related to strain SM-3. This implies that penA mosaic allele XXXIV was transferred horizontally. Such isolates also possessed decreased susceptibility and resistance to oral extended-spectrum cephalosporins. These findings support that genetic screening for particular penA mosaic alleles can be a valuable method for tracking strains with decreased susceptibility as well as resistance to oral extended-spectrum cephalosporins worldwide and that screening using only NG-MAST may not be sufficient. PMID:22908152

  7. Genome sequencing of a Neisseria gonorrhoeae isolate of a successful international clone with decreased susceptibility and resistance to extended-spectrum cephalosporins.

    PubMed

    Hess, David; Wu, Abel; Golparian, Daniel; Esmaili, Sarah; Pandori, Will; Sena, Emilee; Klausner, Jeffrey D; Barry, Pennan; Unemo, Magnus; Pandori, Mark

    2012-11-01

    The recent emergence of Neisseria gonorrhoeae strains with decreased susceptibility to extended-spectrum cephalosporins is a major concern globally. We sequenced the genome of an N. gonorrhoeae multiantigen sequence typing (NG-MAST) ST1407 isolate (SM-3) with decreased susceptibility and resistance to oral extended-spectrum cephalosporins. The isolate was cultured in 2008 in San Francisco, CA, and possessed mosaic penA allele XXXIV, which is associated with an international clone that possesses decreased susceptibility as well as resistance to oral extended-spectrum cephalosporins globally. The genome sequence of strain NCCP11945 was used as a scaffold, and our assembly resulted in 91 contigs covering 2,029,064 bp (91%; >150× coverage) of the genome. Numerous instances of suspected horizontal genetic transfer events with other Neisseria species were identified, and two genes, opa and txf, acquired from nongonococcal Neisseria species, were identified. Strains possessing mosaic penA alleles (n = 108) and nonmosaic penA alleles (n = 169) from the United States and Europe (15 countries), cultured in 2002 to 2009, were screened for the presence of these genes. The opa gene was detected in most (82%) penA mosaic-containing isolates (mainly from 2007 to 2009) but not in any penA nonmosaic isolates. The txf gene was found in all strains containing opa but also in several (18%) penA nonmosaic strains. Using opa and txf as genetic markers, we identified a strain that possesses mosaic penA allele XXXIV, but the majority of its genome is not genetically related to strain SM-3. This implies that penA mosaic allele XXXIV was transferred horizontally. Such isolates also possessed decreased susceptibility and resistance to oral extended-spectrum cephalosporins. These findings support that genetic screening for particular penA mosaic alleles can be a valuable method for tracking strains with decreased susceptibility as well as resistance to oral extended-spectrum cephalosporins worldwide and that screening using only NG-MAST may not be sufficient. PMID:22908152

  8. New anticancer antibiotic acts through diradical rearrangement

    SciTech Connect

    Stinson, S. (C and EN, Washington, DC (US))

    1990-05-28

    This paper reports that chemists have found and characterized an anticancer antibiotic, dynemicin A, that may be the fouth of a series of antibiotics that act by metabolic rearrangement to a diradical. If true, diradical precursors may represent an antibiotic strategy that evolved widely in nature. And, there may be many more anticancer antibiotics awaiting discovery. Also, the unique internal trigger that seems to set off the dynemicin rearrangement gives chemists a new understanding of how these compounds work. If, indeed, the anthraquinone nucleus in dynemicin A binds by intercalation between strands of DNA as is now thought, chemists will learn more about how to deliver drugs to specific sites.

  9. Treating Children Without Antibiotics in Primary Healthcare

    PubMed Central

    Kutty, Narayanan

    2011-01-01

    The overuse of antibiotics in children is becoming a major public health problem. Although most of the common childhood infections such as diarrhea and upper respiratory tract infections are caused by viruses, large volumes of antibiotics are prescribed for these infections in children in the primary care settings. Excessive use of antibiotics is the fundamental risk factor for the development of antibiotic resistance. It is estimated that 90% of upper respiratory tract infections are self limiting viral illnesses and even bacterial infections like acute otitis media often run a self limiting course. Clinical trials have shown that antibiotic use to treat common upper respiratory tract infections like sore throat, nasopharyngitis and otitis media has no or minimal benefit on the clinical outcome. This report discusses two strategies considered to reduce the use of antibiotic in these conditions: i) No prescription, and ii) Delayed prescription of antibiotics for common upper respiratory tract infections. Moreover, this report calls for a significant modification of the prescribing habits of physicians, and to also extend community awareness on the harms of the misuse and overuse of antibiotics. It is imperative to educate health workers as well as the Community in a coordinated and sustainable manner about the growing public health problem of antibiotic resistance. PMID:22125722

  10. Prophylactic Antibiotics and Wound Infection

    PubMed Central

    Elbur, Abubaker Ibrahim; M.A., Yousif; El-Sayed, Ahmed S.A.; Abdel-Rahman, Manar E.

    2013-01-01

    Introduction: Surgical site infections account for 14%-25% of all nosocomial infections. The main aims of this study were to audit the use of prophylactic antibiotic, to quantify the rate of post-operative wound infection, and to identify risk factors for its occurrence in general surgery. Methodology: A cross-sectional study was conducted in the General Surgery Department in Khartoum Teaching Hospital– Sudan. All Adult patients (age ?18 years) admitted during March 1st to 31st October 2010 were recruited. Multivariable logistic analysis was done to identify wound infection risk factors. Prescriptions were audited against predetermined criteria. Results: A total of 540 patients were recruited; (females73.7% of total ). The performed surgical procedures were 547. The rate of wound infection was 10.9%. Multivariable logistic analysis showed that; ASA score ? 3; (p= <0.001), wound class (p= 0.001), and laparoscopic surgical technique; (p= 0.002) were significantly associated with prevalence of wound infection. Surgical prophylaxis was unnecessarily given to 311 (97.5%) of 319 patients for whom it was not recommended. Prophylaxis was recommended for 221 patients; of them 218 (98.6 %) were given preoperative dose in the operating rooms. Evaluation of prescriptions for those patients showed that; spectrum of antibiotic was adequate for 160 (73.4%) patients, 143 (65.6%) were given accurate doses, only 4 (1.8%) had the first preoperative dose/s in proper time window, and for 186 (85.3%) of them prophylaxis was extended post-operatively. Only 36 (6.7%) prescriptions were found to be complying with the stated criteria. Conclusion: The rate of wound infection was high and prophylactic antibiotics were irrationally used. Multiple interventions are needed to correct the situation. PMID:24551629

  11. Reducing Parental Demand for Antibiotics by Promoting Communication Skills

    ERIC Educational Resources Information Center

    Alder, Stephen C.; Trunnell, Eric P.; White, George L., Jr.; Lyon, Joseph L.; Reading, James P.; Samore, Matthew H.; Magill, Michael K.

    2005-01-01

    Antibiotic-resistant strains of bacteria are continuing to emerge as high rates of antibiotic use persist. Children are among the highest users of antibiotics, with parents influencing physician decision-making regarding antibiotic prescription. An intervention based on Social Cognitive Theory (SCT) to reduce parents' expectations for antibiotics

  12. The Pros of Procalcitonin: Reducing Antibiotic Duration in the ICU

    E-print Network

    Pillow, Jonathan

    hospitalizations and prior antibiotic exposure b. Resistance genes can be transferred to other types of bacteria. Consequences of antibiotic overuse i. Promotion of multi-drug resistant (MDR) pathogens 1. Antibiotic use to antibiotics than any other drug class iv. Excess cost 1. Cost of treating antibiotic-resistant infections may

  13. Identification of Multiresistant Salmonella Isolates Capable of Subsisting on Antibiotics?

    PubMed Central

    Barnhill, Alison E.; Weeks, Katherine E.; Xiong, Nalee; Day, Tim A.; Carlson, Steve A.

    2010-01-01

    This study assessed the ability of Salmonella (572 isolates) to subsist on 12 different antibiotics. The majority (11/12) of the antibiotics enabled subsistence for at least 1 of 140 isolates. Furthermore, 40 isolates were able to subsist on more than one antibiotic. Antibiotic resistance and antibiotic subsistence do not appear to be equivalent. PMID:20173063

  14. UTILIZATION OF RESTRICTED ANTIBIOTICS IN A UNIVERSITY HOSPITAL IN THAILAND

    Microsoft Academic Search

    Sasima Kusuma Na Ayuthya; Oraphan P Matangkasombut; Sayomporn Sirinavin; Kumthorn Malathum; Boonmee Sathapatayavongs

    Antibiotic resistance, a major negative consequence of antibiotic overuse, is an im- portant problem worldwide. Various means have been used to control antibiotic usage including the use of an antibiotic order form (AOF), restricted antibiotic formularies and provision of educational information. The present study was designed to evaluate the use of antimicrobials in a 1,000-bed university hospital. Antimicrobial agents, likely

  15. An In Vitro Study on the Effects of Nisin on the Antibacterial Activities of 18 Antibiotics against Enterococcus faecalis

    PubMed Central

    Ling, Junqi; Ma, Jinglei; Huang, Lijia; Zhang, Luodan

    2014-01-01

    Enterococcus faecalis rank among the leading causes of nosocomial infections worldwide and possesses both intrinsic and acquired resistance to a variety of antibiotics. Development of new antibiotics is limited, and pathogens continually generate new antibiotic resistance. Many researchers aim to identify strategies to effectively kill this drug-resistant pathogen. Here, we evaluated the effect of the antimicrobial peptide nisin on the antibacterial activities of 18 antibiotics against E. faecalis. The MIC and MBC results showed that the antibacterial activities of 18 antibiotics against E. faecalis OG1RF, ATCC 29212, and strain E were significantly improved in the presence of 200 U/ml nisin. Statistically significant differences were observed between the results with and without 200 U/ml nisin at the same concentrations of penicillin or chloramphenicol (p<0.05). The checkerboard assay showed that the combination of nisin and penicillin or chloramphenicol had a synergetic effect against the three tested E. faecalis strains. The transmission electron microscope images showed that E. faecalis was not obviously destroyed by penicillin or chloramphenicol alone but was severely disrupted by either antibiotic in combination with nisin. Furthermore, assessing biofilms by a confocal laser scanning microscope showed that penicillin, ciprofloxacin, and chloramphenicol all showed stronger antibiofilm actions in combination with nisin than when these antibiotics were administered alone. Therefore, nisin can significantly improve the antibacterial and antibiofilm activities of many antibiotics, and certain antibiotics in combination with nisin have considerable potential for use as inhibitors of this drug-resistant pathogen. PMID:24586598

  16. An in vitro study on the effects of nisin on the antibacterial activities of 18 antibiotics against Enterococcus faecalis.

    PubMed

    Tong, Zhongchun; Zhang, Yuejiao; Ling, Junqi; Ma, Jinglei; Huang, Lijia; Zhang, Luodan

    2014-01-01

    Enterococcus faecalis rank among the leading causes of nosocomial infections worldwide and possesses both intrinsic and acquired resistance to a variety of antibiotics. Development of new antibiotics is limited, and pathogens continually generate new antibiotic resistance. Many researchers aim to identify strategies to effectively kill this drug-resistant pathogen. Here, we evaluated the effect of the antimicrobial peptide nisin on the antibacterial activities of 18 antibiotics against E. faecalis. The MIC and MBC results showed that the antibacterial activities of 18 antibiotics against E. faecalis OG1RF, ATCC 29212, and strain E were significantly improved in the presence of 200 U/ml nisin. Statistically significant differences were observed between the results with and without 200 U/ml nisin at the same concentrations of penicillin or chloramphenicol (p<0.05). The checkerboard assay showed that the combination of nisin and penicillin or chloramphenicol had a synergetic effect against the three tested E. faecalis strains. The transmission electron microscope images showed that E. faecalis was not obviously destroyed by penicillin or chloramphenicol alone but was severely disrupted by either antibiotic in combination with nisin. Furthermore, assessing biofilms by a confocal laser scanning microscope showed that penicillin, ciprofloxacin, and chloramphenicol all showed stronger antibiofilm actions in combination with nisin than when these antibiotics were administered alone. Therefore, nisin can significantly improve the antibacterial and antibiofilm activities of many antibiotics, and certain antibiotics in combination with nisin have considerable potential for use as inhibitors of this drug-resistant pathogen. PMID:24586598

  17. Antibiotics

    NASA Astrophysics Data System (ADS)

    Anhalt, John P.

    A 28-year-old man was transferred to our hospital and underwent surgery for resection of an aortic graft infected with Klebsiella pneumoniae. Antimicrobial therapy consisted of amikacin, cefazolin, chloramphenicol, sulfamethoxazole, and trimethoprim. A request for amikacin and sulfamethoxazole assays was received by the laboratory along with information that the patient had received tobramycin until 24 h before the serum was obtained.

  18. Antibiotic contamination and occurrence of antibiotic-resistant bacteria in aquatic environments of northern Vietnam

    Microsoft Academic Search

    Phan Thi Phuong Hoa; Satoshi Managaki; Norihide Nakada; Hideshige Takada; Akiko Shimizu; Duong Hong Anh; Pham Hung Viet; Satoru Suzuki

    2011-01-01

    The ubiquitous application and release of antibiotics to the environment can result in bacterial antibiotic resistance, which in turn can be a serious risk to humans and other animals. Southeast Asian countries commonly apply an integrated recycling farm system called VAC (Vegetable, Aquaculture and Caged animal). In the VAC environment, antibiotics are released from animal and human origins, which would

  19. The role of aquatic ecosystems as reservoirs of antibiotic resistant bacteria and antibiotic resistance genes

    Microsoft Academic Search

    P. T. Biyela; J. Lin; C. C. Bezuidenhout

    The widespread and indiscriminate use of antibiotics has led to the development of antibiotic resistance in pathogenic, as well as commensal, microorganisms. Resistance genes may be horizontally or vertically transferred between bacterial communities in the environment. The recipient bacterial communities may then act as a reservoir of these resistance genes. In this study, we report the incidence of antibiotic resistance

  20. Antibiotics and antibiotic-resistant bacteria in waters associated with a hospital in Ujjain, India

    Microsoft Academic Search

    Vishal Diwan; Ashok J Tamhankar; Rakesh K Khandal; Shanta Sen; Manjeet Aggarwal; Yogyata Marothi; Rama V Iyer; Karin Sundblad-Tonderski; Cecilia Stålsby-Lundborg

    2010-01-01

    BACKGROUND: Concerns have been raised about the public health implications of the presence of antibiotic residues in the aquatic environment and their effect on the development of bacterial resistance. While there is information on antibiotic residue levels in hospital effluent from some other countries, information on antibiotic residue levels in effluent from Indian hospitals is not available. Also, concurrent studies

  1. Prevalence and predictors of antibiotic prescription errors in an emergency department, Central Saudi Arabia

    PubMed Central

    Alanazi, Menyfah Q; Al-Jeraisy, Majed I; Salam, Mahmoud

    2015-01-01

    Background Inappropriate antibiotic (ATB) prescriptions are a threat to patients, leading to adverse drug reactions, bacterial resistance, and subsequently, elevated hospital costs. Our aim was to evaluate ATB prescriptions in an emergency department of a tertiary care facility. Methods A cross-sectional study was conducted by reviewing charts of patients complaining of infections. Patient characteristics (age, sex, weight, allergy, infection type) and prescription characteristics (class, dose, frequency, duration) were evaluated for appropriateness based on the AHFS Drug Information and the Drug Information Handbook. Descriptive and analytic statistics were applied. Results Sample with equal sex distribution constituted of 5,752 cases: adults (?15 years) =61% and pediatrics (<15 years) =39%. Around 55% complained of respiratory tract infections, 25% urinary tract infections (UTIs), and 20% others. Broad-spectrum coverage ATBs were prescribed for 76% of the cases. Before the prescription, 82% of pediatrics had their weight taken, while 18% had their weight estimated. Allergy checking was done in 8% only. Prevalence of inappropriate ATB prescriptions with at least one type of error was 46.2% (pediatrics =58% and adults =39%). Errors were in ATB selection (2%), dosage (22%), frequency (4%), and duration (29%). Dosage and duration errors were significantly predominant among pediatrics (P<0.001 and P<0.0001, respectively). Selection error was higher among adults (P=0.001). Age stratification and binary logistic regression were applied. Significant predictors of inappropriate prescriptions were associated with: 1) cephalosporin prescriptions (adults: P<0.001, adjusted odds ratio [adj OR] =3.31) (pediatrics: P<0.001, adj OR =4.12) compared to penicillin; 2) UTIs (adults: P<0.001, adj OR =2.78) (pediatrics: P=0.039, adj OR =0.73) compared to respiratory tract infections; 3) obtaining weight for pediatrics before the prescription of ATB (P<0.001, adj OR =1.83) compared to those whose weight was estimated; and 4) broad-spectrum ATBs in adults (P=0.002, adj OR =0.67). Conclusion Prevalence of ATB prescription errors in this emergency department was generally high and was particularly common with cephalosporin, narrow-spectrum ATBs, and UTI infections.

  2. Disrupting antibiotic resistance propagation by inhibiting the conjugative DNA relaxase

    PubMed Central

    Lujan, Scott A.; Guogas, Laura M.; Ragonese, Heather; Matson, Steven W.; Redinbo, Matthew R.

    2007-01-01

    Conjugative transfer of plasmid DNA via close cell–cell junctions is the main route by which antibiotic resistance genes spread between bacterial strains. Relaxases are essential for conjugative transfer and act by cleaving DNA strands and forming covalent phosphotyrosine linkages. Based on data indicating that multityrosine relaxase enzymes can accommodate two phosphotyrosine intermediates within their divalent metal-containing active sites, we hypothesized that bisphosphonates would inhibit relaxase activity and conjugative DNA transfer. We identified bisphosphonates that are nanomolar inhibitors of the F plasmid conjugative relaxase in vitro. Furthermore, we used cell-based assays to demonstrate that these compounds are highly effective at preventing DNA transfer and at selectively killing cells harboring conjugative plasmids. Two potent inhibitors, clodronate and etidronate, are already clinically approved to treat bone loss. Thus, the inhibition of conjugative relaxases is a potentially novel antimicrobial approach, one that selectively targets bacteria capable of transferring antibiotic resistance and generating multidrug resistant strains. PMID:17630285

  3. Role of Pseudomonas aeruginosa AmpR on ?-lactam and non-?-lactam transient cross-resistance upon pre-exposure to subinhibitory concentrations of antibiotics

    PubMed Central

    Kumari, Hansi; Balasubramanian, Deepak; Zincke, Diansy

    2014-01-01

    Pseudomonas aeruginosa is one of the most dreaded opportunistic pathogens accounting for 10?% of hospital-acquired infections, with a 50?% mortality rate in chronically ill patients. The increased prevalence of drug-resistant isolates is a major cause of concern. Resistance in P. aeruginosa is mediated by various mechanisms, some of which are shared among different classes of antibiotics and which raise the possibility of cross-resistance. The goal of this study was to explore the effect of subinhibitory concentrations (SICs) of clinically relevant antibiotics and the role of a global antibiotic resistance and virulence regulator, AmpR, in developing cross-resistance. We investigated the induction of transient cross-resistance in P. aeruginosa PAO1 upon exposure to SICs of antibiotics. Pre-exposure to carbapenems, specifically imipenem, even at 3 ng ml?1, adversely affected the efficacy of clinically used penicillins and cephalosporins. The high ?-lactam resistance was due to elevated expression of both ampC and ampR, encoding a chromosomal ?-lactamase and its regulator, respectively. Differences in the susceptibility of ampR and ampC mutants suggested non-AmpC-mediated regulation of ?-lactam resistance by AmpR. The increased susceptibility of P. aeruginosa in the absence of ampR to various antibiotics upon SIC exposure suggests that AmpR plays a major role in the cross-resistance. AmpR was shown previously to be involved in resistance to quinolones by regulating MexEF–OprN efflux pump. The data here further indicate the role of AmpR in cross-resistance between quinolones and aminoglycosides. This was confirmed using quantitative PCR, where expression of the mexEF efflux pump was further induced by ciprofloxacin and tobramycin, its substrate and a non-substrate, respectively, in the absence of ampR. The data presented here highlight the intricate cross-regulation of antibiotic resistance pathways at SICs of antibiotics and the need for careful assessment of the order of antibiotic regimens as this may have dire consequences. Targeting a global regulator such as AmpR that connects diverse pathways is a feasible therapeutic approach to combat P. aeruginosa pathogenesis. PMID:24464693

  4. A biosensing strategy for the rapid detection and classification of antibiotic resistance.

    PubMed

    Chen, Qun; Andersson, Anneli; Mecklenburg, Michael; Xie, Bin

    2015-11-15

    Antibiotic resistance (AR) poses an ever growing threat to global public health. Methods are urgently needed that simplify and accelerate the clinical detection and classification of AR. Here we describe a function-based antibiotic resistance assay (FARA) biosensing strategy. The scheme comprises three key components: i) FARA directly measures the thermal signal generated from the catalytic break-down of antibiotics by AR enzymes, ii) a sample specific AR profile is created by analyzing a panel of antibiotics which enhances informational content and iii) meta-analysis of the AR profile database to correlate profiles with diagnosis, treatments and outcomes. In order to test the ability of the scheme to identify and classify AR, two well-studied antibiotic resistance enzymes, penicillinase and metallo-beta-lactamase (MBL), were profiled using a panel of 5 antibiotics: penicillin G, penicillin V, ampicillin, oxacillin and imipenem. The results show that the profiles of the two enzymes could easily detect AR and differentially classified these enzymes. More importantly, both enzymes showed a significant and distinct secondary catalytic profile, which dramatically increases informational content. FARA profiles can be generated and analyzed in 1h. FARA is a fast, simple, cost effective alternative for detecting and classifying AR. FARA will speed up AR detection and classification will allow more accurate individualized treatment. This will reduce the spread of resistance and personalized treatments will improve patient outcomes. Other potential applications of FARA technology are discussed, including the possibility of developing an in vitro blood model for studying AR. PMID:26092129

  5. Comparison of two methods for collecting antibiotic use data on small dairy farms

    PubMed Central

    Redding, L. E.; Cubas-Delgado, F.; Sammel, M.D.; Smith, G.; Galligan, D.T.; Levy, M.Z.; Hennessy, S.

