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

SciTech Connect

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.

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



Cephalosporin antibiotics accelerate gastric emptying in mice.  


Gastroparesis is a common debilitating complication in many diabetic patients. While several drugs are available for gastroparesis, many patients are not adequately treated. Many patients do not respond to available drugs or appear to develop tachyphylaxis after an initial response. New agents are needed. Erythromycin is a macrolide antibiotic that accelerates gastric emptying through interaction with motilin receptors. Many antibiotics, like erythromycin itself, have significant gastrointestinal side effects. We investigated the ability of cephalosporin antibiotics to alter gastric emptying in mice by employing phenol red spectrophotometry to monitor gastric emptying. Our results indicate that several cephalosporin antibiotics, particularly cefazolin, accelerate gastric emptying. In some cases these drugs appear more efficacious than either erythromycin or metoclopramide. At very high doses, many drugs, including erythromycin, appear to delay gastric emptying. We hypothesize that the gastrointestinal side effects of nausea and vomiting may result from delayed gastric emptying occurring at high doses while lower doses are prokinetic in the stomach. PMID:9724153

Kuo, W H; Wadwa, K S; Ferris, C D



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

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.



Cephalosporin Antibiotics Accelerate Gastric Emptying in Mice  

Microsoft Academic Search

Gastroparesis is a common debilitatingcomplication in many diabetic patients. While severaldrugs are available for gastroparesis, many patients arenot adequately treated. Many patients do not respond to available drugs or appear to developtachyphylaxis after an initial response. New agents areneeded. Erythromycin is a macrolide antibiotic thataccelerates gastric emptying through interaction with motilin receptors. Many antibiotics, likeerythromycin itself, have significant gastrointestinalside effects.

Wu-Hsien Kuo; Kalayan S. Wadwa; Christopher D. Ferris



An audit of first generation cephalosporin usage  

Microsoft Academic Search

Cefadroxil is a semi-synthetic first generation oral cephalosporin with advantages of almost 100% excretion in the urine within six hours and low cost. It was freely available in the formulary and we undertook an audit of its usage, the indications cited, underlying clinical conditions and relevant microbiology in 106 cases. Following the audit, cefadroxil was restricted, available only on the

N. Shetty; R. I. Shulmant; G. M. Scott




Technology Transfer Automated Retrieval System (TEKTRAN)

Background: Extended-spectrum *-lactamases (ESBLs) are important resistance mechanisms which affect *-lactam antibiotics, including cephalosporins. Extended-spectrum 3rd generation cephalosporins are considered drugs of choice for serious Salmonella infections. The emergence of ESBL-producing orga...


In Vitro Evaluation of BL-S640 Cephalosporin Antibiotic  

PubMed Central

BL-S640, a new oral cephalosporin analogue, was evaluated in vitro against 102 gram-negative and 80 gram-positive bacteria. The antimicrobial spectrum was similar to that of previous cephalosporin analogues. Good antimicrobial activity against strains of Escherichia coli, Klebsiella, staphylococci, and streptococci was demonstrated. Relatively poor activity and/or resistance was noted among most strains of Proteus, Providencia, Pseudomonas, and Serratia. In comparative studies BL-S640 had better activity against strains of Hemophilus influenzae, Staphylococcus aureus, and Enterobacteriaceae than many cephalosporin analogues. Variation of susceptibility results was dependent upon the type of media and inoculum size. Cross-resistance between BL-S640 cephalexin, cephalothin, and cefazolin was demonstrated. Among strains of Klebsiella the more rapid selection of resistance ot other cephalosporins was in contrast to BL-S640. Experience in vitro with BL-S640 has documented its antimicrobial activity,and further studies of pharmacokinetics and therapeutic efficacy are indicated.

Overturf, Gary D.; Ressler, Ronald L.; Marengo, Paul B.; Wilkins, Jeanette



Specific Assay of Aminoglycosidic- or Polymyxin-Type Antibiotics Present in Human Sera in Combination with Cephalosporins  

PubMed Central

Monitoring of serum concentrations of aminoglycosidic or polymyxin antibiotics when administered concurrently with cephalosporins or penicillins requires a special assay technique. Selective enzymatic degradation of the ?-lactam antibiotic from the serum specimen allows subsequent assay of the antibiotic being monitored. This report gives details of a simple procedure for laboratory production of a crude enzyme capable of degrading cephalosporins or penicillins. An assay procedure for quantitating aminoglycosidic or polymyxin antibiotics after enzymatic degradation of a coexisting ?-lactam antibiotic is described. Images

Stroy, S. Ann; Preston, David A.



Third-Generation Cephalosporin-Resistant Vibrio cholerae, India  

PubMed Central

Vibrio cholerae resistance to third-generation cephalosporins is rarely reported. We detected a strain that was negative for extended-spectrum ?-lactamase and positive for the AmpC disk test, modified Hodge test, and EDTA disk synergy test and harbored the blaDHA-1 and blaNDM-1 genes. The antimicrobial drug susceptibility profile of V. cholerae should be monitored.

Mandal, Jharna; Sangeetha, Vilwanathan; Ganesan, Vithiya; Parveen, Mohamudha; Preethi, Venkatesan; Harish, Belgode Narasimha; Srinivasan, Sampath



Third-generation cephalosporin-resistant Vibrio cholerae, India.  


Vibrio cholerae resistance to third-generation cephalosporins is rarely reported. We detected a strain that was negative for extended-spectrum ?-lactamase and positive for the AmpC disk test, modified Hodge test, and EDTA disk synergy test and harbored the blaDHA-1 and blaNDM-1 genes. The antimicrobial drug susceptibility profile of V. cholerae should be monitored. PMID:22840562

Mandal, Jharna; Sangeetha, Vilwanathan; Ganesan, Vithiya; Parveen, Mohamudha; Preethi, Venkatesan; Harish, Belgode Narasimha; Srinivasan, Sampath; Parija, Subhash Chandra



Ceftriaxone, an FDA-approved cephalosporin antibiotic, suppresses lung cancer growth by targeting Aurora B.  


Ceftriaxone, an FDA-approved third-generation cephalosporin antibiotic, has antimicrobial activity against both gram-positive and gram-negative organisms. Generally, ceftriaxone is used for a variety of infections such as community-acquired pneumonia, meningitis and gonorrhea. Its primary molecular targets are the penicillin-binding proteins. However, other activities of ceftriaxone remain unknown. Herein, we report for the first time that ceftriaxone has antitumor activity in vitro and in vivo. Kinase profiling results predicted that Aurora B might be a potential 'off' target of ceftriaxone. Pull-down assay data confirmed that ceftriaxone could bind with Aurora B in vitro and in A549 cells. Furthermore, ceftriaxone (500 µM) suppressed anchorage-independent cell growth by targeting Aurora B in A549, H520 and H1650 lung cancer cells. Importantly, in vivo xenograft animal model results showed that ceftriaxone effectively suppressed A549 and H520 lung tumor growth by inhibiting Aurora B. These data suggest the anticancer efficacy of ceftriaxone for the treatment of lung cancers through its inhibition of Aurora B. PMID:22962305

Li, Xiang; Li, Haitao; Li, Shengqing; Zhu, Feng; Kim, Dong Joon; Xie, Hua; Li, Yan; Nadas, Janos; Oi, Naomi; Zykova, Tatyana A; Yu, Dong Hoon; Lee, Mee-Hyun; Kim, Myoung Ok; Wang, Lei; Ma, Weiya; Lubet, Ronald A; Bode, Ann M; Dong, Ziming; Dong, Zigang



Antistaphylococcal Activity of TD-1792, a Multivalent Glycopeptide-Cephalosporin Antibiotic  

PubMed Central

TD-1792 is a new multivalent glycopeptide-cephalosporin antibiotic with potent activity against Gram-positive bacteria. The in vitro activity of TD-1792 was tested against 527 Staphylococcus aureus isolates, including multidrug-resistant isolates. TD-1792 was highly active against methicillin-susceptible S. aureus (MIC90, 0.015 ?g/ml), methicillin-resistant S. aureus, and heterogeneous vancomycin-intermediate S. aureus (MIC90, 0.03 ?g/ml). Time-kill studies demonstrated the potent bactericidal activity of TD-1792 at concentrations of ?0.12 ?g/ml. A postantibiotic effect of >2 h was observed after exposure to TD-1792.

Blais, Johanne; Lewis, Stacey R.; Krause, Kevin M.



Evaluation of Antibiotic Efficacy Using Electron Microscopy: Morphological Effects of Guanylureido Cephalosporin, Chlorobenzoylureido Cephalosporin, BL-P1654, and Carbenicillin on Pseudomonas aeruginosa  

PubMed Central

The response of Pseudomonas aeruginosa to carbenicillin, BL-P1654, and two cephalosporins (112384 and 112883) was evaluated by minimal inhibitory concentration determinations, [14C]leucine uptake studies, morphological studies of colonial growth, and mouse intraperitoneal inoculations. Spheroplast formation and bacterial lysis were not the early response; instead, cell division was inhibited and long filaments were formed. Spheroplast formation and bacterial lysis were not observed in the first 7 h of incubation in minimal inhibitory concentrations of antibiotic. Images

Ellis, L. F.; Herron, D. K.; Preston, D. A.; Simmons, L. K.; Schlegel, R. A.



Frequency of symptomatic relapses of group A beta-hemolytic streptococcal tonsillopharyngitis in children from 4 pediatric practices following penicillin, amoxicillin, and cephalosporin antibiotic treatment.  


The objective was to determine the frequency of early symptomatic relapses following antibiotic treatment for group A beta-hemolytic streptococcal (GABHS) tonsillopharyngitis in children from Rochester, New York; Houston, Texas; Spokane, Washington; and Los Angeles, California (2004--2006). The study included 4278 patients. The proportion with a bacteriologic relapse of GABHS tonsillopharyngitis within 1 to 5 days of completing a 10-day treatment course was 8% (penicillin and bicillin), 6% (amoxicillin), 2% (first-generation cephalosporin), and 1% (second-generation and third-generation cephalosporin; P = .0001); symptomatic relapses occurred within 6 to 20 days after completion of therapy in 16%, 14%, 9%, and 7% of cases (P = .0001). Cases from New York and Washington had higher penicillin or amoxicillin failure rates than cases from Texas and California. The frequency of symptomatic relapses of GABHS tonsillopharyngitis, therefore, differs according to the antibiotic treatment selected; the trend for such relapses being penicillin or amoxicillin > cephalosporins although geographic differences may occur. PMID:18490665

Casey, Janet R; Kahn, Raymond; Gmoser, Dean; Atlas, Elissa; Urbani, Karen; Luber, Stephen; Pellman, Harry; Pichichero, Michael E



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

PubMed Central

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 testing. We have examined 95 clinical isolates reportedly susceptible to ceftazidime and ceftriaxone, as originally determined by either KBDD or MIC methods. The organisms studied here were isolated in 2002 from two pediatric hospital centers (Seattle, USA and Shanghai, China). They belong to the inducible ?-lactamase producing Gram-negative bacilli, such as Enterobacter spp., Citrobacter spp., Serratia spp., Morganella spp., Providencia spp., and Proteus vulgaris. A Kirby-Bauer disc approximation (KBDA) method identified inducible phenotypes of third-generation cephalosporin resistance in 76% of isolates, which would otherwise be considered susceptible by standard KBDD methods.

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



Molecular docking analysis of new generation cephalosporins interactions with recently known SHV-variants  

PubMed Central

Extended-spectrum-?-lactamases (ESBLs), constitutes the growing class of betalactamses, these are enzymes produced by bacteria which impart resistance against advanced-generation-cephalosporins. SHV enzymes are among the most prevalent ESBLs. The mode of molecular interactions of recent SHV-variants to advanced generation cephalosporins has not been reported yet. This is the first time we are reporting the insilico study of these recent variants with new generation cephaosporins. Homology models for SHV-105, SHV-95, SHV-89, SHV-61 and SHV-48 were generated using MODELLER9v3. New generation Cephalosporins were selected to target the active site amino acid residues of these modeled SHV enzymes for predicting comparative efficacies of these inhibitors against the said enzymes on the basis of interaction energies of docking. The docked complexes were analyzed by using DISCOVERY STUDIO 2.5. In this study A237, S70, K234, R275, N132, R244 and S130 were found crucial to the correct positioning of drugs within the binding site of SHV enzymes in 11, 6, 6, 6, 5, 5 and 5 instances, respectively. On the basis of interaction energy and Ki calculations cefatoxime emerged as the most efficient among the other advanced cephalosporins against all the studied SHV variants, excluding SHV-48 where ceftazidime was found to be most effective drug. Furthermore, this study identified amino acid residues crucial to ‘SHV-Cephalosporins’ interactions and this information will be useful in designing effective and versatile drug candidates.

Khan, Asad Ullah; Baig, Mohd Hassan; Wadhwa, Gulshan



Antibiotic therapy and acute outcome of meningitis due to Streptococcus pneumoniae considered intermediately susceptible to broad-spectrum cephalosporins.  

PubMed Central

Children with meningitis due to Streptococcus pneumoniae isolates that are relatively or fully resistant to penicillin and have decreased susceptibility to broad-spectrum cephalosporins (MIC, > or = 2.0 micrograms/ml) who have failed treatment with broad-spectrum cephalosporins have been reported. The National Committee for Clinical Laboratory Standards has newly revised guidelines indicating that S. pneumoniae isolates associated with meningitis for which the MICs are > or = 0.5 micrograms/ml should be considered resistant to broad-spectrum cephalosporins. This recommendation is not clearly based on data related to clinical outcome and may be too conservative. We present data on five children who had S. pneumoniae meningitis due to isolates that were relatively or fully resistant to penicillin (MIC range, 0.125 to 4.0 micrograms/ml) and had cefotaxime or ceftriaxone MICs of 0.50 to 2.0 micrograms/ml. Their clinical courses and outcomes were comparable to those of five children with S. pneumoniae meningitis due to strains that were relatively or fully resistant to penicillin and were inhibited by cefotaxime at concentrations of < or = 0.25 micrograms/ml, as well as to those of 25 patients with S. pneumoniae meningitis due to penicillin-susceptible isolates identified during the same period. Children with meningitis due to S. pneumoniae with cefotaxime or ceftriaxone MICs of < or = 1.0 micrograms/ml may be adequately treated with these antibiotics. Further clinical data are required before solid recommendations can be made regarding cephalosporin breakpoints for S. pneumoniae.

Tan, T Q; Schutze, G E; Mason, E O; Kaplan, S L



[Antibiotic susceptibility and molecular mechanisms of cephalosporins resistance in Klebsiella isolates from patients with hospital-acquired infections].  


Antibiotic susceptibility of nosocomial Klebsiella isolates from inpatients of 30 medical centres in 15 various regions of Russia was studied. In total 212 strains were tested. The Klebsiella genus was represented by the following species: Klebsiella pmeumoniae ss. pneumoniae (182 isolates, 85.8%), Klebsiella pneumonia ss. ozaenae (1 isolate, 0.5%), Klebsiella oxytoca (29 isolates, 13.7%). The susceptibility was determined by the broth microdilution method. Carbapenems (imipenem and meropenem) remained to be the most active antibacterial agents. However, 1 imipenem resistant strain and 2 meropenem resistant strains were isolated. As for the 3rd generation cephalosporins, the lowest MICs were observed with the use of the inhibitor-protected agents, such as ceftazidime/clavulanic acid (MIC50 0.25 mcg/ml, MIC90 64 mcg/ml). 48.8%, 16.9%, 29.7% and only 10.5% of the isolates was susceptible to cefepime, cefotaxime, ceftazidime and cefoperazone respectively. Detecting of the beta-lactamase genes (TEM, SHV and CTX) was performed by PCR in 42 strains of Klebsiella pneumoniae ss. pneumoniae. Alone or in various combination the TEM type beta-lactamases were detected in 16 (38.1%) isolates. SHV and CTX were detected in 29 (69%) and 27 (64.3%) isolates respectively. Combinations of 2 and 3 different determinants of resistance to beta-lactams were revealed in 23.8% and 26.2% of the isolates respectively. No isolates producing class B MBL among the carbapenem resistant nosocomial Klebsiella strains were detected. PMID:18318145

Ivanov, D V



Noninferiority trial comparing a first-generation cephalosporin with a third-generation cephalosporin in the treatment of nonsevere clinical mastitis in dairy cows.  


The objective of this study was to evaluate the noninferiority of 2 intramammary treatments for nonsevere clinical mastitis. The 2 treatments were a first-generation cephalosporin (cephapirin sodium, 2 treatments 12h apart) and a third-generation cephalosporin (ceftiofur hydrochloride, treatments once a day for 5d). A total of 296 cases on 7 farms met the enrollment criteria for the study. Streptococcus dysgalactiae was the most common bacterial species identified in milk samples from cows with mild to moderate clinical mastitis, followed by Escherichia coli, other esculin-positive cocci, Streptococcus uberis, and Klebsiella spp. Treatment was randomly allocated as either cephapirin sodium or ceftiofur hydrochloride via intramammary infusion according to label standards. Bacteriological cure was defined based on 2 posttreatment milk samples taken at 10 and 17d after enrollment. Noninferiority of cephapirin relative to ceftiofur was shown for bacteriological cure of gram-positive cases and for clinical cure of all cases. Ceftiofur showed a significantly higher bacteriological cure in gram-negative cases. Treatments showed no significant difference in bacteriological cure of all cases and in time to exit from the study, where the absence of a difference does not imply noninferiority. Based on the findings from this study, farm-specific treatment protocols that differ for gram-positive and gram-negative cased may be developed. PMID:23958017

Schukken, Y H; Zurakowski, M J; Rauch, B J; Gross, B; Tikofsky, L L; Welcome, F L



In Vitro Activity of TD-1792, a Multivalent Glycopeptide-Cephalosporin Antibiotic, against 377 Strains of Anaerobic Bacteria and 34 Strains of Corynebacterium Species  

PubMed Central

TD-1792 is a multivalent glycopeptide-cephalosporin heterodimer antibiotic with potent activity against Gram-positive bacteria. We tested TD-1792 against 377 anaerobes and 34 strains of Corynebacterium species. Against nearly all Gram-positive strains, TD-1792 had an MIC90 of 0.25 ?g/ml and was typically 3 to 7 dilutions more active than vancomycin and daptomycin.

Citron, Diane M.; Warren, Yumi A.; Goldstein, Ellie J. C.



In Vitro and In Vivo Activity of First Generation Cephalosporins Against Leptospira  

PubMed Central

Third generation cephalosporins are commonly used in the treatment of leptospirosis. The efficacy of first generation cephalosporins has been less well-studied. Susceptibility testing of 13 Leptospira strains (11 serovars) to cefazolin and cephalexin was conducted using broth microdilution. Median minimal inhibitory concentration (MIC) for cefazolin and cephalexin ranged from < 0.016 to 2 ?g/mL (MIC90 = 0.5 ?g/mL) and from 1 to 8 ?g/mL (MIC90 = 8 ?g/mL), respectively. Efficacy of cefazolin and cephalexin in an acute lethal hamster model of leptospirosis was studied. Survival rates for cefazolin were 80%, 100%, and 100%, and survival rates for cephalexin were 50%, 80%, and 100% (treated with 5, 25, and 50 mg/kg per day for 5 days, respectively). Each treatment group showed improved survival compared with no treatment (P < 0.01), and none of the therapies, regardless of dose, was statistically significantly different than doxycycline. These results support a potential role for first generation cephalosporins as alternative therapies for leptospirosis.

Harris, Brande M.; Blatz, Peter J.; Hinkle, Mary K.; McCall, Suzanne; Beckius, Miriam L.; Mende, Katrin; Robertson, Janelle L.; Griffith, Matthew E.; Murray, Clinton K.; Hospenthal, Duane R.



Cephalosporins in surgical prophylaxis.  


Controlled clinical trials have shown that antimicrobial prophylaxis can lower the incidence of infection after certain operations, thus reducing morbidity, hospital stay, antibiotic usage and mortality due to sepsis. An effective prophylactic regimen should be directed against the most likely infecting organisms, but need not be active against every potential pathogen. Infection can be prevented when effective concentrations are present in the blood and the tissue during and shortly after the procedure. Therefore, antimicrobial prophylaxis should begin just before the operation: beginning earlier is unnecessary and potentially dangerous, beginning later is less effective. A single-dose prophylaxis after the induction of anesthesia is sufficient. If surgery is delayed or prolonged, a second dose is advisable if an antimicrobial drug with a short half-life is used. Postoperative administration is unnecessary and is harmful. Cephalosporins are considered to be the drug of choice, because they offer fewer allergic reactions. From the first generation cephalosporins, cefazolin has been widely recommended with success. From the second generation cephalosporins, cefuroxime, cefamandole and cefoxitin are increasingly recommended. Their antistaphylococcal activity is somewhat less strong but their activity against gram-negative bacteria is stronger. In addition, cefoxitin has good activity against anaerobes. Third generation cephalosporins, such as cefotaxime, cefoperazone, ceftriaxone, ceftazidime or ceftizoxime are generally not recommended for surgical prophylaxis. Despite these recommendations, they have been accepted by the medical community and are today in use in many countries as the most common drugs in surgical prophylaxis. Ceftriaxone in particular, is far exceeding the sales of any other drug for prophylaxis. Contra-indications, limitations, additional or other drugs and practical recommendations for specific procedures are discussed and the results of several prospective randomized studies are presented. PMID:11936371

Geroulanos, S; Marathias, K; Kriaras, J; Kadas, B



The control of invasive Candida infection in very low birth weight infants by reduction in the use of 3rd generation cephalosporin  

PubMed Central

Purpose To evaluate the effectiveness of new management policies on the incidence of invasive Candida infections Methods This observational study involved a retrospective analysis of the patients' medical records. In total, 99 very low birth weight infants, who were admitted to the neonatal intensive care unit at Ajou University Hospital from January 2010 to December 2011, were enrolled for the study. Period I, defined as the period before the revision of management policies, comprised 57 infants; whereas, period II, defined as the period after the implementation of new management policies, comprised 42 infants. The new management policies entailed a reduction in antibiotic and histamine type 2 receptor blocker (H2 blocker) use, duration of central venous catheterization, and duration of endotracheal intubation. Results There was a significant overall decrease in the use of antibiotics including 3rd generation cephalosporin and H2 blockers (P<0.05), and a significantly lower incidence of invasive Candida infections in period II as compared to period I (0/42 vs. 6/57, respectively; P=0.037). Comparison between infants with invasive Candida infections (n=6) and those without (n=93) showed that gestational age (odds ratio [OR], 0.909; 95% confidence interval [CI], 0.829 to 0.996; P=0.042) and the duration of 3rd generation cephalosporin use (OR, 1.093; 95% CI, 1.009 to 1.183; P=0.029) were statistically significant risk factors. Conclusion The new management policies effectively decreased overall use of antibiotics, especially 3rd generation cephalosporin, and H2 blockers, which led to a significantly lower incidence of invasive Candida infections.

Chang, Yu Jin; Choi, Il Rak; Shin, Won Sub; Kim, Yun Kyung; Park, Moon Sung



Increased Structural Flexibility at the Active Site of a Fluorophore-conjugated ?-Lactamase Distinctively Impacts Its Binding toward Diverse Cephalosporin Antibiotics*  

PubMed Central

The ?-loop at the active site of ?-lactamases exerts significant impact on the kinetics and substrate profile of these enzymes by forming part of the substrate binding site and posing as steric hindrance toward bulky substrates. Mutating certain residues on the ?-loop has been a general strategy for molecular evolution of ?-lactamases to expand their hydrolytic activity toward extended-spectrum antibiotics through a mechanism believed to involve enhanced structural flexibility of the ?-loop. Yet no structural information is available that demonstrates such flexibility or its relation to substrate profile and enzyme kinetics. Here we report an engineered ?-lactamase that contains an environment-sensitive fluorophore conjugated near its active site to probe the structural dynamics of the ?-loop and to detect the binding of diverse substrates. Our results show that this engineered ?-lactamase has improved binding kinetics and positive fluorescence signal toward oxyimino-cephalosporins, but shows little such effect to non-oxyimino-cephalosporins. Structural studies reveal that the ?-loop adopts a less stabilized structure, and readily undergoes conformational change to accommodate the binding of bulky oxyimino-cephalosporins while no such change is observed for non-oxyimino-cephalosporins. Mutational studies further confirm that this substrate-induced structural change is directly responsible for the positive fluorescence signal specific to oxyimino-cephalosporins. Our data provide mechanistic evidence to support the long-standing model that the evolutionary strategy of mutating the ?-loop leads to increased structural flexibility of this region, which in turn facilitates the binding of extended spectrum ?-lactam antibiotics. The oxyimino-cephalosporin-specific fluorescence profile of our engineered ?-lactamase also demonstrates the possibility of designing substrate-selective biosensing systems.

Wong, Wai-Ting; Chan, Kwok-Chu; So, Pui-Kin; Yap, Hong-Kin; Chung, Wai-Hong; Leung, Yun-Chung; Wong, Kwok-Yin; Zhao, Yanxiang



Quantification of the cephalosporin antibiotic cefditoren in human plasma by high-performance liquid chromatography.  


A simple, sensitive and selective high-performance liquid chromatography (HPLC) method with ultraviolet detection (305 nm) was developed and validated for quantification of cefditoren (CAS 104145-95-1), a broad-spectrum orally administered cephalosporin in human plasma. Following solid-phase extraction using Waters Oasis SPE cartridges, the analyte and internal standard (hydrochlorothiazide, CAS 58-93-5) were separated using an isocratic mobile phase of 0.03 % trifluoro acetic acid buffer / acetonitrile (81/19, v/ v) on reverse phase Waters symmetry C18 column. The lower limit of quantification was 50 ng/mL, with a relative standard deviation of less than 4%. A linear range of 50 to 5000 ng/mL was established. This HPLC method was validated with between-batch and within-batch precision of 0.5 to 3.7 % and 0.5 to 2.5%, respectively. The between-batch and within-batch accuracy was 96.9 to 103.8% and 97.5 to 102.3%, respectively. Stability of cefditoren in plasma was excellent, with no evidence of degradation during sample processing (autosampler) and 30 days storage in a freezer. This validated method is sensitive, simple and repeatable enough to be used in pharmacokinetic studies. PMID:16724518

Nirogi, Ramakrishna V S; Kandikere, Vishwottam N; Shrivastava, Wishu; Mudigonda, Koteshwara



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

Microsoft Academic Search

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

N Modi; V Damjanovic; R W Cooke



High rates of antimicrobial co-resistance among Enterobacteriaceae: comparative analysis between clinical isolates resistant and susceptible to third-generation cephalosporins  

Microsoft Academic Search

SUMMARY We compared the antimicrobial co-resistance of 3,402 clinical isolates of Enterobacteriaceae resistant to third-generation cephalosporins (2,569 ESBL-producing and 833 AmpC overproducing) with that of 16,220 susceptible isolates, in order to determine the impact of resistance to third-generation cephalosporins on the likelihood of resistance to other antimicrobial classes. Enterobacteriaceae resistant to third-genera- tion cephalosporins, independently of their mechanism of resistance,

M. J. Goyanes; E. Cercenado; R. Insa; A. Morente; L. Alcalá; E. Bouza


Gonococcal Resistance: Are Cephalosporins Next?  

Microsoft Academic Search

The development of resistance to multiple antibiotics has limited treatment options for gonorrhea in many countries. Currently,\\u000a the Centers for Disease Control and Prevention only recommend cephalosporin antibiotics for treatment of uncomplicated gonorrhea.\\u000a Although the cephalosporins remain effective, the demonstrated ability of Neisseria gonorrhoeae to develop resistance has raised concerns about the possibility of multidrug-resistant N. gonorrhoeae strains, which include

Robert D. Kirkcaldy; Ronald C. Ballard; Deborah Dowell



Perspectives of beta-lactamases inhibitors in therapy of infections caused by Escherichia coli or Klebsiella with plasmidic resistance to third generation cephalosporins  

Microsoft Academic Search

Summary New plasmidic ß-lactamases inactivating so far stable cephalosporins, aztreonam and cephamycins restrict the use of these antibiotics in therapy of infections, e.g., byEscherichia coli and Klebsiella. Thus, combinations of ß-lactamase inhibitors and ß-lactam antibiotics were investigatedin vitro with regard to their therapeutic perspectives. Minimal inhibitory concentrations and the kinetics of killing in a pharmacodynamic model were determined. Extended broad

A. Bauernfeind



Cephalosporin C acylase: dream and(/or) reality.  


Cephalosporins currently constitute the most widely prescribed class of antibiotics and are used to treat diseases caused by both Gram-positive and Gram-negative bacteria. Cephalosporins contain a 7-aminocephalosporanic acid (7-ACA) nucleus which is derived from cephalosporin C (CephC). The 7-ACA nucleus is not sufficiently potent for clinical use; however, a series of highly effective antibiotic agents could be produced by modifying the side chains linked to the 7-ACA nucleus. The industrial production of higher-generation semi-synthetic cephalosporins starts from 7-ACA, which is obtained by deacylation of the naturally occurring antibiotic CephC. CephC can be converted to 7-ACA either chemically or enzymatically using D-amino acid oxidase and glutaryl-7-aminocephalosporanic acid acylase. Both these methods show limitation, including the production of toxic waste products (chemical process) and the expense (the enzymatic one). In order to circumvent these problems, attempts have been undertaken to design a single-step means of enzymatically converting CephC to 7-ACA in the course of the past 10 years. The most suitable approach is represented by engineering the activity of a known glutaryl-7-aminocephalosporanic acid acylase such that it will bind and deacylate CephC more preferentially over glutaryl-7-aminocephalosporanic acid. Here, we describe the state of the art in the production of an effective and specific CephC acylase. PMID:23417342

Pollegioni, Loredano; Rosini, Elena; Molla, Gianluca



HPLC separation of antibiotics present in formulated and unformulated samples  

Microsoft Academic Search

Analysis of antibiotics in formulated and unformulated samples demand a highly specific and rapid method as many antibiotics (e.g. ?-lactams) have serious stability problems. HPLC techniques can provide a valuable tool for generating highly pure preparations for characterizing the antimicrobial activities. In the present review article, column and mobile phase conditions for the various classes of antibiotics viz. penicillins, cephalosporins,

Shalini Joshi



Comparison of the antibacterial spectra of cephalexin and cefaclor with those of cephalothin and newer cephalosporins: reevaluation of the class representative concept of susceptibility testing.  

PubMed Central

The validity of the class representative concept for in vitro susceptibility testing of older cephalosporins was reevaluated. Two oral cephalosporins, cephalexin and cefaclor, were compared with the established cephalosporin class representative, cephalothin, by using reference microdilution minimal inhibitory concentrations of 528 isolates of a wide variety of gram-positive and gram-negative bacterial pathogens. For each comparison, there were only 15 (2.8%) random major and very major interpretive discrepancies. Additional comparisons confirmed the need to test second-generation (cefamandole) and third-generation (cefotaxime) cephalosporins separately. These results provide reasonable assurance that the use of cephalothin as an in vitro predictor of qualitative bacterial susceptibility to these two oral cephalosporins remains an acceptable alternative to testing each antibiotic individually.

Preston, D A; Jones, R N; Barry, A L; Thornsberry, C



The Effect of a 4th Generation-Cephalosporin Introduction upon the Incidence of Multidrug-Resistant Gram-Negative Bacteria in a Non-Teaching Hospital  

Microsoft Academic Search

Problem statement: Antimicrobial resistance is a worrisome situation in hospitals around the world and the misuse of certain classes of anti microbials has contributed for this situation. Approach: We performed a prospective surveillance study on t he incidence of multi-drug resistant bacteria before (phase 1) and after (phase 2) the introduction of a 4th-generation cephalosporin in a non-teaching hospital. Results:

Guilherme Henrique; Campos Furtado; Luciana Baria Perdiz



[The role of cefepime, a 4th-generation cephalosporin, in treating patients with surgical sepsis].  


Cefepime (Maxipime) was used in the management of 22 patients at the age of 18 to 73 years with the surgical sepsis syndrome (SAPS > 15). In 16 patients surgical sepsis was due to pancreatitis, appendititis, abdominal wound or trauma or complications after planned surgical interventions on the organs of the abdominal cavity. In the other 6 patients surgical sepsis was due to inflammatory processes in soft tissues after minor trauma. In 10 patients (group 1) cefepime was used after the pathogen verification and antibioticogram examination. In 12 patients (group 2) the antibiotic was used in the empirical therapy as the first line drug after the patients acceptance from another unit when the pathogen nature was obscure. Cefepime was administered intravenously in a dose of 2.0 g twice daily for 7 to 10 days in combination with metronidazole in a dose of 0.5 g thrice daily. After 5-6 days of the treatment the patients of group 1 were switched to the cefepime intramuscular regimen. The lethality totaled 18 per cent (4 patients). Three of them were from group 2. The patients died of progressive polyorgan insufficiency. It is characteristic that in no cases cefepime induced septic shock due to the endotoxin escape. No septicopyemia was as well observed even in the patients with verified bacteremia due to Staphylococcus aureus. PMID:10629740

Shliapnikov, S A; Rybkin, A K



Cefditoren, a new aminothiazolyl cephalosporin.  


Cefditoren pivoxil, an oral third-generation cephalosporin, was approved by the Food and Drug Administration in September 2001. It has been used in Japan for several years. The greatest therapeutic potential of cefditoren appears to be its activity against gram-positive and gram-negative organisms causing respiratory tract infections and skin and skin-structure infections, such as Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. Cefditoren is also effective against methicillin-susceptible strains of Staphylococcus aureus. Nevertheless, cefditoren has no activity against atypical pathogens, including Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella sp. Moreover, cefditoren does not inhibit Pseudomonas aeruginosa or Bacteroides fragilis. In virtually all studies, cefditoren has compared favorably against other orally administered antibiotics used against the most commonly isolated respiratory tract pathogens. Its side effect profile includes diarrhea, nausea, vomiting, headache, and dyspepsia. Cefditoren is indicated for treatment of mild-to-moderate acute exacerbations of chronic bronchitis, pharyngitis-tonsillitis, and uncomplicated skin and skin-structure infections caused by susceptible strains of organisms in adults and adolescents (> or = 12 yrs of age). Based on its reported antimicrobial activity, cefditoren has potential for empiric management of most commonly encountered respiratory tract infections. Additional studies will further define its role in clinical practice. PMID:12389878

Balbisi, Ebrahim A



A rapid assay method for cephalosporins  

PubMed Central

A simple, rapid assay for cephalosporins is described. The method is based on the inhibition by cephalosporins of the fermentation of glucose or inositol by a strain of Providence resistant to aminoglycoside antibiotics. The method gives answers which are as accurate as those obtained by standard agar diffusion techniques within four hours, and utilizes skills and resources readily available in most routine bacteriology departments. Results are not affected by gentamicin or kanamycin concurrently administered to the patient. This method will be of value in helping to monitor cephalosporin therapy in patients with serious sepsis, especially those with impaired renal function, and may help in elucidating and preventing the problem of nephrotoxicity associated with cephalosporin administration.

Noone, Paul



Resistance to cephalosporins and carbapenems in Gram-negative bacterial pathogens  

Microsoft Academic Search

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

Yvonne Pfeifer; Angela Cullik; Wolfgang Witte



Fluidized bed adsorption of Cephalosporin C  

Microsoft Academic Search

Fluidized bed adsorption can substantially simplify the recovery of products from fermentation. There are, however, several critical parameters, which have a significant influence on the performance of such systems. This paper presents experimental results on the adsorption of an antibiotic, Cephalosporin C, on macroporous adsorbents of the polystyrene type and on an ion exchanger. Internals (static mixers) were used to

M Hicketier; K Buchholz



Some biological properties of cephalosporin c and a derivative  

PubMed Central

Some biological properties of cephalosporin C and of a pyridinium derivative, “cephalosporin CA (pyridine),” were examined. Staphylococci, both penicillinase-producing and non-penicillinase-producing, and some other bacteria tested, were inhibited by 60 to 125 ?g cephalosporin C/ml., and 5 to 20 ?g cephalosporin CA (pyridine)/ml. The ratio of the activity of the two antibiotics varied for different organisms. Resistance developed slowly on repeated subculture of penicillinase-producing staphylococci in presence of either antibiotic. The minimum inhibitory concentration of cephalosporin CA (pyridine) upon penicillinase-producing staphylococci increased 4 to 8-fold with a 500-fold increase in inoculum size; with cephalosporin C there was a 2-fold increase. Their activity was not reduced by serum. Both substances were non-toxic. They were excreted quantitatively in the urine when given intravenously or subcutaneously to mice. After oral administration less than 5% of the dose was excreted. Cephalosporin CA (pyridine) was about 8 times more active than cephalosporin C in protecting mice from an experimental streptococcal infection, nine doses of 6.25 mg/kg affording complete protection.

Jago, M.; Heatley, N. G.



Cephalosporin antimicrobial agents and related compounds.  


Cephalosporins are broad-spectrum antimicrobial agents that are often used empirically to treat suspected bacterial infections and also to treat culture-proven infections due to selected gram-positive and gram-negative microorganisms. Cephalosporins differ widely in their spectrum of activity, susceptibility to beta-lactamases, serum half-life, and penetration of the central nervous system. In general, the first-generation and second-generation agents are most active against staphylococci and streptococci, and the third-generation agents are most active against the Enterobacteriaceae and Pseudomonas. As a group, cephalosporins have a favorable profile of toxicity in comparison with other antimicrobial agents. The development of bacterial resistance has affected all steps of the cephalosporin mechanism of action, including production of beta-lactamases, alterations in penicillin-binding proteins, and modification of the cell wall. New cephalosporins are among the most expensive pharmaceutical agents in use today. Maintaining expertise in the choice and use of these agents will remain a challenge to physicians as additional investigational cephalosporins continue to be developed and introduced into clinical practice. PMID:1921490

Gustaferro, C A; Steckelberg, J M



Reciprocal Regulation of Cephalosporin Resistance in Enterococcus faecalis  

PubMed Central

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.

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



Relationship between ceftriaxone use and resistance to third-generation cephalosporins among clinical strains of Enterobacter cloacae  

Microsoft Academic Search

Objective: To investigate the potential correlation between the use of extended-spectrum cephalospor- ins (ESCs) and resistance to this antibiotic class among clinical isolates of Enterobacter cloacae in a university-affiliated hospital. Materials and methods: Data on antimicrobial resistance and antimicrobial use concerning E. cloacae and ESCs were collected over a 4 year period. Various statistical tools were used to explore the

A. Muller; J. M. Lopez-Lozano; X. Bertrand; D. Talon



Correlation of extended spectrum beta lactamases production with cephalosporin resistance in gram negative bacilli.  


Beta lactamase production is an important mechanism of developing resistance to beta lactam group of antibiotics. Cephlosporins with extended spectrum of activity and stability were introduced to overcome this resistance, but soon production of extended spectrum beta lactamases (ESBLs), which are inducible in nature was reported. In this study Klebsiella aerogenes--166, Escherichia coli--120, Citrobacter spps--116, Pseudomonas spps--50, Proteus spps--32 and S. typhi--16, strains were subjected to sensitivity testing against various generations of cephalosporins by disc diffusion method and for the production of ESBLs using disc approximation method. Klebsiella aerogenes, Escherichia coli, Citrobacter spps and Pseudomonas spps showed statistically significant difference in the resistance pattern to all three generations of cephalosporins and ESBLs production. PMID:15471144

Ghatole, Mangala; Manthalkar, Pramod; Kandle, Suresh; Yemul, Vishwanath; Jahagirdar, Vilas



[Cephalosporins and enzymuria].  


Urinary enzyme excretion was studied in 56 patients treated with cephalosporins in order to evaluate their potential nephrotoxicity. Only in 4 out of 56 patients (7%) was increased NAG, gamma-GT, AlP excretion seen. A rapid return to normal values was observed just after the end of the therapy. PMID:2869451

Daghero, O; Andreoni, G; Arione, R; Bendiscioli, L; Bramato, C; Cimino, T; Salassa, B; Spezia, C; Soranzo, M L



Cephalosporin-resistant Pneumococci and Sickle Cell Disease  

PubMed Central

Sickle cell anemia patients have 600 times the risk for invasive pneumococcal disease than their healthy peers. High-level cephalosporin resistance was described in the 1990s in healthy children from Tennessee, but its prevalence in sickle cell disease patients is unknown. Pneumococcal isolates from sickle cell disease patients from Tennessee were subjected to multilocus sequence typing to characterize antimicrobial drug–resistant strains. Twenty-one percent of strains were resistant to cefotaxime and penicillin. Of the 14 cephalosporin-resistant strains, 9 were sequence types previously described as highly cephalosporin resistant, while resistance was found for the first time in 3 clones: Maryland6B, ST660, and a novel clone, ST1753. High-level cephalosporin resistance exists in more settings than initially recognized, and its high prevalence in sickle cell disease patients may decrease the efficacy of third-generation cephalosporins in invasive pneumococcal disease.

Miller, Martha L.; Obert, Caroline A.; Gao, Geli; Daw, Najat C.; Flynn, Patricia



Fluidized bed adsorption of cephalosporin C.  


Fluidized bed adsorption can substantially simplify the recovery of products from fermentation. There are, however, several critical parameters, which have a significant influence on the performance of such systems. This paper presents experimental results on the adsorption of an antibiotic, Cephalosporin C, on macroporous adsorbents of the polystyrene type and on an ion exchanger. Internals (static mixers) were used to control bed expansion and mixing, the range of flow rates could thus be extended significantly. An integrated mathematical model was developed comprising bed expansion, residence time distribution and mixing, adsorption kinetics and equilibria. PMID:11755989

Hicketier, M; Buchholz, K



Theoretical aspects of cephalosporin isomerism  

SciTech Connect

The {triangle}{sup 3} double bond of cephalosporins isomerizes to the {triangle}{sup 2} position, resulting in biological inactivation of these antibiotics. This phenomenon occurs slowly in the case of cephalosporanic acids, but is rapid when the 4-carboxylate moiety is esterified or otherwise derivatized, leading to an equilibrium between the {triangle}{sup 2} and {triangle}{sup 3} forms. A theoretical study of this isomerization is described in the framework of two semiempirical all-valence electron molecular orbital (MO) approximations, namely MNDO and AMI. Specifically, the methyl ester and free carboxylate derivatives of both the {triangle}{sup 3} and {triangle}{sup 2} isomers of 7-phenylacetamidocephalosporin were studied. The results obtained indicated that the {triangle}{sup 3} derivatives were thermodynamically more stable than were the {triangle}{sup 2} isomers both in the case of the free acids and methyl esters. These data are consistent with experimental findings and suggest that the more rapid isomerization demonstrated in the case of the esters is due primarily to kinetic rather than to thermodynamic factors. Examination of the calculated molecular structures lend support to various theories that correlate the inactivity of the {triangle}{sup 2} isomers with spatial considerations and the degree of {beta}-lactam amide resonance.

Pop, E.; Brewster, M.E.; Bodor, N. (Pharmatec, Inc., Alachua, FL (USA) Univ. of Florida, Gainesville (USA)); Kaminski, J.J. (Schering-Plough Corp., Bloomfield, NJ (USA))



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...


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

PubMed Central

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.

Little, Jaime L.



Eradication of bacterial persisters with antibiotic-generated hydroxyl radicals  

PubMed Central

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 capable of yielding a phenotypically antibiotic-tolerant subpopulation of cells, often called persisters, within populations of Mycobacterium smegmatis and M. tuberculosis. We find that persisters are distinct from the larger antibiotic-susceptible population, as a small drop in dissolved oxygen (DO) saturation (20%) allows for their survival in the face of bactericidal antibiotics. In contrast, if high levels of DO are maintained, all cells succumb, sterilizing the culture. With increasing evidence that bactericidal antibiotics induce cell death through the production of reactive oxygen species (ROS), we hypothesized that the drop in DO decreases the concentration of ROS, thereby facilitating persister survival, and maintenance of high DO yields sufficient ROS to kill persisters. Consistent with this hypothesis, the hydroxyl-radical scavenger thiourea, when added to M. smegmatis cultures maintained at high DO levels, rescues the persister population. Conversely, the antibiotic clofazimine, which increases ROS via an NADH-dependent redox cycling pathway, successfully eradicates the persister population. Recent work suggests that environmentally induced antibiotic tolerance of bulk populations may result from enhanced antioxidant capabilities. We now show that the small persister subpopulation within a larger antibiotic-susceptible population also shows differential susceptibility to antibiotic-induced hydroxyl radicals. Furthermore, we show that stimulating ROS production can eradicate persisters, thus providing a potential strategy to managing persistent infections.

Grant, Sarah Schmidt; Kaufmann, Benjamin B.; Chand, Nikhilesh S.; Haseley, Nathan; Hung, Deborah T.



Differences in the changes in resistance patterns to third- and fourth-generation cephalosporins and piperacillin/tazobactam among Klebsiella pneumoniae and Escherichia coli clinical isolates following a restriction policy in a Greek tertiary care hospital.  


The aim of the present study was to investigate whether replacement of broad-spectrum cephalosporins (CEPs) by piperacillin/tazobactam (TZP) as first-line empirical therapy may have an effect on beta-lactam resistance among Klebsiella pneumoniae and Escherichia coli in a tertiary care hospital. Data regarding CEP and TZP consumption and resistance were collected on a bimonthly basis during an open-label 2-year (1 year observational and 1 year interventional) study. Consumption of ceftazidime was reduced by 64.5%. In contrast, consumption of the other third-generation CEPs (cefotaxime and ceftriaxone) remained almost stable, whereas an increase in consumption of TZP by 2.8-fold was observed. A significant decrease in resistance to third-generation cephalosporins among K. pneumoniae isolates was observed, and the incidence of extended-spectrum beta-lactamase-producing isolates was notably reduced. These findings were less evident among E. coli isolates. Despite the significant increase in TZP consumption, the respective resistance rates of both bacterial species examined have remained almost unchanged. PMID:17189092

Petrikkos, George; Markogiannakis, Antonios; Papaparaskevas, Joseph; Papapareskevas, Joseph; Daikos, George L; Stefanakos, George; Zissis, Nicholas P; Avlamis, Athina



Potential of old-generation antibiotics to address current need for new antibiotics.  


Despite the constantly increasing need for new antimicrobial agents, antibiotic drug discovery and development seem to have greatly decelerated in recent years. Presented with the significant problem of advancing antimicrobial resistance, the global scientific community has attempted to find alternative solutions; one of the most promising ones is the evaluation and use of old antibiotic compounds. Due to the low-level use of many of the old antibiotic compounds, these have remained active against a large number of currently prevalent bacterial isolates. Thus, clinicians are beginning to re-evaluate their use in various patient populations and infections, despite the fact that they were previously thought to be less effective and/or more toxic than newer agents. A number of old antibiotic compounds, such as polymyxins, fosfomycin, fusidic acid, cotrimoxazole, aminoglycosides and chloramphenicol, are re-emerging as valuable alternatives for the treatment of difficult-to-treat infections. The availability of novel genetic and molecular modification methods provides hope that the toxicity and efficacy drawbacks presented by some of these agents can be surpassed in the future. PMID:18847400

Falagas, Matthew E; Grammatikos, Alexandros P; Michalopoulos, Argyris



Antibacterial activity of various antibiotics against oral streptococci isolated in the oral cavity.  


A total of 550 oral streptococci: 270 Streptococcus mitis, 110 Streptococcus sanguis, 90 Streptococcus anginosus, 50 Streptococcus mutans, 30 Streptococcus salivarius, were isolated from dental plaque and gengival crevices of patients and tested for their susceptibility to 12 ?-lactam antibiotics and to 5 non-?-lactam antibiotics, using the microdiluition method. Overall, a reduced susceptibility to penicillin was recorded in 13.4% of cases. The percentage of strains resistant to penicillin appeared significantly higher in S. mitis (24%) than in S. sanguis (19%), in S. mutans (14%) and in S. salivarius (10%). No levels of penicillin resistance were shown by 90 strains of S. anginosus. In susceptibility test to antibiotics, imipenem was the most active molecule tested, confirming its general good activity against oral streptococci. Also third generation cephalosporins such as ceftriaxone and fourth generation cephalosporins such as cefepime, showed good activity. Chinolones, glycopeptides and rifampicin confirmed a good activity against oral streptococci. PMID:23058035

Pasquantonio, G; Condň, S; Cerroni, L; Bikiqu, L; Nicoletti, M; Prenna, M; Ripa, S


Do antibiotic residues in soils play a role in amplification and transmission of antibiotic resistant bacteria in cattle populations?  


