Note: This page contains sample records for the topic generation cephalosporin antibiotic from
While these samples are representative of the content of,
they are not comprehensive nor are they the most current set.
We encourage you to perform a real-time search of
to obtain the most current and comprehensive results.
Last update: August 15, 2014.

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.



Extraction and purification of cephalosporin antibiotics.  


The biologically active natural and semisynthetic cephalosporin antibiotics require proper methods of extraction and purification for their isolation and subsequent pharmacological studies. This article reviews the various methods useful for extraction and purification of individual compounds as well as the enzymes involved in their biosynthesis. Applicability of the methods for downstream processing of the spent medium has been critically analysed. Adsorption chromatography, particularly with reverse phase materials, in combination with membrane separation is the most successful technique for extraction as well as purification of most of the enzymes and individual compounds. Techniques such as reactive extraction in liquid membrane, non-dispersive extraction in hollow fiber membrane and aqueous two-phase extraction are likely to emerge in new generation processes. Finally, some aspects of process design and scale-up have been discussed, highlighting the research needs of pragmatic importance. PMID:8939060

Ghosh, A C; Mathur, R K; Dutta, N N



Transport of cephalosporin antibiotics in rat renal basolateral membranes.  


Transport mechanisms of cephalosporin antibiotics in rat renal basolateral membranes have been studied in isolated membrane vesicles. Uptake of [14C]p-aminohippurate, a typical organic anion, by basolateral membrane vesicles was enhanced when membrane vesicles were preloaded with unlabelled p-aminohippurate (counter-transport). Cephalosporins such as cephradine, cephalexin, and cefazolin inhibited the counter-transport of [14C]p-aminohippurate, as did unlabelled p-aminohippurate and probenecid. In contrast, cephalexin did not affect the uptake of [3H]tetraethylammonium, an organic cation, by basolateral membrane vesicles. These results suggest that most cephalosporins are transported via organic anion transport systems in rat renal basolateral membranes. PMID:2576053

Takano, M; Okano, T; Inui, K; Hori, R



Perspectives in liquid membrane extraction of cephalosporin antibiotics.  


In this paper an overview of the developments in liquid membrane extraction of cephalosporin antibiotics has been presented. The principle of reactive extraction via the so-called liquid-liquid ion exchange extraction mechanism can be exploited to develop liquid membrane processes for extraction of cephalosporin antibiotics. The mathematical models that have been used to simulate experimental data have been discussed. Emulsion liquid membrane and supported liquid membrane could provide high extraction flux for cephalosporins, but stability problems need to be fully resolved for process application. Non-dispersive extraction in hollow fiber membrane is likely to offer an attractive alternative in this respect. The applicability of the liquid membrane process has been discussed from process engineering and design considerations. PMID:11783841

Sahoo, G C; Dutta, N N



Tetracycline derivatives and ceftriaxone, a cephalosporin antibiotic, protect neurons against apoptosis induced by ionizing radiation.  


DNA damage induced by low doses of ionizing radiation causes apoptosis, which is partially mediated via the generation of free radicals. Both free radicals and apoptosis are involved in the majority of brain diseases, including stroke, Alzheimer's disease and amyotrophic lateral sclerosis. Because previous studies have shown that tetracycline derivatives doxycycline and minocycline have anti-inflammatory effects and are protective against brain ischemia, we studied whether minocycline and doxycycline or ceftriaxone, a cephalosporin antibiotic with the potential to inhibit excitotoxicity, protect neurons against ionizing radiation in primary cortical cultures. A single dose of 1 Gy significantly increased lactate dehydrogenase release, induced DNA fragmentation in neurons and triggered microglial proliferation. Treatment with minocycline (20 nM), doxycycline (20 nM) and ceftriaxone (1 microM) significantly reduced irradiation-induced lactate dehydrogenase release and DNA fragmentation. The most efficient protection was achieved by minocycline treatment, which also inhibited the irradiation-induced increase in microglial cell number. Our results suggest that some tetracycline derivatives, such as doxycycline and minocycline, and ceftriaxone, a cephalosporin derivative, protect neurons against apoptotic death. PMID:11579149

Tikka, T; Usenius, T; Tenhunen, M; Keinänen, R; Koistinaho, J



Increasing use of third-generation cephalosporins for pneumonia in the emergency department: may some prescriptions be avoided?  


Third-generation cephalosporins are used to treat inpatients with community-acquired pneumonia. Some of these prescriptions may be avoided, i.e. replaced by agents less likely to promote ESBL-mediated resistance. Our objectives were to assess the recent trend of third-generation cephalosporins use for pneumonia in the emergency department, and the proportion of avoidable prescriptions. This was a retrospective study of patients treated for community-acquired pneumonia in an emergency department, and subsequently hospitalized in non ICU wards. Third-generation cephalosporin prescriptions were presumed unavoidable if they met both criteria: (i) age???65 yr or comorbid condition, and (ii) allergy or intolerance to penicillin, or failure of penicillin first-line therapy, or treatment with penicillin in three previous months. Prescriptions were otherwise deemed avoidable. The proportion of patients treated with a third generation cephalosporin increased significantly from 13.9 % (6.9-24.1 %) in 2002 to 29.5 % (18.5-42.6 %) in 2012 (OR?=?1.07 [1.01-1.14] , P?=?0.02). This increase was independent from other factors associated with the prescription of a third-generation cephalosporin (immunocompromising condition, antibacterial therapy in three previous months, fluid resuscitation and REA-ICU class). Treatment with third-generation cephalosporin was avoidable in 118 out of 147 patients (80.3 % [72.7-86.2 %]). On day 7 after admission in the ED, treatment with third-generation cephalosporins was stopped or de-escalated in, respectively, 17 % and 32 % of patients. Antibiotic stewardship programs should be implemented to restrict the third-generation cephalosporins use for pneumonia in the emergency department. PMID:24442608

Goffinet, N; Lecadet, N; Cousin, M; Peron, C; Hardouin, J-B; Batard, E; Montassier, E



Application of Thin-Layer Chromatography to High-Performance Liquid Chromatographic Separation of Steroidal Hormones and Cephalosporin Antibiotics  

Microsoft Academic Search

High-performance liquid chromatographic (HPLC) separation of steroidal hormones and cephalosporin antibiotics was investigated by adsorption chromatography and reversed-phase chromatography, respectively.Prior to the HPLC separation of these pharmaceuticals, silica gel thin-layer adsorption chromatography of steroidal hormones and reversed-phase thin-layer partition chromatography of cephalosporin antibiotics with chemically bonded dimethylsilyl silica gel were performed in order to obtain suitable HPLC separation systems.In the

T. Okumura



Case report: Long-standing complex regional pain syndrome relieved by a cephalosporin antibiotic.  


We describe a young woman who had had treatment-refractory complex regional pain syndrome (CRPS) for 6years before receiving antibiotic treatment with cefadroxil (a cephalosporin derivative) for a minor infection. Cefadroxil reduced the patient's pain and motor dysfunction (dystonia and impaired voluntary movement) within days; the pain and motor disorder returned when cefadroxil was discontinued; and both again abated when cefadroxil was re-instituted. The patient has now had symptom relief for more than 3years on continuing cefadroxil therapy. We discuss this case in the context of previous reports of antibiotic treatment relieving neuropathic pain in experimental animals. PMID:24667741

Ware, Mark A; Bennett, Gary J



[A comparative study of liposome-incorporated beta-lactam antibiotics, fluoroquinolones and cephalosporin conjugates with fluoroquinolones].  


Beta-lactam antibiotics (some penicillins and cephalosporins), a fluorquinolone (pefloxacin) and cephalosporin conjugates with fluorquinolones were liposome-encapsulated by the method of detergent dialysis. Under the experimental conditions the entrapment of the beta-lactams and pefloxacin to liposomes did not exceed 20 and 12.5 per cent of the initial quantity respectively. The liposome entrapment of the cephalosporin conjugates with fluorquinolones was much higher. The entrapment of the cefotaxime conjugate with ciprofloxacin amounted to 40 per cent and that of the cefamandol conjugate with pefloxacin amounted to 95 per cent of the initial quantity. PMID:8085906

Griaznova, N S; Beliavskaia, I V; Afonin, V I; Zinchenko, E Ia; Sazykin, Iu O; Navashin, S M



Phototransformation of cephalosporin antibiotics in an aqueous environment results in higher toxicity.  


Photodegradation may be the most important elimination process for cephalosporin antibiotics in surface water. Cefazolin (CFZ) and cephapirin (CFP) underwent mainly direct photolysis (t(1/2) = 0.7, 3.9 h), while cephalexin (CFX) and cephradine (CFD) were mainly transformed by indirect photolysis, which during the process a bicarbonate-enhanced nitrate system contributed most to the loss rate of CFX, CFD, and cefotaxime (CTX) (t(1/2) = 4.5, 5.3, and 1.3 h, respectively). Laboratory data suggested that bicarbonate enhanced the phototransformation of CFD and CFX in natural water environments. When used together, NO(3)(-), HCO(3)(-), and DOM closely simulated the photolysis behavior in the Jingmei River and were the strongest determinants in the fate of cephalosporins. TOC and byproducts were investigated and identified. Direct photolysis led to decarboxylation of CFD, CFX, and CFP. Transformation only (no mineralization) of all cephalosporins was observed through direct photolysis; byproducts were found to be even less photolabile and more toxic (via the Microtox test). CFZ exhibited the strongest acute toxicity after just a few hours, which may be largely attributed to its 5-methyl-1,3,4-thiadiazole-2-thiol moiety. Many pharmaceuticals were previously known to undergo direct sunlight photolysis and transformation in surface waters; however, the synergistic increase in toxicity caused by this cocktail (via pharmaceutical photobyproducts) cannot be ignored and warrants future research attention. PMID:23062112

Wang, Xiao-Huan; Lin, Angela Yu-Chen



An assessment of the hidden and total antibiotic costs of four parenteral cephalosporins.  


The aim of this study was to compare the hidden costs, and their impact on total antibiotic costs, of ceftriaxone therapy with those of cefotaxime, ceftazidime and cefuroxime in nosocomial infection. The total antibiotic costs of 7-day standard courses of the 4 cephalosporins were compared. The costs were divided into 3 parts: (i) the cost of the drug itself; (ii) the preparation and administration (labour) costs; and (iii) the consumables and waste costs. The latter 2 costs together comprised the hidden cost of an antibiotic course. Hidden costs were higher for cefotaxime, ceftazidime and cefuroxime, which are normally administered 3 times a day, than for ceftriaxone, which is administered once daily. The percentage contribution of hidden costs to total antibiotic costs increased with decreasing antibiotic cost, and were lower with higher dosages of all antibiotics. With cefotaxime, ceftazidime and cefuroxime, and with ceftriaxone at the lower dosage given by bolus intravenous (IV) injection, the labour component of hidden costs exceeded the consumables/waste component. However, when costs were calculated for ceftriaxone administered at the higher dosage by IV infusion, the costs of consumables and waste were greater than the labour costs. Ceftriaxone had the lowest hidden costs of all the antibiotics studied. The total antibiotic cost of low dosage ceftriaxone (1 g per dose) was comparable with that of cefuroxime, and was substantially less than the costs of cefotaxime and ceftazidime. At the high ceftriaxone dosage (2g per dose), the total antibiotic cost of cefuroxime was less than that of ceftriaxone; however, the total antibiotic cost of ceftriaxone remained substantially less than that of cefotaxime or ceftazidime. PMID:10160082

Smyth, E T; Barr, J G; O'Neill, C A; Hogg, G M



Antibiotic prophylaxis in vascular surgery: pharmacokinetic study of four commonly used cephalosporins.  


Plasma levels of antibiotics often do not correlate well with their tissue levels. To determine optimal antibiotic coverage for prophylactic effect in vascular surgery, we studied the tissue pharmacokinetics of four cephalosporins in dogs: cefazolin, cefoxitin, cefamandole, and moxalactam for 3 hours after a single (25 mg/kg) intravenous injection. The minimal inhibitory concentration (MIC) of these antibiotics for the three most common pathogens involved in graft infections (Staphylococcus aureus, S. albus, and Escherichia coli) and their tissue concentration (TC) in the plasma, muscle, subcutaneous tissue, and aortic wall were assayed. The data are presented as TC/MIC ratio. Cefoxitin and moxalactam failed to achieve an effective therapeutic TC/MIC ratio (greater than 10) for S. aureus and S. albus in all the tissues studied whereas cefoxitin and cefamandole were above therapeutic levels. All antibiotics achieved an effective therapeutic ratio against E. coli, but cefamandole performed better (p less than 0.05) than cefoxitin; the latter reached effective levels at 3 hours. Cefamandole attained the most effective bioactive aortic tissue levels when the three most common pathogens were considered together and should therefore be considered as an antibiotic agent of choice for prophylaxis in vascular surgery. PMID:3512862

Fradet, G; Brister, S; Richards, G K; Prentis, J; Brown, R A; Chiu, R C; Mulder, D S



Renal and hepatic function in rats treated with cyclosporin A in combination with gentamicin or cephalosporin antibiotics.  