    2014-01-01

    Antibiotics are commonly used in animal agriculture; they can improve animal health and productivity, but their use may also represent a public health threat. Very little is known about antibiotic use on small farms in lower/middle income countries. To understand antibiotic use on these farms and promote the judicious use of these drugs, pharmacoepidemiologic data are necessary. However, acquiring such data can be difficult, as farmers are often illiterate (and therefore cannot participate in written surveys or keep treatment records), antibiotics can be obtained over-the-counter (in which case no prescriptions are generated) and monitoring and surveillance systems for drug use are often non-existent. The goal of this study was to compare two methods of acquiring pharmacoepidemiologic data pertaining to antibiotics that are well-adapted to farms in lower-middle income countries: self-report and the collection of discarded drug packaging. A convenience sample of 20 farmers in Cajamarca, Peru, participated in the study. Farmers placed discarded antibiotic packaging in bins for six months. At the end of the six-month period, farmers were interviewed and asked to recall the antibiotic usage that occurred on their farm over the past month and past six months; these self-reported data were quantitatively and qualitatively compared to the bin contents collected in the last month and previous six months. We found that the agreement between the bins and self-report was relatively poor for both the quantity and types of antibiotics used. The bins appeared to perform better than self-report when bottles and mLs of antibiotics were measured, while self-report appeared to perform better for intra-mammary infusions. The bins also appeared to perform better when data pertaining to an extended time period (six months) were collected. The results of this study will provide guidance to investigators seeking to collect pharmacoepidemiologic data in similar environments. PMID:24630404

  6. Antibiotic use, resistance development and environmental factors: a qualitative study among healthcare professionals in Orissa, India

    PubMed Central

    2010-01-01

    Background Antibiotic resistance is a major public health problem affecting both current and future generations. The influence of environmental factors on antibiotic use and resistance development in bacteria is largely unknown. This study explored the perceptions of healthcare providers on antibiotic use and resistance development in relation to environmental factors i.e. physical, natural, social and behavioural factors. Methods A qualitative interview study was conducted using face-to-face, semi-structured interviews among registered allopathic doctors, veterinarians and drug dispensers in Orissa, India. The interview transcripts were analyzed using latent content analysis. Results The main findings of this study relate to two themes: 'Interrelationship between antibiotic use, resistance development and environment' and 'Antibiotic management contributing to the development and spread of resistance'. The interviewees viewed the following as possible contributors to antibiotic use/misuse and resistance development: changes in the natural and physical environment i.e. climate variability, pollution, physiography and population growth; the socioeconomic environment affecting health-seeking behaviour and noncompliance with medication; a lack of healthcare facilities and poor professional attitudes; and ineffective law enforcement regarding medicine dispensing and disposal. Conclusions Generally, the interviewees perceived that although behavioural and social environmental factors are major contributors to resistance development, changes in the physical and natural environment also influence development of antibiotic resistance. The respondents also perceived that there is a lack of information about, and poor awareness of, what constitutes prudent use of antibiotics. They suggested a need for information, education, dissemination and proper implementation and enforcement of legislation at all levels of the drug delivery and disposal system in order to improve antibiotic use and prevent pharmaceutical contamination of the environment. PMID:20964815

  7. Comparison of two methods for collecting antibiotic use data on small dairy farms.

    PubMed

    Redding, L E; Cubas-Delgado, F; Sammel, M D; Smith, G; Galligan, D T; Levy, M Z; Hennessy, S

    2014-06-01

    Antibiotics are commonly used in animal agriculture; they can improve animal health and productivity, but their use may also represent a public health threat. Very little is known about antibiotic use on small farms in lower/middle income countries. To understand antibiotic use on these farms and promote the judicious use of these drugs, pharmacoepidemiologic data are necessary. However, acquiring such data can be difficult, as farmers are often illiterate (and therefore cannot participate in written surveys or keep treatment records), antibiotics can be obtained over-the-counter (in which case no prescriptions are generated) and monitoring and surveillance systems for drug use are often non-existent. The goal of this study was to compare two methods of acquiring pharmacoepidemiologic data pertaining to antibiotics that are well-adapted to farms in lower-middle income countries: self-report and the collection of discarded drug packaging. A convenience sample of 20 farmers in Cajamarca, Peru, participated in the study. Farmers placed discarded antibiotic packaging in bins for six months. At the end of the six-month period, farmers were interviewed and asked to recall the antibiotic usage that occurred on their farm over the past month and past six months; these self-reported data were quantitatively and qualitatively compared to the bin contents collected in the last month and previous six months. We found that the agreement between the bins and self-report was relatively poor for both the quantity and types of antibiotics used. The bins appeared to perform better than self-report when bottles and mLs of antibiotics were measured, while self-report appeared to perform better for intra-mammary infusions. The bins also appeared to perform better when data pertaining to an extended time period (six months) were collected. The results of this study will provide guidance to investigators seeking to collect pharmacoepidemiologic data in similar environments. PMID:24630404

  8. Challenges and future prospects of antibiotic therapy: from peptides to phages utilization

    PubMed Central

    Mandal, Santi M.; Roy, Anupam; Ghosh, Ananta K.; Hazra, Tapas K.; Basak, Amit; Franco, Octavio L.

    2014-01-01

    Bacterial infections are raising serious concern across the globe. The effectiveness of conventional antibiotics is decreasing due to global emergence of multi-drug-resistant (MDR) bacterial pathogens. This process seems to be primarily caused by an indiscriminate and inappropriate use of antibiotics in non-infected patients and in the food industry. New classes of antibiotics with different actions against MDR pathogens need to be developed urgently. In this context, this review focuses on several ways and future directions to search for the next generation of safe and effective antibiotics compounds including antimicrobial peptides, phage therapy, phytochemicals, metalloantibiotics, lipopolysaccharide, and efflux pump inhibitors to control the infections caused by MDR pathogens. PMID:24860506

  9. Evolution of resistance to a last-resort antibiotic in Staphyloccocus aureus via bacterial competition

    PubMed Central

    Koch, Gudrun; Yepes, Ana; Förstner, Konrad U.; Wermser, Charlotte; Stengel, Stephanie T.; Modamio, Jennifer; Ohlsen, Knut; Foster, Kevin R.; Lopez, Daniel

    2014-01-01

    Summary Antibiotic resistance is a key medical concern, with antibiotic use likely being an important cause. However, here we describe an alternative route to clinically-relevant antibiotic resistance that occurs solely due to competitive interactions between bacterial cells. We consistently observe that isolates of Methicillin-resistant Staphylococcus aureus diversify spontaneously into two distinct, sequentially arising strains. The first evolved strain outgrows the parent strain via secretion of surfactants and a toxic bacteriocin. The second is resistant to the bacteriocin. Importantly, this second strain is also resistant to intermediate levels of vancomycin. This so-called VISA (vancomycin-intermediate S. aureus) phenotype is seen in many hard-to-treat clinical isolates. This strain diversification also occurs during in vivo infection in a mouse model, consistent with the fact that both coevolved phenotypes resemble strains commonly found in clinic. Our study shows how competition between coevolving bacterial strains can generate antibiotic resistance and recapitulate key clinical phenotypes. PMID:25171407

  10. Misconceptions about Antibiotics: MedlinePlus Health News Video

    MedlinePLUS

    ... how concerned they were about the development of antibiotic resistance. Overall, parents did well identifying illnesses in which ... they were very concerned about the development of antibiotic resistance in their child. Fewer were concerned about antibiotic ...

  11. Antibiotics: When They Can and Can't Help

    MedlinePLUS

    ... and most coughs and sore throats. What is "antibiotic resistance?" “Antibiotic resistance” and “bacterial resistance” are two ways of describing the same thing. Usually, antibiotics kill bacteria or stop them from growing. However, ...

  12. Applying antibiotic selection markers for nematode genetics.

    PubMed

    Cornes, Eric; Quéré, Cécile A L; Giordano-Santini, Rosina; Dupuy, Denis

    2014-08-01

    Antibiotic selection markers have been recently developed in the multicellular model organism Caenorhabditis elegans and other related nematode species, opening great opportunities in the field of nematode transgenesis. Here we describe how these antibiotic selection systems can be easily combined with many well-established genetic approaches to study gene function, improving time- and cost-effectiveness of the nematode genetic toolbox. PMID:24821108

  13. POULTRY PRODUCTION WITHOUT THE USE OF ANTIBIOTICS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Regulatory pressures to limit antibiotic use in livestock and recent international marketing agreements that prohibit treating poultry with antibiotics have limited the disease-fighting tools available to poultry and livestock producers, particularly in Europe. There is a need to evaluate potential...

  14. Analysis of antibiotic consumption in burn patients

    PubMed Central

    Soleymanzadeh-Moghadam, Somayeh; Azimi, Leila; Amani, Laleh; Rastegar Lari, Aida; Alinejad, Faranak; Rastegar Lari, Abdolaziz

    2015-01-01

    Infection control is very important in burn care units, because burn wound infection is one of the main causes of morbidity and mortality among burn patients. Thus, the appropriate prescription of antibiotics can be helpful, but unreasonable prescription can have detrimental consequences, including greater expenses to patients and community alike. The aim of this study was to determine the effect of antibiotic therapy on the emergence of antibiotic-resistant bacteria. 525 strains of Pseudomonas aeruginosa, Acinetobacter baumannii and Staphylococcus aureus were isolated from 335 hospitalized burn patients. Antibiotic susceptibility tests were performed after identification the strains. The records of patients were audited to find the antibiotic used. The results indicated that P. aeruginosa is the most prevalent Gram-negative bacteria. Further, it showed a relation between abuse of antibiotics and emergence of antibiotic resistance. Control of resistance to antibiotics by appropriate prescription practices not only facilitates prevention of infection caused by multi-drug resistant (MDR) microorganisms, but it can also decrease the cost of treatment. PMID:26124986

  15. Antibiotic activity of pyrenomycetes under submerged conditions.

    PubMed

    Bandre, T R; Sasek, V

    1977-01-01

    Twenty-three pyrenomycete species were tested for antibiotic activity in submerged cultures. When they were screened against bacteria and fungi, 15 showed positive results. Among these, Eutypa acharii, Diaporthe pustulata, Melanconis flavovirens and Camarops microspora were quite promising against bacteria and/or fungi. An antibacterial antibiotic from Camarops microspora was partially purified and characterized. PMID:408247

  16. Can CAM Therapies Help Reduce Antibiotic Resistance?

    Microsoft Academic Search

    Douglas MacKay

    2003-01-01

    The Centers for Disease Control and Prevention (CDC) reported the consumption of 235 million doses of antibiotics in 2001. It is estimated that 20-50 percent of these were unnecessarily prescribed for viral infections. Bacteria that antibiotics have controlled in the past are increasingly developing resistance to these drugs. Today, virtually all important bacterial infections in the United States and throughout

  17. Transforming User Needs into Functional Requirements for an Antibiotic Clinical Decision Support System

    PubMed Central

    Bright, T.J.

    2013-01-01

    Summary Background Many informatics studies use content analysis to generate functional requirements for system development. Explication of this translational process from qualitative data to functional requirements can strengthen the understanding and scientific rigor when applying content analysis in informatics studies. Objective To describe a user-centered approach transforming emergent themes derived from focus group data into functional requirements for informatics solutions and to illustrate these methods to the development of an antibiotic clinical decision support system (CDS). Methods The approach consisted of five steps: 1) identify unmet therapeutic planning information needs via Focus Group Study-I, 2) develop a coding framework of therapeutic planning themes to refine the domain scope to antibiotic therapeutic planning, 3) identify functional requirements of an antibiotic CDS system via Focus Group Study-II, 4) discover informatics solutions and functional requirements from coded data, and 5) determine the types of information needed to support the antibiotic CDS system and link with the identified informatics solutions and functional requirements. Results The coding framework for Focus Group Study-I revealed unmet therapeutic planning needs. Twelve subthemes emerged and were clustered into four themes; analysis indicated a need for an antibiotic CDS intervention. Focus Group Study-II included five types of information needs. Comments from the Barrier/Challenge to information access and Function/Feature themes produced three informatics solutions and 13 functional requirements of an antibiotic CDS system. Comments from the Patient, Institution, and Domain themes generated required data elements for each informatics solution. Conclusion This study presents one example explicating content analysis of focus group data and the analysis process to functional requirements from narrative data. Illustration of this 5-step method was used to develop an antibiotic CDS system, resolving unmet antibiotic prescribing needs. As a reusable approach, these techniques can be refined and applied to resolve unmet information needs with informatics interventions in additional domains. PMID:24454586

  18. The N-terminal nucleophile serine of cephalosporin acylase executes the second autoproteolytic cleavage and acylpeptide hydrolysis.

    PubMed

    Yin, Jun; Deng, Zixin; Zhao, Guoping; Huang, Xi

    2011-07-01

    Cephalosporin acylase (CA) precursor is translated as a single polypeptide chain and folds into a self-activating pre-protein. Activation requires two peptide bond cleavages that excise an internal spacer to form the mature ?? heterodimer. Using Q-TOF LC-MS, we located the second cleavage site between Glu(159) and Gly(160), and detected the corresponding 10-aa spacer (160)GDPPDLADQG(169) of CA mutants. The site of the second cleavage depended on Glu(159): moving Glu into the spacer or removing 5-10 residues from the spacer sequence resulted in shorter spacers with the cleavage at the carboxylic side of Glu. The mutant E159D was cleaved more slowly than the wild-type, as were mutants G160A and G160L. This allowed kinetic measurements showing that the second cleavage reaction was a first-order, intra-molecular process. Glutaryl-7-aminocephalosporanic acid is the classic substrate of CA, in which the N-terminal Ser(170) of the ?-subunit, is the nucleophile. Glu and Asp resemble glutaryl, suggesting that CA might also remove N-terminal Glu or Asp from peptides. This was indeed the case, suggesting that the N-terminal nucleophile also performed the second proteolytic cleavage. We also found that CA is an acylpeptide hydrolase rather than a previously expected acylamino acid acylase. It only exhibited exopeptidase activity for the hydrolysis of an externally added peptide, supporting the intra-molecular interaction. We propose that the final CA activation is an intra-molecular process performed by an N-terminal nucleophile, during which large conformational changes in the ?-subunit C-terminal region are required to bridge the gap between Glu(159) and Ser(170). PMID:21576250

  19. Clonally Related Neisseria gonorrhoeae Isolates with Decreased Susceptibility to the Extended-Spectrum Cephalosporin Cefotaxime in Amsterdam, the Netherlands

    PubMed Central

    Heymans, Raymond; Bruisten, Sylvia M.; Golparian, Daniel; Unemo, Magnus; de Vries, Henry J. C.

    2012-01-01

    From 2006 to 2008, Neisseria gonorrhoeae isolates were identified with decreased susceptibility to the extended-spectrum cephalosporin (ESC) cefotaxime among visitors of the Amsterdam sexually transmitted infections (STI) clinic, the Netherlands. Spread, clonality, and characteristics of 202 isolates were examined using antibiograms, conventional penA mosaic gene PCR, and N. gonorrhoeae multiple-locus variable-number tandem repeat analysis (NG-MLVA). A strictly defined subset was further characterized by N. gonorrhoeae multiantigen sequence typing (NG-MAST) and sequencing of ESC resistance determinants (penA, mtrR, and porB1b). Seventy-four N. gonorrhoeae isolates with a cefotaxime MIC of >0.125 ?g/ml (group A), 54 with a cefotaxime MIC of 0.125 ?g/ml (group B), and a control group of 74 with a cefotaxime MIC of <0.125 ?g/ml (group C) were included. Fifty-three clonally related penA mosaic-positive isolates (penicillin-binding protein 2 type XXXIV) were identified in group A (n = 47 isolates; 64%) and B (n = 6 isolates; 11%). The 53 penA mosaic-positive isolates were predominantly NG-MAST ST1407 (87%) and contained an mtrR promoter A deletion (98%) and porB1b alterations G101K/A102N. All were assigned to the same NG-MLVA cluster that comprised in total 56 isolates. A correlation was found between decreased cefotaxime susceptibility and ST1407 that was highly prevalent among visitors of the Amsterdam STI clinic. The rapid spread of this strain, which also has been identified in many other countries, might be facilitated by high-risk sexual behavior and should be monitored closely to identify potential treatment failure. Quality-assured surveillance of ESC susceptibility on the national and international levels and exploration of new drugs and/or strategies for treatment of gonorrhea are crucial. PMID:22214779

  20. Clonally related Neisseria gonorrhoeae isolates with decreased susceptibility to the extended-spectrum cephalosporin cefotaxime in Amsterdam, the Netherlands.

    PubMed

    Heymans, Raymond; Bruisten, Sylvia M; Golparian, Daniel; Unemo, Magnus; de Vries, Henry J C; van Dam, Alje P

    2012-03-01

    From 2006 to 2008, Neisseria gonorrhoeae isolates were identified with decreased susceptibility to the extended-spectrum cephalosporin (ESC) cefotaxime among visitors of the Amsterdam sexually transmitted infections (STI) clinic, the Netherlands. Spread, clonality, and characteristics of 202 isolates were examined using antibiograms, conventional penA mosaic gene PCR, and N. gonorrhoeae multiple-locus variable-number tandem repeat analysis (NG-MLVA). A strictly defined subset was further characterized by N. gonorrhoeae multiantigen sequence typing (NG-MAST) and sequencing of ESC resistance determinants (penA, mtrR, and porB1b). Seventy-four N. gonorrhoeae isolates with a cefotaxime MIC of >0.125 ?g/ml (group A), 54 with a cefotaxime MIC of 0.125 ?g/ml (group B), and a control group of 74 with a cefotaxime MIC of <0.125 ?g/ml (group C) were included. Fifty-three clonally related penA mosaic-positive isolates (penicillin-binding protein 2 type XXXIV) were identified in group A (n = 47 isolates; 64%) and B (n = 6 isolates; 11%). The 53 penA mosaic-positive isolates were predominantly NG-MAST ST1407 (87%) and contained an mtrR promoter A deletion (98%) and porB1b alterations G101K/A102N. All were assigned to the same NG-MLVA cluster that comprised in total 56 isolates. A correlation was found between decreased cefotaxime susceptibility and ST1407 that was highly prevalent among visitors of the Amsterdam STI clinic. The rapid spread of this strain, which also has been identified in many other countries, might be facilitated by high-risk sexual behavior and should be monitored closely to identify potential treatment failure. Quality-assured surveillance of ESC susceptibility on the national and international levels and exploration of new drugs and/or strategies for treatment of gonorrhea are crucial. PMID:22214779

  1. In Vitro Activity of S-3578, a New Broad-Spectrum Cephalosporin Active against Methicillin-Resistant Staphylococci

    PubMed Central

    Fujimura, Takaji; Yamano, Yoshinori; Yoshida, Isamu; Shimada, Jingoro; Kuwahara, Shogo

    2003-01-01

    The in vitro antibacterial activity of S-3578, a new parenteral cephalosporin, against clinical isolates was evaluated. The MICs of the drug at which 90% of the isolates were inhibited were 4 ?g/ml for methicillin-resistant Staphylococcus aureus (MRSA) and 2 ?g/ml for methicillin-resistant Staphylococcus epidermidis, which were fourfold higher than and equal to those of vancomycin, respectively. The anti-MRSA activity of S-3578 was considered to be due to its high affinity for penicillin-binding protein 2a (50% inhibitory concentration, 4.5 ?g/ml). In time-kill studies with 10 strains each of MRSA and methicillin-susceptible S. aureus, S-3578 caused more than a 4-log10 decrease of viable cells on the average at twice the MIC after 24 h of exposure, indicating that it had potent bactericidal activity. Furthermore, in population analysis of MRSA strains with heterogeneous or homogeneous resistance to imipenem, no colonies emerged from about 109 cells on agar plates containing twice the MIC of S-3578, suggesting the low frequency of emergence of S-3578-resistant strains from MRSA. S-3578 was also highly active against penicillin-resistant Streptococcus pneumoniae (PRSP), with a MIC90 of 1 ?g/ml, which was comparable to that of ceftriaxone. S-3578 also had antibacterial activity against a variety of gram-negative bacteria including Pseudomonas aeruginosa, though its activity was not superior to that of cefepime. In conclusion, S-3578 exhibited a broad antibacterial spectrum and, particularly, had excellent activity against gram-positive bacteria including methicillin-resistant staphylococci and PRSP. Thus, S-3578 was considered to be worthy of further evaluation. PMID:12604523

  2. Linking microbial community structure and function to characterize antibiotic resistant bacteria and antibiotic resistant genes from cattle feces

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There is widespread interest in monitoring the development of antibiotic resistant bacteria and antibiotic resistance genes in agriculturally impacted environments, however little is known about the relationships between bacterial community structure, and antibiotic resistance gene profiles. Cattl...

  3. Antibiotics and antibiotic-resistant bacteria in waters associated with a hospital in Ujjain, India

    PubMed Central

    2010-01-01

    Background Concerns have been raised about the public health implications of the presence of antibiotic residues in the aquatic environment and their effect on the development of bacterial resistance. While there is information on antibiotic residue levels in hospital effluent from some other countries, information on antibiotic residue levels in effluent from Indian hospitals is not available. Also, concurrent studies on antibiotic prescription quantity in a hospital and antibiotic residue levels and resistant bacteria in the effluent of the same hospital are few. Therefore, we quantified antibiotic residues in waters associated with a hospital in India and assessed their association, if any, with quantities of antibiotic prescribed in the hospital and the susceptibility of Escherichia coli found in the hospital effluent. Methods This cross-sectional study was conducted in a teaching hospital outside the city of Ujjain in India. Seven antibiotics - amoxicillin, ceftriaxone, amikacin, ofloxacin, ciprofloxacin, norfloxacin and levofloxacin - were selected. Prescribed quantities were obtained from hospital records. The samples of the hospital associated water were analysed for the above mentioned antibiotics using well developed and validated liquid chromatography/tandem mass spectrometry technique after selectively isolating the analytes from the matrix using solid phase extraction. Escherichia coli isolates from these waters were tested for antibiotic susceptibility, by standard Kirby Bauer disc diffusion method using Clinical and Laboratory Standard Institute breakpoints. Results Ciprofloxacin was the highest prescribed antibiotic in the hospital and its residue levels in the hospital wastewater were also the highest. In samples of the municipal water supply and the groundwater, no antibiotics were detected. There was a positive correlation between the quantity of antibiotics prescribed in the hospital and antibiotic residue levels in the hospital wastewater. Wastewater samples collected in the afternoon contained both a higher number and higher levels of antibiotics compared to samples collected in the morning hours. No amikacin was found in the wastewater, but E.coli isolates from all wastewater samples were resistant to amikacin. Although ciprofloxacin was the most prevalent antibiotic detected in the wastewater, E.coli was not resistant to it. Conclusions Antibiotics are entering the aquatic environment of countries like India through hospital effluent. In-depth studies are needed to establish the correlation, if any, between the quantities of antibiotics prescribed in hospitals and the levels of antibiotic residues found in hospital effluent. Further, the effect of this on the development of bacterial resistance in the environment and its subsequent public health impact need thorough assessment. PMID:20626873

  4. Tackling antibiotic resistance in India.

    PubMed

    Wattal, Chand; Goel, Neeraj

    2014-12-01

    Infectious diseases are major causes of mortality in India. This is aggravated by the increasing prevalence of antimicrobial resistance (AMR) both in the community and in hospitals. Due to the emergence of resistance to all effective antibiotics in nosocomial pathogens, the situation calls for emergency measures to tackle AMR in India. India has huge challenges in tackling AMR, ranging from lack of surveillance mechanisms for monitoring AMR and use; effective hospital control policies; sanitation and non-human use of antimicrobial. The Ministry of Health and Family Welfare of Govt. of India has taken initiatives to tackle AMR. Extensive guidelines have been drafted and a model worksheet has been developed as a roadmap to tackle AMR. PMID:25353717

  5. Development of a Humanized Disulfide-stabilized Anti-pl85HER2 Fv-ß-Lactamase Fusion Protein for Activation of a Cephalosporin Doxorubicin Prodrug

    Microsoft Academic Search

    Maria L. Rodrigues; Leonard G. Presta; Claire E. Kotts; Cindy Wirth; Joyce Mordenti; Gary Osaka; Wai Lee; T. Wong; Andrew Nuijens; Brent Blackburn; Paul Carter

    The humanized anti-pl85HER2 antibody, humAb4D5-8, has completed Phase II clinical trials for pl85HER2-overexpressing breast cancer. Here, this antibody is used as a building block to engineer a disulfide-linked Fv (dsFv) ß-lactamase fusion protein for use in antibody-dependent enzyme- mediated prodrug therapy using cephalosporin-based prodrugs. Three Fv variants were designed with an interchain disulfide bond buried at the VL\\/VH interface and

  6. The antibiotic effects of vitamin D.

    PubMed

    Guo, Chunxiao; Gombart, Adrian F

    2014-01-01

    The recent discovery that vitamin D regulates expression of the cathelicidin antimicrobial peptide gene has generated renewed interest in using vitamin D to fight infectious diseases. This review describes the historical use of vitamin D or its sources to treat infections, the mechanism of action through which vitamin D mediates its "antibiotic" effects, findings from epidemiological studies associating vitamin D deficiency with increased susceptibility to infection and clinical trials with vitamin D supplementation to treat or prevent infections. Further studies examining an association between vitamin D levels and cathelicidin expression are discussed. The role of cathelcidin throughout the course of infection from the initial encounter of the pathogen to the resolution of tissue damage and inflammation indicates that individuals need to maintain adequate levels of vitamin D for an optimal immune response. In addition, for treating infections, carefully designed randomized, clinical trials that are appropriately powered to detect modest effects, target populations that are severely deficient in vitamin D,and optimized dose, dosing frequency and safety are needed. PMID:25008764

  7. Identification of patients at high risk for Clostridium difficile infection: development and validation of a risk prediction model in hospitalized patients treated with antibiotics.