When we consider factors that contribute to the emergence, amplification, and persistence of antibiotic resistant bacteria, the conventional assumption is that antibiotic use is the primary driver in these processes and that selection occurs primarily in the patient or animal. Evidence suggests that this may not always be the case. Experimental trials show that parenteral administration of a third-generation cephalosporin (ceftiofur) in cattle has limited or short-term effects on the prevalence of ceftiofur-resistant bacteria in the gastrointestinal tract. While this response may be sufficient to explain a pattern of widespread resistance to cephalosporins, approximately two-thirds of ceftiofur metabolites are excreted in the urine raising the possibility that environmental selection plays an important additive role in the amplification and maintenance of antibiotic resistant E. coli on farms. Consequently, we present a rationale for an environmental selection hypothesis whereby excreted antibiotic residues such as ceftiofur are a significant contributor to the proliferation of antibiotic resistant bacteria in food animal systems. We also present a mathematical model of our hypothesized system as a guide for designing experiments to test this hypothesis. If supported for antibiotics such as ceftiofur, then there may be new approaches to combat the proliferation of antibiotic resistance beyond the prudent use mantra. PMID:23874327

Call, Douglas R; Matthews, Louise; Subbiah, Murugan; Liu, Jinxin



Cephalothin, a New Cephalosporin with a Broad Antibacterial Spectrum  

PubMed Central

Cephalothin is 7-(thiophene-2-acetamido) cephalosporanic acid; it was prepared by N-acylation of the nucleus of cephalosporin C, 7-aminocephalosporanic acid. Cephalothin had a broad spectrum of antibiotic activity that was essentially unaffected by human serum or inoculum level, the activity of penicillinase, or pH variation of the growth medium. In vitro development of resistance by staphylococci could not be demonstrated, but the gram-negative organisms did develop a stepwise type of resistance to the antibiotic. Staphylococci made resistant in vitro to 5-methyl-3-phenyl-4-isoxazole penicillin were also resistant to cephalothin and to 6-(2,6-dimethoxybenzamido) penicillin; however, the mechanism of resistance to each antibiotic may have differed. Some complications involved in the laboratory evaluation methods currently in use in the field of antibiotics are examined.

Godzeski, C. W.; Brier, Gordon; Pavey, D. E.



[Influence of the displacement of protein binding by ibuprofen in the activity of a third-generation cephalosporin against Streptococcus pneumoniae].  


The clinical significance of protein binding remains to be fully elucidated. The aim of this study was to evaluate the effect in the in vitro bactericidal activity of cefditoren through killing curves at Cmax concentrations against three Streptococcus pneumoniae strains (cefditoren MICs of 0.12, 0.25 and 0.5 mg/l) with or without human albumin (4 g/dl) and ibuprofen at Cmax concentrations (32.3 mg/l) and 10 times the Cmax (323 mg/l). Cefditoren was rapidly bactericidal (3 log(10) CFU/ml reduction) against the three strains at 4.2 mg/l concentration in Mueller-Hinton broth plus 5% lysed horse blood. In presence of human albumin, this effect was maintained against the most susceptible strain (MIC = 0.12 mg/l). Regrowths were observed with higher MIC values. The presence of ibuprofen (32.3 mg/l) slightly delayed regrowth while the increase of ibuprofen concentration up to 10 x Cmax recovered the bactericidal activity against all strains. The activity of an antimicrobial with high protein binding should not be linked exclusively with the theoretical unbound fraction extrapolated from the plasma concentration. The role of protein binding antagonists merits analysis due to their frequent use associated with cephalosporins in respiratory tract infections. PMID:17235401

Cafini, F; González, N; Torrico, M; Echeverría, O; Sevillano, D; Alou, L; Giménez, M J; Aguilar, L; Gómez-Lus, M L



Generation of Novel Pikromycin Antibiotic Products Through Mutasynthesis  

PubMed Central

Mutasynthesis in pikromycin PKS: The amenability of pikromycin polyketide synthase to mutational biosynthesis has been demonstrated. A natural triketide and its analogues, activated as N-acetyl-cysteamine thioesters, were synthesized and fed to a pikAI-deleted strain; this led to the production of new antibiotics. A vinyl analogue was found to have better antibacterial activity than pikromycin. The pikromycin polyketide synthase (PKS) of S. venezuelae, which consists of one loading module and six extension modules, is responsible for the formation of the hexaketide narbonolide, a key intermediate ok? in the biosynthesis of the antibiotic pikromycin. S. venezuelae strains in which PikAI, which houses the loading domain and first two modules of the PKS, is either absent or catalytically inactive, produce no pikromycin product. When these strains are grown in the presence of a synthetically prepared triketide product, activated as the N-acetylcysteamine thioester, pikromycin yields are restored to as much as 11 % of that seen in the wild-type strain. Feeding analogues of the triketide intermediate provides pikromycin analogues bearing different alkyl substituents at C13 and C14. One of these analogues, ?15,16-dehydropikromycin, exhibits improved antimicrobial activity relative to pikromycin.

Gupta, Shuchi; Lakshmanan, Venkatraman; Kim, Beom Seok; Fecik, Robert



Association of broad-spectrum antibiotic use with faecal carriage of oxyiminocephalosporin-resistant enterobacteriaceae in an intensive care unit.  


The link between administration of antibiotics and detection of third-generation-cephalosporin-resistant (TGCR) enterobacteriaceae in faeces was studied in patients in a burns intensive care unit (ICU). The presence of extended-spectrum beta-lactamase producers was also determined in these isolates. At least two rectal swab samples were taken from 43 of 72 patients admitted to the ICU from January 1998 to June 1999. Antibiotic resistance tests were performed for all isolated enterobacteriaceae using the methods of the National Committee for Clinical Laboratory Standards. Only 10 out of 30 antibiotic-treated patients showed TGCR enterobacteriaceae in faeces. Fisher's exact test showed a relationship between the administration of oxyiminocephalosporins (third-generation cephalosporins) (P=0.002) or carbapenems (P=0.003) and the isolation of TGCR enterobacteriaceae from faeces. The administration of oxyiminocephalosporins led to the selection of resistant strains in the faecal flora. PMID:16650501

Vignoli, R; Calvelo, E; Cordeiro, N F; Lucero, R; Ingold, E; Quintana, A; Del Monte, A; Schelotto, F



Industrial production of ß-lactam antibiotics  

Microsoft Academic Search

The industrial production of ?-lactam antibiotics by fermentation over the past 50 years is one of the outstanding examples of biotechnology. Today, the ?-lactam antibiotics, particularly penicillins and cephalosporins, represent the world's major biotechnology products with worldwide dosage form sales of ~US$ 15 billion or ~65% of the total world market for antibiotics. Over the past five decades, major improvements in the

R. P. Elander



Adherence to perioperative antibiotic prophylaxis among orthopedic trauma patients  

PubMed Central

Background The goal of this study was to assess whether patients receive their antibiotic prophylaxis as prescribed. We also investigated what doses and durations of antibiotics are typically ordered, which patients actually receive antibiotics and factors causing the ordered antibiotic regimen to be altered. Methods We performed a retrospective review of 205 patient charts and sent a national survey to all surgeon members of the Canadian Orthopaedic Trauma Society (COTS) about antibiotic prophylaxis in the setting of surgical treatment for closed fractures. Results In all, 93% (179 of 193) of patients received an appropriate preoperative dose of antibiotics, whereas less than 32% (58 of 181) of patients received their postoperative antibiotics as ordered. The most commonly stated reason for patients not receiving their postoperative antibiotics as ordered was patients being discharged before completing 3 postoperative doses. There was a 70% (39 of 56) response rate to the survey sent to COTS surgeons. A single dose of a first-generation cephalosporin preoperatively followed by 3 doses postoperatively is the most common practice among orthopedic trauma surgeons across Canada, but several surgeons give only preoperative prophylaxis. Conclusion Adherence to multidose postoperative antibiotic regimens is poor. Meta-analyses have failed to demonstrate the superiority of multidose regimens over single-dose prophylaxis. Single-dose preoperative antibiotic prophylaxis may be a reasonable choice for most orthopedic trauma patients with closed fractures.

Lundine, Kristopher M.; Nelson, Susan; Buckley, Richard; Putnis, Sven; Duffy, Paul J.



Klebsiella pneumoniae resistant to third-generation cephalosporins in five African and two Vietnamese major towns: multiclonal population structure with two major international clonal groups, CG15 and CG258.  


The molecular epidemiology of third-generation cephalosporin-resistant (3GC-R) Klebsiella pneumoniae in developing countries is poorly documented. From February 2007 to March 2008, we collected 135 3GC-R K. pneumoniae isolates from seven major towns in Maghreb (Morocco), West Africa (Senegal, Côte d'Ivoire), Central Africa (Cameroon), East Africa (Madagascar) and Southeast Asia (Vietnam). Their genetic diversity, assessed by multilocus sequence typing, was high (60 sequence types), reflecting multiclonality. However, two major clonal groups, CG15 (n = 23, 17% of isolates) and CG258 (n = 18, 13%), were detected in almost all participating centres. The two major clonal groups have previously been described in other parts of the world, indicating their global spread. The high diversity of enterobacterial repetitive intergenic consensus sequence-PCR banding patterns at the local level indicates that most isolates were epidemiologically unrelated. The isolates were characterized by the presence of multiple resistance determinants, most notably the concomitant presence of the aac(6')-Ib-cr, qnr and blaCTX-M-15 genes in 61 isolates (45%) belonging to 31 sequence types. These isolates were detected across a large geographical area including Cameroon (n = 1), Vietnam (n = 4), Madagascar (n = 10), Côte d'Ivoire (n = 12), Morocco (n = 13) and Senegal (n = 21). These results have major implications for patient management and highlight a potential reservoir for resistance determinants. PMID:22390772

Breurec, S; Guessennd, N; Timinouni, M; Le, T A H; Cao, V; Ngandjio, A; Randrianirina, F; Thiberge, J M; Kinana, A; Dufougeray, A; Perrier-Gros-Claude, J D; Boisier, P; Garin, B; Brisse, S



Identifying Genetic Susceptibility to Sensitization to Cephalosporins in Health Care Workers  

PubMed Central

Exposure to cephalosporins could cause occupational allergic diseases in health care workers (HCWs). We evaluated the prevalence of serum specific IgE and IgG antibodies to cephalosporin-human serum albumin (HSA) conjugate and to identify potential genetic risk factors associated with sensitization to cephalosporins in exposed HCWs. The study population consisted of 153 HCWs who had been exposed to antibiotics in a single university hospital and 86 unexposed healthy controls. A questionnaire survey of work-related symptoms (WRS) was administered. A skin-prick test (SPT) was performed, and serum-specific IgE and IgG antibodies to 3 commonly prescribed cephalosporins were measured by ELISA. Four single-nucleotide polymorphisms of the candidate genes related to IgE sensitization were genotyped. The prevalence of WRS to cephalosporins was 2.6%. The prevalence rates of serum-specific IgE and IgG antibodies to cephalosporins were 20.3% and 14.7%, respectively. The Fc?R1?-109T > C polymorphism was significantly associated with IgE sensitization to cephalosporins in HCWs (P = 0.036, OR = 3.553; CI, 1.324-9.532). The in vitro functional assay demonstrated that the T allele of Fc?R1?-109T had greater promoter activity than did the C allele (P < 0.001). The Fc?R1?-109T > C polymorphism may be a potential genetic risk factor for increased IgE sensitization to cephalosporins.

Nam, Young-Hee; Kim, Jeong-Eun; Kim, Seung-Hyun; Jin, Hyun Jung; Hwang, Eui-Kyung; Shin, Yoo-Seob; Ye, Young-Min



Antibiotic Resistance to Third Generation Cephalosporins Due to CTX-M-Type Extended-Spectrum ?-Lactamases in Clinical Isolates of Escherichia coli  

Microsoft Academic Search

Background: Organisms producing CTX-M-?-lactamase are emerging around the world as a source of resistance to oxyiminocephalosporins such as cefotaxime. However, the laboratory detection of these strains is not well defined. The aim of this study was to determine the presence and prevalence of known CTX-M-?-lactamases genes in clinical isolates of Escherichia coli from hospitals of Tehran. Methods: During six months

M Mirzaee; M R Pourmand; M Chitsaz; S Mansouri


Magnetic separation of antibiotics by electrochemical magnetic seeding  

Microsoft Academic Search

Magnetic separation of several classes of antibiotics was investigated using electrochemical magnetic seeding. Electrocoagulation with a sacrificial anode followed by addition of magnetite particles was applied for the magnetic seeding of antibiotics. With electrochemical magnetic seeding using an iron anode, tetracycline antibiotics (oxytetracycline, chlortetracycline, doxycycline and tetracycline) and cephalosporin antibiotic (cefdinir) were rapidly removed from synthetic wastewater by magnetic separation

I. Ihara; K. Toyoda; N. Beneragama; K. Umetsu



Ceftaroline: A New Cephalosporin with Activity against Methicillin-Resistant Staphylococcus aureus (MRSA)  

PubMed Central

Microbial resistance has reached alarming levels, threatening to outpace the ability to counter with more potent antimicrobial agents. In particular, methicillin-resistant Staphylococcus aureus (MRSA) has become a leading cause of skin and soft-tissue infections and PVL-positive strains have been associated with necrotizing pneumonia. Increasing reports of growing resistance to glycopeptides have been noted, further limiting the efficacy of standard antibiotics, such as vancomycin. Ceftaroline is a novel fifth-generation cephalosporin, which exhibits broad-spectrum activity against Gram-positive bacteria, including MRSA and extensively-resistant strains, such as vancomycin-intermediate S. aureus (VISA), heteroresistant VISA (hVISA), and vancomycin-resistant S. aureus (VRSA). In addition to being an exciting new agent in the anti-MRSA armamentarium, ceftaroline provides efficacy against many respiratory pathogens including Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Ceftaroline (600 mg intravenously every 12 hours) has been shown effective in phase III studies in the treatment of complicated skin and soft tissue infections and community-acquired pneumonia. To date, this unique antibiotic exhibits a low propensity for inducing resistance and has a good safety profile, although further post-marketing data and clinical experience are needed. In summary, ceftaroline provides an additional option for the management of complex multidrug resistant infections, including MRSA.

Duplessis, Christopher; Crum-Cianflone, Nancy F.



MurAA Is Required for Intrinsic Cephalosporin Resistance of Enterococcus faecalis  

PubMed Central

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.

Vesic, Dusanka



Neue Entwicklungen bei den Cephalosporin-Antibiotika  

Microsoft Academic Search

Zusammenfassung Cephalosporine sind bakterizide ß-Laktamring-Antibiotika mit einem breiten antibakteriellen Spektrum. Ihre molekularbiologische Wirkung beruht auf der Hemmung der Biosynthese der Bakterienzellwand. Die neuentwickelten Cephalosporine (Cefamandol, Cefoxitin, Cefuroxim) zeichnen sich durch eine verbesserte und verbreiterte Wirkung gegenüberEnterobacteriaceae aus. Bei den klinisch häufigsten gramnegativen Keimen ist Cefamandol die aktivste Substanz, Cefuroxim ist nur unwesentlich weniger aktiv. Cefoxitin bietet Vorteile bei indolpositivenProteus-Spezies,Serratia und

H. Lode; B. Baruch; P. Koeppe; S. Lehmann-Brauns



Therapeutic activities of antibiotics in listeriosis  

Microsoft Academic Search

Summary In vitro practically all common antibiotics except cephalosporins are active against nearly all natural isolates ofListeria monocytogenes; the therapeutic efficacy of antibiotic treatment is, however, rather limited, since up to 30% listeriosis patients will succumb to this infection. At least one reason for this lowin vivo efficiency is the intracellular habitat ofL. monocytogenes. In animal experiments ampicillin or amoxicillin,

H. Hof



Differences in the changes in resistance patterns to third- and fourth-generation cephalosporins and piperacillin\\/tazobactam among Klebsiella pneumoniae and Escherichia coli clinical isolates following a restriction policy in a Greek tertiary care hospital  

Microsoft Academic Search

The aim of the present study was to investigate whether replacement of broad-spectrum cephalosporins (CEPs) by piperacillin\\/tazobactam (TZP) as first-line empirical therapy may have an effect on ?-lactam resistance among Klebsiella pneumoniae and Escherichia coli in a tertiary care hospital. Data regarding CEP and TZP consumption and resistance were collected on a bimonthly basis during an open-label 2-year (1 year

George Petrikkos; Antonios Markogiannakis; Joseph Papapareskevas; George L. Daikos; George Stefanakos; Nicholas P Zissis; Athina Avlamis



Comparative photodynamic inactivation of antibiotic resistant bacteria by first and second generation cationic photosensitizers.  


Photodynamic inactivation (PDI) is an efficient approach against a wide range of microorganisms and can be viewed as an alternative for the treatment of microbial infections. In this work we synthesized "first" and "second" generation photosensitizers (PSs), the tetra-cationic porphyrin and the new penta-cationic chlorin , respectively, and evaluated their efficiency against two antibiotic resistant bacterial strains, Staphylococcus aureus and Pseudomonas aeruginosa. The PS was obtained in very good yield by an easy synthesis method. The PDI studies were performed in parallel with 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin tetra-iodide (), a widely studied PS in PDI, and the obtained results were compared. Two different light ranges were used: white light (400-800 nm) and red light (530-800 nm) delivered at a fluence rate of 150 mW cm(-2). The results show that both strains, even though antibiotic resistant, were efficiently inactivated by the three PSs, chlorin being the most effective. For the Gram positive bacterium S. aureus a 7.0 log reduction was observed after 5-10 min of irradiation, at a concentration of 0.5 ?M, whereas for the Gram negative P. aeruginosa, similar photoinactivation occurred at a higher PS concentration (10 ?M) and after a longer irradiation period (30 min). The synthetic chlorin can be regarded as promising for the treatment of bacterial infections under red light, which penetrates deeper in living tissues. The results of this study open the possibility to prepare a new series of chlorin-type derivatives to efficiently photoinactivate Gram (+) and (-) antibiotic resistant bacteria. The efficient PDI with the chlorin indicates high potential for the use of a scaffold in the preparation of new generation PSs based on cationic chlorin derivatives. PMID:22940776

Costa, Dora C S; Gomes, Maria C; Faustino, Maria A F; Neves, Maria G P M S; Cunha, Angela; Cavaleiro, José A S; Almeida, Adelaide; Tomé, Joăo P C



Electrochemical degradation of the antibiotic sulfachloropyridazine by hydroxyl radicals generated at a BDD anode.  


The treatment of aqueous solutions of the antibiotic sulfachloropyridazine (SCP) was carried out at the natural pH of the solution (pH 4.5) with hydroxyl radicals (OH) generated at a BDD anode surface by electro-oxidation using an undivided electrochemical cell equipped with a three-dimensional carbon-felt cathode. Hydroxyl radicals are powerful oxidants and react with the antibiotic leading to its overall mineralization. The kinetic study showed that oxidative degradation of SCP follows pseudo first-order reaction kinetics, with a relatively short degradation time. The degree of mineralization of SCP solutions increased with the applied current, being higher than 95% after 8 h of electrolysis at 350 mA or higher current. To determine the degradation pathway upon the action of hydroxyl radicals, the cyclic and aliphatic by-products, as well as the released inorganic ions, were identified and quantified over electrolysis time. The values of the rate constants of reactions between OH and the SCP and its intermediates were determined by the competition kinetics method using p-hydroxybenzoic acid. The absolute rate constant for the OH-mediated degradation of SCP was found to be 1.92 × 10(9)M(-1)s(-1). Toxicity assessment by the Microtox method during the electro-oxidation of SCP solutions revealed the formation of compounds that can be more toxic than the parent molecule, but the overall results confirm the effectiveness of this electrochemical process for the removal of the antibiotic SCP and its by-products from aqueous media. PMID:23541359

Haidar, Mariam; Dirany, Ahmad; Sirés, Ignasi; Oturan, Nihal; Oturan, Mehmet A



Cephalosporin 3'-phloroglucide esters and 7-(phloroglucidamido) cephalosporins as novel antibacterial agents.  


Two series of new phloroglucide derivatives were synthesized that possessed antibacterial activities. The first series includes cephalosporin 3'-phloroglucide esters 19 and 20, which were obtained by condensation of cephalosporin 16 with bioactive phloroglucides 14 and 15, respectively. They exhibited a dual mode of antibacterial action. In comparison with cephalosporins 26 and 27, bearing an acetoxy unit at the C-3' position, the bifunctional cephalosporins 19 and 20 showed a broadened spectrum of activity. Results from the consistent valence force field (CVFF) calculations indicate that the most stable conformational isomer of phenolic acid 14, holding a cis-syn-syn geometry, possessed a cavity. It provides an ideal environment to accommodate metal ions of holoenzymes. Phenolic keto acid 15, however, possessed a trans-anti-syn conformation, which allowed chelation between metal ions and the phenolic hydroxyl groups as well as the carbonyl functionalities. Our biological results show that the cavity formed in phloroglucides plays an important role. The second series includes 7-(phloroglucidamido)cephalosporins 24 and 25, which were synthesized by condensation of cephalosporin 21 with 14 and 15, respectively. Results from the CVFF calculations indicate that cephalosporin 24 also possessed a cavity. Unlike cephalosporin 3'-phloroglucide esters 19 and 20, cephalosporins 24 and 25 were found resistant to beta-lactamases from Staphylococcus aureus 95 and Pseudomonas aeruginosa 18S-H. These new compounds, however, showed notable activities against S. aureus FDA 209P, S. aureus 95, Candida albicans, P. aeruginosa 1101-75, and P. aeruginosa 18S-H. PMID:9341918

Hwu, J R; Moshfegh, A A; Tsay, S C; Lin, C C; Tseng, W N; Azaripour, A; Mottaghian, H; Hakimelahi, G H



Use of selected cephalosporins in penicillin-allergic patients: a paradigm shift.  


Recent analysis of clinical data and a clearer understanding of the role of chemical structure in the development of cross-reactivity indicate that the increased risk of an allergic reaction to certain cephalosporins in penicillin-allergic patients is smaller than previously postulated. Medline and EMBASE databases were searched using the following keywords: cephalosporin, penicillin, allergy, and cross-sensitivity for the years 1960 to 2005. Among 219 articles retrieved, 106 served as source material for this review. A significant increase in allergic reactions to cephalothin, cephaloridine, cephalexin, cefazolin, and cefamandole was observed in penicillin-allergic patients; no increase was observed with cefprozil, cefuroxime, ceftazidime, or ceftriaxone. Clinical challenges, skin testing, and monoclonal antibody studies point to the paramount importance of similarities in side chain structure to predict cross-allergy between cephalosporins and penicillins. First-generation cephalosporins have a modest cross-allergy with penicillins, but cross-allergy is negligible with 2nd- and 3rd-generation cephalosporins. Particular emphasis is placed on the role of chemical structure in determining the risk of cross-reactivity between specific agents. PMID:17349459

Pichichero, Michael E



Urine from Treated Cattle Drives Selection for Cephalosporin Resistant Escherichia coli in Soil  

PubMed Central

The U.S. Food and Drug Administration recently issued new rules for using ceftiofur in food animals in part because of an increasing prevalence of enteric bacteria that are resistant to 3rd-generation cephalosporins. Parenteral ceftiofur treatment, however, has limited effects on enteric bacteria so we tested the hypothesis that excreted ceftiofur metabolites exert significant selection pressure for ceftiofur-resistant Escherichia coli in soil. Test matrices were prepared by mixing soil with bovine feces and adding urine containing ceftiofur metabolites (CFM) (0 ppm, ?50 ppm and ?100 ppm). Matrices were incubated at 23°C or 4°C for variable periods of time after which residual CFM was quantified using a bioassay. BlaCMY-2 plasmid-bearing ceftiofur resistant (cefR) E. coli and one-month old calves were used to study the selection effects of CFM and transmission of cefR bacteria from the environment back to animals. Our studies showed that urinary CFM (?13 ppm final concentration) is biologically degraded in soil within 2.7 days at 23°C, but persists up to 23.3 days at 4°C. Even short-term persistence in soil provides a >1 log10 advantage to resistant E. coli populations, resulting in significantly prolonged persistence of these bacteria in the soil (?two months). We further show that resistant strains readily colonize calves by contact with contaminated bedding and without antibiotic selection pressure. Ceftiofur metabolites in urine amplify resistant E. coli populations and, if applicable to field conditions, this effect is far more compelling than reported selection in vivo after parenteral administration of ceftiofur. Because ceftiofur degradation is temperature dependent, these compounds may accumulate during colder months and this could further enhance selection as seasonal temperatures increase. If cost-effective engineered solutions can be developed to limit ex vivo selection, this may limit proliferation for ceftiofur resistant enteric bacteria while preserving the ability to use this important antibiotic in food animal production.

Subbiah, Murugan; Shah, Devendra H.; Besser, Thomas E.; Ullman, Jeffrey L.; Call, Douglas R.



Novel metagenome-derived carboxylesterase that hydrolyzes ?-lactam antibiotics.  


It has been proposed that family VIII carboxylesterases and class C ?-lactamases are phylogenetically related; however, none of carboxylesterases has been reported to hydrolyze ?-lactam antibiotics except nitrocefin, a nonclinical chromogenic substrate. Here, we describe the first example of a novel carboxylesterase derived from a metagenome that is able to cleave the amide bond of various ?-lactam substrates and the ester bond of p-nitrophenyl esters. A clone with lipolytic activity was selected by functional screening of a metagenomic library using tributyrin agar plates. The sequence analysis of the clone revealed the presence of an open reading frame (estU1) encoding a polypeptide of 426 amino acids, retaining an S-X-X-K motif that is conserved in class C ?-lactamases and family VIII carboxylesterases. The gene was overexpressed in Escherichia coli, and the purified recombinant protein (EstU1) was further characterized. EstU1 showed esterase activity toward various chromogenic p-nitrophenyl esters. In addition, it exhibited hydrolytic activity toward nitrocefin, leading us to investigate whether EstU1 could hydrolyze ?-lactam antibiotics. EstU1 was able to hydrolyze first-generation ?-lactam antibiotics, such as cephalosporins, cephaloridine, cephalothin, and cefazolin. In a kinetic study, EstU1 showed a similar range of substrate affinities for both p-nitrophenyl butyrate and first-generation cephalosporins while the turnover efficiency for the latter was much lower. Furthermore, site-directed mutagenesis studies revealed that the catalytic triad of EstU1 plays a crucial role in hydrolyzing both ester bonds of p-nitrophenyl esters and amide bonds of the ?-lactam ring of antibiotics, implicating the predicted catalytic triad of EstU1 in both activities. PMID:21908637

Jeon, Jeong Ho; Kim, Soo-Jin; Lee, Hyun Sook; Cha, Sun-Shin; Lee, Jung Hun; Yoon, Sang-Hong; Koo, Bon-Sung; Lee, Chang-Muk; Choi, Sang Ho; Lee, Sang Hee; Kang, Sung Gyun; Lee, Jung-Hyun



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

Microsoft Academic Search

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

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



[Structure peculiarities of cell walls of Acremonium chrysogenum--an autotroph of cephalosporin C].  


Alterations of cell walls of Acremonium chrysogenum occurring at intensive synthesis of cephalosporin C has been studied. It is shown, using electron microscopy, that the cell wall of the cells ofATCC 11550 strain ("wild" type) became looser and thicker during growth. The cell wall of the cells of strain 26/8 (hyperautotroph of cephalosporin C) considerably degraded by the end of the stationary phase. Biochemical analysis has shown that these alterations entailed decrease of the proteins' content covalently or noncovalently linked with the polysaccharides of cell walls of both strains. An increase of sensitivity of cell walls of the strain-superproducer to an activity of lytic enzymes of chitinase, laminarinase, proteinase K, and lyticase preparation has been observed during the growth, but this increase has not been found in the case of "wild" type strain. The obtained results evidence to the structure failure of the cell wall of A. chrysogenum entailing the intensive creation of antibiotic. PMID:21261077

Kelebina, T S; Seliakh, I O; Gorkovski?, A A; Bezsonov, E E; El'darov, M A; Novak, M I; Domracheva, A G; Bartoshevich, Iu E


Ready for a world without antibiotics? The Pensičres Antibiotic Resistance Call to Action.  


Resistance to antibiotics has increased dramatically over the past few years and has now reached a level that places future patients in real danger. Microorganisms such as Escherichia coli and Klebsiella pneumoniae, which are commensals and pathogens for humans and animals, have become increasingly resistant to third-generation cephalosporins. Moreover, in certain countries, they are also resistant to carbapenems and therefore susceptible only to tigecycline and colistin. Resistance is primarily attributed to the production of beta-lactamase genes located on mobile genetic elements, which facilitate their transfer between different species. In some rare cases, Gram-negative rods are resistant to virtually all known antibiotics. The causes are numerous, but the role of the overuse of antibiotics in both humans and animals is essential, as well as the transmission of these bacteria in both the hospital and the community, notably via the food chain, contaminated hands, and between animals and humans. In addition, there are very few new antibiotics in the pipeline, particularly for Gram-negative bacilli. The situation is slightly better for Gram-positive cocci as some potent and novel antibiotics have been made available in recent years. A strong and coordinated international programme is urgently needed. To meet this challenge, 70 internationally recognized experts met for a two-day meeting in June 2011 in Annecy (France) and endorsed a global call to action ("The Pensičres Antibiotic Resistance Call to Action"). Bundles of measures that must be implemented simultaneously and worldwide are presented in this document. In particular, antibiotics, which represent a treasure for humanity, must be protected and considered as a special class of drugs. PMID:22958833

Carlet, Jean; Jarlier, Vincent; Harbarth, Stephan; Voss, Andreas; Goossens, Herman; Pittet, Didier



Antibiotic Resistance Among Anaerobes: What Does it Mean?  

Microsoft Academic Search

Antibiotic resistance among anaerobes is increasing, with significant resistance to clindamycin, cephalosporins, cephamycins, and penicillins noted at community hospitals and major medical centers. A total of 615 anaerobes isolated from various Chicago area hospitals in 1996 were tested against 13 antibiotics, and the resistance patterns compared with similar data from 1991. For the Bacteroides fragilis group anaerobes, the most effective

David W. Hecht; Gayatri Vedantam; James R. Osmolski



Evidence for the involvement of GABA(A) receptor blockade in convulsions induced by cephalosporins.  


There is accumulating evidence that most beta-lactam antibiotics (i.e., cephalosporins and penicillins) have some degree of convulsive activity, both in laboratory animals as well as in clinical settings. The proposed mechanism is suppression of inhibitory postsynaptic responses, mainly mediated by gamma-amino butyric acid (GABA)(A)-receptors (GABA(A)-R). However, comprehensive studies on the convulsive activities of various beta-lactam antibiotics in vivo and in vitro have not been performed. We have therefore examined the convulsive activities of seven different cephalosporins using both in vivo and in vitro models: intracerebroventricular (ICV) administration in mouse; [(3)H]muscimol binding assay (BA) in mouse brain synaptosome; and inhibition of recombinant mouse alpha1beta2gamma2s GABA(A)-Rs in Xenopus oocyte (GR). The rank orders of convulsive activities in mouse (cefazolin>cefoselis>cefotiam>cefpirome>cefepime>ceftazidime>cefozopran) correlated with those of inhibitory potencies on [(3)H]muscimol binding and GABA-induced currents of GABA(A)-R in vitro, with correlation coefficients of ICV:GR, ICV:BA and BA:GR of 0.882, 0.821 and 0.832, respectively. In contrast, none of the antibiotics had affinities for N-methyl-D-aspartate (NMDA) receptors nor facilitatory actions on NMDA receptor-mediated current in oocytes. These results clearly demonstrate that the mechanism of cephalosporin-induced convulsions is mediated predominantly through the inhibition of GABA(A)-R function and not through NMDA receptor modulation. PMID:12871648

Sugimoto, Masahiro; Uchida, Ichiro; Mashimo, Takashi; Yamazaki, Shunji; Hatano, Kazuo; Ikeda, Fumiaki; Mochizuki, Yoshitaka; Terai, Takao; Matsuoka, Nobuya



Antibiotics and Antibiotic Resistance  

Center for Drug Evaluation (CDER)

... use of antibiotics and the serious health threat of antibiotic resistance; Fighting the Impact of Antibiotic-Resistant Bacteria FDA Consumer Update ... More results from


Antibiotics for the newborn.  


Because of the high susceptibility to infections, antibiotics are the most widely used drugs in newborns. The result of antibiotic use, however, may be strongly influenced by the peculiar physiology of the neonate, characterized by the delicate process of adaptation from intra- to extra-uterine life. Additional important factors that may affect antibiotic therapy are gestational age, birth weight, the intrauterine growth restriction, chronological age and, especially, the kidney and liver function immaturity. Dosing, timing and route of administration must, therefore, take in careful consideration the neonatal variability of bioavailability, distribution, metabolism, biotransformation, and excretion. The fine adjustment of dosing and duration of therapy should be based on pharmacokinetic and pharmacodynamic parameters. In spite of significant variations of sepsis etiology, the best initial empiric therapy of a suspected systemic infection still remains, as several years ago, the association of ampicillin and gentamicin. Other very effective and useful antibiotics, as cephalosporins, carbanepems or glycopeptides should be administered judiciously to infants, following the recommendations of a restricted use, to obtain maximal efficacy and minimal toxicity. Finally, because of their peculiar features, macrolide antibiotics have recently been proposed for different indications than the antibacterial activity. Use of oral erythromycin for the treatment of gastrointestinal dysmotility in preterm infants could reduce the incidence of parenteral nutrition-associated cholestasis by almost 50%, while azithromycin because of the combined antibiotic and anti-inflammatory effects, has been successfully used in a pilot study in the extremely low birth weight infant for the prevention of bronchopulmonary dysplasia. PMID:19718590

Chirico, Gaetano; Barbieri, Fabiana; Chirico, Claudia



Prospective Randomized Study for Antibiotic Prophylaxis in Spine Surgery: Choice of Drug, Dosage, and Timing  

PubMed Central

Study Design Prospective randomized study of antibiotic prophylaxis in elective spine surgery. Purpose The aim of this study was to compare the rate of postoperative surgical site infection for a single dose of two different generations of cephalosporin with different dosage and timing of the antibiotics. Overview of Literature Current recommendation for prophylaxis in elective spine surgery is up to 60 minutes prior to incision. No study has investigated between different generation of cephalosporin for prophylaxis in elective spine surgery with respect to choice, dosage and timing. Methods This study was a prospective randomized study of 90 patients, assessed for the occurrence of surgical site infection (defined by the Centers for Disease Control and Prevention criteria) and other infections for up to 6 months after surgery. Demographic, surgical and further data were collected on subsequent operations, including hardware removal. Results Mean age in our group was 47 years (range, 19-71 years). The male to female ratio was 49:41 and the average timing of administration of antibiotics was 77 minutes (range, 30-120 minutes). The average blood loss was 626 mL (range, 150-3,000 mL) with a mean duration of surgery for 3.2 hours (range, 1.5-6 hours). One case of superficial infection and one case of deep infection met the exclusion criteria. Conclusions Our results support the use of a single preoperative dose of antibiotics in instrumented and non-instrumented elective spine surgery up to one hour prior to incision. There was no difference in terms of occurrence of surgical site infection with respect to dosage, choice and timing of antibiotics.

Kailash, Kannan Karthick; Vijayraghavan, P.V.



Die Resistenz methicillinresistenter Staphylokokken gegenüber neuen Cephalosporin-Antibiotika  

Microsoft Academic Search

Zusammenfassung An einem Kollektiv von 60 Koagulase-positiven staphylokokkenstämmen mit Methicillin-resistenz wurde die Aktivität neuer Cephalosporine geprüft und mit der von Cefalotin, Methicillin und Oxacillin verglichen. Dabei ergab sich, daß das Cefamandol als aktivste Substanz der neuen Cephalosporine in seiner Aktivität dem Cefalotin gleichkommt, Cefoxitin dem Oxacillin und Methicillin gleichzusetzen ist und Cefuroxim, Cefoperazon, Cefotaxim sowie das Moxalactam gegen Staphylokokken mit

F. H. Kayser



The realm of penicillin G acylase in ?-lactam antibiotics  

Microsoft Academic Search

Penicillin G acylase (PGA; EC is a hydrolytic enzyme that acts on the side chains of penicillin G, cephalosporin G and related antibiotics to produce the ?-lactam antibiotic intermediates 6-amino penicillanic acid (6-APA) and 7-amino des-acetoxy cephalosporanic acid (7-ADCA), with phenyl acetic acid (PAA) as a common by-product. These antibiotic intermediates are among the potential building blocks of semi-synthetic

Anuj K. Chandel; L. Venkateswar Rao; M. Lakshmi Narasu; Om V. Singh



Novel plasmid-mediated beta-lactamase from Escherichia coli that inactivates oxyimino-cephalosporins.  

PubMed Central

A highly cephem-resistant Escherichia coli strain, FP1546, isolated from the fecal flora of laboratory dogs previously administered beta-lactam antibiotics was found to produce a beta-lactamase, FEC-1, of 48-kilodalton size and pI 8.2. FEC-1 hydrolyzed cefuroxime, cefotaxime, cefmenoxime, and ceftriaxone, as well as the enzymatically less-stable antibiotics cephaloridine, cefotiam, and cefpiramide. Of the oxyimino-cephalosporins, ceftizoxime was fairly stable to FEC-1. FEC-1 differed notably from chromosomal E. coli cephalosporinase, especially in its broad-spectrum substrate profile and its high inhibition by clavulanic acid, sulbactam, and imipenem. A conjugation study revealed that FEC-1 was encoded by a 74-megadalton plasmid, pFCX1. This may be the first instance of a plasmid-mediated oxyimino-cephalosporinase from E. coli.

Matsumoto, Y; Ikeda, F; Kamimura, T; Yokota, Y; Mine, Y



Surveillance of Antibiotic Consumption Using the "Focus of Infection" Approach in 2 Hospitals in Ujjain, India  

PubMed Central

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.

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



Synergism between aminoglycosides and cephalosporins with antipseudomonal activity: interaction index and killing curve method.  

PubMed Central

Combinations of gentamicin with cefotaxime, moxalactam, and ceftazidime were tested against 43 bacterial strains, most of them blood isolates. With an interaction index of less than or equal to 0.5 as borderline, synergism was demonstrated against 30 to 40% of the strains by the fractional inhibitory concentration index and against 50 to 70% by the fractional bactericidal concentration index. The reproducibility of the index was within +/- 0.2 for two-thirds of 40 repetitive assays and within +/- 0.4 to 0.5 for all of these assays. Similar results were obtained when netilmicin was substituted for gentamicin. The killing curve system for studying antibiotic synergism was standardized to give results comparable to those obtained with the interaction index. This was achieved when one-half of a previously determined minimum bactericidal concentration was used for single drugs and the amount of antibiotic was at least halved again when drugs were used in combination. An initial bacterial concentration of 10(5) to 10(6) colony-forming units per ml is recommended. Given these conditions, synergism could be defined as a 2-log 10 or more decrease in viable count given by both drugs together, as compared with the more active of the pair after 24 h. Prediction of killing curve results could then be obtained with the fractional bactericidal concentration index. When cephalosporins and gentamicin were combined from the start, the beta-lactam antibiotics were less susceptible to inactivation, as demonstrated in time-killing assays. If one of the antibiotics were added after 24 h, synergism was not demonstrable. The results indicate that the new cephalosporins may be advantageously combined with aminoglycosides.

Hallander, H O; Dornbusch, K; Gezelius, L; Jacobson, K; Karlsson, I



Cross-sectional study on fecal carriage of enterobacteriaceae with resistance to extended-spectrum cephalosporins in primary care patients.  


The aim of this study was to gain knowledge of the local epidemiology of extended-spectrum cephalosporin-resistant bacteria in primary care patients in a Swiss community. Fecal swabs were obtained from 291 primary care patients. Phenotyping and genotyping methods were used for further characterization of the isolates. Risk factors associated with carriage of ß-lactam-resistant strains were determined. Extended-spectrum cephalosporin-resistant Enterobacteriaceae were detected in 15 (5.2%) of the primary care patients. Thirteen isolates were CTX-M producers, one produced SHV-12, and three carried CMY-2. The pathogenic pandemic clone Escherichia coli ST131 was detected in 26.6% of the patients. Two patients (13.3%) carried two distinct strains simultaneously. There was a statistically significant risk of carriage of resistant strains for persons with a history of antibiotic therapy 4 months before sampling (p=0.05), markedly for therapy with ß-lactam (p=0.01). Age, gender, or history of hospitalization 4 months before sampling was not a risk factor for the acquisition of resistant bacteria in the analyzed patients. The relatively low prevalence of extended-spectrum cephalosporin-resistant strains in the community reflects the nationwide restrictive policy of antibiotic prescription as well as local implementation thereof. Nevertheless, our study shows that a potent antimicrobial resistance reservoir is present in primary care patients. PMID:23611297

Nüesch-Inderbinen, Magdalena T; Abgottspon, Helga; Zurfluh, Katrin; Nüesch, Hans J; Stephan, Roger; Hächler, Herbert



Identity of Cephalosporin N and Synnematin B  

Microsoft Academic Search

A SPECIES of Cephalosporium isolated in Sardinia was reported, in 1948, to produce an antibiotic which inhibited the growth of a number of Gram-positive and Gram-negative bacteria1. This antibiotic, which was only obtained in a crude form, was not characterized chemically. In 1949 certain members of the genus Cephalosporium, including one that was believed to constitute a new species, were

E. P. Abraham; G. G. F. Newton



The use of cephalosporins for gonorrhea: The impending problem of resistance  

PubMed Central

Gonorrhea remains an important clinical and public health problem throughout the world. Gonococcal infections have historically been diagnosed by Gram stain and culture, but are increasingly diagnosed through nucleic acid tests thereby eliminating the opportunity for antimicrobial susceptibility testing. Gonococcal infections are typically treated with single-dose therapy with an agent found to cure >95% of cases. Unfortunately, the gonococcus has repeatedly developed resistance to antimicrobials including sulfonamides, penicillin, tetracyclines, and fluoroquinolones. This has left third-generation cephalosporins as the lone class of antimicrobials currently recommended as first line therapy for gonorrhea in some regions. However, resistance to oral third-generation cephalosporins has emerged and spread in Asia, Australia and elsewhere. The mechanism of this resistance seems to be associated with a mosaic penicillin binding protein (penA) in addition to other chromosomal mutations previously found to confer resistance to beta-lactam antimicrobials (ponA, mtrR, penB, pilQ). Few good options exist or are in development for treating cephalosporin resistant isolates as most have had multidrug resistance. Preventing the spread of resistant isolates will depend on ambitious antimicrobial management programs, strengthening and expanding surveillance networks, and through effective sexually transmitted disease control and prevention.

Barry, Pennan M.; Klausner, Jeffrey D.



Polarographic determination of certain cephalosporins in pharmaceutical preparations  

PubMed Central

Polarographic methods have been developed for the determination of two cephalosporins namely cefotaxime (CTX) and ceftriaxone (CTR) in pharmaceutical formulations. Well defined peaks at potentials –1.432 V vs. SCE for CTX and –1.627 V vs. SCE for CTR were obtained in the presence of tungsten (VI). The method has been successfully applied for the determination of above mentioned cephalosporins in commercial dosage forms. The salient features of this investigation are presented in this communication.

Guru Prasad, A.R.; Rao, V.S.



Cephalosporin and carbacephem nephrotoxicity. Roles of tubular cell uptake and acylating potential.  


Three beta-lactams, desacetylcephaloglycin, ampicillin, and loracarbef, were studied to test a hypothesis derived from retrospective analysis of previously studied cephalosporins: that beta-lactam nephrotoxicity develops in approximate proportion to tubular cell antibiotic concentrations and lactam ring reactivities. Concentrations of each beta-lactam (and insulin) in rabbit renal cortex and serum were measured at the end of 0.5-hr infusions of 100 mg antibiotic/kg body weight and 0.5 to 0.67 hr later. Total cortical AUCs (total areas under the curve of concentration and time in renal cortex) and transported cortical AUCs (total minus insulin-space beta lactam) were calculated from these measurements. Reactivities, determined by the rate constants of lactam-ring opening at pH 10, were taken from the literature. Nephrotoxicity was quantified by grades of proximal tubular cell necrosis and by serum creatinine concentrations 2 days after infusion of 100-1500 mg/kg of the antibiotics. Desacetylcephaloglycin was slightly less nephrotoxic than cephaloglycin; the AUCs reactivities, and toxicities of these two cephalosporins fit the proposed model, particularly when allowance is made for hepatic and renal deacetylation of cephaloglycin. The very low AUCs, limited reactivity, and absence of nephrotoxicity of ampicillin also fit the model. Loracarbef had a transported AUC less than three times, and reactivity one-thirtieth, those of cefaclor, respectively. Although only at 1500 mg/kg, loracarbef was significantly more nephrotic than cefaclor. If the relativity of loracarbef with its targeted bacterial proteins, which is essentially the same as that of cefaclor, is considered instead of the base hydrolysis rate constant, than loracarbef also fits the model. By the same analysis, the comparatively high in vitro stability of other carbacephems, although pharmaceutically convenient, may not limit their nephrotoxicity. PMID:8619902

Tune, B M; Hsu, C Y; Fravert, D



Purification and characterization of a cephalosporin esterase from Rhodosporidium toruloides.  


A novel cephalosporin esterase (EC from Rhodosporidium toruloides was purified to gel electrophoretic homogeneity. The enzyme is a glycoprotein with a molecular mass of 80 kDa. Upon deglycosylation, several forms of the enzyme were observed with a molecular mass range between 60 and 66 kDa. The isoelectric point of the enzyme is approximately 5.6, with the pH optimum for activity occurring at 6.0. The optimal activity of the enzyme occurred at 25 degrees C, with the enzyme rapidly losing activity at temperatures above 25 degrees C. The enzyme deacetylated a variety of cephalosporin derivatives, including cephalosporin C; the Km for this substrate is 51.8 mM, and the Vmax is 7.9 mumol/min/mg. In addition to cephalosporins, the enzyme hydrolyzed short-chain p-nitrophenyl esters, with the activity decreasing with increasing ester chain length. The enzyme also has the ability to acetylate desacetyl cephalosporins in high yields under mild conditions in the presence of various acetyl donors. A comparison of the physical properties of the esterase with those of other well-characterized cephalosporin esterases indicates that the enzyme is unique in this class. PMID:9406399

Politino, M; Tonzi, S M; Burnett, W V; Romancik, G; Usher, J J



Pharmacokinetics of cephalosporins in the neonate: a review  

PubMed Central

The aim of this work was to review the published data on the pharmacokinetics of cephalosporins in neonates to provide a critical analysis of the literature as a useful tool for physicians. The bibliographic search was performed for articles published up to December 3, 2010, using PubMed. In addition, the book Neofax: A Manual of Drugs Used in Neonatal Care by Young and Mangum was consulted. The cephalosporins are mainly eliminated by the kidneys, and their elimination rates are reduced at birth. As a consequence, clearance is reduced and t1/2 is more prolonged in the neonate than in more mature infants. The neonate's substantial body water content creates a large volume of distribution (Vd) of cephalosporins, as these drugs are fairly water soluble. Postnatal development is an important factor in the maturation of the neonate, and as postnatal age proceeds, the clearance of cephalosporins increases. The maturation of the kidney governs the pharmacokinetics of cephalosporins in the infant. Clearance and t1/2 are influenced by development, and this must be taken into consideration when planning a cephalosporin dosage regimen for the neonate.

Pacifici, Gian Maria



Bacteriology and antibiotic resistance pattern in community acquired urinary tract infection.  