Sprague-Dawley rats received cyclosporin A (25 mg/kg) together with either the aminoglycoside gentamicin (50 mg/kg) or one of 3 cephalosporin antibiotics (100 mg/kg) daily for 14 days. Only minor impairment of renal or hepatic function was observed when either cyclosporin A or gentamicin was given on its own and no abnormality was seen in response to cephalosporins. However, concomitant administration of cyclosporin A and gentamicin caused acute renal failure, accompanied by cyclosporin A-induced damage to the proximal straight tubule and gentamicin-induced proximal convoluted tubular cell necrosis. In contrast, the structural abnormalities present in the 3 groups given cephalosporins in addition to cyclosporin A were attributable only to the immune suppressant. Liver functional changes previously found only at higher doses of cyclosporin A were observed in the cyclosporin A/gentamicin group and there was some evidence of possible interactions between cyclosporin A and each cephalosporin affecting liver function. The results indicate that treatment of infection with cephalosporin antibiotics or a less nephrotoxic aminoglycoside is preferable to gentamicin in cyclosporin A-treated patients. PMID:6661399

Whiting, P H; Thomson, A W; Simpson, J G



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

PubMed Central

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



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



Biosynthesis of Cephalosporin C  

PubMed Central

A series of complex and synthetic media have been developed that are suitable for the production of cephalosporin C and cephalosporin N by a mutant strain of Cephalosporium (C.M.I. 49,137). dl-Methionine increased the yield of both antibiotics, with more effect on cephalosporin N. l-Cystine had a greater enhancing effect on formation of cephalosporin C than on formation of cephalosporin N in synthetic media; serine increased yields of cephalosporin C under certain conditions. Disaccharides or polysaccharides appeared to be the best source for carbohydrates. No evidence was found for precursor action such as is found in penicillin fermentations. The ability of resting cells to produce antibiotic was demonstrated.

Ott, J. L.; Godzeski, C. W.; Pavey, D.; Farran, J. D.; Horton, D. R.



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

PubMed Central

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

Renvoise, Aurelie; Decre, Dominique; Amarsy-Guerle, Rishma; Huang, Te-Din; Jost, Christelle; Podglajen, Isabelle; Raskine, Laurent; Genel, Nathalie; Bogaerts, Pierre; Jarlier, Vincent



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



Symposium on antimicrobial therapy. IV. The cephalosporins.  


Hopefully this review has brought some cephalosporin contentment to replace cephalosporin confusion. From the classification of these antibiotics in Table 1, we have made some significant reductions. One should know how to use cefazolin for staphylococcal/streptococcal infections and for surgical prophylaxis. One should know that cephalexin is massively overused, and really now not all that useful an agent. Cefuroxime is a useful agent for beta-lactamase producing H. influenzae infections. Cefotetan has a role in surgical prophylaxis in ob/gyn and represents the best antianaerobic activity of the cephalosporins; although no cephalosporin is a primary drug for anaerobic infections. Cefuroxime axetil or cefprozil can be useful for comparatively minor infections due to beta-lactamase producing H. influenzae. A third generation cephalosporin represents a reasonable alternative, in certain situations, to aminoglycoside therapy for infections due to multiply drug-resistant Gram-negative bacilli. Ceftazidime is an alternative antipseudomonal beta-lactam antibiotic. Despite the lack of indications for use of cephalosporins as drugs of choice, rational use of these agents can provide safe, effective, and efficient therapy for a variety of infectious diseases. They will likely remain an important part of the physicians' antimicrobial armamentarium for the foreseeable future. PMID:8426246

Greenfield, R A



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



Diagnosis and management of immediate hypersensitivity reactions to cephalosporins.  


Cephalosporins are one of the most commonly prescribed classes of antibiotics. Immediate IgE-mediated hypersensitivity reactions have been reported with use of a specific cephalosporin, as a cross-reaction between different cephalosporins or as a cross-reaction to other ?-lactam antibiotics, namely, penicillin. Historically, frequent reports of anaphylaxis following administration of first- and second-generation cephalosporins to patients with a history of penicillin allergy led to the belief of a high degree of allergic cross-reactivity. More recent evidence reveals a significantly lower risk of cross-reactivity between penicillins and the newer-generation cephalosporins. The current thought is that a shared side chain, rather than the ?-lactam ring structure, is the determining factor in immunologic cross-reactivity. Understanding the chemical structure of these agents has allowed us to identify the allergenic determinants for penicillin; however, the exact allergenic determinants of cephalosporins are less well understood. For this reason, standardized diagnostic skin testing is not available for cephalosporins as it is for penicillin. Nevertheless, skin testing to the cephalosporin in question, using a nonirritating concentration, provides additional information, which can further guide the work-up of a patient suspected of having an allergy to that drug. Together, the history and the skin test results can assist the allergist in the decision to recommend continued drug avoidance or to perform a graded challenge versus an induction of tolerance procedure. PMID:23546989

Dickson, Scott D; Salazar, Kimberly C



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



Rapid and sensitive high-performance liquid chromatographic determination of four cephalosporin antibiotics in pharmaceuticals and body fluids.  


A rapid, accurate and sensitive method has been developed and validated for the quantitative simultaneous determination of four cephalosporins, cephalexin and cefadroxil (first-generation), cefaclor (second-generation) and cefataxim (third-generation), in pharmaceuticals as well as in human blood serum and urine. A Spherisorb ODS-2 250 x 4-mm, 5-microm analytical column was used with an eluting system consisting of a mixture of acetate buffer (pH 4.0)-CH(3)OH 78-22% (v/v) at a flow-rate 1.2 ml/min. Detection was performed with a variable wavelength UV-Vis detector at 265 nm resulting in limit of detection of 0.2 ng for cefadroxil and cephalexin, but only 0.1 ng for cefotaxime and cefaclor per 20-microl injection. Hydrochlorothiazide (HCT) (6-chloro-3,4-dihydro-7 sulfanyl-2H-1,2,4-benzothiadiazine-1-1-dioxide) was used as internal standard at a concentration of 2 ng/microl. A rectilinear relationship was observed up to 8, 5, 12 and 35 ng/microl for cefadroxil, cefotaxime, cefaclor, cephalexin, respectively. Analysis time was less than 7 min. The statistical evaluation of the method was examined by means of within-day repeatability (n=8) and day-to-day precision (n=9) and was found to be satisfactory with high accuracy and precision. The method was applied to the determination of the cephalosporins in commercial pharmaceuticals and in biological fluids: human blood serum after solid-phase extraction and urine simply after filtration and dilution. Recovery of analytes in spiked samples was in the range from 76.3 to 112.0%, over the range of 1-8 ng/microl. PMID:12668080

Samanidou, V F; Hapeshi, E A; Papadoyannis, I N



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

PubMed Central

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

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



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


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

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



The Study of Genetic Relationship Among Third Generation Cephalosporin-resistant Salmonella enterica Strains by ERIC-PCR  

PubMed Central

Background and Objectives: Salmonella is an important food-borne pathogen responsible for disease in humans and animals. The aim of this study was to investigate the genetic relationship among third generation cephalosporin-resistant Salmonella enterica strains by Enterobacterial Repetitive Intergenic Consensus (ERIC)-PCR. Methods: The study included all Salmonella isolates obtained from clinical cases in a pediatric hospital in Tehran, Iran during 2006 to 2009. Antimicrobial susceptibility testing was performed according to the Clinical and Laboratory Standards Institute. The genetic relationship between third generation cephalosporins-resistant Salmonella enterica strains was determined using ERIC-PCR. Results: Of 136 Salmonella enterica isolates recovered from pediatric patients, six isolates including four Salmonella enterica serotype Infantis and two Salmonella enterica serotype Enteritidis showed an extended-spectrum cephalosporins resistant phenotype. ERIC-PCR differentiated Salmonella enterica serotypes Infantis and Enteritidis into 2 distinct clusters arbitrarily named as E1 and E2. Profile E1 was found in two Salmonella enterica serotype Enteritidis isolates, and profile E2 was found in four Salmonella enterica serotype Infantis isolates. Conclusion: Extended-spectrum cephalosporins resistant Salmonella could be attributed to a few predominant serotypes including Enteritidis and Infantis in this study. Genetic analysis using ERIC-PCR showed that closely related clones are responsible for the occurrence of extended-spectrum cephalosporins resistant Salmonella infection in Tehran.

Ranjbar, Reza; Naghoni, Ali; Yousefi, Soheila; Ahmadi, Ali; Jonaidi, Nematollah; Panahi, Yunes



Cefotetan: a second-generation cephalosporin active against anaerobic bacteria. Committee on Antimicrobial Agents, Canadian Infectious Disease Society.  

PubMed Central

OBJECTIVE: To offer guidelines for the use of cefotetan, a cephamycin antibiotic, in order to minimize its overprescription. OPTIONS: Clinical practice options considered were treatment of infections with the use of second- and third-generation cephalosporins, carbapenems such as imipenem as well as combination regimens of agents active against anaerobic bacteria, such as metronidazole or clindamycin with an aminoglycoside. OUTCOMES: In order of importance: efficacy, side effects and cost. EVIDENCE: A MEDLINE search of articles published between January 1982 and December 1993. In-vitro and pharmacokinetic studies published in recognized peer-reviewed journals that used recognized standard methods with appropriate controls were reviewed. For results of clinical trials, the reviewers emphasized randomized double-blind trials with appropriate controls. VALUES: The Antimicrobial Agents Committee of the Canadian Infectious Disease Society (CIDS) and a recognized expert (M.J.G.) recommended use of cefotetan to prevent and treat infections against which it has proved effective in randomized controlled trials. BENEFITS, HARMS AND COSTS: These guidelines should lead to less inappropriate prescribing of cefotetan, with its attendant costs and risk of development of resistant bacteria. RECOMMENDATIONS: Cefotetan could be considered an alternative single agent for prophylaxis of infection in patients undergoing elective bowel surgery. It may be used to treat patients with acute pelvic inflammatory disease and endometritis. VALIDATION: This article was prepared, reviewed and revised by the Committee on Antimicrobial Agents of the CIDS. It was then reviewed by the Council of the CIDS, and any further necessary revisions were made by the chairman of the committee.

Gribble, M J



Association of veterinary third-generation cephalosporin use with the risk of emergence of extended-spectrum-cephalosporin resistance in Escherichia coli from dairy cattle in Japan.  


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

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



Comprehensive analysis of ß-lactam antibiotics including penicillins, cephalosporins, and carbapenems in poultry muscle using liquid chromatography coupled to tandem mass spectrometry.  


A comprehensive method for the quantitative residue analysis of trace levels of 22 ß-lactam antibiotics, including penicillins, cephalosporins, and carbapenems, in poultry muscle by liquid chromatography in combination with tandem mass spectrometric detection is reported. The samples analyzed for ß-lactam residues are hydrolyzed using piperidine in order to improve compound stability and to include the total residue content of the cephalosporin ceftifour. The reaction procedure was optimized using a full experimental design. Following detailed isotope labeling, tandem mass spectrometry studies and exact mass measurements using high-resolution mass spectrometry reaction schemes could be proposed for all ß-lactams studied. The main reaction occurring is the hydrolysis of the ß-lactam ring under formation of the piperidine substituted amide. For some ß-lactams, multiple isobaric hydrolysis reaction products are obtained, in accordance with expectations, but this did not hamper quantitative analysis. The final method was fully validated as a quantitative confirmatory residue analysis method according to Commission Decision 2002/657/EC and showed satisfactory quantitative performance for all compounds with trueness between 80 and 110% and within-laboratory reproducibility below 22% at target level, except for biapenem. For biapenem, the method proved to be suitable for qualitative analysis only. PMID:23430185

Berendsen, Bjorn J A; Gerritsen, Henk W; Wegh, Robin S; Lameris, Steven; van Sebille, Ralph; Stolker, Alida A M; Nielen, Michel W F



National Prevalence of Resistance to Third-Generation Cephalosporins in Escherichia coli Isolates from Layer Flocks in France  

PubMed Central

Resistance of Escherichia coli to third-generation cephalosporin (3GC) in fecal samples representative of French egg production was studied. The susceptibility to cefotaxime of E. coli isolates obtained by culture on nonselective media was determined. Twenty-two nonsusceptible isolates were obtained (7.51%; 95% confidence interval, 4.49 to 10.54%), the majority of which came from young birds. Most isolates carried a blaCTX-M-1 group gene, and a few carried a blaCMY-2-like gene. Control of 3GC resistance in laying hens is needed.

Chauvin, Claire; Le Devendec, Laetitia; Jouy, Eric; Le Cornec, Maena; Francart, Sylvie; Marois-Crehan, Corinne



Antibiotic susceptibility of bacteria most commonly isolated from bone related infections: the role of cephalosporins in antimicrobial therapy  

Microsoft Academic Search

Bone infections, which can be acute or chronic, often require aggressive antibiotic therapy, whether treated at home or in the community. Surveillance programmes are essential tools in the monitoring of antimicrobial resistance and can act as a resource to maintain effective prescribing. The Surveillance Network® (TSN®), which collects organism and patient-specific data from a network of laboratories across the United

Mark E Jones; James A Karlowsky; Deborah C Draghi; Clyde Thornsberry; Daniel F Sahm; Dilip Nathwani



Carrier-mediated transport of cefixime, a new cephalosporin antibiotic, via an organic anion transport system in the rat renal brush-border membrane.  