    PubMed

    van Werkhoven, C H; van der Tempel, J; Jajou, R; Thijsen, S F T; Diepersloot, R J A; Bonten, M J M; Postma, D F; Oosterheert, J J

    2015-08-01

    To develop and validate a prediction model for Clostridium difficile infection (CDI) in hospitalized patients treated with systemic antibiotics, we performed a case-cohort study in a tertiary (derivation) and secondary care hospital (validation). Cases had a positive Clostridium test and were treated with systemic antibiotics before suspicion of CDI. Controls were randomly selected from hospitalized patients treated with systemic antibiotics. Potential predictors were selected from the literature. Logistic regression was used to derive the model. Discrimination and calibration of the model were tested in internal and external validation. A total of 180 cases and 330 controls were included for derivation. Age >65 years, recent hospitalization, CDI history, malignancy, chronic renal failure, use of immunosuppressants, receipt of antibiotics before admission, nonsurgical admission, admission to the intensive care unit, gastric tube feeding, treatment with cephalosporins and presence of an underlying infection were independent predictors of CDI. The area under the receiver operating characteristic curve of the model in the derivation cohort was 0.84 (95% confidence interval 0.80-0.87), and was reduced to 0.81 after internal validation. In external validation, consisting of 97 cases and 417 controls, the model area under the curve was 0.81 (95% confidence interval 0.77-0.85) and model calibration was adequate (Brier score 0.004). A simplified risk score was derived. Using a cutoff of 7 points, the positive predictive value, sensitivity and specificity were 1.0%, 72% and 73%, respectively. In conclusion, a risk prediction model was developed and validated, with good discrimination and calibration, that can be used to target preventive interventions in patients with increased risk of CDI. PMID:25889357

  8. Development of a direct ELISA based on carboxy-terminal of penicillin-binding protein BlaR for the detection of ?-lactam antibiotics in foods.

    PubMed

    Peng, Juan; Cheng, Guyue; Huang, Lingli; Wang, Yulian; Hao, Haihong; Peng, Dapeng; Liu, Zhenli; Yuan, Zonghui

    2013-11-01

    ?-Lactam antibiotics, including penicillins and cephalosporins, are commonly used in veterinary medicine. Illegal use and abuse of ?-lactams could cause allergy and selected bacterial resistance. BlaR-CTD, the carboxy-terminal of penicillin-recognizing protein BlaR from Bacillus licheniformis ATCC 14580, was utilized in this study to develop a receptor-based ELISA for detection and determination of ?-lactam antibiotics in milk, beef, and chicken. This assay was based on directly competitive inhibition of binding of horseradish peroxidase-labeled ampicillin to the immobilized BlaR-CTD by ?-lactams. The assay was developed as screening test with the option as semiquantitative assay, when the identity of a single type of residual ?-lactam was known. The IC50 values of 15 ?-lactam antibiotics, including benzylpenicillin, ampicillin, amoxicillin, dicloxacillin, oxacillin, nafcillin, cefapirin, cefoperazone, cefalotin, cefazolin, cefquinome, ceftriaxone, cefotaxime, cefalexin, ceftiofur and its metabolite desfuroylceftiofur were evaluated and ranged from 0.18 to 170.81 ?g L(-1). Simple sample extraction method was carried out with only phosphate-buffered saline, and the recoveries of selected ?-lactam antibiotics in milk, beef, and chicken were in the range of 53.27 to 128.29 %, most ranging from 60 to 120 %. The inter-assay variability was below 30 %. Limits of detection in milk, beef, and chicken muscles with cefquinome matrix calibration were 2.10, 30.68, and 31.13 ?g kg(-1), respectively. This study firstly established a rapid, simple, and accurate method for simultaneous detection of 15 ?-lactams in edible tissues, among which 11 ?-lactams controlled by European Union could be detected below maximum residue limits. PMID:24013636

  9. Antibiotic resistance in ocular bacterial pathogens.

    PubMed

    Sharma, S

    2011-01-01

    Bacterial infections of the eye are common and ophthalmologists are spoilt for choice with a variety of antibiotics available in the market. Antibiotics can be administered in the eye by a number of routes; topical, subconjunctival, subtenon and intraocular. Apart from a gamut of eye drops available, ophthalmologists also have the option of preparing fortified eye drops from parenteral formulations, thereby, achieving high concentrations; often much above the minimum inhibitory concentration (MIC), of antibiotics in ocular tissues during therapy. Antibiotic resistance among ocular pathogens is increasing in parallel with the increase seen over the years in bacteria associated with systemic infections. Although it is believed that the rise in resistant ocular bacterial isolates is linked to the rise in resistant systemic pathogens, recent evidence has correlated the emergence of resistant bacteria in the eye to prior topical antibiotic therapy. One would like to believe that either of these contributes to the emergence of resistance to antibiotics among ocular pathogens. Until recently, ocular pathogens resistant to fluoroquinolones have been minimal but the pattern is currently alarming. The new 8-fluoroquinolone on the scene-besifloxacin, is developed exclusively for ophthalmic use and it is hoped that it will escape the selective pressure for resistance because of lack of systemic use. In addition to development of new antibacterial agents, the strategies to halt or control further development of resistant ocular pathogens should always include judicious use of antibiotics in the treatment of human, animal or plant diseases. PMID:21860100

  10. Antibiotic activity of iron-sequestering polymers.

    PubMed

    El-Gendy, Nashwa; Qian, Jian; Eshelman, Kate; Rivera, Mario; Berkland, Cory

    2015-05-11

    Increasing antibiotic resistance has compelled the development of novel antibiotics and adjuvant therapies that enhance the efficacy of existing antibiotics. Iron plays a critical role in bacterial infections, yet the use of iron chelators as adjuvant therapy with antibiotics has yielded highly variable outcomes. Multivalent polymeric materials offer an alternative approach to bind and sequester iron via high avidity interactions. Here, a biomimetic iron-sequestering polymer (PAI-DHBA) was synthesized by modifying side chains of cross-linked polyallylamine (cPAI) with 2,3-dihydroxybenzoic acid (DHBA). PAI-DHBA polymer gels with various DHBA contents showed high iron affinity indices and high selectivity for iron. The polymers showed mild antibiotic properties when used to treat established bacterial cultures. Pretreating culture media with PAI-DHBA polymer, however, removed all detectable iron from media and effectively inhibited the growth of Pseudomonas aeruginosa. In addition, bacterial growth was more susceptible to antibiotics combined with PAI-DHBA. Multivalent polymers that bind and sequester iron, such as PAI-DHBA, offer a promising early intervention or adjuvant to antibiotics. PMID:25872681

  11. Mechanisms of antibiotic resistance in Staphylococcus aureus.

    PubMed

    Pantosti, Annalisa; Sanchini, Andrea; Monaco, Monica

    2007-06-01

    Staphylococcus aureus can exemplify better than any other human pathogen the adaptive evolution of bacteria in the antibiotic era, as it has demonstrated a unique ability to quickly respond to each new antibiotic with the development of a resistance mechanism, starting with penicillin and methicillin, until the most recent, linezolid and daptomycin. Resistance mechanisms include enzymatic inactivation of the antibiotic (penicillinase and aminoglycoside-modification enzymes), alteration of the target with decreased affinity for the antibiotic (notable examples being penicillin-binding protein 2a of methicillin-resistant S. aureus and D-Ala-D-Lac of peptidoglycan precursors of vancomycin-resistant strains), trapping of the antibiotic (for vancomycin and possibly daptomycin) and efflux pumps (fluoroquinolones and tetracycline). Complex genetic arrays (staphylococcal chromosomal cassette mec elements or the vanA operon) have been acquired by S. aureus through horizontal gene transfer, while resistance to other antibiotics, including some of the most recent ones (e.g., fluoroquinolones, linezolid and daptomycin) have developed through spontaneous mutations and positive selection. Detection of the resistance mechanisms and their genetic basis is an important support to antibiotic susceptibility surveillance in S. aureus. PMID:17661706

  12. Molecular Regulation of Antibiotic Biosynthesis in Streptomyces

    PubMed Central

    Liu, Gang; Chandra, Govind; Niu, Guoqing

    2013-01-01

    SUMMARY Streptomycetes are the most abundant source of antibiotics. Typically, each species produces several antibiotics, with the profile being species specific. Streptomyces coelicolor, the model species, produces at least five different antibiotics. We review the regulation of antibiotic biosynthesis in S. coelicolor and other, nonmodel streptomycetes in the light of recent studies. The biosynthesis of each antibiotic is specified by a large gene cluster, usually including regulatory genes (cluster-situated regulators [CSRs]). These are the main point of connection with a plethora of generally conserved regulatory systems that monitor the organism's physiology, developmental state, population density, and environment to determine the onset and level of production of each antibiotic. Some CSRs may also be sensitive to the levels of different kinds of ligands, including products of the pathway itself, products of other antibiotic pathways in the same organism, and specialized regulatory small molecules such as gamma-butyrolactones. These interactions can result in self-reinforcing feed-forward circuitry and complex cross talk between pathways. The physiological signals and regulatory mechanisms may be of practical importance for the activation of the many cryptic secondary metabolic gene cluster pathways revealed by recent sequencing of numerous Streptomyces genomes. PMID:23471619

  13. Increased Antibiotic Release from a Bone Cement Containing Bacterial Cellulose

    PubMed Central

    Nakai, Takahisa; Enomoto, Koichi; Uchio, Yuji; Yoshino, Katsumi

    2010-01-01

    Background Major disadvantages of antibiotic bone cements include limited drug release and reduced strength resulting from the addition of high doses of antibiotics. Bacterial cellulose, a three-dimensional hydrophilic mesh, may retain antibiotics and release them gradually. We hypothesized that the addition of cellulose to antibiotic bone cement would improve mechanical strength and antibiotic release. Questions/purposes We therefore examined the mechanical strength and antibiotic release of cellulose antibiotic cement. Methods A high dose of antibiotics (5 g per 40 g cement powder) was incorporated into bacterial cellulose and then mixed with bone cement. We compared the compression strength, fracture toughness, fatigue life, and elution kinetics of this formulation with those of plain cement and a traditional antibiotic cement. Results The average values for compression strength, fracture toughness, and fatigue life of the cellulose antibiotic cement were 97%, 97%, and 78% of the values obtained for plain cement, respectively. The corresponding values for the traditional antibiotic cement were 79%, 82%, and 17%, respectively. The cumulative elution over 35 days was 129% greater from the cellulose antibiotic cement than from the traditional antibiotic cement. Conclusions With a high dose of antibiotics, incorporating cellulose into the bone cement prevented compression and fracture fragility, improved fatigue life, and increased antibiotic elution. Clinical Relevance Antibiotic cements containing cellulose may have applications in clinical situations that require high levels of antibiotic release and preservation of the mechanical properties of the cement. PMID:20945120

  14. Antibiotic treatment of bacterial infections of the respiratory tract

    Microsoft Academic Search

    Roger Small

    2008-01-01

    Treatment of bacterial infections of the respiratory tract should allow for factors such as the patient’s history, the treatment situation and the result of any bacteriological diagnosis. Haemophilus influenzae epiglottitis is treated with cefotaxime (a cephalosporin inhibitor of cell wall synthesis) or with chloramphenicol (an inhibitor of bacterial protein synthesis). Exacerbations of chronic bronchitis are treated with broad-spectrum penicillins (inhibitors

  15. Facilitation of horizontal transfer of antimicrobial resistance by transformation of antibiotic-induced cell-wall-deficient bacteria.

    PubMed

    Woo, P C Y; To, A P C; Lau, S K P; Yuen, K Y

    2003-10-01

    It is universally accepted that the use of antibiotics will lead to antimicrobial resistance. Traditionally, the explanation to this phenomenon was random mutation and horizontal gene transfer and amplification by selective pressure. Subsequently, a second mechanism of antibiotic-induced antimicrobial resistance acquisition was proposed, when Davies et al. discovered that genes encoding antimicrobial resistance are present in bacteria that produce antibiotics, and during the process of antibiotic purification from these antibiotic-producing organisms, remnants of the organisms' DNA that contain antibiotic resistance genes are also co-extracted, and can be recovered in antibiotic preparations. In addition to selective pressure and antimicrobial resistance genes in antibiotic preparations, we hypothesize the third mechanism by which administration of antibiotics leads to antimicrobial resistance. beta-Lactams and glycopeptides damage bacteria by inhibiting cell wall murein synthesis. During the process, cell-wall-deficient forms are generated before the bacteria die. These cell-wall-deficient forms have an increased ability to uptake DNA by transformation. It has been demonstrated that plasmids encoding antimicrobial resistance of Staphylococcus aureus can be transformed to Bacillus subtilis after the B. subtilis was treated with penicillin or lysostaphin, a chemical that damage the cell walls of some Gram-positive bacteria; and that short treatment of Escherichia coli with antibiotics disturbing bacterial cell wall synthesis rendered the cells capable of absorbing foreign DNA. Since bacteria occupying the same ecological niche, such as the lower gastrointestinal tract, is common, bacteria are often incubated with foreign DNA encoding resistance coming from the administration of antibiotics or other bacteria that undergone lysis unrelated to antibiotic-induced killing. As few as a single antibiotic resistant gene is taken up by the cell-wall-deficient form, it will develop into a resistant clone, despite most of the other bacteria are killed by the antibiotic. If the hypothesis is correct, one should reduce the use of antibiotics that perturb bacterial cell wall synthesis, such as beta-lactams, which is the largest group being manufactured, in both humans and animals, in order to reduce the acquisition of antibiotic resistance through this mechanism. In contrast to the old theory that antibiotics only provide selective pressures for the development of antimicrobial resistance, antibiotics by themselves are able to generate the whole chain of events towards the development of antimicrobial resistance. Antibiotics provide a source of antimicrobial resistance genes, facilitate the horizontal transfer of antimicrobial resistance genes through facilitating transformation, and provide selective pressures for amplification of the antimicrobial resistance genes. That is perhaps an important reason why antimicrobial resistance is so difficult to control. Further experiments should be performed to delineate which particular type of beta-lactam antibiotics are associated with increase in transformation efficiencies more than the others, so that we can select those less resistance generating beta-lactam for routine usage. PMID:13679020

  16. Something old, something new: revisiting natural products in antibiotic drug discovery.

    PubMed

    Wright, Gerard D

    2014-03-01

    Antibiotic discovery is in crisis. Despite a growing need for new drugs resulting from the increasing number of multi-antibiotic-resistant pathogens, there have been only a handful of new antibiotics approved for clinical use in the past 2 decades. Faced with scientific, economic, and regulatory challenges, the pharmaceutical sector seems unable to respond to what has been called an "apocalyptic" threat. Natural products produced by bacteria and fungi are genetically encoded products of natural selection that have been the mainstay sources of the antibiotics in current clinical use. The pharmaceutical industry has largely abandoned these compounds in favor of large libraries of synthetic molecules because of difficulties in identifying new natural product antibiotics scaffolds. Advances in next-generation genome sequencing, bioinformatics, and analytical chemistry are combining to overcome barriers to natural products. Coupled with new strategies in antibiotic discovery, including inhibition of resistance, novel drug combinations, and new targets, natural products are poised for a renaissance to address what is a pressing health care crisis. PMID:24588388

  17. Antibiotics for the treatment of rheumatoid arthritis

    PubMed Central

    Ogrendik, Mesut

    2014-01-01

    Antibiotic treatment for rheumatoid arthritis (RA) commenced in the 1930s with the use of sulfasalazine. Later, tetracyclines were successfully used for the treatment of RA. In double-blind and randomized studies, levofloxacin and macrolide antibiotics (including clarithromycin and roxithromycin) were also shown to be effective in the treatment of RA. There have been several reports in the literature indicating that periodontal pathogens are a possible cause of RA. Oral bacteria are one possible cause of RA. In this review, we aimed to investigate the effects of different antibiotics in RA treatment. PMID:24403843

  18. [Use of antibiotics in food animals].

    PubMed

    Gharbi, M; Messadi, L; Benzarti, M; Bouzghaia, H

    1999-01-01

    The authors present in this paper a review on a major problem which is less evoked in Tunisia and concerns the use of antibiotics in Veterinary Medicine for reared animals for human consumption. Antibiotics are often mis used; this is true for the practitioner as well as for the breeder. The rules of antibiotic associations and their related problems are also discussed. Specific recommendations to Tunisian users are suggested; the pharmaceutical industry, the veterinarian and the breeder. Each from its side must contribute to the preservation of this valuable therapeutic tool. PMID:14666750

  19. Chronological change of antibiotic use and antibiotic resistance in Escherichia coli causing urinary tract infections

    Microsoft Academic Search

    Katsumi Shigemura; Kazushi Tanaka; Masayo Adachi; Masuo Yamashita; Soichi Arakawa; Masato Fujisawa

    Overuse of antibiotics can cause the emergence of resistant bacterial strains. This study retrospectively investigated recent\\u000a trends in Escherichia coli causing urinary tract infections (UTIs), focusing on antibiotic use and antibiotic susceptibilities. Patients diagnosed with\\u000a UTIs caused by E. coli in Akashi Municipal Hospital between April 2004 and March 2010 were enrolled in the study. A total of 858 UTI

  20. Multiple strategies to activate gold nanoparticles as antibiotics

    NASA Astrophysics Data System (ADS)

    Zhao, Yuyun; Jiang, Xingyu

    2013-08-01

    Widespread antibiotic resistance calls for new strategies. Nanotechnology provides a chance to overcome antibiotic resistance by multiple antibiotic mechanisms. This paper reviews the progress in activating gold nanoparticles with nonantibiotic or antibiotic molecules to combat bacterial resistance, analyzes the gap between experimental achievements and real clinical application, and suggests some potential directions in developing antibacterial nanodrugs.

  1. Regulatory RNAs Involved in Bacterial Antibiotic David Lalaouna1.

    E-print Network

    Boyer, Edmond

    Pearls Regulatory RNAs Involved in Bacterial Antibiotic Resistance David Lalaouna1. , Alex Eyraud2 in antibiotic resistance. In this report, we provide evidence that illustrates the growing number of s of antibiotics raise the important question whether sRNAs play a role in antibiotic resistance. How Can s

  2. Novel approaches to developing new antibiotics for bacterial infections

    Microsoft Academic Search

    A R M Coates; Y Hu

    2007-01-01

    Antibiotics are an essential part of modern medicine. The emergence of antibiotic-resistant mutants among bacteria is seemingly inevitable, and results, within a few decades, in decreased efficacy and withdrawal of the antibiotic from widespread usage. The traditional answer to this problem has been to introduce new antibiotics that kill the resistant mutants. Unfortunately, after more than 50 years of success,

  3. Mechanisms of antibiotic resistance in enterococci

    PubMed Central

    Miller, William R; Munita, Jose M; Arias, Cesar A

    2015-01-01

    Multidrug-resistant (MDR) enterococci are important nosocomial pathogens and a growing clinical challenge. These organisms have developed resistance to virtually all antimicrobials currently used in clinical practice using a diverse number of genetic strategies. Due to this ability to recruit antibiotic resistance determinants, MDR enterococci display a wide repertoire of antibiotic resistance mechanisms including modification of drug targets, inactivation of therapeutic agents, overexpression of efflux pumps and a sophisticated cell envelope adaptive response that promotes survival in the human host and the nosocomial environment. MDR enterococci are well adapted to survive in the gastrointestinal tract and can become the dominant flora under antibiotic pressure, predisposing the severely ill and immunocompromised patient to invasive infections. A thorough understanding of the mechanisms underlying antibiotic resistance in enterococci is the first step for devising strategies to control the spread of these organisms and potentially establish novel therapeutic approaches. PMID:25199988

  4. Improper Antibiotic Use Often Due to Misdiagnosis

    MedlinePLUS

    ... The study was published online May 18 in Infection Control & Hospital Epidemiology , the journal of the Society for Healthcare ... and potentially harmful antibiotic use" Filice said. SOURCE: Infection Control & Hospital Epidemiology , news release, May 18, 2015 HealthDay Copyright ( ...

  5. A Strategy for Fighting Antibiotic Resistance

    NSDL National Science Digital Library

    Drlica, Karl.

    The American Society for Microbiology posted this recent paper online, addressing the critical issue of how to fight antibiotic resistance. Several strategies to slow the development of resistance are presented.

  6. Metagenomic exploration of antibiotic resistance in soil.

    PubMed

    Monier, Jean-Michel; Demanèche, Sandrine; Delmont, Tom O; Mathieu, Alban; Vogel, Timothy M; Simonet, Pascal

    2011-06-01

    The ongoing development of metagenomic approaches is providing the means to explore antibiotic resistance in nature and address questions that could not be answered previously with conventional culture-based strategies. The number of available environmental metagenomic sequence datasets is rapidly expanding and henceforth offer the ability to gain a more comprehensive understanding of antibiotic resistance at the global scale. Although there is now evidence that the environment constitutes a vast reservoir of antibiotic resistance gene determinants (ARGDs) and that the majority of ARGDs acquired by human pathogens may have an environmental origin, a better understanding of their diversity, prevalence and ecological significance may help predict the emergence and spreading of newly acquired resistances. Recent applications of metagenomic approaches to the study of ARGDs in natural environments such as soil should help overcome challenges concerning expanding antibiotic resistances. PMID:21601510

  7. Antibiotics Myths Still Common Among Parents

    MedlinePLUS

    ... City; Steven Wexberg, M.D., pediatrician, Cleveland Clinic Children's; August 2015, Pediatrics HealthDay Copyright (c) 2015 HealthDay . All rights reserved. More Health News on: Antibiotics Health Literacy Parenting Recent Health News

  8. Antibiotic stewardship in the intensive care unit.

    PubMed

    Luyt, Charles-Edouard; Bréchot, Nicolas; Trouillet, Jean-Louis; Chastre, Jean

    2014-01-01

    The rapid emergence and dissemination of antimicrobial-resistant microorganisms in ICUs worldwide constitute a problem of crisis dimensions. The root causes of this problem are multifactorial, but the core issues are clear. The emergence of antibiotic resistance is highly correlated with selective pressure resulting from inappropriate use of these drugs. Appropriate antibiotic stewardship in ICUs includes not only rapid identification and optimal treatment of bacterial infections in these critically ill patients, based on pharmacokinetic-pharmacodynamic characteristics, but also improving our ability to avoid administering unnecessary broad-spectrum antibiotics, shortening the duration of their administration, and reducing the numbers of patients receiving undue antibiotic therapy. Either we will be able to implement such a policy or we and our patients will face an uncontrollable surge of very difficult-to-treat pathogens. PMID:25405992

  9. Selective decontamination and antibiotic resistance in ICUs.

    PubMed

    Plantinga, Nienke L; Bonten, Marc Jm

    2015-01-01

    Selective digestive decontamination (SDD) and selective oropharyngeal decontamination (SOD) have been associated with reduced mortality and lower ICU-acquired bacteremia and ventilator-associated pneumonia rates in areas with low levels of antibiotic resistance. However, the effect of selective decontamination (SDD/SOD) in areas where multidrug-resistant Gram-negative bacteria are endemic is less clear. It will be important to determine whether SDD/SOD improves patient outcome in such settings and how these measures affect the epidemiology of multidrug-resistant Gram-negative bacteria. Here we review the current evidence on the effects of SDD/SOD on antibiotic resistance development in individual ICU patients as well as the effect on ICU ecology, the latter including both ICU-level antibiotic resistance and antibiotic resistance development during long-term use of SDD/SOD. PMID:26104045

  10. Metabolic engineering, new antibiotics and biofilm viscoelasticity

    PubMed Central

    Daniels, Craig; Espinosa?Urgel, Manuel; Niqui?Arroyo, José?Luis; Michán, Carmen; Ramos, Juan L.