Extensive use of antibiotics have resulted in development of resistance among most commonly used drugs in community acquired urinary tract infection (UTI). This study was conducted to identify the resistance pattern in community acquired UTI .We collected urine for routine examination and culture from suprapubic urine in all the cases to avoid any contamination. E. Coli was the most common organism identified. Among oral antibiotics, there was high degree of resistance to penicillin group and cephalosporin groups. Among parentral antibiotics, all the cephalosporins were variably resistant except cephaperazone-salbactum. PMID:23942441

Sharan, Rajiv; Kumar, Dhananjay; Mukherjee, B



Clusters of genes for the biosynthesis of antibiotics: Regulatory genes and overproduction of pharmaceuticals  

Microsoft Academic Search

Summary In the last decade numerous genes involved in the biosynthesis of antibiotics, pigments, herbicides and other secondary metabolites have been cloned. The genes involved in the biosynthesis of penicillin, cephalosporin and cephamycins are organized in clusters as occurs also with the biosynthetic genes of other antibiotics and secondary metabolites (see review by Martín and Liras [65]). We have cloned

Juan F. Martin



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

Microsoft Academic Search

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

Xiaojun Wang; George Minasov; Brian K. Shoichet



[Bacterial resistance to antibiotics in the Czech Republic. The Working Group for Monitoring Resistance in the Czech Republic].  


In 1991 the authors made an investigation on the resistance of clinically important bacteria. Seventeen antibiotic centres in the Czech Republic participated in the investigation. The resistance to antibiotics of 32,567 strains of twelve bacterial species isolated from hospitalized patients depends on 1. the type of bacteria and antibiotics, 2. the source (specimen of pathological material) and 3. the locality (hospital). The resistance of Staphylococcus aureus to oxacillin with the exception of one hospital is not more than 6%, in rare instances also resistance to vancomycin was encountered. The frequency of resistance of gram-negative rods to so-called reserve antibiotics (cephalosporins of the third generation, quinolones and amikacin) depends markedly on the type of bacteria, being highest in typical causal agents of hospital infections--Enterobacter cloacae, Serratia marcescens, Providencia rettgeri and Pseudomonas aeruginosa. With the exception of cephalosporins the resistance of gram-negative rods and Pseudomonas aeruginosa isolated from urine is much greater than in strains from other clinical materials. The frequency of resistance in faculty hospitals which concentrate patients with more serious diseases is high, the highest resistance was, however, recorded in the North Bohemian area--in pneumococci against penicillin (13%) and in haemophili against ampicillin (17%). Every hospital is a closed ecological niche with a typical bacterial population and resistance rate. A competent estimate of an adequate and probably effective antibiotic for immediate initiation of treatment of an urgent infection can thus be made only by somebody with close and steady knowledge of the state of resistance in a given hospital. PMID:8111828

Urbásková, P; Schindler, J



Protein antigens of encapsulated Klebsiella pneumoniae surface exposed after growth in the presence of subinhibitory concentrations of cephalosporins.  

PubMed Central

It recently has been reported by us that cephalosporins, at a concentration below that influencing growth rate, reduced the production of enterochelin and capsule formation of iron-depleted Klebsiella pneumoniae. We now report on the antigenicity of the outer membrane components and surface-exposed protein antigens of iron-depleted cells grown in the presence or absence of cephalosporins. All major outer membrane proteins, including iron-regulated membrane proteins, were immunogenic. Encapsulated K. pneumoniae grown in antibiotic-free media had three protein antigens (60, 35.5, and 32.5 kilodaltons) exposed on the surface that were accessible to antibodies. Growth of the same cultures in the presence of subinhibitory concentrations of cephalosporins resulted in the exposure of a greater number of protein antigenic determinants, including iron-regulated membrane proteins, which become readily accessible to antibodies. It was also found that immunoblotting was generally more sensitive than conventional staining of the acrylamide gel with Coomassie blue in the detection of proteins. Images

Kadurugamuwa, J L; Anwar, H; Brown, M R; Zak, O



Recent advances in the biosynthesis of penicillins, cephalosporins and clavams and its regulation.  


The beta-lactam antibiotics have been serving mankind for over 70 years. Despite this old age, they continue to provide health to the world population by virtue of industrial production and discoveries of new secondary metabolite molecules with useful activities. Sales of these remarkable compounds have reached over $20 billion dollars per year. They include penicillins, cephalosporins, cefoxitin, monobactams, clavulanic acid and carbapenems. Strain improvement of the penicillin-producing species of Penicillium has been truly remarkable, with present strains producing about 100,000 times more penicillin that the original Penicillium notatum of Alexander Fleming. A tremendous amount of information has been gathered on the biosynthetic enzymes involved, the pathways of biosynthesis of beta-lactams as well as their regulation, and the genomics and proteomics of the producing organisms. Modern aspects of the processes are discussed in the present review including genetics, molecular biology, metabolic engineering, genomics and proteomics. PMID:23228980

Ozcengiz, Gulay; Demain, Arnold L



Penicillins, cephalosporins, and tetracyclines in treatment of hamsters with fatal leptospirosis.  

PubMed Central

A predictable 6- to 7-day course of a fatal Leptospira interrogans serovar bataviae infection in experimentally infected mature 110- to 150-g hamsters was used to evaluate the therapeutic efficacy of conventionally used and newer antibiotics. Active drugs were ampicillin, bacampicillin, cyclacillin, piperacillin, mezlocillin, doxycycline, chlortetracycline, cefotaxime, and moxalactam. Cephalexin, cefadroxil, cefamandole, and cefoperazone showed little or no activity in preliminary studies. In delayed treatment studies, all nine active drugs prevented death of hamsters even when treatment was delayed until 1 to 2.5 days before expected time of death. Leptospires in kidneys of surviving animals could be demonstrated in one or more hamsters treated with doxycycline, chlortetracycline, cyclacillin, and piperacillin, but in none of the animals treated with ampicillin, bacampicillin, mezlocillin, cefotaxime, and moxalactam. The potential usefulness of newer penicillins and cephalosporins, as well as ampicillin, chlortetracycline, and doxycycline, for treatment of severe leptospirosis is reported.

Alexander, A D; Rule, P L



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


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

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



Antibiotic use in 3 European university hospitals.  


The use of antibiotic drugs was studied in university teaching hospitals in Tartu, Estonia, Huddinge, Sweden and Badajoz, Spain. Data on drug deliveries to hospital wards during 1992 are presented in defined daily doses (DDD) per 100 bed-days (DDD/100 bed-days). In addition, the time trends of antibiotic use in Tartu University Hospital from 1992 to 1995 are shown. The total amount of antibiotic drugs used for systemic treatment in 1992 was similar in the 3 hospitals, 41 DDD/100 bed-days in Tartu vs. 51 DDD/100 bed-days in Badajoz and 47 DDD/100 bed-days in Huddinge. The antibiotics used most frequently were tetracyclines and aminoglycosides in Tartu, broad-spectrum penicillins and cephalosporins in Badajoz and narrow-spectrum penicillins and cephalosporins in Huddinge. Injectable preparations accounted for one-half of the antibiotics used. Among the medical departments, the total use of antibiotics varied up to 3-fold (from 19 to 61 DDD/100 bed-days), less than among the surgical departments (18-94 DDD/100 bed-days). The frequency of antibiotic use was very similar in departments of similar profile in the 3 hospitals (i.e. in departments of neurology, urology, etc.). The use of antibiotic drugs in intensive care units was twice as high in Huddinge (243 DDD/100 bed-days) as in Badajoz (106 DDD/100 bed-days) and Tartu (135 DDD/100 bed-days) in 1992. In conclusion, the international differences in the use of antibiotics in hospital were not in the frequency of use, but in the predominant prescription preferences in the hospital. PMID:9790137

Kiivet, R A; Dahl, M L; Llerena, A; Maimets, M; Wettermark, B; Berecz, R



The Development of ?-Lactam Antibiotics in Response to the Evolution of ?-Lactamases  

Microsoft Academic Search

ß-Lactam antibiotics, viz., penicillin, penicillin derivatives, cephalosporins, cephamycins, carbapenems, monobactams, and monocarbams, are the most widely used of all antimicrobial classes by virtue of their high efficacy and specificity and the availability of several derivatives. The expression of one or several ß-lactamases (ß-lactam antibiotic-inactivating enzymes) represents the most widespread and the most clinically relevant resistance mechanism to these antibiotics. The

Sabiha Y. Essack



Antibiotic sensitivity pattern of bacterial pathogens in the intensive care unit of Fatmawati Hospital, Indonesia  

PubMed Central

Objective To evaluate the sensitivity pattern of bacterial pathogens in the intensive care unit (ICU) of a tertiary care of Fatmawati Hospital Jakarta Indonesia. Methods A cross sectional retrospective study of bacterial pathogen was carried out on a total of 722 patients that were admitted to the ICU of Fatmawati Hospital Jakarta Indonesia during January 2009 to March 2010. All bacteria were identified by standard microbiologic methods, and their antibiotic susceptibility testing was performed using disk diffusion method. Results Specimens were collected from 385 patients who were given antimicrobial treatment, of which 249 (64.68%) were cultured positive and 136 (35.32%) were negative. The most predominant isolate was Pseudomonas aeruginosa (P. aeruginosa) (26.5%) followed by Klebsiella pneumoniae (K. pneumoniae) (15.3%) and Staphylococcus epidermidis (14.9%). P. aeruginosa isolates showed high rate of resistance to cephalexin (95.3%), cefotaxime (64.1%), and ceftriaxone (60.9%). Amikacin was the most effective (84.4%) antibiotic against P. aeruginosa followed by imipenem (81.2%), and meropenem (75.0%). K. pneumoniae showed resistance to cephalexin (86.5%), ceftriaxone (75.7%), ceftazidime (73.0%), cefpirome (73.0%) and cefotaxime (67.9%), respectively. Conclusions Most bacteria isolated from ICU of Fatmawati Hospital Jakarta Indonesia were resistant to the third generation of cephalosporins, and quinolone antibiotics. Regular surveillance of antibiotic susceptibility patterns is very important for setting orders to guide the clinician in choosing empirical or directed therapy of infected patients.

Radji, Maksum; Fauziah, Siti; Aribinuko, Nurgani



Colonisation with Escherichia coli resistant to "critically important" antibiotics: a high risk for international travellers.  


Antimicrobial resistance among community-acquired isolates of Escherichia coli is increasing globally, with international travel emerging as a risk for colonisation and infection. The aim was to determine the rate and duration of colonisation with resistant E. coli following international travel. One hundred and two adult hospital staff and contacts from Canberra, Australia, submitted perianal/rectal swabs before and following international travel. Swabs were cultured selectively to identify E. coli resistant to gentamicin, ciprofloxacin and/or third-generation cephalosporins. Those with resistant E. coli post-travel were tested monthly for persistent colonisation. Colonisation with antibiotic-resistant E. coli increased significantly from 7.8% (95% confidence interval [CI] 3.8-14.9) pre-travel to 49% (95% CI 39.5-58.6) post-travel. Those colonised were more likely to have taken antibiotics whilst travelling; however, travel remained a risk independent of antibiotic use. Colonisation with resistant E. coli occurred most frequently following travel to Asia. While over half of those carrying resistant E. coli post-travel had no detectable resistant strains two months after their return, at least 18% remained colonised at six months. Colonisation with antibiotic-resistant E. coli occurs commonly after international travel, and can be persistent. Medical practitioners should be aware of this risk, particularly when managing patients with suspected Gram-negative sepsis. PMID:20835879

Kennedy, K; Collignon, P



Preparation and evaluation of 99mTc-cefuroxime, a potential infection specific imaging agent: a reliable thin layer chromatographic system to delineate impurities from the 99mTc-antibiotic.  


Technetium-99m labelled cefuroxime, a second-generation cephalosporin antibiotic and potential bacteria specific infection imaging agent was evaluated. A good radiochemical purity (95%) of the labelled product was obtained after filtering the reaction mixture through a 0.22 ?m filter. Scintigraphy study of the purified product showed uptake in infectious lesions 45 min after injection and abscess-to-muscle ratios were found to be 1.80, 1.85 and 1.88 at 45 min, 1.5 hr and 3 hr, respectively. A versatile and reliable chromatographic technique to assess the radiochemical purity of (99m)Tc-cefuroxime has also been described. PMID:22871442

Chattopadhyay, Sankha; Ghosh, Mayuri; Sett, Sucharita; Das, Malay Kanti; Chandra, Susmita; De, Kakali; Mishra, Mridula; Sinha, Samarendu; Ranjan Sarkar, Bharat; Ganguly, Shantanu



Skin and skin structure infections: treatment with newer generation fluoroquinolones  

PubMed Central

Skin and skin structure infections (SSSI) are an emerging issue in healthcare. They are responsible for increasing heathcare utilization, both in hospitalizations and intravenous antibiotic use. SSSI are caused by an evolving variety of pathogens, including Gram-positive, Gram-negative, and anaerobic bacteria. In combination with mounting resistance patterns, this diverse range of bacteria mandate empiric broad-spectrum antibiotic coverage. Historically, cephalosporins and penicillins have been the mainstay of treatment, but recent data suggest newer generation fluoroquinolones are being used with increasing frequency. In 2005, moxifloxacin joined gatifloxacin and levofloxacin as newer generation fluoroquionolones with Food and Drug Administration indications for SSSIs. Even within this group there exist subtle differences that impact optimal management. This paper offers the clinician a comparative review of the antimicrobial spectrum, pharmacodynamics, pharmacokinetics, and clinical efficacy data to support the appropriate use of fluoroquinolones in SSSIs.

Giordano, Philip; Weber, Kurt; Gesin, Gail; Kubert, Jason



Generation of Leishmania mutants lacking antibiotic resistance genes using a versatile hit-and-run targeting strategy  

Microsoft Academic Search

The development of a method to create defined mutants of Leishmania parasites lacking foreign genes conferring resistance to antibiotics has both experimental and practical applications. Mutants deficient in specific virulence genes have potential as attenuated live vaccines, but these can only be of clinical relevance if the antibiotic resistance genes used for selection of the mutants are subsequently removed. In

Hubert Denise; Graham H. Coombs; Jeremy C. Mottram



Generation of Leishmania mutants lacking antibiotic resistance genes using a versatile hit-and-run targeting strategy  

Microsoft Academic Search

The development of a method to create defined mutants of Leishmania parasites lacking foreign genes conferring resistance to antibiotics has both experimental and practical applications. Mutants deficient in specific virulence genes have potential as atten- uated live vaccines, but these can only be of clinical relevance if the antibiotic resistance genes used for selection of the mutants are subsequently removed.

Hubert Denise; Graham H. Coombs; Jeremy C. Mottram



Reaction of picrate with creatinine and cepha antibiotics.  


The concentration of creatinine in serum, which is used to estimate glomerular filtration rate, is measured by reaction with alkaline picrate, but this reaction is not specific for creatinine. Although several other cephalosporin antibiotics have been reported not to react with picrate, we reacted picrate with creatinine, cefoxitin, penicillin, and eight different cephalosporins, and found that all compounds reacted with picrate and showed superimposable spectrophotograms with absorption maxima at 485 nm. From these results we conclude that the color-absorbing moiety of the product is the picrate molecule. Further, the structure common to creatinine and the cephalosporins, cefoxitin, or penicillin is the carbonyl group attached to a nitrogen and a carbon atom. We postulate that the carbonyl group with the adjacent carbon and nitrogen atoms is probably the chemical moiety that reacts with picrate to absorb energy at 485 nm. PMID:6478596

Kroll, M H; Hagengruber, C; Elin, R J



Improving the quality of antibiotic prescribing in the NHS by developing a new Antimicrobial Stewardship Programme: Start Smart--Then Focus.  


There has been dramatic change in antibiotic use in English hospitals. Data from 2004 and 2009 show that the focus on reducing fluoroquinolone and second- and third-generation cephalosporin use seems to have been heeded in NHS secondary care, and has been associated with a substantial decline in hospital Clostridium difficile rates. However, there has been a substantial increase in use of co-amoxiclav, carbapenems and piperacillin/tazobactam. In primary care, antibiotic prescribing fell markedly from 1995 to 2000, but has since risen steadily to levels seen in the early 1990s. There remains a 2-fold variation in antimicrobial prescribing among English General Practices. In 2010, the NHS Atlas of Variation documented a 3-fold variation in the prescription of quinolones and an 18-fold variation in cephalosporins by Primary Care Trusts across England. There is a clear need to improve antimicrobial prescribing. This paper describes the development of new antimicrobial stewardship programmes for primary care and hospitals by the Department of Health's Advisory Committee on Antimicrobial Resistance and Healthcare Associated Infection: Antimicrobial Stewardship in Primary Care Initiative. The secondary care programme promotes the rapid prescription of the right antibiotic at the right dose at the right time, followed by active review for all patients still on antibiotics 48 h after admission. The five options available are to stop, switch to oral, continue and review again, change (if possible to a narrower spectrum) or move to outpatient parenteral antibiotic therapy. A range of audit and outcome tools has been developed, but to maintain optimal antimicrobial usage, monitoring of local and national quantitative and qualitative data on prescribing and consumption is required, linked to the development of key performance indicators in primary, secondary and tertiary care. PMID:22855879

Ashiru-Oredope, Diane; Sharland, Mike; Charani, Esmita; McNulty, Cliodna; Cooke, Jonathan



Antibiotic susceptibility profiles of uncommon bacterial species causing severe infections in Italy.  


This study presents the results of the italian "Severe infections project" involving bacteria that can be considered rare causes of disease. we isolated 30 uncommon human pathogens from a total of 60 strains (1.2% of all the isolates). The most frequent sources of uncommon human pathogens were primary bloodstream infections (48.3%) and pneumonia (20%). Species such as Comamonas testosteroni, Enterococcus hirae, Kluyvera ascorbata, Kluyvera cryocrescens, Leclercia adecarboxylata and Ochrobactrum anthropi were recovered from bacteremia patients. Clinically useful antimicrobial agents were tested against each isolate. Resistance to 4 or more antibiotics tested was found in Achromobacter xylosoxidans, O. anthropi, Pseudomonas stutzeri, Citrobacter braakii, Enterobacter sakazakii, K. ascorbata, Proteus penneri and Serratia plymuthica. About 16% of the Gram-negative species were resistant to third-generation cephalosporins and 28.6% of the staphylococci were oxacillin-resistant. the results from this study offer indications for empirical therapy for severe infections from uncommon human pathogens. PMID:19567344

Nicolosi, D; Nicolosi, V M; Cappellani, A; Nicoletti, G; Blandino, G



Antibiotic resistance.  


This article reviews the causes and consequences of antibiotic resistance and efforts to control its growth. Antibiotic-resistant infections and related morbidity and mortality are on the rise in the United States and around the world. At the same time, the effectiveness of many antibiotics has declined. Antibiotic resistance is a natural biological outcome of antibiotic use. Although it cannot be prevented, antibiotic resistance can be controlled. New health care reform laws focus on prevention and safety, offering occupational health nurses an opportunity to raise public awareness of antibiotic resistance and promote disease prevention in the workplace. PMID:20839727

Emanuele, Patricia



Emergence of decreased susceptibility to extended-spectrum cephalosporins in Neisseria gonorrhoeae in India.  


Background. In the past, Neisseria gonorrhoeae has developed resistance to antimicrobial agents used for its treatment. Consequently, extended-spectrum cephalosporins form the mainstay of treatment for gonorrhoea. Methods. Samples from 88 patients attending the sexually transmitted diseases clinics from December 2009 to January 2011 in two referral hospitals in New Delhi were studied. Antimicrobial susceptibility testing was done using the disc diffusion method as per the calibrated dichotomous sensitivity technique against the following antibiotics: penicillin (0.5 i.u.), tetracycline (10 ?g), nalidixic acid (30 ?g), ciprofloxacin (1 ?g), spectinomycin (100 ?g), ceftriaxone (0.5 ?g) and cefpodoxime (10 ?g) (Oxoid UK). Azithromycin (15 ?g) (Oxoid, UK) was tested as per the guidelines of the Clinical and Laboratory Standards Institute. Minimum inhibitory concentrations were determined using the Etest for penicillin, tetracycline, ciprofloxacin, ceftriaxone, spectinomycin and azithromycin as per the manufacturer's instruction (Biomerieux, France). Results. Eighteen isolates of Neisseria gonorrhoeae were obtained. Three of these had decreased susceptibility to ceftriaxone and cefpodoxime by the disc diffusion method. The minimum inhibitory concentrations of ceftriaxone for two isolates were 0.064 ?g/ml and for one isolate it was 0.125 ?g/ml. Conclusion. Higher minimum inhibitory concentrations to extended-spectrum cephalosporins is of concern as it has been shown to precede treatment failure. This may warrant its use in increased/multiple dosages alone or possibly in combination (dual therapy), thereby complicating effective disease control. Our report is in accordance with earlier reports from different parts of the world. Therefore, a continuous surveillance of antimicrobial resistance is crucial to tailor treatment schedules for Neisseria gonorrhoeae in a particular geographical region. PMID:24066990

Sood, S; Mahajan, N; Verma, R; Kar, H K; Sharma, V K


Reduction in colonization and nosocomial infection by multiresistant bacteria in a neonatal unit after institution of educational measures and restriction in the use of cephalosporins  

Microsoft Academic Search

Introduction: Previous administration of third-generation cephalosporins predisposes to colonization and infections by multiresistant Enterobacter sp. The emergence of multiresistant bacteria infections in a neonatal unit during 1995, especially Enterobacter cloacae, stimulated this study. Objective: To evaluate the efficacy of measures to control colonization and nosocomial infection by multiresistant bacteria in a neonatal unit. Setting: A tertiary care university hospital. Patients

Roseli Calil; Sérgio Tadeu Martins Marba; Angela von Nowakonski; Antonia Teresinha Tresoldi



Persistence of antibiotic resistant bacteria  

Microsoft Academic Search

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

Dan I Andersson



Cephalosporin-induced Hemolytic Anemia in a Sicilian Child; Erythropoiesis.  


A 27-month-old child developed acute hemolysis on two occasions after the administration of cephalosporin. On the first occasion, hemolysis was intravascular and was due to the formation of complexes between antibodies and the drug, which bound to red blood cells and caused severe hemolysis. On the second occasion, hemolysis was extravascular and was probably due to antibody-dependent cell-mediated cytotoxicity. Marked increases in levels of CD(19) (+) and CD(57) (+) CD(8) (+) cells were detected among the subpopulations of the patient's lymphocytes but only in the level of CD(19) (+) cells from the patient's father, after incubation of a sample of whole blood with a solution of cephalosporins. These results might explain the differences between the immune response of the patient and those of other members of his family and of an unrelated control. PMID:11399632

Malaponte, G.; Arcidiacono, C.; Mazzarino, C.; Pelligra, S.; Li Volti, G.; Bevelacqua, V.; Li Volti, S.



Crystallization and preliminary diffraction analysis of an engineered cephalosporin acylase  

PubMed Central

Crystallization conditions are reported for an engineered cephalosporin acylase based on the sequence of glutaryl-7-aminocephalosporanic acid acylase from Pseudomonas strain N176. Initial crystals were grown using polyethylene glycol as a crystallizing agent; however, these crystals diffracted poorly and exhibited high mosaicity. A dehydration procedure in which crystals were transferred to a solution containing a higher concentration of polyethylene glycol as well as glycerol improved the diffraction quality such that a 1.57?Ĺ diffraction data set could be obtained.

Anandan, Anandhi; Vallet, Corinne; Coyle, Travis; Moustafa, Ibrahim M.; Vrielink, Alice



Study of volatile compounds from the radiosterilization of solid cephalosporins  

NASA Astrophysics Data System (ADS)

The use of ?-rays is a promising method to sterilize thermosensitive drugs. Although radiosterilization does not modify drugs activity, this mode of sterilization produces new radiolytic products. This study is devoted to the analysis of volatile compounds which may induce a modification of odour. The volatile compounds produced by radiolysis of cefotaxime, cefuroxime and ceftazidime, three cephalosporins, were analyzed by gas chromatography with headspace sampling. They were detected and identified by mass and infrared spectrometry. An explanation of their origin is proposed.

Barbarin, N.; Crucq, A. S.; Tilquin, B.



Expanded-Spectrum Cephalosporin-Resistant Salmonella Strains in Romania  

Microsoft Academic Search

Thirteen Salmonella enterica serotype Typhimurium and one Salmonella enterica serotype Heidelberg strain resistant to expanded-spectrum cephalosporins were isolated from October 2000 to February 2001 from infants with gastroenteritis in Iasi, Romania. In all but one serotype Typhimurium isolate, resistance was due to the production of a CMY-2 cephalosporinase encoded by a nonconjugative plasmid. The remaining isolate pro- duced an SHV-5-type

Vivi Miriagou; Roxana Filip; Gabriela Coman; Leonidas S. Tzouvelekis


Activity of faropenem against cephalosporin-resistant Enterobacteriaceae  

Microsoft Academic Search

Methods: We tested 847 consecutive cephalosporin-resistant Enterobacteriaceae collected at 16 centres in South-East England in 2004, 501 of them with CTX-M enzymes; we also tested reference strains and transconjugants with acquired b-lactamases and various modes of AmpC expression. MICs were determined by the BSAC agar dilution method. Results: Modal MICs of faropenem for Escherichia coli or Klebsiella spp. with CTX-M

Shazad Mushtaq; Russell Hope; Marina Warner; David M. Livermore


Purification and Characterization of a Cephalosporin Esterase from Rhodosporidium toruloides  

Microsoft Academic Search

A novel cephalosporin esterase (EC from Rhodosporidium toruloides was purified to gel electro- phoretic homogeneity. The enzyme is a glycoprotein with a molecular mass of 80 kDa. Upon deglycosylation, several forms of the enzyme were observed with a molecular mass range between 60 and 66 kDa. The isoelectric point of the enzyme is approximately 5.6, with the pH optimum




Antistaphylococcal Activity of Ceftobiprole, a New Broad-Spectrum Cephalosporin  

Microsoft Academic Search

Ceftobiprole (formerly BAL9141), the active component of the prodrug BAL5788 (ceftobiprole medocaril), is a novel cephalosporin with expanded activity against gram-positive bacteria. Among 152 Staphylococcus aureus isolates, including 5 vancomycin-intermediate and 2 vancomycin-resistant strains, MIC50 and MIC90 values for ceftobiprole were each 0.5 g\\/ml against methicillin-susceptible strains and 2 g\\/ml against methicillin- resistant strains. Against 151 coagulase-negative staphylococci (including 4

Tatiana Bogdanovich; Lois M. Ednie; Stuart Shapiro; P. C. Appelbaum



Expanded-Spectrum Cephalosporin-Resistant Salmonella Strains in Romania  

PubMed Central

Thirteen Salmonella enterica serotype Typhimurium and one Salmonella enterica serotype Heidelberg strain resistant to expanded-spectrum cephalosporins were isolated from October 2000 to February 2001 from infants with gastroenteritis in Iasi, Romania. In all but one serotype Typhimurium isolate, resistance was due to the production of a CMY-2 cephalosporinase encoded by a nonconjugative plasmid. The remaining isolate produced an SHV-5-type ?-lactamase. Typing by pulsed-field gel electrophoresis indicated that the CMY-2-producing serotype Typhimurium isolates were related.

Miriagou, Vivi; Filip, Roxana; Coman, Gabriela; Tzouvelekis, Leonidas S.



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


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

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



Rational antibiotic use in China: lessons learnt through introducing surgeons to Australian guidelines  

PubMed Central

Background World-wide concern about increasing antibiotic resistance has focused attention on strategies to improve antibiotic use. This research adapted Australian best-practice guidelines on the prophylactic use of antibiotics in surgery to a Beijing teaching hospital and then used them as a quality assessment and improvement tool, supplemented by educational interventions. Qualitative data about factors influencing antibiotic use was also obtained. Methods Australian and international guideline materials were amalgamated with the help of Chinese experts. Antibiotics prescribed for surgical prophylaxis in 60 consecutive patients undergoing clean or clean-contaminated surgery (120 total) were then compared with guideline recommendations in three phases; a pre-intervention period from June to August, 2002, an intervention period from June to August 2003 and post-intervention period from September to November 2003. During the intervention phase, feedback about prescriptions not in accord with the guideline was discussed with around 25 prescribers every two weeks. In addition, local factors influencing antibiotic use were explored with 13 junior surgeons and 8 high level informants. Results While agreement was reached on the principles of antibiotic surgical prophylaxis there was no consensus on detail. Of 180 patients undergoing clean surgery throughout all phases of the study, antibiotic prophylaxis was administered to 78% compared to 98% of the 180 patients undergoing clean-contaminated surgery. Second and third generation cephalosporin antibiotics predominated in both low-risk clean and clean-contaminated operations. The timing of prophylaxis was correct in virtually all patients. The duration of prophylaxis was less than 24 hours in 96% of patients undergoing clean surgery compared to only 62% of patients undergoing clean-contaminated surgery. The intervention produced no improvement in the duration of prophylaxis nor the overuse and inappropriate choice of unnecessary broad-spectrum and expensive drugs. Interviews and focus groups revealed that an important explanation for the latter problem was Chinese government policy which expected hospitals to support themselves largely through the sale of drugs. Conclusion Improving antibiotic use in China will require hospital funding reform, more authoritative best-practice guidelines, and hospital authorities embracing quality improvement.

Zhang, Yan; Harvey, Ken



BL-S786, a new parenteral cephalosporin. II. In vitro antimicrobial activity comparison with six related cephalosporins.  


BL-S786 was compared by in vitro studies with 6 other parenteral cephalosporins (cefamandole, cefazolin, cefoxitin, cephaloridine, cephalothin and cephradine). The following parameters were assessed: Comparative MICs against a wide variety of bacterial isolates, MIC/MBC comparisons and the effect of inoculum size on the MIC. BL-S786 showed the greatest antimicrobial activity against K. pneumoniae, C. diversus and Salmonella species; was equal to cefamandole against E. coli, E. agglomerans and P. mirabilis; and was second to cefamandole against Shigella, E. tarda, C. freundii, E. cloacae, E. aerogenes and the pathogenic Neisseriae. Essentially no activity against Serratia and Pseudomonas species was observed. Compared to the other cephalosporins tested BL-S786 showed poor activity against staphylococci and streptococci. For most species tested, the MBC of the various cephalosporins was the same or within one dilution of their respective MICs. However, for Enterobacter and indole-positive Proteus species, the MBC of BL-S786 and cefamandole was usually larger than or equal to 8-fold higher than the MICs. Cefoxitin, on the other hand, showed little MIC/MBC variations against indole-positive Proteus species. Inoculum size had only a small effect on the MICs against most gram-negative species--in some instances greater than 64-fold increases in MIC resulted by increasing inoculum size from 10(5) to 10(7) organisms per ml. PMID:893227

Jones, R N; Thornsberry, C; Barry, A L; Fuchs, P C; Gavin, T L; Gerlach, E H



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

Microsoft Academic Search

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 β-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

Xiaojun Wang; George Minasov; Brian K. Shoichet



Role of ceftiofur in selection and dissemination of blaCMY-2-mediated cephalosporin resistance in Salmonella enterica and commensal Escherichia coli isolates from cattle.  


Third-generation cephalosporin resistance of Salmonella and commensal Escherichia coli isolates from cattle in the United States is predominantly conferred by the cephamycinase CMY-2, which inactivates beta-lactam antimicrobial drugs used to treat a wide variety of infections, including pediatric salmonellosis. The emergence and dissemination of bla(CMY-2)(-)-bearing plasmids followed and may in part be the result of selection pressure imposed by the widespread utilization of ceftiofur, a third-generation veterinary cephalosporin. This study assessed the potential effects of ceftiofur on bla(CMY-2) transfer and dissemination by (i) an in vivo experimental study in which calves were inoculated with competent bla(CMY-2)-bearing plasmid donors and susceptible recipients and then subjected to ceftiofur selection and (ii) an observational study to determine whether ceftiofur use in dairy herds is associated with the occurrence and frequency of cephalosporin resistance in Salmonella and commensal E. coli. The first study revealed bla(CMY-2) plasmid transfer in both ceftiofur-treated and untreated calves but detected no enhancement of plasmid transfer associated with ceftiofur treatment. The second study detected no association (P = 0.22) between ceftiofur use and either the occurrence of ceftiofur-resistant salmonellosis or the frequency of cephalosporin resistance in commensal E. coli. However, herds with a history of salmonellosis (including both ceftiofur-resistant and ceftiofur-susceptible Salmonella isolates) used more ceftiofur than herds with no history of salmonellosis (P = 0.03) These findings fail to support a major role for ceftiofur use in the maintenance and dissemination of bla(CMY-2)-bearing plasmid mediated cephalosporin resistance in commensal E. coli and in pathogenic Salmonella in these dairy cattle populations. PMID:19376926

Daniels, Joshua B; Call, Douglas R; Hancock, Dale; Sischo, William M; Baker, Katherine; Besser, Thomas E



Role of Ceftiofur in Selection and Dissemination of blaCMY-2-Mediated Cephalosporin Resistance in Salmonella enterica and Commensal Escherichia coli Isolates from Cattle?  

PubMed Central

Third-generation cephalosporin resistance of Salmonella and commensal Escherichia coli isolates from cattle in the United States is predominantly conferred by the cephamycinase CMY-2, which inactivates ?-lactam antimicrobial drugs used to treat a wide variety of infections, including pediatric salmonellosis. The emergence and dissemination of blaCMY-2--bearing plasmids followed and may in part be the result of selection pressure imposed by the widespread utilization of ceftiofur, a third-generation veterinary cephalosporin. This study assessed the potential effects of ceftiofur on blaCMY-2 transfer and dissemination by (i) an in vivo experimental study in which calves were inoculated with competent blaCMY-2-bearing plasmid donors and susceptible recipients and then subjected to ceftiofur selection and (ii) an observational study to determine whether ceftiofur use in dairy herds is associated with the occurrence and frequency of cephalosporin resistance in Salmonella and commensal E. coli. The first study revealed blaCMY-2 plasmid transfer in both ceftiofur-treated and untreated calves but detected no enhancement of plasmid transfer associated with ceftiofur treatment. The second study detected no association (P = 0.22) between ceftiofur use and either the occurrence of ceftiofur-resistant salmonellosis or the frequency of cephalosporin resistance in commensal E. coli. However, herds with a history of salmonellosis (including both ceftiofur-resistant and ceftiofur-susceptible Salmonella isolates) used more ceftiofur than herds with no history of salmonellosis (P = 0.03) These findings fail to support a major role for ceftiofur use in the maintenance and dissemination of blaCMY-2-bearing plasmid mediated cephalosporin resistance in commensal E. coli and in pathogenic Salmonella in these dairy cattle populations.

Daniels, Joshua B.; Call, Douglas R.; Hancock, Dale; Sischo, William M.; Baker, Katherine; Besser, Thomas E.



Cefamandole: Antimicrobial Activity In Vitro of a New Cephalosporin  

PubMed Central

Cefamandole, a new cephalosporin derivative, was found to have a broad spectrum of activity against a cross-section of both gram-positive and gram-negative bacteria isolated from clinical material. Gram-positive cocci, except for Streptococcus faecalis, were very susceptible. Penicillin G-resistant Staphylococcus aureus also was susceptible to cefamandole. Minimal bactericidal concentrations for gram-positive cocci approximated the minimal inhibitory concentrations. Strains of Haemophilus influenzae were very susceptible to the drug. Most strains of Escherichia coli, Klebsiella sp., and Proteus sp. were inhibited by low concentrations. Increasing resistance occurred with larger inocula. Strains of Pseudomonas sp. were resistant to cefamandole.

Meyers, Burt R.; Leng, Bernard; Hirschman, Shalom Z.



Characteristics of ciprofloxacin and cephalosporin resistant Escherichia coli isolated from turkeys in Great Britain.  


1. A field study was performed to investigate the presence and characteristics of ciprofloxacin-resistant, extended spectrum ?-lactamase (ESBL) and AmpC Escherichia coli from turkeys in Great Britain. E. coli were isolated from ~9000 boot swab samples from 27 different farms owned by four different companies. Between 1 and 14 visits were made to each farm (mean 3) at between 0 and 15?m intervals (mean ~5?m). 2. CHROMagar ECC with and without ciprofloxacin or cephalosporin antibiotics was used as selective isolation media. Representative isolates with different phenotypes were tested for mutations in gyrA and for: qnrA, B, S, qepA and aac(6')-Ib genes, for ESBL phenotype, the presence of bla genes and plasmid type, and for ampC genes Representative ciprofloxacin-resistant and CTX-M isolates were further tested for serotype and PFGE type. On ciprofloxacin selective media 55% of samples yielded ciprofloxacin resistant E. coli and of those further analysed, most had ciprofloxacin MICs >4 mg/l and mutations in gyrA. 3. For the different companies, the mean number of samples per farm with cefoxitin- or cefotaxime-resistant isolates ranged from 1·0% to 61·9% and 4·7% to 31·7% respectively. Cefotaxime-resistance was most commonly associated with an ESBL phenotype, a CTX-M-1 or CTX-M-14 sequence type and an I1-? or K plasmid inc type. The mechanism of cefoxitin resistance was not determined for most isolates, but where determined it was bla . 4. PFGE and serotyping showed clonally-related isolates persisting over multiple visits suggesting both more prudent use of antibiotics and improved farm hygiene are needed to address the issue of antimicrobial resistance in isolates from turkeys. PMID:23444859

Randall, L P; Mueller-Doblies, D; Lemma, F L; Horton, R A; Teale, C J; Davies, R H



Antibiotic Prophylaxis in the Surgical Treatment of Peritrochanteric Fractures: A Comparative Trial between Two Cephalosporins  

Microsoft Academic Search

In a study of 200 patients scheduled for orthopedic surgery, prophylaxis with either ceftriaxone or cefotaxime was equally effective. No patient developed bacterial infection, either systemic or local, during the first 10 postoperative days. In the 1-year follow-up period, 2 patients developed deep wound infection (1 from each group). Ceftriaxone 1 g was given once only as a single preoperative

Th. Karachalios; G. P. Lyritis; E. Hatzopoulos



Considerations in the use of antibiotics for streptococcal pharyngitis.  


Microbiologic testing is recommended to diagnose GABHS pharyngitis and is required to maximize the selection of patients at highest risk of complications from true infection. The primary goal of therapy is eradication of GABHS. Penicillin has been the first-line treatment of choice for nonallergic patients; yet, there may be reason to reexamine the role of penicillin since there are now considerable data from clinical trials, pooled multicenter studies, and meta-analyses demonstrating frequent bacteriologic and clinical failure. While the contribution of pathogen resistance remains unclear, evolving evidence suggests that these failures also may be related to bacterial coaggregation or copathogenicity; GABHS reinfection; antibiotic nonadherence or subtherapeutic drug levels; penicillin tolerance; or blunting of an effective immune response. At the same time, some clinical evidence suggests that treatment failure with some cephalosporins may occur less frequently than with penicillin. Although cephalosporins are generally more expensive than oral penicillin, the benefits of cephalosporins include activity against BLPB and evolving data that support less frequent dosing than penicillin. Consequently, a reassessment of the role of cephalosporins in the treatment of pharyngitis may be appropriate. PMID:16913668

Brunton, Stephen; Pichichero, Michael



Irreversible Effects of Serum Proteins on Beta-Lactam Antibiotics  

PubMed Central

The chromogenic cephalosporin nitrocefin (87/312) demonstrates rapid and visible instability to serum from many species. This phenomenon was distinct from serum binding, being significantly slower. Destruction of another cephalosporin, 10485, by serum appeared to account for some anomalous results during investigation into its human pharmacokinetics. Many cephalosporins of very different structures also showed serum instability, unrelated to their degrees of serum binding as measured by plate assay. Extrapolation could not be made from one species to another with regard to either binding or instability. Small changes in the chemical structures of the 3- and 7-substituents of the cephalosporins made profound changes in their susceptibility to serum attack. The decomposition is pH dependent, occurring more slowly at acid pH, and is due to a high-molecular-weight component of serum that resists boiling for several minutes. Isoelectric focusing of serum from several animal species gave various species-specific bands that decomposed nitrocefin. The inactivation of nitrocefin was not entirely parallel with that of 10485 and was inhibited by it. All other ?-lactam compounds tested also inhibited the reaction, much greater concentrations usually being necessary when the inhibitor was stable to serum. The complex that causes breakdown of the ?-lactam compounds is not necessarily the same as the one causing serum binding. It is postulated that serum may affect most other ?-lactam antibiotics in a similar way, although in most cases, this only occurs to a very slight extent.

O'Callaghan, Cynthia H.



Bactericidal Activity against Cephalosporin-ResistantStreptococcus pneumoniaein Cerebrospinal Fluid of Children with Acute Bacterial Meningitis  

Microsoft Academic Search

There are reports of failure of extended-spectrum cephalosporin treatment in pneumococcal meningitis. On the basis of in vitro and animal experimental studies, the addition of vancomycin or rifampin to an extended- spectrum cephalosporin has been recommended for empiric treatment of these patients. Cerebrospinal fluid (CSF) was taken from 31 children with bacterial meningitis randomized to receive ceftriaxone alone (n 511),



New spectrofluorimetric method for determination of cephalosporins in pharmaceutical formulations.  


Simple, accurate and sensitive spectrofluorimetric method has been proposed for the determination of three cephalosporins, namely; cefixime (cefi), cephalexine (ceph), cefotaxime sodium (cefo) in pharmaceutical formulations. The method is based on a reaction between cephalosporins with 1, 2-naphthoquinone-4-sulfonic (NQS) in alkaline medium, at pH values of 12.0 for cefi and 13.0 for ceph and cefo to give highly fluorescent derivatives extracted with chloroform and subsequently measured at 600,580 and 580 nm after excitation at 520,455 and 490 nm for cefi, ceph and cefo respectively. The optimum experimental conditions have been studied. Beer's law is obeyed over the concentrations of 10-35 ng/mL, 10-60 ng/mL and 20-45 ng/mL for cefi,ceph and cefo, respectively. The detection limits were 2.02 ng/mL, 2.09 ng/mL and 2.30 ng/mL for cefi, ceph and cefo, respectively, with a linear regression correlation coefficient of 0.9987, 0.9995 and 0.9991 and recoveries in range from 98.5-107.04, 95.17-101.00 and 95.00-109.55% 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:22160361

Elbashir, Abdalla A; Ahmed, Shazalia M Ali; Aboul-Enein, Hassan Y



New spectrofluorimetric method for determination of cephalosporins in pharmaceutical formulations.  


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. Copyright © 2012 John Wiley & Sons, Ltd. PMID:22991324

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



Antibiotic sensitivity profile of bacterial pathogens in postoperative wound infections at a tertiary care hospital in Gujarat, India  

PubMed Central

Objective: To find out the most common bacterial pathogens responsible for post-operative wound infection and their antibiotic sensitivity profile. Materials and Methods: This prospective, observational study was carried out in patients of postoperative wound infection. Samples from wound discharge were collected using a sterile swab and studied for identification of isolates by Gram stains and culture growth followed by in vitro antibiotic susceptibility testing performed by disc diffusion method on Mueller Hinton agar. Results: Out of 183 organisms, 126 (68.85%) isolated organisms were gram negative. Staphylococcus aureus, 48 (26.23%), was the predominant organism. S. aureus was sensitive to rifampicin (89.58%), levofloxacin (60.42%), and vancomycin (54.17%). Pseudomonas aeruginosa was sensitive to ciprofloxacin (83.78%), gatifloxacin (51.35%), and meropenem (51.35%). Escherichia coli was sensitive to levofloxacin (72.41%) and ciprofloxacin (62.07%). Klebsiella pneumoniae was sensitive to ciprofloxacin (63.16%), levofloxacin (63.16%), gatifloxacin (63.16%), and linezolid (56.52%). Proteus mirabilis was sensitive to ciprofloxacin (75%) and linezolid (62.50). Proteus vulgaris was sensitive to ampicillin+sulbactam (57.14%) followed by levofloxacin (50%). Conclusions: There is an alarming increase of infections caused by antibiotic-resistant bacteria, particularly in the emergence of VRSA/VISA, meropenem, and third generation cephalosporin resistant Pseudomonas aeruginosa. Linezolid showing sensitivity against Gram negative bacteria.

Goswami, Nutanbala N.; Trivedi, Hiren R.; Goswami, Alpesh Puri P.; Patel, Tejas K.; Tripathi, C. B.



Molecular Analysis of and Identification of Antibiotic Resistance Genes in Clinical Isolates of Salmonella typhi from India  

PubMed Central

A representative sample of 21 Salmonella typhi strains isolated from cultures of blood from patients at the Christian Medical College and Hospital, Vellore, India, were tested for their susceptibilities to various antimicrobial agents. Eleven of the S. typhi strains possessed resistance to chloramphenicol (256 mg/liter), trimethoprim (64 mg/liter), and amoxicillin (>128 mg/liter), while four of the isolates were resistant to each of these agents except for amoxicillin. Six of the isolates were completely sensitive to all of the antimicrobial agents tested. All the S. typhi isolates were susceptible to cephalosporin agents, gentamicin, amoxicillin plus clavulanic acid, and imipenem. The antibiotic resistance determinants in each S. typhi isolate were encoded by one of four plasmid types. Plasmid-mediated antibiotic resistance genes were identified with specific probes in hybridization experiments; the genes responsible for chloramphenicol, trimethoprim, and ampicillin resistance were chloramphenicol acetyltransferase type I, dihydrofolate reductase type VII, and TEM-1 ?-lactamase, respectively. Pulsed-field gel electrophoresis analysis of XbaI-generated genomic restriction fragments identified a single distinct profile (18 DNA fragments) for all of the resistant isolates. In comparison, six profiles, different from each other and from the resistance profile, were recognized among the sensitive isolates. It appears that a single strain containing a plasmid conferring multidrug-resistance has emerged within the S. typhi bacterial population in Vellore and has been able to adapt to and survive the challenge of antibiotics as they are introduced into clinical medicine.

Shanahan, Philippa M. A.; Jesudason, Mary V.; Thomson, Christopher J.; Amyes, Sebastian G. B.



Enhancing effect of serum ultrafiltrate on the activity of cephalosporins against gram-negative bacilli.  

PubMed Central

A few studies have suggested that the inhibitory effect of serum on activity of broad-spectrum cephalosporins is less than that predicted by the degree of protein binding. Microdilution MICs of ceftriaxone, cefoperazone, moxalactam, and ceftizoxime were therefore determined against ATCC and clinical strains of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus in Mueller-Hinton broth containing either human albumin (as 0, 2.5, or 5% solution) or heat-inactivated human serum (as 0, 25, 50, or 95% solution). Arithmetic linear dilutions were used to improve accuracy. For standard bacterial strains, MICs in the presence of 5% albumin were higher than in broth alone by multiples of 10.9 to 21 for ceftriaxone, 5.5 to 16.4 for cefoperazone, 1.9 to 3.7 for moxalactam, and 1.1 to 1.4 for ceftizoxime, as expected by their protein binding. MICs in the presence of 95% serum were similar to those in 5% albumin for all four drugs against S. aureus and P. aeruginosa but were 2.2- to 4.8-fold lower (P less than 0.001) against E. coli and K. pneumoniae. Similar findings were observed at lower protein concentrations and with clinical isolates, except that for some strains of P. aeruginosa MICs were lower in serum than in albumin. Individual sera from five subjects gave comparable results. The addition of serum ultrafiltrate to albumin-containing solutions reduced MICs of ceftriaxone and cefoperazone 1.6- to 7.4-fold against E. coli and K. pneumoniae (P less than 0.01) but did not alter the MICs for S. aureus. Serum may contain an ultrafiltrable component(s) that enhances the activity of third-generation cephalosporins against many gram-negative bacilli.

Leggett, J E; Craig, W A



Relentless increase of resistance to fluoroquinolones and expanded-spectrum cephalosporins in Escherichia coli: 20 years of surveillance in resource-limited settings from Latin America.  