The renal excretion mechanism of cefixime, a newly developed and p.o. effective cephalosporin antibiotic, was investigated by using the renal brush-border membrane vesicles from the rat kidney cortex. The initial uptake rate of cefixime into an osmotically sensitive vesicular space showed concentration and temperature dependencies, indicating the presence of a carrier-mediated transport mechanism for cefixime. Kinetic parameters for apparently saturable and nonsaturable components were evaluated as follows: maximum uptake rate was 7.32 +/- 1.07 nmol/30 sec/mg of protein; Michaelis constant was 7.35 +/- 2.04 mM; and the first-order rate constant was 0.34 +/- 0.02 nmol/30 sec/mg of protein per mM. The uptake was not affected by an inward-directed gradient of Na+, K+, Li+, Rb+ or H+. In contrast, the initial uptake rate was enhanced by an inside-positive membrane potential imposed by valinomycin. Although amino acids, dipeptides and organic cations had no effects on the uptake of cefixime, organic anions such as probenecid and p-aminohippuric acid and anion transport inhibitors such as 4,4'-diisothiocyano-stilbene-2,2'-disulfonic acid and furosemide reduced the uptake significantly. Twenty beta-lactam antibiotics including both zwitter-ionic and anionic derivatives inhibited significantly the uptake of cefixime. Furthermore, by adding probenecid in the extravesicular medium, an efflux of cefixime from the brush-border membrane vesicles was enhanced significantly at the initial stage. Benzylpenicillin, cephalothin and cephradine also enhanced an efflux of cefixime to the same extent as observed by the addition of probenecid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3392660

Tamai, I; Tsuji, A; Kin, Y



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


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

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



Pharmacodynamics of TD-1792, a novel glycopeptide-cephalosporin heterodimer antibiotic used against Gram-positive bacteria, in a neutropenic murine thigh model.  


TD-1792 is a novel glycopeptide-cephalosporin heterodimer investigational antibiotic that displays potent bactericidal effects against clinically relevant Gram-positive organisms in vitro. The present studies evaluated the in vivo pharmacokinetics (PK) and pharmacodynamics (PD) of TD-1792 in the neutropenic murine thigh infection animal model. TD-1792, dosed subcutaneously (SC), produced dose-dependent reduction in the thigh bacterial burden of several organisms, including methicillin-susceptible and -resistant strains of Staphylococcus aureus and Staphylococcus epidermidis (MSSA, MRSA, MSSE, MRSE, respectively), penicillin-susceptible strains of Streptococcus pneumoniae (PSSP), Streptococcus pyogenes, and vancomycin-intermediate-susceptible Staphylococcus aureus (VISA). In single-dose efficacy studies, the 1-log(10) CFU kill effective dose (ED(1-log kill)) estimates for TD-1792 ranged from 0.049 to 2.55 mg/kg of body weight administered SC, and the bacterial burden was reduced by up to 3 log(10) CFU/g from pretreatment values. Against S. aureus ATCC 33591 (MRSA), the total 24-h log(10) stasis dose (ED(stasis)) and ED(1-logkill) doses for TD-1792 were 0.53 and 1.11 mg/kg/24 h, respectively, compared to 23.4 and 54.6 mg/kg/24 h for vancomycin, indicating that TD-1762 is 44- to 49-fold more potent than vancomycin. PK-PD analysis of data from single-dose and dose-fractionation studies for MRSA (ATCC 33591) demonstrated that the total-drug 24-h area under the concentration-time curve-to-MIC ratio (AUC/MIC ratio) was the best predictor of efficacy (r(2) = 0.826) compared to total-drug maximum plasma concentration of drug-to-MIC ratio (Cmax/MIC ratio; r(2) = 0.715) and percent time that the total-drug plasma drug concentration remains above the MIC (%Time>MIC; r(2) = 0.749). The magnitudes of the total-drug AUC/MIC ratios associated with net bacterial stasis, a 1-log(10) CFU reduction from baseline and near maximal effect, were 21.1, 37.2, and 51.8, respectively. PK-PD targets based on such data represent useful inputs for analyses to support dose selection decisions for clinical studies of patients. PMID:22155835

Hegde, Sharath S; Okusanya, Olanrewaju O; Skinner, Robert; Shaw, Jeng-Pyng; Obedencio, Glenmar; Ambrose, Paul G; Blais, Johanne; Bhavnani, Sujata M



Antibiotic sensitivity profiles determined with an Escherichia coli gene knockout collection: generating an antibiotic bar code.  


We have defined a sensitivity profile for 22 antibiotics by extending previous work testing the entire KEIO collection of close to 4,000 single-gene knockouts in Escherichia coli for increased susceptibility to 1 of 14 different antibiotics (ciprofloxacin, rifampin [rifampicin], vancomycin, ampicillin, sulfamethoxazole, gentamicin, metronidazole, streptomycin, fusidic acid, tetracycline, chloramphenicol, nitrofurantoin, erythromycin, and triclosan). We screened one or more subinhibitory concentrations of each antibiotic, generating more than 80,000 data points and allowing a reduction of the entire collection to a set of 283 strains that display significantly increased sensitivity to at least one of the antibiotics. We used this reduced set of strains to determine a profile for eight additional antibiotics (spectinomycin, cephradine, aztreonem, colistin, neomycin, enoxacin, tobramycin, and cefoxitin). The profiles for the 22 antibiotics represent a growing catalog of sensitivity fingerprints that can be separated into two components, multidrug-resistant mutants and those mutants that confer relatively specific sensitivity to the antibiotic or type of antibiotic tested. The latter group can be represented by a set of 20 to 60 strains that can be used for the rapid typing of antibiotics by generating a virtual bar code readout of the specific sensitivities. Taken together, these data reveal the complexity of intrinsic resistance and provide additional targets for the design of codrugs (or combinations of drugs) that potentiate existing antibiotics. PMID:20065048

Liu, Anne; Tran, Lillian; Becket, Elinne; Lee, Kim; Chinn, Laney; Park, Eunice; Tran, Katherine; Miller, Jeffrey H



Disk diffusion testing, quality control guidelines, and antimicrobial spectrum of HR810, a fourth-generation cephalosporin, in clinical microbiology laboratories.  

PubMed Central

HR810 is a new, very broad-spectrum cephalosporin with significant activity against members of the family Enterobacteriaceae, pseudomonads, gram-positive cocci, and anaerobes that is generally greater than the third-generation cephalosporins (99.6% of 4,128 clinical facultative enteric isolates were inhibited by less than or equal to 8.0 micrograms of HR810 per ml). Tests and statistical methods to establish in vitro antimicrobial susceptibility test criteria favor tentative breakpoints of greater than or equal to 18 mm (less than or equal to 8.0 micrograms/ml) as susceptible and less than or equal to 14 mm (greater than or equal to 32 micrograms/ml) as resistant. This provides a 93.7 to 98.3% absolute interpretive accuracy. Several preliminary ranges for zone sizes obtained with quality control organisms are proposed for the 30-micrograms HR810 disk diffusion test used during the clinical trials.

Jones, R N; Thornsberry, C; Barry, A L; Ayers, L; Brown, S; Daniel, J; Fuchs, P C; Gavan, T L; Gerlach, E H; Matsen, J M



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



Antibiotic sensitivities of Aeromonas hydrophila cultured from medicinal leeches.  


Increased use of medicinal leeches (Hirudo medicinalis) for the treatment of venous congestion in flaps and replanted parts has coincided with reports of soft tissue infections following leech application. We cultured the gullets of 20 medicinal leeches to re-examine the antibiotic sensitivities of Aeromonas hydrophila, the leech enteric organism associated with reported infections. These isolates reflected reported resistance to penicillin and first generation cephalosporins as well as sensitivity to gentamicin, tetracycline and chloramphenicol. Additionally, the cultures were sensitive to cefamandol, cefoxitin and two third generation cephalosporins (cefoperazone and cefotaxime). These findings suggest that cefamandol, cefoxitin and some third generation cephalosporins may have a role as perioperative antibiotics in replantation and flap surgery. These antibiotics might provide prophylaxis against Aeromonas hydrophila infection when leech use is required. PMID:3207967

Hermansdorfer, J; Lineaweaver, W; Follansbee, S; Valauri, F A; Buncke, H J



Antibiotic consumption and antibiotic stewardship in Swedish hospitals.  


Abstract Background. The aim of this paper was to describe and analyze the effect of antibiotic policy changes on antibiotic consumption in Swedish hospitals and to review antibiotic stewardship in Swedish hospitals. Results. The main findings were: 1) Antibiotic consumption has significantly increased in Swedish hospitals over the last decade. The consumption of cephalosporins has decreased, whereas that of most other drugs including piperacillin-tazobactam, carbapenems, and penicillinase-sensitive and -resistant penicillins has increased and replaced cephalosporins. 2) Invasive infections caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae have increased, but the proportion of pathogens resistant to third-generation cephalosporins causing invasive infections is still very low in a European and international perspective. Furthermore, the following gaps in knowledge were identified: 1) lack of national, regional, and local data on the incidence of antibiotic resistance among bacteria causing hospital-acquired infections e.g. bloodstream infections and hospital-acquired pneumonia-data on which standard treatment guidelines should be based; 2) lack of data on the incidence of Clostridium difficile infections and the effect of change of antibiotic policies on the incidence of C. difficile infections and infections caused by antibiotic-resistant pathogens; and 3) lack of prospective surveillance programs regarding appropriate antibiotic treatment, including selection of optimal antimicrobial drug regimens, dosage, duration of therapy, and adverse ecological effects such as increases in C. difficile infections and emergence of antibiotic-resistant pathogens. Conclusions. Evidence-based actions to improve antibiotic use and to slow down the problem of antibiotic resistance need to be strengthened. The effect of such actions should be analyzed, and standard treatment guidelines should be continuously updated at national, regional, and local levels. PMID:24724823

Hanberger, Håkan; Skoog, Gunilla; Ternhag, Anders; Giske, Christian G



Antibiotic consumption and antibiotic stewardship in Swedish hospitals  

PubMed Central

Background The aim of this paper was to describe and analyze the effect of antibiotic policy changes on antibiotic consumption in Swedish hospitals and to review antibiotic stewardship in Swedish hospitals. Results The main findings were: 1) Antibiotic consumption has significantly increased in Swedish hospitals over the last decade. The consumption of cephalosporins has decreased, whereas that of most other drugs including piperacillin-tazobactam, carbapenems, and penicillinase-sensitive and -resistant penicillins has increased and replaced cephalosporins. 2) Invasive infections caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae have increased, but the proportion of pathogens resistant to third-generation cephalosporins causing invasive infections is still very low in a European and international perspective. Furthermore, the following gaps in knowledge were identified: 1) lack of national, regional, and local data on the incidence of antibiotic resistance among bacteria causing hospital-acquired infections e.g. bloodstream infections and hospital-acquired pneumonia—data on which standard treatment guidelines should be based; 2) lack of data on the incidence of Clostridium difficile infections and the effect of change of antibiotic policies on the incidence of C. difficile infections and infections caused by antibiotic-resistant pathogens; and 3) lack of prospective surveillance programs regarding appropriate antibiotic treatment, including selection of optimal antimicrobial drug regimens, dosage, duration of therapy, and adverse ecological effects such as increases in C. difficile infections and emergence of antibiotic-resistant pathogens. Conclusions Evidence-based actions to improve antibiotic use and to slow down the problem of antibiotic resistance need to be strengthened. The effect of such actions should be analyzed, and standard treatment guidelines should be continuously updated at national, regional, and local levels.

Skoog, Gunilla; Ternhag, Anders; Giske, Christian G.



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.



In Vitro Synergistic Effect of Curcumin in Combination with Third Generation Cephalosporins against Bacteria Associated with Infectious Diarrhea  

PubMed Central

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

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





Antibiotics are powerful medicines that fight bacterial infections. Used properly, antibiotics can save lives. They either kill bacteria or ... natural defenses can usually take it from there. Antibiotics do not fight infections caused by viruses, such ...


Production of Cephalosporin C by Paecilomyces persicinus P-10  

PubMed Central

After the growth of Paecilomyces persicinus P-10 in a glucose-peptone medium, filtrates were collected and analyzed for antibiotic antivity. Activities against Salmonella gallinarum ATCC 3030 and Alcaligenes faecalis ATCC 8750 (penicillin N-resistant strain) were obtained. Part of the former activity was readily inactivated by penicillinase. The fraction active against A. faecalis was isolated by passage through Amberlite XAD-2 and Amberlite IRA-68. The powder eventually obtained was subjected to paper chromatography followed by bioautography, and the activity obtained corresponded to that of a sample of cephalosporin C. Thin-layer chromatography was also employed to verify the presence of cephalosporin C in the P-10 powder. The active solids were further purified by means of paper chromatography in a solvent system consisting of n-butanol-acetic acid-water (60:15:25, vol/vol). The material obtained from this procedure yielded an infrared absorption spectrum identical to that of cephalosporin C. Similarly, the ultraviolet absorption of the purified preparation coincided with that of cephalosporin C. Exposure of the purified solids to cephalosporinase resulted in rapid inactivation of the antibiotic. In addition to penicillin N and cephalosporin C, filtrates of P. persicinus P-10 also contained deacetylcephalosporin C, deacetoxycephalosporin C, and cephalosporin P.

Pisano, M. A.; Vellozzi, E. M.



Role of Methionine in Cephalosporin Synthesis  

PubMed Central

Methionine has an almost unique stimulatory effect on biosynthesis of cephalosporins (by Cephalosporium acremonium). No other sulfur-containing compound tested, except dl-methionine-dl-sulfoxide, replaced methionine. dl-Methionine stimulated the synthesis of cephalosporins when added after the growth phase. The utilization of inorganic sulfate was repressed by methionine. Experiments with l-methionine-S35 showed that essentially all the sulfur in the cephalosporins was derived from methionine. Sulfur-labeled compounds found in the soluble pool from cells grown with methionine-S35 were methionine, homocysteine, taurine, cystathionine, cysteic acid, glutathionine, and cysteine. dl-Serine-3-C14 was incorporated into the antibiotics, and its utilization was stimulated by methionine. l-Cysteine had a sparing effect on the incorporation of methionine-S35 and serine-C14 into the antibiotics. The data are consistent with the hypothesis that a cystathionine-mediated pathway is operative in the transfer of sulfur between methionine and cysteine.