    2010-01-01

    In the following highlight we refer to a number of new advances in the field of Biotechnology that address issues relating to the synthesis of new antibiotics, new biocatalysts and matrices in biofilms. PMID:21255301

  11. Metabolic engineering, new antibiotics and biofilm viscoelasticity.

    PubMed

    Daniels, Craig; Espinosa-Urgel, Manuel; Niqui-Arroyo, José-Luis; Michán, Carmen; Ramos, Juan L

    2010-01-01

    In the following highlight we refer to a number of new advances in the field of Biotechnology that address issues relating to the synthesis of new antibiotics, new biocatalysts and matrices in biofilms. PMID:21255301

  12. Therapeutic strategies to combat antibiotic resistance.

    PubMed

    Brooks, Benjamin D; Brooks, Amanda E

    2014-11-30

    With multidrug resistant bacteria on the rise, new antibiotic approaches are required. Although a number of new small molecule antibiotics are currently in the development pipeline with many more in preclinical development, the clinical options and practices for infection control must be expanded. Biologics and non-antibiotic adjuvants offer this opportunity for expansion. Nevertheless, to avoid known mechanisms of resistance, intelligent combination approaches for multiple simultaneous and complimentary therapies must be designed. Combination approaches should extend beyond biologically active molecules to include smart controlled delivery strategies. Infection control must integrate antimicrobial stewardship, new antibiotic molecules, biologics, and delivery strategies into effective combination therapies designed to 1) fight the infection, 2) avoid resistance, and 3) protect the natural microbiome. This review explores these developing strategies in the context of circumventing current mechanisms of resistance. PMID:25450262

  13. Plasmid encoded antibiotic resistance: acquisition and transfer of antibiotic resistance genes in bacteria

    PubMed Central

    Bennett, P M

    2008-01-01

    Bacteria have existed on Earth for three billion years or so and have become adept at protecting themselves against toxic chemicals. Antibiotics have been in clinical use for a little more than 6 decades. That antibiotic resistance is now a major clinical problem all over the world attests to the success and speed of bacterial adaptation. Mechanisms of antibiotic resistance in bacteria are varied and include target protection, target substitution, antibiotic detoxification and block of intracellular antibiotic accumulation. Acquisition of genes needed to elaborate the various mechanisms is greatly aided by a variety of promiscuous gene transfer systems, such as bacterial conjugative plasmids, transposable elements and integron systems, that move genes from one DNA system to another and from one bacterial cell to another, not necessarily one related to the gene donor. Bacterial plasmids serve as the scaffold on which are assembled arrays of antibiotic resistance genes, by transposition (transposable elements and ISCR mediated transposition) and site-specific recombination mechanisms (integron gene cassettes). The evidence suggests that antibiotic resistance genes in human bacterial pathogens originate from a multitude of bacterial sources, indicating that the genomes of all bacteria can be considered as a single global gene pool into which most, if not all, bacteria can dip for genes necessary for survival. In terms of antibiotic resistance, plasmids serve a central role, as the vehicles for resistance gene capture and their subsequent dissemination. These various aspects of bacterial resistance to antibiotics will be explored in this presentation. PMID:18193080

  14. Antibiotic use in US hospitals: quantification, quality measures and stewardship.

    PubMed

    Reddy, Sujan C; Jacob, Jesse T; Varkey, Jay B; Gaynes, Robert P

    2015-07-01

    A majority of patients hospitalized in the US hospitals receive an antibiotic during their hospitalization. Furthermore, up to half of antibiotics prescribed in hospitals are inappropriate. In the setting of continued emergence of antibiotic-resistant pathogens and a limited pipeline of new antimicrobials, attention to optimizing antibiotic use in healthcare settings is essential. We review the measures of antibiotic consumption in the USA, the evolving metrics for comparing antibiotic use (known as benchmarking), trends in antibiotic use, the structure and outcome measures of Antimicrobial Stewardship Programs and interventions to optimize antimicrobial use. PMID:25925531

  15. Emergence and dissemination of antibiotic resistance: a global problem.

    PubMed

    Choudhury, R; Panda, S; Singh, D V

    2012-01-01

    Antibiotic resistance is a major problem in clinical health settings. Interestingly the origin of many of antibiotic resistance mechanisms can be traced back to non-pathogenic environmental organisms. Important factors leading to the emergence and spread of antibiotic resistance include absence of regulation in the use of antibiotics, improper waste disposal and associated transmission of antibiotic resistance genes in the community through commensals. In this review, we discussed the impact of globalisation on the transmission of antibiotic resistance genes in bacteria through immigration and export/import of foodstuff. The significance of surveillance to define appropriate use of antibiotics in the clinic has been included as an important preventive measure. PMID:23183460

  16. A model assessment of the importance of direct photolysis in the photo-fate of cephalosporins in surface waters: Possible formation of toxic intermediates.

    PubMed

    Fabbri, Debora; Minella, Marco; Maurino, Valter; Minero, Claudio; Vione, Davide

    2015-09-01

    The direct and indirect photodegradation of six cephalosporins was predicted using a photochemical model, on the basis of literature values of photochemical reactivity. Environmental photodegradation would be important in surface water bodies with depth ?2-3m, and/or in deeper waters with low values of the dissolved organic carbon (DOC?1mgCL(-1)). The half-life times would range from a few days to a couple of weeks in summertime. In deeper and higher-DOC waters and/or in different seasons, hydrolysis could prevail over photodegradation. The direct photolysis of cephalosporins is environmentally concerning because it is known to produce toxic intermediates. It would be a major pathway for cefazolin, an important one for amoxicillin and cefotaxime and, at pH<6.5, for cefapirin as well. In contrast, direct photolysis would be negligible for cefradine and cefalexin. The DOC values would influence the fraction of photodegradation accounted for by direct photolysis in shallow water, to a different extent depending on the role of sensitisation by the triplet states of chromophoric dissolved organic matter. PMID:26001938

  17. Development and validation of an ultra high performance liquid chromatography tandem mass spectrometry method for determination of 10 cephalosporins and desacetylcefapirin in milk.

    PubMed

    Hou, Xiao-Lin; Wu, Yin-Liang; Lv, Yan; Xu, Xiu-Qin; Zhao, Jian; Yang, Ting

    2013-07-15

    A simple, sensitive and reliable analytical method was developed for the simultaneous determination of 10 cephalosporins and desacetylcefapirin in bovine milk by ultra high performance liquid chromatography-positive electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS). Samples were directly purified through HLB cartridge after dilution with 50mM phosphate buffer solution (pH 8.5). Then the eluate was dried under nitrogen and the residue was redissolved in mobile phase. Samples were analyzed by LC-MS/MS on an Acquity UPLC BEH Shield RP18 column with gradient elution. The samples were quantified using ceftiofur-D3 as internal standard. The proposed method was validated according to the European Commission Decision 2002/657/EC. The CC? values were 111, 0.04, 140, 55, 55, 67, 23, 23, 68, 0.10 and 113?g/kg for cefalexin, cefradine, cefacetrile, cefazolin, cefoperazone, cefapirin, cefalonium, cefquinome, desacetylcefapirin, cefotaxime and ceftiofur, respectively. The mean recoveries, repeatability (expressed as coefficient of variation, CVr), and reproducibility (CVR) varied from 94.6% to 117.1%, from 5.6% to 13.6% (CVr), and from 5.9% to 27.9% (CVR), respectively. The method is demonstrated to be suitable for the determination of 10 cephalosporins and desacetylcefapirin in bovine milk. The total time required for the analysis of one sample, including sample preparation, was about 40min. PMID:23747425

  18. Syphilis: antibiotic treatment and resistance.

    PubMed

    Stamm, L V

    2015-06-01

    Syphilis is a chronic, multi-stage infectious disease that is usually transmitted sexually by contact with an active lesion of a partner or congenitally from an infected pregnant woman to her fetus. Although syphilis is still endemic in many developing countries, it has re-emerged in several developed countries. The resurgence of syphilis is a major concern to global public health, particularly since the lesions of early syphilis increase the risk of acquisition and transmission of infection with human immunodeficiency virus (HIV). Because there is no vaccine to prevent syphilis, control is mainly dependent on the identification and treatment of infected individuals and their contacts with penicillin G, the first-line drug for all stages of syphilis. The emergence of clinically significant azithromycin resistance in Treponema pallidum subsp. pallidum, the syphilis agent, has resulted in treatment failures, thus precluding the routine use of this second-line drug. Information is presented here on the diagnosis and recommended antibiotic treatment of syphilis and the challenge of macrolide-resistant T. pallidum. PMID:25358292

  19. Quinolones: from antibiotics to autoinducers

    PubMed Central

    Heeb, Stephan; Fletcher, Matthew P; Chhabra, Siri Ram; Diggle, Stephen P; Williams, Paul; Cámara, Miguel

    2011-01-01

    Since quinine was first isolated, animals, plants and microorganisms producing a wide variety of quinolone compounds have been discovered, several of which possess medicinally interesting properties ranging from antiallergenic and anticancer to antimicrobial activities. Over the years, these have served in the development of many synthetic drugs, including the successful fluoroquinolone antibiotics. Pseudomonas aeruginosa and related bacteria produce a number of 2-alkyl-4(1H)-quinolones, some of which exhibit antimicrobial activity. However, quinolones such as the Pseudomonas quinolone signal and 2-heptyl-4-hydroxyquinoline act as quorum-sensing signal molecules, controlling the expression of many virulence genes as a function of cell population density. Here, we review selectively this extensive family of bicyclic compounds, from natural and synthetic antimicrobials to signalling molecules, with a special emphasis on the biology of P. aeruginosa. In particular, we review their nomenclature and biochemistry, their multiple properties as membrane-interacting compounds, inhibitors of the cytochrome bc1 complex and iron chelators, as well as the regulation of their biosynthesis and their integration into the intricate quorum-sensing regulatory networks governing virulence and secondary metabolite gene expression. PMID:20738404

  20. Prophylactic antibiotics prevent bacterial biofilm graft infection.

    PubMed

    Bergamini, T M; Peyton, J C; Cheadle, W G

    1992-02-01

    Bacterial biofilm graft infection is due to prostheses colonization by Staphylococcus epidermidis, a pathogen frequently recovered from perigraft tissues of man during vascular procedures despite the use of asepsis and prophylactic antibiotics. The effect of preoperative intraperitoneal cefazolin, administered at a standard (15 or 30 mg/kg) and high (120 mg/kg) dose, on the prevention of bacterial biofilm infection was studied in a rat model. Seventy-four Dacron grafts, colonized in vitro with S. epidermidis to produce an adherent biofilm (3.19 +/- 0.71 x 10(7) colony-forming units/cm2 graft), were implanted in the dorsal subcutaneous tissue at 0.5, 2, and 4 hr after antibiotic administration. The study strain was a slime-producing clinical isolate with minimum inhibitory concentration (MIC) of 15-30 micrograms/ml to cefazolin. Subcutaneous tissue antibiotic levels were determined at each time interval. One week after implantation, the concentration of bacteria in the surface biofilm by quantitative agar culture was significantly decreased (P less than 0.05) only for grafts implanted when antibiotic tissue levels were greater than or equal to the MIC of the study strain. The result of no growth by biofilm broth culture was significantly achieved (P less than 0.01) only for grafts implanted 0.5 hr after high dose cefazolin, in which the tissue antibiotic level was above the MIC of the study strain. Antibiotics can markedly reduce the bacteria concentration of a prosthetic surface biofilm. The effectiveness of prophylactic antibiotics on the prevention of graft infection is dependent upon maintaining an adequate antibiotic level in the perigraft tissues for the duration of the procedure. PMID:1346815

  1. Autotoxic antibiotic production by a marine Chromobacterium

    Microsoft Academic Search

    R. J. Andersen; M. S. Wolfe; D. J. Faulkner

    1974-01-01

    An antibiotic-producing Chromobacter was isolated from a sea-water sample from the North Pacific Gyre. The bacterium produces 3 bromine-containing metabolites: tetrabromopyrrole, 2-(2'-hydroxy-3', 5'-dibromophenyl)-3, 4, 5-tribromopyrrole, and hexabromo-2, 2'-bipyrrole. It also synthesizes n-propyl 4-hydroxybenzoate and 4-hydroxybenzaldehyde. Some of these compounds were shown to be responsible for autoinhibition of the Chromobacterium itself, as well as for antibiotic action against other kinds of

  2. Antibiotic Metabolites from a Marine Pseudomonad

    PubMed Central

    Wratten, Stephen J.; Wolfe, Margaret S.; Andersen, Raymond J.; Faulkner, D. John

    1977-01-01

    An antibiotic-producing pseudomonad was isolated from a seawater sample from a La Jolla, Calif., tidepool. The pseudomonad produces two novel antibacterial compounds, 2-n-pentyl-4-quinolinol and 2-n-heptyl-4-quinolinol. It also synthesizes indole-3-carboxaldehyde, 6-bromoindole-3-carboxaldehyde, and the known antibiotic p-hydroxybenzaldehyde. Each of these compounds was identified by analysis of spectral data, and the structures were confirmed by synthesis or comparison with authentic samples. PMID:324390

  3. Modeling empiric antibiotic therapy evaluation of QID.

    PubMed Central

    Warner, H.; Reimer, L.; Suvinier, D.; Li, L.; Nelson, M.

    1999-01-01

    At AMIA 1997, we reported on the design and development of a new computer-based tool, called QID, for empiric antibiotic decision support. QID was designed to help physicians identify the antibiotic regimens with the highest probability of covering the pathogens that are most likely to be present in individual patients. QID creates a list of antibiotics, ordered by potential benefit in treatment, for a patient with a suspected infection before culture results are available. Since our initial publication, a "before and after" study has been done using 20 internal medicine residents and the same number of internal medicine attendings. In order to test the hypothesis that physician's would make more appropriate empiric antibiotic choices with the aid of QID, we chose University of Utah physicians and had each evaluate four infectious disease cases that were abstracted from medical record infectious disease cases. Immediately following their initial review and determination of antibiotic therapy for each case, the study participants were presented with QID's antibiotic recommendations on the same case to see if this information would change their initial drug regimen. The tool was shown to have a greater impact on the most difficult cases but statistically improved scores overall (p < .001). Details of our study design and results are presented. PMID:10566397

  4. The “sleeper” issue in medicine : Clem Tisdell’s academic scribbling on the economics of antibiotic resistance

    Microsoft Academic Search

    D. P. Doessel

    1998-01-01

    Presents a brief account of the development of antibiotics so as to put such drugs in perspective. Then the issue of antibiotic resistance is considered and Tisdell’s economic analysis of the phenomenon is presented. Emphasis is placed on the inter-generational trade-off that is associated with this important social issue. The paper concludes by discussing Australia’s institutional arrangements for funding pharmaceutical,

  5. Development of an enzyme immunoassay for the antibiotic cefquinome and its application for residue determination in cow's milk after therapeutical mastitis treatment.

    PubMed

    Thal, Johannes; Steffen, Monika; Meier, Bianca; Schneider, Elisabeth; Adriany, Ansgar; Usleber, Ewald

    2011-01-01

    The aim of this study was to develop and evaluate an enzyme immunoassay (EIA) for the cephalosporin antibiotic in milk, in combination with a new microbiological test system (brilliant black reduction test, BRT-P). Polyclonal antibodies against cefquinome were produced in rabbits, using cefquinome-keyhole limpet hemocyanine as the immunogen. These antibodies and a cefquinome-glucose oxidase conjugate were used in a competitive indirect EIA. The detection limit for cefquinome in milk was 1.5 ng ml(-1), recoveries were 80-128% at 4-40 ng ml(-1). Cross-reactivities with other cephalosporins/penicillins were all <1%. The EIA was used to determine cefquinome in incurred raw milk, the BRT-P (detection limit ? 20 ng ml(-1)) and a receptor assay (ßeta-s.t.a.r., detection limit ? 15 ng ml(-1)) were used in parallel. Five lactating cows, suffering from clinical mastitis, were treated with cefquinome by simultaneous intramammary and intramuscular injection. Cefquinome residues (maximum 10-27 ?g?ml(-1)) were most exclusively found in the udder quarter which was treated intramammary, residue levels in the other three quarters were low (<20 ng ml(-1)). Even in milk from intramammary-dosed quarters, residue levels fell below European Union maximum residue level (MRL, 20 ?g kg(-1)) 2 days before the end of the withdrawal period. EIA, BRT-P, and ßeta-s.t.a.r. results showed acceptable agreement for milk samples, but the newly developed EIA is superior in aspects of sensitivity. In conclusion, this is the first one description of immunoassay and microbiological tests capable to determine cefquinome in milk at the MRL in incurred sample material. PMID:21103866

  6. Hospital and Community Isolates of Uropathogens and their Antibiotic Sensitivity Pattern from a Tertiary Care Hospital in North West India

    PubMed Central

    Singhal, A; Sharma, R; Jain, M; Vyas, L

    2014-01-01

    Background: Urinary tract infection remains one of the most common infections, both in the community and in the hospital. The causative pathogen profile varies from region to region, but Escherichia coli (E. coli) remains the most common causative pathogen. The sensitivity of uropathogens to different drugs varies in different areas, and changes with time. This necessitates periodic studies of the causative uropathogens and their antibiotic sensitivity pattern. Aim: To investigate the profile of common uropathogens and assess their antibiotic sensitivity patterns to commonly used antimicrobial agents. Materials and Methods: Analysis of all urine specimens submitted for culture and sensitivity was carried out over a 1-year period in a tertiary care hospital in North West India. Urine culture was done by a semi-quantitative method. Antibiotic sensitivity was done on bacterial isolates according to the Clinical and Laboratory Standards Institute CLSI guidelines for disc diffusion susceptibility test. Data was analysed for significance using Chi square test. Results: Of a total of 6348 urine specimens received over the 1-year study period, 41.8% (2653) of the urine samples were culture positive. The most common bacterial isolate was E. coli (45.7%, 1103/2412), followed by Coagulase-negative Staphylococci (18.6%, 449/2412) and Klebsiella species (8.3%, 199/2412). The Candida species’ isolation rate was 10.3% (277/2689). The uropathogens displayed a very high level of resistance to fluroquinolones 70.3% (1084/1542)[Inpatient Department (IPD) – 70.5%(572/812), Outpatient Department (OPD) – 70.2%(512/730)] and cephalosporins 75.1%(1158/1542)[IPD – 73.8%(599/812), OPD – 76.6%(559/730)], whereas resistance to nitrofurantoin 19.8%(305/1542) [ IPD – 23.9%, OPD – 15.2%(111/730)], amikacin 32.4%(573/1769) [IPD – 36.1%(235/934), OPD – 28.1%(235/835)] and cephoperazone + sulbactam combination 22%(349/1583) [IPD – 26.2%(244/914), OPD – 15.8%(105/669)] was low. Conclusion: Empiric selection of antimicrobial agents should be based on the antibiotic sensitivity pattern of the uropathogens prevalent in that area, which is derived from epidemiological studies carried out in that environment. PMID:24669331

  7. Harnessing the Power of the Genome in the Search for New Antibiotics

    Microsoft Academic Search

    John Rosamond; Aileen Allsop

    2000-01-01

    Over the past 40 years, the search for new antibiotics has been largely restricted to well-known compound classes active against a standard set of drug targets. Although many effective compounds have been discovered, insufficient chemical variability has been generated to prevent a serious escalation in clinical resistance. Recent advances in genomics have provided an opportunity to expand the range of

  8. Management Options for Reducing the Release of Antibiotics and Antibiotic Resistance Genes to the Environment

    PubMed Central

    Pruden, Amy; Amézquita, Alejandro; Collignon, Peter; Brandt, Kristian K.; Graham, David W.; Lazorchak, James M.; Suzuki, Satoru; Silley, Peter; Snape, Jason R.; Topp, Edward; Zhang, Tong; Zhu, Yong-Guan

    2013-01-01

    Background: There is growing concern worldwide about the role of polluted soil and water environments in the development and dissemination of antibiotic resistance. Objective: Our aim in this study was to identify management options for reducing the spread of antibiotics and antibiotic-resistance determinants via environmental pathways, with the ultimate goal of extending the useful life span of antibiotics. We also examined incentives and disincentives for action. Methods: We focused on management options with respect to limiting agricultural sources; treatment of domestic, hospital, and industrial wastewater; and aquaculture. Discussion: We identified several options, such as nutrient management, runoff control, and infrastructure upgrades. Where appropriate, a cross-section of examples from various regions of the world is provided. The importance of monitoring and validating effectiveness of management strategies is also highlighted. Finally, we describe a case study in Sweden that illustrates the critical role of communication to engage stakeholders and promote action. Conclusions: Environmental releases of antibiotics and antibiotic-resistant bacteria can in many cases be reduced at little or no cost. Some management options are synergistic with existing policies and goals. The anticipated benefit is an extended useful life span for current and future antibiotics. Although risk reductions are often difficult to quantify, the severity of accelerating worldwide morbidity and mortality rates associated with antibiotic resistance strongly indicate the need for action. PMID:23735422

  9. Isolation of soil Streptomyces as source antibiotics active against antibiotic-resistant bacteria

    Microsoft Academic Search

    Ozgur Ceylan; Gulten Okmen; Aysel Ugur

    2008-01-01

    The focus of this study was the in vitro antimicrobial activities of Streptomycetes, bacteria commonly found in soil and known antibiotic-producers. Streptomycete isolates obtained from different fields in Muðla, Turkey were evaluated for their inhibitory activities on seven microorganisms including multiple antibiotic resistant Staphylococcus aureus and Stenotrophomonas maltophilia. Fifteen Streptomycete isolates which exhibited antimicrobial activity against at least two of

  10. Antibiotic Resistant Bacteria in Mud of Shrimp Farming Ponds and Bacterial Degradation of Antibiotic

    Microsoft Academic Search

    Jatindra Nath Bhakta; Yukihiro Munekage

    An investigation was conducted to determine the occurrence, resistant efficiency of bacteria collected from four shrimp farming zones, Vunh Tau (VT), Nha Trang (NT), Da Nang (DN) and Hue (HU) of Viet Nam against five commonly applied antibiotics (sulphamethoxazole (SMX), trimethoprim (TMP), norfloxacin (NFC), amoxillin (AXC) and streptomycin (SMC)) and bacterial degradation of antibiotic. Mud samples were employed to examine

  11. Improving antibiotic prescribing in Hai Phong Province, Viet Nam: the ''antibiotic-dose'' indicator

    Microsoft Academic Search

    John Chalker

    Objective To improve the use and dosage of antibiotics prescribed at Commune Health Stations in Viet Nam, and in so doing find out whether antibiotic dosage can be easily and reliably measured as a drug-use indicator. Methods All commune health workers from the 217 commune health stations in Hai Phong Province, Viet Nam, were enlisted over an 18-month study period

  12. Urine Antibiotic Activity in Patients Presenting to Hospitals in Laos: Implications for Worsening Antibiotic Resistance

    PubMed Central

    Khennavong, Manisone; Davone, Viengmon; Vongsouvath, Manivanh; Phetsouvanh, Rattanaphone; Silisouk, Joy; Rattana, Olay; Mayxay, Mayfong; Castonguay-Vanier, Josée; Moore, Catrin E.; Strobel, Michel; Newton, Paul N.