Previous studies on commensal Escherichia coli from healthy children in the Bolivian Chaco have shown remarkable resistance rates to the old antibiotics since the early 1990s, and the emergence of resistance to newer drugs (fluoroquinolones and expanded-spectrum cephalosporins) in the 2000s. Here we report the results of a new survey conducted in 2011 in the same setting. Rectal swabs were obtained from 482 healthy children (aged 6-72 months) from three urban areas of the Bolivian Chaco. Screening for antibiotic-resistant E. coli was performed by a direct plating method, as in the previous studies. The blaCTX-M genes were investigated by PCR/sequencing, and CTX-M-producing isolates were subjected to genotyping and detection of several plasmid-mediated quinolone resistance mechanisms. Results showed high rates of resistance to nalidixic acid (76%), ciprofloxacin (44%) and expanded-spectrum cephalosporins (12.4%), demonstrating a relentless increase of resistance to those drugs over the past two decades. CTX-M-type extended-spectrum beta-lactamases were found to be widespread (12%, 97% of extended-spectrum beta-lactamase producers). Compared with the previous studies, CTX-M-producing E. coli underwent a dramatic dissemination (120-fold increase since early 2000s) and a radical change of dominant CTX-M groups (CTX-M-1 and CTX-M-9 groups versus CTX-M-2 group). Most CTX-M producers were not susceptible to quinolones (91%), and 55% carried plasmid-mediated quinolone resistance genes (different combinations of aac(6')-Ib-cr, qnrB and qepA). This study shows the rapid and remarkable increasing trend for resistance to fluoroquinolones and expanded-spectrum cephalosporins in one of the poorest regions of Latin America, and underscores the need for urgent control strategies aimed at preserving the efficacy of those drugs in similar settings. PMID:22414066

Bartoloni, A; Pallecchi, L; Riccobono, E; Mantella, A; Magnelli, D; Di Maggio, T; Villagran, A L; Lara, Y; Saavedra, C; Strohmeyer, M; Bartalesi, F; Trigoso, C; Rossolini, G M



Bactericidal activity of oral beta-lactam antibiotics in plasma and urine versus isogenic Escherichia coli strains producing broad- and extended-spectrum beta-lactamases.  


Bacteria harbouring extended-spectrum beta-lactamases (ESBLs), derived by mutation from TEM-1, TEM-2 or SHV-1 beta-lactamases, have been described world-wide. The in vitro activities of these enzymes against beta-lactam antibiotics, including oral cephalosporins, are well recognised. The aim of this investigation was to assess the bactericidal activity of oral beta-lactam antibiotics available in Croatia (amoxicillin/clavulanate, cephalexin, cefuroxime, cefadroxil and ceftibuten), in biological fluids against isogenic Escherichia coli strains producing broad-spectrum (TEM-1, TEM-2 and SHV-1) and extended-spectrum beta-lactamases (SHV-2, SHV-3, SHV-4, SHV-5, SHV-12). Bactericidal activity of oral beta-lactams in plasma and urine was tested in time-kill experiments and by determining bactericidal titres at different time intervals post-dose. The killing rate of antibiotics in urine was slower than in plasma, but faster than in Mueller-Hinton broth. High bactericidal titres in urine were only maintained throughout the whole dosing interval by ceftibuten against strains producing broad-, SHV-2 and SHV-3 beta-lactamases. The older generation cephalosporins can be considered for the therapy of urinary tract infections caused by E. coli harbouring TEM-1, TEM-2 and SHV-1 beta-lactamases but a shorter dosing interval is needed. Ceftibuten can be recommended with caution in ESBL producing E. coli except those producing SHV-4, SHV-5 and SHV-12 that confer resistance to it. If these enzymes are produced, fluoroquinolones or carbapenems could be considered. PMID:15894465

Bedenic, Branka; Vranes, Jasmina; Suto, Sandra; Zagar, Zivojin



Expression of a cephalosporin C esterase gene in Acremonium chrysogenum for the direct production of deacetylcephalosporin C  

Microsoft Academic Search

A recombinant fungal microorganism capable of producing deacetylcephalosporin C was constructed by transforming a cephalosporin C esterase gene from Rhodosporidium toruloides into Acremonium chrysogenum. The cephalosporin C esterase gene can be expressed from its endogenous R. toruloides promoter or from the Aspergillus nidulans trpC promoter under standard Acremonium chrysogenum fermentation conditions. The expression of an active cephalosporin C esterase enzyme

J. Basch; T. Franceschini; S. Tonzi; S.-J. D. Chiang



[Sensitivity of urogenital aerobic microflora to antibiotics].  


The following aerobic opportunistic bacteria have been isolated in women with different inflammatory processes of the reproductive system: staphylococci--62%, enterobacteria--30%, streptococci--11%, pseudomonads--7%. Gram-positive cocci (staphylococci and streptococci, except for Streptococcus faecium) manifested the highest sensitivity to amoxycillin/clavulanic acid. Clinical isolates of enterobacteria were characterized by high percentage of strains sensitive to cyprofloxacine and cephalosporines of the third generation. The highest number of sensitive strains was registered in fluoroquinolon for Pseudomonas aeruginosa. PMID:11785424

Sirokvasha, E A; Krysenko, A V; Skliar, T V; Vinnikov, A I


Antibiotic resistance patterns among respiratory pathogens at a german university children’s hospital over a period of 10 years  

Microsoft Academic Search

Growing antimicrobial resistance among Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis is raising major concern worldwide. Strains of S. pneumoniae, H. influenzae and M. catarrhalis isolated from children with respiratory tract as well as invasive infection in a South-Western region of Germany between 1993 and 2002 were tested for susceptibility to common antibiotics including penicillins, cephalosporins and macrolides. A total

Sandra J. Arri; Kirsten Fluegge; Urban Mueller; Reinhard Berner



Antibiotic resistant bacterial profiles of anaerobic swine lagoon effluent.  


Although land application of swine (Sus scrofa) manure lagoon effluent is a common and effective method of disposal, the presence of antibiotic-resistant bacteria, both pathogenic and commensal can complicate already understood issues associated with its safe disposal. The aim of this study was to assess antibiotic resistance in swine lagoon bacteria from sow, nursery, and finisher farms in the southeastern United States. Effluents from 37 lagoons were assayed for the presence of Escherichia coli, Campylobacter, Listeria, and Salmonella. Antibiotic resistance profiles were determined by the Kirby-Bauer swab method for 12 antibiotics comprising eight classes. Statistical analyses indicated that farm type influenced the amount and type of resistance, with nurseries and sow farms ranking as most influential, perhaps due to use of more antibiotic treatments. Finisher farms tended to have the least amount of antibiotic class resistance, signaling an overall healthier market pig, and less therapeutic or prophylactic antibiotic use. Many bacterial isolates were resistant to penicillin, cephalosporin, and tetracycline class antibiotics, while nearly all were susceptible to quinolone antibiotics. It appeared that swine farm type had a significant association with the amount of resistance associated with bacterial genera sampled from the lagoons; nurseries contributed the largest amount of bacterial resistance. PMID:19875799

Brooks, J P; McLaughlin, M R



Novel cephalosporins for the treatment of MRSA infections.  


Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are among the most difficult to treat, Efforts toward the development of cephalosporin antimicrobial agents with activity against MRSA have been ongoing for the last decade. In spite of advancement of several potential drugs into clinical trials no such drugs are available for anti-MRSA therapy yet. The recent emergence of MRSA strains resistant to vancomycin, which is the treatment of choice for MRSA infection, has made the clinical need for new effective drugs even more pressing. In the present review structure-activity relationships are discussed with an emphasis on anti-MRSA activity, pharmacokinetics and efficacy in animal models. Clinical trial status of promising drug candidates is also provided where available. PMID:12020048

Glinka, Tomasz W



Outcome measurement of extensive implementation of antimicrobial stewardship in patients receiving intravenous antibiotics in a Japanese university hospital  

PubMed Central

Background Antimicrobial stewardship has not always prevailed in a wide variety of medical institutions in Japan. Methods The infection control team was involved in the review of individual use of antibiotics in all inpatients (6348 and 6507 patients/year during the first and second annual interventions, respectively) receiving intravenous antibiotics, according to the published guidelines, consultation with physicians before prescription of antimicrobial agents and organisation of education programme on infection control for all medical staff. The outcomes of extensive implementation of antimicrobial stewardship were evaluated from the standpoint of antimicrobial use density, treatment duration, duration of hospital stay, occurrence of antimicrobial-resistant bacteria and medical expenses. Results Prolonged use of antibiotics over 2 weeks was significantly reduced after active implementation of antimicrobial stewardship (2.9% vs. 5.2%, p < 0.001). Significant reduction in the antimicrobial consumption was observed in the second-generation cephalosporins (p = 0.03), carbapenems (p = 0.003), aminoglycosides (p < 0.001), leading to a reduction in the cost of antibiotics by 11.7%. The appearance of methicillin-resistant Staphylococcus aureus and the proportion of Serratia marcescens to Gram-negative bacteria decreased significantly from 47.6% to 39.5% (p = 0.026) and from 3.7% to 2.0% (p = 0.026), respectively. Moreover, the mean hospital stay was shortened by 2.9 days after active implementation of antimicrobial stewardship. Conclusion Extensive implementation of antimicrobial stewardship led to a decrease in the inappropriate use of antibiotics, saving in medical expenses, reduction in the development of antimicrobial resistance and shortening of hospital stay.

Niwa, T; Shinoda, Y; Suzuki, A; Ohmori, T; Yasuda, M; Ohta, H; Fukao, A; Kitaichi, K; Matsuura, K; Sugiyama, T; Murakami, N; Itoh, Y



Mechanical Bowel Preparation and Prophylactic Antibiotic Administration in Colorectal Surgery: A Survey of the Current Status in Korea  

PubMed Central

Purpose The usefulness of mechanical bowel preparation (MBP) in colon surgery was recently challenged by many multicenter clinical trials and meta-analyses. The objectives of this study were to investigate current national opinions about MBP and prophylactic antibiotics (PA) and to provide preliminary data for developing future Korean guidelines for MBP and PA administration in colorectal surgery. Methods A questionnaire was mailed to 129 colorectal specialists. The questionnaires addressed the characteristics of the hospital, the MBP methods, and the uses of oral and intravenous antibiotics. Results A total of 73 questionnaires (56.6%) were returned. First, in regard to MBP methods, most surgeons (97.3%) used MBP for a mean of 1.36 days. Most surgeons (98.6%) implemented whole bowel irrigation and used polyethylene glycol (83.3%). Oral antibiotic use was indicated in over half (52.1%) of the responses, the average number of preoperative doses was three, and the mean time of administration was 24.2 hours prior to the operation. Finally, the majority of responders stated that they used intravenous antibiotics (95.9%). The responses demonstrated that second-generation cephalosporin-based regimens were most commonly prescribed, and 75% of the surgeons administered these regimens until three days after the operation. Conclusion The results indicate that most surgeons used MBP and intravenous antibiotics and that half of them administered oral PA in colorectal surgery preparations. The study recommends that the current Korean guidelines should be adapted to adequately reflect the medical status in Korea, to consider the medical environment of the various hospitals, and to establish more accurate and relevant guidelines.

Kang, Byung Mo; Lee, Kil Yeon; Park, Sun Jin



Expression of a cephalosporin C esterase gene in Acremonium chrysogenum for the direct production of deacetylcephalosporin C.  


A recombinant fungal microorganism capable of producing deacetylcephalosporin C was constructed by transforming a cephalosporin C esterase gene from Rhodosporidium toruloides into Acremonium chrysogenum. The cephalosporin C esterase gene can be expressed from its endogenous R. toruloides promoter or from the Aspergillus nidulans trpC promoter under standard Acremonium chrysogenum fermentation conditions. The expression of an active cephalosporin C esterase enzyme in A. chrysogenum results in the conversion of cephalosporin C to deacetylcephalosporin C in vivo, a novel fermentation process for the production of deacetylcephalosporin C. The stability of deacetylcephalosporin C in the fermentation broth results in a 40% increase in the cephalosporin nucleus. PMID:15672283

Basch, J; Franceschini, T; Tonzi, S; Chiang, S-J D



Generating elastic, biodegradable polyurethane/poly(lactide-co-glycolide) fibrous sheets with controlled antibiotic release via two-stream electrospinning.  


Damage control laparotomy is commonly applied to prevent compartment syndrome following trauma but is associated with new risks to the tissue, including infection. To address the need for biomaterials to improve abdominal laparotomy management, we fabricated an elastic, fibrous composite sheet with two distinct submicrometer fiber populations: biodegradable poly(ester urethane) urea (PEUU) and poly(lactide-co-glycolide) (PLGA), where the PLGA was loaded with the antibiotic tetracycline hydrochloride (PLGA-tet). A two-stream electrospinning setup was developed to create a uniform blend of PEUU and PLGA-tet fibers. Composite sheets were flexible with breaking strains exceeding 200%, tensile strengths of 5-7 MPa, and high suture retention capacity. The blending of PEUU fibers markedly reduced the shrinkage ratio observed for PLGA-tet sheets in buffer from 50% to 15%, while imparting elastomeric properties to the composites. Antibacterial activity was maintained for composite sheets following incubation in buffer for 7 days at 37 degrees C. In vivo studies demonstrated prevention of abscess formation in a contaminated rat abdominal wall model with the implanted material. These results demonstrate the benefits derivable from a two-stream electrospinning approach wherein mechanical and controlled-release properties are contributed by independent fiber populations and the applicability of this composite material to abdominal wall closure. PMID:18318501

Hong, Yi; Fujimoto, Kazuro; Hashizume, Ryotaro; Guan, Jianjun; Stankus, John J; Tobita, Kimimasa; Wagner, William R



Generating Elastic, Biodegradable Polyurethane/Poly(lactide-co-glycolide) Fibrous Sheets with Controlled Antibiotic Release via Two-Stream Electrospinning  

PubMed Central

Damage control laparotomy is commonly applied to prevent compartment syndrome following trauma but is associated with new risks to the tissue, including infection. To address the need for biomaterials to improve abdominal laparotomy management, we fabricated an elastic, fibrous composite sheet with two distinct submicrometer fiber populations: biodegradable poly(ester urethane) urea (PEUU) and poly(lactide-co-glycolide) (PLGA), where the PLGA was loaded with the antibiotic tetracycline hydrochloride (PLGA-tet). A two-stream electrospinning setup was developed to create a uniform blend of PEUU and PLGA-tet fibers. Composite sheets were flexible with breaking strains exceeding 200%, tensile strengths of 5–7 MPa, and high suture retention capacity. The blending of PEUU fibers markedly reduced the shrinkage ratio observed for PLGA-tet sheets in buffer from 50% to 15%, while imparting elastomeric properties to the composites. Antibacterial activity was maintained for composite sheets following incubation in buffer for 7 days at 37 °C. In vivo studies demonstrated prevention of abscess formation in a contaminated rat abdominal wall model with the implanted material. These results demonstrate the benefits derivable from a two-stream electrospinning approach wherein mechanical and controlled-release properties are contributed by independent fiber populations and the applicability of this composite material to abdominal wall closure.

Hong, Yi; Fujimoto, Kazuro; Hashizume, Ryotaro; Guan, Jianjun; Stankus, John J.; Tobita, Kimimasa; Wagner, William R.



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.  


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

Thakuria, Bhaskar; Lahon, Kingshuk



Antibiotic concentration in human wound fluid after intravenous administration.  

PubMed Central

Since the wound is the most common focus of infection in the surgical patient, adequate levels of antibiotic within the wound ar essential. This study examines the concentrations of antibiotic achieved in human wounds. Fluid was collected at timed intervals on the first postoperative day from the wounds of 56 patients receiving antibiotics after regional lymph node dissection. Antibiotic concentration was determined by bioassay. Six antibiotics were studied: cephalothin, cefazolin, cephapirin, oxacillin, ampicillin and clindamycin. The cephalosporins and penicillins showed similar patterns of appearance in the wound fluid. The peak level occurred early (1--1 1/2 hours) with subsequent slow decrease. Clindamycin produced nearly constant levels in wound fluid. The concentration of each antibiotic in wound fluid surpassed the serum levels after 2.5 hours. At the dosages studied each antibiotic produced wound fluid concentrations greater than the MIC for most susceptible organisms. Higher doses provided higher wound fluid levels. The rate of appearance and the levels achieved should be considered in the choice of antibiotics in the surgical subject. Images Fig. 1.

Bagley, D H; Mac Lowry, J; Beazley, R M; Gorschboth, C; Ketcham, A S



Anaerobic stabilization and conversion of transformed intermediates of antibiotic pharmaceutical effluent in a fluidized bed reactor.  


The formulation and implementation of regulatory standards for the ultimate disposal and reuse of transformed products of antibiotic drugs and solvents have been a pending issue in the waste management of pharmaceutical industries especially in the developing countries like India. A case study has been identified and the current issues in one of the major pharmaceutical industry (manufacturing cephalosporin drugs) located in Chennai, India, has been discussed for the possible implementation of anaerobically transformed intermediates of antibiotic pharmaceutical waste sludge. The objective of the study was to determine the effect of bioaugmentation on the convertibility of anaerobically transformed intermediates of antibiotic pharmaceutical waste sludge into residuals and biocompost. Cephalosporin is a common name refers to cephradine (C16H19N3O4S) and cephalexin (C16H17N3O4S.H2O). Based on the critical examination of results, the industry is looking for the alternatives of either direct disposal of 7-amino-3-deacetoxycephalosporanic acid (7-ADCA) and phenyl acetic acid or for further degradation and disposal, which will essentially require additional cost and maintenance. The present regulatory standard implemented in India does not envisage such disposal alternatives and hence this would invite suggestions and recommendations of the expertise for the possible implementation on the pending issue in the antibiotic based pharmaceutical industries. The presence of cephalosporin increases total strength (Chemical Oxygen Demand) of the effluent and indirectly increases the cost of the treatment. Hence the biotransformation of cephalosporin either alone or in combination with other energetic compounds, offers the potential for an economical and environment friendly disposal alternative for the anaerobically transformed intermediates of antibiotic pharmaceutical waste sludge. PMID:23029922

Tamijevendane, S; Saravanane, R; Rajesh, R; Sivacoumar, R



Cephalothin susceptibility testing as class representative for oral cephalosporins: is it time to move on?  


Based on current epidemiologic and resistance trends, we propose reconsideration of the use of cephalothin susceptibility to predict susceptibility to oral narrow-spectrum cephalosporins among Enterobacteriaceae, particularly in predicting cephalexin susceptibility for urinary tract isolates. PMID:23680238

Nguyen, Hien M; Graber, Christopher J



The synthesis and evaluation of 2-substituted-7-(alkylidene)cephalosporin sulfones as ?-lactamase inhibitors  

Microsoft Academic Search

A series of 2-substituted-7-(alkylidene)cephalosporin sulfones were prepared and evaluated as ?-lactamase inhibitors. Compound 11c showed excellent activity as an inhibitor of the class C ?-lactamase derived from Enterobacter cloacae, strain P99.

John D Buynak; Venkata Ramana Doppalapudi; A. Srinivasa Rao; Sirishkumar D Nidamarthy; Greg Adam



Laboratory Evaluation of BL-S786, a Cephalosporin with Broad-Spectrum Antibacterial Activity  

PubMed Central

Biological and physicochemical properties of BL-S786 were compared with those of cephalothin, cephaloridine, and cefazolin. With few exceptions, BL-S786 was more active than the reference compounds against major gram-negative pathogenic species and its antibacterial spectrum was broader than that of cephalosporins currently available for clinical use. Although BL-S786 was generally less active than the control cephalosporins against gram-positive pathogens, it inhibited their growth at concentrations that should readily be achieved in humans after standard parenteral dosage. Streptococcus faecalis, a species relatively unsusceptible to cephalosporins in general, was an exception. BL-S786 was an effective bactericidal agent for strains of various gram-negative organisms. After intramuscular administration to mice, BL-S786 achieved high concentrations in blood, and its biological half-life was longer than that of the other three cephalosporins.

Leitner, F.; Misiek, M.; Pursiano, T. A.; Buck, R. E.; Chisholm, D. R.; DeRegis, R. G.; Tsai, Y. H.; Price, K. E.



Cephalosporin-induced hypoprothrombinemia: is the N-methylthiotetrazole side chain the culprit?  

PubMed Central

The reported high incidence of vitamin-K-reversible hypoprothrombinemia associated with the new beta-lactamase-stable cephalosporins prompted us to evaluate the effect on hemostasis of three cephalosporins (cefamandole, ceftriaxone, and ceftazidime) in 30 patients with serious infections. Cefamandole and ceftriaxone, both containing a sulfhydryl group, induced a significant and similar prolongation of prothrombin time and decrease in factor VII activity. Ceftazidime, in contrast, had no effect on these two parameters.

Agnelli, G; Del Favero, A; Parise, P; Guerciolini, R; Pasticci, B; Nenci, G G; Ofosu, F



In vitro and in vivo Antibacterial Activities of FK037, a New Parenteral Cephalosporin  

Microsoft Academic Search

In vitro and in vivo antibacterial activities of FK037, a new parenteral cephalosporin, were compared with those of cefpirome, ceftazidime and flo-moxef. The advantages of in vitro activity of FK037 were as follows: (1) a broad-spectrum antibacterial activity, (2) the most potent activity (MIC90: 25 ?g\\/ml) of the cephalosporins tested against highly methicillin-resistant Staphylococcus aureus (H-MRSA), (3) a strong activity

Takeshi Nishino; Masako Otsuki; Kazuo Hatano; Yutaka Nishihara



Interrelationship between pharmacokinetics and pharmacodynamics in determining dosage regimens for broad-spectrum cephalosporins  

Microsoft Academic Search

The broad-spectrum cephalosporins exhibit time-dependent bactericidal activity and produce prolonged postantibiotic effects only with staphylococci. The duration of time that serum levels exceed the minimum inhibitory concentration (MIC) is the important pharmacodynamic parameter correlating with efficacy for these drugs. Maximal efficacy for cephalosporins in several animal infection models is approached when serum levels are above the MIC for 60%–70% of

William A. Craig



Human Pharmacology of Cefotaxime (HR 756), a New Cephalosporin  

PubMed Central

Cefotaxime (HR 756) is a new semisynthetic parenteral cephalosporin with exceptional activity against gram-negative organisms and considerable stability against their ?-lactamases. To study its pharmacokinetic properties, 0.5-, 1-, and 2-g doses were administered to each of six volunteers intravenously over 15 min, followed by a sustaining infusions of 0.5, 1, and 2 g/h, respectively, for 3 consecutive hours. The loading doses produced mean peak levels of 41, 93, and 160 ?g/ml, and mean steady-state serum concentrations were 27, 64, and 138 ?g/ml, respectively. The mean terminal half-life was 75 ± 7 min. The total volume of distribution averaged 0.22 ± 0.03 liters/kg of body weight. Total body and renal clearances were 232 ± 30 and 145 ± 24 ml/min per 1.73 m2, respectively; 63 ± 9% of the administered dose was excreted through the kidneys in 24 h. To determine the effect of cefotaxime on the renal tubules, urinary alanine aminopeptidase excretion was measured before, during, and after the infusions. It remained within the normal range in all instances; however, 48 ± 14% of the total daily alanine aminopeptidase output was recovered during the infusion period. Side effects were dose related and included fatigue, loose stools, and night sweats. No significant changes in hematology, serum chemistry, or urinalysis were recorded.

Luthy, Ruedi; Munch, Reiner; Blaser, Jurg; Bhend, Hansjorg; Siegenthaler, Walter



Antistaphylococcal Activity of Ceftobiprole, a New Broad-Spectrum Cephalosporin  

PubMed Central

Ceftobiprole (formerly BAL9141), the active component of the prodrug BAL5788 (ceftobiprole medocaril), is a novel cephalosporin with expanded activity against gram-positive bacteria. Among 152 Staphylococcus aureus isolates, including 5 vancomycin-intermediate and 2 vancomycin-resistant strains, MIC50 and MIC90 values for ceftobiprole were each 0.5 ?g/ml against methicillin-susceptible strains and 2 ?g/ml against methicillin-resistant strains. Against 151 coagulase-negative staphylococci (including 4 vancomycin-intermediate strains), MIC50 and MIC90 values were, respectively, 0.125 ?g/ml and 1 ?g/ml against methicillin-susceptible and 1 ?g/ml and 2 ?g/ml against methicillin-resistant strains. Teicoplanin was less active than vancomycin against coagulase-negative strains. Linezolid, quinupristin-dalfopristin, and daptomycin were active against all strains, whereas increased MICs for amoxicillin-clavulanate, cefazolin, minocycline, gentamicin, trimethoprim-sulfamethoxazole, levofloxacin, rifampin, mupirocin, fusidic acid, and fosfomycin were sometimes observed. At 2× MIC, ceftobiprole was bactericidal against 11 of 12 test strains by 24 h. Prolonged serial passage in the presence of subinhibitory concentrations of ceftobiprole failed to select for clones with MICs >4 times those of the parents; the maximum MIC achieved for ceftobiprole after 50 passages (in 1 of 10 strains) was 8 ?g/ml. Single-passage selections showed very low frequencies of resistance to ceftobiprole irrespective of genotype or phenotype; the maximal ceftobiprole MIC of recovered clones was 8 ?g/ml.

Bogdanovich, Tatiana; Ednie, Lois M.; Shapiro, Stuart; Appelbaum, Peter C.



Antibiotic resistance  

Microsoft Academic Search

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

Geoff Scott



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


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

Bush, Karen



Determination of antibiotic substances in hospital sewage water using solid phase extraction and liquid chromatography\\/mass spectrometry and group analogue internal standards  

Microsoft Academic Search

A method for determination of antibiotics in hospital sewage water has been developed and validated. Analogue internal standards for fluoroquinolones, sulfonamides, trimethoprim, ?-lactams (penicillins and cephalosporines), nitroimidazoles and tetracyclines were successfully used for calibration and shown to generally improve precision compared to external calibration. Matrix components caused ion suppression\\/enhancement effects during the MS detection for all analytes studied. Two effects

Richard Lindberg; Per-Ĺke Jarnheimer; Björn Olsen; Magnus Johansson; Mats Tysklind



Changes in nature and antibiotic resistance of bacteria causing peritonitis in cirrhotic patients over a 20 year period.  

PubMed Central

AIM: To assess all clinically and bacteriologically documented episodes of spontaneous bacterial peritonitis diagnosed in a single unit over a 20 year period, to identify changes in the nature and antibiotic resistance of the causative bacteria. SETTING: A specialist liver disease unit in a tertiary care centre. MATERIAL: Cultured ascitic fluid obtained in the course of 240 consecutive episodes of clinically and bacteriologically proven spontaneous bacterial peritonitis. Patient recruitment remained stable during the 20 year period in terms of the number of cirrhotic patients admitted and the severity of their condition. RESULTS: 78.7% of isolates were Enterobacteriaceae (Escherichia coli in 51%) and 19% were Gram positive cocci. Until 1979 all the Enterobacteriaceae had the wild phenotype, compared with only 50% at the end of the study period. Since 1993, 22% of Enterobacteriaceae have been resistant to third generation cephalosporins. Methicillin resistant staphylococci were only isolated after 1989. CONCLUSIONS: Changes in the epidemiology and antibiotic resistance of bacteria causing spontaneous bacterial peritonitis must be monitored for optimal treatment.

Dupeyron, C; Campillo, B; Mangeney, N; Richardet, J P; Leluan, G



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

Microsoft Academic Search

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

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



Novel reaction of elastase with cephalosporin. beta. -lactams  

SciTech Connect

Porcine pancreatic elastase (PPE) was inactivated by two cephalosporin ..beta..-lactams, 3-acetoxymethyl-7-..cap alpha..-chloro-3-cephem-4-carboxylate-1,1-dioxide t-butylester (I) and its 7-..cap alpha..-methoxy analog (II) with the first-order rate constants for inactivation, 0.023 and 0.018 s-1 respectively at pH 7.4, 25/sup 0/C. The inhibition was caused by stoichiometric binding of the compounds with PPE (KI, 80 and 30 nM at pH 7.4, respectively) followed by acylation of the active site serine with opening of the lactam ring. PPE inactivated by II (E-II) spontaneously regenerated enzyme activity with a t1/2 of 100 min at both pH 7.4 and 5.0. The reactivation of E-II was slowed with 1% SDS. The major /sup 14/C-labeled tryptic peptide of PPE modified with (/sup 14/C)MeO-labeled II had the amino acid composition of the sequence Ser182 to Arg211. PPE inactivation with I did not reactivate but showed a time-dependent resistance to reactivation by treatment with 0.5 M NH2OH at pH 7.5 and 37/sup 0/C for 10 min. The acid hydrolyzate of PPE-I contained 5 residues of histidine/mole rather than 6 for native PPE. PPE crystals soaked with I in 35% PEG 4000, 0.1 M NaOAc, pH 5.0 were subjected to high resolution x-ray diffraction analysis. The cross-linking of the active site at Ser188 OH and His45 N/sup 2/ by a 2-substituted, 5-methylene-1,3-thiazine dioxide was clearly demonstrated.

Lin, T.Y.; Williams, H.R.; Navia, M.A.; Springer, J.P.; Hoogsteen, K.; Shah, S.K.; Finke, P.E.; Doherty, J.B.; Firestone, R.A.



How Antibiotics Work  

NSDL National Science Digital Library

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.

Vu Bioengineering Ret Program


Effect of loading rate and HRT on the removal of cephalosporin and their intermediates during the operation of a membrane bioreactor treating pharmaceutical wastewater.  


The viability of treating high-concentration antibiotic wastewater by an anaerobic membrane bioreactor was studied using submerged flat sheet membrane. The objective of the study was to determine the effect of organic loading rate and hydraulic retention time on the removal of cephalosporin derivative, viz. cephalexin, and the intermediates 7-amino-3-deacetoxycephalosporanic acid (7-ADCA) and acyl group (phenyl acetic acid) in an anaerobic membrane bioreactor with enhanced biodegradation using the bioaugmentation technique. The pharmaceutical industry is looking for alternatives to either direct disposal of 7-amino-3-deacetoxycephalosporanic acid and phenyl acetic acid, or further degradation and disposal, which will essentially require additional costs and maintenance. The present regulatory standard, implemented at a global level, does not allow for such disposal alternatives and hence the present study was aimed at the complete removal of the intermediates 7-ADCA and phenyl acetic acid prior to discharge. PMID:19886426

Saravanane, R; Sundararaman, S



Phage-Antibiotic Synergy (PAS): ?-Lactam and Quinolone Antibiotics Stimulate Virulent Phage Growth  

PubMed Central

Although the multiplication of bacteriophages (phages) has a substantial impact on the biosphere, comparatively little is known about how the external environment affects phage production. Here we report that sub-lethal concentrations of certain antibiotics can substantially stimulate the host bacterial cell's production of some virulent phage. For example, a low dosage of cefotaxime, a cephalosporin, increased an uropathogenic Escherichia coli strain's production of the phage ?MFP by more than 7-fold. We name this phenomenon Phage-Antibiotic Synergy (PAS). A related effect was observed in diverse host-phage systems, including the T4-like phages, with ?-lactam and quinolone antibiotics, as well as mitomycin C. A common characteristic of these antibiotics is that they inhibit bacterial cell division and trigger the SOS system. We therefore examined the PAS effect within the context of the bacterial SOS and filamentation responses. We found that the PAS effect appears SOS-independent and is primarily a consequence of cellular filamentation; it is mimicked by cells that constitutively filament. The fact that completely unrelated phages manifest this phenomenon suggests that it confers an important and general advantage to the phages.

Trojet, Sabrina N.; Prere, Marie-Francoise; Krisch, H.M.



Extended-spectrum cephalosporin-resistant Gram-negative organisms in livestock: an emerging problem for human health?  


Escherichia coli, Salmonella spp. and Acinetobacter spp. are important human pathogens. Serious infections due to these organisms are usually treated with extended-spectrum cephalosporins (ESCs). However, in the past two decades we have faced a rapid increasing of infections and colonization caused by ESC-resistant (ESC-R) isolates due to production of extended-spectrum-?-lactamases (ESBLs), plasmid-mediated AmpCs (pAmpCs) and/or carbapenemase enzymes. This situation limits drastically our therapeutic armamentarium and puts under peril the human health. Animals are considered as potential reservoirs of multidrug-resistant (MDR) Gram-negative organisms. The massive and indiscriminate use of antibiotics in veterinary medicine has contributed to the selection of ESC-R E. coli, ESC-R Salmonella spp. and, to less extent, MDR Acinetobacter spp. among animals, food, and environment. This complex scenario is responsible for the expansion of these MDR organisms which may have life-threatening clinical significance. Nowadays, the prevalence of food-producing animals carrying ESC-R E. coli and ESC-R Salmonella (especially those producing CTX-M-type ESBLs and the CMY-2 pAmpC) has reached worryingly high values. More recently, the appearance of carbapenem-resistant isolates (i.e., VIM-1-producing Enterobacteriaceae and NDM-1 or OXA-23-producing Acinetobacter spp.) in livestock has even drawn greater concerns. In this review, we describe the aspects related to the spread of the above MDR organisms among pigs, cattle, and poultry, focusing on epidemiology, molecular mechanisms of resistance, impact of antibiotic use, and strategies to contain the overall problem. The link and the impact of ESC-R organisms of livestock origin for the human scenario are also discussed. PMID:23395305

Seiffert, Salome N; Hilty, Markus; Perreten, Vincent; Endimiani, Andrea



Non-phenotypic tests to detect and characterize antibiotic resistance mechanisms in Enterobacteriaceae.  


In the past 2 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, MALDI-TOF 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

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



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

PubMed Central

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.

Watanakunakorn, Chatrchai; Bannister, Thomas; Glotzbecker, Cheryl



A novel impeller configuration to improve fungal physiology performance and energy conservation for cephalosporin C production.  


Effects of impeller configuration on fungal physiology and cephalosporin C production were investigated by an industrial strain Acremonium chrysogenum in a 12 m(3) bioreactor equipped with conventional and novel impeller configuration, respectively. The cell growth and oxygen uptake rate (OUR) profiles were little affected by the impeller configurations. However, differing impeller combinations significantly affected the morphology, which in turn influenced cephalosporin C production. Under the novel impeller configuration, the production of cephalosporin C was 10% higher and an excessive amount of dispersed arthrospores was also observed. Computational fluid dynamics (CFD) simulation further revealed that poor mass and energy exchange as well as inhomogeneous environment existed in the bioreactor equipped with conventional impeller configuration. For equivalent power dissipation, the volume oxygen transfer coefficient (K(L)a) could be enhanced by 15% compared with that of conventional impeller configuration. Power consumption was dramatically decreased by 25% by using novel impeller configuration. PMID:22835853

Yang, Yiming; Xia, Jianye; Li, Jianhua; Chu, Ju; Li, Liang; Wang, Yonghong; Zhuang, Yingping; Zhang, Siliang



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


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

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



Comparison of European and U.S. results for cephalosporin versus penicillin treatment of group A streptococcal tonsillopharyngitis  

Microsoft Academic Search

The outcome of cephalosporin versus penicillin treatment of group A streptococcal tonsillopharyngitis may differ between Europe and the USA. In the present study, Medline, Embase, reference lists, and abstract searches were used to identify randomized, controlled trials of cephalosporin versus penicillin treatment of group A streptococcal (GAS) tonsillopharyngitis. The outcomes of interest were bacteriologic and clinical cure rates from investigations

M. Pichichero; J. Casey



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


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

Karpiuk, Izabela; Tyski, Stefan



Management of Infections Due to Antibiotic-Resistant Streptococcus pneumoniae  

PubMed Central

Antibiotic-resistant strains of Streptococcus pneumoniae are becoming more prevalent throughout the world; this has resulted in modifications of treatment approaches. Management of bacterial meningitis has the greatest consensus. Strategies for treating other systemic infections such as pneumonia, bacteremia, and musculoskeletal infections are evolving, in part related to the availability of new antibiotics which are active in vitro against isolates resistant to penicillin and the extended-spectrum cephalosporins. However, there are currently very limited data related to the clinical efficacy of these new agents. The studies upon which current recommendations are based are reviewed. Otitis media represents the single most common infection due to S. pneumoniae. Recommendations for treatment of acute otitis media due to drug-resistant strains and the rationale for these recommendations are discussed.

Kaplan, Sheldon L.; Mason, Edward O.



Epidemiology of antibiotic resistance  

Microsoft Academic Search

Three biological processes contribute to the accumulation of bacterial drug resistance: new selection, gene epidemics and strain epidemics. New resistance emerges by (i) the advantaging of entire species, (ii) by mutation, and (iii) by the escape of resistance genes to mobile DNA. Organisms to have ?benefited' from modern patterns of cephalosporins and quinolone use include enterococci, Clostridium difficile, coagulase-negative staphylococci

D. M. Livermore



Educational Resources: Antibiotics and Antibiotic Resistance  

Center for Drug Evaluation (CDER)

... Know When Antibiotics Work" disclaimer icon (CDC website ... CDC to address the problem of antimicrobial ... CDC to promote appropriate antibiotic use ... More results from


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

PubMed Central

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.

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



New cephalosporins cefotaxime, cefpimizole, BMY 28142, and HR 810 in experimental pneumococcal meningitis in rabbits.  

PubMed Central

Four new cephalosporins, cefotaxime, cefpimizole (U 63196E), BMY 28142, and HR 810 were evaluated in experimental pneumococcal meningitis. Cefotaxime penetrated only moderately into the cerebrospinal fluid of rabbits with meningitis, whereas cefpimizole, BMY 28142, and HR 810 all exhibited unusually good penetration. The bactericidal activity in infected cerebrospinal fluid was comparable for the four drugs.

Tauber, M G; Hackbarth, C J; Scott, K G; Rusnak, M G; Sande, M A



In vitro Susceptibility of Mycobacteria Species Other than Mycobacterium tuberculosis to Amikacin, Cephalosporins and Cefoxitin  

Microsoft Academic Search

The susceptibility of different species of mycobacteria, other than M. tuberculosis, to a range of cephalosporins and to amikacin was studied. Susceptibility patterns varied with species. M. fortuitum, M. marinum and M. szulgai were the most susceptible species to amikacin and to cefoxitin, whereas M. kansasii, M. scrojulaceum and MAIS complex the most resistant. Cefoxitin appears to be much more

Hava Haas; Jacques Michel; Theodore G. Sacks



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

PubMed Central

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.

Boyd, D B; Ott, J L



Antibiotic prescription rate for upper respiratory tract infections and risks for unnecessary prescription in Croatia.  


Overprescribing of antibiotics in primary care has been recognized as public health problem. We investigated visits prescription rate of antibiotics to patients with upper respiratory tract infections (URTI) and unnecessary prescription for tonsillopharyngitis, in Croatia. In prospective observational study in November 2007. 25 GPs in Croatia recorded all patients' visits with URTI episode according ICPC-2. Clinical status of patients with tonsillopharyngitis were categorized according to Centor Criteria. 689 visits were analysed, 82% of visits were initial. Antibiotics were prescribed in 44.7% visits with URTI. There were no significant differences in antibiotic prescription rates regarding non-clinical factors. Antibiotics were prescribed to patients with tonsillopharyngitis in 62.2% visits. Unnecessary antibiotics were prescribed (Centor 1,2) in 49.6% visits with tonsillopharyngitis. Logistic regression analysis showed significant differences in unnecessary antibiotic prescription rates only with respect to the workday--Wednesday, CI (1.117-2.671), p = 0.0139. Leading antibiotic was amoxicillin + clavulonic acid, second was amoxicillin, the third were macrolides, the fourth was narrow spectrum penicillin and fifth were cephalosporins. This study shows over prescription for URTI. Unnecessary prescription for tonsillopharyngitis depend on non clinical factor--day of the week. This should be further explored and help to improved prescribe antibiotics. PMID:23940988

Botica, Marija Vrca; Botica, Iva; Stameni?, Valerija; Andrasevi?, Arjana Tambi?; Kern, Josipa; Spehar, Stanislava Stojanovi?



Oral versus intravenous antibiotics for community acquired lower respiratory tract infection in a general hospital: open, randomised controlled trial  

Microsoft Academic Search

AbstractObjective: To see whether there is a difference in outcome between patients treated with oral and intravenous antibiotics for lower respiratory tract infection.Design: Open controlled trial in patients admitted consecutively and randomised to treatment with either oral co-amoxiclav, intravenous followed by oral co-amoxiclav, or intravenous followed by oral cephalosporins.Setting: Large general hospital in Dublin.Patients: 541 patients admitted for lower respiratory

Robert Chan; Linda Hemeryck; Myra ORegan; Luke Clancy; John Feely



Antibiotics for surgical prophylaxis  

Microsoft Academic Search

Summary Surgical antibiotic prophylaxis is defined as the use of antibiotics to prevent infections at the surgical site. Prophylaxis has become the standard of care for contaminated and clean- contaminated surgery and for surgery involving insertion of artificial devices. The antibiotic selected should only cover the likely pathogens. It should be given at the correct time. For most parenteral antibiotics

Wendy Munckhof; Infectious Diseases Physician; Clinical Microbiologist


Antibiotics and the ribosome  

Microsoft Academic Search

Summary The ribosome is one of the main antibiotic targets in the cell. Recent years brought important insights into the mode of interaction of antibiotics with the ribo- some and mechanisms of antibiotic action. Ribosome crystallography provided a detailed view of the inter- actions between antibiotics and rRNA. Advances in biochemical techniques let us better understand how the binding of

Tanel Tenson; Alexander Mankin



Microbial resistance to antibiotics  

Microsoft Academic Search

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



Rapid Detection of Ampicillin-Resistant Haemophilus influenzae and Their Susceptibility to Sixteen Antibiotics  

PubMed Central

Ampicillin-resistant and -susceptible strains of Haemophilus influenzae were tested for susceptibility to 16 antibiotics. Chloramphenicol and a new cephalosporin, cefamandole, were most active with minimal inhibitory concentrations (MICs) for all bacteria tested between 0.5 to 2.0 ?g/ml. All but two organisms were susceptible to tetracycline. Ampicillin-resistant strains of H. influenzae were less susceptible (MIC, 4 to 32 ?g/ml) to carbenicillin and ticarcillin than ampicillin-susceptible organisms (MIC, 0.25 to 1.0 ?g/ml). A rapid assay for ?-lactamase, utilizing a chromogenic cephalosporin substrate, detected enzyme production in all 17 ampicillin-resistant strains of H. influenzae. Images

Kammer, Robert B.; Preston, David A.; Turner, Jan R.; Hawley, Lois C.



Nosocomial infections due to serratia marcescens — Clinical findings, antibiotic susceptibility patterns and fine typing  

Microsoft Academic Search

Summary We report on nosocomial infections caused bySerratia marcescens occurring in a neonatal intensive care unit and a children's ward for cardiac intensive care. According to the plasmid pattern analysis, all isolated epidemic strains belonged to one clone. Multidrug resistance, even to cephalosporins of the third generation and amikacin, was characteristic for all strains. Certain markers ofS. marcescens (haemolysin, proteases,

Renate Bollmann; Elke Halle; Wanda Sokolowska-Köhler; Petra Buchholz; E. L. Grauel; I. Klare; H. Tschäpe; W. Witte



GPs' antibiotic prescription patterns for respiratory tract infections - still room for improvement  

PubMed Central

Objective Inappropriate use of antibiotics is associated with increased antibiotic resistance in the community. About 90% of all antibiotic prescriptions in Norway are issued by general practitioners and in 60% issued for respiratory tract infections. The article describes and analyses antibiotic prescription patterns by general practitioners in Vestfold, Norway. Design Prospective cohort study. Subjects A total of 145 list-holding general practitioners in Vestfold, Norway in February to March 2003. Methods Merging of two electronic administrative data sets: antibiotic prescriptions dispensed in pharmacies and general practitioners’ electronic bills from the National Insurance Agency. Main outcome measures Proportion and type of antibiotic prescribed for different respiratory tract infectious diagnoses. Results We found large variations among general practitioners’ antibiotic prescription habits. In 27% of consultations with RTI diagnoses, an antibiotic was prescribed; 37% were for Penicillin V and 28% for a macrolide. Quinolones and cephalosporins were only rarely prescribed. In a logistic regression analysis the following factors were independently associated with antibiotic prescription rate: type of infection, type of contact, being a general practitioner specialist, and years since medical exam. In another logistic regression analysis the following factors were independently associated with broad-spectrum antibiotic prescription: type of infection, age of patient, type of contact, being a specialist, length of list, and being a high prescriber of antibiotics. Conclusion The variation in proportion of total antibiotic prescribing and broad-spectrum prescription for respiratory tract infections is high, and reveals potentials to change general practitioners’ prescription behaviour, in order to maintain the positive situation in Norway as to antibiotic resistance.

Gjelstad, Svein; Dalen, Ingvild; Lindbaek, Morten



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


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 0.9mM 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 1.25g of ammonium sulfate as salting-out agent. The separation of cephalosporins using a Luna C18 (150mm×0.3mm, 5µm, 100Ĺ) 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 20µlmin(-1), column temperature 35°C and injection volume 7µl with UV detection at 250nm. 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

Quesada-Molina, Carolina; García-Campańa, Ana M; Del Olmo-Iruela, Monsalud



How to cope with the quest for new antibiotics  

Microsoft Academic Search

Since their introduction in therapy, antibiotics have played an essential role in human society, saving millions of lives, allowing safe surgery, organ transplants, cancer therapy. Antibiotics have also helped to elucidate several biological mechanisms and boosted the birth and growth of pharmaceutical companies, generating profits and royalties. The golden era of antibiotics and the scientific and economical drive of big

Attilio Fabbretti; Claudio O. Gualerzi; Letizia Brandi



Antibiotic prescription in intensive care units in Latin America.  


The intensive care units (ICUs) are often considered as the epicenters of antibiotic resistance. Therefore, the total antibiotic consumption is approximately ten fold greater in ICU wards than in general hospital wards. The aim of this study was to evaluate the current use of antibiotics in Latin American ICUs. Three cross-sectional (one-day point) prevalence studies were undertaken in 43 Latin American ICUs. Of 1644 patients admitted, 688 received antibiotic treatment on the days of the study (41.8 %) and, 392 cases (57 %) were due to nosocomial-acquired infections. Of all infections, 22 % (151/688) corresponded to septic shock; and 22 % (151/688) to nosocomial pneumonia (50/151 [33 %], ventilator-associated pneumonia). In 485 patients (70.5 %), cultures were performed before starting antibiotic treatment. The most common microorganisms isolated were extended-spectrum ß-lactamase Enterobacteriaceae, (30.5 %), and Pseudomonas aeruginosa (17 %). Carbapenems (imipenem or meropenem) were the antibiotics most frequently prescribed (151/688, 22 %), followed by vancomycin (103/688, 15 %), piperacillin-tazobactam (86/688, 12.5 %) and broad-spectrum cephalosporins (mainly cefepime) (83/688, 12 %). In summary, carbapenems were the most frequent antibiotics prescribed in Latin American ICUs. This practice seems justified for the high rates of ESBL-producing Gram-negatives found in our patients. Beyond this reason, the problem of bacterial resistance in LA requires that physicians improve the use of carbapenems. The high prevalence of carbapenem-resistant A. baumannii and P. aeruginosa in the region, along with the prevalence of carbapenem-resistant Enterobacteriaceae, have increased markedly. A comprehensive evidence-based stewardship program based on local antimicrobial use and resistance problems should be implemented in our clinical settings. PMID:22430995

Curcio, Daniel J


Production of cephalosporin intermediates by feeding adipic acid to recombinant Penicillium chrysogenum strains expressing ring expansion activity.  


We demonstrate a novel and efficient bioprocess for production of the cephalosporin intermediates, 7-aminocephalosporanic acid (7-ACA) or 7-amino deacetoxycephalosporanic acid (7-ADCA). The Streptomyces clavuligerus expandase gene or the Cephalosporium acremonium expandase-hydroxylase gene, with and without the acetyltransferase gene, were expressed in a penicillin production strain of Penicillium chrysogenum. Growth of these transformants in media containing adipic acid as the side chain precursor resulted in efficient production of cephalosporins having an adipyl side chain, proving that adipyl-6-APA is a substrate for either enzyme in vivo. Strains expressing expandase produced adipyl-7-ADCA, whereas strains expressing expandase-hydroxylase produced both adipyl-7-ADCA and adipyl-7-ADAC (aminodeacetylcephalosporanic acid). Strains expressing expandase-hydroxylase and acetyltransferase produced adipyl-7-ADCA, adipyl-7-ADAC and adipyl-7-ACA. The adipyl side chain of these cephalosporins was easily removed with a Pseudomonas-derived amidase to yield the cephalosporin intermediates. PMID:9634750

Crawford, L; Stepan, A M; McAda, P C; Rambosek, J A; Conder, M J; Vinci, V A; Reeves, C D



The epidemiology of antibiotic resistance in Streptococcus pneumoniae and the clinical relevance of resistance to cephalosporins, macrolides and quinolones  

Microsoft Academic Search

Invasive non-meningeal pneumococcal infections remain a major cause of morbidity and mortality worldwide. The factors affecting the epidemiology and mortality of pneumococcal infections are discussed. The increase and spread of resistance to antimicrobial agents among pneumococci is a cause of concern to the clinician. There are links between the usage of antibacterial agents and the development of resistance. Resistance to

Roman Pallares; Asuncion Fenoll; Josefina Lińares



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

Microsoft Academic Search

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,

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



Synthesis and biological activity of novel cephalosporins containing a (Z)-vinyl dimethylphosphonate group.  