Caltrider, P. G.; Niss, H. F.



In vitro susceptibility of Helicobacter pylori to the new oral cephalosporins cefpodoxime, ceftibuten and cefixime.  


The in vitro activity against 30 Helicobacter pylori strains of three new third generation cephalosporins, cefpodoxime, ceftibuten and cefixime, which can be administered orally, was determined using an agar dilution technique under microaerophilic conditions. The MIC50 and MIC90 of cefpodoxime was 0.5 and 4.0 micrograms/ml respectively, of ceftibuten 2.0 and 8.0 micrograms/ml, and of cefixime 0.06 and 0.5 microgram/ml. All antibiotics showed good activity against Helicobacter pylori, cefixime having the highest activity of the three agents. PMID:2226500

Westblom, T U; Gudipati, S; Midkiff, B R



[Antibiotic prophylaxis in surgery].  


Infection remains a serious complication after surgical produces. The main risk factors for developing infection are: 1. endogenous-host related, 2. exogenous-produce related, 4. environmental-related ones. Systemic antibiotic prophylaxis significantly reduces the incidence of potentially serious infective complications. It is indicated in procedures with incidence of infective complications more as 5%, in clean contaminated wounds and also in produces, in which infection has fatal consequences (vascular surgery, heart surgery, traumatology). The decision to use antibiotic prophylaxis depends upon the operation to be performed, the findings at operations, the general health of the patient and pharmacological and antibacterial properties of the agent. Timing of the first dose (administration not more as 1 hour preoperatively) and duration not more as 24 hours are very important. We use the second generations of cephalosporins (cefuroxim and after antibiotic rotation cefamandol) in antibiotic prophylaxis obligatory in vascular surgery, pacemaker implantation, traumatology and in colorectal surgery (there in combination with metronidasol) with mean infection rate in clean surgical procedures from 0.5 to 1.5%. Complications after antibiotic prophylaxis are very rare. However antibiotic prophylaxis can not compensate the correction of medical problems preoperatively and the meticulous surgical technique. PMID:10847748

Simo, J; Matis, P; Durdík, S; Martinec, A; Kubis, J



Dual-Action Cephalosporin Utilizing a Novel Therapeutic Principle  

PubMed Central

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

Greenwood, D.; O'Grady, F.



[Antibiotic prophylaxis in orthopedic surgery].  


In orthopaedics where a great number of implants are in use, the chance for infection is high. To keep up the aseptic condition and giving antibiotic in the perioperative time is necessary. According to the effect on postoperative bleeding authors did compare two second generation cephalosporin, the cefamandol and the cefuroxim, which are mainly used in antibiotic prophylaxis. The gamma carboxylation of glutaminic acid is inhibited by cefamandol in the liver, which is necessary in the prothrombin synthesis. The cefuroxim is without any effect on prothrombin synthesis. The postoperative bleeding was significantly higher following cefamandol administration. According to the authors in orthopaedics, where the blood loss could be high, that type of antibiotic prophylaxis is recommended, which has no effect on bleeding. PMID:7833988

Faluhelyi, A; Vánkos, L



Clinical pharmacodynamics of antipseudomonal cephalosporins in patients with ventilator-associated pneumonia.  


Advanced-generation cephalosporins are frequently used for empirical coverage of ventilator-associated pneumonia (VAP) due to their activity against a broad spectrum of Gram-positive and Gram-negative aerobic bacteria, including Pseudomonas aeruginosa and Enterobacteriaceae. Providing optimal antibiotic exposure is essential to achieving successful response in patients with VAP. We evaluated exposures of two antipseudomonal cephalosporins, ceftazidime and cefepime, in patients with VAP due to Gram-negative bacilli to identify the pharmacodynamic parameter predictive of microbiological success. Population pharmacokinetic models were used to estimate individual free drug exposures. Pharmacodynamic indices were determined for each patient using the baseline Gram-negative bacilli with the highest drug MIC. Classification and regression tree analysis was utilized to partition exposure breakpoints, and multivariate logistic regression was conducted to identify predictors of microbiological success. A total of 73 patients (18 receiving ceftazidime therapy and 55 receiving cefepime therapy) were included. MICs ranged widely from 0.047 to 96 ?g/ml. The microbiological success rate was 58.9%. Predictive breakpoints were identified for all pharmacodynamic parameters, including a serum fT>MIC greater than 53% (P=0.02). When controlling for APACHE II (odds ratio [OR], 1.01; 95% confidence interval, 0.93 to 1.09; P=0.85) and combination therapy (OR, 0.74; 95% confidence interval, 0.25 to 2.19; P=0.59), achieving a greater than 53% fT>MIC remained a significant predictor of success (OR, 10.3; 95% confidence interval, 1.1 to 92.3; P=0.04). In patients with VAP due to Gram-negative bacilli, serum exposure of greater than 53% fT>MIC was found to be a significant predictor of favorable microbiological response for antipseudomonal cephalosporins. These data are useful when determining dosing regimens for cephalosporin agents under development for pneumonia. PMID:24342637

MacVane, Shawn H; Kuti, Joseph L; Nicolau, David P



[Diffusion in bone tissue of antibiotics].  


DIFFICULT ASSESSMENT: Bone and joint infections are difficult to treat. Therapeutic success depends greatly on the diffusion of antibiotics into bone tissue. Few studies have been devoted to this subject and the variable nature of those reported hinders interpretation. Bone biopsies are generally obtained during orthopedic procedures. Antibiotic administration routes vary although intravenous infusion predominates. Agar gel diffusion is generally used for antibiotic assays but methodology varies depending of the study. The most recent reports use high-performance liquid chromatography. DIFFUSION STUDIES: The different studies examining antibiotic diffusion in bone tissue describe three classes: good diffusion (greater than 30%), moderate diffusion (between 15% and 30%), and low diffusion (less than 15%). Antibiotics in the good diffusion class include fluoroquinolones, teicoplanin, macrolides, rifampicin and trimethoprime. Antibiotics with moderate bone diffusion are ureidopenicillins, second and third generation cephalosporins, aminoglycosides, clindamycin, fosfomycin and vancomycin. Those with low bone diffusion are aminopenicillins, penicillin M and first generation cephalosporins. No data is available on the bone diffusion of pristinamycin. DATA INTERPRETATION: The clinical impact of these classifications must be interpreted with precaution when considering bone and joint infections as they were established on the basis of pharmacokinetic studies and not clinical trials. They would however appear to be useful in guiding antibiotic prophylaxis for orthopedic surgery in protocols with administration conditions and concentration goals similar to the experimental conditions. PRACTICAL ATTITUDES: These laboratory results could be used in clinical practice by comparing the MIC50 of the germs regularly encountered in bone infections (staphylococci, streptococci including enterococci, Gram negative bacilli including P. aeruginosa and H. influenzae) with concentrations obtained in the different studies, i.e. by calculating the inhibitor coefficient (IQ) of each antibiotic for each susceptible germ. This gives a classification by efficacy (excellent IQ > 10, good 1 < IQ < 10, poor IQ < 1) useful for guiding antibiotic choice in the difficult situation of bone and joint infection. PMID:10636023

Boselli, E; Allaouchiche, B


[Probiotics for the prevention of antibiotic-induced diarrhea].  


Between 5 and 49% of patients treated with antibiotics suffer from diarrhoea. Principally all microbial agents can cause diarrhoea, especially oral agents like cephalosporines, clindamycin, broad-spectrum penicillins, and quinolones of the 3 ?rd and 4th generation. Manifestations of antibiotic-associated diarrhoea range from mild self-limiting forms to severe life-threatening courses. The potentially most severe form of antibiotic-associated diarrhoea is caused by Clostridium diffcile accounting for approx. 25 ?% of antibiotic-associated diarrhoea. In the past two decades a broad spectrum of different probiotic strains has been evaluated for the primary prevention of antibiotic-associated diarrhoea in children and adults. Based on their efficacy and clinical data, different levels of evidence and recommendations are emerging on the preventive use of probiotics in antibiotic-associated diarrhoea. PMID:23059802

Eser, A; Thalhammer, F; Burghuber, F; Högenauer, C; Stockenhuber, F; Wenisch, C; Widhalm, K; Reinisch, W



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

PubMed Central

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.

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



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



Antibiotic-resistant soil bacteria in transgenic plant fields.  


Understanding the prevalence and polymorphism of antibiotic resistance genes in soil bacteria and their potential to be transferred horizontally is required to evaluate the likelihood and ecological (and possibly clinical) consequences of the transfer of these genes from transgenic plants to soil bacteria. In this study, we combined culture-dependent and -independent approaches to study the prevalence and diversity of bla genes in soil bacteria and the potential impact that a 10-successive-year culture of the transgenic Bt176 corn, which has a blaTEM marker gene, could have had on the soil bacterial community. The bla gene encoding resistance to ampicillin belongs to the beta-lactam antibiotic family, which is widely used in medicine but is readily compromised by bacterial antibiotic resistance. Our results indicate that soil bacteria are naturally resistant to a broad spectrum of beta-lactam antibiotics, including the third cephalosporin generation, which has a slightly stronger discriminating effect on soil isolates than other cephalosporins. These high resistance levels for a wide range of antibiotics are partly due to the polymorphism of bla genes, which occur frequently among soil bacteria. The blaTEM116 gene of the transgenic corn Bt176 investigated here is among those frequently found, thus reducing any risk of introducing a new bacterial resistance trait from the transgenic material. In addition, no significant differences were observed in bacterial antibiotic-resistance levels between transgenic and nontransgenic corn fields, although the bacterial populations were different. PMID:18292221

Demanèche, Sandrine; Sanguin, Hervé; Poté, John; Navarro, Elisabeth; Bernillon, Dominique; Mavingui, Patrick; Wildi, Walter; Vogel, Timothy M; Simonet, Pascal



Pharmacokinetic properties of the cephalosporins.  


Most cephalosporins can only be administered parenterally. Among agents that are absorbed from the gastrointestinal tract, those with bioavailabilities of 85 to 90% include cefroxadine, cefadroxil, cefsumide, cephalexin, cephradine, cephacetrile, and cefazaflur. Most cephalosporins are eliminated rapidly, with serum half-lives (t1/2s) of 1 to 2 hours. Exceptions are cefonicid with a t1/2 of 4.4 hours, cefpiramide with a t1/2 of 5.0 hours, and cefotetan with a t1/2 of 3.5 hours. The longest half-life is shown by ceftriaxone with a t1/2 of 8.5 hours. Cephalosporins are eliminated mostly by the kidneys, some with a substantial contribution from active tubular secretion, which is blocked by probenecid. The degree of metabolism varies. Only a few cephalosporins have a high biliary elimination. For example, with intravenously administered cefoperazone, about 70% appears in bile. High biliary elimination is also observed with cefmenoxime, ceftriaxone, cefbuperazone, and latamoxef (moxalactam). Because these are not appreciably absorbed from the gastrointestinal tract, the consequence is high intraintestinal concentrations of the drugs and a marked ensuing depression of the normal microflora with simultaneous emergence of resistant bacteria. The untoward ecological impact may even lead to Clostridium difficile-associated enterocolitis. PMID:3319507

Bergan, T



Liquid-chromatographic determination of cephalosporins and chloramphenicol in serum.  


A "high-performance" liquid-chromatographic technique involving a radial compression module is used for measuring chloramphenicol and five cephalosporin antibiotics: cefotaxime, cefoxitin, cephapirin, and cefamandol. Serum proteins are precipitated with acetonitrile solution containing 4'-nitroacetanilide as the internal standard. The drugs are eluted with a mobile phase of methanol/acetate buffer (30/70 by vol), pH 5.5. Absorbance of the cephalosporins is monitored at 254 nm. Standard curves are linear to at least 100 mg/L. The absorbance of chloramphenicol is monitored at 254 nm and 280 nm, and its standard curve is linear to at least 50 mg/L. The elution times for various other drugs were also determined, to check for potential interferents. PMID:6839466

Danzer, L A



Disulfiram-like reactions with newer cephalosporins: cefmenoxime.  


A 54-year-old woman with recurrent adenocarcinoma of the uterus was treated with new third-generation cephalosporin, cefmenoxime, for a urinary tract infection. She received an alcohol-containing tylenol elixir while receiving the drug on two occasions. A disulfiram-like reaction was noticed each time. Such reactions have been described in patients receiving certain drugs such as 5-nitroimidazoles, nitrofurans, sulfonylureas and certain newer cephalosporins with a methyltetrazolethiol side chain. This is the first report of a disulfiram-like reaction with cefmenoxime. The mechanism, causes, and significance of disulfiram-like reactions are discussed. PMID:6324592

Kannangara, D W; Gallagher, K; Lefrock, J L



New Generation of Plasmid Backbones Devoid of Antibiotic Resistance Marker for Gene Therapy Trials  

PubMed Central

Since it has been established that the injection of plasmid DNA can lead to an efficient expression of a specific protein in vivo, nonviral gene therapy approaches have been considerably improved, allowing clinical trials. However, the use of antibiotic resistance genes as selection markers for plasmid production raises safety concerns which are often pointed out by the regulatory authorities. Indeed, a horizontal gene transfer to patient's bacteria cannot be excluded, and residual antibiotic in the final product could provoke allergic reactions in sensitive individuals. A new generation of plasmid backbones devoid of antibiotic resistance marker has emerged to increase the safety profile of nonviral gene therapy trials. This article reviews the existing strategies for plasmid maintenance and, in particular, those that do not require the use of antibiotic resistance genes. They are based either on the complementation of auxotrophic strain, toxin–antitoxin systems, operator–repressor titration, RNA markers, or on the overexpression of a growth essential gene. Minicircles that allow removing of the antibiotic resistance gene from the initial vector will also be discussed. Furthermore, reported use of antibiotic-free plasmids in preclinical or clinical studies will be listed to provide a comprehensive view of these innovative technologies.