    2011-01-01

    Widespread use of antibiotics may be important in the spread of antimicrobial resistance. We estimated the proportion of Lao in- and outpatients who had taken antibiotics before medical consultation by detecting antibiotic activity in their urine added to lawns of Bacillus stearothermophilus, Escherichia coli, and Streptococcus pyogenes. In the retrospective (N = 2,058) and prospective studies (N = 1,153), 49.7% (95% confidence interval [CI] = 47.4–52.0) and 36.2% (95% CI = 33.4–38.9), respectively, of Vientiane patients had urinary antibiotic activity detected. The highest frequency of estimated antibiotic pre-treatment was found in patients recruited with suspected central nervous system infections and community-acquired septicemia (both 56.8%). In Vientiane, children had a higher frequency of estimated antibiotic pre-treatment than adults (60.0% versus 46.5%; P < 0.001). Antibiotic use based on patients histories was significantly less frequent than when estimated from urinary antibiotic activity (P < 0.0001). PMID:21813851

  13. Resins Do not Adsorb All Antibiotics at Peak Serum Concentrations, Especially the Newer Betalactam Antibiotics

    Microsoft Academic Search

    Vincent LaBombardi; Josh Sotos; Sara Allen; Nadine Sullivan; Becton Dickinson; Resin Bottle

    Background: Several publications have described the performance of resins for clinical blood samples and for seeded blood culture studies. Of interest were the studies that showed poor or discrepant results in the ability of the resins to adsorb out sufficient antibiotic to allow organism growth. Methods: We developed a microtiter plate assay that semi-quantitatively shows the amount of antibiotic adsorption

  14. Antibiotics cure anthrax in animal models.

    PubMed

    Weiss, Shay; Kobiler, David; Levy, Haim; Pass, Avi; Ophir, Yakir; Rothschild, Nili; Tal, Arnon; Schlomovitz, Josef; Altboum, Zeev

    2011-04-01

    Respiratory anthrax, in the absence of early antibiotic treatment, is a fatal disease. This study aimed to test the efficiency of antibiotic therapy in curing infected animals and those sick with anthrax. Postexposure prophylaxis (24 h postinfection [p.i.]) of guinea pigs infected intranasally with Bacillus anthracis Vollum spores with doxycycline, ofloxacin, imipenem, and gentamicin conferred protection. However, upon termination of treatment, the animals died from respiratory anthrax. Combined treatment with antibiotics and active vaccination with a protective antigen-based vaccine leads to full protection even after cessation of treatment. Delaying the initiation of antibiotic administration to over 24 h p.i. resulted in treatment of animals with anthrax exhibiting various degrees of bacteremia and toxemia. Treatment with doxycycline or ciprofloxacin cured sick guinea pigs and rabbits exhibiting bacteremia levels up to 10(5) CFU/ml. Addition of anti-protective antigen (PA) antibodies augmented the efficiency of protection, allowing the cure of guinea pigs and rabbits with 10- to 20-fold-higher bacteremia levels, up to 7 × 10(5) CFU/ml and 2 × 10(6) CFU/ml, respectively. Treatment with ciprofloxacin and a monoclonal anti-PA antibody rescued rabbits with bacteremia levels up to 4 × 10(6) CFU/ml. During antibiotic administration, all surviving animals developed a protective immune response against development of a fatal disease and subcutaneous challenge with Vollum spores. In conclusion, these results demonstrate that antibiotic treatment can prevent the development of fatal disease in respiratory-anthrax-infected animals and can cure animals after disease establishment. A therapeutic time window of 40 h to 48 h from infection to initiation of efficient antibiotic-mediated cure was observed. PMID:21263056

  15. Influence of therapeutic ceftiofur treatments of feedlot cattle on fecal and hide prevalences of commensal Escherichia coli resistant to expanded-spectrum cephalosporins, and molecular characterization of resistant isolates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the United States the bla**CMY-2** gene contained within incompatibility type A/C (IncA/C) plasmids is frequently identified in extended-spectrum cephalosporin-resistant Escherichia coli (ESCr) from both human and cattle sources. Concerns have been raised that therapeutic use of ceftiofur in catt...

  16. Antibiotic-Loaded Cement in Orthopedic Surgery: A Review

    PubMed Central

    Bistolfi, Alessandro; Massazza, Giuseppe; Verné, Enrica; Massè, Alessandro; Deledda, Davide; Ferraris, Sara; Miola, Marta; Galetto, Fabrizio; Crova, Maurizio

    2011-01-01

    Infections in orthopaedic surgery are a serious issue. Antibiotic-loaded bone cement was developed for the treatment of infected joint arthroplasties and for prophylaxes in total joint replacement in selected cases. Despite the widespread use of the antibiotic-loaded bone cement in orthopedics, many issues are still unclear or controversial: bacterial adhesion and antibiotic resistance, modification of mechanical properties which follows the addition of the antibiotic, factors influencing the release of the antibiotic from the cement and the role of the surface, the method for mixing the cement and the antibiotic, the choice and the effectiveness of the antibiotic, the combination of two or more antibiotics, and the toxicity. This review discusses all these topics, focusing on properties, merits, and defects of the antibiotic loaded cement. The final objective is to provide the orthopaedic surgeons clear and concise information for the correct choice of cement in their clinical practice. PMID:24977058

  17. Concentration-dependent activity of antibiotics in natural environments

    PubMed Central

    Bernier, Steve P.; Surette, Michael G.

    2013-01-01

    Bacterial responses to antibiotics are concentration-dependent. At high concentrations, antibiotics exhibit antimicrobial activities on susceptible cells, while subinhibitory concentrations induce diverse biological responses in bacteria. At non-lethal concentrations, bacteria may sense antibiotics as extracellular chemicals to trigger different cellular responses, which may include an altered antibiotic resistance/tolerance profile. In natural settings, microbes are typically in polymicrobial communities and antibiotic-mediated interactions between species may play a significant role in bacterial community structure and function. However, these aspects have not yet fully been explored at the community level. Here we discuss the different types of interactions mediated by antibiotics and non-antibiotic metabolites as a function of their concentrations and speculate on how these may amplify the overall antibiotic resistance/tolerance and the spread of antibiotic resistance determinants in a context of polymicrobial community. PMID:23422936

  18. Novel approaches to developing new antibiotics for bacterial infections

    PubMed Central

    Coates, A R M; Hu, Y

    2007-01-01

    Antibiotics are an essential part of modern medicine. The emergence of antibiotic-resistant mutants among bacteria is seemingly inevitable, and results, within a few decades, in decreased efficacy and withdrawal of the antibiotic from widespread usage. The traditional answer to this problem has been to introduce new antibiotics that kill the resistant mutants. Unfortunately, after more than 50 years of success, the pharmaceutical industry is now producing too few antibiotics, particularly against Gram-negative organisms, to replace antibiotics that are no longer effective for many types of infection. This paper reviews possible new ways to discover novel antibiotics. The genomics route has proven to be target rich, but has not led to the introduction of a marketed antibiotic as yet. Non-culturable bacteria may be an alternative source of new antibiotics. Bacteriophages have been shown to be antibacterial in animals, and may find use in specific infectious diseases. Developing new antibiotics that target non-multiplying bacteria is another approach that may lead to drugs that reduce the emergence of antibiotic resistance and increase patient compliance by shortening the duration of antibiotic therapy. These new discovery routes have given rise to compounds that are in preclinical development, but, with one exception, have not yet entered clinical trials. For the time being, the majority of new antibiotics that reach the marketplace are likely to be structural analogues of existing families of antibiotics or new compounds, both natural and non-natural which are screened in a conventional way against live multiplying bacteria. PMID:17704820

  19. Mobile Display of Information about Aggregated Antibiotic Resistance in the Hospital Setting Supported by Near Field Communication.

    PubMed

    Meng, Philipp; Fehre, Karsten; Rappelsberger, Andrea; Adlassnig, Klaus-Peter

    2014-01-01

    Antibiotic resistance is a heterogeneous phenomenon. It does not only differ between countries or states, but also between wards of hospitals, where different resistance patterns have been found. To support clinicians in administering empiric antibiotic therapy, we developed software to present information about antibiotic resistance using a mobile concept. A pre-existing infrastructure was deployed as the server component. The systems analyze and aggregate data from laboratory information systems, generating statistical data on antibiotic resistance. The information is presented to the Android client using a Representational State Transfer (REST) interface. Geographical localization is performed using near field communication (NFC) tags. The prototype provides tabulated data concerning antibiotic resistance patterns in the wards of a hospital. Using Android, NFC, and data caching, the usability of the system is estimated to be high. We hypothesize that antibiotic stewardship in hospitals can be supported by this software, thus improving medical monitoring of antibiotic resistance. Future studies in a productive environment are needed to measure the impact of the system on the outcome of patient care. PMID:24851968

  20. Clonal Expansion during Staphylococcus aureus Infection Dynamics Reveals the Effect of Antibiotic Intervention

    PubMed Central

    McVicker, Gareth; Prajsnar, Tomasz K.; Williams, Alexander; Wagner, Nelly L.; Boots, Michael; Renshaw, Stephen A.; Foster, Simon J.

    2014-01-01

    To slow the inexorable rise of antibiotic resistance we must understand how drugs impact on pathogenesis and influence the selection of resistant clones. Staphylococcus aureus is an important human pathogen with populations of antibiotic-resistant bacteria in hospitals and the community. Host phagocytes play a crucial role in controlling S. aureus infection, which can lead to a population “bottleneck” whereby clonal expansion of a small fraction of the initial inoculum founds a systemic infection. Such population dynamics may have important consequences on the effect of antibiotic intervention. Low doses of antibiotics have been shown to affect in vitro growth and the generation of resistant mutants over the long term, however whether this has any in vivo relevance is unknown. In this work, the population dynamics of S. aureus pathogenesis were studied in vivo using antibiotic-resistant strains constructed in an isogenic background, coupled with systemic models of infection in both the mouse and zebrafish embryo. Murine experiments revealed unexpected and complex bacterial population kinetics arising from clonal expansion during infection in particular organs. We subsequently elucidated the effect of antibiotic intervention within the host using mixed inocula of resistant and sensitive bacteria. Sub-curative tetracycline doses support the preferential expansion of resistant microorganisms, importantly unrelated to effects on growth rate or de novo resistance acquisition. This novel phenomenon is generic, occurring with methicillin-resistant S. aureus (MRSA) in the presence of ?-lactams and with the unrelated human pathogen Pseudomonas aeruginosa. The selection of resistant clones at low antibiotic levels can result in a rapid increase in their prevalence under conditions that would previously not be thought to favor them. Our results have key implications for the design of effective treatment regimes to limit the spread of antimicrobial resistance, where inappropriate usage leading to resistance may reduce the efficacy of life-saving drugs. PMID:24586163

  1. The Biogeography of Putative Microbial Antibiotic Production

    PubMed Central

    Bryant, Jessica A.; Charkoudian, Louise K.; Docherty, Kathryn M.; Jones, Evan; Kembel, Steven W.; Green, Jessica L.; Bohannan, Brendan J. M.

    2015-01-01

    Understanding patterns in the distribution and abundance of functional traits across a landscape is of fundamental importance to ecology. Mapping these distributions is particularly challenging for species-rich groups with sparse trait measurement coverage, such as flowering plants, insects, and microorganisms. Here, we use likelihood-based character reconstruction to infer and analyze the spatial distribution of unmeasured traits. We apply this framework to a microbial dataset comprised of 11,732 ketosynthase alpha gene sequences extracted from 144 soil samples from three continents to document the spatial distribution of putative microbial polyketide antibiotic production. Antibiotic production is a key competitive strategy for soil microbial survival and performance. Additionally, novel antibiotic discovery is highly relevant to human health, making natural antibiotic production by soil microorganisms a major target for bioprospecting. Our comparison of trait-based biogeographical patterns to patterns based on taxonomy and phylogeny is relevant to our basic understanding of microbial biogeography as well as the pressing need for new antibiotics. PMID:26102275

  2. Factors influencing antibiotics adsorption onto engineered adsorbents.

    PubMed

    Xia, Mingfang; Li, Aimin; Zhu, Zhaolian; Zhou, Qin; Yang, Weiben

    2013-07-01

    The study evaluated the adsorption of two antibiotics by four engineered adsorbents (hypercrosslinked resin MN-202, macroporous resin XAD-4, activated carbon F-400, and multi-walled carbon nanotubes (MWCNT)) from aqueous solutions. The dynamic results demonstrated the dominant influence of pore size in adsorption. The adsorption amounts of antibiotics on XAD-4 were attributed to the hydrophobic effect, whereas steric hindrance or micropore-filling played a main role in the adsorption of antibiotics by F-400 because of its high microporosity. Aside from F-400, similar patterns of pH-dependent adsorption were observed, implying the importance of antibiotic molecular forms to the adsorption process for adsorbents. Increasing the ionic concentration with CaC12 produced particular adsorption characteristics on MWCNT at pH 2.0 and F-400 at pH 8.0, which were attributed to the highly available contact surfaces and molecular sieving, respectively. Its hybrid characteristics incorporating a considerable portion of mesopores and micropores made hypercross linked MN-202 a superior antibiotic adsorbent with high adsorption capacity. Furthermore, the adsorption capacity of MWCNT on the basis of surface area was more advantageous than that of the other adsorbents because MWCNT has a much more compact molecular arrangement. PMID:24218839

  3. Intrapartum Antibiotics and Childhood Atopic Dermatitis

    PubMed Central

    Wohl, Debra L.; Curry, William J.; Mauger, Dave; Miller, Jennifer; Tyrie, Kaitlyn

    2015-01-01

    Introduction Atopic dermatitis (AD) in children significantly impacts families due to medical costs, “lost” hours, and secondary characteristics like asthma and ancillary infections. We investigate whether children delivered vaginally to women receiving intrapartum antibiotics have a greater risk of AD under the age of 2 years than their counterparts. Methods We conducted a retrospective analysis of women who delivered child(ren) vaginally between 1996 and 2008. Women were identified as those who received intrapartum antibiotics and those who did not. Pediatric records were used to determine incidence of AD. Results We collected data for 492 mother-child pairs. Intrapartum antibiotics were administered during 128 births; 28.9% of those children were diagnosed with AD by 2 years (RR 1.03 [0.75-1.41], p=0.854). Factors with greatest risks of diagnosis with AD by 2 years were intrapartum antibiotic exposure for >24hrs (RR 1.99 [1.13-3.49], p=0.0173), first born (RR 1.78 [1.33-2.38], p<0.0001) and higher maternal education (RR 1.43[0.99-2.06], p=0.039). No statistical difference in prevalence of AD related to parental eczema, maternal Group B Streptococcus status, or gestational age existed. Conclusions Exposure to antibiotics for <24hrs during a vaginal delivery does not increase the risk of AD. Studies are needed to understand if exposures >24hrs during the intrapartum period increase the risk of AD. PMID:25567826

  4. Antibiotics in development targeting protein synthesis.

    PubMed

    Sutcliffe, Joyce A

    2011-12-01

    The resolution of antibiotic-ribosomal subunit complexes and antibacterial-protein complexes at the atomic level has provided new insights into modifications of clinically relevant antimicrobials and provided new classes that target the protein cellular apparatus. New chemistry platforms that use fragment-based drug design or allow novel modifications in known structural classes are being used to design new antibiotics that overcome known resistance mechanisms and extend spectrum and potency by circumventing ubiquitous efflux pumps. This review provides details on seven antibiotics in development for treatment of moderate-to-severe community-acquired bacterial pneumonia and/or acute bacterial skin and skin structure infections: solithromycin, cethromycin, omadacycline, CEM-102, GSK1322322, radezolid, and tedizolid. Two antibiotics of the oxazolidinone class, PF-02341272 and AZD5847, are being developed as antituberculosis agents. Only three antibiotics that target the protein cellular machinery, TP-434, GSK2251052, and plazomicin, have a spectrum that encompasses multidrug-resistant Gram-negative pathogens. These compounds provide hope for treating key pathogens that cause serious disease in both the community and the hospital. PMID:22191530

  5. Survey of prophylactic antibiotic use amongst UK cochlear implant surgeons.

    PubMed

    Barker, Emma; Pringle, Mike

    2008-06-01

    Cochlear implant patients are at an increased risk of pneumococcal meningitis. Recent government guidelines require all implant patients to undergo pneumococcal vaccination. The guidelines also suggest antibiotic prophylaxis but no clear guidelines regarding which antibiotic to use or for how long were issued.We asked each implant centre within the UK to describe their antibiotic protocol for cochlear implantation.Our results have showed that 100% of UK implant surgeons use antibiotic prophylaxis. The type of antibiotic and duration vary significantly between centres. Interestingly, however, the regimes followed by most practices do not adhere to surgical principles of antibiotic prophylaxis. PMID:18618432

  6. Enhanced killing of antibiotic-resistant bacteria enabled by massively parallel combinatorial genetics

    PubMed Central

    Cheng, Allen A.; Ding, Huiming; Lu, Timothy K.

    2014-01-01

    New therapeutic strategies are needed to treat infections caused by drug-resistant bacteria, which constitute a major growing threat to human health. Here, we use a high-throughput technology to identify combinatorial genetic perturbations that can enhance the killing of drug-resistant bacteria with antibiotic treatment. This strategy, Combinatorial Genetics En Masse (CombiGEM), enables the rapid generation of high-order barcoded combinations of genetic elements for high-throughput multiplexed characterization based on next-generation sequencing. We created ?34,000 pairwise combinations of Escherichia coli transcription factor (TF) overexpression constructs. Using Illumina sequencing, we identified diverse perturbations in antibiotic-resistance phenotypes against carbapenem-resistant Enterobacteriaceae. Specifically, we found multiple TF combinations that potentiated antibiotic killing by up to 106-fold and delivered these combinations via phagemids to increase the killing of highly drug-resistant E. coli harboring New Delhi metallo-beta-lactamase-1. Moreover, we constructed libraries of three-wise combinations of transcription factors with >4 million unique members and demonstrated that these could be tracked via next-generation sequencing. We envision that CombiGEM could be extended to other model organisms, disease models, and phenotypes, where it could accelerate massively parallel combinatorial genetics studies for a broad range of biomedical and biotechnology applications, including the treatment of antibiotic-resistant infections. PMID:25114216

  7. Time lapse investigation of antibiotic susceptibility using a microfluidic linear gradient 3D culture device.

    PubMed

    Hou, Zining; An, Yu; Hjort, Karin; Hjort, Klas; Sandegren, Linus; Wu, Zhigang

    2014-09-01

    This study reports a novel approach to quantitatively investigate the antibacterial effect of antibiotics on bacteria using a three-dimensional microfluidic culture device. In particular, our approach is suitable for studying the pharmacodynamics effects of antibiotics on bacterial cells temporally and with a continuous range of concentrations in a single experiment. The responses of bacterial cells to a linear concentration gradient of antibiotics were observed using time-lapse photography, by encapsulating bacterial cells in an agarose-based gel located in a commercially available microfluidics chamber. This approach generates dynamic information with high resolution, in a single operation, e.g., growth curves and antibiotic pharmacodynamics, in a well-controlled environment. No pre-labelling of the cells is needed and therefore any bacterial sample can be tested in this setup. It also provides static information comparable to that of standard techniques for measuring minimum inhibitory concentration (MIC). Five antibiotics with different mechanisms were analysed against wild-type Escherichia coli, Staphylococcus aureus and Salmonella Typhimurium. The entire process, including data analysis, took 2.5-4 h and from the same analysis, high-resolution growth curves were obtained. As a proof of principle, a pharmacodynamic model of streptomycin against Salmonella Typhimurium was built based on the maximal effect model, which agreed well with the experimental results. Our approach has the potential to be a simple and flexible solution to study responding behaviours of microbial cells under different selection pressures both temporally and in a range of concentrations. PMID:25007721

  8. Synergistic effect and antibiofilm activity between the antimicrobial peptide coprisin and conventional antibiotics against opportunistic bacteria.

    PubMed

    Hwang, In-sok; Hwang, Jae-Sam; Hwang, Ji Hong; Choi, Hyemin; Lee, Eunjung; Kim, Yangmee; Lee, Dong Gun

    2013-01-01

    Coprisin is a 43-mer defensin-like peptide from the dung beetle, Copris tripartitus. In this study, we tested its minimum inhibitory concentration and performed combination assays to confirm the antibacterial susceptibility of coprisin and synergistic effects with antibiotics. The synergistic effects were evaluated by testing the effects of coprisin in combination with ampicillin, vancomycin, and chloramphenicol. The results showed that coprisin possessed antibacterial properties and had synergistic activities with the antibiotics. To understand the synergistic mechanism(s), we conducted hydroxyl radical assays. Coprisin alone and in combination with antibiotics generated hydroxyl radicals, which are highly reactive oxygen forms and the major property of bactericidal agents. Furthermore, the antibiofilm effect of coprisin alone and in combination with antibiotics was investigated. Biofilm formation is the source of many relentless and chronic bacterial infections. The results indicated that coprisin alone and in combination with antibiotics also had antibiofilm activity. Therefore, we conclude that coprisin has the potential to be used as a combinatorial therapeutic agent for the treatment of infectious diseases caused by bacteria. PMID:23053486

  9. The fitness costs of antibiotic resistance mutations

    PubMed Central

    Melnyk, Anita H; Wong, Alex; Kassen, Rees

    2015-01-01

    Antibiotic resistance is increasing in pathogenic microbial populations and is thus a major threat to public health. The fate of a resistance mutation in pathogen populations is determined in part by its fitness. Mutations that suffer little or no fitness cost are more likely to persist in the absence of antibiotic treatment. In this review, we performed a meta-analysis to investigate the fitness costs associated with single mutational events that confer resistance. Generally, these mutations were costly, although several drug classes and species of bacteria on average did not show a cost. Further investigations into the rate and fitness values of compensatory mutations that alleviate the costs of resistance will help us to better understand both the emergence and management of antibiotic resistance in clinical settings. PMID:25861385

  10. Bacterial resistance to antibiotics: modified target sites.

    PubMed

    Lambert, Peter A

    2005-07-29

    Alteration in the target sites of antibiotics is a common mechanism of resistance. Examples of clinical strains showing resistance can be found for every class of antibiotic, regardless of the mechanism of action. Target site changes often result from spontaneous mutation of a bacterial gene on the chromosome and selection in the presence of the antibiotic. Examples include mutations in RNA polymerase and DNA gyrase, resulting in resistance to the rifamycins and quinolones, respectively. In other cases, acquisition of resistance may involve transfer of resistance genes from other organisms by some form of genetic exchange (conjugation, transduction, or transformation). Examples of these mechanisms include acquisition of the mecA genes encoding methicillin resistance in Staphylococcus aureus and the various van genes in enterococci encoding resistance to glycopeptides. PMID:15964098

  11. Rediscovering the antibiotics of the hive.

    PubMed

    Boukraâ, Laïd; Sulaiman, Siti A

    2009-11-01

    Honey and other bee products were subjected to laboratory and clinical investigations during the past few decades and the most remarkable discovery was their antibacterial activity. Honey has been used since ancient times for the treatment of some diseases and for the healing of wounds but its use as an anti-infective agent was superseded by modern dressings and antibiotic therapy. However, the emergence of antibiotic resistant strains of bacteria has confounded the current use of antibiotic therapy leading to the re-examination of former remedies. Honey, propolis, royal jelly and bee venom have a strong antibacterial activity. Even antibiotic-resistant strains such as epidemic strains of methicillin-resistant Staphylococcus aureus (MRSA) and Vancomycine resistant Enterococcus (VRE) have been found to be as sensitive to honey as the antibiotic-sensitive strains of the same species. Sensitivity of bacteria to bee products varies considerably within the product and the varieties of the same product. Botanical origin plays a major role in its antibacterial activity. Propolis has been found to have the strongest action against bacteria. This is probably due to its richness in flavonoids. The most challenging problems of using hive products for medical purposes are dosage and safety. Honey and royal jelly produced as a food often are not well filtered, and may contain various particles. Processed for use in wound care, they are passed through fine filters which remove most of the pollen and other impurities to prevent allergies. Also, although honey does not allow vegetative bacteria to survive, it does contain viable spores, including clostridia. With the increased availability of licensed medical stuffs containing bee products, clinical use is expected to increase and further evidence will become available. Their use in professional care centres should be limited to those which are safe and with certified antibacterial activities. The present article is a short review of recent patents on antibiotics of hives. PMID:19673699