A series of cephalosporins containing a novel 7-[2-(Z)-(2-amino-thiazol-4- yl)-3-(dimethoxy-phosphoryl)-acryloylamino] group were prepared and their antibacterial activity measured against a range of pathogens. In general the compounds displayed a broad spectrum of activity against both Gram positive and Gram negative organisms, except Pseudomonas aeruginosa. Activity against the latter could be achieved by introducing a catechol moiety at the 3 position of the cephalosporin. The methyl phosphonates in general were stable to a wide range of beta-lactamases, including the TEM enzymes and the Enterobacter cloacae P99 chromosomal enzyme. In addition, they showed the advantage of being highly water soluble. PMID:7868393

Smith, P W; Chamiec, A J; Chung, G; Cobley, K N; Duncan, K; Howes, P D; Whittington, A R; Wood, M R



Plasmid-Mediated Resistance to Expanded-Spectrum Cephalosporins among Enterobacter aerogenes Strains  

Microsoft Academic Search

Resistance to expanded-spectrum cephalosporins commonly develops in Enterobacter aerogenes during ther- apy due to selection of mutants producing high levels of the chromosomal Bush group 1 b-lactamase. Recently, resistant strains producing plasmid-mediated extended-spectrum b-lactamases (ESBLs) have been isolated as well. A study was designed to investigate ESBL production among 31 clinical isolates of E. aerogenes from Richmond, Va., with decreased




In vitro activities of cefcanel and some other cephalosporins against Pasteurella multocida.  

PubMed Central

Thirty-five strains of Pasteurella multocida from humans and animals were tested for susceptibility to five cephalosporins by a broth dilution method. Cefcanel showed high activity against all isolates (MIC and MBC, less than or equal to 0.64 micrograms/ml). The corresponding figure for cefaclor and cefuroxime was 2.56 micrograms/ml. Cefadroxil and cephalexin were the least active compounds tested.

Holst, E; Rollof, J; Miorner, H



Prodrugs of cephalosporin RWJ-333441 (MC-04,546) with improved aqueous solubility.  


To improve the aqueous solubility of anti-methicillin-resistant Staphylococcus aureus cephalosporin RWJ-333441 for parenteral administration, acyl derivatives of the C-3 primary amino group were prepared and evaluated for solubility, cleavage in serum in vitro, and conversion to RWJ-333441 in vivo. Improved solubility at physiologic pH values and release of RWJ-333441 in vitro and in vivo were observed for several prodrugs, including the aspartate derivative RWJ-333442. PMID:12760896

Hecker, Scott J; Calkins, Trevor; Price, Mary E; Huie, Keith; Chen, Sharon; Glinka, Tomasz W; Dudley, Michael N



Batch production of deacetyl 7-aminocephalosporanic acid by immobilized cephalosporin-C deacetylase  

Microsoft Academic Search

Bacillus subtilis SHS0133 cephalosporin-C deacetylase (CAH) overexpressed in Escherichia coli was immobilized on an anion-exchange resin, KA-890, using glutaraldehyde. The activity yield of immobilized enzyme was approximately 55% of the free enzyme. The pH range for stability of the immobilized enzyme (pH 5–10) was broader than that for free enzyme. The K m app value of immobilized enzyme for 7-aminocephalosporanic

Akio Takimoto; Tomoaki Takakura; Hiroyoshi Tani; Shigeo Yagi; Kenji Mitsushima



Prodrugs of Cephalosporin RWJ-333441 (MC04,546) with Improved Aqueous Solubility  

Microsoft Academic Search

The need for new agents with which to treat nosocomial infections due to multiply resistant gram-positive bacteria, par- ticularly methicillin-resistant staphylococci, continues to be ur- gent. Our previous reports have described the discovery (6) and in vitro activity (3) of RWJ-54428 (MC-02,479), a new cephalosporin expected to have utility in this setting. Further discovery efforts have identified RWJ-333441 (Fig. 1,

Scott J. Hecker; Trevor Calkins; Mary E. Price; Keith Huie; Sharon Chen; Tomasz W. Glinka; Michael N. Dudley



Characteristics of demand for pharmaceutical products: an examination of four cephalosporins.  


We model demand for four cephalosporins and compute own- and cross-price elasticities between branded and generic versions of the four drugs. We model demand as a multistage budgeting problem, and we argue that such a model is appropriate to the multistage nature of the purchase of pharmaceutical products, in particular the prescribing and dispensing stages. We find quite high elasticities between generic substitutes and also significant elasticities between some therapeutic substitutes. PMID:11794359

Ellison, S F; Cockburn, I; Griliches, Z; Hausman, J



Bioconversion of cephalosporin C with D-amino acid oxidase from the yeast Rhodosporidium toruloides  

Microsoft Academic Search

Summary A D-amino acid oxidase-producing yeast,Rhodosporidium toruloides CCRC 20306, was used to convert cephalosporin C (Ceph C) into a-ketoadipyl cephalosporanic acid. A part of Ceph C could be directly converted into glutaryl-7-aminocephalosporanic acid (GL-7-ACA) by permeated cells of CCRC 20306. There were unknown side products formed during the conversion. The side products could be substantially reduced in amount by heating

Yun-Huey Lee; Wen-Shen Chu; Wen-Hwei Hsu



In vitro evaluation of Ro 09-1227, a novel catechol-substituted cephalosporin.  

PubMed Central

Ro 09-1227 is a novel 7-position catechol-substituted parenteral cephalosporin that also has a 3-position radical similar to previously described cephems. The Ro 09-1227 spectrum was slightly wider than that of ceftazidime against members of the family Enterobacteriaceae tested, principally because of greater activity against species producing Richmond-Sykes type I beta-lactamases. Ro 09-1227 was also more active than ceftazidime against some strains producing extended-spectrum plasmid-encoded beta-lactamases, such as TEM-3, -4, -5, -6, -7, and -9, SHV-2 and -3, and CAZ-2. Most strains of Pseudomonas aeruginosa, Xanthomonas maltophilia, and Acinetobacter spp. were also more susceptible to Ro 09-1227 than cefotaxime, ceftriaxone, cefoperazone, and ceftazidime. Haemophilus influenzae (MIC for 90% of strains tested [MIC90], 0.5 micrograms/ml), Neisseria gonorrhoeae (MIC90, 0.015 micrograms/ml), and Moraxella (Branhamella) catarrhalis (MIC90, 0.5 micrograms/ml) were also Ro 09-1227 susceptible. Ro 09-1227 activity against important gram-positive cocci was most comparable to that of ceftazidime. Bacteroides fragilis (MIC90, greater than 32 micrograms/ml) and the enterococci (MIC90, greater than 32 micrograms/ml) were resistant to Ro 09-1227. These in vitro results indicate that this catechol-substituted cephalosporin may be useful as an empiric agent, especially for some isolates resistant to currently available broad-spectrum cephalosporins.

Jones, R N; Erwin, M E



Spectrophotometric complexation of cephalosporins with palladium (II) chloride in aqueous and non-aqueous solvents  

NASA Astrophysics Data System (ADS)

The complexation reaction of cephalosporins namely cefotaxime (CTX), cefuroxime (CRX), and cefazolin (CEFAZ) with palladium (II) ions have been studied in water and DMF in 25 °C by the spectrophotometric methods. The 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 sulfate (SLS) as surfactant. The complexation process was optimized in terms of pH, temperature and contact time. The stoichiometry of all the complexes was found to be 2:1 (metal ion/ligand) for CTX, CRX, and 1:2 for CEFAZ. The stoichiometry of palladium (II)-cephalosporins was estimated by mole ratio and continuous variation methods and emphasized by the KINFIT program. These drugs could be determined by measuring the absorbance of each complex at its specific ?max. The results obtained are in good agreement with those obtained using the official methods. The proposed method was successfully applied for the determination of these compounds in their dosage forms.

Bagheri Gh., A.; Yosefi rad, A.; Rezvani, M.; Roshanzamir, S.



Antibiotic resistance determinants of multidrug-resistant Acinetobacter baumannii clinical isolates in Algeria.  


Antibiotic susceptibility testing was performed on 71 Acinetobacter baumannii clinical isolates, and presence of antibiotic resistance genes was screened for by PCR amplification and sequencing. Resistance rates were very high for aminoglycosides (22-80%), fluoroquinolones (>90%), and cephalosporins (>90%) but remained low for rifampin (2.8%) or null for colistin. Antibiotic resistance encoding genes detected were as follows: blaTEM-128 gene (74.6%), aph(3')-VI (50.7 %), aadA (63.4%), ant(2?)-I (14.1%), aac(3)-Ia (91.1%), aac(6')-Ib (4.2%), mutation Ser83Leu in gyrA (94.4%), double mutations Ser83Leu and Ser80Leu (or Ser84Leu) in gyrA and parC (69.0%), and mutation I581N in RRDR of the rpoB gene. PMID:23688522

Bakour, Sofiane; Touati, Abdelaziz; Sahli, Farida; Ameur, Abdennour Ait; Haouchine, Djamila; Rolain, Jean-Marc



Designed to penetrate: Time-resolved interaction of single antibiotic molecules with bacterial pores  

NASA Astrophysics Data System (ADS)

Membrane permeability barriers are among the factors contributing to the intrinsic resistance of bacteria to antibiotics. We have been able to resolve single ampicillin molecules moving through a channel of the general bacterial porin, OmpF (outer membrane protein F), believed to be the principal pathway for the -lactam antibiotics. With ion channel reconstitution and high-resolution conductance recording, we find that ampicillin and several other efficient penicillins and cephalosporins strongly interact with the residues of the constriction zone of the OmpF channel. Therefore, we hypothesize that, in analogy to substrate-specific channels that evolved to bind certain metabolite molecules, antibiotics have "evolved" to be channel-specific. Molecular modeling suggests that the charge distribution of the ampicillin molecule complements the charge distribution at the narrowest part of the bacterial porin. Interaction of these charges creates a region of attraction inside the channel that facilitates drug translocation through the constriction zone and results in higher permeability rates.

Nestorovich, Ekaterina M.; Danelon, Christophe; Winterhalter, Mathias; Bezrukov, Sergey M.



Literacy Measure B - Antibiotics  

Center for Drug Evaluation (CDER)

... Literacy Measure B - Antibiotics. ANTIBIOTICS. Frequency. Percent. Valid Percent. Cumulative Percent. Valid, Correct, 852, 94.2, 94.2, 94.2. ... More results from


Changing trend of empirical antibiotic regimen: experience of two studies at different periods in a neonatal intensive care unit in Tehran, Iran.  


Bacterial sepsis is one of the most common causes of mortality and morbidity in neonates. It has been recognized a gradual change in spectrum of organisms responsible for neonatal sepsis. In this study we have evaluated changing trend of incidence and antibiotic susceptibility in neonatal late - onset sepsis (LOS) in 2-periods. This study is based on results of blood culture in neonatal late-onset sepsis, in 2--periods study throughout 12 - years. Neonatal LOS was defined as clinical signs suggestive of infection with a positive blood culture (B/C) after 72 hrs of birth. During first study (period: 1990-1992), the most common bacteremia in LOS was staphylococcus aureus (staph aureus) (34%). Overall gram- negative bacteria (GNB) were the predominant organism (66%). It was shown that 60% of GNB were resisted to gentamicin and 3% to amikacin, while in case of gram-positive bacteria (GPB); about 95% were resisted to ampicillin and 28% to cephalothin. In the second study (period: 2004-2007), the vast majority (56.6%) of septic cases were caused by GNB. The most common cause of late- onset sepsis was klebsiela p. (31%). The GPB were resistant to cephalothin (90%). There has been a dramatic increase resistance to cephalothin and aminoglycosides and 3rd -generation cephalosporins. The combination of cephalothin plus amikacin in suspected LOS was no longer the effective therapeutic regimen in our neonatal intensive care unit (NICU). Now, it seems the best choice for empiric antibiotic regimen in suspected LOS is the combination vancomycin plus amikacin. Constant surveillance is important to guide empirical antibiotic therapy and changes in trends. PMID:21287464

Marzban, Asghar; Samaee, Hadi; Mosavinasab, Noredien


Hematologic Impact of Antibiotic Administration on Patients Taking Clozapine  

PubMed Central

Objective: The purpose of this study was to determine if the drop in white blood cell/absolute neutrophil count for clozapine patients on antibiotics is a normal response to the resolution of infection or if the concurrent administration resulted in an abnormal drop in blood counts and further reduction of white blood cell/absolute neutrophil below baseline prior to infection. Design: This was a retrospective record review of all patients who received clozapine and antibiotics concurrently between June 30, 2010, and June 30, 2011. Setting: Subjects included inpatients on clozapine therapy at a state psychiatric facility. Participants: This protocol was approved by the Institutional Review Board of record. A total of 42 patients prescribed 93 antibiotic regimens were found to meet all of the above requirements. Measurements and methods: Medications were placed into distinct groups based on approved use and mechanism of action. Pearson Correlation Coefficients were utilized and were found to be 0.409 (p<0.01), indicating that a statistically significant relationship existed between the use of systemic antibiotics and alterations in hematologic parameters. Results: Each regimen was classified by specific agent as well as whether the final white blood cell/absolute neutrophil was above or below the baseline established for each patient. Conclusion: Antibiotics have been identified as one category of medications that may cause decreased white blood cell/absolute neutrophil counts when combined with clozapine. Our study supports the use of either ciprofloxacin or moxifloxacin as agents that may have less risk of reductions in white blood cell/absolute neutrophil counts than are seen with penicillins, cephalosporins, and other antibiotics that may ultimately require interruption or discontinuation of clozapine therapy.

Shuman, Michael; Trigoboff, Eileen; Opler, Lewis A.



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


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

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



Bacterial Profile, Antibiotic Sensitivity and Resistance of Lower Respiratory Tract Infections in Upper Egypt  

PubMed Central

Background Lower respiratory tract infections (LRTI) account for a considerable proportion of morbidity and antibiotic use. We aimed to identify the causative bacteria, antibiotic sensitivity and resistance of hospitalized adult patients due to LRTI in Upper Egypt. Methods A multicentre prospective study was performed at 3 University Hospitals for 3 years. Samples included sputum or bronchoalveolar lavage (BAL) for staining and culture, and serum for serology. Samples were cultured on 3 bacteriological media (Nutrient, Chocolate, MacConkey's agars). Colonies were identified via MicroScan WalkAway-96. Pneumoslide IgM kit was used for detection of atypical pathogens via indirect immunofluorescent assay. Results The predominant isolates in 360 patients with CAP were S. pneumoniae (36%), C. pneumoniae (18%), and M. pneumoniae (12%). A higher sensitivity was recorded for moxifloxacin, levofloxacin, macrolides, and cefepime. A higher of resistance was recorded for doxycycline, cephalosporins, and ?-lactam-?-lactamase inhibitors. The predominant isolates in 318 patients with HAP were, methicillin-resistant Staphylococcus aureus; MRSA (23%), K. pneumoniae (14%), and polymicrobial in 12%. A higher sensitivity was recorded for vancomycin, ciprofloxacin, and moxifloxacin. Very high resistance was recorded for ?-lactam-?-lactamase inhibitors and cephalosporins. The predominant organisms in 376 patients with acute exacerbation of chronic obstructive pulmonary diseases (AECOPD) were H. influnzae (30%), S. pneumoniae (25%), and M. catarrhalis (18%). A higher sensitivity was recorded for moxifloxacin, macrolides and cefepime. A higher rate of resistance was recorded for aminoglycosides and cephalosporins. Conclusions The most predominant bacteria for CAP in Upper Egypt are S. pneumoniae and atypical organisms, while that for HAP are MRSA and Gram negative bacteria. For acute exacerbation of COPD, H. influnzae was the commonest organism. Respiratory quinolones, macrolides, and cefepime are the most efficient antibiotics in treatment of LRTI in our locality.

Agmy, Gamal; Mohamed, Sherif; Gad, Yaser; Farghally, Esam; Mohammedin, Hamdy; Rashed, Hebba



[Comparative urinary bactericidal activity of oral antibiotics against gram-positive pathogens].  


In routine bacteriological laboratories the antibacterial activity of antibiotics is determined by in vitro testing, usually by disk-diffusion test. However, in vitro testing does not always reflect antibacterial efficiency of antibiotics in vivo. In this investigation, the urine samples obtained in a single oral dose pharmacokinetic study were examined for their bactericidal activity against a range of relevant Gram-positive urinary tract pathogens. Urinary bactericidal activity of linezolid had been previously compared with ciprofloxacin but not with other oral antibiotics such as beta-lactams. Linezolid showed satisfactory urinary bactericidal titres throughout the whole testing period against all Gram-positive cocci. Fluoroquinolones displayed high and persisting levels of urinary bactericidal activity against staphylococci, but their activity against enterococci was weaker. According to the results of ex-vivo testing amoxycillin could be recommended only for infections caused by E. faecalis. Amoxycillin combined with clavulanic acid can be considered as a therapeutic option for infections caused by S. saprophyticus and E. faecalis. Older cephalosporins had high titres only against S. saprophyticus. Their drawback is a short elimination half-time in urine resulting in rapid decrease of urinary bactericidal titers during dosing interval. Furthermore, they do not show activity against enterococci due to their intrinsic resistance to cephalosporins. PMID:22930932

Bedeni?, Branka; Budimir, Ana; Gveri?, Ana; Plecko, Vanda; Vranes, Jasmina; Bubonja-Sonje, Marina; Kaleni?, Smilja


Treatment of severe infections caused by penicillin-resistant pneumococci. Role of third generation cephalosporins  

Microsoft Academic Search

Summary Penicillin resistance occurred soon after the discovery of penicillin, first in the test tube and subsequently in patients. The prevalence of invasive pneumococcal disease has been estimated to be as high as 15–18\\/100,000 in the elderly population and even higher in AIDS patients, children and the very old. While prevention with pneumococcal vaccine seems the most reasonable solution, under-utilization

E. Rubinstein; Bina Rubinovitch



[Sensitivity spectrum of Francisella tularensis to antibiotics and synthetic antibacterial drugs].  


Sensitivity of 6 F. tularensis strains to 57 antibiotics and synthetic antibacterial drugs was studied. It was shown that the strains were highly sensitive to aminoglycosides, tetracyclines, anzamycins, quinolones, chloramphenicol, nitrofurantoin, nitroxoline, novobiocin and fusidin and resistant to penicillins, cephalosporins, polypeptides, vancomycin and sulfanylamides. The interrace differences in F. tularensis could be detected only by sensitivity to erythromycin, oleandomycin and spiramycin. There was observed no cross resistance to streptomycin and other aminoglycosides in F. tularensis. Assay of F. tularensis sensitivity to antibacterial drugs of various groups with the rapid photometric procedure and the agar diffusion method revealed that the results were highly comparable. PMID:2610533

Vasi'lev, N T; Oborin, V A; Vasi'lev, P G; Glushkova, O V; Kravets, I D; Levchuk, B A



Developing New Antibiotics with Combinatorial Biosynthesis  

NASA Astrophysics Data System (ADS)

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.

Pohl, Nicola L.



Functional characterisation of a metagenome derived family VIII esterase with a deacetylation activity on ?-lactam antibiotics.  


Family VIII esterases represent a poorly characterised esterase family, with high sequence identity to class C ?-lactamases, peptidases and penicillin binding proteins. This study reports on the metagenomic library screening and biochemical characterisation of a novel esterase (Est22) derived from an acidic Leachate environment. The enzyme is 423 amino acids in length and contained 22 aa signal peptide. The Est22 primary structure revealed the presence of N-terminus S-x-x-K sequence, which is also highly conserved in class C ?-lactamases, peptidases as well as carboxylesterases belonging to family VIII. Phylogenetic analysis using the representative sequences from class C ?-lactamases and family VIII esterases indicated that Est22 is a member of family VIII esterases. Substrate specificity profiling using p-nitrophenyl esters (C2-C16) indicated that Est22 preferred shorter chain p-nitrophenyl esters (C2-C5), a characteristic that is typical for true carboxylesterases. In addition of hydrolysing Nitrocefin, Est22 also hydrolysed first generation cephalosporin based derivatives. Detailed selectivity study using different cephalosporin based substrates indicated that Est22 selectively hydrolyse the ester bond of a cephalosporin derivatives leaving the amide bond of the ?-lactam ring intact. The selective nature of Est22 makes this enzyme a potential candidate for the use in the synthesis and modification cephalosporin based molecules. PMID:23827391

Mokoena, Nobalanda; Mathiba, Kgama; Tsekoa, Tsepo; Steenkamp, Paul; Rashamuse, Konanani



Antibiotic susceptibility survey of Neisseria gonorrhoeae in Thailand.  


The antibiotic susceptibilities of Neisseria gonorrhoeae isolates obtained from patients attending sexually transmitted disease clinics in Cholburi and Bangkok, Thailand, were determined by agar dilution. Some 28.2% of isolates produced beta-lactamase. A total of 97.9% of beta-lactamase-positive and 51% of beta-lactamase-negative isolates tested were resistant to penicillin (MICs, greater than or equal to 2 micrograms/ml), 70% of isolates tested were resistant to tetracycline (MICs, greater than or equal to 2 micrograms/ml), and 91% of isolates tested were susceptible to spectinomycin (MICs, less than or equal to 64 micrograms/ml). The MICs for 90% of isolates for the other drugs tested were 2 micrograms/ml for erythromycin, 2 micrograms/ml for cefoxitin, 1 micrograms/ml for cefuroxime, 0.125 micrograms/ml for cefpodoxime, 0.06 micrograms/ml for cefotaxime, 0.25 micrograms/ml for ceftazidime, 0.03 micrograms/ml for ceftizoxime, 0.03 micrograms/ml for ceftriaxone, 0.03 micrograms/ml for cefixime, 0.06 micrograms/ml for aztreonam, 0.008 micrograms/ml for ciprofloxacin, 0.125 micrograms/ml for norfloxacin, and 0.075 micrograms/ml for ofloxacin. Fewer than 1.5% of isolates were resistant to the extended-spectrum cephalosporins tested. Some 0.3% or fewer isolates were resistant to broad-spectrum cephalosporins, fluoroquinolones, or the monobactam aztreonam. Antibiotic resistance among N. gonorrhoeae isolates from Cholburi and Bangkok in May 1990 appeared to be primarily limited to penicillin and tetracycline, which are no longer used to control gonorrhea. Spectinomycin, which has been in general use against gonorrhea in Thailand since 1983, has dwindling utility, with resistance at a level of 8.9%. PMID:1416851

Clendennen, T E; Echeverria, P; Saengeur, S; Kees, E S; Boslego, J W; Wignall, F S



Natural antibiotic susceptibility of Escherichia coli, Shigella, E. vulneris, and E. hermannii strains.  


The natural antibiotic susceptibility of 139 Escherichia coli strains (including 18 enterohemorrhagic E. coli), 73 Shigella strains (S. sonnei (n = 37), S. flexneri (n = 29), S. boydii (n = 6), S. dysenteriae (n = 1)), 23 E. vulneris, and 20 E. hermannii strains toward 71 antibiotics was examined. MICs were determined using a microdilution procedure. All examined taxa were naturally sensitive/intermediate toward tetracyclines, aminoglycosides, some penicillins (amoxycillin/clavulanate, ampicillin/sulbactam, piperacillin [with and without tazobactam], mezlocillin, azlocillin), cephalosporins, carbapenems, monobactams, quinolones, trimethoprim, cotrimoxazole, and chloramphenicol and were naturally resistant/intermediate toward benzylpenicillin, oxacillin, macrolides, lincosamides, glycopeptides, rifampicin, and fusidic acid. No differences in natural antibiotic susceptibility were seen between enterohemorrhagic and other E. coli strains. Likewise, with one exception, no significant differences in natural antibiotic susceptibility were seen either among the Shigella subgroups or between Shigella and E. coli. The natural population of S. flexneri was slightly more susceptible to chloramphenicol than the natural populations of other taxa within the Shigella-E. coli complex. E. vulneris and E. hermannii showed susceptibility patterns to many antibiotics similar to Shigella and E. coli, but there were other antibiotics toward which there were significant differences in natural susceptibility. E. vulneris and E. hermannii were less susceptible to nitrofurantoin and slightly more susceptible to several aminoglycosides than E. coli and Shigella. E. hermannii was the only species that was naturally resistant/intermediate to ticarcillin and amoxycillin (DIN standard). The addition of clavulanic acid to the latter resulted in a decrease of seven twofold dilution steps (E. vulneris: four twofold dilution steps, E. coli/Shigella: two twofold dilution steps) of the MICs of the natural population. With the exception of cefoperazone and cefepime, E. hermannii was more susceptible to cephalosporins than strains of the other species. E. vulneris was the species most susceptible to ticarcillin and the only species that was highly resistant to fosfomycin (MIC > 256 micrograms/mL). The antibiotic susceptibility to fosfomycin was also unique for E. hermannii (MIC 32-128 micrograms/mL), whereas the natural populations of E. coli and Shigella showed lower MIC values. The data of this study represent an assessment of the natural susceptibility of strains of Escherichia spp. and Shigella subgroups to a wide range of antibiotics. These databases can be used for the validation of antibiotic susceptibility test results of Escherichia spp. and shigellae. The conformity of the natural antibiotic susceptibility test results not only among the Shigella subgroups but also between Shigella and E. coli support the status of Shigella as a subgroup of the species E. coli. PMID:10092968

Stock, I; Wiedemann, B



The utilization of beet molasses as a novel carbon source for cephalosporin C production by Acremonium chrysogenum: Optimization of process parameters through statistical experimental designs.  


In this work, cephalosporin C (CPC) production on pilot scale fermenters of 600l capacity with 350l working volume by Acremonium chrysogenum EMCC 904 was performed. The effects of fermentation medium composition, inoculum concentration, initial pH and aeration rate on CPC production by A. chrysogenum strain was investigated by using response surface methodology (RSM). The Plackett-Burman design which involves two concentrations of each nutrient was effective in searching for the major medium components promoting CPC production. Under our experimental conditions; Soya oil, beet molasses and corn steep liquor were found to be the major factors contributing to the antibiotic production. Subsequently, a Box-Behnken design was used for outlining the concentration of the most effective medium constituents. Estimated optimum composition for the production of CPC was as follows: soya oil, 40g/l; beet molasses, 180g/l; and corn steep liquor, 330g/l. The central composite design was used for outlining the optimum values of the fermentation parameters. Estimated optimum values for the production of CPC are as follows: inoculum level, 10(5.5)spores/ml; initial pH, 4.3; and aeration rate, 9364ml/min. PMID:17222554

Lotfy, Walid A



Influence of cephalosporins and iron on surface protein antigens of Klebsiella pneumoniae in vivo.  

PubMed Central

The outer membrane protein (OMP) profiles of Klebsiella pneumoniae grown in a rabbit peritonitis model in the presence or absence of cephalosporins were investigated. Six high-molecular-weight OMPs (Mr 69,000 to 83,000) were induced under iron-depleted conditions in vitro. Three of these proteins (the 69,000-Mr protein [69K protein] and the 70K and 78K proteins) and trace amounts of the 73K and 75K proteins were induced in the OM of bacteria infecting the peritoneal cavity of rabbits. Addition of iron either to the growth medium in vitro or to the peritoneum in vivo repressed the expression of these proteins. Cephaloridine had no significant effect on the OMP profiles. An additional 56,000-Mr protein was observed in the OM of bacteria cultivated in vivo in the presence of CGP 17520 and also to a lesser extent in vivo under conditions of iron excess. A difference in recognition of OM antigens between cells grown in vitro and in vivo was observed by immunoblotting techniques. The 26K, 27.5K, and 28.5K antigens present in the OM of cells grown in vitro (but not in vivo) were recognized by antibodies raised against bacteria cultivated in vitro under conditions of iron depletion, but were not recognized by antisera raised against bacteria harvested directly from infections. Antisera raised against a nonencapsulated K. pneumoniae strain caused no agglutination of encapsulated K. pneumoniae grown in vivo in the absence of cephalosporins. Rapid agglutination was observed with this antiserum when the same encapsulated strain was grown in vivo in the presence of either cephalosporin, indicating less occlusion of critical antigens by the capsule. Images

Kadurugamuwa, J L; Anwar, H; Brown, M R; Hengstler, B; Kunz, S; Zak, O



In vitro evaluation of CENTA, a new beta-lactamase-susceptible chromogenic cephalosporin reagent.  

PubMed Central

CENTA is a newly synthesized, beta-lactamase-labile, chromogenic cephalosporin reagent which changes color from light yellow (lambda maximum ca. 340 nm) to chrome yellow (lambda maximum ca. 405 nm) concomitant with hydrolysis of the beta-lactam ring. This compound offers promise as a diagnostic reagent comparable to other chromogens (PADAC and nitrocefin) for the early detection of beta-lactamase-producing clinical isolates, while retaining some antimicrobial effect against Escherichia coli, Klebsiella spp., Proteus mirabilis, Staphylococcus aureus, and non-enterococcal Streptococcus spp. CENTA is relatively unaffected by commonly used microbiological media and human serum.

Jones, R N; Wilson, H W; Novick, W J; Barry, A L; Thornsberry, C



The antibiotic susceptibility patterns of uropathogenic Escherichia coli, with special reference to the fluoroquinolones.  


Context: The emergence of drug resistance to trimethoprim-sulfamethoxazole, the penicillins, cephalosporins, and fluoroquinolones by Uropathogenic Escherichia coli (UPEC) has limited the options for selecting the appropriate antibiotic for the treatment of urinary tract infections. Aims: The The E. coli isolates, which were obtained from the culture of urine samples,were studied for their antibiotic resistance patterns, with special reference to the antimicrobial activity of the fluoroquinolones and the production of the extended spectrum ?-lactamases. (ESBL), Settings and Design: This was a hospital based, prospective study which was done for a period of eighteen months. Material and Methods: This study was done by using the standard culture techniques for urine samples, the modified Kirby-Bauer disk diffusion method for the antibiotic susceptibility testing and the disk diffusion method to confirm the ESBL production by the clinical isolates of E. coli in urine. The sensitivity pattern was correlated with the clinical condition and the presence of the risk factors. The statistical analysis which was used: The statistical analysis was done by using the proportions of sensitive, resistant and intermediates. Descriptive statistics like the total, mean and percentage were done by using the Statistical Package for the Social Sciences (SPSS), version 15.0. Results: The hospital isolates showed high degrees of resistance to the penicillins, cephalosporins, nalidixic acid and the fluoroquinolones, with 59% of the isolates being ESBL producers. Conclusions: The incidence of the multidrug resistant strains of Escherichia coli has been steadily increasing over the past few years. The knowledge on the resistance pattern of the bacterial strains in a geographical area will help in guiding the appropriate and the judicious use of antibiotics. Also, the formulation of an appropriate hospital antibiotic policy will go a long way in controlling these infections. PMID:23905095

Shariff V A, Abdul Rahaman; Shenoy M, Suchitra; Yadav, Taruna; M, Radhakrishna



[Compilation of antibiotic use in farm animals via veterinary surgeries].  


A feasibility study with 20 voluntarily participating veterinary surgeries was carried out in order to test, if the consumption of antibiotics in livestock can be determined systematically. Information about the statutory documents on the application of drugs of the participating surgeries were entered in a central database and analysed systematically. Surgeries that treat only livestock used significantly more antibiotics (number of treatment units per veterinarian) per veterinarian than surgeries that treat also small animals. The comparison of small and large surgeries showed that veterinarians in small surgeries treated fewer pigs and more cattle than their colleagues in large surgeries (number of treatment units per veterinarian). All in all, tetracyclines counted for more than 50% of all substances used (regarding the amount), followed by beta-lactams (25%) and sulfonamides incl. trimethoprim (11%). In poultry, polypeptides and beta-lactams were used most frequently. While cephalosporines were used only in cattle in a noteworthy frequency, fluoroquinolones were applied to poultry in almost 12% of all applications (application of one substance to one animal at one day). In total, it was shown, that harmonized documentation of consumption of antibiotics is feasible, but the relation of antibiotics to the treated population is problematic which has to be considered in the future.The number of applications is more suitable to assess the antibiotic use than the amount in kg, because the latter is dependent of the dosage. The impact of highly dosed substances like e.g. tetracyclines is overestimated by regarding the amount, while substances with low dosages are underestimated. PMID:23901586

Merle, Roswitha; Hegger-Gravenhorst, Christine; Robanus, Matthias; Hajek, Peter; Honscha, Walther; Käsbohrer, Annemarie; Kreienbrock, Lothar


Antibiotic susceptibility pattern of urinary tract pathogens in Ibadan, Nigeria.  


Urinary tract infections (UTI) affect all age groups and occur in both hospitalized and non-hospitalized individuals and have serious impact on the socioeconomic life of the individual and the society, and also account for a large proportion of antibacterial drug consumption. Treatment failure has been attributed to increasing resistance to common antibiotics, but there is paucity of data from this part of Nigeria. This prospective study was carried out to determine the prevalence and antibiotic susceptibility pattern of uropathogens in Ibadan using standard microbiological diagnostic methods. Statistical analysis was by simple percentages among related variables. Four hundred and nine urinary isolates, 239 (58.4%) and 170 (41.6%) from hospitalized and non-hospitalized patients respectively were studied. Frequency of occurrence of urinary pathogens were Klebsiella spp 171 (41.8%), Pseudomonas species (including Pseudomonas aeruginosa) 81 (19.8%), Escherichia coli 78 (19.1%), Staphylococcus aureus 31 (7.6%) and Proteus mirabilis 31 (7.6%). Resistance to commonly used antibiotics such as ampicillin 97%, tetracycline 93%, cotrimoxazole 98%, and amoxycillin 89% was observed among most uropathogens. Seventy-five to 100% Pseudomonas spp. were resistant to the common antibiotics and also 87.1% and 82.4% were resistant to nalidixic acid and cefuroxime respectively. However, appreciable susceptibility by all uropathogens was found with amikacin 75%, ciprofloxacin 72.2%, ceftriaxone 68.4%, and pefloxacin 64.9%. Isolates from the community showed more susceptibility to tested drugs. In conclusion, widespread resistance to most antibiotics including cephalosporins and quinolones was found among all uropathogens. PMID:21416786

Dada-Adegbola, H O; Muili, K A



Study of developed resistance due to antibiotic treatment of coagulase-negative Staphylococci.  


Coagulase-negative Staphylococci (CoNS) are a major cause of postoperative infections. These infections are often associated with foreign material implants and/or a compromised immune system in the patient. Multiresistant strains are increasingly common in the hospital environment and there is concern that the infections will become difficult or impossible to treat. This report is based on a study of 75 patients, with postoperative infections caused by CoNS after thoracic surgery. All patients were treated with surgical revision and antibiotic therapy. One or more bacterial cultures were made in each case, and the resistance pattern of the CoNS found was determined. The goal of the study was to evaluate possible relationships between antibiotic therapy and the appearance of resistance to antibiotics in CoNS found. To describe this relationship, three models were constructed and analyzed by multiple logistic regression. The results indicate an increased resistance to beta-lactam antibiotics and clindamycin after the use of cephalosporins. Also, the use of vancomycin or vancomycin in combination with rifampicin or fusidic acid increases the risk for development of resistance to beta-lactam antibiotics, ciprofloxacin, fusidic acid, clindamycin, netilmycin, and rifampicin. The hypothesis that a combination of antibiotics will curtail the development of resistance was not supported in this study. PMID:12705677

Tegnell, Anders; Grabowska, Katarzyna; Jacobsson, Anders; Andersson, Mikael; Giesecke, Johan; Ohman, Lena



Frontline antibiotic therapy.  


The need to use front-line antibiotics wisely has never been greater. Antibiotic resistance and multi-drug resistant infection, driven by antibiotic use, remain major public health and professional concerns. To overcome these infection problems, use of older antibiotics active against multi drug-resistant pathogens is increasing - for example, colistin, fosfomycin, pivmecillinam, pristinamycin, temocillin and oral tetracyclines. The number of new antibacterials reaching clinical practice has reduced significantly in the last 20 years, most being focused on therapy of Gram-positive infection - eg linezolid, daptomycin, telavancin and ceftaroline. Recent guidance on antibiotic stewardship in NHS trusts in England is likely to provide a backdrop to antibiotic use in hospitals in the next 5 years. PMID:23760700

MacGowan, Alasdair; Albur, Maha



Biotic acts of antibiotics  

PubMed Central

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.

Aminov, Rustam I.



Competing Doctors, Antibiotic Use, and Antibiotic Resistance in Taiwan  

Microsoft Academic Search

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

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


Antibiotic prescriptions in children  

Microsoft Academic Search

Results: In the year surveyed, 511270 antibiotic prescriptions in 219 257 children were identified. In all, 52.9% of children received at least one antibiotic; this percentage decreased with age, ranging from 70.4% in children 1-2 years old to 35.8% in children >11 years old. Fifty-two per cent of inhabitants under the age of 15 years were treated with systemic antibiotics

D. Resi; M. Milandri; M. L. Moro; Viale Aldo Moro



Process for preparing antibiotics  

US Patent & Trademark Office Database

Culturing aerobically Agrobacterium radiobacter no. 31700 in a culture medium containing carbon and nitrogen sources yields the antibiotic substance EM5400, comprising salts of certain azetidinesulfonic acid derivatives.

Sykes; Richard B. (Belle Mead, NJ); Parker; William L. (Pennington, NJ)



Declining cephalosporin and fluoroquinolone non-susceptibility among bloodstream Enterobacteriaceae from the UK: links to prescribing change?  


OBJECTIVES: The UK saw major increases in cephalosporin and quinolone resistance amongst Enterobacteriaceae from 2001 to 2006, with cephalosporin resistance largely reflecting dissemination of CTX-M extended-spectrum ?-lactamases (ESBLs). We review subsequent trends. METHODS: Data were extracted from Public Health England's national database (LabBase), which collects susceptibility results for bloodstream isolates from hospital microbiology laboratories in England, Wales and Northern Ireland, and from the BSAC Bacteraemia Resistance Surveillance System, which centrally tests bloodstream isolates from 25-40 sentinel UK and Irish laboratories. Reference laboratory submissions were also reviewed. RESULTS: LabBase and BSAC data showed that rates of non-susceptibility to cephalosporins and quinolones rose amongst Escherichia coli and Klebsiella spp. until mid-decade (2004-07) before plateauing or falling; similar falls in non-susceptibility began slightly earlier in Enterobacter spp. These reversals in trend occurred whilst the incidence of E. coli bacteraemias was rising, the incidence of Klebsiella bacteraemias was stable and the incidence of Enterobacter bacteraemias was falling; they were not paralleled in EARS-Net data for continental Europe and did not reflect the displacement of single mechanisms. They coincided with large reductions in hospital cephalosporin and quinolone use, owing to concern about Clostridium difficile, with replacement by penicillin/?-lactamase inhibitor combinations, which have borderline activity against ESBL producers, but consistently lack activity against carbapenemase producers. CONCLUSIONS: Non-susceptibility to cephalosporins and quinolones has declined among bloodstream Enterobacteriaceae in the UK, probably reflecting prescribing shifts. The penicillin/?-lactamase inhibitor combinations that have largely replaced cephalosporins and quinolones may add to selection for carbapenemase producers. PMID:23766490

Livermore, David M; Hope, Russell; Reynolds, Rosy; Blackburn, Ruth; Johnson, Alan P; Woodford, Neil



AcFKH1, a novel member of the forkhead family, associates with the RFX transcription factor CPCR1 in the cephalosporin C-producing fungus Acremonium chrysogenum  

Microsoft Academic Search

In the filamentous fungus Acremonium chrysogenum, a complex regulatory network of transcription factors controls the expression of at least seven cephalosporin C biosynthesis genes. The RFX transcription factor CPCR1 binds to regulatory sequences in the promoter region of cephalosporin C biosynthesis genes, and is involved in the transcriptional regulation of the pcbC gene which encodes isopenicillin N synthase. In this

Esther K. Schmitt; Birgit Hoff; Ulrich Kück



Synthesis and preliminary antimicrobial evaluation of new 7-(N-pyrrolyl) derivatives of cephalosporins.  


A series of seven new cephalosporins was prepared for preliminary microbiological evaluation by N-acylation of 7-aminocephalosporanic acid with substituted N-pyrrolylcarboxylic acids via mixed anhydrides. The chemical structure of the compounds were confirmed by IR, 1H-NMR and mass spectral data. The 7-(N-pyrrolyl) cephalosporin derivatives were tested in vitro by the disc diffusion method upon 3 strains and subsequent determination of the minimal inhibitory concentration (MIC) of the most active ones upon 29 strains. The products of the series exhibited antibacterial activity. They showed selective potency against gram-positive and were practically inactive against gram-negative microorganisms. The compound 3-[(acetyloxy)methyl]-7-([2-[3-(ethoxycarbonyl)-2-methyl-5-phenyl-1H-1-pyrrolyl]acetyl]amino)-6-oxo-7,7a-dihydro-2H,6H-aceto[2,1-b][1,3]thiazine-4-carboxylic acid (4a) was outlined as more active than the reference cefazolin (CAS 23325-78-2) in regard to S. pyogenes and some strains of S. aureus, the MIC of 4a against S. pyogenes were at least 4-fold lower. The toxicological evaluations of the starting N-pyrrolylcarboxylic acids showed no acute toxicity. PMID:15038462

Bijev, Atanas; Nankov, Atanas; Keuleyan, Emma; Markovska, Rumiana; Daneva, Elitsa



Expression of genes and processing of enzymes for the biosynthesis of penicillins and cephalosporins.  


The genes pcbAB, pcbC and penDE encoding the enzymes (alpha-aminoadipyl-cysteinyl-valine synthetase, isopenicillin N synthase and isopenicillin N acyltransferase, respectively) involved in the biosynthesis of penicillin have been cloned from Penicillin chrysogenum and Aspergillus nidulans. They are clustered in chromosome I (10.4 Mb) of P. chrysogenum, in chromosome II of Penicillium notatum (9.6 Mb) and in chromosome VI (3.0 Mb) of A. nidulans. Each gene is expressed as a single transcript from separate promoters. Enzyme regulation studies and gene expression analysis have provided useful information to understand the control of genes involved in penicillin biosynthesis. The enzyme isopenicillin N acyltransferase encoded by the penDE gene is synthesized as a 40 kDa protein that is (self)processed into two subunits of 29 and 11 kDa. Both subunits appear to be required for acyl-CoA 6-APA acyltransferase activity. The isopenicillin N acyltransferase was shown to be located in microbodies, whereas the isopenicillin N synthase has been reported to be present in vesicles of the Golgi body and in the cell wall. A mutant in the carboxyl-terminal region of the isopenicillin N acyltransferase lacking the three final amino acids of the enzymes was not properly located in the microbodies and failed to synthesize penicillin in vivo. In C. acremonium the genes involved in cephalosporin biosynthesis are separated in at least two clusters. Cluster I (pcbAB-pcbC) encodes the first two enzymes (alpha-aminoadipyl-cysteinyl) valine synthetase and isopenicillin N synthase) of the cephalosporin pathway which are very similar to those involved in penicillin biosynthesis. Cluster II (cefEF-cefG), encodes the last three enzymatic activities (deacetoxycephalosporin C synthetase/hydroxylase and deacetylcephalosporin C acetyltransferase) of the cephalosporin pathway. It is unknown, at this time, if the cefD gene encoding isopenicillin epimerase is linked to any of these two clusters. Methionine stimulates cephalosporin biosynthesis in cultures of three different strains of A. chrysogenum. Methionine increases the levels of enzymes (isopenicillin N synthase and deacetylcephalosporin C acetyltransferase) expressed from genes (pcbC and cefG respectively) which are separated in the two different clusters of cephalosporin biosynthesis genes. This result suggests that both clusters of genes have regulatory elements which are activated by methionine. Methionine-supplemented cells showed higher levels of transcripts of the pcbAB, pcbC, cefEF genes and to a lesser extent of cefG than cells grown in absence of methionine. The levels of the cefG transcript were very low as compared to those of pcbAB, pcbC and cefEF.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:7847890

Martín, J F; Gutiérrez, S; Fernández, F J; Velasco, J; Fierro, F; Marcos, A T; Kosalkova, K



?-Lactams and Florfenicol Antibiotics Remain Bioactive in Soils while Ciprofloxacin, Neomycin, and Tetracycline Are Neutralized?  

PubMed Central

It is generally assumed that antibiotic residues in soils select for antibiotic-resistant bacteria. This assumption was tested by separately adding 10 different antibiotics (?200 ppm) to three soil-water slurries (silt-loam, sand-loam, and sand; 20% soil [wt/vol]) and incubating mixtures for 24 h at room temperature. The antibiotic activity of the resultant supernatant was assessed by culturing a sensitive Escherichia coli strain in the filter-sterilized supernatant augmented with Luria-Bertani broth. We found striking differences in the abilities of supernatants to suppress growth of the indicator E. coli. Ampicillin, cephalothin, cefoxitin, ceftiofur, and florfenicol supernatants completely inhibited growth while bacterial growth was uninhibited in the presence of neomycin, tetracycline, and ciprofloxacin supernatants. High-performance liquid chromatography (HPLC) analysis demonstrated that cefoxitin and florfenicol were almost completely retained in the supernatants, whereas tetracycline and ciprofloxacin were mostly removed. Antibiotic dissipation in soil, presumably dominated by adsorption mechanisms, was sufficient to neutralize 200 ppm of tetracycline; this concentration is considerably higher than reported contamination levels. Soil pellets from the tetracycline slurries were resuspended in a minimal volume of medium to maximize the interaction between bacteria and soil particles, but sensitive bacteria were still unaffected by tetracycline (P = 0.6). Thus, residual antibiotics in soil do not necessarily exert a selective pressure, and the degree to which the pharmaceutical remains bioactive depends on the antibiotic. Efforts to control antibiotic contamination would be better directed toward compounds that retain biological activity in soils (e.g., cephalosporins and florfenicol) because these are the antibiotics that could exert a selective pressure in the environment.

Subbiah, Murugan; Mitchell, Shannon M.; Ullman, Jeffrey L.; Call, Douglas R.



Antibiotic Resistance in Poultry  

Microsoft Academic Search

The worldwide increase in the use of antibiotics as an integral part of the poultry and livestock production industry to treat and prevent infectious bacterial diseases and as growth promoters at sub - therapeutic levels in feeds has led to the problem of the development of bacterial antibiotic resistance during the past years. Recent scientific evidence has shown that resistance

D. F. Apata



Tackling antibiotic resistance  

Microsoft Academic Search

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 it must be tackled in the most effective ways possible. To explore how the problem of antibiotic resistance might best be addressed, a group of 30 scientists from academia and industry

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



Antibiotic resistance is ancient  

Microsoft Academic Search

The discovery of antibiotics more than 70years ago initiated a period of drug innovation and implementation in human and animal health and agriculture. These discoveries were tempered in all cases by the emergence of resistant microbes. This history has been interpreted to mean that antibiotic resistance in pathogenic bacteria is a modern phenomenon; this view is reinforced by the fact

Vanessa M. D'Costa; Christine E. King; Lindsay Kalan; Mariya Morar; Wilson W. L. Sung; Carsten Schwarz; Duane Froese; Grant Zazula; Fabrice Calmels; Regis Debruyne; G. Brian Golding; Hendrik N. Poinar; Gerard D. Wright



Antibiotic-Resistant Bacteria.  