Vandermeulen, Gaelle; Marie, Corinne; Scherman, Daniel; Preat, Veronique



[Clinical use of new cephalosporins for severe infections in internal medicine].  


Our clinical experience with new antibiotics giving special consideration to the individual cephalosporin groups is discussed. Although newer cephalosporins from cefamandol and cefoxitin to cefotiam and cefoperazon already showed increased effectiveness (for example, cefoxitin in bacteroides infection) in comparison to older ones, the real breakthrough regarding enterobacteriaceae was only made with cephalosporins of the cefotaxime group. This group's main indication is non-specific initial therapy of severe nosocomial infections, especially processes in which the presence of resistant enterobacteriaceae must be assumed. Because of its broad spectrum of action, cefotaxime can to a large extent replace the combinations with aminoglycosides which were used previously. When required, cefotaxime proves to be a good partner for combinations with pseudomonas antibiotics. PMID:6316668

Stille, W



Surveillance of antibiotic resistance in Neisseria gonorrhoeae in the WHO Western Pacific and South East Asian Regions, 2009.  


Long-term surveillance of antimicrobial resistance in Neisseria gonorrhoeae has been conducted in the World Health Organization (WHO) Western Pacific Region (WPR) to optimise antibiotic treatment of gonococcal disease since 1992. From 2007, the Gonococcal Antimicrobial Surveillance Programme (GASP) has been enhanced by the inclusion of data from the South East Asian Region (SEAR) and recruitment of additional centres in the WPR. Approximately 8,704 isolates of N. gonorrhoeae were examined for their susceptibility to one or more antibiotics used for the treatment of gonorrhoea, incorporating External Quality Assurance controlled methods, from reporting centres in 21 countries and/or jurisdictions. A high proportion of penicillin and/or quinolone resistance was again detected amongst isolates tested in North Asia and the WHO SEAR. In contrast, from the Pacific Island states Fiji reported low penicillin and quinolone resistance, New Caledonia again reported no penicillin resistance and little quinolone resistance, Tonga reported no penicillin resistance and there was a continued absence of quinolone resistance reported in Papua New Guinea in 2009. The proportion of gonococci reported as 'decreased susceptibility' and 'resistant' to the third-generation cephalosporin antibiotic ceftriaxone varied widely but no major changes were evident in cephalosporin minimum inhibitory concentrations (MIC) patterns in 2009. Altered cephalosporin susceptibility has been associated with treatment failures following therapy with oral third-generation cephalosporins. There is a need for revision and clarification of some of the in vitro criteria that are currently used to categorise the clinical importance of gonococci with different ceftriaxone and oral cephalosporin MIC levels. The number of instances of spectinomycin resistance remained low. A high proportion of strains tested continued to exhibit high-level plasmid mediated resistance to tetracyclines. The continuing emergence and spread of antibiotic resistant gonococci in and from the WHO WPR and SEAR suggests that surveillance programs such as GASP be maintained and expanded. PMID:21698977



[Gonococci change more quickly than prescribing practices; resistance to frequently prescribed antibiotics].  


Gonococcal resistance to antibiotics is increasing worldwide. In patients tested in Dutch STI clinics in 2009, gonococcal resistance to ciprofloxacin was over 50%. Ceftriaxone, a third-generation cephalosporin, has been the first-choice medication since 2004. General practitioners treated 25% of their gonorrhoea patients with ciprofloxacin in 2010. There is a need for up-to-the-minute, dynamic guidelines for treating gonorrhoea as well as the more systematic use of an up-to-date digital prescription system. PMID:23759175

Koedijk, Femke D H; van den Broek, Ingrid V F; Stirbu-Wagner, Irina; van Bergen, Jan E A M



Structural determinants of antibiotic allergy  

Microsoft Academic Search

Allergies to antibiotics, mainly the ?-lactam antibiotics (penicillins and cephalosporins), are a common, costly, and potentially\\u000a dangerous clinical problem encountered in everyday practice. Although studies on the role of non-?-lactam antibiotics in allergic\\u000a diseases, particularly the development of specific diagnostic tests and the immunochemical identification of allergenic structures,\\u000a have been too few and relatively superficial, the situation with the ?-lactam

Brian A. Baldo; Zhenjun Zhao; Nghia H. Pham



In vitro susceptibilities of Plesiomonas shigelloides to 24 antibiotics and antibiotic-beta-lactamase-inhibitor combinations.  

PubMed Central

The antibiotic susceptibilities of 29 isolates of Plesiomonas shigelloides were studied with 24 antibiotics and antibiotic-inhibitor combinations. Results indicated that all isolates were susceptible to the cephalosporins, penicillins combined with a beta-lactamase inhibitor, aztreonam, and ciprofloxacin. Most isolates were resistant to the penicillins, possibly via production of a penicillinase.

Clark, R B; Lister, P D; Arneson-Rotert, L; Janda, J M



A chromogenic cephalosporin for ?-lactamase inhibitor screening assays.  


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

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



Sequential therapy with intravenous and oral cephalosporins.  


The pharmacokinetic, economic and practical aspects of sequential therapy with iv and oral cephalosporins are reviewed. New broad spectrum oral cephalosporins, such as cefixime, cefpodoxime proxetil and cefetamet pivoxil achieve serum concentrations above the MICs for most Enterobacteriaceae for at least as long as for parenteral cefuroxime. Substantial cost reductions are possible with an early switch from iv to oral cephalosporins. The clinical studies that have been performed so far have important shortcomings. Well designed clinical studies are necessary to prove the feasibility of sequential therapy with cephalosporins for serious infections in hospitalized patients. PMID:8157558

Janknegt, R; van der Meer, J W



Increased Use of Second-Generation Macrolide Antibiotics for Children in Nine Health Plans in the United States  

Microsoft Academic Search

ABSTRACT. Background. Widespread use of broad- spectrum antibiotics contributes to increasing rates of bacterial resistance to antibiotics. Second-generation macrolides have become popular for use among children because of their broad spectrum and favorable dosing and side-effect profiles, although experts do not gener- ally recommend them for use as initial treatment of in- fections among younger children. Objective. To assess trends

Christopher J. Stille; Mph Susan E. Andrade; Scd Susan S. Huang; James Nordin; Mph Marsha A. Raebel; Pharmd Alan S. Go; K. Arnold Chan; Jonathan A. Finkelstein


Cephalosporin penetration into soft tissue of paralyzed limbs.  

PubMed Central

Poor penetration of antibiotics into paralyzed tissue may contribute to the difficulty of curing soft tissue infections in paralyzed limbs. A novel model of spinal cord hemisection was used to induce paralysis of one hind leg in mice. Five, 10, or 20 days after induction of paralysis, six groups of 10 mice were injected intravenously with a single dose or with four sequential doses of cefepime, a new broad-spectrum cephalosporin, and then sacrificed. High-performance liquid chromatography was used to compare cefepime levels in soft tissue homogenates of paralyzed and normal hind legs; no significant differences were found in any group. Factors other than antibiotic delivery may be responsible for difficulty in curing infections in paralyzed soft tissue. Images

Darouiche, R; Musher, D; Hamill, R; Ou, C; Rognerud, C



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

PubMed Central

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



Heteroresistance to Cephalosporins and Penicillins in Acinetobacter baumannii  

PubMed Central

Heteroresistance to antimicrobial agents may affect susceptibility test results and therapeutic success. In this study, we investigated heteroresistance to cephalosporins and penicillins in Acinetobacter baumannii, a major pathogen causing nosocomial infections. Two A. baumannii isolates exhibited heteroresistance to ampicillin-sulbactam, ticarcillin-clavulanic acid, cefepime, and cefpirome, showing a distinct colony morphology of circular rings within the inhibition halos. Pulsed-field gel electrophoresis (PFGE) and outer membrane protein (OMP) analysis demonstrated that subpopulations around the disks/Etest strips and the original strains all belonged to the same PFGE type and OMP profile. Population analysis profile (PAP) showed the presence of heteroresistant subpopulations with high cefepime resistance levels in two isolates (008 and 328). Interestingly, A. baumannii 008 contained two peaks: one was grown in the presence of up to 1 ?g of cefepime/ml, the other apparently occurred when the concentration of cefepime was raised to 256 ?g/ml. After serial passages without exposure to cefepime, the PAP curve maintained the same trend observed for the original strain of A. baumannii 008. However, the PAP curve showed a shift to relatively lower cefepime resistance (from 256 to 64 ?g/ml) in A. baumannii 328 after 10 passages in antibiotic-free Mueller-Hinton agar plates. Convergence to a monotypic resistance phenotype did not occur. Growth rate analysis revealed that slower growth in resistant subpopulations may provide a strategy against antibiotic challenge. To our knowledge, this is the first report of heteroresistance to cephalosporins and penicillins in A. baumannii.

Hung, Kuei-Hsiang; Wang, Ming-Cheng; Huang, Ay-Huey; Yan, Jing-Jou



Cephalosporin Resistance in Neisseria gonorrhoeae  

PubMed Central

Gonorrhea, a disease of public health importance, not only leads to high incidence of acute infections and complications but also plays a major role in facilitating human immunodeficiency virus (HIV) acquisition and transmission. One of the major public health needs for gonorrhea control is appropriate, effective treatment. However, treatment options for gonorrhea are diminishing as Neisseria gonorrhoeae have developed resistance to several antimicrobial drugs such as sulfonamides, penicillin, tetracyclines and quinolones. Antimicrobial resistance (AMR) surveillance of N. gonorrhoeae helps establish and maintain the efficacy of standard treatment regimens. AMR surveillance should be continuous to reveal the emergence of new resistant strains, monitor the changing patterns of resistance, and be able to update treatment recommendations so as to assist in disease control. Current treatment guidelines recommend the use of single dose injectable or oral cephalosporins. The emergence and spread of cephalosporin resistant and multi drug resistant N. gonorrhoeae strains, represents a worrying trend that requires monitoring and investigation. Routine clinical laboratories need to be vigilant for the detection of such strains such that strategies for control and prevention could be reviewed and revised from time to time. It will be important to elucidate the genetic mechanisms responsible for decreased susceptibility and future resistance. There is also an urgent need for research of safe, alternative anti-gonococcal compounds that can be administered orally and have effective potency, allowing high therapeutic efficacy (greater than 95.0% cure rate).

Bala, Manju; Sood, Seema



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.



Risk Factors for Emergence of Resistance to Broad-Spectrum Cephalosporins among Enterobacter spp  

Microsoft Academic Search

Among 477 patients with susceptible Enterobacter spp., 49 subsequently harbored third-generation cephalo- sporin-resistant Enterobacter spp. Broad-spectrum cephalosporins were independent risk factors for resistance (relative risk (OR) 5 2.3, P 5 0.01); quinolone therapy was protective (OR 5 0.4, P 5 0.03). There were trends toward decreased risk for resistance among patients receiving broad-spectrum cephalosporins and either aminoglycosides or imipenem. Of




Clinical Pharmacokinetics of Penicillins, Cephalosporins and Aminoglycosides in the Neonate: A Review  

PubMed Central

Bacterial infections are common in the neonates and are a major cause of morbidity and mortality. Sixty percent of preterm infants admitted to neonatal intensive care units received at least one antibiotic during the first week of life. Penicillins, aminoglycosides and cephalosporins comprised 53, 43 and 16%, respectively. Kinetic parameters such as the half-life (t1/2), clearance (Cl), and volume of distribution (Vd) change with development, so the kinetics of penicillins, cephalosporins and aminoglycosides need to be studied in order to optimise therapy with these drugs. The aim of this study is to review the pharmacokinetics of penicillins, cephalosporins and aminoglycosides in the neonate in a single article in order to provide a critical analysis of the literature and thus provide a useful tool in the hands of physicians. The bibliographic search was performed electronically using PubMed, as the search engine, until February 2nd, 2010. Medline search terms were as follows: pharmacokinetics AND (penicillins OR cephalosporins OR aminoglycosides) AND infant, newborn, limiting to humans. Penicillins, cephalosporins and aminoglycosides are fairly water soluble and are mainly eliminated by the kidneys. The maturation of the kidneys governs the pharmacokinetics of penicillins, cephalosporins and aminoglycosides in the neonate. The renal excretory function is reduced in preterms compared to term infants and Cl of these drugs is reduced in premature infants. Gestational and postnatal ages are important factors in the maturation of the neonate and, as these ages proceed, Cl of penicillins, cephalosporins and aminoglycosides increases. Cl and t1/2 are influenced by development and this must be taken into consideration when planning a dosage regimen with these drugs. More pharmacokinetic studies are required to ensure that the dose recommended for the treatment of sepsis in the neonate is evidence based.

Pacifici, Gian Maria



A highly active adipyl-cephalosporin acylase obtained via rational randomization.  