  12. Discovery and preclinical development of new antibiotics

    PubMed Central

    Karlén, Anders

    2014-01-01

    Antibiotics are the medical wonder of our age, but an increasing frequency of resistance among key pathogens is rendering them less effective. If this trend continues the consequences for cancer patients, organ transplant patients, and indeed the general community could be disastrous. The problem is complex, involving abuse and overuse of antibiotics (selecting for an increasing frequency of resistant bacteria), together with a lack of investment in discovery and development (resulting in an almost dry drug development pipeline). Remedial approaches to the problem should include taking measures to reduce the selective pressures for resistance development, and taking measures to incentivize renewed investment in antibiotic discovery and development. Bringing new antibiotics to the clinic is critical because this is currently the only realistic therapy that can ensure the level of infection control required for many medical procedures. Here we outline the complex process involved in taking a potential novel antibiotic from the initial discovery of a hit molecule, through lead and candidate drug development, up to its entry into phase I clinical trials. The stringent criteria that a successful drug must meet, balancing high efficacy in vivo against a broad spectrum of pathogens, with minimal liabilities against human targets, explain why even with sufficient investment this process is prone to a high failure rate. This emphasizes the need to create a well-funded antibiotic discovery and development pipeline that can sustain the continuous delivery of novel candidate drugs into clinical trials, to ensure the maintenance of the advanced medical procedures we currently take for granted. PMID:24646082

  13. Removal of antibiotics and antibiotic resistance genes in rural wastewater by an integrated constructed wetland.

    PubMed

    Chen, Jun; Liu, You-Sheng; Su, Hao-Chang; Ying, Guang-Guo; Liu, Feng; Liu, Shuang-Shuang; He, Liang-Ying; Chen, Zhi-Feng; Yang, Yong-Qiang; Chen, Fan-Rong

    2015-02-01

    Integrated constructed wetlands (ICWs) are regarded as one of the most important removal technology for pollutants in rural domestic wastewaters. This study investigated the efficiency of an ICW consisting of a regulating pool, four surface and subsurface flow-constructed wetlands, and a stabilization unit for removing antibiotics and antibiotic resistance genes (ARGs) from rural domestic wastewaters. The results showed that antibiotics leucomycin, ofloxacin, lincomycin, and sulfamethazine, and ARGs sul1, sul2, tetM, and tetO were the predominant antibiotics and ARGs in the influent, respectively. The ICW system could significantly reduce most of the detected antibiotics and ARGs with their aqueous removal rates of 78 to 100 % and >99 %, respectively. Based on the measured concentrations, the total pollution loadings of antibiotics were 3,479 ?g/day in the influent and 199 ?g/day in the final effluent. Therefore, constructed wetlands could be a promising technology for rural wastewater in removing contaminants such as antibiotics and ARGs. PMID:24687794

  14. Collateral sensitivity of antibiotic-resistant microbes.

    PubMed

    Pál, Csaba; Papp, Balázs; Lázár, Viktória

    2015-07-01

    Understanding how evolution of microbial resistance towards a given antibiotic influences susceptibility to other drugs is a challenge of profound importance. By combining laboratory evolution, genome sequencing, and functional analyses, recent works have charted the map of evolutionary trade-offs between antibiotics and have explored the underlying molecular mechanisms. Strikingly, mutations that caused multidrug resistance in bacteria simultaneously enhanced sensitivity to many other unrelated drugs (collateral sensitivity). Here, we explore how this emerging research sheds new light on resistance mechanisms and the way it could be exploited for the development of alternative antimicrobial strategies. PMID:25818802

  15. Polyamine effects on antibiotic susceptibility in bacteria.

    PubMed

    Kwon, Dong-Hyeon; Lu, Chung-Dar

    2007-06-01

    Biogenic polyamines (e.g., spermidine and spermine) are a group of essential polycationic compounds found in all living cells. The effects of spermine and spermidine on antibiotic susceptibility were examined with gram-negative Escherichia coli and Salmonella enterica serovar Typhimurium bacteria and clinical isolates of Pseudomonas aeruginosa and with gram-positive Staphylococcus aureus bacteria, including methicillin-resistant S. aureus (MRSA). Exogenous spermine exerted a dose-dependent inhibition effect on the growth of E. coli, S. enterica serovar Typhimurium, and S. aureus but not P. aeruginosa, as depicted by MIC and growth curve measurements. While the MICs of polymyxin and ciprofloxacin were in general increased by exogenous spermine and spermidine in P. aeruginosa, this adverse effect was not observed in enteric bacteria and S. aureus. It was found that spermine and spermidine can decrease the MICs of beta-lactam antibiotics in all strains as well as other types of antibiotics in a strain-dependent manner. Significantly, the MICs of oxacillin for MRSA Mu50 and N315 were decreased more than 200-fold in the presence of spermine, and this effect of spermine was retained when assessed in the presence of divalent ions (magnesium or calcium; 3 mM) or sodium chloride (150 mM). The effect of spermine on the sensitization of P. aeruginosa and MRSA to antibiotics was further demonstrated by population analysis and time-killing assays. The results of checkerboard assays with E. coli and S. aureus indicated a strong synergistic effect of spermine in combination with beta-lactams and chloramphenicol. The decreased MICs of beta-lactams implied that the possible blockage of outer membrane porins by exogenous spermine or spermidine did not play a crucial role in most cases. In contrast, only the MIC of imipenem against P. aeruginosa was increased by exogenous spermine and spermidine, and this resistance effect was abolished in a mutant strain devoid of the outer membrane porin OprD. In E. coli, the MICs of carbenicillin, chloramphenicol, and tetracycline were decreased in two acrA mutants devoid of a major efflux pump, AcrAB. However, retention of the spermine effect on antibiotic susceptibility in two acrA mutants of E. coli suggested that the AcrAB efflux pump was not the target for a synergistic effect by spermine and antibiotics and ruled out the hypothesis of spermine serving as an efflux pump inhibitor in this organism. In summary, this interesting finding of the effect of spermine on antibiotic susceptibility provides the basis for a new potential approach against drug-resistant pathogens by use of existing beta-lactam antibiotics. PMID:17438056

  16. Combination of essential oils and antibiotics reduce antibiotic resistance in plasmid-conferred multidrug resistant bacteria.

    PubMed

    Yap, Polly Soo Xi; Lim, Swee Hua Erin; Hu, Cai Ping; Yiap, Beow Chin

    2013-06-15

    In this study we investigated the relationship between several selected commercially available essential oils and beta-lactam antibiotics on their antibacterial effect against multidrug resistant bacteria. The antibacterial activity of essential oils and antibiotics was assessed using broth microdilution. The combined effects between essential oils of cinnamon bark, lavender, marjoram, tea tree, peppermint and ampicillin, piperacillin, cefazolin, cefuroxime, carbenicillin, ceftazidime, meropenem, were evaluated by means of the checkerboard method against beta-lactamase-producing Escherichia coli. In the latter assays, fractional inhibitory concentration (FIC) values were calculated to characterize interaction between the combinations. Substantial susceptibility of the bacteria toward natural antibiotics and a considerable reduction in the minimum inhibitory concentrations (MIC) of the antibiotics were noted in some paired combinations of antibiotics and essential oils. Out of 35 antibiotic-essential oil pairs tested, four of them showed synergistic effect (FIC?0.5) and 31 pairs showed no interaction (FIC>0.5-4.0). The preliminary results obtained highlighted the occurrence of a pronounced synergistic relationship between piperacillin/cinnamon bark oil, piperacillin/lavender oil, piperacillin/peppermint oil as well as meropenem/peppermint oil against two of the three bacteria under study with a FIC index in the range 0.26-0.5. The finding highlighted the potential of peppermint, cinnamon bark and lavender essential oils being as antibiotic resistance modifying agent. Reduced usage of antibiotics could be employed as a treatment strategy to decrease the adverse effects and possibly to reverse the beta-lactam antibiotic resistance. PMID:23537749

  17. Relationships between antibiotics and antibiotic resistance gene levels in municipal solid waste leachates in Shanghai, China.

    PubMed

    Wu, Dong; Huang, Zhiting; Yang, Kai; Graham, David; Xie, Bing

    2015-04-01

    Many studies have quantified antibiotics and antibiotic resistance gene (ARG) levels in soils, surface waters, and waste treatment plants (WTPs). However, similar work on municipal solid waste (MSW) landfill leachates is limited, which is concerning because antibiotics disposal is often in the MSW stream. Here we quantified 20 sulfonamide (SA), quinolone (FQ), tetracycline (TC), macrolide (ML), and chloramphenicol (CP) antibiotics, and six ARGs (sul1, sul2, tetQ, tetM, ermB, and mefA) in MSW leachates from two Shanghai transfer stations (TS; sites Hulin (HL) and Xupu (XP)) and one landfill reservoir (LR) in April and July 2014. Antibiotic levels were higher in TS than LR leachates (985 ± 1965 ng/L vs 345 ± 932 ng/L, n = 40), which was because of very high levels in the HL leachates (averaging at 1676 ± 5175 ng/L, n = 40). The mean MLs (3561 ± 8377 ng/L, n = 12), FQs (975 ± 1608 ng/L, n = 24), and SAs (402 ± 704 ng/L, n = 42) classes of antibiotics were highest across all samples. ARGs were detected in all leachate samples with normalized sul2 and ermB levels being especially elevated (-1.37 ± 1.2 and -1.76 ± 1.6 log (copies/16S-rDNA), respectively). However, ARG abundances did not correlate with detected antibiotic levels, except for tetW and tetQ with TC levels (r = 0.88 and 0.81, respectively). In contrast, most measured ARGs did significantly correlate with heavy metal levels (p < 0.05), especially with Cd and Cr. This study shows high levels of ARGs and antibiotics can prevail in MSW leachates and landfills may be an underappreciated as a source of antibiotics and ARGs to the environment. PMID:25760223

  18. CURRENT ISSUES REGARDING ENDOCRINE DISRUPTING CHEMICALS AND ANTIBIOTIC RESISTANCE

    EPA Science Inventory

    Recently public concern has increased regarding industrial and environmental substances that may have adverse hormonal effects in human and wildlife populations. This concern has also been expanded to include antibiotic-resistant bacteria and the presence of various antibiotics a...

  19. Engineering Synthetic Bacteriophage to Combat Antibiotic-Resistant Bacteria

    E-print Network

    Lu, Timothy Kuan-Ta

    Antibiotic resistance is a rapidly evolving problem that is not being adequately met by new antimicrobial drugs. Thus, there is a pressing need for effective antibacterial therapies that can be adapted against antibiotic-resistant ...

  20. Doctors May Play Big Role in Antibiotic Overuse

    MedlinePLUS

    ... HealthDay . All rights reserved. More Health News on: Antibiotic Resistance Recent Health News Related MedlinePlus Health Topics Antibiotic Resistance About MedlinePlus Site Map FAQs Contact Us Get ...

  1. Antibiotic-containing polymers for localized, sustained drug delivery.

    PubMed

    Stebbins, Nicholas D; Ouimet, Michelle A; Uhrich, Kathryn E

    2014-11-30

    Many currently used antibiotics suffer from issues such as systemic toxicity, short half-life, and increased susceptibility to bacterial resistance. Although most antibiotic classes are administered systemically through oral or intravenous routes, a more efficient delivery system is needed. This review discusses the chemical conjugation of antibiotics to polymers, achieved by forming covalent bonds between antibiotics and a pre-existing polymer or by developing novel antibiotic-containing polymers. Through conjugating antibiotics to polymers, unique polymer properties can be taken advantage of. These polymeric antibiotics display controlled, sustained drug release and vary in antibiotic class type, synthetic method, polymer composition, bond lability, and antibacterial activity. The polymer synthesis, characterization, drug release, and antibacterial activities, if applicable, will be presented to offer a detailed overview of each system. PMID:24751888

  2. Antibiotic-Resistant Typhoid Spreading Across Asia, Africa

    MedlinePLUS

    ... these countries appear to have led to increased antibiotic resistance, Wong said. "Vaccinations are not currently in widespread ... As a consequence, there is a rise in antibiotic resistance to many pathogens and in particular a resurgence ...

  3. Germs in Foodborne Illness Gaining Resistance to Antibiotics

    MedlinePLUS

    ... 9, 2015 TUESDAY, June 9, 2015 (HealthDay News) -- Antibiotic resistance in foodborne germs remains a public health threat ... for Disease Control and Prevention reported online Tuesday. "Antibiotic resistance can arise spontaneously, but the greatest contribution to ...

  4. Doctors Can Cut Back on Antibiotics After Abdominal Surgery

    MedlinePLUS

    ... help efforts to battle the growing problem of antibiotic resistance, the study authors said. The study -- led by ... has an obvious downside. "The increasing prevalence of antibiotic resistance is a problem, so anything we can do ...

  5. FDA Puts Antibiotics for Food Animals Under Vet's Supervision

    MedlinePLUS

    ... them up contributes to the growing problem of antibiotic resistance in people, the agency said. The Veterinary Feed ... HealthDay . All rights reserved. More Health News on: Antibiotic Resistance Food Safety Recent Health News Related MedlinePlus Health ...

  6. Antibiotic resistance gene discovery in food-producing animals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Numerous environmental reservoirs contribute to the widespread antibiotic resistance problem in human pathogens. One environmental reservoir of particular importance is the intestinal bacteria of food-producing animals. In this review I examine recent discoveries of antibiotic resistance genes in ...

  7. Prevalence and antibiotic resistance of Salmonella in feedlot cattle 

    E-print Network

    Hudnall, Jennifer Ann

    2002-01-01

    associated with foodborne illness. Since these pathogens may be associated with consumption of undercooked meat, the importance of studying antibiotic resistance starting with the food source is apparent. We proposed to evaluate the prevalence of antibiotic...

  8. Combating biofilms and antibiotic resistance using synthetic biology

    E-print Network

    Lu, Timothy K. (Timothy Kuan-Ta), 1981-

    2008-01-01

    Bacterial infections represent a significant source of morbidity and mortality. Biofilms and antibiotic resistance pose challenges to our future ability to treat bacterial diseases with antibiotics (1). Bacteria frequently ...

  9. Sweeteners, flavorings, and dyes in antibiotic preparations.

    PubMed

    Kumar, A; Weatherly, M R; Beaman, D C

    1991-03-01

    Even though a variety of adverse effects caused by sweeteners, flavorings, and dyes in susceptible individuals have been reported, there is no good single reference with information about these substances in pediatric antimicrobials. Data on sweeteners, flavorings, and dyes in 91 antimicrobial preparations were collected. Sucrose was present in 74 (85%) of 87 preparations, followed by saccharin in 30 (34%) preparations. Mannitol, lactose, and sorbitol were each present in 7 preparations. None of the preparations were free of sweeteners. Thirty-four (37%) of 91 preparations did not specify the flavoring content. While cherry was the most common flavoring used, there were 25 other flavorings. Thirteen different dyes and coloring agents were used in these antimicrobials. Red dye no. 40 was present in 45% of preparations. Tables detailing sweeteners, flavorings, and dyes in different groups of antimicrobials (amoxicillin, ampicillin, cephalosporins, erythromycin, penicillins, sulfonamides, and others) and adverse effects reported with these inert ingredients are presented. These tables should be helpful to physicians in selecting an antimicrobial containing a different sweetener and/or dye when an adverse reaction occurs. PMID:2000275

  10. The world alliance against antibiotic resistance: consensus for a declaration.

    PubMed

    Carlet, Jean

    2015-06-15

    Antibiotic resistance is increasing worldwide and has become a very important threat to public health. The overconsumption of antibiotics is the most important cause of this problem. We created a World Alliance Against Antibiotic Resistance (WAAAR), which now includes 720 people from 55 different countries and is supported by 145 medical societies or various groups. In June 2014, WAAAR launched a declaration against antibiotic resistance. This article describes the process and the content of this declaration. PMID:25847976

  11. Emergence of antibiotic resistance from multinucleated bacterial filaments

    PubMed Central

    Bos, Julia; Zhang, Qiucen; Vyawahare, Saurabh; Rogers, Elizabeth; Rosenberg, Susan M.; Austin, Robert H.

    2015-01-01

    Bacteria can rapidly evolve resistance to antibiotics via the SOS response, a state of high-activity DNA repair and mutagenesis. We explore here the first steps of this evolution in the bacterium Escherichia coli. Induction of the SOS response by the genotoxic antibiotic ciprofloxacin changes the E. coli rod shape into multichromosome-containing filaments. We show that at subminimal inhibitory concentrations of ciprofloxacin the bacterial filament divides asymmetrically repeatedly at the tip. Chromosome-containing buds are made that, if resistant, propagate nonfilamenting progeny with enhanced resistance to ciprofloxacin as the parent filament dies. We propose that the multinucleated filament creates an environmental niche where evolution can proceed via generation of improved mutant chromosomes due to the mutagenic SOS response and possible recombination of the new alleles between chromosomes. Our data provide a better understanding of the processes underlying the origin of resistance at the single-cell level and suggest an analogous role to the eukaryotic aneuploidy condition in cancer. PMID:25492931

  12. Immobilized antibiotics to prevent orthopedic implant infections

    PubMed Central

    Hickok, Noreen J.; Shapiro, Irving M.

    2012-01-01

    Many surgical procedures require the placement of an inert or tissue-derived implant deep within the body cavity. While the majority of these implants do not become colonized by bacteria, a small percentage develops a biofilm layer that harbors invasive microorganisms. In orthopaedic surgery, unresolved periprosthetic infections can lead to implant loosening, arthrodeses, amputations and sometimes death. The focus of this review is to describe development of an implant in which an antibiotic tethered to the metal surface is used to prevent bacterial colonization and biofilm formation. Building on well-established chemical syntheses, studies show that antibiotics can be linked to titanium through a self-assembled monolayer of siloxy amines. The stable metal-antibiotic construct resists bacterial colonization and biofilm formation while remaining amenable to osteoblastic cell adhesion and maturation. In an animal model, the antibiotic modified implant resists challenges by bacteria that are commonly present in periprosthetic infections. While the long-term efficacy and stability is still to be established, ongoing studies support the view that this novel type of bioactive surface has a real potential to mitigate or prevent the devastating consequences of orthopaedic infection. PMID:22512927

  13. THE FOOD SAFETY PERSPECTIVE OF ANTIBIOTIC RESISTANCE

    Microsoft Academic Search

    P. F. McDermott; S Zhao; D. D. Wagner; S Simjee; R. D. Walker; D. G. White

    2002-01-01

    Bacterial antimicrobial resistance in both the medical and agricultural fields has become a serious problem worldwide. Antibiotic resistant strains of bacteria are an increasing threat to animal and human health, with resistance mechanisms having been identified and described for all known antimicrobials currently available for clinical use. There is currently increased public and scientific interest regarding the administration of therapeutic

  14. Macrocyclic Antibiotic Selectors in Direct HPLC Enantioseparations

    Microsoft Academic Search

    István Ilisz; Zoltán Pataj; Anita Aranyi; Antal Péter

    2012-01-01

    In the past few decades, macrocyclic antibiotic molecules have become among the most useful chiral selectors in analytical HPLC, thin-layer chromatography and capillary electrophoresis and also in preparative methods. The macrocyclic glycopeptides, such as teicoplanin, vancomycin and ristocetin A and its analogs, are perhaps the most useful selectors for the enantioseparation of nonprotected and N-protected peptides and amino acids, ?-blockers,

  15. Fast measurement of bacterial susceptibility to antibiotics

    NASA Technical Reports Server (NTRS)

    Chappelle, E. W.; Picciolo, G. L.; Schrock, C. G.

    1977-01-01

    Method, based on photoanalysis of adenosine triphosphate using light-emitting reaction with luciferase-luciferin technique, saves time by eliminating isolation period required by conventional methods. Technique is also used to determine presence of infection as well as susceptibilities to several antibiotics.

  16. Salinomycin, A Polyether Ionophoric Antibiotic, Inhibits Adipogenesis

    PubMed Central

    Szkudlarek-Mikho, Maria; Saunders, Rudel A.; Yap, Sook Fan; Ngeow, Yun Fong; Chin, Khew-Voon

    2012-01-01

    The polyether ionophoric antibiotics including monensin, salinomycin, and narasin, are widely used in veterinary medicine and as food additives and growth promoters in animal husbandry including poultry farming. Their effects on human health, however, are not fully understood. Recent studies showed that salinomycin is a cancer stem cell inhibitor. Since poultry consumption has risen sharply in the last three decades, we asked whether the consumption of meat tainted with growth promoting antibiotics might have effects on adipose cells. We showed in this report that the ionophoric antibiotics inhibit the differentiation of preadipocytes into adipocytes. The block of differentiation is not due to the induction of apoptosis nor the inhibition of cell proliferation. In addition, salinomycin also suppresses the transcriptional activity of the CCAAT/enhancer binding proteins and the peroxisome proliferator-activated receptor ?. These results suggest that the ionophoric antibiotics can be exploited as novel anti-obesity therapeutics and as pharmacological probes for the study of adipose biology. Further, the pharmacological effects of salinomycin could be a harbinger of its toxicity on the adipose tissue and other susceptible target cells in cancer therapy. PMID:23123626

  17. Properties and identification of antibiotic drug targets

    PubMed Central

    2010-01-01

    Background We analysed 48 non-redundant antibiotic target proteins from all bacteria, 22 antibiotic target proteins from E. coli only and 4243 non-drug targets from E. coli to identify differences in their properties and to predict new potential drug targets. Results When compared to non-targets, bacterial antibiotic targets tend to be long, have high ?-sheet and low ?-helix contents, are polar, are found in the cytoplasm rather than in membranes, and are usually enzymes, with ligases particularly favoured. Sequence features were used to build a support vector machine model for E. coli proteins, allowing the assignment of any sequence to the drug target or non-target classes, with an accuracy in the training set of 94%. We identified 319 proteins (7%) in the non-target set that have target-like properties, many of which have unknown function. 63 of these proteins have significant and undesirable similarity to a human protein, leaving 256 target like proteins that are not present in humans. Conclusions We suggest that antibiotic discovery programs would be more likely to succeed if new targets are chosen from this set of target like proteins or their homologues. In particular, 64 are essential genes where the cell is not able to recover from a random insertion disruption. PMID:20406434

  18. Physics and the Production of Antibiotics: 2

    ERIC Educational Resources Information Center

    Fairbrother, Robert; Riddle, Wendy; Fairbrother, Neil

    2006-01-01

    In an article in the preceding issue we discussed the design and construction of fermenters in which antibiotics are cultured. For industrial purposes these fermenters can range in size up to 500 m[cube]. They have to be sterilized, filled with sterile culture medium and the culture itself and supplied with oxygen continuously. In some cases they…

  19. Salinomycin, a polyether ionophoric antibiotic, inhibits adipogenesis

    SciTech Connect

    Szkudlarek-Mikho, Maria; Saunders, Rudel A. [Department of Medicine, Biochemistry and Cancer Biology, Center for Diabetes and Endocrine Research, College of Medicine, University of Toledo, Toledo, OH 43614 (United States)] [Department of Medicine, Biochemistry and Cancer Biology, Center for Diabetes and Endocrine Research, College of Medicine, University of Toledo, Toledo, OH 43614 (United States); Yap, Sook Fan [Faculty of Medicine and Health Sciences, Department of Pre-Clinical Sciences, University of Tunku Abdul Rahman (Malaysia)] [Faculty of Medicine and Health Sciences, Department of Pre-Clinical Sciences, University of Tunku Abdul Rahman (Malaysia); Ngeow, Yun Fong [Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603 (Malaysia)] [Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603 (Malaysia); Chin, Khew-Voon, E-mail: khew-voon.chin@utoledo.edu [Department of Medicine, Biochemistry and Cancer Biology, Center for Diabetes and Endocrine Research, College of Medicine, University of Toledo, Toledo, OH 43614 (United States)] [Department of Medicine, Biochemistry and Cancer Biology, Center for Diabetes and Endocrine Research, College of Medicine, University of Toledo, Toledo, OH 43614 (United States)

    2012-11-30

    Highlights: Black-Right-Pointing-Pointer Salinomycin inhibits preadipocyte differentiation into adipocytes. Black-Right-Pointing-Pointer Salinomycin inhibits transcriptional regulation of adipogenesis. Black-Right-Pointing-Pointer Pharmacological effects of salinomycin suggest toxicity in cancer therapy. -- Abstract: The polyether ionophoric antibiotics including monensin, salinomycin, and narasin, are widely used in veterinary medicine and as food additives and growth promoters in animal husbandry including poultry farming. Their effects on human health, however, are not fully understood. Recent studies showed that salinomycin is a cancer stem cell inhibitor. Since poultry consumption has risen sharply in the last three decades, we asked whether the consumption of meat tainted with growth promoting antibiotics might have effects on adipose cells. We showed in this report that the ionophoric antibiotics inhibit the differentiation of preadipocytes into adipocytes. The block of differentiation is not due to the induction of apoptosis nor the inhibition of cell proliferation. In addition, salinomycin also suppresses the transcriptional activity of the CCAAT/enhancer binding proteins and the peroxisome proliferator-activated receptor {gamma}. These results suggest that the ionophoric antibiotics can be exploited as novel anti-obesity therapeutics and as pharmacological probes for the study of adipose biology. Further, the pharmacological effects of salinomycin could be a harbinger of its toxicity on the adipose tissue and other susceptible target cells in cancer therapy.