ERIC Educational Resources Information Center

A study conducted by high school advanced bacteriology students appears to confirm the hypothesis that the incremental administration of antibiotics on several species of bacteria (Escherichia coli, Staphylococcus epidermis, Bacillus sublitus, Bacillus megaterium) will allow for the development of antibiotic-resistant strains. (PEB)

Longenecker, Nevin E.; Oppenheimer, Dan



Antibiotic-Resistant Bacteria.  

ERIC Educational Resources Information Center

|A study conducted by high school advanced bacteriology students appears to confirm the hypothesis that the incremental administration of antibiotics on several species of bacteria (Escherichia coli, Staphylococcus epidermis, Bacillus sublitus, Bacillus megaterium) will allow for the development of antibiotic-resistant strains. (PEB)|

Longenecker, Nevin E.; Oppenheimer, Dan



[Antibiotics: present and future].  


The author discuss the up to date interpretation of the concept of antibiotics and antibiotic research, as well as the present role of various natural, semisynthetic and synthetic antibiotic compounds in various areas of the human therapy. The origin and the total number of all antibiotics and applied antibiotics in the practice, as well as the bioactive microbial metabolites (antibiotics) in other therapeutical, non-antibiotic fields (including agriculture) are also reviewed. The author discusses main problems, such as increasing (poly)resistance, virulence of pathogens and the non-scientific factors (such as a decline of research efforts and their sociological, economic, financial and regulatory reasons). A short summary of the history of Hungarian antibiotic research is also provided. The author briefly discusses the prospects in the future and the general advantages of the natural products over synthetic compounds. It is concluded that new approaches for the investigation of the unlimited possibilities of the living world are necessary. The discovery of new types or simply neglected (micro)organisms and their biosynthetic capabilities, the introduction of new biotechnological and genetic methods (genomics, metagenom, genome mining) are absolutely required in the future. PMID:23567874

Bérdy, János



Antibiotic resistance in animals  

Microsoft Academic Search

There is currently no systematic surveillance or monitoring of antibiotic resistance in Australian animals. Registration of antibiotics for use in animals is tightly controlled and has been very conservative. Fluoroquinolones have not been registered for use in food producing animals and other products have been removed from the market because of human health concerns. In the late 1970s, the Animal

Mary D Barton; Rachael Pratt; Wendy S Hart


Antibiotic efflux pumps  

Microsoft Academic Search

Active efflux from procaryotic as well as eucaryotic cells strongly modulates the activity of a large number of antibiotics. Effective antibiotic transport has now been observed for many classes of drug efflux pumps. Thus, within the group of primary active transporters, predominant in eucaryotes, six families belonging to the ATP-binding cassette superfamily, and including the P-glycoprotein in the MDR (Multi

Françoise Van Bambeke; Elisabetta Balzi; Paul M. Tulkens



Aerosolized antibiotics for ventilator-associated pneumonia: lessons from experimental studies.  


The aim of this review is to perform a critical analysis of experimental studies on aerosolized antibiotics and draw lessons for clinical use in patients with ventilator-associated pneumonia. Ultrasonic or vibrating plate nebulizers should be preferred to jet nebulizers. During the nebulization period, specific ventilator settings aimed at decreasing flow turbulence should be used, and discoordination with the ventilator should be avoided. The appropriate dose of aerosolized antibiotic can be determined as the intravenous dose plus extrapulmonary deposition. If these conditions are strictly respected, then high lung tissue deposition associated with rapid and efficient bacterial killing can be expected. For aerosolized aminoglycosides and cephalosporins, a decrease in systemic exposure leading to reduced toxicity is not proven by experimental studies. Aerosolized colistin, however, does not easily cross the alveolar-capillary membrane even in the presence of severe lung infection, and high doses can be delivered by nebulization without significant systemic exposure. PMID:23135264

Rouby, Jean-Jacques; Bouhemad, Belaďd; Monsel, Antoine; Brisson, Hélčne; Arbelot, Charlotte; Lu, Qin



A colorimetric assay for the determination of acetyl xylan esterase or cephalosporin C acetyl esterase activities using 7-amino cephalosporanic acid, cephalosporin C, or acetylated xylan as substrate.  


A bromothymol blue-based colorimetric assay has been devised to screen for acetyl xylan esterase or cephalosporin C (CPC) deacetylase activities using 7-amino cephalosporanic acid (7-ACA), CPC, or acetylated xylan as substrate. These enzymes are not screened with their natural substrates because of the tedious procedures available previously. Acetyl xylan esterase from Bacillus pumilus CECT 5072 was cloned, expressed in Escherichia coli Rosetta (DE3), and characterized using this assay. Similar K(M) values for 7-ACA and CPC were obtained when compared with those described using HPLC methods. The assay is easy to perform and can be carried out in robotic high-throughput colorimetric devices normally used in directed evolution experiments. The assay allowed us to detect improvements in activity at a minimum of twofold with a very low coefficient of variance in 96-well plates. This method is significantly faster and more convenient to use than are known HPLC and pH-stat procedures. PMID:17651681

Martínez-Martínez, Irene; Montoro-García, Silvia; Lozada-Ramírez, José Daniel; Sánchez-Ferrer, Alvaro; García-Carmona, Francisco



A prospective, randomised trial of prophylactic antibiotics versus bag extraction in the prophylaxis of wound infection in laparoscopic cholecystectomy.  

PubMed Central

Septic complications are rare following laparoscopic cholecystectomy if prophylactic antibiotics are given, as demonstrated in previous studies. Antibiotic treatment may be unnecessary and, therefore, undesirable, so we compared two forms of prophylaxis: a cephalosporin antibiotic and bag extraction of the dissected gallbladder. A total of 76 patients undergoing laparoscopic cholecystectomy were randomised to either receive an antibiotic or to have their gallbladder removed from the abdomen in a plastic bag. Complicated cases were excluded. There was a total of 6 wound infections (7.9%), 3 in each of the study groups. All these were associated with skin commensals. There were no other septic complications. Bacteriological studies grouped the organisms isolated from the bile and the wound as potential pathogens and likely commensals. A total of 10 potential pathogens were isolated, 9 of which were found in the group receiving antibiotics. We conclude that septic sequelae of uncomplicated laparoscopic cholecystectomy are uncommon, but clearly not entirely prevented by antibiotic or mechanical prophylaxis. Prophylactic antibiotics may not be required in uncomplicated laparoscopic cholecystectomy. Further study is warranted.

Harling, R.; Moorjani, N.; Perry, C.; MacGowan, A. P.; Thompson, M. H.



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 ...


Epidemiology of hospital-acquired infections in cirrhotic patients: effect of carriage of methicillin-resistant Staphylococcus aureus and influence of previous antibiotic therapy and norfloxacin prophylaxis.  


We assessed the prevalence of carriage of methicillin-resistant Staphylococcus aureus (MRSA) in anterior nares and stools, and of third-generation cephalosporin resistant enterobacteriaceae and non-fermenting gram-negative bacilli (RE/RNF) in stools of 748 hospitalized long-stay cirrhotic patients. We also evaluated the consequences of carriage on the epidemiology of hospital-acquired spontaneous bacterial peritonitis, bacteraemia and urinary tract infection (UTI) in these patients. The prevalence of carriage of MRSA and RE/RNF was 16.7% and 14.7% respectively. Whereas RE/RNF carriage did not lead to an increased risk of infection due to RE/RNF, the overall risk of infections caused by MRSA was more than tenfold higher in MRSA carriers. MRSA and RE/RNF carriers had received prior antibiotic therapy to a greater extent than non-carriers (P < 0.001) and MRSA carriers had received prior norfloxacin prophylaxis to a greater extent than the two other groups (P < 0.02). The mortality rate during hospital stay was higher in MRSA and RE/RNF carriers than in non-carriers (P < 0.001). Pugh score (P < 0.0001), age (P < 0.0001), MRSA carriage (P = 0.0018) and bacteraemia (P = 0.0017) were associated independently with mortality. MRSA carriage in hospitalized cirrhotic patients leads to the emergence of infections due to this strain, mainly SBP and bacteraemia. Prior antibiotic therapy and norfloxacin prophylaxis increase the risk of carriage of MRSA. PMID:11811877

Campillo, B; Dupeyron, C; Richardet, J P



The role of antibiotics after surgical treatment of simple hand infections: a prospective pilot study.  


ABSTRACT Background: Manifested hand infections are usually treated by sufficient debridement and drainage followed by splinting and elevation of the corresponding upper extremity. The role of antibiotics in the postoperative prognosis of hand infections is contradictory. Methods: Three groups of 30 patients each with subcutaneous or subfascial localized hand infections without infiltration of tendons, joints, or bones, have been treated in a different way regarding the use of antibiotics postoperatively. Group 1 was treated with systemic cephalosporins as well as locally inserted Gentamycin bead chains in the wound after debridement. Group 2 was only treated locally with Gentamycin bead chains but no systemic antibiots, while Group 3 did not receive any antibiotics at all. Results: No substantial differences could be observed between the three patient groups regarding the convalescence in terms of duration of splinting and recovery of hand function in relation to hand mobility as assessed by the sum of finger-palm distance and to the disabilities of the arm, shoulder, and hand score. Conclusions: The use of antibiotics after surgical treatment of simple hand infections seems to be unnecessary. PMID:23514060

Manoli, Theodora; Rahmanian-Schwarz, Ashin; Konheiser, Kathrin; Gonser, Phillipp; Schaller, Hans-Eberhard



Antibiotic susceptibility of bacteria isolated from respiratory tract of pigs in Poland between 2004 and 2008.  


Antibiotic susceptibility of bacteria isolated from nasal swabs and lungs of pigs, to 16 commonly used antibiotics, was determined by disc diffusion test. beta-lactams showed the best activity against Streptococcus suis (S. suis) (> 99% of susceptible strains). The lowest sensitivity of S. suis was evidenced to: tylosin, tetracycline and neomycin (50%, 40% and 25%, respectively). Isolates of Escherichia coli (E. coli) demonstrated the highest susceptibility to cephalosporin (85% strains), gentamicin and norfloxacin (over 74%). The lowest susceptibility of E. coli was demonstrated to tiamulin and penicillin (11.3% and 1.9%, respectively). Over 80% of Actinobacillus pleuropneumoniae (App) strains were susceptible to all antibiotics tested. The highest resistance of App, but demonstrated by below 20% of tested isolates only, was evidenced to neomycin and LxS. Isolates of Pasteurella multocida (Pm), Haemophilus parasuis (Hps) and Arcanobacterium pyogenes (A. pyogenes) were highly susceptible to the most antibiotics included in the analysis. The comparison of the in vitro susceptibility of pathogens to the chemotherapeutics used on Polish farms for the therapy of bacterial infection of pigs within the last five years and the last 10 years, showed an increasing percent of E. coli and S. suis strains resistant to commonly used antibiotics. It is also shown that Pm, Hps, App and A. pyogenes isolates were continuously susceptible to the most chemotherapeutics applied. PMID:21077428

Markowska-Daniel, I; Urbaniak, K; Stepniewska, K; Pejsak, Z



Meta-analysis of antibiotics and the risk of community-associated Clostridium difficile infection.  


The rising incidence of Clostridium difficile infection (CDI) could be reduced by lowering exposure to high-risk antibiotics. The objective of this study was to determine the association between antibiotic class and the risk of CDI in the community setting. The EMBASE and PubMed databases were queried without restriction to time period or language. Comparative observational studies and randomized controlled trials (RCTs) considering the impact of exposure to antibiotics on CDI risk among nonhospitalized populations were considered. We estimated pooled odds ratios (OR) for antibiotic classes using random-effect meta-analysis. Our search criteria identified 465 articles, of which 7 met inclusion criteria; all were observational studies. Five studies considered antibiotic risk relative to no antibiotic exposure: clindamycin (OR = 16.80; 95% confidence interval [95% CI], 7.48 to 37.76), fluoroquinolones (OR = 5.50; 95% CI, 4.26 to 7.11), and cephalosporins, monobactams, and carbapenems (CMCs) (OR = 5.68; 95% CI, 2.12 to 15.23) had the largest effects, while macrolides (OR = 2.65; 95% CI, 1.92 to 3.64), sulfonamides and trimethoprim (OR = 1.81; 95% CI, 1.34 to 2.43), and penicillins (OR = 2.71; 95% CI, 1.75 to 4.21) had lower associations with CDI. We noted no effect of tetracyclines on CDI risk (OR = 0.92; 95% CI, 0.61 to 1.40). In the community setting, there is substantial variation in the risk of CDI associated with different antimicrobial classes. Avoidance of high-risk antibiotics (such as clindamycin, CMCs, and fluoroquinolones) in favor of lower-risk antibiotics (such as penicillins, macrolides, and tetracyclines) may help reduce the incidence of CDI. PMID:23478961

Brown, Kevin A; Khanafer, Nagham; Daneman, Nick; Fisman, David N



Design and synthesis of a cephalosporin-retinoic acid prodrug activated by a monoclonal antibody-beta-lactamase conjugate.  


Two novel series of all-trans-beta-retinoic acid derivatives were synthesized and found to possess anticancer activity. The first series, cephalosporin 3'-retinoic esters 6 and 7 were, respectively, obtained by the condensation of all-trans-beta-retinoic acid (2) with cephalosporins 4 and 5. The second series, 7-(retinamido)cephalosporins 11 and 12, were synthesized, respectively, by the condensation of 2 with cephalosporins 9 and 10. These four heretofore undescribed compounds 6, 7, 11, and 12 showed inhibitory activity against murine leukemias (L1210 and P388), sarcoma 180, breast carcinoma (MCF7), and human T-lymphocytes (Molt4/C8 and CEM/0). They also inhibited squamous metaplasia and keratinization in tracheal organ cultures derived from vitamin-A-deficient hamsters. Moreover, cephalosporin 3'-retinoic ester 7 exhibited enhanced activity against keratinization with ED(50)=3.91 x 10(-11) M in the presence of a beta-lactamase from Staphylococcus aureus 95. A tumor targeting fusion protein (dsFv3-beta-lactamase) was also used in conjunction with cephem-based retinoid 7 and the potency of 7 toward L1210, P388, and MCF7 was found to approach that of the free retinoic acid (2). In the presence of dsFv3-beta-lactamase, tumor cells were found to be much more susceptible to retinoid 7 than normal human embryonic lung cells. These notions provide a new approach to the use of beta-retinoic acid for antitumor therapy. PMID:11504650

Hakimelahi, G H; Ly, T W; Yu, S F; Zakerinia, M; Khalafi-Nezhad, A; Soltani, M N; Gorgani, M N; Chadegani, A R; Moosavi-Movahedi, A A



Inactivation of Mycobacterium tuberculosis l,d-transpeptidase LdtMt? by carbapenems and cephalosporins.  


The structure of Mycobacterium tuberculosis peptidoglycan is atypical since it contains a majority of 3?3 cross-links synthesized by l,d-transpeptidases that replace 4?3 cross-links formed by the d,d-transpeptidase activity of classical penicillin-binding proteins. Carbapenems inactivate these l,d-transpeptidases, and meropenem combined with clavulanic acid is bactericidal against extensively drug-resistant M. tuberculosis. Here, we used mass spectrometry and stopped-flow fluorimetry to investigate the kinetics and mechanisms of inactivation of the prototypic M. tuberculosis l,d-transpeptidase Ldt(Mt1) by carbapenems (meropenem, doripenem, imipenem, and ertapenem) and cephalosporins (cefotaxime, cephalothin, and ceftriaxone). Inactivation proceeded through noncovalent drug binding and acylation of the catalytic Cys of Ldt(Mt1), which was eventually followed by hydrolysis of the resulting acylenzyme. Meropenem rapidly inhibited Ldt(Mt1), with a binding rate constant of 0.08 ?M(-1) min(-1). The enzyme was unable to recover from this initial binding step since the dissociation rate constant of the noncovalent complex was low (<0.1 min(-1)) in comparison to the acylation rate constant (3.1 min(-1)). The covalent adduct resulting from enzyme acylation was stable, with a hydrolysis rate constant of 1.0 × 10(-3) min(-1). Variations in the carbapenem side chains affected both the binding and acylation steps, ertapenem being the most efficient Ldt(Mt1) inactivator. Cephalosporins also formed covalent adducts with Ldt(Mt1), although the acylation reaction was 7- to 1,000-fold slower and led to elimination of one of the drug side chains. Comparison of kinetic constants for drug binding, acylation, and acylenzyme hydrolysis indicates that carbapenems and cephems can both be tailored to optimize peptidoglycan synthesis inhibition in M. tuberculosis. PMID:22615283

Dubée, Vincent; Triboulet, Sébastien; Mainardi, Jean-Luc; Ethčve-Quelquejeu, Mélanie; Gutmann, Laurent; Marie, Arul; Dubost, Lionel; Hugonnet, Jean-Emmanuel; Arthur, Michel



In vitro evaluation of GR69153, a novel catechol-substituted cephalosporin.  

PubMed Central

GR69153 is a C-7 catechol cephalosporin with a broad spectrum of activity against members of the family Enterobacteriaceae (MICs for 50% of strains tested [MIC50s], 0.008 to 0.5 micrograms/ml), Staphylococcus aureus (MIC50, 4 micrograms/ml), Pseudomonas aeruginosa (MIC50, 0.25 micrograms/ml), Haemophilus influenzae (MIC50, 0.03 micrograms/ml), Neisseria gonorrhoeae (MIC50, 0.03 micrograms/ml), and Acinetobacter spp. (MIC50, 2 micrograms/ml). Potent GR69153 activity was also demonstrated against Moraxella catarrhalis, pneumococci, beta-hemolytic streptococci, gram-positive anaerobes, and most species of coagulase-negative staphylococci. The activity of GR69153 was generally two- to fourfold greater than that of ceftazidime. Resistance level GR69153 MICs for 90% of strains tested (greater than or equal to 32 micrograms/ml) were found most often among Citrobacter freundii, Enterobacter spp. and Morganella morganii strains. GR69153 did not significantly inhibit enterococci, Xanthomonas maltophilia, the Bacteroides fragilis group, Corynebacterium jeikeium, or Listeria monocytogenes. GR69153 was bactericidal and was generally beta-lactamase stable, and MICs were only slightly increased by high inoculum concentrations. Activity was enhanced in an iron-deficient medium, and a modest MIC difference attributed to iron availability was noted between standard agar and broth test results. GR69153 was confirmed to be a potent, catechol-substituted cephalosporin with a spectrum slightly wider than that of ceftazidime, but it was less active than cefpirome or imipenem against some gram-positive pathogens and anaerobes.

Erwin, M E; Jones, R N; Barrett, M S; Briggs, B M; Johnson, D M



Tensions in antibiotic prescribing  

Microsoft Academic Search

BACKGROUND: To reduce the prevalence of antibioticresistant bacteria in the community, physicians must optimize their use of antibiotics.\\u000a However, optimal use from the perspective of the community (reserving newer agents for future use) is not always consistent\\u000a with optimal use from the perspective of the individual patient (prescribing newer, broader agents).\\u000a \\u000a \\u000a OBJECTIVES: To identify preferred patterns of antibiotic prescribing for

Joshua P. Metlay; Judy A. Shea; Linda B. Crossette; David A. Asch



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.  


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

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



Antibiotics produced by Streptomyces.  


Streptomyces is a genus of Gram-positive bacteria that grows in various environments, and its shape resembles filamentous fungi. The morphological differentiation of Streptomyces involves the formation of a layer of hyphae that can differentiate into a chain of spores. The most interesting property of Streptomyces is the ability to produce bioactive secondary metabolites, such as antifungals, antivirals, antitumorals, anti-hypertensives, immunosuppressants, and especially antibiotics. The production of most antibiotics is species specific, and these secondary metabolites are important for Streptomyces species in order to compete with other microorganisms that come in contact, even within the same genre. Despite the success of the discovery of antibiotics, and advances in the techniques of their production, infectious diseases still remain the second leading cause of death worldwide, and bacterial infections cause approximately 17 million deaths annually, affecting mainly children and the elderly. Self-medication and overuse of antibiotics is another important factor that contributes to resistance, reducing the lifetime of the antibiotic, thus causing the constant need for research and development of new antibiotics. PMID:22975171

Procópio, Rudi Emerson de Lima; Silva, Ingrid Reis da; Martins, Mayra Kassawara; Azevedo, Joăo Lúcio de; Araújo, Janete Magali de



Antibiotic Resistant Bacteria  

NSDL National Science Digital Library

This week's Topic In Depth is about antibiotic resistant bacteria.The first site is a recent news report from BBC news (1) that describes some recent research on resistant strains of two "of the world's most dangerous bacteria. Next is a Centers for Disease Control (CDC) page (2) with a brief background on antibiotic resistance and how to prevent it. A much more in-depth report is provided by the Select Committee on Science and Technology of the British House of Lords (3). There has been some public concern over the use of antibiotic resistant bacteria strains as markers in genetically modified food crops. The next two resources present information specific to this topic. The first is from the European Federation of Biotechnology (4), and the second is a shorter report from the Council for Biotechnology Information (5). The Alliance for the Prudent Use of Antibiotics (6) has a consumer and patient information section that explains what individuals can do to help prevent the problem from increasing. Readers who need a brief primer on antibiotics may appreciate this Web site from the University of Edinburgh (7). The last site is a "bugs in the news" feature from the University of Kansas (8), which is an easy-to-read explanation of "what the heck" antibiotic resistance is.

Lee, Amy.



On the specificity of antibiotics targeting the large ribosomal subunit.  


The peptidyltransferase center of the large ribosomal subunit is responsible for catalyzing peptide bonds. This active site is the target of a variety of diverse antibiotics, many of which are used clinically. The past decade has seen a plethora of structures of antibiotics in complex with the large ribosomal subunit, providing unprecedented insight into the mechanism of action of these inhibitors. Ten distinct antibiotics (chloramphenicol, clindamycin, linezolid, tiamulin, sparsomycin, and five macrolides) have been crystallized in complex with four distinct ribosomal species, three bacterial, and one archaeal. This review aims to compare these structures in order to provide insight into the conserved and species-specific modes of interaction for particular members of each class of antibiotics. Coupled with the wealth of biochemical data, a picture is emerging defining the specific functional states of the ribosome that antibiotics preferentially target. Such mechanistic insight into antibiotic inhibition will be important for the development of the next generation of antimicrobial agents. PMID:22191523

Wilson, Daniel N



Strategies to Minimize Antibiotic Resistance  

PubMed Central

Antibiotic resistance can be reduced by using antibiotics prudently based on guidelines of antimicrobial stewardship programs (ASPs) and various data such as pharmacokinetic (PK) and pharmacodynamic (PD) properties of antibiotics, diagnostic testing, antimicrobial susceptibility testing (AST), clinical response, and effects on the microbiota, as well as by new antibiotic developments. The controlled use of antibiotics in food animals is another cornerstone among efforts to reduce antibiotic resistance. All major resistance-control strategies recommend education for patients, children (e.g., through schools and day care), the public, and relevant healthcare professionals (e.g., primary-care physicians, pharmacists, and medical students) regarding unique features of bacterial infections and antibiotics, prudent antibiotic prescribing as a positive construct, and personal hygiene (e.g., handwashing). The problem of antibiotic resistance can be minimized only by concerted efforts of all members of society for ensuring the continued efficiency of antibiotics.

Lee, Chang-Ro; Cho, Ill Hwan; Jeong, Byeong Chul; Lee, Sang Hee



Aminoglycoside Kinases and Antibiotic Resistance  

Microsoft Academic Search

The evolution of antibiotic-resistant bacteria represents a serious public health concern. The appearance of strains with\\u000a resistance to multiple antibiotics threatens to render some infections untreatable by existing drugs. As a result, there is\\u000a considerable interest in understanding the mechanisms of antibiotic resistance and in identifying ways in which antibiotic\\u000a resistance can be overcome. Aminoglycoside antibiotics are broad-spectrum bactericidal compounds

D. H. Fong; D. Burk; A. Berghuis


The dynamic relationship between antibiotic use and the incidence of vancomycin-resistant Enterococcus: time-series modelling of 7-year surveillance data in a tertiary-care hospital.  


The role of antibiotics in the epidemiology of vancomycin-resistant Enterococcus (VRE) has been studied extensively, but controversies remain as to which, and to what extent, antibiotics facilitate the emergence and dissemination of VRE in hospitals. Aggregate data on the use of several antibiotic classes in terms of defined daily doses (DDD) per 100 patient-days (PD), and VRE incidence rates in terms of clinical isolates per 1000 PD, were evaluated during a 7-year period at a tertiary-care hospital. Time-series analysis (autoregressive integrated moving average (ARIMA) and transfer function models) was used to quantify the temporal effect of antibiotic use on VRE incidence and estimate effect-delays. The incidence rate of VRE observed in a specific bimester was found to be a function of its value during the preceding bimester and of prior changes in the volume of use of four antibiotic classes. In particular, an increase of one DDD/100 PD in the use of glycopeptides, fluoroquinolones, extended-spectrum cephalosporins and beta-lactam-beta-lactamase inhibitor combinations resulted, independently, in average changes of +0.024, +0.015, + 0.020 and -0.010 isolates per 1000 PD in the incidence of VRE, with average delays of 2, 4, 2 and 6 months, respectively, which explained 56% of the observed variation in VRE rates over time. Efforts to reduce VRE cross-transmission should be supplemented by targeted antibiotic control policies. The use of glycopeptides, broad-spectrum cephalosporins and fluoroquinolones in high amounts should be the targets of such policies. Penicillin-beta-lactamase inhibitor combinations might be suitable substitutes for extended-spectrum cephalosporins. PMID:18727798

Kritsotakis, E I; Christidou, A; Roumbelaki, M; Tselentis, Y; Gikas, A



Efficient biocatalyst for large-scale synthesis of cephalosporins, obtained by combining immobilization and site-directed mutagenesis of penicillin acylase.  


We describe the rational design of a new efficient biocatalyst and the development of a sustainable green process for the synthesis of cephalosporins bearing a NH? group on the acyl side chain. The new biocatalyst was developed starting from the WT penicillin acylase (PA) from Escherichia coli by combining enzyme mutagenesis, in position ?146 and ?24 (?F24A/?F146Y), and immobilization on an appropriate modified industrial support, glyoxyl Eupergit C250L. The obtained derivative was used in the kinetically controlled synthesis of cephalexin, cefprozil and cefaclor and compared to the WT-PA and an already described mutant, PA-?F24A, with improved properties. The new biocatalyst posses a very high ratio between the rates of the synthesis and two undesired hydrolyses (acylating ester and the amidic product). In particular, a very low amidase activity was observed with PA-?F24A/?F146Y and, consequently, the hydrolysis of the produced antibiotic was avoided during the process. Taking advantage of this property, higher conversions in the synthesis of cephalexin (99% versus 76%), cefaclor (99% versus 65%) and cefprozil (99% versus 60%) were obtained compared to the WT enzyme. Furthermore, the new mutant also show a higher synthetic activity compared to PA-?F24A immobilized on the same support, allowing the maximum yields to be achieved in very short reaction times. The production of cephalexin with the immobilized ?F24A/?F146Y acylase has been developed on a pre-industrial scale (30 l). After 20 cycles, the average yield was 93%. The biocatalyst showed good stability properties and no significant decrease in performance. PMID:22228258

Cecchini, Davide A; Pavesi, Roberto; Sanna, Sara; Daly, Simona; Xaiz, Roberto; Pregnolato, Massimo; Terreni, Marco



The crystal structure of the cephalosporin deacetylating enzyme acetyl xylan esterase bound to paraoxon explains the low sensitivity of this serine hydrolase to organophosphate inactivation.  


Organophosphorus insecticides and nerve agents irreversibly inhibit serine hydrolase superfamily enzymes. One enzyme of this superfamily, the industrially important (for ?-lactam antibiotic synthesis) AXE/CAH (acetyl xylan esterase/cephalosporin acetyl hydrolase) from the biotechnologically valuable organism Bacillus pumilus, exhibits low sensitivity to the organophosphate paraoxon (diethyl-p-nitrophenyl phosphate, also called paraoxon-ethyl), reflected in a high K(i) for it (~5 mM) and in a slow formation (t(˝)~1 min) of the covalent adduct of the enzyme and for DEP (E-DEP, enzyme-diethyl phosphate, i.e. enzyme-paraoxon). The crystal structure of the E-DEP complex determined at 2.7 Ĺ resolution (1 Ĺ=0.1 nm) reveals strain in the active Serą?ą-bound organophosphate as a likely cause for the limited paraoxon sensitivity. The strain results from active-site-size limitation imposed by bulky conserved aromatic residues that may exclude as substrates esters having acyl groups larger than acetate. Interestingly, in the doughnut-like homohexamer of the enzyme, the six active sites are confined within a central chamber formed between two 60°-staggered trimers. The exclusive access to this chamber through a hole around the three-fold axis possibly limits the size of the xylan natural substrates. The enzyme provides a rigid scaffold for catalysis, as reflected in the lack of movement associated with paraoxon adduct formation, as revealed by comparing this adduct structure with that also determined in the present study at 1.9 Ĺ resolution for the paraoxon-free enzyme. PMID:21382014

Montoro-García, Silvia; Gil-Ortiz, Fernando; García-Carmona, Francisco; Polo, Luis Mariano; Rubio, Vicente; Sánchez-Ferrer, Álvaro



Virulence and antibiotic resistance of Escherichia coli isolated from rooks.  


With regard to antibiotic resistance studies in various model animals in the urban environment, the presented study focused on the rook, many behavioural and ecological aspects of which are important from an epidemiological point of view. A total of 130 Escherichia coli strains isolated from rook faeces during a two-year period (2011-2012) were investigated for antibiotic resistance and virulence. Resistance to ampicillin (60%) and streptomycin (40%) were the most frequent, followed by resistance to fluoroquinolones (ciprofloxacin-22% and enrofloxacin-24%), tetracycline (18%), cotrimoxazol (17%) and florfenicol (14%). Ceftiofur resistance occured in 10.7% of strains and cefquinom resistance in 1.5% of strains. Twenty-five E.coli strains with a higher level of MICs of cephalosporins (over 2mg/L of ceftazidime and ceftriaxon) and fluoroquinolones were selected for detection of betalactamase genes (CTX-M, CMY), plasmid-mediated quinolone resistance qnrS, integrase 1, and for APEC (avian pathogenic E.coli) virulence factors (iutA, cvaC, iss, tsh, ibeA, papC, kpsII). Genes of CTX-M1, CMY-2, integrase 1, papC, cvaC, iutA were detected in one strain of E.coli, and qnrS, integrase 1, iss, cvaC, tsh were detected in another E.coli. DNA microarray revealed the absence of verotoxin and enterotoxin genes and pathogenicity islands. The results show that rooks can serve as a reservoir of antibiotic-resistant E. coli with avian pathogenic virulence factors for the human population, and potentially transmit such E.coli over long distances. PMID:23772573

Kmet, Vladimir; Drugdova, Zuzana; Kmetova, Marta; Stanko, Michal



What is the optimum antibiotic prophylaxis in patients undergoing implantation of a left ventricular assist device?  

PubMed Central

A best evidence topic was written according to a structured protocol. The question addressed was what the optimum antibiotic prophylaxis in patients undergoing implantation of a left ventricular assist device (LVAD) is. A total of 373 papers were found, of which 11 represented the best evidence. The authors, date, journal, study type, population, main outcome measures and results are tabulated. Eight retrospective and two prospective studies, including one randomized controlled trial (RCT), were identified. Although highly variable, the prophylactic antibiotic protocols employed in these studies generally favour the use of vancomycin, a cephalosporin, beta-lactam and quinolone, with the option of additional fluconazole and mupirocin. However, the lack of standardized definitions for infection, and variations in the choice, timing and duration of prophylactic antibiotics complicates the interpretation of reported infection rates. Driveline and pocket infections comprised the majority of infectious complications, and were principally attributed to Gram-positive organisms, such as Staphylococcus, as well as Pseudomonas species. We conclude that a beta-lactam be used for primary prophylaxis, with vancomycin where the risk of MRSA is high. Topical mupirocin and an anti-fungal are also recommended. Prophylaxis should commence prior to device insertion, and be continued into the peri- and post-operative period. Large-scale RCTs are necessary to assess the impact of different antibiotic regimens on infection within LVAD recipients.

Acharya, Metesh Nalin; Som, Robin; Tsui, Steven



Effects of N-methyl-thiotetrazole cephalosporin on haemostasis in patients with reduced serum vitamin K1 concentrations.  

PubMed Central

Two patients with low random serum vitamin K1 concentrations but with normal prothrombin times and normal biological assays of the vitamin K dependent coagulation proteins were treated with an N-methyl-thiotetrazole cephalosporin (cefotetan) postoperatively. Four to six days later both patients developed a prolonged prothrombin time and a noticeable and specific lowering of the clotting activities of factors II, VII, IX and X, though the serum vitamin K1 concentrations remained unchanged. Crossed immunoelectrophoresis of prothrombin showed the appearance of a second peak corresponding to descarboxyprothrombin (PIVKA II). These abnormalities corrected after vitamin K administration. These data are consistent with the hypothesis that cephalosporins with an N-methyl-thiotetrazole side chain inhibit the hepatic utilisation of vitamin K but that this only causes hypoprothrombinaemia when liver reserves of vitamin K are low. Images Figure

Mackie, I J; Walshe, K; Cohen, H; McCarthy, P; Shearer, M; Scott, S D; Karran, S J; Machin, S J



Monitoring and identifying antibiotic resistance mechanisms in bacteria.  


Sub-therapeutic administration of antibiotics to animals is under intense scrutiny because they contribute to the dissemination of antibiotic-resistant bacteria into the food chain. Studies suggest that there is a link between the agricultural use of antibiotics and antibiotic-resistant human infections. Antibiotic-resistant organisms from animal and human wastes reenter the human and animal populations through a number of pathways including natural waters, irrigation water, drinking water, and vegetables and foods. Antibiotic usage in the United States for animal production (disease prevention and growth promotion) is estimated to be 18 million pounds annually. As much as 25 to 75% of the antibiotics administered to feedlot animals are excreted unaltered in feces. Because about 180 million dry tons of livestock and poultry waste is generated annually in the United States, it is not surprising that animal-derived antibiotic-resistant organisms are found contaminating groundwater, surface water, and food crops. It is extremely important to clearly understand the molecular mechanisms that could potentially cause lateral or horizontal gene transfer of antibiotic resistance genes among bacteria. Once the mechanisms and magnitude of resistance gene transfer are clearly understood and quantified, strategies can be instituted to reduce the potential for dissemination of these genes. PMID:12710483

Roe, M T; Pillai, S D



[Spreading and mechanisms of antibiotic resistance of microorganisms, producing beta-lactamases. Molecular mechanisms of resistance to beta-lactams of Klebsiella spp. strains, isolated in cases of nosocomial infections].  


Antibiotic sensivity of nosocomial Klebsiella spp. strains (n = 212), isolated from patients treated in 30 medical centers of 15 various regions of Russia was investigated. The Klebsiella genus was represented by the following species: Klebsiella pneumoniae ss. pneumoniae--182 (85.8%), Klebsiella pneumoniae ss. ozaenae--1 (0.5%), Klebsiella oxytoca--29 (13.7%) isolates. The most active antibacterial agents against the investigated strains were carbapenems (imipenem and meropenem). Among 3rd generation cephalosporine the lowest MICs were observed for ceftazidime/clavulanic acid (MIC50--0.25 microg/ml, MIC90--64 microg/ml) and cefoperazone/sulbactam (MIC50--16 microg/ml, MIC90--64 microg/ml). Beta-lactamase genes (TEM, SHV, CTX) were detected in 42 Klebsiella pneumoniae ss. pneumoniae strains by PCR. Alone or in various combinations TEM type beta-lactamases have been found in 16 (38.1%) isolates, SHV--in 29 (69%), and CTX--in 27 (64.3%). Combinations of 2 different determinants were detected in 23.8% of the isolates, 3--in 26.2%. There were not isolates producing MBL class B among resistant to carbapenems nosocomial Klebsiella spp. strains. PMID:18421915

Ivanov, D V; Egorov, A M


Single-Dose Pharmacokinetics and Safety of a Novel Broad-Spectrum Cephalosporin (BAL5788) in Healthy Volunteers  

Microsoft Academic Search

BAL5788 is the water-soluble prodrug of BAL9141, a novel broad-spectrum cephalosporin with potent bactericidal activities against methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae. We investigated the safety and pharmacokinetics of BAL5788 in a double-blind, single-ascending-dose study with 40 healthy male subjects. The subjects were randomized to receive placebo (n 2 subjects per dose) or BAL5788 (n 6 subjects per

Anne Schmitt-Hoffmann; Brigitte Roos; Michael Schleimer; Jill Sauer; Anthony Man; Norman Nashed; Thomas Brown; Antonio Perez; Erhard Weidekamm; Peter Kovacs



Epidemiological Investigation of Bloodstream Infections by Extended Spectrum Cephalosporin-Resistant Escherichia coli in a Taiwanese Teaching Hospital  

PubMed Central

In an epidemiologic and case-control study including 30 case patients over a 3.5-year period in a Taiwanese university hospital, only ?-lactamase inhibitor use and extended-spectrum cephalosporin use were identified as independent risk factors for nosocomial CMY-2-producing Escherichia coli bloodstream infection, and CMY-2 producers were found more prevalent than extended-spectrum ?-lactamase-producing isolates.

Yan, Jing-Jou; Ko, Wen-Chien; Wu, Jiunn-Jong; Tsai, Shu-Huei; Chuang, Chin-Luan



Complexity of Klebsiella pneumoniae Isolates Resistant to Both Cephamycins and Extended-Spectrum Cephalosporins at a Teaching Hospital in Taiwan  

PubMed Central

Among 99 clinical Klebsiella pneumoniae isolates resistant to cefoxitin and extended-spectrum cephalosporins, coexistence of AmpC (DHA-1, CMY-2, or CMY-8) and extended-spectrum ?-lactamases (CTX-M and/or SHV) was detected in a total of 35. The remainder produced AmpC (n = 42), extended-spectrum ?-lactamases (n = 9), metallo-?-lactamases (n = 2), or none of these enzymes (n = 11). Phenotypic characteristics of these isolates were demonstrated.

Yan, Jing-Jou; Ko, Wen-Chien; Wu, Hsiu-Mei; Tsai, Shu-Huei; Chuang, Chin-Luan; Wu, Jiunn-Jong



Antibiotics in Animal Products  

NASA Astrophysics Data System (ADS)

The administration of antibiotics to animals to prevent or treat diseases led us to be concerned about the impact of these antibiotics on human health. In fact, animal products could be a potential vehicle to transfer drugs to humans. Using appropri ated mathematical and statistical models, one can predict the kinetic profile of drugs and their metabolites and, consequently, develop preventive procedures regarding drug transmission (i.e., determination of appropriate withdrawal periods). Nevertheless, in the present chapter the mathematical and statistical concepts for data interpretation are strictly given to allow understanding of some basic pharma-cokinetic principles and to illustrate the determination of withdrawal periods

Falcăo, Amílcar C.


Antibiotic Rotation and Development of Gram-Negative Antibiotic Resistance  

Microsoft Academic Search

To attain a better understanding of antibiotic cycling and its effects on the epidemiology of antibiotic resistance in gram-negative microorganisms, two different antibiotic classes (quinolone and -lactam) were cycled during four 4-month periods in a surgical intensive care unit. Respiratory aspirates and rectal swabs were obtainedandDNAfingerprintingwasperformed.Primaryendpoint of the study was the acquisition rate with gram-negative bacteria resistant to the antibiotic

Harald J. van Loon; Menno R. Vriens; Ad C. Fluit; Annet Troelstra; Christiaan van der Werken; Jan Verhoef; Marc J. M. Bonten


Formulations of antibiotics for children in primary care: effects on compliance and efficacy.  


This review article is designed for pediatricians as well as primary care physicians in the outpatient setting as a clinical guide to antibiotic selection. It emphasizes variables related to compliance as well as efficacy. The aim is to give recommendations as to the choice of antibiotics, depending on factors such as taste, cost, efficacy, and compliance. Common bacterial pathogens causing infections in children are reviewed, along with their susceptibility patterns to antimicrobial agents. Emerging mechanisms of resistance, particularly the increasing resistance of pneumococci to beta-lactam antibiotics, are discussed because of their importance to antibiotic selection. Previously published studies that have examined the treatment of common outpatient infections in children, such as otitis media, streptococcal tonsillopharyngitis, and sinusitis, are summarized. Adverse reactions associated with antibiotics, second in importance only to efficacy, are reviewed. Finally, compliance issues, which include palatability, cost, duration of therapy, and administration frequency, are analyzed using recently published information related to each of these issues. The efficacy of the commonly used antibiotics for urinary tract infections, pneumonia, and streptococcal pharyngitis does not vary significantly; however, for otitis media and sinusitis, some studies have shown that treatment efficacy with the antibiotic does not vary significantly from that with placebo. Likewise, adverse reactions rarely provide a basis for antibiotic selection, since virtually all antibiotics are generally well tolerated. The final factor, compliance, is a major issue in determining both first- and second-line therapy of common outpatient infections in children. Although cost is not a factor in compliance in countries such as the UK where no copayment is required for pediatric drugs, it is of major importance in the US. This is followed by palatability, administration duration and finally administration frequency. As a group, cephalosporins are generally the best tasting but are relatively more expensive than macrolides. Antibiotics that can be given for 5 days, and just once or twice daily, are preferred by most parents and physicians. Since final assessment of antibiotic choice is likely to vary considerably among healthcare personnel, decisions must be made on an individual basis. PMID:11994037

Ramgoolam, Andres; Steele, Russell



Health Care Competition, Antibiotic Use, and Antibiotic Resistance in Taiwan  

Microsoft Academic Search

While antibiotics are critical to modern health care, their overuse has fostered an- tibiotic resistance. Since patients in many settings prefer to visit doctors who freely prescribe antibiotics, doctors may have an incentive to attract patients through greater prescription. This paper examines the eect of health care competition on antibiotic prescription in a large, nationally-representative sample of outpatient visits from

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


High-level resistance to fluoroquinolones and cephalosporins in Burkholderia pseudomallei and closely related species.  


The molecular mechanisms involved in the development of a high level of resistance to a wide range of antimicrobials in Burkholderia pseudomallei and closely related species have not been sufficiently investigated. In the present study, the properties of B. pseudomallei, B. mallei and B. thailandensis mutants with increased resistance to fluoroquinolones and cephalosporins were analysed. Resistance to pefloxacin, ofloxacin and ceftazidime in B. pseudomallei and B. thailandensis was accompanied by an increased resistance to aminoglycosides, beta-lactams, macrolides and chloramphenicol, whereas mutants of B. mallei were characterized by a narrower spectrum of resistance. With the use of the differential display technique, we demonstrated that multiple resistant variants of B. pseudomallei, B. mallei and B. thailandensis had an increased expression of putative efflux transporters belonging to the resistance-nodulation division superfamily and the major facilitator superfamily. With the application of PCR-single-stranded conformational polymorphism (PCR-SSCP) and sequencing, point mutations in gyrA quinolone-resistance determining region were detected in the part of multiple resistant B. pseudomallei and B. mallei mutants. These results indicate that various molecular mechanisms are involved in the development of multiple drug resistance in pathogenic Burkholderia and may be useful for further studying the adaptability of this microorganism and optimization of treatment. PMID:19121669

Viktorov, Dimitry V; Zakharova, Irina B; Podshivalova, Maria V; Kalinkina, Elena V; Merinova, Olga A; Ageeva, Natalya P; Antonov, Valery A; Merinova, Lyudmila K; Alekseev, Vladimir V



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

PubMed Central

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.

Moya, Bartolome; Zamorano, Laura; Juan, Carlos; Ge, Yigong; Oliver, Antonio



Minocycline: far beyond an antibiotic.  


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

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



Naphthoquinone Antibiotics from 'Fusarium solani'.  

National Technical Information Service (NTIS)

The invention relates to new naphthoquinone derivatives which exhibit antibiotic activity. Three naphthoquinones isolated from cultures of Fusarium solani were found to be effective antibiotics against gram-positive bacteria. Controlling the dissolved oxy...

R. A. Baker J. H. Tatum



Antibiotic resistance: an overview  

Microsoft Academic Search

The results of large scale surveys have indicated that in general terms antibiotic resistance in bacteria has not increased, especially in Europe and North America. When the prevalence of resistance in specific bacteria has increased the increase has usually been associated with the introduction of a novel antimicrobial agent, whether in human or veterinary clinical practice, but the prevalence of

JR Walton



Analysis of macrolide antibiotics  

Microsoft Academic Search

The following macrolide antibiotics have been covered in this review: erythromycin and its related substances, azithromycin, clarithromycin, dirithromycin, roxithromycin, flurithromycin, josamycin, rokitamycin, kitasamycin, mycinamycin, mirosamycin, oleandomycin, rosaramicin, spiramycin and tylosin. The application of various thin-layer chromatography, paper chromatography, gas chromatography, high-performance liquid chromatography and capillary zone electrophoresis procedures for their analysis are described. These techniques have been applied to the

Isadore Kanfer; Michael F. Skinner; Roderick B. Walker



Antibiotic resistance in Salmonella  

Microsoft Academic Search

Immediately after their introduction in the beginning of the fourties of the previous century, the agents used to combat infectious diseases caused by bacteria were regarded with suspicion, but not long thereafter antibiotics had the status of miracle drugs. For decades mankind has lived under the impression that infectious diseases were no longer a threat to human health. This optimism

A. T. T. Vo



Predicting antibiotic resistance  

Microsoft Academic Search

The treatment of bacterial infections is increasingly complicated because microorganisms can develop resistance to antimicrobial agents. This article discusses the information that is required to predict when antibiotic resistance is likely to emerge in a bacterial population. Indeed, the development of the conceptual and methodological tools required for this type of prediction represents an important goal for microbiological research. To

Fernando Baquero; Dan I. Andersson; José L. Martínez



Antibiotic use for common cold  

Microsoft Academic Search

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

Timothy W. Kenealy; Bruce Arroll


Global Perspectives of Antibiotic Resistance  

Microsoft Academic Search

\\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.

Carlos F. Amábile-Cuevas


Economics of antibiotic resistance  

Microsoft Academic Search

Antibiotics are developed to kill microorganisms; however, microorganisms develop and disseminate resistance as a reaction to antimicrobials in accordance with the laws of evolution and natural selection. Resistant and multidrug-resistant bacterial infections comprise a great problem in both the community and hospital setting. Increasing values of health expenditures, including antibiotics, is a global problem. Antibiotic resistance is not always, but

Oguz Resat Sipahi



Investigating the Antibiotic Resistance Problem.  

ERIC Educational Resources Information Center

|Seeks to give teachers useful information on the extent of the problem of antibiotic-resistant bacteria, mechanisms bacteria use to resist antibiotics, the causes of the emergence of antibiotic-resistant organisms, and practices that can prevent or reverse this trend. Contains 19 references. (DDR)|

Lawson, Michael; Lawson, Amy L.



Prescribing antibiotics in primary care  

Microsoft Academic Search

Extract: Antibiotic resistance will probably eventually appear by natural selection for every new antibiotic developed by the drug industry, and the race to produce new drugs ahead of resistance is run ever closer. Antibiotics should be thought of like oil, a non-renewable resource to be carefully husbanded. What we use now cannot be used some time in the future.

Chris Del Mar



Hybrid antibiotics with the nikkomycin nucleoside and polyoxin peptidyl moieties.  


Acting as competitive inhibitors of chitin synthase, nikkomycins and polyoxins are potent antibiotics against pathogenic fungi. Taking advantage of the structural similarities between these two peptidyl nucleoside antibiotics, genes required for the biosynthesis of the dipeptidyl moiety of polyoxin from Streptomyces cacaoi were introduced into a Streptomyces ansochromogenes mutant producing the nucleoside moiety of nikkomycin X. Two hybrid antibiotics were generated. One of them was identified as polyoxin N, and the other, a novel compound, was named polynik A. The hybrid antibiotics exhibited merits from both parents: they had better inhibitory activity against phytopathogenic fungi than polyoxin B, and were more stable under different pH and temperature conditions than nikkomycin X. This study demonstrates the use of the combinatorial biosynthetic approach to produce valuable and novel hybrid antibiotics with improved properties. PMID:21292022

Li, Jine; Li, Lei; Tian, Yuqing; Niu, Guoqing; Tan, Huarong



Use of oral cephalosporins in the treatment of acute otitis media in children  

Microsoft Academic Search

The selection of the most effective antimicrobial to treat acute otitis media (AOM) has become more difficult in recent years because of increasing antibiotic resistance among all AOM pathogens. Resistance of Streptococcus pneumoniae to penicillin as well as amoxicillin ranges from 30 to 55% in the USA. Currently, 40–55% of Haemophilus influenzae and 90–100% of Moraxella catarrhalis are resistant to

Itzhak Brook



Overcoming resistance to ?-lactam antibiotics.  