There is strong interest in creating an enzyme that can deacylate natural cephalosporins such as cephalosporin C in order to efficiently acquire the starting compound for the industrial production of semisynthetic cephalosporin antibiotics. In this study, the active site of the glutaryl acylase from Pseudomonas SY-77 was randomized rationally. Several mutations that were found in previous studies to enhance the activity of the enzyme towards adipyl-7-aminodesacetoxycephalosporanic acid (ADCA) and cephalosporin C have now been combined, and libraries have been made in which random amino acid substitutions at these positions are joined. The mutants were expressed in a leucine-deficient Escherichia coli strain and subjected to growth selection with adipyl-leucine or amino-adipyl-leucine as sole leucine source. The mutants growing on these media were selected and purified, and their hydrolysis activities towards adipyl-7-ADCA and cephalosporin C were tested. Several mutants with highly improved activities towards the desired substrates were found in these rationally randomized libraries. The best mutant was selected from a library of totally randomized residues: 178, 266, and 375. This mutant comprises two mutations, Y178F + F375H, which synergistically improve the catalytic efficiency towards adipyl-7-ADCA 36-fold. The activity of this mutant towards adipyl-7-ADCA is 50% of the activity of the wild-type enzyme towards the preferred substrate glutaryl-7-aminocephalosporanic acid, and therefore the characteristics of this mutant approach those needed for industrial application. PMID:17922842

Otten, Linda G; Sio, Charles F; Reis, Carlos R; Koch, Gudrun; Cool, Robbert H; Quax, Wim J



National Practice in Antibiotic Prophylaxis in Breast Cancer Surgery  

PubMed Central

Background Although breast cancer surgery is regarded as a “clean” surgery, surgical site infection (SSI) rates are higher than expected. There is no consensus regarding the use of antibiotic prophylaxis in elective breast surgery. The nationwide survey was conducted to determine the trend of antibiotic prophylaxis in breast cancer among Turkish surgeons. Methods The survey was sent to surgeons who are member of Turkish Surgical Association (TSA) via e-mail from TSA web address. A 15 item web-based survey consisted of surgeon demographics and the use of prophylactic antibiotic in patients with risk factors related to SSI. Results The number of completed questionnaires was 245. The most common antibiotic used was first generation of cephalosporins. A majority of respondents indicated that prophylaxis was preferred in patients with high risk of SSI including preoperative chemotherapy or radiotherapy, older age, diabetes mellitus, immunodeficiency, immediate reconstruction (P < 0.05). However, the use of drain did not significantly influence antibiotic prophylaxis (P = 0.091). Conclusions The use of prophylactic antibiotic was strongly dependent on the presence of some risk factors; however, the variation in current practice regarding antibiotic prophylaxis demonstrated a lack of its effect on preventing SSI after breast cancer surgery.

Eroglu, Aydan; Karasoy, Durdu; Kurt, Halil; Baskan, Semih



[Tigecycline: CMI 50/90 towards 1766 Gram-negative bacilli (3rd generation cephalosporins resistant enterobacteriaceae), Acinetobacter baumannii and Bacteroides fragilis group, University Hospital - Montpellier, 2008-2011].  


Tigecycline is a new glycylcyclin with a wide spectre including multi-resistant bacteria. Our laboratory tests in routine the in vitro activity of the TGC towards clinically significant isolates of 3rd generation cephalosporins resistant enterobacteriaceae (EC3R), Acinetobacter baumannii and Bacteroides fragilis group (BFG). The objective of this study is to describe the in vitro activity of TGC against these strains isolated between 2008 and 2011 in the university hospital of Montpellier. In this study period, 1070 isolates EC3R including 541 extended spectrum ?-lactamase-producers (ESBL) strains, 47 isolates of A. baumannii including 40 multi-resistant isolates and 645 isolates of BFG were tested. Minimum inhibitory concentrations (MIC) were determined using the E-test method. TGC was active against 86.2% of EC3R with a MIC 90 less or equal to 1mg/L (Escherichia coli being the most sensitive species). A. baumannii and BFG were also inhibited at low concentrations of TGC with a MIC 90 less or equal to 2mg/L respectively for 47% and 84.2% of the isolates. Our study confirms the activity of TGC against the EC3R including ESBL-producers strains. The relevance of the therapeutic use of TGC on the BFG isolates with a MIC greater than 2mg/L should be better documented. Often prescribed in therapeutic impasse, the proper use of TGC would require: clarifying the threshold of sensitivity for some species (i.e., A. baumannii, Bacteroides fragilis group); a better understanding of correlation between in vitro and in vivo activity. PMID:23478078

Froment Gomis, P; Jean-Pierre, H; Rousseau-Didelot, M-N; Compan, B; Michon, A-L; Godreuil, S



Antibiotic Prophylaxis for Cesarean Delivery: Survey of Maternal-Fetal Medicine Physicians in the U.S.  

PubMed Central

Objective To briefly describe practices concerning antibiotic prophylaxis for cesarean delivery among maternal-fetal medicine (MFM) physicians in the United States (US). Methods A 10-item self-administered survey about their routine use of antibiotics for cesarean delivery was mailed once only to a random sample of 1000 US-based fellows of the Society of Maternal-Fetal Medicine (SMFM) in November 2009. Results There were a total of 250 respondents from 40 US states between 10/09 and 4/2010, corresponding to a response rate of 25%. Among respondents, 95.5% reported routine use of a cephalosporin only (including 84.4% who reported use of cefazolin) as antibiotic prophylaxis for cesarean delivery; less than 3% reported use of an extended spectrum regimen such as cefazolin+azithromycin. Pre-incision administration of antibiotics was reported by 83.6% compared to 15.0% who reported giving prophylactic antibiotics after umbilical cord clamp. Administration of a single dose of antibiotics was reported by 96%. Conclusion The majority of MFM specialists in the US report routine use of a single prophylactic dose of a 1st generation cephalosporin prior to incision for cesarean delivery.

Doss, Amy E.; Davidson, Jennifer D.; Cliver, Suzanne P.; Wetta, Luisa A.L.; Andrews, William W.; Tita, Alan T.N.



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

PubMed Central

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

Greenwood, D.; O'Grady, F.



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


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

Greenwood, D; O'Grady, F



Antibiotic consumption and its influence on the resistance in Enterobacteriaceae  

PubMed Central

Background Increasing bacterial resistance to antibiotics is one of the most serious problems in current medicine. An important factor contributing to the growing prevalence of multiresistant bacteria is application of antibiotics. This study aimed at analyzing the development of resistance of Enterobacteriaceae to selected beta-lactam, fluoroquinolone and aminoglycoside antibiotics in the University Hospital Olomouc and assessing the effect of selection pressure of these antibiotics. Methods For the period between 1 January 2000 and 31 December 2011, resistance of Klebsiella pneumoniae, Escherichia coli, Enterobacter cloacae and Proteus mirabilis to third- and fourth-generation cephalosporins, meropenem, piperacillin/tazobactam, fluoroquinolones and aminoglycosides was retrospectively studied. For the assessment of selection pressure of antibiotics, a parameter of defined daily dose in absolute annual consumption (DDDatb) based on the ATC/DDD classification and in relative annual consumption (RDDDatb) as the number of defined daily doses per 100 bed-days was used. The relationship between frequency of strains resistant to a particular antibiotic and antibiotic consumption was assessed by linear regression analysis using Spearman’s correlation. The level of statistical significance was set at p?antibiotic in the following cases: piperacillin/tazobactam in Klebsiella pneumoniae, gentamicin in Klebsiella pneumoniae and Escherichia coli and amikacin in Escherichia coli and Enterobacter cloacae. Also, there was significant correlation between resistance to ceftazidime and consumption of piperacillin/tazobactam in Klebsiella pneumoniae and Escherichia coli. No relationship was found between consumption of third- and fourth-generation cephalosporins and resistance to ceftazidime or between fluoroquinolone consumption and resistance to ciprofloxacin. Conclusion The study showed the effects of both direct and indirect selection pressure on increasing resistance to gentamicin, amikacin, piperacillin/tazobactam and ceftazidime. Given the fact that no correlation was found between resistance to fluoroquinolones and consumption of either primary or secondary antibiotics, we assume that the increasing resistance to fluoroquinolones is probably due to circulation of resistance genes in the bacterial population and that this resistance was not affected by reduced use of these antibiotics.



Serotypes, biotypes and antibiotic susceptibility of 126 clinical isolates of Haemophilus influenzae.  


Serotypes, biotypes, and antibiotic susceptibility of 126 Haemophilus influenzae isolates were determined. Five of the 126 isolates were from blood and were encapsulated type b strains; those taken from other sites were not typable. There were 13% biotype I, 36% biotype II, 38% biotype III, 5% biotype IV, 4% biotype V, and 4% biotype VI isolates. Antibiotic susceptibility tests using the standard disk diffusion method showed the following resistance: ampicillin 51%, cefamandole 10%, cefuroxime 3%, chloramphenicol 28%, tetracycline 37% and sulfamethoxazole-trimethoprim 49%. None of the five type b isolates were resistant to cefotaxime, a third generation cephalosporin. The second generation cephalosporins, cefamandole and cefuroxime, showed a superior activity against H. influenzae isolates, compared to other antibiotics. Multiple drug resistance was found in 64 (51%) isolates. Four of the five type b isolates were resistant to multiple drugs. The multiple-resistance pattern most frequently observed was to ampicillin, chloramphenicol, tetracycline and sulfamethoxazole-trimethoprim. Most clinical isolates did not contain plasmids; therefore, the antibiotic resistance of these H. influenzae strains was probably chromosome-mediated. PMID:7549556

Chiu, C H; Ou, J T; Su, H C



Aminopenicillin-induced exanthema allows treatment with certain cephalosporins or phenoxymethyl penicillin  

Microsoft Academic Search

Objectives: Aminopenicillin-induced exanthema poses a problem in the management of infectious dis- eases. Due to theoretically possible immunological cross-reactivity, all b-lactam drugs, i.e. penicillins, penicillin derivatives and cephalosporins, are usually avoided. The available alternative antibiotics (macrolides, quinolones and glycopeptides) may be less effective, have more side effects, and their use increases medical costs. Moreover, their use contributes to the increasing

Jiri Trcka; Cornelia S. Seitz; Eva-B. Brocker; Gerd E. Gross; Axel Trautmann



The Absorption of Cephalosporin on Vinyl Polymers to Form Antibacterial Surfaces  

Microsoft Academic Search

In order to obtain antimicrobial polymer compositions potentially suitable for catheter fabrication, a cephalosporin was bonded to ethylene-vinyl alcohol copolymers and to their derivatives containing hydrophilic positively or negatively charged groups. The polymers were characterized by chemical and physico-chemical techniques. The antibiotic was adsorbed at a density of 1.3 mg\\/cm2 onto the unaffected polymer surface. The density was increased up

W. Marconi; G. Monopoli; A. Piozzi; R. di Rosa



Kinetic Spectrophotometric Determination of Certain Cephalosporins in Pharmaceutical Formulations  

PubMed Central

A simple, reliable, and sensitive kinetic spectrophotometric method was developed for determination of eight cephalosporin antibiotics, namely, Cefotaxime sodium, Cephapirin sodium, Cephradine dihydrate, Cephalexin monohydrate, Ceftazidime pentahydrate, Cefazoline sodium, Ceftriaxone sodium, and Cefuroxime sodium. The method depends on oxidation of each of studied drugs with alkaline potassium permanganate. The reaction is followed spectrophotometrically by measuring the rate of change of absorbance at 610?nm. The initial rate and fixed time (at 3 minutes) methods are utilized for construction of calibration graphs to determine the concentration of the studied drugs. The calibration graphs are linear in the concentration ranges 5–15??g?mL?1 and 5–25??g?mL?1 using the initial rate and fixed time methods, respectively. The results are validated statistically and checked through recovery studies. The method has been successfully applied for the determination of the studied cephalosporins in commercial dosage forms. Statistical comparisons of the results with the reference methods show the excellent agreement and indicate no significant difference in accuracy and precision.

Omar, Mahmoud A.; Abdelmageed, Osama H.; Attia, Tamer Z.



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



A novel cephalosporin deacetylating acetyl xylan esterase from Bacillus subtilis with high activity toward cephalosporin C and 7-aminocephalosporanic acid.  


A cephalosporin deacetylating acetyl xylan esterase was cloned from the genomic DNA of Bacillus subtilis CICC 20034 and functionally expressed in Escherichia coli. Its gene contained an open reading frame of 957 bp encoding 318 amino acids with a calculated mass of 35,607 Da, and it displayed significant identity to acetyl xylan esterases from Bacillus sp. 916, B. subtilis 168, and Bacillus pumilus Cect5072. The enzyme was a native homohexamer but a trimer under the condition of 1% sodium dodecyl sulfate (SDS); both forms were active and could transit to each other by incubating in or removing SDS. The enzyme belongs to carbohydrate esterase family 7 and had a double specificity on both the acetylated oligosaccharide and cephalosporin C (CPC) and 7-aminocephalosporanic acid (7-ACA). The activity of this purified enzyme toward CPC and 7-ACA was highest among all the acetyl xylan esterase from CE family 7, which were 484 and 888 U/mg, respectively, and endowed itself with great industrial interest on semi-synthetic ?-lactam antibiotics. The optimum pH of the purified enzyme was 8.0, and the optimum temperature was 50 °C, and the enzyme had high thermal stability, broad range of pH tolerance, and extremely organic solvent tolerance. PMID:23828600

Tian, Qianqian; Song, Ping; Jiang, Ling; Li, Shuang; Huang, He



[Study on cephalosporins with terahertz time-domain spectroscopy technique].  