  20. Phenotypic Tolerance: Antibiotic Enrichment of Noninherited Resistance in Bacterial Populations

    Microsoft Academic Search

    C. Wiuff; R. M. Zappala; R. R. Regoes; K. N. Garner; F. Baquero; B. R. Levin

    2005-01-01

    When growing bacteria are exposed to bactericidal concentrations of antibiotics, the sensitivity of the bacteria to the antibiotic commonly decreases with time, and substantial fractions of the bacteria survive. Using Escherichia coli CAB1 and antibiotics of five different classes (ampicillin, ciprofloxacin, rifampin, streptomycin, and tetracycline), we examine the details of this phenomenon and, with the aid of mathematical models, develop

  1. Analysis of Antibiotic Resistant Genes in Aquacultural Bacteria

    E-print Network

    Kane, Andrew S.

    1 Analysis of Antibiotic Resistant Genes in Aquacultural Bacteria JY Wang* YJ Geng RX Wang J Feng transfer among different bacteria · Resistant bacteria transfer to human · Antibiotic agents residue human resistance genes Su1II of Vibrio harveyi contents #12;2 Introduction 1. present status · Antibiotics

  2. Antibiotic Resistance: New Approaches to a Historical Problem

    NSDL National Science Digital Library

    Sean Kardar (Emory University; )

    2005-03-01

    The issue-focused, peer-reviewed article explains how antibiotic resistance is a continually evolving and dangerous problem that requires: future research and planning to impede a global health crisis, consideration of methods other than current antibiotic therapies, and active participation by physicians and patients in curbing antibiotic misuse.

  3. Antibiotic-Resistant Bacteria: A Challenge for the Food Industry

    Microsoft Academic Search

    Rosa Capita; Carlos Alonso-Calleja

    2011-01-01

    Antibiotic-resistant bacteria were first described in the 1940s, but whereas new antibiotics were being discovered at a steady rate, the consequences of this phenomenon were slow to be appreciated. At present, the paucity of new antimicrobials coming onto the market has led to the problem of antibiotic resistance fast escalating into a global health crisis. Although the selective pressure exerted

  4. Antibiotic efficacy is linked to bacterial cellular respiration

    PubMed Central

    Lobritz, Michael A.; Belenky, Peter; Porter, Caroline B. M.; Gutierrez, Arnaud; Yang, Jason H.; Schwarz, Eric G.; Dwyer, Daniel J.; Khalil, Ahmad S.; Collins, James J.

    2015-01-01

    Bacteriostatic and bactericidal antibiotic treatments result in two fundamentally different phenotypic outcomes—the inhibition of bacterial growth or, alternatively, cell death. Most antibiotics inhibit processes that are major consumers of cellular energy output, suggesting that antibiotic treatment may have important downstream consequences on bacterial metabolism. We hypothesized that the specific metabolic effects of bacteriostatic and bactericidal antibiotics contribute to their overall efficacy. We leveraged the opposing phenotypes of bacteriostatic and bactericidal drugs in combination to investigate their activity. Growth inhibition from bacteriostatic antibiotics was associated with suppressed cellular respiration whereas cell death from most bactericidal antibiotics was associated with accelerated respiration. In combination, suppression of cellular respiration by the bacteriostatic antibiotic was the dominant effect, blocking bactericidal killing. Global metabolic profiling of bacteriostatic antibiotic treatment revealed that accumulation of metabolites involved in specific drug target activity was linked to the buildup of energy metabolites that feed the electron transport chain. Inhibition of cellular respiration by knockout of the cytochrome oxidases was sufficient to attenuate bactericidal lethality whereas acceleration of basal respiration by genetically uncoupling ATP synthesis from electron transport resulted in potentiation of the killing effect of bactericidal antibiotics. This work identifies a link between antibiotic-induced cellular respiration and bactericidal lethality and demonstrates that bactericidal activity can be arrested by attenuated respiration and potentiated by accelerated respiration. Our data collectively show that antibiotics perturb the metabolic state of bacteria and that the metabolic state of bacteria impacts antibiotic efficacy. PMID:26100898

  5. A FRAMEWORK FOR IDENTIFYING ANTIBIOTIC RESISTANCE IN THE HUMAN MICROBIOME

    E-print Network

    A FRAMEWORK FOR IDENTIFYING ANTIBIOTIC RESISTANCE IN THE HUMAN MICROBIOME by Robert Armin Schmieder #12;#12;Abstract A Framework for Identifying Antibiotic Resistance in the Human Microbiome by Robert on antibiotics for the treatment of infectious diseases and they are critical for the suc- cess of advanced

  6. Veterinary antibiotics in the aquatic and terrestrial environment

    Microsoft Academic Search

    Nicole Kemper

    2008-01-01

    The fate of antibiotics in the environment, and especially antibiotics used in animal husbandry, is subject to recent studies and the issue of this review. The assumed quantity of antibiotics excreted by animal husbandry adds up to thousands of tonnes per year. Administered medicines, their metabolites or degradation products reach the terrestrial and aquatic environment by the application of manure

  7. Perioperative antibiotic prophylaxis in elective surgeries in Iran

    PubMed Central

    Foroutan, Behzad; Foroutan, Reza

    2014-01-01

    Background: The use of antibiotic prior to surgery is widely accepted. The WHO has recommended the use of ATC/DDD (Anatomical Therapeutic Chemical / Defined Daily Dose) for the analysis of drug utilization. The aims of the present study are 1) to analyze the assessment of prophylactic antibiotic usage prior to surgery, 2) to assess the drug administration based on antibiograms and 3) to compare the results with the national and international standards. Methods: The present study used ATC/DDD, in a retrospective manner. Cefazolin, ceftazidime, gentamicin, ciprofloxacin, metronidazole, vancomycin, imipenem and penicillin G from 21st March to 21st June 2011 were analyzed in a hospital. Out of 516 medical records, 384 patients had received prophylactic antibiotics. Results: In comparison, the orthopaedic ward had used more antibiotics. The results showed that antibiotics were not selected based on the antibiogram antibiotic programs. Patients in the age range of 20-30 years were the most recipients of the antibiotics. Men had received more antibiotic in comparison with women. About 75% (384 out of 516) of patients in the study received antibiotics as prophylaxis. Cefazolin was the most frequently prescribed antibiotic. Conclusion: Our findings showed differences in comparison with national and international studies, but insignificant differences. Data on in-hospital antibiotic usage are varying widely not only due to different antibiotic policies but also due to different methods of mesurement. These differences make the comparison difficult. PMID:25405131

  8. A Large Scale Data Mining Approach to Antibiotic Resistance Surveillance

    E-print Network

    Yang, Junfeng

    A Large Scale Data Mining Approach to Antibiotic Resistance Surveillance Eugenia G. Giannopoulou1 of antibiotic resistance. Several traditional methods used to measure it do not provide adequate and promising Undoubtedly, antibiotic resistance is a global problem whose origins can be traced to hospitals; places where

  9. PHARMACOLOGY RESEARCH, SAFETY TESTING AND REGULATION SERIES ANTIBIOTIC RESISTANCE

    E-print Network

    Hemminga, Marcus A.

    #12;#12;PHARMACOLOGY ­ RESEARCH, SAFETY TESTING AND REGULATION SERIES ANTIBIOTIC RESISTANCE: CAUSES Substances S. B. Zotov and O. I. Tuzhikov ISBN: 978-1-60741-973-0 Antibiotic Resistance: Causes and Risk-1-60741-623-4 #12;PHARMACOLOGY ­ RESEARCH, SAFETY TESTING AND REGULATION SERIES ANTIBIOTIC RESISTANCE: CAUSES

  10. Evaluating state-specific antibiotic resistance measures derived from central line-associated bloodstream infections, national healthcare safety network, 2011.

    PubMed

    Soe, Minn M; Edwards, Jonathan R; Sievert, Dawn M; Ricks, Philip M; Magill, Shelley S; Fridkin, Scott K

    2015-01-01

    DISCLOSURE The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention or the Agency for Toxic Substances and Diseases Registry. OBJECTIVE Describe the impact of standardizing state-specific summary measures of antibiotic resistance that inform regional interventions to reduce transmission of resistant pathogens in healthcare settings. DESIGN Analysis of public health surveillance data. METHODS Central line-associated bloodstream infection (CLABSI) data from intensive care units (ICUs) of facilities reporting to the National Healthcare Safety Network in 2011 were analyzed. For CLABSI due to methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum cephalosporin (ESC)-nonsusceptible Klebsiella species, and carbapenem-nonsusceptible Klebsiella species, we computed 3 state-level summary measures of nonsusceptibility: crude percent nonsusceptible, model-based adjusted percent nonsusceptible, and crude infection incidence rate. RESULTS Overall, 1,791 facilities reported CLABSIs from ICU patients. Of 1,618 S. aureus CLABSIs with methicillin-susceptibility test results, 791 (48.9%) were due to MRSA. Of 756 Klebsiella CLABSIs with ESC-susceptibility test results, 209 (27.7%) were due to ESC-nonsusceptible Klebsiella, and among 661 Klebsiella CLABSI with carbapenem susceptibility test results, 70 (10.6%) were due to carbapenem-nonsusceptible Klebsiella. All 3 state-specific measures demonstrated variability in magnitude by state. Adjusted measures, with few exceptions, were not appreciably different from crude values for any phenotypes. When linking values of crude and adjusted percent nonsusceptible by state, a state's absolute rank shifted slightly for MRSA in 5 instances and only once each for ESC-nonsusceptible and carbapenem-nonsusceptible Klebsiella species. Infection incidence measures correlated strongly with both percent nonsusceptibility measures. CONCLUSIONS Crude state-level summary measures, based on existing NHSN CLABSI data, may suffice to assess geographic variability in antibiotic resistance. As additional variables related to antibiotic resistance become available, risk-adjusted summary measures are preferable. PMID:25627762

  11. Effect of River Landscape on the sediment concentrations of antibiotics and corresponding antibiotic resistance genes (ARG)

    Microsoft Academic Search

    Ruoting Pei; Sung-Chul Kim; Kenneth H. Carlson; Amy Pruden

    2006-01-01

    The purpose of this study was to quantify antibiotic resistance genes (ARG) in the sediments of the mixed-landscape Cache La Poudre River, which has previously been studied and shown to have high concentrations of antibiotics related to urban and agricultural activities. River sediments were sampled during two events (high-flow and low-flow) from five sites with varying urban and agricultural impact

  12. Perceptions among Swedish hospital physicians on prescribing of antibiotics and antibiotic resistance

    Microsoft Academic Search

    I. Bjorkman; J. Berg; M. Roing; M. Erntell; C. S. Lundborg

    2010-01-01

    ObjectiveTo explore and describe perceptions of antibiotic prescribing among Swedish hospital physicians, with special reference to whether the perceptions included awareness of antibiotic resistance (AR).DesignA phenomenographic approach was used and data were collected in face-to-face interviews.SettingHospitals in seven different counties in central Sweden.ParticipantsA strategic sample of 20 hospital physicians specialising in internal medicine, surgery or urology.Main outcomeThe variation of perceptions

  13. Burden of Antibiotic Resistance in Common Infectious Diseases: Role of Antibiotic Combination Therapy

    PubMed Central

    Dargad, Ramesh R; Borade, Dhammraj M; Swami, Onkar C

    2014-01-01

    Globally, antimicrobial resistance is alarming concern especially in commonly reported disease entities like respiratory tract infection, enteric fever and infections associated with gram-negative bacilli (GNB). Rational use of antimicrobial drugs reported significant decrease in bacterial burden and may also reduce the risk of disease progression. However, at times in particular indication, certain patient and pathogen factor limits the selection and use of specific antibiotic therapy while in some case, due to presence of additional risk factor, aggressive therapy is required to achieve clinical reemission and prevent complications. Delay in start of suitable antibiotic therapy is another imperative factor for treatment failure and rise of drug resistance. With rapidly increasing antibiotic resistance and decline in new antibiotic drug development, the toughest challenge remains to maintain and preserve the efficacy of currently available antibiotics. Therefore, the best rational approach to fight these infections is to ‘hit early and hit hard’ and kills drug-susceptible bacteria before they become resistant. The preferred approach is to deploy two antibiotics that produce a stronger effect in combination than if either drug were used alone. Various society guidelines in particular indications also justify and recommend the use of combination of antimicrobial therapy. Combination therapies have distinct advantage over monotherapy in terms of broad coverage, synergistic effect and prevention of emergence of drug resistance. PMID:25121020

  14. Antibiotic stewardship and consumption: findings from a pan-European hospital study

    Microsoft Academic Search

    J. Bruce; F. M. MacKenzie; B. Cookson; J. Mollison; V. Krcmery; I. M. Gould

    2009-01-01

    OBJECTIVES: Much has been written about antibiotic stewardship although less is known about the structure and content of antibiotic policies at hospital level. As part of the European Commission Concerted Action Antibiotic Resistance Prevention And Control (ARPAC) Project, data on antibiotic stewardship were collated and relationships investigated by antibiotic consumption in European hospitals. METHODS: A questionnaire survey on antibiotic stewardship

  15. The effects of subtherapeutic antibiotic use in farm animals on the proliferation and persistence of antibiotic resistance among soil bacteria

    Microsoft Academic Search

    Sudeshna Ghosh; Timothy M LaPara

    2007-01-01

    The use of antibiotics at subtherapeutic concentrations for agricultural applications is believed to be an important factor in the proliferation of antibiotic-resistant bacteria. The goal of this study was to determine if the application of manure onto agricultural land would result in the proliferation of antibiotic resistance among soil bacteria. Chlortetracycline-resistant bacteria were enumerated and characterized from soils exposed to

  16. Antibiotics in Canadian poultry productions and anticipated alternatives.

    PubMed

    Diarra, Moussa S; Malouin, François

    2014-01-01

    The use of antibiotics in food-producing animals has significantly increased animal health by lowering mortality and the incidence of diseases. Antibiotics also have largely contributed to increase productivity of farms. However, antibiotic usage in general and relevance of non-therapeutic antibiotics (growth promoters) in feed need to be reevaluated especially because bacterial pathogens of humans and animals have developed and shared a variety of antibiotic resistance mechanisms that can easily be spread within microbial communities. In Canada, poultry production involves more than 2600 regulated chicken producers who have access to several antibiotics approved as feed additives for poultry. Feed recipes and mixtures vary greatly geographically and from one farm to another, making links between use of a specific antibiotic feed additive and production yields or selection of specific antibiotic-resistant bacteria difficult to establish. Many on-farm studies have revealed the widespread presence of antibiotic-resistant bacteria in broiler chickens. While some reports linked the presence of antibiotic-resistant organisms to the use of feed supplemented with antibiotics, no recent studies could clearly demonstrate the benefit of antimicrobial growth promoters on performance and production yields. With modern biosecurity and hygienic practices, there is a genuine concern that intensive utilization of antibiotics or use of antimicrobial growth promoters in feed might no longer be useful. Public pressure and concerns about food and environmental safety (antibiotic residues, antibiotic-resistant pathogens) have driven researchers to actively look for alternatives to antibiotics. Some of the alternatives include pre- and probiotics, organic acids and essential oils. We will describe here the properties of some bioactive molecules, like those found in cranberry, which have shown interesting polyvalent antibacterial and immuno-stimulatory activities. PMID:24987390

  17. Antibiotics in Canadian poultry productions and anticipated alternatives

    PubMed Central

    Diarra, Moussa S.; Malouin, François

    2014-01-01

    The use of antibiotics in food-producing animals has significantly increased animal health by lowering mortality and the incidence of diseases. Antibiotics also have largely contributed to increase productivity of farms. However, antibiotic usage in general and relevance of non-therapeutic antibiotics (growth promoters) in feed need to be reevaluated especially because bacterial pathogens of humans and animals have developed and shared a variety of antibiotic resistance mechanisms that can easily be spread within microbial communities. In Canada, poultry production involves more than 2600 regulated chicken producers who have access to several antibiotics approved as feed additives for poultry. Feed recipes and mixtures vary greatly geographically and from one farm to another, making links between use of a specific antibiotic feed additive and production yields or selection of specific antibiotic-resistant bacteria difficult to establish. Many on-farm studies have revealed the widespread presence of antibiotic-resistant bacteria in broiler chickens. While some reports linked the presence of antibiotic-resistant organisms to the use of feed supplemented with antibiotics, no recent studies could clearly demonstrate the benefit of antimicrobial growth promoters on performance and production yields. With modern biosecurity and hygienic practices, there is a genuine concern that intensive utilization of antibiotics or use of antimicrobial growth promoters in feed might no longer be useful. Public pressure and concerns about food and environmental safety (antibiotic residues, antibiotic-resistant pathogens) have driven researchers to actively look for alternatives to antibiotics. Some of the alternatives include pre- and probiotics, organic acids and essential oils. We will describe here the properties of some bioactive molecules, like those found in cranberry, which have shown interesting polyvalent antibacterial and immuno-stimulatory activities. PMID:24987390

  18. Rational Design of Antibiotic Treatment Plans: A Treatment Strategy for Managing Evolution and Reversing Resistance

    PubMed Central

    Mira, Portia M.; Crona, Kristina; Greene, Devin; Meza, Juan C.; Sturmfels, Bernd; Barlow, Miriam

    2015-01-01

    The development of reliable methods for restoring susceptibility after antibiotic resistance arises has proven elusive. A greater understanding of the relationship between antibiotic administration and the evolution of resistance is key to overcoming this challenge. Here we present a data-driven mathematical approach for developing antibiotic treatment plans that can reverse the evolution of antibiotic resistance determinants. We have generated adaptive landscapes for 16 genotypes of the TEM ?-lactamase that vary from the wild type genotype “TEM-1” through all combinations of four amino acid substitutions. We determined the growth rate of each genotype when treated with each of 15 ?-lactam antibiotics. By using growth rates as a measure of fitness, we computed the probability of each amino acid substitution in each ?-lactam treatment using two different models named the Correlated Probability Model (CPM) and the Equal Probability Model (EPM). We then performed an exhaustive search through the 15 treatments for substitution paths leading from each of the 16 genotypes back to the wild type TEM-1. We identified optimized treatment paths that returned the highest probabilities of selecting for reversions of amino acid substitutions and returning TEM to the wild type state. For the CPM model, the optimized probabilities ranged between 0.6 and 1.0. For the EPM model, the optimized probabilities ranged between 0.38 and 1.0. For cyclical CPM treatment plans in which the starting and ending genotype was the wild type, the probabilities were between 0.62 and 0.7. Overall this study shows that there is promise for reversing the evolution of resistance through antibiotic treatment plans. PMID:25946134

  19. Managing Expectations of Antibiotics for Upper Respiratory Tract Infections: A Qualitative Study

    PubMed Central

    Mustafa, Mohammed; Wood, Fiona; Butler, Christopher C.; Elwyn, Glyn

    2014-01-01

    PURPOSE Communication experts have suggested that it is good practice to ask patients’ directly whether they expect to receive antibiotics as part of asking about the triad of ideas, concerns, and expectations for health care. Our aim was to explore the views and experiences of family physicians about using this strategy with their patients, focusing the interview on the problem of eliciting expectations of antibiotics as a possible treatment for upper respiratory tract infections. METHODS We conducted a qualitative study using semistructured interviews with 20 family physicians in South Wales, United Kingdom, and performing thematic analysis. RESULTS Family physicians assumed most patients or parents wanted antibiotics, as well as wanting to be “checked out” to make sure the illness was “nothing serious.” Physicians said they did not ask direct questions about expectations, as that might lead to confrontation. They preferred to elicit expectations for antibiotics in an indirect manner, before performing a physical examination. The majority described reporting their findings of the examination as a “running commentary” so as to influence expectations and help avoid generating resistance to a soon-to-be-made-explicit plan not to prescribe antibiotics. The physicians used the running commentary to preserve and enhance the physician-patient relationship. CONCLUSIONS Real-world family physicians use indirect methods to explore expectations for treatment and, on the basis of their physical examination, build an argument for reassuring the patient or parent. In contrast to proposed models in the communication literature, interventions to promote appropriate antibiotic prescribing might include a focus on training in communication skills that (1) integrates these indirect methods as part of building collaborative physician-patient relationships and (2) uses the running commentary of examination findings to facilitate participation in clinical decisions. PMID:24445101

  20. Increased Antibiotic Release from a Bone Cement Containing Bacterial Cellulose

    Microsoft Academic Search

    Ryuji Mori; Takahisa Nakai; Koichi Enomoto; Yuji Uchio; Katsumi Yoshino

    2011-01-01

    Background  Major disadvantages of antibiotic bone cements include limited drug release and reduced strength resulting from the addition\\u000a of high doses of antibiotics. Bacterial cellulose, a three-dimensional hydrophilic mesh, may retain antibiotics and release\\u000a them gradually. We hypothesized that the addition of cellulose to antibiotic bone cement would improve mechanical strength\\u000a and antibiotic release.\\u000a \\u000a \\u000a \\u000a \\u000a Questions\\/purposes  We therefore examined the mechanical strength and

  1. Photochemical behavior of antibiotics impacted by complexation effects of concomitant metals: a case for ciprofloxacin and Cu(ii).