?-Lactam antibiotics are one of the most important antibiotic classes but are plagued by problems of resistance, and the development of new ?-lactam antibiotics through side-chain modification of existing ?-lactam classes is not keeping pace with resistance development. In this JOCSynopsis, we summarize small molecule strategies to overcome resistance to ?-lactam antibiotics. These approaches include the development of ?-lactamase inhibitors and compounds that interfere with the ability of the bacteria to sense an antibiotic threat and activate their resistance mechanisms. PMID:23530949

Worthington, Roberta J; Melander, Christian



The comprehensive antibiotic resistance database.  


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; 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

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



In Vitro Activities of Antibiotics against Plasmodium falciparum Are Inhibited by Iron  

PubMed Central

The in vitro activities of cyclines (tetracycline, doxycycline, minocycline, oxytetracycline, and rolitetracycline), macrolides (erythromycin, spiramycin, roxithromycin, and lincomycin), quinolones (norfloxacin and ofloxacin), rifampin, thiamphenicol, tobramycin, metronidazole, vancomycin, phosphomycin, and cephalosporins (cephalexin, cefaclor, cefamandole, cefuroxime, ceftriazone, cefotaxime, and cefoxitin) were evaluated on Plasmodium falciparum clones, using an isotopic, micro-drug susceptibility test. Only tetracyclines, macrolides, quinolones, and rifampin demonstrated in vitro activity against P. falciparum, which increased after a prolonged exposure (96 or 144 h). In the presence of iron (FeCl3), only the activities of tetracyclines and norfloxacin were decreased. Their in vitro activity against intraerythrocytic stages of multidrug-resistant P. falciparum and their efficacy in vivo favor the use of antibiotics as antimalarial drugs. However, due to their slow antimalarial action and to the fact that they act better after prolonged contact, they probably need to be administered in conjunction with a rapidly acting antimalarial drug, such as a short course of chloroquine or quinine.

Pradines, Bruno; Rogier, Christophe; Fusai, Thierry; Mosnier, Joel; Daries, William; Barret, Eric; Parzy, Daniel



National hospital antibiotic timing measures for pneumonia and antibiotic overuse.  


The development of drug-resistant bacteria from the overuse of antibiotics is a serious problem, with overutilization threatening to disarm caregivers and their patients even as together they face increasingly virulent strains of microbes. On the other hand, the speedy treatment of pneumonia with antibiotics is a firmly established, evidence-based practice, enshrined in Joint Commission on Accreditation for Healthcare Organizations Core Measures used in hospital accrediting and public reporting, and in Centers for Medicare and Medicaid Services (CMS) public-reporting and pay-for-performance hospital measures. This sets the stage for a potential conflict between (a) not doing the wrong thing by overprescribing antibiotics and (b) prescribing antibiotics on time for pneumonia. In November 2005, pneumonia antibiotic timing results were announced for the 133 top-performing hospitals in the first year of the 3-year CMS Hospital Quality Incentive Demonstration (HQID) pay-for-performance project, conducted in collaboration with Premier Inc, a hospital purchasing and informatics alliance. Premier client hospitals participating in the HQID also submit drug utilization and other comparative data to Premier for client access for benchmarking purposes; this makes it possible to see how the antibiotics specified for pneumonia are used by Premier hospitals for other conditions. In this study we look at where increased success in meeting the HQID pneumonia antibiotic timing measure is tied to an increase in antibiotic use for conditions where antibiotics are unwarranted--with the potential for promoting antibiotic resistance. PMID:17426609

Drake, Douglas E; Cohen, Abigail; Cohn, Jeffrey


[Antibiotic prophylaxis in urology].  


There is little reason why the organism could benefit from the presence of micro-organisms in the urine. In the case of severe infection, the consequences can be devastating, both for the health of the individual and for the overall effect in terms of health care costs. There is thus a clear need for a reduction in the number and severity of urinary tract infections by a strictly controlled, well-planned, antibiotic prophylaxy. Beyond well-established rules concerning timing, duration, dose and, in certain cases, indications of antibiotics, there remains a number of questions yet to be fully understood. What is the ecologic impact of antibiotic prophylaxy? What is the original source of infection in patients undergoing multiple procedures? What is the relationship between serum concentrations and efficacy? What is the role of in situ germs and nosocomial agents? These and other questions require rigorously conducted research where not only urologists but also bacteriologists, infectiologists and public health specialists all have an important role to play. PMID:8545349

Botto, H



[Antibiotic profylaxis in obstetrics].  


Nosocomial infections increase health care costs significantly and they are a real threat for all hospitalised patients as well. Surgical procedures affect imunological integrity in patients and increase risk of contamination and subsequent incidence of surgical site infections (SSIs). Antibiotic profylaxis according to recent trials has been shown to be effective in reducing the risks of postoperative infectious complications particularly in women undergoing cesarean section, termination of pregnancy in I. and II. trimester and repair of extensive obstetric perineal injuries. Benefit of antibiotic profylaxis hasn t been proven in procedures such as amniocentesis, cerclage and manual uterine evacuation. The routine antibiotic administration isnt recommanded in cases of spontaneous preterm labour without membrane rupture due to an increased risk of worse long-term outcome of children.The authors present also recent studies regarding antivirotic profylaxis in pregnant women with hepatitis B and herpes genitalis recidivans. In the end of the article differences in antimicrobial administration in obese women and in patients with penicillin allergy anamnesis are mentioned. PMID:23869838

Menzlová, E; Záhumenský, J; Ku?era, E



Mutacin II, a bactericidal antibiotic from Streptococcus mutans.  

PubMed Central

Mutacin II is an antibiotic that is produced by group II Streptococcus mutans. It inhibits the growth of other streptococci as well as many other gram-positive microorganisms by a hitherto unknown mechanism. Mutacin II possess bactericidal activity against susceptible cells. It transiently depolarizes the transmembrane electrical potential (delta psi) and the transmembrane pH gradient (delta pH) and partially inhibits amino acid transport. However, it rapidly depletes the intracellular ATP pool in glucose-energized cells and prevents the generation of ATP. It is concluded that mutacin II does not belong to the group of pore-forming antibiotics (type A) or to the type B antibiotics, which inhibit phospholipases or interfere with peptidoglycan biosynthesis. Mutacin II acts by inhibiting essential enzyme functions at the level of metabolic energy generation, an activity that has not yet been classified for antibiotics.

Chikindas, M L; Novak, J; Driessen, A J; Konings, W N; Schilling, K M; Caufield, P W



Antibiotic susceptibility and beta-lactamase production in clinical isolates of Enterobacter spp.  


The in vitro susceptibility of 237 clinical isolates of Enterobacter spp. (E. aerogenes, E. agglomerans and E. cloacae; 41, 64 and 132 respectively) to 16 different antibiotics is described. Four quinolones (ciprofloxacin, lomefloxacin, norfloxacin and ofloxacin), two new cephalosporins (cefpirome and cefepime) and imipenem, all showed high activity against the three Enterobacter species tested (MIC50 less than or equal to 0.125 mg/l, MIC90 less than or equal to 0.5 mg/l). Also the aminoglycosides gentamicin and tobramycin were highly active antibiotics (MIC50 less than or equal to 0.5 mg/l, MIC90 less than or equal to 1.0 mg/l). The susceptibility of beta-lactam-antibiotics to beta-lactamase produced by Enterobacter spp. was evaluated, and imipenem and cefepime were found to be most stable. Different methods for detection of inducible beta-lactamases were used, the agar dilution method being more sensitive than the double-disc diffusion test. Elevated beta-lactamase production was detected, via induction, in 83% of E. aerogenes strains and 70% of E. cloacae strains, with cefamandole used as the substrate and cefoxitin as the inducer. Constitutive, high level enzyme production was detected in 7 and 13% respectively of the E. aerogenes and the E. cloacae strains. In all the strains of E. agglomerans, 10% of E. aerogenes and 13% of E. cloacae, no beta-lactamases could be detected with the methods studied. PMID:2162681

Lindh, E; Dornbusch, K; Jalakas, K; Forsgren, A



Antibiotic use after cefuroxime prophylaxis in hip and knee joint replacement.  


The amount of additional antibiotics measured by defined daily dose (DDD) methods after 2651 hip and 362 knee replacements was assessed after prophylaxis with one or three doses (1502/1511 patients) of cefuroxime. No differences were observed between the two regimens with respect to total amount, type, indication, and duration of additional antibiotics. The incidence of joint sepsis did not differ significantly between the two trial arms, but the sample was too small for definite conclusions. There were 11.4 DDD/100 bed days of additional antibiotics used in 21% of patients after hip replacement and 15.7 DDD/100 bed days in 31% after knee replacement. For wound problems, 3.8 and 6.9 DDD/100 bed days were given in the hip- and knee-replacement groups. For distant infection, 6.5 DDD/100 bed days was administered in both groups. Duration of therapy varied only in relation to indication. Prescribed were penicillins (43% to 50%), sulfonamides (18%), cephalosporins (10% to 16%), and nitrofurantoin (8% to 13%); drug use was related to the type of infection. PMID:1868681

Wymenga, A B; Hekster, Y A; Theeuwes, A; Muytjens, H L; van Horn, J R; Slooff, T J



Rationalizing antibiotic use to limit antibiotic resistance in India+  

PubMed Central

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.



Discovery of RWJ-54428 (MC-02,479), a new cephalosporin active against resistant gram-positive bacteria.  


The discovery of RWJ-54428 (MC-02,479), a new cephalosporin displaying promising activity against sensitive and resistant Gram-positive bacteria, is described. Progressive structural modification from the previously reported 3-phenylthiocephem MC-02,331 afforded an overall increase in potency against MRSA while retaining other key properties such as acceptable solubility and serum binding. Evaluation of the in vitro potency and in vivo efficacy of a series of closely related compounds resulted in selection of RWJ-54428 (MC-02,479) for further studies. PMID:11213288

Hecker, S J; Glinka, T W; Cho, A; Zhang, Z J; Price, M E; Chamberland, S; Griffith, D; Lee, V J



Diversity of plasmid replicons encoding the bla(CMY-2) gene in broad-spectrum cephalosporin-resistant Escherichia coli from livestock animals in Japan.  


Broad-spectrum cephalosporin (BSC) resistance has increased in Escherichia coli isolates from broiler chickens in Japan since 2004. The purpose of this study was to understand the epidemiology of BSC-resistant E. coli in livestock animals. Among 3274 E. coli isolates from 1767 feces of apparently healthy animals on 1767 farms between 2004 and 2009, 118 ceftiofur (CTF)-resistant isolates (CTF MIC ?4??g/mL) were identified on 74 farms. After elimination of apparently clonal isolates from a single animal, 75 selected CTF-resistant isolates (62 isolates from 61 broiler chickens, 10 isolates from 10 layer chickens, two isolates from two cows, and one isolate from a pig) were characterized. The bla(CMY-2) gene was most frequently detected in 50 isolates, followed by bla(CTX-M) (CTX-M-2: six isolates; CTX-M-14: four isolates; CTX-M-25: two isolates; CTX-M-1: one isolate) and bla(SHV) (SHV-12: seven isolates; SHV-2, SHV-2a, SHV-5: one isolate each). In particular, 42 of 62 broiler chicken isolates harbored bla(CMY-2). Pulsed-field gel electrophoresis analyses using XbaI revealed divergent profiles among the BSC-resistant isolates. The incompatibility groups of bla(CMY-2) plasmids from 34 of the 42 broiler chicken isolates belonged to IncI? (10 isolates), IncA/C (nine isolates), IncB/O (seven isolates) and IncI1 (six isolates), or were nontypeable (two isolates). Co-transmission of resistance to non-?-lactam antibiotics was observed in transconjugants with IncA/C plasmids, but not with IncI1, IncI?, and IncB/O plasmids except for one isolate with IncB/O. Our findings suggest that the bla(CMY-2) gene is a key player in BSC-resistant E. coli isolates and that coselection is unlikely to be associated with the abundance of bla(CMY-2) plasmids, except for IncA/C plasmids. PMID:23489047

Hiki, Mototaka; Usui, Masaru; Kojima, Akemi; Ozawa, Manao; Ishii, Yoshikazu; Asai, Tetsuo



Natural antibiotic susceptibility of Klebsiella pneumoniae, K. oxytoca, K. planticola, K. ornithinolytica and K. terrigena strains.  


The natural susceptibility of 221 Klebsiella strains to 71 antibiotics was examined. The strains were isolated from clinical specimens and the environment, and belonged to K. pneumoniae subsp. pneumoniae (n = 40), K. pneumoniae subsp. ozaenae (37), K. pneumoniae subsp. rhinoscleromatis (10), K. oxytoca (44), K. planticola (40), K. ornithinolytica (25) and K. terrigena (25). MIC values were determined by a microdilution procedure in IsoSensitest broth according to the German standard (DIN). All Klebsiella spp. were naturally resistant or intermediate to amoxicillin, ticarcillin and to antibiotics to which other Enterobacteriaceae are also intrinsically resistant. Klebsiella spp. were naturally sensitive or intermediate to several penicillins, all tested cephalosporins, aminoglycosides, quinolones, tetracyclines, trimethoprim, cotrimoxazole, chloramphenicol and nitrofurantoin. K. pneumoniae subsp. ozaenae and subsp. rhinoscleromatis strains were generally more susceptible to antibiotics than strains of other Klebsiella taxa. K pneumoniae subsp. rhinoscleromatis was the most susceptible taxon, being highly susceptible to cefuroxime, anti-folates and naturally intermediate to erythromycin and clarithromycin. K. pneumoniae subsp. ozaenae was most susceptible to glycopeptides. K. oxytoca and K. terrigena strains were least susceptible to cefazoline, cefoperazone and fosfomycin, respectively. The results of the present study describe a database of the natural antimicrobial susceptibility of Klebsiella spp., which can be used for the validation of antibiotic susceptibility results of these bacteria. MIC patterns to beta-lactams indicate the expression of chromosomally encoded class A gamma-lactamases in all the species, including the subspecies of K. pneumoniae. Similar natural susceptibility patterns of K. planticola and K. ornithinolytica to all tested antibiotics support the status of K. ornithinolytica as a biovar of K. planticola. PMID:11339246

Stock, I; Wiedemann, B



Use of antibiotics in bronchiectasis.  


Bronchiectasis is defined by the presence of abnormal bronchial widening and occurs as a consequence of chronic airway infection. It is an important and common cause of respiratory disease. Antibiotics are the main therapy used for the treatment of this condition. The article will review the use of antibiotics for the treatment of bronchiectasis. Antibiotics can be given as short-term therapy for exacerbations or as long-term/maintenance therapy. Antibiotics given by the inhalational route and macrolides are two relatively new classes of medication that may be useful for long-term therapy. There are significant concerns about the overuse resulting in antibiotic resistance. It should be emphasized that nearly all of the trials in the literature have only had small numbers of subjects. The data that is available describing the use of antibiotics in bronchiectasis can generally be regarded as preliminary. PMID:22023177

King, Paul T; Holmes, Peter W



Antibiotic Bead Production  

PubMed Central

We are reporting a practical technique for the production of antibiotic beads for use in combating musculoskeletal infections. The technique utilizes bead molds with tobramycin powder mixed with polymethylmethacr ylate on twisted wire strands to produce strands of 25 beads of various sizes. These beads are gas sterilized and available for use "off the shelf" in a manner that is much more efficient than traditional production by hand on the back table in the operating room. Our technique was also utilized at a second institution to demonstrate its efficacy at another site.

Cunningham, Amy; Demarest, Gerald; Rosen, Philip; DeCoster, Thomas A



Antibiotic overuse versus chronic suppression  

Microsoft Academic Search

Because of the increasing use of antibiotics in the inpatient and outpatient setting, the emergence of resistance to antimicrobial\\u000a agents has progressed significantly. Traditionally, antibiotic resistance has been a problem only in the management of complicated\\u000a nosocomial urinary tract infections (UTIs). However, we now are seeing an emergence of antibiotic resistance in uncomplicated\\u000a community-acquired UTIs. Although uncomplicated UTIs constitute most

Kevin Bigelow; Alexis E. Te



Phylogenetic Analysis of Antibiotic Glycosyltransferases  

Microsoft Academic Search

Catalyzed by a family of enzymes called glycosyltransferases, glycosylation reactions are essential for the bioactivities\\u000a of secondary metabolites such as antibiotics. Due to the special characters of antibiotic glycosyltransferases (AGts), antibiotics\\u000a can function by attaching some unusual deoxy-sugars to their aglycons. Comprehensive similarity searches on the amino acid\\u000a sequences of AGts have been performed. We reconstructed the molecular phylogeny of

Dongmei Liang; Jianjun Qiao



Non-inherited antibiotic resistance  

Microsoft Academic Search

In addition to their impressive, well-publicized and well-researched propensity to evolve and acquire genetically determined mechanisms for resistance to antibiotics, bacteria that are inherently susceptible to these drugs can also be phenotypically refractory to their action. This phenomenon of 'non-inherited resistance' to antibiotics has been known since the beginning of the antibiotic era but, relative to inherited resistance, it has

Daniel E. Rozen; Bruce R. Levin



Antibiotic overkill of trauma victims?  


Antibiotic usage was assessed in a prospective, randomized trial of recombinant interferon-gamma (rIFN-gamma) versus placebo for 212 severely injured trauma patients in four university hospitals. All patients were observed until death or discharge from the hospital. We found the number of antibiotics used and their associated costs staggering and difficult to justify, although serious antibiotic-related complications were infrequent. Regular antibiotic administration following severe trauma should be re-evaluated since clinical evidence supports the use of shorter courses for these patients, with presumed similar outcomes and much-reduced expenses. PMID:8080071

Hadjiminas, D; Cheadle, W G; Spain, D A; Wilson, M A; Short, A; Starko, K M; Harris, B J; Livingston, D H; Rodriguez, J L



Evaluation of Antibiotic Efficacy Using Electron Microscopy: Morphological Effects of Guanylureido Cephalosporin, BL-P1654, and Carbenicillin on Escherichia coli  

PubMed Central

Early response of Escherichia coli to minimal inhibitory concentrations of 112883, BL-P1654, and carbenicillin was determined by [14C]leucine uptake and scanning electron microscopy morphology studies. [14C]leucine uptake was inhibited later by carbenicillin than by BL-P1654 or 112883. Cellular swelling at 30 min, septal region swelling, and lysis were the progressive morphological changes with BL-P1654 and 112883. Carbenicillin-treated cells showed septal region swelling, beaded chains, and lysis. Images

Ellis, L. F.; Herron, D. K.; Preston, D. A.; Simmons, L. K.; Schlegel, R. A.



Antibiotic resistance in animals.  


There is currently no systematic surveillance or monitoring of antibiotic resistance in Australian animals. Registration of antibiotics for use in animals is tightly controlled and has been very conservative. Fluoroquinolones have not been registered for use in food producing animals and other products have been removed from the market because of human health concerns. In the late 1970s, the Animal Health Committee coordinated a survey of resistance in Salmonella and Escherichia coli isolates from cattle, pigs and poultry and in bovine Staphylococcus aureus. Some additional information is available from published case reports. In samples collected prior to the withdrawal of avoparcin from the market, no vancomycin resistant Enterococcus faecium or Enterococcus faecalis were detected in samples collected from pigs, whereas some vanA enterococci, including E. faecium and E. faecalis, were found in chickens. No vanB enterococci were detected in either species. Virginiamycin resistance was common in both pig and poultry isolates. Multiple resistance was common in E. coli and salmonellae isolates. No fluoroquinolone resistance was found in salmonellae, E. coli or Campylobacter. Beta-lactamase production is common in isolates from bovine mastitis, but no methicillin resistance has been detected. However, methicillin resistance has been reported in canine isolates of Staphylococcus intermedius and extended spectrum beta-lactamase producing E. coli has been found in dogs. PMID:12807287

Barton, Mary D; Pratt, Rachael; Hart, Wendy S



Characterization of extended-spectrum cephalosporin-resistant Salmonella enterica serovar Heidelberg isolated from humans in the United States.  


During the past decade, extended-spectrum cephalosporin resistance has increased among human isolates of Salmonella enterica serovar Heidelberg, the fourth most common serotype in the United States. We therefore characterized 54 Heidelberg isolates with decreased susceptibility (minimum inhibitory concentrations >or=2 mg/L) to ceftriaxone or ceftiofur; 49 (90.7%) contained the CMY-type beta-lactamase (bla(CMY)) gene. The 49 bla(CMY)-positive human Heidelberg isolates demonstrated a high degree of relatedness; 4 clusters (25 isolates total) had indistinguishable XbaI and BlnI patterns by pulsed-field gel electrophoresis and were indistinguishable from 42 retail meat Heidelberg isolates. Further characterization of 15 of these isolates demonstrated that all of the bla genes were bla(CMY-2) and plasmid-encoded, and most (11/15) of the plasmids were approximately 100 kb in size and belong to the incompatibility group I1 (IncI1). All five IncI1 plasmids tested by plasmid multilocus sequence typing analysis were ST12. This report suggests that extended-spectrum cephalosporin resistance among human Heidelberg isolates is mediated by the spread of a common IncI1 bla(CMY-2) plasmid, which may have a preference for a particular genetic background. PMID:19785533

Folster, Jason P; Pecic, Gary; Bolcen, Shanna; Theobald, Lisa; Hise, Kelley; Carattoli, Alessandra; Zhao, Shaohua; McDermott, Patrick F; Whichard, Jean M



Beta-lactam resistance in Aeromonas spp. caused by inducible beta-lactamases active against penicillins, cephalosporins, and carbapenems.  

PubMed Central

Use of cefoperazone in a patient with Aeromonas caviae in the respiratory tract selected a mutant that constitutively produced beta-lactamase. This mutant, in contrast to its parental strain with an inducible beta-lactamase, showed enhanced resistance to newer cephalosporins and aztreonam. This observation suggested that species of Aeromonas, like those of other genera with inducible beta-lactamases, may pose therapeutic problems associated with the rapid development of multiple beta-lactam resistance. Thus, a study was designed to identify the beta-lactamases in 12 strains representing four species of Aeromonas and assess their role in drug resistance. Eleven strains possessed inducible beta-lactamases. One strain showed no detectable activity. An analysis of substrate and inhibitor profiles, isoelectric points, and beta-lactam susceptibility patterns revealed the presence of at least four distinguishable inducible beta-lactamases. These enzymes were involved in the resistance of strains within the genus to penicillins, cephalosporins, aztreonam, and imipenem but not cefoxitin. Unlike most other organisms with inducible beta-lactamases, all four strains of A. caviae, one of four strains of A. sobria, and one of three strains of A. hydrophila possessed two distinct inducible beta-lactamases. Furthermore, substrate and inhibitor profiles revealed that many of these Aeromonas beta-lactamases were distinct from inducible enzymes that have been characterized in other genera of gram-negative bacteria. Images

Bakken, J S; Sanders, C C; Clark, R B; Hori, M



Antibiotic utilisation for hospitalised paediatric patients  

Microsoft Academic Search

Antibiotics are among the most commonly prescribed drugs in paediatrics. Because of an overall rise in health care costs, lack of uniformity in drug prescribing and the emergence of antibiotic resistance, monitoring and control of antibiotic use is of growing concern and strict antibiotic policies are warranted. Before such policies can be implemented, detailed knowledge of antibiotic prescribing patterns is

Marlies A van Houten; Klarieke Luinge; Marian Laseur; Jan L. L Kimpen



The effect of amphotericin B, aztreonam, imipenem and cephalosporins on the bone marrow progenitor cell activity.  


The effects of certain antibiotics on the colony forming activity of human bone marrow cells in semisolid methylcellulose medium in vitro and on murine BM cells in spleen colony forming units (cfu-s) in vivo were evaluated. Amikacin, gentamicin, piperacillin, co-trimoxazole and pentamidine had little or no effect on human bone marrow progenitor cell function; amphotericin B, aztreonam, ceftazidime and imipenem caused significant suppression of human colony forming unit-erythroid (cfu-e), burst forming unit-erythroid (bfu-e) and colony forming unit-granulocyte macrophage (cfu-gm) at both peak and trough serum concentrations. At molar equivalent concentrations ceftazidime, cefotaxime and cefoperazone caused significant decreases in human cfu-e, bfu-e and cfu-gm in vitro (P less than 0.01) and murine cfu-s in vivo (P less than 0.05); cefoxitin, cefuroxime, ceftizoxime and ceftriaxone did not suppress human bone marrow progenitor cell activity. Gentamicin, piperacillin and ceftriaxone had no effect on murine cfu-s formation. Further studies to evaluate the effect of these antibiotics on human bone marrow in vivo are suggested. PMID:2050599

Charak, B S; Louie, R; Malloy, B; Twomey, P; Mazumder, A



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


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

Capita, Rosa; Alonso-Calleja, Carlos



Macrolide antibiotics and pulmonary inflammation  

Microsoft Academic Search

Many clinically effective therapeutic agents can exhibit localized and systemic effects that are manifestly different from their intended primary pharmacological mode of action. Macrolide antibiotics such as erythromycin and its derivatives are no exception. In addition to their antibacterial action, this class of antibiotics exhibits anti-inflammatory activity in a variety of airway diseases such as asthma and diffuse panbronchiolitis that

Jeffrey C Hoyt; Richard A Robbins



Epidemiology of resistance to antibiotics  

Microsoft Academic Search

An inevitable side effect of the use of antibiotics is the emergence and dissemination of resistant bacteria. Most retrospective and prospective studies show that after the introduction of an antibiotic not only the level of resistance of pathogenic bacteria, but also of commensal bacteria increases. Commensal bacteria constitute a reservior of resistance genes for (potentially) pathogenic bacteria. Their level of

Anthony E. van den Bogaard; Ellen E. Stobberingh



Antibiotic prophylaxis at caesarean section  

Microsoft Academic Search

4 noted that endometritis after caesarean section may be reduced by up to 75%, thereby justifying a policy of administering prophylactic anti- biotics to all women undergoing elective or non-elective caesarean delivery. However, within and across maternity units in the UK, inconsistency exists in the use of antibiotic prophylaxis at caesarean section. 5 Many units encourage a policy of antibiotic

Victor Siskind; Antonio Tomassini; Stephen Mark Wild; Boggess KA; Watts DH; Hillier SL; Krohn MA; Benedetti TJ


Fulvic acid and antibiotic combination  

US Patent & Trademark Office Database

This invention relates to a fulvic acid and antibiotic combination for use in the treatment of various diseases and conditions. The invention further relates to the use of the combination for the treatment of various diseases and conditions, including bacterial infection. In particular, the bacteria are antibiotic resistant bacteria.



The Antibiotic Resistance Problem Revisited  

ERIC Educational Resources Information Center

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…

Lawson, Michael A.



The Antibiotic Resistance Problem Revisited  

ERIC Educational Resources Information Center

|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…

Lawson, Michael A.



ARDB - Antibiotic Resistance Genes Database  

Microsoft Academic Search

The treatment of infections is increasingly compro- mised by the ability of bacteria to develop resis- tance to antibiotics through mutations or through the acquisition of resistance genes. Antibiotic resis- tance genes also have the potential to be used for bio-terror purposes through genetically modified organisms. In order to facilitate the identification and characterization of these genes, we have cre-

Bo Liu; Mihai Pop



Resistance-induced antibiotic substitution  

Microsoft Academic Search

In many cases, physicians prescribe antibiotics without knowing whether an individual patient is infected with a susceptible or resistant pathogen. As the proportion of resistant organisms in a community increases, physicians substitute away from older-inexpensive drugs to newer, more expensive agents as first line therapy. This paper explores the implications of resistance-induced antibiotic substitution for epidemiological models to predict future

David H. Howard



Preserve a Treasure: Know When Antibiotics Work  

Center for Drug Evaluation (CDER)

... A: Taking antibiotics when they aren't needed contributes to the serious problem of antibiotic resistance. Q: What is antibiotic resistance? ... More results from


Antibiotics, microbiota, and immune defense  

PubMed Central

The gastrointestinal tract microbiota contributes to the development and differentiation of the mammalian immune system. The composition of the microbiota affects immune responses and affects susceptibility to infection by intestinal pathogens and development of allergic and inflammatory bowel diseases. Antibiotic administration, while facilitating clearance of targeted infections, also perturbs commensal microbial communities and decreases host resistance to antibiotic-resistant microbes. Here, we review recent advances that begin to define the interactions between complex intestinal microbial populations and the mammalian immune system and how this relation is perturbed by antibiotic administration. We further discuss how antibiotic-induced disruption of the microbiota and immune homeostasis can lead to disease and we review strategies to restore immune defenses during antibiotic administration.

Ubeda, Carles; Pamer, Eric G.



Current status of carbapenem antibiotics.  


?-Lactam antibiotics are the most prescribed antibacterial agents. They comprise more than half of all antibiotics. They are considered as the cornerstone of the antibiotic armamentarium. By inhibiting bacterial cell wall biosynthesis, they are highly effective against Gram-positive and Gram-negative bacteria. Antibiotic resistance among Gram-negative pathogens in hospitals represents a dangerous threat to public health. Since many bacteria have developed resistance to older agents, new ?-lactam antibiotics have been continuously developed. In the late 1970s, a new class of exceptionally broad-spectrum non-traditional ?-lactams, carbapenems, was developed. This review article focuses on the new developments related to the field of carbapenems for treatment of bacterial infections, especially those caused by Gram-negative bacteria. The structural features, principal characteristics, and clinical implications of carbapenems including thienamycin, imipenem/cilastatin, panipenem/betamipron, biapenem, tebipenem, tebipenem pivoxil, meropenem, ertapenem, doripenem, lenapenem, and tomopenem are discussed herein. PMID:20615191

El-Gamal, Mohammed I; Oh, Chang-Hyun



Mortality and Hospital Stay Associated with Resistant Staphylococcus aureus and Escherichia coli Bacteremia: Estimating the Burden of Antibiotic Resistance in Europe  

PubMed Central

Background The relative importance of human diseases is conventionally assessed by cause-specific mortality, morbidity, and economic impact. Current estimates for infections caused by antibiotic-resistant bacteria are not sufficiently supported by quantitative empirical data. This study determined the excess number of deaths, bed-days, and hospital costs associated with blood stream infections (BSIs) caused by methicillin-resistant Staphylococcus aureus (MRSA) and third-generation cephalosporin-resistant Escherichia coli (G3CREC) in 31 countries that participated in the European Antimicrobial Resistance Surveillance System (EARSS). Methods and Findings The number of BSIs caused by MRSA and G3CREC was extrapolated from EARSS prevalence data and national health care statistics. Prospective cohort studies, carried out in hospitals participating in EARSS in 2007, provided the parameters for estimating the excess 30-d mortality and hospital stay associated with BSIs caused by either MRSA or G3CREC. Hospital expenditure was derived from a publicly available cost model. Trends established by EARSS were used to determine the trajectories for MRSA and G3CREC prevalence until 2015. In 2007, 27,711 episodes of MRSA BSIs were associated with 5,503 excess deaths and 255,683 excess hospital days in the participating countries, whereas 15,183 episodes of G3CREC BSIs were associated with 2,712 excess deaths and 120,065 extra hospital days. The total costs attributable to excess hospital stays for MRSA and G3CREC BSIs were 44.0 and 18.1 million Euros (63.1 and 29.7 million international dollars), respectively. Based on prevailing trends, the number of BSIs caused by G3CREC is likely to rapidly increase, outnumbering the number of MRSA BSIs in the near future. Conclusions Excess mortality associated with BSIs caused by MRSA and G3CREC is significant, and the prolongation of hospital stay imposes a considerable burden on health care systems. A foreseeable shift in the burden of antibiotic resistance from Gram-positive to Gram-negative infections will exacerbate this situation and is reason for concern. Please see later in the article for the Editors' Summary

de Kraker, Marlieke E. A.; Davey, Peter G.; Grundmann, Hajo



Clinical and Microbiologic Characteristics of Cephalosporin-Resistant Escherichia coli at Three Centers in the United States  

PubMed Central

We investigated the clinical and microbiologic features of 300 cases of cephalosporin-resistant Escherichia coli producing extended-spectrum ?-lactamase (ESBL) or plasmid-mediated AmpC ?-lactamase (pAmpC) at three medical centers in the United States. Solid-organ malignancy, connective tissue disease, and a recent history of surgery were more common among pAmpC-producing cases (n = 49), whereas urinary catheter at enrollment, diabetes, and hospitalization in the past year were more common among ESBL-producing cases (n = 233). The factors independently associated with clinical outcome were the following: the presence of cardiovascular disease (odds ratio [OR], 2.88; 95% confidence interval [CI], 1.29 to 6.43), intra-abdominal infection (OR, 6.35; 95% CI, 1.51 to 26.7), other or multiples sources of infection (OR, 8.12; 95% CI, 2.3 to 28.6), age of 65 years or greater (OR, 0.43; 95% CI, 0.2 to 0.95), favorable baseline health status (OR, 0.39; 95% CI, 0.16 to 0.95), and appropriate empirical antimicrobial therapy given in the first 72 h (OR, 0.42; 95% CI, 0.20 to 0.88). ?-Lactamase genes responsible for cephalosporin resistance were identified in 291 cases. CTX-M-type ESBLs accounted for 72.0%. Of those, 88.0% were CTX-M-15. The next most common type was CMY-type pAmpC (16.7%), followed by SHV- and TEM-type ESBLs (6.3 and 1.3%, respectively). Seven cases (2.3%) had KPC-type ?-lactamase. Ertapenem, imipenem, meropenem, doripenem, piperacillin-tazobactam, amikacin, nitrofurantoin, and tigecycline were highly active, with greater than 90% of the isolates being susceptible. Cefepime was less active, with only 74.2% being susceptible due to the predominance of CTX-M-15. These findings have implications in the selection of appropriate empirical therapy when infection due to cephalosporin-resistant E. coli is suspected.

Park, Yoon Soo; Adams-Haduch, Jennifer M.; Shutt, Kathleen A.; Yarabinec, Daniel M.; Johnson, Laura E.; Hingwe, Ameet; Lewis, James S.; Jorgensen, James H.



Clinical and microbiologic characteristics of cephalosporin-resistant Escherichia coli at three centers in the United States.  


We investigated the clinical and microbiologic features of 300 cases of cephalosporin-resistant Escherichia coli producing extended-spectrum ?-lactamase (ESBL) or plasmid-mediated AmpC ?-lactamase (pAmpC) at three medical centers in the United States. Solid-organ malignancy, connective tissue disease, and a recent history of surgery were more common among pAmpC-producing cases (n = 49), whereas urinary catheter at enrollment, diabetes, and hospitalization in the past year were more common among ESBL-producing cases (n = 233). The factors independently associated with clinical outcome were the following: the presence of cardiovascular disease (odds ratio [OR], 2.88; 95% confidence interval [CI], 1.29 to 6.43), intra-abdominal infection (OR, 6.35; 95% CI, 1.51 to 26.7), other or multiples sources of infection (OR, 8.12; 95% CI, 2.3 to 28.6), age of 65 years or greater (OR, 0.43; 95% CI, 0.2 to 0.95), favorable baseline health status (OR, 0.39; 95% CI, 0.16 to 0.95), and appropriate empirical antimicrobial therapy given in the first 72 h (OR, 0.42; 95% CI, 0.20 to 0.88). ?-Lactamase genes responsible for cephalosporin resistance were identified in 291 cases. CTX-M-type ESBLs accounted for 72.0%. Of those, 88.0% were CTX-M-15. The next most common type was CMY-type pAmpC (16.7%), followed by SHV- and TEM-type ESBLs (6.3 and 1.3%, respectively). Seven cases (2.3%) had KPC-type ?-lactamase. Ertapenem, imipenem, meropenem, doripenem, piperacillin-tazobactam, amikacin, nitrofurantoin, and tigecycline were highly active, with greater than 90% of the isolates being susceptible. Cefepime was less active, with only 74.2% being susceptible due to the predominance of CTX-M-15. These findings have implications in the selection of appropriate empirical therapy when infection due to cephalosporin-resistant E. coli is suspected. PMID:22290945

Park, Yoon Soo; Adams-Haduch, Jennifer M; Shutt, Kathleen A; Yarabinec, Daniel M; Johnson, Laura E; Hingwe, Ameet; Lewis, James S; Jorgensen, James H; Doi, Yohei



Characterization and Prevalence of the Different Mechanisms of Resistance to Beta-Lactam Antibiotics in Clinical Isolates of Escherichia coli  

PubMed Central

A survey of clinical isolates from a hospital laboratory showed that Escherichia coli could be grouped into three classes of beta-lactam-antibiotic resistance by results of routine susceptibility testing to ampicillin, cephalothin, and carbenicillin. E. coli highly resistant to ampicillin and carbenicillin but not to cephalothin (class I) were found to have one of two levels of R factor-mediated, periplasmic-?-lactamase which resembled RTEM and was located behind a permeability barrier to penicillins but not to cephalosporins. This permeability barrier appeared to act synergistically with the ?-lactamase in producing high levels of resistance to penicillins. E. coli highly resistant to ampicillin and cephalothin but not carbenicillin (class II) were found to have a ?-lactamase with predominantly cephalosporinase activity which was neither transferable nor releasable by osmotic shock. E. coli moderately resistant to one or to all three of these antibiotics (class III) were found to have low levels of different ?-lactamases including a transferable ?-lactamase which resembled R1818. Thus, different mechanisms producing resistance to ?-lactam antibiotics could be deduced from the patterns of resistance to ampicillin, cephalothin, and carbenicillin found on routine susceptibility testing. E. coli of class I were much more prevalent than the other classes and the proportion of E. coli that were class I increased with duration of patient hospitalization. The incidence of class I E. coli rose only slightly over the past 7 years and that of class II E. coli remained constant despite increased usage of both cephalothin and ampicillin. These observations emphasize that the properties of the apparently limited number of individual resistance mechanisms that exist in a bacterial flora, such as their genetic mobility and linkages and the spectrum of their antibiotic inactivating enzymes and permeability barriers, may govern the effect that usage of an antibiotic has upon the prevalence of resistance to it and to other antibiotics.

Medeiros, Antone A.; Kent, Ralph L.; O'Brien, Thomas F.



Antibiotic consumption at 46 VINCat hospitals from 2007 to 2009, stratified by hospital size and clinical services.  


The aim of the study was to assess the evolution of antibiotic consumption in acute care hospitals in Catalonia (population 7.5 million), according to hospital size and department, during the period 2007-2009. The methodology used for monitoring antibiotic consumption was the ATC/DDD system, and the unit of measurement was DDD/100 occupied bed-days (DDD/100 OBD). Hospitals were stratified according to size: I) large university hospitals (with more than 500 beds); II) medium-sized hospitals (between 200 and 500 beds); and III) small hospitals (fewer than 200 beds). The consumption was also analyzed and stratified according to department: medical, surgical and intensive care unit (ICU). Specific training in data management on antibiotic consumption was given to all participant hospitals before the implementation of the program. The mean antibiotic (J01) consumption, calculated in DDD/100 OBD, increased although without statistical significance (p=0.640): 74.68 (2007), 75.13 (2008) and 78.04 (2009). The values of the medians expressed in DDD/100 OBD in group I were 83.27 (in 2007), 82.16 (2008) and 86.93 (2009), in group II 72.60 (2007), 70.78 (2008) and 75.17 (2009) and in group III 65.66 (2007), 69.32 (2008) and 72.39 (2009). Antibiotic consumption was higher in large hospitals than in medium-sized or small hospitals. Catalan hospitals recorded an increase of 4.49% from 2007 to 2009, especially due to the rising use of carbapenems, cephalosporins, monobactams and the other antibiotic groups. PMID:22776154

Grau, Santiago; Fondevilla, Esther; Mojal, Sergi; Palomar, Mercedes; Vallčs, Jordi; Gudiol, Francesc



Risk Factors for Colonization and Infection in a Hospital Outbreak Caused by a Strain of Klebsiella pneumoniae with Reduced Susceptibility to Expanded-Spectrum Cephalosporins  

Microsoft Academic Search

Between February 2001 and January 2002, an increase in the number of Klebsiella pneumoniae isolates with reduced susceptibility to expanded-spectrum cephalosporins (RSKp) was detected in the neonatal unit of the Juan Canalejo Hospital, and 21 patients were either colonized or infected by the bacterial isolates. The current \\

Monica Cartelle; Maria del Mar Tomas; Sonia Pertega; Alejandro Beceiro; David Velasco; Francisca Molina; Rosa Villanueva; German Bou



Microbial uropathogens and their antibiotic resistance profile from hospitalized patients in Central Alabama.  


Urinary tract infections remain a common problem in inpatient care. They are highly challenging to provide effective initial therapy without sensitivity data. The purpose of this study was to survey the uropathogens and their sensitivity profile at a hospital in Central Alabama and to guide experiential antibiotic selection. This was the first reported study on bacterial uropathogens and their antibiotic resistance profile at this Central Alabama hospital. The survey period was between July 2009 and June 2010, a total of 473 urine cultures were reviewed and susceptibility testing was determined using the Clinical and Laboratory Standards Institute (CLSI) microdilution method. The results indicated that Escherichia coli (45.5%) was the most common organism, followed by Klebsiella pneumoniae (18.2%), Pseudomonas aeruginosa (10.1%), Proteus mirabilis (7.8%), Enterobacter cloacae (4.2%), methicillin-resistant Staphylococcus aureus (3.0%), Klebsiella oxytoca and Citrobacter freundii (1.5%), Morganella morganii (1.3%), and the other species (7.0%). For the 215 E. coli isolates, imipenem and cephalosporins (except for cefazolin) had the highest sensitivity (99-100%, P < 0.05). In contrast, ampicillin had the highest resistance (57%, P < 0.05) as compared to other antibiotics (about 30%) including ampicillin/ sulbactam, ciprofloxacin, levofloxacin, tetracycline, and trimethoprim/sulfamethoxazole. The major finding of this study was that ciprofloxacin, levofloxacin and trimethoprim/sulfamethoxazole had comparable sensitivity patterns for Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Enterobacter cloacae, the most common uropathogens at this Central Alabama hospital. Additionally, this study found that E. coli had a resistant rate of 31% to ciprofloxacin and levofloxacin compared to the resistance rate of 28.4% and 15.8% in earlier reports (Lee et al. 2010; Rattanaumpawan et al. 2010), likely indicating the continuing evolution of resistance due to antibiotic exposure. It is imperative to monitor the resistance of P. aeruginosa considering their high resistance to imipenem found in this study. PMID:23330509

Qian, Li; Camara, Tracy; Taylor, J Kyle; Jones, Kathy W



Surveillance and Correlation of Antibiotic Prescription and Resistance of Gram-Negative Bacteria in Singaporean Hospitals? †  

PubMed Central

A surveillance study was performed in four Singapore public hospitals from 2006 to 2008 to determine the correlation between antibiotic prescription and Gram-negative bacterial antimicrobial resistance. Targeted organisms included ceftriaxone- and ciprofloxacin-resistant Escherichia coli and Klebsiella pneumoniae, as well as imipenem-resistant Pseudomonas aeruginosa and Acinetobacter spp. Antibiotic prescription data were collated in the WHO anatomical therapeutic chemical (ATC)/defined daily dose (DDD) format, while antibiotic resistance was expressed as incidence density adjusted for total inpatient-days every quarter. Individual trends were determined by linear regression, while possible associations between antibiotic prescription and resistance were evaluated via cross-correlation analysis. Results over 3 years indicated significantly rising incidence densities of ceftriaxone- and ciprofloxacin-resistant E. coli and imipenem-resistant Acinetobacter spp. (blood isolates only). Antimicrobial-resistant Klebsiella pneumoniae rates declined. The prescription rates of piperacillin-tazobactam, ertapenem, meropenem, ciprofloxacin, and levofloxacin increased significantly, while imipenem and moxifloxacin prescription decreased. Cross-correlation analysis demonstrated possible associations between prescription of fluoroquinolones and ciprofloxacin-resistant E. coli (R2 = 0.46), fluoroquinolones and ceftriaxone-resistant E. coli (R2 = 0.47), and carbapenems and imipenem-resistant Acinetobacter spp. (R2 = 0.48), all at zero time lag. Changes in meropenem prescription were associated with a similar trend in imipenem-resistant Acinetobacter blood isolates after a 3-month time lag. No correlation was found between cephalosporin use and resistance. In conclusion, our data demonstrated correlation between prescription of and Gram-negative bacterial resistance to several, but not all, key antimicrobial agents in Singapore hospitals. In areas where Gram-negative bacterial resistance is endemic and prescription of broad-spectrum antimicrobial agents is high, factors other than antimicrobial usage may be equally important in maintaining high resistance rates.

Hsu, Li-Yang; Tan, Thean-Yen; Tam, Vincent H.; Kwa, Andrea; Fisher, Dale Andrew; Koh, Tse-Hsien



[Antibiotic treatment of hidradenitis suppurativa].  


Bacterial infection plays an important role in hidradenitis suppurativa (HS). This infection has a number of unique features: chronicity, absence of lymph node involvement, and absence in most cases of acute super-infection by Staphylococcus aureus and/or streptococci. Treatment is based mainly on antibiotics. Various bacteria are involved; they are often part of the resident flora and may combine in polymicrobial infections, and they consist mainly of two families: coagulase-negative staphylococci (CNS) and anaerobes. Numerous antibiotics are active against CNS: betalactamins, lincosamides, macrolides, rifampicin, tetracyclines and fluoroquinolones. Antibiotics active against anaerobes include metronidazole, betalactamins, lincosamides and one fluoroquinolone (moxifloxacine). Antibiotics are given per os and in combination. Treatment is usually long-term, with a frequent need for maintenance therapy. It has to be tailored to various clinical situations: intermittent development, in which "abortive" emergency treatment is used; major or major continuous forms, where combined antibiotics are used, most frequently rifampicin and clindamycin. The global treatment strategy involves a surgical approach, which can be aided but not replaced by antibiotics. While the risks of long-term antibiotic use are reduced in this specific population of "healthy" young adults, they are not absent. PMID:22963962

Revuz, J



Bacterial evolution of antibiotic hypersensitivity.  


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

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



In vitro antibiotic susceptibilities of Neisseria gonorrhoeae isolates in the Philippines.  


Antibiotic susceptibility surveillance testing was performed on clinical isolates of Neisseria gonorrhoeae collected in September 1989 in the Philippines. beta-Lactamase was produced by 77 (55%) of 140 isolates. In vitro MIC testing revealed significant resistance to penicillin (MIC for 90% of isolates [MIC90], greater than 64 micrograms/ml), tetracycline (MIC90, 4 micrograms/ml), and cefmetazole (MIC90, 8 micrograms/ml). Spectinomycin resistance was rare (10 of 117), but the MIC90 was 32 micrograms/ml. Isolates were susceptible to fluoroquinolones and cephalosporins at the time of this survey, as evidenced by the MIC90s of ciprofloxacin (0.25 microgram/ml), norfloxacin (2.0 micrograms/ml), ofloxacin (0.625 microgram/ml), cefpodoxime (2.0 micrograms/ml), cefotaxime (1.0 microgram/ml), ceftazidime (0.25 microgram/ml), ceftizoxime (0.25 microgram/ml), and ceftriaxone (0.06 microgram/ml). To date, ceftriaxone resistance has not emerged, despite the widespread use of this antibiotic in the Philippines. PMID:1605592

Clendennen, T E; Hames, C S; Kees, E S; Price, F C; Rueppel, W J; Andrada, A B; Espinosa, G E; Kabrerra, G; Wignall, F S



Determination of beta-lactamase activities and antibiotic susceptibility of some Bacillus strains causing food poisoning.  