Terahertz Time-Domain Spectroscopy (THz-TDS) technique has a wide range of applications in substances identification and quantitative analysis. In the present paper, we report absorption spectra and index of refraction of 14 kinds of pure cephalosporins in 0.2-2.6 THz, in which eight kinds have apparent absorption peaks, while the others have different index of refraction. Based on these results, different kinds of antibiotics can be identified. Besides, according to THz absorption spectra of both pure sample and real pills we calculated the contents of cefixime in the two pills produced by two manufacturers. Compared with the contents marked on the package, relative errors are 9.38% and 0.92%, respectively. The results manifest that THz-TDS technique is reliable and promising in medicine detection. PMID:23697105

Zhang, Man; Zhu, Si-Yuan; Li, Qing-Mei; Shen, Jing-Ling



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


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

Allen, Vanessa G; Seah, Christine; Martin, Irene; Melano, Roberto G



Clinical pharmacokinetics of five oral cephalosporins in calves.  


The minimal inhibitory concentrations (MIC) of cephalexin, cephradine, cefaclor, cefatrizine and cefadroxil for Salmonella species, Escherichia coli and Pasteurella multocida isolated previously from young calves were determined. The MIC90 values for cephalexin, cephradine and cefadroxil ranged between 3.12 micrograms ml-1 and 12.5 micrograms ml-1, whereas those of cefatrizine and cefaclor were 3.12 micrograms ml-1 and 0.78 microgram ml-1, respectively. Each drug was administered intravenously and orally to groups of pre-ruminating calves and orally to early ruminating calves. Although the pharmacokinetic characteristics of the drugs after intravenous injection were similar to other beta-lactam antibiotics, significant differences between the cephalosporins examined were found in respect of certain kinetic parameters. The drugs showed rapid absorption into the systemic circulation after oral administration to pre-ruminating calves but the elimination half-life values (t1/2 beta) varied between three hours (cefaclor and cefadroxil) and nine hours (cefatrizine). The bioavailability of the drugs was about 35 per cent of the administered dose. Co-administration of probenecid with each antibiotic caused a twofold or greater increase in peak serum drug concentrations (Cmax) but the effect on t1/2 beta was variable. Cephalexin, cephradine and cefaclor given to the ruminating calves resulted in very low serum or plasma concentrations and their use should be restricted to younger calves. Cefadroxil was found to give the highest serum concentrations in this age group but had significantly lower bioavailability when compared with the unweaned calves. Provisional oral dosage regimens were computed for each cephalosporin on the basis of the MIC data and the kinetic parameters derived from intravenous and oral drug administration. PMID:3317582

Soback, S; Ziv, G; Kurtz, B; Paz, R



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


During the past 15 years, emergence and dissemination of beta-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 beta-lactamases (ESBL) according to the original definition due to extension of the spectrum of already widely disseminated plasmid-encoded beta-lactamases by amino acid substitution; (b) acquisition of genes encoding ESBL from environmental bacteria as, for instance the CTX-M-type beta-lactamases from Kluyvera spp.; (c) high-level expression of chromosome-encoded beta-lactamase (bla) genes as bla(OXA) or bla(ampC) genes due to modifications in regulatory genes, mutations of the beta-lactamase promoter sequence as well as integration of insertion sequences containing an efficient promoter for intrinsic bla genes; (d) mobilization of bla genes by incorporation in integrons and horizontal transfer into other Gram-negative species such as the transfer of the ampC gene from Citrobacter freundii to Klebsiella spp.; (e) dissemination of plasmid-mediated carbapenemases as KPC and metallo-beta-lactamases, e.g. VIM and IMP; (f) non-expression of porin genes and/or efflux pump-based antibiotic resistance. This mini-review summarizes the historical emergence of beta-lactam resistance and beta-lactamases as major resistance mechanism in enteric bacteria, and also highlights recent developments such as multidrug- and carbapenem resistance. PMID:20537585

Pfeifer, Yvonne; Cullik, Angela; Witte, Wolfgang



Ready for a world without antibiotics? The Pensi?res Antibiotic Resistance Call to Action  

PubMed Central

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 Pensières 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.



Novel Metagenome-Derived Carboxylesterase That Hydrolyzes ?-Lactam Antibiotics?†  

PubMed Central

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.

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



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



Magnetic separation of antibiotics by electrochemical magnetic seeding  

NASA Astrophysics Data System (ADS)

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 using a neodymium magnet. Iron and aluminium anodes were suitable for magnetic seeding of the antibiotics. The results indicated that the ability of antibiotics to form strong complex with iron and aluminium allowed the higher removal by magnetic separation. This method would be appropriate for rapid treatment of antibiotics in wastewater.

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



[Emerging and important antibiotic resistance in Gram negatives: epidemiology, theory and practice].  


Emerging and clinically-relevant antibiotic resistance mechanisms among Gram-negative rods are the extended-spectrum beta-lactamases (ESBL), carbapenemases, and 16S RNA methylases conferring resistance to aminoglycosides. Those resistance determinants do confer multiresistance to antibiotics. They are found in Enterobacteriaceae (especially community-acquired isolates, Pseudomonas aeruginosa and Acinetobacter baumannii). Detection of ESBL-producing and carbapenemase-producing isolates rely on the use of rapid diagnostic techniques that have to be performed when a reduced susceptibility to 3rd/4th generation cephalosporins or to carbapenems is observed, respectively. Only an early detection of those emerging resistance traits may contribute to limit their nosocomial spread and to optimize the antibiotic stewardship. PMID:24843986

Nordmann, P; Poirel, L



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.



Cephalosporin C production by immobilized Cephalosporium acremonium cells in a repeated batch tower bioreactor.  


The industrial production of antibiotics with filamentous fungi is usually carried out in conventional aerated and agitated tank fermentors. Highly viscous non-Newtonian broths are produced and a compromise must be found between convenient shear stress and adequate oxygen transfer. In this work, cephalosporin C production by bioparticles of immobilized cells of Cephalosporium acremonium ATCC 48272 was studied in a repeated batch tower bioreactor as an alternative to the conventional process. Also, gas-liquid oxygen transfer volumetric coefficients, k(L)a, were determined at various air flow-rates and alumina contents in the bioparticle. The bioparticles were composed of calcium alginate (2.0% w/w), alumina ( < 44 micra), cells, and water. A model describing the cell growth, cephalosporin C production, oxygen, glucose, and sucrose consumption was proposed. To describe the radial variation of oxygen concentration within the pellet, the reaction-diffusion model forecasting a dead core bioparticle was adopted. The k(L)a measurements with gel beads prepared with 0.0, 1.0, 1.5, and 2.0% alumina showed that a higher k(L)a value is attained with 1.5 and 2.0%. An expression relating this coefficient to particle density, liquid density, and air velocity was obtained and further utilized in the simulation of the proposed model. Batch, followed by repeated batch experiments, were accomplished by draining the spent medium, washing with saline solution, and pouring fresh medium into the bioreactor. Results showed that glucose is consumed very quickly, within 24 h, followed by sucrose consumption and cephalosporin C production. Higher productivities were attained during the second batch, as cell concentration was already high, resulting in rapid glucose consumption and an early derepression of cephalosporin C synthesizing enzymes. The model incorporated this improvement predicting higher cephalosporin C productivity. PMID:14705016

Cruz, Antonio J G; Pan, Tai; Giordano, Roberto C; Araujo, Maria Lucia G C; Hokka, Carlos O



Recent analytical methods for cephalosporins in biological fluids.  

PubMed Central

Since 1980, RP chromatography has been the principal analytical technique used for cephalosporins. This technology offers selectivity, accuracy, and ease of use. Most of the methods rely on protein precipitation and, to a lesser extent, solid-phase isolation or extraction procedures. The proper selection of a method depends on the analytical constraints imposed by the overall objective of the study. For example, pharmacokinetic datum interpretation mandates that the method be validated and provide specific and accurate results. LC is the preferred technique, since it not only meets these specifications but may also distinguish between the drug and metabolites. Those chromatographic methods which quantify several different cephalosporins are not desirable for pharmacokinetic datum interpretation, since accuracy and precision are usually compromised in order that many different drugs may be quantified in a single analysis. The proper selection of sample preparation method is dependent on the presence of potential interferences and the acceptable lower limit of quantitation. Protein precipitation methods offer ease of sample preparation but may suffer from nonselectivity. Solid-phase isolation and extraction procedures may increase selectivity and improve the limit of quantitation. Although LC provides specific and accurate results, clinical laboratories may prefer to use the less specific methods for therapeutic drug monitoring. In this case, microbiological, enzymatic, and fluorimetric methods offer improved sample throughput but less specificity. However, these methods should not be used for drugs that may have a low margin of safety or if the patient is on multiple-antibiotic therapy. Future methods may involve incorporating solid-phase isolation columns to enhance the specificity of chromatographic, microbiological, enzymatic, and fluorescence methods. Advancements in microbore column technology may allow improvements in the selectivity and sensitivity of LC methods. Many investigators prefer to use simple protein precipitation procedures for sample preparation because of sample throughput constraints. However, advances in robotic sample preparation may allow the more cumbersome solid-phase isolation or extraction techniques to be used to improved sample throughput and specificity.

Toothaker, R D; Wright, D S; Pachla, L A



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.



Hepatotoxicity of antibiotics.  


Several antibiotics can cause severe hepatic injury. It is the purpose of this paper to review the main antibiotics that can cause hepatic injury and discuss the presentation, pattern, and outcome of hepatic injury. In the case of the penicillins, the combination amoxycillin-clavulanate and the penicillinase-resistant penicillins oxacillin, (di-)cloxacillin, and flucloxacillin can cause (mainly cholestatic) hepatitis. Cephalosporins have little hepatotoxicity; ceftriaxone can cause drug-induced gallstones. The potential of erythromycin and several other macrolides to cause (usually cholestatic) hepatitis is well established. Tetracyclines can cause a syndrome mimicking acute fatty liver of pregnancy, but this complication has virtually disappeared. Quinolones seem to be able to cause cholestasis. Sulfamethoxazole/trimethoprim can cause severe hepatotoxicity, especially in patients with acquired immunodeficiency syndrome (AIDS). Finally, nitrofurantoin can cause acute cholestatic and hepatocellular reactions as well as chronic hepatitis mimicking chronic auto-immune hepatitis. PMID:7491842

Hautekeete, M L



[Penicillin-resistance as indicator of resistance of Staphylococcus aureus towards cephalosporines and structure-related substances (author's transl)].  


81 strains of Staphylococcus aureus (41 methicillin-resistant and 40 -sensitive ones) were tested against older and newer cephalosporines in both broth-dilution and agardiffusion-tests using Mueller-Hinton (MH)-broth and MH-agar respectively in order to establish the degree of parallel-resistance. The substances used were cephalothin, cefazolin, cephalexin, cefamandol, cefuroxim, cefoxitin, cefotaxim and cefsulodin. Furthermore, for reasons of comparison the relatively new substance "Oxabetalaktam" was included in the investigation. As shown in Fig. 1 and Table 1 all methicillin-resistant strains required at the average at least 10 times the concentrations of cephalosporine (excepting cefsulodin) which was necessary to inhibit methicillin-sensitive strains. Again excepting cefsulodin, for each cephalosporine there was a clear bimodal distribution indicating a clear separation of both populations of strains: methicillin-sensitive and -resistant ones. Cephalothin cannot be used as test substance in agardiffusion-tests with staphylococci as there is no correlation between MIC and the inhibition zone size (Fig. 2). This is not necessary, anyway, since all methicillin-resistant strains must be regarded as resistant against virtually all cephalosporines available on the market (with the possible exception of cefamandol). By contrast, all methicillin-sensitive strains may be attacked successfully by concentrations of cephalosporines that are thought to be also effective in vivo. Since in agardiffusion-tests methicillin-resistant strains of staphylococcus aureus are recognizable as easily as are otherwise merely penicillinase-producing ones (5) by using a paper disk loaded with 6 microgram benzyl-penicillin and since infections due to other grampositive organisms than staphylococci are no indication for treatment with cephalosporines there is no need to test any other betalactam-antibiotic than benzyl-penicillin with gram-positive organisms. PMID:6784390

Hirschl, A; Stanek, G; Rotter, M



"Affect of anaerobiosis on the antibiotic susceptibility of H. influenzae"  

PubMed Central

Background Haemophilus influenzae is a human-restricted facultative anaerobe which resides mostly in the oropharynx. The majority of isolates recovered from the throat are unencapsulated commensals (NTHi), but depending on host susceptibility they cause bronchitis, otitis media and on occasion bacteremia and meningitis. Because of the variable oxygen availability in the various niche permitting bacterium replication, the organism must thrive in well oxygenated surfaces, such as pharyngeal epithelium to anoxic environments like the bottom of a Biofilm and in airway mucus. Other reports indicate that H. influenzae use aerobic respiration, anaerobic respiration and fermentation to generate ATP. To gain insight in to the activity of several classes of antibiotics against five well-characterized unencapsulated H. influenzae in room air, in 5% CO2 and under strict anaerobiosis. We also tested for the role of oxidative killing by all cidal antibiotics. Results In comparison to room air, testing in 5% CO2 had minimal effects on the susceptibility to aminoglycosides, cephalosporins, tetracycline and chloramphenicol: the MIC of rifampin and ciprofloxacin increased eight fold with certain strains in 5% CO2. All antibiotics, except trimethoprim were cidal under both growth conditions. Aminoglycosides remained bactericidal in a strict anaerobic environment, while a reliable MBC was obtained with trimethoprim only under anaerobic conditions. Kinetic analysis of the cidal action of spectinomycin and tetracycline indicated slower killing anaerobically. An oxidative mechanism for aerobic killing could not be demonstrated. Conclusions We conclude that ?-lactams, cephalosporins, macrolides, tetracycline’s, aminoglycosides, chloramphenicol, rifampin and ciprofloxacin are bactericidal against five well-characterizes H. influenzae in an aerobic and anaerobic environment. The activity of trimethoprim was increased in anaerobic conditions.