    PubMed

    Wei, Xiaoxuan; Chen, Jingwen; Xie, Qing; Zhang, Siyu; Li, Yingjie; Zhang, Yifei; Xie, Hongbin

    2015-07-01

    Many water bodies, especially those adjacent to aquaculture and livestock breeding areas, are contaminated by both antibiotics and transition metals. However, the effects of the interaction between antibiotics and transition metals on the environmental behavior and the ecotoxicology of antibiotics are largely unknown. We hypothesized that antibiotics may coordinately bind with metal ions, and this complexation may affect the environmental photochemical behavior of antibiotics. We took ciprofloxacin (CIP) and Cu(ii) as a case, and employed simulated sunlight experiments and density functional theory calculations to investigate the underlying reaction mechanisms. The results showed that monovalent cationic ciprofloxacin (H2CIP(+)) that is predominant in the normal pH range (6-9) of surface waters can chelate with hydrated Cu(ii) to form [Cu(H2CIP)(H2O)4](3+). Compared with H2CIP(+), [Cu(H2CIP)(H2O)4](3+) has different molecular orbitals, and atomic charge distribution. As a result, [Cu(H2CIP)(H2O)4](3+) showed dissimilar light absorption properties, slower direct photolytic rates, lower (1)O2 generation ability and weaker reactivity towards (1)O2. Due to the Cu(ii) complexation, the apparent photodegradation of H2CIP(+) was inhibited, and the photolytic pathways and product distribution were altered. This study implies that for an accurate ecological risk assessment of antibiotics under transition metal co-contamination conditions, the effects of metal complexation should be considered. PMID:26114263

  2. Delayed commitment to evolutionary fate in antibiotic resistance fitness landscapes.

    PubMed

    Palmer, Adam C; Toprak, Erdal; Baym, Michael; Kim, Seungsoo; Veres, Adrian; Bershtein, Shimon; Kishony, Roy

    2015-01-01

    Predicting evolutionary paths to antibiotic resistance is key for understanding and controlling drug resistance. When considering a single final resistant genotype, epistatic contingencies among mutations restrict evolution to a small number of adaptive paths. Less attention has been given to multi-peak landscapes, and while specific peaks can be favoured, it is unknown whether and how early a commitment to final fate is made. Here we characterize a multi-peaked adaptive landscape for trimethoprim resistance by constructing all combinatorial alleles of seven resistance-conferring mutations in dihydrofolate reductase. We observe that epistatic interactions increase rather than decrease the accessibility of each peak; while they restrict the number of direct paths, they generate more indirect paths, where mutations are adaptively gained and later adaptively lost or changed. This enhanced accessibility allows evolution to proceed through many adaptive steps while delaying commitment to genotypic fate, hindering our ability to predict or control evolutionary outcomes. PMID:26060115

  3. In-feed antibiotic effects on the swine intestinal microbiome

    PubMed Central

    Looft, Torey; Johnson, Timothy A.; Allen, Heather K.; Bayles, Darrell O.; Alt, David P.; Stedtfeld, Robert D.; Sul, Woo Jun; Stedtfeld, Tiffany M.; Chai, Benli; Cole, James R.; Hashsham, Syed A.; Tiedje, James M.; Stanton, Thad B.

    2012-01-01

    Antibiotics have been administered to agricultural animals for disease treatment, disease prevention, and growth promotion for over 50 y. The impact of such antibiotic use on the treatment of human diseases is hotly debated. We raised pigs in a highly controlled environment, with one portion of the littermates receiving a diet containing performance-enhancing antibiotics [chlortetracycline, sulfamethazine, and penicillin (known as ASP250)] and the other portion receiving the same diet but without the antibiotics. We used phylogenetic, metagenomic, and quantitative PCR-based approaches to address the impact of antibiotics on the swine gut microbiota. Bacterial phylotypes shifted after 14 d of antibiotic treatment, with the medicated pigs showing an increase in Proteobacteria (1–11%) compared with nonmedicated pigs at the same time point. This shift was driven by an increase in Escherichia coli populations. Analysis of the metagenomes showed that microbial functional genes relating to energy production and conversion were increased in the antibiotic-fed pigs. The results also indicate that antibiotic resistance genes increased in abundance and diversity in the medicated swine microbiome despite a high background of resistance genes in nonmedicated swine. Some enriched genes, such as aminoglycoside O-phosphotransferases, confer resistance to antibiotics that were not administered in this study, demonstrating the potential for indirect selection of resistance to classes of antibiotics not fed. The collateral effects of feeding subtherapeutic doses of antibiotics to agricultural animals are apparent and must be considered in cost-benefit analyses. PMID:22307632

  4. Low-density polypropylene meshes coated with resorbable and biocompatible hydrophilic polymers as controlled release agents of antibiotics.

    PubMed

    Fernandez-Gutierrez, Mar; Olivares, Enrique; Pascual, Gemma; Bellon, Juan M; San Román, Julio

    2013-04-01

    The application of bioactive meshes in abdominal surgery for the repair of hernias is an increasing clinical activity in a wide sector of the population. The main secondary effect is the appearance of infections from bacteria, specifically Staphylococcus aureus and S. epidermidis. This paper describes the development and application of low-density polypropylene meshes coated with a biocompatible and resorbable polymer as a controlled release system of the antibiotic vancomycin. The polymeric coating (a non-cross-linked copolymer of 2-hydroxyethyl methacrylate and 2-acrylamido-2-methylpropanesulfonic acid) has a thickness of 14-15?m and contains 0.32mgcm(-2) of the antibiotic vancomycin. The in vitro experiments demonstrate the excellent inhibitory character of the coated meshes loaded with the antibiotic, following the standard protocol of inhibition of halo in agar diffusion test. This inhibitory effect is maintained for a relatively long period (at least 14days) with a low concentration of antibiotic. The acrylic polymer system regulates the release of the antibiotic with a rate of 24?gh(-1), due to its slow dissolution in the medium. Experiments in vivo, based on the implantation of coated meshes, demonstrate that the system controls the infection in the animal (rabbits) for at least 30days. The concentration of antibiotic in the blood stream of the rabbits was below the detection limit of the analytical technique (<1-2?gml(-1)), which demonstrates that the antibiotic is released in the local area of the implant and remains concentrated at the implantation site, without diffusion to the blood stream. The systems can be applied to other medical devices and implants for the application of new-generation antibiotics in a controlled release and targeted applications. PMID:23261925

  5. Botanical alternatives to antibiotics for use in organic poultry production.

    PubMed

    Diaz-Sanchez, Sandra; D'Souza, Doris; Biswas, Debrabrata; Hanning, Irene

    2015-06-01

    The development of antibiotic resistant pathogens has resulted from the use of sub-therapeutic concentrations of antibiotics delivered in poultry feed. Furthermore, there are a number of consumer concerns regarding the use of antibiotics in food animals including residue contamination of poultry products and antibiotic resistant bacterial pathogens. These issues have resulted in recommendations to reduce the use of antibiotics as growth promoters in livestock in the United States. Unlike conventional production, organic systems are not permitted to use antibiotics. Thus, both conventional and organic poultry production need alternative methods to improve growth and performance of poultry. Herbs, spices, and various other plant extracts are being evaluated as alternatives to antibiotics and some do have growth promoting effects, antimicrobial properties, and other health-related benefits. This review aims to provide an overview of herbs, spices, and plant extracts, currently defined as phytobiotics as potential feed additives. PMID:25743421

  6. Generic antibiotic industries: Challenges and implied strategies with regulatory perspectives

    PubMed Central

    Venkatesh, M.; Bairavi, V. G.; Sasikumar, K. C.

    2011-01-01

    Ever since the discovery of antibiotics, the quality of human life greatly improved in the 20th century. The discovery of penicillin transformed the medicine industry and initiated a search for a better antibiotic every time resulting in several synthetic and semi-synthetic antibiotics. Beginning with the 1937 sulfa drug tragedy, the drug regulations had a parallel growth along with the antibiotics and the antibiotic-based generic Pharma industries. This review article is focused on the scenario depicting current global Pharma industries based on generic antibiotics. Several regulatory aspects involved with these industries have been discussed along with the complexity of the market, issues that could affect their growth, their struggle for quality, and their compliance with the tightened regulations. With the skyrocketing commercialization of antibiotics through generics and the leveraging technologic renaissance, generic industries are involved in providing maximum safer benefits for the welfare of the people, highlighting its need today.. PMID:21430959

  7. Systemic Antibiotic Therapy for Chronic Osteomyelitis in Adults

    PubMed Central

    Lipsky, Benjamin A.

    2012-01-01

    The standard recommendation for treating chronic osteomyelitis is 6 weeks of parenteral antibiotic therapy. However, oral antibiotics are available that achieve adequate levels in bone, and there are now more published studies of oral than parenteral antibiotic therapy for patients with chronic osteomyelitis. Oral and parenteral therapies achieve similar cure rates; however, oral therapy avoids risks associated with intravenous catheters and is generally less expensive, making it a reasonable choice for osteomyelitis caused by susceptible organisms. Addition of adjunctive rifampin to other antibiotics may improve cure rates. The optimal duration of therapy for chronic osteomyelitis remains uncertain. There is no evidence that antibiotic therapy for >4–6 weeks improves outcomes compared with shorter regimens. In view of concerns about encouraging antibiotic resistance to unnecessarily prolonged treatment, defining the optimal route and duration of antibiotic therapy and the role of surgical debridement in treating chronic osteomyelitis are important, unmet needs. PMID:22157324

  8. Engineering persister-specific antibiotics with synergistic antimicrobial functions.

    PubMed

    Schmidt, Nathan W; Deshayes, Stephanie; Hawker, Sinead; Blacker, Alyssa; Kasko, Andrea M; Wong, Gerard C L

    2014-09-23

    Most antibiotics target growth processes and are ineffective against persister bacterial cells, which tolerate antibiotics due to their reduced metabolic activity. These persisters act as a genetic reservoir for resistant mutants and constitute a root cause of antibiotic resistance, a worldwide problem in human health. We re-engineer antibiotics specifically for persisters using tobramycin, an aminoglycoside antibiotic that targets bacterial ribosomes but is ineffective against persisters with low metabolic and cellular transport activity. By giving tobramycin the ability to induce nanoscopic negative Gaussian membrane curvature via addition of 12 amino acids, we transform tobramycin itself into a transporter sequence. The resulting molecule spontaneously permeates membranes, retains the high antibiotic activity of aminoglycosides, kills E. coli and S. aureus persisters 4-6 logs better than tobramycin, but remains noncytotoxic to eukaryotes. These results suggest a promising paradigm to renovate traditional antibiotics. PMID:25130648

  9. Antibiotic Administration Routes Significantly Influence the Levels of Antibiotic Resistance in Gut Microbiota

    PubMed Central

    Zhang, Lu; Huang, Ying; Zhou, Yang; Buckley, Timothy

    2013-01-01

    This study examined the impact of oral exposure to antibiotic-resistant bacteria and antibiotic administration methods on antibiotic resistance (AR) gene pools and the profile of resistant bacteria in host gastrointestinal (GI) tracts using C57BL/6J mice with natural gut microbiota. Mice inoculated with a mixture of tet(M)-carrying Enterococcus spp. or blaCMY-2-carrying Escherichia coli were treated with different doses of tetracycline hydrochloride (Tet) or ampicillin sodium (Amp) and delivered via either feed or intravenous (i.v.) injection. Quantitative PCR assessment of mouse fecal samples revealed that (i) AR gene pools were below the detection limit in mice without prior inoculation of AR gene carriers regardless of subsequent exposure to corresponding antibiotics; (ii) oral exposure to high doses of Tet and Amp in mice inoculated with AR gene carriers led to rapid enrichment of corresponding AR gene pools in feces; (iii) significantly less or delayed development of AR in the GI tract of the AR carrier-inoculated mice was observed when the same doses of antibiotics were administered via i.v. injection rather than oral administration; and (iv) antibiotic dosage, and maybe the excretion route, affected AR in the GI tract. The shift of dominant AR bacterial populations in the gut microbiota was consistent with the dynamics of AR gene pools. The emergence of endogenous resistant bacteria in the gut microbiota corresponding to drug exposure was also observed. Together, these data suggest that oral administration of antibiotics has a prominent effect on AR amplification and development in gut microbiota, which may be minimized by alternative drug administration approaches, as illustrated by i.v. injection in this study and proper drug selection. PMID:23689712

  10. Vancomycin Molecular Interactions: Antibiotic and Enantioselective Mechanisms

    NASA Astrophysics Data System (ADS)

    Ward, Timothy J.; Gilmore, Aprile; Ward, Karen; Vowell, Courtney

    Medical studies established that vancomycin and other related macrocyclic antibiotics have an enhanced antimicrobial activity when they are associated as dimers. The carbohydrate units attached to the vancomycin basket have an essential role in the dimerization reaction. Covalently synthesized dimers were found active against vancomycin-resistant bacterial strains. A great similarity between antibiotic potential and enantioselectivity was established. A covalent vancomycin dimer was studied in capillary electrophoresis producing excellent chiral separation of dansyl amino acids. Balhimycin is a macrocyclic glycopeptide structurally similar to vancomycin. The small differences are, however, responsible for drastic differences in enantioselectivity in the same experimental conditions. Contributions from studies examining vancomycin's mechanism for antimicrobial activity have substantially aided our understanding of its mechanism in chiral recognition.

  11. Antibiotic resistant bacteria in Chesapeake Bay

    Microsoft Academic Search

    R. C. Morgan; P. Guerry; R. R. Colwell

    1976-01-01

    Water and shellfish samples were collected in Chesapeake Bay during February and March 1975, for bacteriological analyses,\\u000a which included enumeration and identification of coliform bacteria resistant to multiple antibioties. Water samples were analyzed\\u000a using eosin-methylene blue (EMB) agar supplemented with antibiotics. Shellfish samples were analyzed following accepted methods\\u000a for examination of shellfish for coliforms and fecal coliforms. Pure cultures were

  12. HLA and antibiotic allergic skin eruption.

    PubMed

    Chan, S H; Tan, T; Wee, G B; Lim, A Y

    1988-10-01

    Chinese patients with cutaneous eruption due to antibiotics were found to be positively associated with HLA-BW46 (RR = 2.5; 95% confidence limit 1.2-4.9) and negatively associated with HLA-B40 (RR = 0.46; 95% confidence limit 0.22-0.98). The association with HLA-BW46 was even higher in patients with ampicillin sensitivity (RR = 3.5; 95% confidence limit 1.4-9.0). PMID:2975936

  13. Assay of the Antibiotic Activity of Serum

    PubMed Central

    Traub, Walter H.

    1969-01-01

    One of the drawbacks of the “tube dilution” method for the assay of antibiotics in human serum has been illustrated by utilizing serum-sensitive and serum-resistant strains of Escherichia coli. In the case of serum-sensitive strains, it was found that fresh serum alone may account for the same degree of inhibition and thus yield minimal inhibitory concentrations identical to those obtained with serum combined with antibiotics, that is, “simulated” serum assay specimens. This fallacy of the method is discussed with regard to those instances in which laboratories were merely to utilize the patient's own coliform organism as the test organism, or with respect to the assay of, for example, polymyxins, in which inadvertently a R(ough) and therefore, serum-sensitive strain of E. coli were to be used as the indicator organism. It is recommended that serum-resistant laboratory strains of Staphylococcus aureus or E. coli of known antibiotic susceptibility be employed as the test organisms proper in order to circumvent the inherent bactericidal activity of serum. PMID:4309084

  14. Colistin: Revival of an Old Polymyxin Antibiotic.

    PubMed

    Dijkmans, Anneke C; Wilms, Erik B; Kamerling, Ingrid M C; Birkhoff, Willem; Ortiz-Zacarías, Natalia V; van Nieuwkoop, Cees; Verbrugh, Henri A; Touw, Daan J

    2015-08-01

    Colistin (polymyxin E) is a positively charged deca-peptide antibiotic that disrupts the integrity of the outer membrane of the cell wall of gram-negative bacteria by binding to the lipid A moiety of lipopolysaccharides, resulting in cell death. The endotoxic activity of lipopolysaccharides is simultaneously inhibited. Colistin is increasingly being prescribed as rescue treatment for infections with multidrug-resistant bacilli. Nephrotoxicity and, to a lesser degree, neurotoxicity occur often during systemic colistin therapy, and have severely limited its application in the past. However, these side effects are largely reversible and can be managed through close monitoring. The prodrug colistimethate sodium (CMS) is less toxic and is, therefore, the preferred formulation for parenteral administration. Importantly, resistance to colistin seems to emerge often unless it is combined with another antibiotic, but further studies into this phenomenon are necessary. Pharmacokinetic and pharmacodynamic properties have received little attention, partly because of the physicochemical peculiarities of polymyxin antibiotics, especially their propensity to stick to other molecules and surfaces. The ratio between the area under the curve of free colistin and the pathogen's Minimal Inhibitory Concentration (MIC) best predicts microbiological and clinical responses, but more studies are needed in this area. Likewise, further standardization is needed in production and labeling of colistin formulations, and in the way the susceptibility of bacteria to colistin is determined. PMID:25549206

  15. Systemic antibiotics in the treatment of periodontitis.

    PubMed

    Feres, Magda; Figueiredo, Luciene C; Soares, Geisla M Silva; Faveri, Marcelo

    2015-02-01

    Despite the fact that several clinical studies have shown additional benefits when certain systemic antibiotics are used as adjuncts to periodontal treatment, clear guidelines for the use of these agents in the clinical practice are not yet available. Basic questions concerning the use of systemic antibiotics to treat periodontitis remain unanswered, such as: which drug(s) should be used; which patients would most benefit from treatment; which are the most effective protocols (i.e. doses and durations); and in which phase of the mechanical therapy should the drug(s) be administered? Although not all of those questions have been directly addressed by controlled randomized clinical trials, recent concepts related to the ecology of periodontal diseases, as well as the major advances in laboratory and clinical research methods that have occurred in the past decade, have significantly broadened our knowledge in this field. This article endeavored to provide a 'state of the art' overview on the use of systemic antibiotics in the treatment of periodontitis, based on the most recent literature on the topic as well as on a compilation of data from studies conducted at the Center of Clinical Trials at Guarulhos University (São Paulo, Brazil) from 2002 to 2012. PMID:25494600

  16. Antibiotic Produced by Fusarium equiseti NRRL 5537

    PubMed Central

    Burmeister, H. R.; Bennett, G. A.; Vesonder, R. F.; Hesseltine, C. W.

    1974-01-01

    Fusarium equiseti NRRL 5537 grown on an autoclaved white corn grit medium for 3 to 4 weeks at room temperature produced a substance in excess of 5 g/kg of substrate that inhibited some gram-positive bacteria including mycobacteria. Most Bacillus subtilis, Mycobacterium phlei, and Staphylococcus aureus strains were inhibited when 1 ?g of the antibiotic per ml was incorporated into the culture medium. Except for Neisseria perflava, gram-negative bacteria, yeasts, and molds were not inhibited by 128 ?g/ml. The antibiotic was recovered as a white powder, had a melting point of 65 to 66 C, and had an intraperitoneal mean lethal dose in white mice of 63 mg/kg of body weight. In thin-layer chromatographic analysis the compound appeared as a single spot in two different solvent systems. Mass spectrometry determined that the molecular weight of the antibiotic was 373 with a molecular formula of C22H31NO4. Chemical microanalysis was in accord with the formula. PMID:15825417

  17. Aminoglycoside antibiotics induce bacterial biofilm formation.

    PubMed

    Hoffman, Lucas R; D'Argenio, David A; MacCoss, Michael J; Zhang, Zhaoying; Jones, Roger A; Miller, Samuel I

    2005-08-25

    Biofilms are adherent aggregates of bacterial cells that form on biotic and abiotic surfaces, including human tissues. Biofilms resist antibiotic treatment and contribute to bacterial persistence in chronic infections. Hence, the elucidation of the mechanisms by which biofilms are formed may assist in the treatment of chronic infections, such as Pseudomonas aeruginosa in the airways of patients with cystic fibrosis. Here we show that subinhibitory concentrations of aminoglycoside antibiotics induce biofilm formation in P. aeruginosa and Escherichia coli. In P. aeruginosa, a gene, which we designated aminoglycoside response regulator (arr), was essential for this induction and contributed to biofilm-specific aminoglycoside resistance. The arr gene is predicted to encode an inner-membrane phosphodiesterase whose substrate is cyclic di-guanosine monophosphate (c-di-GMP)-a bacterial second messenger that regulates cell surface adhesiveness. We found that membranes from arr mutants had diminished c-di-GMP phosphodiesterase activity, and P. aeruginosa cells with a mutation changing a predicted catalytic residue of Arr were defective in their biofilm response to tobramycin. Furthermore, tobramycin-inducible biofilm formation was inhibited by exogenous GTP, which is known to inhibit c-di-GMP phosphodiesterase activity. Our results demonstrate that biofilm formation can be a specific, defensive reaction to the presence of antibiotics, and indicate that the molecular basis of this response includes alterations in the level of c-di-GMP. PMID:16121184

  18. Increases of Antibiotic Resistance in Excessive Use of Antibiotics in Smallholder Dairy Farms in Northern Thailand

    PubMed Central

    Suriyasathaporn, W.; Chupia, V.; Sing-Lah, T.; Wongsawan, K.; Mektrirat, R.; Chaisri, W.

    2012-01-01

    Antibiotic resistance patterns of bacterial isolates from both quarter teat-tip swabs and their quarter milk samples were evaluated in smallholder dairy farms in northern Thailand with excessive use of antibiotics (HIGH) compared with normal use (NORM). Results from teat-tip swab samples showed that the percentage of Bacillus spp. resistance to overall antibiotics was significantly lower in the NORM group than that of the HIGH group, whereas, the resistance percentage of coagulase-negative staphylococci in the NORM group was higher than that of the HIGH one. The overall mastitis-causing bacteria isolated from milk samples were environmental streptococci (13.8%), coagulase-negative staphylococci (9.9%), Staphylococcus aureus (5.4%), and Corynebacterium bovis (4.5%). Both staphylococci and streptococci had significantly higher percentages of resistance to cloxacillin and oxacillin in the HIGH group when compared to the NORM one. An occurrence of vancomycin-resistant bacteria was also observed in the HIGH group. In conclusion, the smallholder dairy farms with excessive use of antibiotics had a higher probability of antibiotic-resistant pattern than the farms with normal use. PMID:25049697

  19. Antibiotic-Releasing Porous Polymethylmethacrylate/Gelatin/Antibiotic Constructs for Craniofacial Tissue Engineering

    PubMed Central

    Shi, Meng; Kretlow, James D.; Spicer, Patrick P.; Tabata, Yasuhiko; Demian, Nagi; Wong, Mark E.; Kasper, F. Kurtis; Mikos, Antonios G.

    2011-01-01

    An antibiotic-releasing porous polymethylmethacrylate (PMMA) construct was developed to maintain the bony space and prime the wound site in the initial step of a two-stage regenerative medicine approach toward reconstructing significant bony or composite craniofacial tissue defects. Porous polymethylmethacrylate (PMMA) constructs incorporating gelatin microparticles (GMPs) were fabricated by the sequential assembly of GMPs, the antibiotic colistin, and a clinically used bone cement formulation of PMMA powder and methylmethacrylate liquid. PMMA/gelatin/antibiotic constructs with varying gelatin incorporation and drug content were investigated to elucidate the relationship between material composition and construct properties (porosity and drug release kinetics). The porosity of PMMA/gelatin/antibiotic constructs ranged between 7.6±1.8–38.4±1.4% depending on the amount of gelatin incorporated and the drug solution added for gelatin swelling. The constructs released colistin over 10 or 14 days with an average release rate per day above 10 µg/ml. The porosity and in vitro colistin release kinetics of PMMA/gelatin/antibiotic constructs were tuned by varying the material composition and fabrication parameters. This study demonstrates the potential of gelatin-incorporating PMMA constructs as a functional space maintainer for both promoting tissue healing/coverage and addressing local infections, enabling better long-term success of the definitive regenerated tissue construct. PMID:21295086

  20. Antibiotic pharmacoeconomics: an attempt to find the real cost of hospital antibiotic prescribing.

    PubMed Central

    Kerr, J. R.; Barr, J. G.; Smyth, E. T.; O'Hare, J.; Bell, P. M.; Callender, M. E.

    1993-01-01

    Antibiotics account for a large part of all hospital pharmacy budgets, but the actual cost of their prescription is unknown. These costs include intravenous administration, labour, serum antibiotic assay, monitoring of haematological and biochemical indices, disposal of sharps and adverse effects. An in-house method of costing antibiotic therapy is presented, to quantify these hidden expenses. Since not only an awareness, but an accurate quantification, of hidden costs is required, a study of various hospital procedures relating directly to antibiotic therapy was undertaken in an acute medical ward; this involved the identification of particular staff members performing various procedures, consumables used and time taken. The cost of five-day courses of gentamicin, penicillin G, ampicillin, flucloxacillin, cefuroxime, ceftotaxime and erythromycin has been calculated; drug and hidden costs for each are presented graphically for comparison. The breakdown cost for gentamicin is presented to illustrate the method. The costing of adverse effects has not been attempted. We suggest that costings of this sort are used in cost-benefit analysis of antibiotic use. These calculations have been incorporated into a computer spreadsheet and this costing service will be offered to clinical areas of our hospital. PMID:8516976