Some Bacillus species are important food pathogens. For example, B. cereus is an opportunistic pathogen found in raw milk that is a common cause of food poisoning. It is of interest to investigate the virulant profiles of Bacillus strains isolated from foods and samples associated with food-poisoning outbreaks. Nineteen Bacillus strains were isolated from various milk samples. Beta-lactamase enzyme activities of these Bacillus strains were evaluated with iodometric and chromogenic cephalosporin (nitrocefin) test methods. Five of 19 Bacillus strains isolated were positive for beta-lactamase activity. Clavulanate-amoxycillin and cephazolin were chosen to test the antibiotic susceptibilities of the beta-lactamase positive and negative Bacillus strains. Of the five beta-lactamase positive Bacillus strains, three were susceptible, and two strains intermediate to clavulanate-amoxycillin; one was susceptible, and four strains were intermediate to cephazolin. None of the beta-lactamase positive Bacillus strains was resistant to both antibiotics. Of the 14 beta-lactamase negative strains, five were susceptible to clavulanate-amoxycillin, four strains were intermediate, and five strains were resistant; three were susceptible, one intermediate, and ten beta-lactamase negative strains were resistant to cephazolin. PMID:11522126

Uraz, G; Sim?ek, H; Mara?, Y



Antibiotic theory in otitis media  

Microsoft Academic Search

Otitis media is currently the most common diagnosis made by clinicians, which has a major impact on managed care. The emergence\\u000a of resistant bacterial pathogens has caused controversy over the use of antibiotics when acute otitis media (AOM) is diagnosed.\\u000a All infants with AOM and all older children with severe AOM should be treated with antibiotics, despite concerns about rising

Anil Gungor; Charles D. Bluestone



Antibiotics increase functional abdominal symptoms  

Microsoft Academic Search

OBJECTIVES:Data suggest that subjects with irritable bowel syndrome are more likely to report a recent course of antibiotics. This study tests the hypothesis that a course of antibiotics is a risk factor for an increase in the number of functional bowel complaints over a 4-month period in a general population sample.METHODS:We initiated a prospective case-control study in three general practices

P. R Maxwell; E Rink; D Kumar; M. A Mendall



Antibiotics increase functional abdominal symptoms  

Microsoft Academic Search

OBJECTIVE:Data suggest that subjects with irritable bowel syndrome are more likely to report a recent course of antibiotics. This study tests the hypothesis that a course of antibiotics is a risk factor for an increase in the number of functional bowel complaints over a 4-month period in a general population sample.METHODS:We initiated a prospective case-control study in three general practices

P. R. Maxwell; E. Rink; D. Kumar; M. A. Mendall



Antibacterial properties of cationic steroid antibiotics  

Microsoft Academic Search

Cationic steroid antibiotics have been developed that display broad-spectrum antibacterial activity. These compounds are comprised of steroids appended with amine groups arranged to yield facially amphiphilic morphology. Examples of these antibiotics are highly bactericidal, while related compounds effectively permeabilize the outer membranes of Gram-negative bacteria sensitizing these organisms to hydrophobic antibiotics. Cationic steroid antibiotics exhibit various levels of eukaryote vs.

Paul B Savage; Chunhong Li; Uale Taotafa; Bangwei Ding; Qunying Guan



The determinants of the antibiotic resistance process  

PubMed Central

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.

Franco, Beatriz Espinosa; Altagracia Martinez, Marina; Sanchez Rodriguez, Martha A; Wertheimer, Albert I



Dielectrophoretic assay of bacterial resistance to antibiotics  

Microsoft Academic Search

The dielectrophoretic collection spectra of antibiotic-sensitive and antibiotic-resistant strains of Staphylococcus epidermidis have been determined. These indicate that in the absence of antibiotic treatment there is a strong similarity between the dielectric properties of sensitive and resistant strains, and that there is a significant difference between the sensitive strains before and after treatment with the antibiotic streptomycin after 24 h

Juliana Johari; Yvonne Hübner; Judith C Hull; Jeremy W Dale; Michael P Hughes



Psalliotin, the Antibiotic of Psalliota xanthoderma  

Microsoft Academic Search

THE antibiotic activity of the edible mushroom Psalliota xanthoderma was first described in some detail by Atkinson1 in Australia. Wilkins2 in England also recorded this mushroom as being antibiotic. Atkinson gave a number of characteristics of the antibiotic substance and also a list of sensitive and insensitive bacterial species, but refrained from naming the substance as a new antibiotic. Its

Nancy Atkinson



Antibiotic prescription preferences in paediatric outpatient setting in Estonia and Sweden.  


Aims of the study were to compare the paediatric outpatient antibiotic use in two countries with low overall antibiotic consumption and antibacterial resistance levels - Sweden and Estonia - and to describe the adherence to Estonian treatment guideline. All prescriptions for systemic antibiotics for children less than 18 years during 2007 from the Swedish Prescribed Drug Register and Estonian Health Insurance Fund database were identified to conduct a descriptive drug utilisation study. The total paediatric antibiotic use was 616 and 353 per 1000 in Estonia and Sweden, respectively. The greatest between country differences occurred in the age group 2 to 6 years -Estonian children received 1184 and Swedish children 528 prescriptions per 1000. Extended spectrum penicillin amoxicillin (189 per 1000) or its combination with beta-lactamase inhibitor (81 per 1000) and a newer macrolide clarithromycin (127 per 1000) were prescribed most often in Estonia whereas narrow spectrum penicillin phenoxymethylpenicillin (169 per 1000) and older generation macrolide erythromycin (21 per 1000) predominated in Sweden. For acute bronchitis, 17 different antibiotics (most commonly clarithromycin) were prescribed in Estonia despite the guideline recommendation not to use antibiotics. The higher rate of antibiotic use especially of extended spectrum antibiotics in Estonia compared to Sweden emphasizes the need for national activities to promote appropriate use of antibiotics while treating children, even when the overall antibiotic consumption is low. PMID:23667800

Lass, Jana; Odlind, Viveca; Irs, Alar; Lutsar, Irja



Sorption of antibiotics to biofilm.  


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

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



The electrocatalytic examination of cephalosporins at carbon paste electrode modified with CoSalophen.  


The electrocatalytic oxidation of cephalexin and cefazolin has been studied at a carbon paste electrode modified with cobalt salophen (CoSal) by cyclic voltammetry. The selectivity of the carbon paste modified with CoSal in detecting cephalexin and cefazolin was examined. To suggest the electrocatalytic mechanism for electro-oxidation of cefazolin, the electrochemical behavior of ceftriaxone was investigated which has a thiol group out of the beta lactam ring. The electrocatalytic oxidation of these antibiotics is shown to be irreversible at the CoSal modified electrode. Scan rate dependence of cefazolin, which is a sulfur-containing compound, has been examined. The results indicated that the electrocatalytic oxidation of the compounds is diffusion controlled. The responses of the modified electrode were compared with those of unmodified electrode and it has shown that the modified electrode has better sensitivity than unmodified electrode to the detection of cefazolin. The overall number of electrons contributed to the oxidation of cefazolin is obtained 1 by chronoamperometry; the number of electron involved in the rate-determining step was 1. The results of differential pulse voltammetry (DPV) using the modified electrode with high sensitivity were applied for the determination of cefazolin in human synthetic serum samples. The linear range was obtained from 1x10(-5) to 1x10(-3)M for DPV determination of cefazolin in buffered solutions (pH 3.0). PMID:19071506

Jamasbi, E S; Rouhollahi, A; Shahrokhian, S; Haghgoo, S; Aghajani, S



Static recipient cells as reservoirs of antibiotic resistance during antibiotic therapy  

Microsoft Academic Search

How does taking the full course of antibiotics prevent antibiotic resistant bacteria establishing in patients? We address this question by testing the possibility that horizontal\\/lateral gene transfer (HGT) is critical for the accumulation of the antibiotic-resistance phenotype while bacteria are under antibiotic stress. Most antibiotics prevent bacterial reproduction, some by preventing de novo gene expression. Nevertheless, in some cases and

Allan R. Willms; Paul D. Roughan; Jack A. Heinemann



Antibiotic Attack (Kinetic City)  

NSDL National Science Digital Library

This game is a part of the Tau Pack of the Kinetic City site (see description below). In this simulation, the patient's bodies are filled with bacteria. The object is to cure as many patients as possible. Learning concepts enforced here are that antibiotics are specific for the type of bacteria they treat, their strength, and that the bacteria may also become resistant to the bacteria by mutations.KINETIC CITY DESCRIPTION: "Kinetic City" ( is a fun, Web-based after-school science club for kids, ages 8 through 11. It combines exciting online animations and activities with boxes of hands-on science experiments. Children earn "Kinetic City" power points and collect stickers as they complete missions and learn standards-based science content. Here's how it works: The "Kinetic City" super crew (Keisha, Curtis, Megan and Max) needs the help of Earth kids to save their planet Vearth, from the science-distorting computer virus Deep Delete. Each of Deep Delete's 60 hideous strains attacks a different area of science with disastrous consequences. After each attack, teams of Earth kids fight back by viewing a short online animation describing the situation on Vearth; performing a series of activities to re-learn the lost science and going on a mission to Vearth during which they answer science questions and gobble up Deep Delete viruses. Their scores appear on their own Kinetic City Club Web page. "Kinetic City" is produced by the American Association for the Advancement of Science (AAAS), with a grant from the National Science Foundation. AAAS writes the "Project 2061 Benchmarks for Science Literacy," which forms the basis of most state science standards.

American Association for the Advancement of Science (;)



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

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.

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



WAAR (World Alliance against Antibiotic Resistance): Safeguarding antibiotics  

PubMed Central

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.



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.  


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

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



Antibiotic resistance of bacterial biofilms.  


A biofilm is a structured consortium of bacteria embedded in a self-produced polymer matrix consisting of polysaccharide, protein and DNA. Bacterial biofilms cause chronic infections because they show increased tolerance to antibiotics and disinfectant chemicals as well as resisting phagocytosis and other components of the body's defence system. The persistence of, for example, staphylococcal infections related to foreign bodies is due to biofilm formation. Likewise, chronic Pseudomonas aeruginosa lung infection in cystic fibrosis patients is caused by biofilm-growing mucoid strains. Characteristically, gradients of nutrients and oxygen exist from the top to the bottom of biofilms and these gradients are associated with decreased bacterial metabolic activity and increased doubling times of the bacterial cells; it is these more or less dormant cells that are responsible for some of the tolerance to antibiotics. Biofilm growth is associated with an increased level of mutations as well as with quorum-sensing-regulated mechanisms. Conventional resistance mechanisms such as chromosomal beta-lactamase, upregulated efflux pumps and mutations in antibiotic target molecules in bacteria also contribute to the survival of biofilms. Biofilms can be prevented by early aggressive antibiotic prophylaxis or therapy and they can be treated by chronic suppressive therapy. A promising strategy may be the use of enzymes that can dissolve the biofilm matrix (e.g. DNase and alginate lyase) as well as quorum-sensing inhibitors that increase biofilm susceptibility to antibiotics. PMID:20149602

Hřiby, Niels; Bjarnsholt, Thomas; Givskov, Michael; Molin, Sřren; Ciofu, Oana



[Antibiotic sensitivity of Corynebacterium amycolatum].  


C. amycolatum strains belongs to opportunistic bacteria considered as etiological factors of hospital infections. It's usually handled as a human natural flora, so antibiotic sensitivity is not checked. There's a few reports relative to antibiotic sensitivity of C. amycolatum in the world literature. So, we decided to examine antibiotic sensitivity of isolated strains. The 70 of C. amycolatum strains isolated from clinical samples from patients hospitalised at Samodzielny Publiczny Szpital Kliniczny in Bydgoszcz were analysed. Antimicrobial susceptibility testing of the strains was performed by means of a disk diffusion method. 28.6% of analysed strains were susceptible to penicillin and 38.6% to ampicillin. Susceptibility to another 16 antibiotics was from 40.0% for ceftazidime to 64.3% for ceftriaxone. Penicillinase was not produced by analysed strains. We stated higher percentage of strains susceptible to combinations of penicillin with inhibitors than to penicillin and ampicillin. The most strains were susceptible to quinupristin-dealfopristin, linezolid and glycopeptide antibiotics but resistance to mupirocin. 35.7% analysed strains were multiresistance; there were resistance to beta-lactams (approximately 100%), lincosamides (96.0%), macrolides (92.0%) and quinolones (92.0%). Multiresistant strains were the most frequently isolated from wound swabs (60.0%) and mainly came from patients treated at the departments of general surgery (28.0%) and vascular surgery (16.0%). PMID:15959988

Zalas, Patrycja; Mikucka, Agnieszka; Gospodarek, Eugenia



Consumer Attitudes and Use of Antibiotics  

PubMed Central

Recent antibiotic use is a risk factor for infection or colonization with resistant bacterial pathogens. Demand for antibiotics can be affected by consumers’ knowledge, attitudes, and practices. In 1998–1999, the Foodborne Diseases Active Surveillance Network (FoodNet) conducted a population-based, random-digit dialing telephone survey, including questions regarding respondents’ knowledge, attitudes, and practices of antibiotic use. Twelve percent had recently taken antibiotics; 27% believed that taking antibiotics when they had a cold made them better more quickly, 32% believed that taking antibiotics when they had a cold prevented more serious illness, and 48% expected a prescription for antibiotics when they were ill enough from a cold to seek medical attention. These misguided beliefs and expectations were associated with a lack of awareness of the dangers of antibiotic use; 58% of patients were not aware of the possible health dangers. National educational efforts are needed to address these issues if patient demand for antibiotics is to be reduced.

Vanden Eng, Jodi; Hadler, James L.; Imhoff, Beth; Vugia, Duc J.; Cieslak, Paul R.; Zell, Elizabeth; Deneen, Valerie; McCombs, Katherine Gibbs; Zansky, Shelley M.; Hawkins, Marguerite A.; Besser, Richard E.



Efficacy and Tolerability of Antibiotic Combinations in Neurobrucellosis: Results of the Istanbul Study  

PubMed Central

No data on whether brucellar meningitis or meningoencephalitis can be treated with oral antibiotics or whether an intravenous extended-spectrum cephalosporin, namely, ceftriaxone, which does not accumulate in phagocytes, should be added to the regimen exist in the literature. The aim of a study conducted in Istanbul, Turkey, was to compare the efficacy and tolerability of ceftriaxone-based antibiotic treatment regimens with those of an oral treatment protocol in patients with these conditions. This retrospective study enrolled 215 adult patients in 28 health care institutions from four different countries. The first protocol (P1) comprised ceftriaxone, rifampin, and doxycycline. The second protocol (P2) consisted of trimethoprim-sulfamethoxazole, rifampin, and doxycycline. In the third protocol (P3), the patients started with P1 and transferred to P2 when ceftriaxone was stopped. The treatment period was shorter with the regimens which included ceftriaxone (4.40 ± 2.47 months in P1, 6.52 ± 4.15 months in P2, and 5.18 ± 2.27 months in P3) (P = 0.002). In seven patients, therapy was modified due to antibiotic side effects. When these cases were excluded, therapeutic failure did not differ significantly between ceftriaxone-based regimens (n = 5/166, 3.0%) and the oral therapy (n = 4/42, 9.5%) (P = 0.084). The efficacy of the ceftriaxone-based regimens was found to be better (n = 6/166 [3.6%] versus n = 6/42 [14.3%]; P = 0.017) when a composite negative outcome (CNO; relapse plus therapeutic failure) was considered. Accordingly, CNO was greatest in P2 (14.3%, n = 6/42) compared to P1 (2.6%, n = 3/117) and P3 (6.1%, n = 3/49) (P = 0.020). Seemingly, ceftriaxone-based regimens are more successful and require shorter therapy than the oral treatment protocol.

Ulu-Kilic, Aysegul; Kilic, Selim; Karahocagil, Mustafa; Shehata, Ghaydaa; Eren-Tulek, Necla; Yetkin, Funda; Celen, Mustafa Kemal; Ceran, Nurgul; Gul, Hanefi Cem; Mert, Gurkan; Tekin-Koruk, Suda; Dizbay, Murat; Inal, Ayse Seza; Nayman-Alpat, Sayg?n; Bosilkovski, Mile; Inan, Dilara; Saltoglu, Nese; Abdel-Baky, Laila; Adeva-Bartolome, Maria Teresa; Ceylan, Bahad?r; Sacar, Suzan; Turhan, Vedat; Y?lmaz, Emel; Elaldi, Nazif; Kocak-Tufan, Zeliha; Ugurlu, Kenan; Dokuzoguz, Basak; Y?lmaz, Hava; Gundes, Sibel; Guner, Rahmet; Ozgunes, Nail; Ulcay, Asim; Unal, Serhat; Dayan, Saim; Gorenek, Levent; Karakas, Ahmet; Tasova, Yesim; Usluer, Gaye; Bayindir, Yasar; Kurtaran, Behice; Sipahi, Oguz Resat; Leblebicioglu, Hakan



Diffusion and activity of antibiotics against Burkholderia pseudomallei biofilms.  


The diffusion and activity of ceftazidime (CAZ), imipenem (IPM) and trimethoprim/sulfamethoxazole (TMP/SMX) against Burkholderia pseudomallei biofilms were comparatively tested using the high biofilm-producing strain B. pseudomallei 377 and the biofilm-defective mutant B. pseudomallei M6. Biofilms were generated by inoculation of bacteria on polycarbonate membranes placed on the surface of tryptic soy agar plates. The results showed that diffusion of TMP/SMX through B. pseudomallei biofilms was similar for both strains. However, diffusion of CAZ and IPM was significantly faster through strain M6 biofilm in comparison with strain 377 biofilm. The viabilities of strain 377 biofilm were significantly higher than those observed with strain M6 for all antibiotics challenged at 4 h, suggesting that the biofilm-forming capacity may be involved in antibiotic susceptibilities in B. pseudomallei. These results re-emphasise the importance of biofilm for antibiotic resistance in B. pseudomallei. PMID:22364716

Pibalpakdee, Phannarai; Wongratanacheewin, Surasakdi; Taweechaisupapong, Suwimol; Niumsup, Pannika R



Antimicrobial activity of ceftobiprole, a novel anti-methicillin-resistant Staphylococcus aureus cephalosporin, tested against contemporary pathogens: results from the SENTRY Antimicrobial Surveillance Program (2005-2006).  


Ceftobiprole is a 1st-in-class anti-methicillin-resistant Staphylococcus aureus (MRSA) extended-spectrum cephalosporin currently in clinical trials for the treatment of complicated skin and skin structure infections (cSSSIs) and nosocomial pneumonia. This agent is also active against other prominent Gram-positive and Gram-negative pathogens, making it an attractive candidate for broad-spectrum therapy. We evaluated the in vitro potency of ceftobiprole tested against the most commonly occurring bacterial pathogens as part of a global surveillance study for the years 2005 to 2006 (>60 medical centers in North America, Latin America, and Europe). All isolates (40 675) were susceptibility tested using reference broth microdilution methods. Ceftobiprole inhibited 100% and >99% of tested S. aureus and coagulase-negative staphylococci at < or =4 and < or =8 microg/mL, respectively, although MIC90 values for oxacillin-resistant strains were 4-fold and 8-fold higher than oxacillin-susceptible isolates for the 2 groups. Ceftobiprole was also broadly active against Streptococcus pneumoniae, beta-hemolytic and viridans group streptococci, inhibiting >98% of isolates at < or =0.5 microg/mL. Although ceftobiprole was generally inactive against Enterococcus faecium, the majority of Enterococcus faecalis strains (95.7%) were inhibited at < or =4 microg/mL. This agent was similar in potency to the "3rd- and 4th-generation" cephems (MIC50 values, < or =0.06 microg/mL) for all tested Enterobacteriaceae. Although cefepime provided enhanced coverage against Klebsiella spp. (86.5% at < or =8 microg/mL versus 76.9-81.7% for ceftobiprole and ceftazidime), ceftobiprole and cefepime were superior to ceftazidime against Enterobacter spp. and Citrobacter spp. Against Pseudomonas aeruginosa, ceftobiprole was equal in potency to ceftazidime (MIC50, 2 microg/mL) and 2-fold more potent than cefepime. None of these agents inhibited >45% of Acinetobacter spp. at 8 mug/mL. Ceftobiprole is a new anti-MRSA beta-lactam with recognized activity against the most commonly occurring Enterobacteriaceae and P. aeruginosa, similar to that of extended-spectrum cephems. These characteristics warrant continued evaluation of the agent as empiric therapy for cSSSIs, and in pneumonia, especially in those institutions/regions where MRSA and P. aeruginosa may be prevalent. PMID:18385000

Fritsche, Thomas R; Sader, Helio S; Jones, Ronald N



How ?-Lactam Antibiotics Enter Bacteria: A Dialogue with the Porins  

PubMed Central

Background Multi-drug resistant (MDR) infections have become a major concern in hospitals worldwide. This study investigates membrane translocation, which is the first step required for drug action on internal bacterial targets. ?-lactams, a major antibiotic class, use porins to pass through the outer membrane barrier of Gram-negative bacteria. Clinical reports have linked the MDR phenotype to altered membrane permeability including porin modification and efflux pump expression. Methodology/Principal Findings Here influx of ?-lactams through the major Enterobacter aerogenes porin Omp36 is characterized. Conductance measurements through a single Omp36 trimer reconstituted into a planar lipid bilayer allowed us to count the passage of single ?-lactam molecules. Statistical analysis of each transport event yielded the kinetic parameters of antibiotic travel through Omp36 and distinguishable translocation properties of ?-lactams were quantified for ertapenem and cefepime. Expression of Omp36 in an otherwise porin-null bacterial strain is shown to confer increases in the killing rate of these antibiotics and in the corresponding bacterial susceptibility. Conclusions/Significance We propose the idea of a molecular “passport” that allows rapid transport of substrates through porins. Deciphering antibiotic translocation provides new insights for the design of novel drugs that may be highly effective at passing through the porin constriction zone. Such data may hold the key for the next generation of antibiotics capable of rapid intracellular accumulation to circumvent the further development MDR infections.

Molitor, Alexander; Bolla, Jean-Michel; Bessonov, Andrey N.; Winterhalter, Mathias; Pages, Jean-Marie



Expression of SHV-2  Lactamase and of Reduced Amounts of OmpK36 Porin in Klebsiella pneumoniae Results in Increased Resistance to Cephalosporins and Carbapenems  

Microsoft Academic Search

A Klebsiella pneumoniae clinical isolate was resistant to cefoxitin, cefotaxime, ceftazidime, ceftazidime- clavulanate, piperacillin-tazobactam (MICs, >256 g\\/ml in all cases), and meropenem (MIC, 16 g\\/ml) and was intermediate to imipenem (MIC, 8 g\\/ml). Decreased expression of the OmpK36 porin and expression of an SHV-2 -lactamase contributed to the observed resistance to these -lactam-containing agents. Expanded-spectrum cephalosporins play an important role

Brendan Crowley; V. J. Benedi; Antonio Domenech-Sanchez



The utilization of beet molasses as a novel carbon source for cephalosporin C production by Acremonium chrysogenum: Optimization of process parameters through statistical experimental designs  

Microsoft Academic Search

In this work, cephalosporin C (CPC) production on pilot scale fermenters of 600l capacity with 350l working volume by Acremonium chrysogenum EMCC 904 was performed. The effects of fermentation medium composition, inoculum concentration, initial pH and aeration rate on CPC production by A. chrysogenum strain was investigated by using response surface methodology (RSM). The Plackett–Burman design which involves two concentrations

Walid A. Lotfy



MICROBIOLOGY: Noninherited Resistance to Antibiotics  

NSDL National Science Digital Library

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.

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



Biological activities of two fungistatic antibiotics produced by Bacillus cereus UW85.  

PubMed Central

Cultures and culture filtrates of Bacillus cereus UW85 suppress damping-off of alfalfa caused by Phytophthora medicaginis. We studied the role in disease suppression of two antibiotics from culture filtrates of UW85 that reversibly inhibited growth of P. medicaginis. We purified the two antibiotics by cation-exchange chromatography and high-voltage paper electrophoresis and showed that one of them, designated zwittermicin A, was an aminopolyol of 396 Da that was cationic at pH 7.0; the second, designated antibiotic B, appeared to be an aminoglycoside containing a disaccharide. Both antibiotics prevented disease of alfalfa seedlings caused by P. medicaginis. Purified zwittermicin A reversibly reduced elongation of germ tubes derived from cysts of P. medicaginis, and antibiotic B caused swelling of the germ tubes. Mutants generated with Tn917 or mitomycin C treatment were screened either for antibiotic accumulation in an agar plate diffusion assay or for the ability to suppress damping-off disease of alfalfa. Of 2,682 mutants screened for antibiotic accumulation, 5 mutants were substantially reduced in antibiotic accumulation and disease-suppressive activity. Of the 1,700 mutants screened for disease-suppressive activity, 3 mutants had reduced activity and they accumulated less of both antibiotics than did the parent strain. The amount of antibiotic accumulated by the mutants was significantly correlated with the level of disease suppression. Addition of either zwittermicin A or antibiotic B to alfalfa plants inoculated with a culture of a nonsuppressive mutant resulted in disease suppression. These results demonstrate that B. cereus UW85 produces two fungistatic antibiotics that contribute to suppression of damping-off disease of alfalfa. Images

Silo-Suh, L A; Lethbridge, B J; Raffel, S J; He, H; Clardy, J; Handelsman, J



Genes for beta-lactam antibiotic biosynthesis.  


The genes pcbAB, pcbC and penDE encoding enzymes involved in the biosynthesis of penicillin have been cloned from Penicillium chrysogenum and Aspergillus nidulans. They are clustered in chromosome I (10.4 Mb) of P. chrysogenum, but they are located in chromosome II of Penicillium notatum (9.6 Mb) and in chromosome VI (3.0 Mb) of A. nidulans. Expression studies have shown that each gene is expressed as a single transcript from separate promoters. Enzyme regulation studies and gene expression analysis have provided useful information to understand the control of gene expression leading to overexpression of the genes involved in penicillin biosynthesis. Cephalosporin genes have been studied in Cephalosporium acremonium and also in cephalosporin-producing bacteria. In C. acremonium the genes involved in cephalosporin biosynthesis are separated in at least two clusters. Cluster I (pcbAB-pcbC) encodes the first two enzymes of the cephalosporin pathway which are very similar to those involved in penicillin biosynthesis. Cluster II (cefEF-cefG), encodes the last three enzymatic activities of the cephalosporin pathway. It is unknown, at this time, if the cefD gene encoding isopenicillin epimerase is linked to any of the two clusters. In cephamycin producing bacteria the genes encoding the entire biosynthetic pathway are located in a single cluster extending for about 30 kb in Nocardia lactamdurans, and in Streptomyces clavuligerus. The cephamycin clusters of N. lactamdurans and S. clavuligerus include a gene lat which encodes lysine-6-aminotransferase an enzyme involved in formation of the precursor alpha-aminoadipic acid. The N. lactamdurans cephamycin cluster includes, in addition, a beta-lactamase (bla) gene, a penicillin binding protein (pbp), and a transmembrane protein gene (cmcT) that is probably involved in secretion of the cephamycin. Little is known however about the mechanism of control of gene expression in the different beta-lactam producers. The availability of most of the structural genes provides a good basis for further studies on gene expression. This knowledge should lead in the next decade to a rational design of strain improvement procedures. The origin and evolution of beta-lactam genes is intriguing since their nucleotide sequences are extremely conserved despite their restricted distribution in the microbial world. PMID:7771766

Martín, J F; Gutiérrez, S



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


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

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



Confirmatory assay for the simultaneous detection of penicillins and cephalosporins in milk using liquid chromatography/tandem mass spectrometry.  


A high-performance liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for the detection of residues of penicillins and cephalosporins in milk has been developed. After a simple extraction with acetonitrile, the extract was directly injected into the LC/MS/MS system on a C(18) column. A gradient consisting of acetonitrile and water, each containing 0.1% formic acid, was applied. The abundant parent ions [M + H](+) produced by positive electrospray ionisation were selected for fragmentation with argon. For each compound at least one fragment was recorded with multiple reaction monitoring. The limits of detection ranged from 1.5 to 25 microg/kg and the limits of quantification ranged from 4 to 50 microg/kg. Recoveries were examined at three levels (MRL, 0.5 x MRL, 2 x MRL) and ranged from 57 to 88%. The coefficients of variation obtained for the repeatability experiments were in agreement with those specified by the Horwitz equation. Linearity was checked by injecting extracts of samples spiked with increasing amounts of the different standards ranging from 0 to 150 microg/kg. The advantage of this method over existing methods is the very simple sample pre-treatment which makes the method very suitable for routine analysis. PMID:10920362

Daeseleire, E; De Ruyck, H; Van Renterghem, R



Origins and Evolution of Antibiotic Resistance  

PubMed Central

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.

Davies, Julian; Davies, Dorothy



Development of Biodegradable Sustained Release Antibiotic Beads.  

National Technical Information Service (NTIS)

This final report details the development, preparation, and characterization of biodegradable antibiotic beads for testing in animal models. A process was developed for preparing 3-6 mm beads from antibiotics and biodegradable polymers. The process was us...

E. S. Nuwayser



Antibiotics and Allergic Disorders in Childhood  

PubMed Central

Aim: This paper explores the possible association between antibiotics prescribed in infancy and allergic disorders, mainly eczema and asthma, in childhood. Background: No-one fully understands why childhood asthma and eczema have become so common. Some authorities suggest that there may be an association between eczema and asthma and antibiotics prescribed in childhood; however, others disagree. Method/Evaluation: The available literature was reviewed to examine the links between prescribed antibiotics and childhood eczema and asthma. Findings/Key Issue: Some, but not all, research indicates that antibiotic administration in pregnancy, childbirth or infancy may be linked to childhood asthma and eczema, but much uncertainty remains. None of the papers identified stated the doses of antibiotics prescribed. In addition, we were unable to locate studies reporting the interactions between antibiotics and the developing immune system. Conclusion: Health care professionals should be selective when prescribing antibiotics. Further prospective work is needed to guide the prescribing of antibiotics in childbirth and infancy.

Jordan, Sue; Storey, Mel; Morgan, Gareth



Bacterial 'Autopsy' Could Speed Antibiotic Discovery  


... according to Pogliano, relates to the problem of antibiotic resistance. "Bacteria are becoming resistant to the drugs we ... come at a time when the problem of antibiotic resistance is getting heightened attention. The U.S. Centers for ...


Seeking and Denying Antibiotic Treatment in Pediatrics.  

National Technical Information Service (NTIS)

As had been widely documented, the U.S. and other developed nations are facing a large scale problem with antibiotic resistant bacteria. However, inappropriate prescribing of antibiotics for viral infections is common. Existing research has documented a s...

T. Stivers



Antibiotics and the burn patient.  


Infection is a major problem in burn care and especially when it is due to bacteria with hospital-acquired multi-resistance to antibiotics. Moreover, when these bacteria are Gram-negative organisms, the most effective molecules are 20 years old and there is little hope of any new product available even in the distant future. Therefore, it is obvious that currently available antibiotics should not be misused. With this aim in mind, the following review was conducted by a group of experts from the French Society for Burn Injuries (SFETB). It examined key points addressing the management of antibiotics for burn patients: when to use or not, time of onset, bactericidia, combination, adaptation, de-escalation, treatment duration and regimen based on pharmacokinetic and pharmacodynamic characteristics of these compounds. The authors also considered antibioprophylaxis and some other key points such as: infection diagnosis criteria, bacterial inoculae and local treatment. French guidelines for the use of antibiotics in burn patients have been designed up from this work. PMID:20510518

Ravat, François; Le-Floch, Ronan; Vinsonneau, Christophe; Ainaud, Pierre; Bertin-Maghit, Marc; Carsin, Hervé; Perro, Gérard



Antibiotic degradation during manure composting.  


On-farm manure management practices, such as composting, may provide a practical and economical option for reducing antibiotic concentrations in manure before land application, thereby minimizing the potential for environmental contamination. The objective of this study was to quantify degradation of chlortetracycline, monensin, sulfamethazine, and tylosin in spiked turkey (Meleagris gallopavo) litter during composting. Three manure composting treatments were evaluated: a control treatment (manure pile with no disturbance or adjustments after initial mixing), a managed compost pile (weekly mixing and moisture content adjustments), and vessel composting. Despite significant differences in temperature, mass, and nutrient losses between the composting treatments and the control, there was no difference in antibiotic degradation among the treatments. Chlortetracycline concentrations declined rapidly during composting, whereas monensin and tylosin concentrations declined gradually in all three treatments. There was no degradation of sulfamethazine in any of treatments. At the conclusion of the composting period (22-35 d), there was >99% reduction in chlortetracycline, whereas monensin and tylosin reduction ranged from 54 to 76% in all three treatments. Assuming first-order decay, the half-lives for chlortetracycline, monensin, and tylosin were 1, 17, and 19 d, respectively. These data suggest that managed compositing in a manure pile or in a vessel is not better than the control treatment in degrading certain antibiotics in manure. Therefore, low-level manure management, such as stockpiling, after an initial adjustment of water content may be a practical and economical option for livestock producers in reducing antibiotic levels in manure before land application. PMID:18453444

Dolliver, Holly; Gupta, Satish; Noll, Sally



Antibiotic Resistance: Consequences of Inaction  

Microsoft Academic Search

Bacterial resistance presents therapeutic dilemmas to clinicians worldwide. The warnings were there long ago, but too few people heeded them. Thus an emerging problem has grown to a crisis. Resistance is an ecological phenomenon stemming from the response of bacteria to the widespread use of antibiotics and their presence in the environment. While determining the consequences of inaction on the



Production and Transport of Antibiotics from CAFOs  

Microsoft Academic Search

The largest source of antibiotics in the environment is likely their application in livestock. In particular, their routine\\u000a use as growth promoters comprises the majority of antibiotic use. Antibiotic use for growth promotion is widespread in the\\u000a US, but banned in Israel, Denmark, and other parts of Europe. Antibiotics consumed by livestock are largely unmetabolized\\u000a and excreted into the environment.

Amy Pruden


Antibiotic Resistance Due to Reduced Uptake  

Microsoft Academic Search

The introduction of antibiotic therapy for the treatment of bacterial infections has led to a greatly increased human lifespan\\u000a compared to that in the pre-antibiotic era. However, a disturbing trend has also been noted in that, within a very short period\\u000a of time following the introduction of a new antibiotic, resistance to that antibiotic begins to emerge, a factor that

Joseph B. McPhee; Sandeep Tamber; Michelle D. Brazas; Shawn Lewenza; Robert E. W. Hancock


Antibiotic cost reduction by providing cost information  

Microsoft Academic Search

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%

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



Antimicrobial susceptibility testing for Klebsiella pneumoniae isolates resistant to extended-spectrum beta-lactam antibiotics.  


Detection of Klebsiella pneumoniae strains with extended-spectrum beta-lactamase (ESBL)-related resistance phenotypes is becoming important in clinical microbiology laboratories. In this study, we investigated the usefulness of three screening methods, the Etest ESBL screen, the double-disk synergy test, and the ceftazidime disk test, for identifying ESBL-producing K. pneumoniae strains. The agar dilution method was used as the standard. We also determined the in vitro activity of several new antimicrobial agents against these organisms. Strains that exhibited an increase in the minimum inhibitory concentration (MIC) to the third-generation cephalosporins or aztreonam of 2 micrograms/mL or more, but were susceptible to the three cephamycins tested, were considered to have ESBL-related resistance phenotypes. The frequency of ESBL-producing K. pneumoniae isolates (according to the disk-diffusion method) has increased markedly in recent years, from 3.4% in 1993 to 10.3% in 1997. A total of 93 preserved isolates of K. pneumoniae collected from December 1995 through March 1997 were found to be resistant to at least one of the third-generation cephalosporins (cefotaxime and ceftazidime) or aztreonam using the routine disk diffusion method. Among these isolates, 35 were classified as having an ESBL phenotype using the agar dilution method. The remaining 58 isolates were classified as cephamycin resistant, which indicated resistance to both cephamycins and third-generation cephalosporins or aztreonam. The susceptibility rates of the ESBL-producing isolates were 11% for cefotaxime, 14% for ceftazidime, and 6% for aztreonam. The susceptibility rates of these 35 isolates to imipenem, ciprofloxacin, and ofloxacin were 100%, 80%, and 86%, respectively. Both the MIC50 and MIC90 of meropenem were 0.06 microgram/mL, while the MIC50 and MIC90 of BAY 12-8039 were 0.125 and 2 micrograms/mL, respectively. Thirty-two (91%) of the 35 isolates of K. pneumoniae with the ESBL-related resistance phenotype were detected by the Etest ESBL screen, while the ceftazidime disk screen test detected 77% of these isolates, and the double-disk synergy test detected 74%. The Etest ESBL screen appears to be an acceptable, convenient, and sensitive method for the detection of ESBL-producing isolates in the clinical microbiology laboratory. PMID:9830274

Jan, I S; Hsueh, P R; Teng, L J; Ho, S W; Luh, K T



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


Methicillin-resistant Staphylococcus aureus (MRSA) induces a pro-thrombotic and pro-inflammatory milieu. Although timely antibiotic administration in MRSAsepsis 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 MRSAinfection, we examined how antibiotics inhibit MRSAinduced 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. MRSAaccelerated thrombin generation in a time- and concentration-dependent manner andinduced 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

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



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

PubMed Central

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.

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.



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

Microsoft Academic Search

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

George G. Khachatourians



Selective pressure by antibiotic use in livestock  

Microsoft Academic Search

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

Wolfgang Witte



Antibiotic Losses from Unprotected Manure Stockpiles  

Microsoft Academic Search

Manure management is a major concern in livestock production systems. Although historically the primary concerns have been nutrients and pathogens, manure is also a source of emerging contaminants, such as antibiotics, to the environment. Th ere is a growing concern that antibiotics in manure are reaching surface and ground waters and contributing to the development and spread of antibiotic resistance

Holly A. S. Dolliver; Satish C. Gupta



Antibiotics in Milk—A Review1  

Microsoft Academic Search

SUIVi I~IARY The widespread use of antibiotics has contributed to the control of diseases and the nutritional well-being of livestock. However, the use of antibiotics in the treatment of mastitis has created problems for the milk processor and consumer. Following treatment of mastitis with antibiotics, they may be found in the milk in sufficient concentrations to inhibit dairy starter microorganisms

J. L. Albright; S. L. Tuckey; G. T. Woods



Appropriate Regulation of Antibiotics in Livestock Feed  

Microsoft Academic Search

For decades, antibiotics have been widely used, saving lives and reducing suffering. Such drugs are routinely employed among both human and farm animal populations. However, scientific data now links the use of antibiotics at subtherapeutic levels in livestock feed to the spread of antibiotic resistant bacteria in the human population. After examining the current research, this Article concludes that despite

Robyn L Goforth; Carol R Goforth



Squalamine: An Aminosterol Antibiotic from the Shark  

Microsoft Academic Search

In recent years, a variety of low molecular weight antibiotics have been isolated from diverse animal species. These agents, which include peptides, lipids, and alkaloids, exhibit antibiotic activity against environmental microbes and are thought to play a role in innate immunity. We report here the discovery of a broad-spectrum steroidal antibiotic isolated from tissues of the dogfish shark Squalus acanthias.

Karen S. Moore; Suzanne Wehrli; Heinrich Roder; Mark Rogers; John N. Forrest Jr.; Donald McCrimmon; Michael Zasloff



Treatment and prevention of antibiotic associated diarrhea  

Microsoft Academic Search

Mild or severe episodes of antibiotic-associated diarrhea (AAD) are common side effects of antibiotic therapy. The incidence of AAD differs with the antibiotic and varies from 5 to 25%. The major form of intestinal disorders is the pseudomembranous colitis associated with Clostridium difficile which occurs in 10–20% of all AAD. In most cases of AAD discontinuation or replacement of the

E Bergogne-Bérézin



Antibiotic treatment for acute otitis media  

Microsoft Academic Search

The major problems encountered in the antibiotic therapy of acute otitis media (AOM) are the tremendous increase in the resistance to antibiotics of its main pathogens and the lack of tight criteria (taking into consideration, as a major determinant, the eradication of the pathogens from the middle ear fluid) in the selection of the appropriate antibiotic drugs for the treatment

Eugene Leibovitz; Ron Dagan



Differences in antibiotic prescribing in paediatric outpatients  

Microsoft Academic Search

Antibiotics represent the most widely prescribed therapeutic agents. The prevalence of drug prescription differs across age, with preschool children being most exposed to antibiotic drugs, especially in the community setting. A review with the aim to compare the profile of antibiotic drug prescription at the multinational, national and regional levels was performed. This overview of drug-utilisation studies found quantitative and

Antonio Clavenna; Maurizio Bonati



A call for antibiotic alternatives research.  


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

Stanton, Thaddeus B



The determinants of the antibiotic resistance process  

Microsoft Academic Search

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 com- prehensively review the

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




Microsoft Academic Search

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.

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



National campaigns to improve antibiotic use  

Microsoft Academic Search

High levels of antibiotic consumption are driving levels of bacterial resistance that threaten public health. Nonetheless, antibiotics still provide highly effective treatments for common diseases with important implications for human health. The challenge for public education is to achieve a meaningful reduction in unnecessary antibiotic use without adversely affecting the management of bacterial infections. This paper focuses on the lessons

Herman Goossens; Didier Guillemot; Matus Ferech; Benoit Schlemmer; Michiel Costers; Marije van Breda; Lee J. Baker; Otto Cars; Peter G. Davey



European Antibiotic Awareness Day 2011: antibiotics--a powerful tool and a dwindling resource.  


The increasing resistance of microorganisms to a range of antibiotics is of growing concern to healthcare professionals world wide. A correlation between antibiotic resistance and high prescribing rates has long been established. However, despite numerous awareness campaigns, antibiotic prescribing rates are still high and increasing in many countries including the UK. The European Antibiotic Awareness Day on 18 November 2011 provides a platform to remind prescribers and the general public about the dangers of antibiotic overuse. The key message is to encourage prudent antibiotic prescribing so that antibiotics remain a safe and effective resource for the future. PMID:21926061

Zenner, Dominik; Shetty, Nandini



Evidence-based adjustment of antibiotic in pediatric complicated appendicitis in the era of antibiotic resistance  

Microsoft Academic Search

Introduction  Antibiotic resistance is a global issue especially in developed areas. With the emergence of antibiotic resistant-bacteria,\\u000a the traditional choice of broad spectrum antibiotics may not be effective in complicated appendicitis. We herein report the\\u000a bacteriology and antibiotic susceptibility of intra-operative peritoneal culture in children with acute appendicitis in Hong\\u000a Kong. This may guide us to adjust the choice of antibiotics

Kin Wai Edwin Chan; Kim Hung Lee; Jennifer Wai Cheung Mou; Sing Tak Cheung; Jennifer Dart Yin Sihoe; Yuk Him Tam



Shift in antibiotic prescribing patterns in relation to antibiotic expenditure in paediatrics  

Microsoft Academic Search

In paediatrics, antibiotics are among the most commonly prescribed drugs. Because of an overall rise in health care costs,\\u000a lack of uniformity in drug prescribing and the emergence of antibiotic resistance, monitoring and control of antibiotic use\\u000a is of growing concern and strict antibiotic policies are warranted. Before such a policy can be implemented, detailed knowledge\\u000a of antibiotic prescribing patterns

M. A. van Houten; M. Laseur; J. L. L. Kimpen



Antibiotic Resistance: A Concern to Veterinary and Human Medicine  

Microsoft Academic Search

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

Sitaram Aryal


Successful treatment of total hip and knee infection with articulating antibiotic components: a modified treatment method.  


There are many problems associated with the use of articulating antibiotic cement spacer blocks and articulating components in the two-stage treatment of total hip replacement and total knee replacement infections. These include loss of motion during and after treatment, bone loss, generation of cement debris, inadequate dosing of cement with the appropriate antibiotic, and biologic failure. Forty-four patients with 54 consecutive periprosthetic hip and knee infections (31 septic total knee arthroplasties and 23 septic total hip arthroplasties) had treatment with a modified two-stage reimplantation protocol using articulating components made of antibiotic-cement-only prosthetic components and antibiotic-cement-covered prosthetic components between January 1995 and May 2002. Second-stage revision, after six weeks of parenteral antibiotics, was completed an average of 84 days after the first stage. A minimum two-year followup after final treatment is evaluated. One of the 23 total hip replacement infections persisted or recurred with the original organism(s) after treatment (95.7% success) as did two of the 31 total knee replacement infections (93.5% success). Combined success rate was 94.4%. This modified treatment method incorporates early range of motion during first-stage treatment with articulating components that provide local high-dose elution of broad-spectrum antibiotics, provides the flexibility of customizing the antibiotic cement components with culture-directed antibiotics, and results in a high biologic success rate. PMID:15552134

Evans, Richard P



Acne vulgaris: a review of antibiotic therapy.  


Antibiotic therapy has been integral to the management of inflammatory acne vulgaris for many years. Systemic antibiotics work via antibacterial, anti-inflammatory and immunomodulatory modes of action, and have been found to be useful in managing moderate-to-severe acne. Commonly prescribed antibiotics include tetracyclines, erythromycin and trimethoprim, with or without sulfamethoxazole. In selecting the appropriate antibiotic for patients needing to receive topical or systemic antibiotic therapy, the clinician should take into account the severity of the acne, cost-effectiveness, the safety profile of the drug and the potential for development of resistance. The widespread and long-term use of antibiotics over the years has unfortunately led to the emergence of resistant bacteria. The global increase in the antibiotic resistance of Propionibacterium acnes may be a significant contributing factor in treatment failures. It is therefore essential that clinicians prescribing antibiotics for the treatment of acne adopt strategies to minimise further development of bacterial resistance. This includes addressing compliance issues, using combination therapies, avoiding prolonged antibiotic treatment, and avoiding concomitant topical and oral antibiotics with chemically dissimilar antibiotics. PMID:15794732

Tan, Audrey W; Tan, Hiok-Hee



The N-terminal Nucleophile Serine of Cephalosporin Acylase Executes the Second Autoproteolytic Cleavage and Acylpeptide Hydrolysis*  

PubMed Central

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 Glu159 and Gly160, and detected the corresponding 10-aa spacer 160GDPPDLADQG169 of CA mutants. The site of the second cleavage depended on Glu159: 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 Ser170 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 Glu159 and Ser170.

Yin, Jun; Deng, Zixin; Zhao, Guoping; Huang, Xi



Use of antibiotics in plant agriculture.  


Antibiotics are essential for control of bacterial diseases of plants, especially fire blight of pear and apple and bacterial spot of peach. Streptomycin is used in several countries; the use of oxytetracycline, oxolinic acid and gentamicin is limited to only a few countries. Springtime antibiotic sprays suppress pathogen growth on flowers and leaf surfaces before infection; after infection, antibiotics are ineffective. Antibiotics are applied when disease risk is high, and consequently the majority of orchards are not treated annually. In 2009 in the United States, 16,465 kg (active ingredient) was applied to orchards, which is 0.12% of the total antibiotics used in animal agriculture. Antibiotics are active on plants for less than a week, and significant residues have not been found on harvested fruit. Antibiotics have been indispensable for crop protection in the United States for more than 50 years without reports of adverse effects on human health or persistent impacts on the environment. PMID:22849276

Stockwell, V O; Duffy, B



[Antibiotic management in oral medicine].  


Although antibiotic therapy cannot replace surgical drainage of pus and ablation of necrotic tissue, it plays an essential role in the treatment of buccodental infections by preventing vascular dissemination responsible for bacterial endocarditis and infection of cardiovascular and hip prostheses. It also prevents complications due to local spread of infection (sinus cavernosus thrombosis, osteomyelitis, maxillary sinusitis, Ludwig's angina). Bacteriology of stomatologic infections of dental origin is complex and usually reflects buccal endogenous flora. Infections due to anaerobic germs are increasing in frequency in line with streptococcal affections. The choice of effective antibacterial treatment is complicated by the difficulty in isolating responsible germs and the need for diffusion of the antibiotic into bone and tonsillar tissues. Penicillin G, ampicillin and amoxicillin, possibly combined with a betalactamase inhibitor, macrolide and imidaxole derivative, are products responding best to bacteriologic and pharmacokinetic criteria for treatment of buccodental infections. PMID:3868812

Modai, J