Evaluation of Vancoplus versus ceftriaxone against cephalosporin resistance MRSA strain in experimental meningitis model.  


The aim of this study was to compare the efficacy of ceftriaxone plus vancomycin (Vancoplus) versus ceftriaxone alone against cephalosporin resistant methicillin-resistant Staphylococcus aureus (MRSA) strain by using meningitis mice model. The MRSA strain ATCC 43300 was used to induce meningitis in mice. The mice were fed standard pelleted diet and water ad libitum. The test room was air conditioned with temperature 23 +/- 2 degrees C, humidity 65+/- 5% and with artificial fluorescent light 10-14 hrs. of light and dark, respectively. Twenty four mice were divided into four group containing six rats in each group. The ceftriaxone group received 28.57 mg/Kg body weight/day and the vancoplus group received 42.8 mg/Kg body weight/day and control as well as infected group received normal saline. The bacterial susceptibility test in CSF was performed for cephalosporin resistance MRSA strain by determining the lytic zone for the vancoplus and ceftriaxone antibiotic. The lytic zone was more in vancoplus as compared to ceftriaxone. It was also found that activities of antioxidant enzymes such as catalase were significantly increased (p<0.001) along with decreased (p<0.001) in lipid peroxidation (malonaldialdehyde) level in CSF of vancoplus treated group as compared to infected as well as ceftriaxone resistance group and come back to normal level. It was concluded that vancoplus beneficial for the patients who suffered from cephalosporin resistant MRSA bacterial strain. PMID:20350284

Soni, A; Chaudhary, M; Dwivedi, V K; Kumar, S; Shrivastava, S M



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

PubMed Central

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

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



Efficacy of cryptdin-2 as an adjunct to antibiotics from various generations against salmonella.  


Emerging drug resistance in Salmonella coupled with the recent poor success rate of antibiotic discovery programs of the pharmaceutical industry is a cause for significant concern. It has forced the scientific community to look for alternative new classes of antimicrobial compounds. In this context, combinations of antimicrobial peptides (AMPs) and conventional antibiotics have gained interest owing to their versatile applications. The present study was therefore planned to evaluate the synergistic effects, if any, of cryptdin-2, a mouse Paneth cell alpha-defensin, in combination with four different antibiotics i.e. ciprofloxacin, ceftriaxone, cefotaxime and chloramphenicol, which are conventionally used against Salmonella. Minimum bactericidal concentrations of the selected antimicrobial agents were determined by micro and macro broth dilution assays. In-vitro synergy between the agents was evaluated by fractional bactericidal concentration index (checkerboard test) and time-kill assay. Cryptdin-2-ciprofloxacin, cryptdin-2-ceftriaxone and cryptdin-2-cefotaxime combinations were found synergistic as evident by in vitro assays. This synergism provides an additional therapeutic choice by allowing the use of conventional antibiotics in conjunction with AMPs against MDR Salmonella. PMID:24891740

Singh, Aman Preet; Prabha, Vijay; Rishi, Praveen



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


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

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



Strategic manipulation of an industrial biocatalyst - evolution of a cephalosporin C acylase.  


Semi-synthetic cephalosporins are synthesized from the 7-amino cephalosporanic acid (7-ACA) nucleus produced from the antibiotic cephalosporin C (CephC). In recent years, a single-step enzymatic process in which CephC is directly converted into 7-ACA by a cephalosporin C acylase (CA) has attracted industrial interest because of the prospects of simplifying the process and reducing costs. CAs are members of the glutaryl acylase family that specifically use CephC as their substrate; however, known natural glutaryl acylases show very low activity on the antibiotic. We previously enhanced the catalytic efficiency on CephC of a glutaryl acylase from Pseudomonas N176 (named VAC) by a protein engineering approach, and solved the structures of the VAC, thus providing insight into the substrate binding and catalytic activity of CAs. However, the properties of such enzymes are not sufficient to encourage 7-ACA manufacturers to shift to single-step enzymatic conversion of CephC. Here, we combine structural knowledge, semi-rational design, computational approaches and evolution analysis to isolate VAC variants with altered substrate specificity (i.e. with a > 11 000-fold increase in specificity constant for CephC versus glutaryl-7-amino cephalosporanic acid, compared to wild-type) and with the highest kinetic efficiency so far obtained for a CA. Indeed, the H57?S-H70?S-L154?Y VAC variant shows the highest conversion of CephC into 7-ACA under conditions resembling those used at industrial level because of its high kinetic efficiency and the absence of substrate or product inhibition effects, and may be suitable for industrial application of the mono-step process for CephC conversion. PMID:24684708

Conti, Gianluca; Pollegioni, Loredano; Molla, Gianluca; Rosini, Elena



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



Probenecid: an unexplained effect on cephalosporin pharmacology.  

PubMed Central

1 The influence of probenecid on serum levels and urinary excretion of orally administered cephradine and cefaclor has been investigated. 2 Probenecid caused serum levels of both antibiotics to be increased and also prolonged. Urinary excretion of antibiotic activity was slightly but not significantly decreased by probenecid during the initial 6 h postdosing. It was significantly increased in 6-12 h urine, but only a small percentage of the doses were excreted during that period. 3 The increased serum levels of antibiotic were greater than could be accounted for by reduced elimination rate alone. Possible mechanisms to account for increased circulating levels of antibiotic in the presence of probenecid are discussed in the light of previous observations on probenecid induced changes in tissue distribution of beta-lactam antibiotics.

Welling, P G; Dean, S; Selen, A; Kendall, M J; Wise, R



Probenecid: an unexplained effect on cephalosporin pharmacology.  


1 The influence of probenecid on serum levels and urinary excretion of orally administered cephradine and cefaclor has been investigated. 2 Probenecid caused serum levels of both antibiotics to be increased and also prolonged. Urinary excretion of antibiotic activity was slightly but not significantly decreased by probenecid during the initial 6 h postdosing. It was significantly increased in 6-12 h urine, but only a small percentage of the doses were excreted during that period. 3 The increased serum levels of antibiotic were greater than could be accounted for by reduced elimination rate alone. Possible mechanisms to account for increased circulating levels of antibiotic in the presence of probenecid are discussed in the light of previous observations on probenecid induced changes in tissue distribution of beta-lactam antibiotics. PMID:508557

Welling, P G; Dean, S; Selen, A; Kendall, M J; Wise, R



National study on the utilization of prophylactic antibiotics in surgery, Belgium, 1986  

PubMed Central

During the last week of May 1986, a 1-week prospective study on antibiotic utilization in surgical patients was held in 104 (42%) of the 247 Belgian acute care hospitals. All surgical patients with a post-operative stay of at least 3 days were studied, involving 3112 patients. Each patient was observed for 7 days, starting from the day before surgery. Antibiotics were administered to 71·9% of all patients; 21·9% received therapeutic antibiotics and 52·9% prophylactic antibiotics; 2·9% received both. Of the 1285 patients undergoing a surgical procedure with no indication for antimicrobial prophylaxis, 50·7% nevertheless received prophylaxis; 92·8% of patients with a generally recognized indication for prophylaxis received antibiotic prophylaxis. Less than one fifth (17·1%) of all prophylactic courses were stopped on the day of the intervention whilst 26·3% were continued up to the fifth post-operative day or beyond. The most frequently prescribed drugs for this indication included first and second generation cephalosporins and nitroimidazoles. The number of different generic drugs utilized per hospital ranged from 1 to 18 (mean: 7·7).

Mertens, R.; Verbist, L.; Gordts, B.; Lauwers, S.; Potvliege, C.; Reybrouck, G.; Verschraegen, G.; Wauters, G.; Berghmans, L.; Dondeyne, F.; Stroobant, A.



Enhancing the antibiotic antibacterial effect by sub lethal tellurite concentrations: tellurite and cefotaxime act synergistically in Escherichia coli.  


The emergence of antibiotic-resistant pathogenic bacteria during the last decades has become a public health concern worldwide. Aiming to explore new alternatives to treat antibiotic-resistant bacteria and given that the tellurium oxyanion tellurite is highly toxic for most microorganisms, we evaluated the ability of sub lethal tellurite concentrations to strengthen the effect of several antibiotics. Tellurite, at nM or µM concentrations, increased importantly the toxicity of defined antibacterials. This was observed with both gram negative and gram positive bacteria, irrespective of the antibiotic or tellurite tolerance of the particular microorganism. The tellurite-mediated antibiotic-potentiating effect occurs in laboratory and clinical, uropathogenic Escherichia coli, especially with antibiotics disturbing the cell wall (ampicillin, cefotaxime) or protein synthesis (tetracycline, chloramphenicol, gentamicin). In particular, the effect of tellurite on the activity of the clinically-relevant, third-generation cephalosporin (cefotaxime), was evaluated. Cell viability assays showed that tellurite and cefotaxime act synergistically against E. coli. In conclusion, using tellurite like an adjuvant could be of great help to cope with several multi-resistant pathogens. PMID:22536386

Molina-Quiroz, Roberto C; Muñoz-Villagrán, Claudia M; de la Torre, Erick; Tantaleán, Juan C; Vásquez, Claudio C; Pérez-Donoso, José M



Enhancing the Antibiotic Antibacterial Effect by Sub Lethal Tellurite Concentrations: Tellurite and Cefotaxime Act Synergistically in Escherichia coli  

PubMed Central

The emergence of antibiotic-resistant pathogenic bacteria during the last decades has become a public health concern worldwide. Aiming to explore new alternatives to treat antibiotic-resistant bacteria and given that the tellurium oxyanion tellurite is highly toxic for most microorganisms, we evaluated the ability of sub lethal tellurite concentrations to strengthen the effect of several antibiotics. Tellurite, at nM or µM concentrations, increased importantly the toxicity of defined antibacterials. This was observed with both Gram negative and Gram positive bacteria, irrespective of the antibiotic or tellurite tolerance of the particular microorganism. The tellurite-mediated antibiotic-potentiating effect occurs in laboratory and clinical, uropathogenic Escherichia coli, especially with antibiotics disturbing the cell wall (ampicillin, cefotaxime) or protein synthesis (tetracycline, chloramphenicol, gentamicin). In particular, the effect of tellurite on the activity of the clinically-relevant, third-generation cephalosporin (cefotaxime), was evaluated. Cell viability assays showed that tellurite and cefotaxime act synergistically against E. coli. In conclusion, using tellurite like an adjuvant could be of great help to cope with several multi-resistant pathogens.

Molina-Quiroz, Roberto C.; Munoz-Villagran, Claudia M.; de la Torre, Erick; Tantalean, Juan C.; Vasquez, Claudio C.; Perez-Donoso, Jose M.



Cefadroxil, a New Broad-Spectrum Cephalosporin  

PubMed Central

Cefadroxil is a new semisynthetic cephalosporin with a broad antibacterial spectrum and a high chemotherapeutic potential when administered orally. The inhibitory activity of this compound was similar to that of cephalexin and cephradine when tested against 602 clinical isolates on Mueller-Hinton medium. In the oral treatment of experimental infections of mice, cefadroxil was more effective than cephalexin against Streptococcus pyogenes, and comparably effective against Streptococcus pneumoniae, Staphylococcus aureus, and several gram-negative species. Administered orally to mice, at doses ranging from 25 to 100 mg/kg, cefadroxil attained peak concentrations in the blood similar to those of cephalexin. At a dose of 200 mg/kg, however, higher peak levels were noted with cefadroxil than with cephalexin. In regard to other properties which were investigated, the behavior of cefadroxil compared favorably to that of cephalexin.

Buck, R. E.; Price, K. E.



Expedient antibiotics production: Final report  

SciTech Connect

The literature on the manufacture, separation and purification, and clinical uses of antibiotics was reviewed, and a bibliography of the pertinent material was completed. Five antimicrobial drugs, penicillin V and G, (and amoxicillin with clavulanic acid), Cephalexin (a cephalosporin), tetracycline and oxytetracycline, Bacitracin (topical), and sulfonamide (chemically produced) were identified for emergency production. Plants that manufacture antibiotics in the continental United States, Mexico, and Puerto Rico have been identified along with potential alternate sites such as those where SCP, enzyme, and fermentation ethanol are produced. Detailed process flow sheets and process descriptions have been derived from the literature and documented. This investigation revealed that a typical antibiotic-manufacturing facility is composed of two main sections: (1) a highly specialized, but generic, fermentation unit and (2) a multistep, complex separation and purification unit which is specific to a particular antibiotic product. The fermentation section requires specialized equipment for operation in a sterile environment which is not usually available in other industries. The emergency production of antibiotics under austere conditions will be feasible only if a substantial reduction in the complexity and degree of separation and purity normally required can be realized. Detailed instructions were developed to assist state and federal officials who would be directing the resumption of antibiotic production after a nuclear attack. 182 refs., 54 figs., 26 tabs.

Bienkowski, P.R.; Byers, C.H.; Lee, D.D.



Penicillin and cephalosporin drug allergies: a paradigm shift.  


Medication hypersensitivity is a constant variable that podiatric physicians face during their professional day. To avoid potential patient harm, an understanding of penicillin and cephalosporin hypersensitivities as it pertains to podiatric medicine needs to be achieved. To accomplish this, a narrative describing the signs, symptoms, and immunologic mechanisms for the basis of penicillin and cephalosporin drug hypersensitivities is presented. Second, specific medical literature serving as clinical-based evidence to support the prescribing of cephalosporins in patients with documented penicillin allergy is presented. Finally, a review of the medical and legal literature describing health-care provider liability regarding subsequent drug hypersensitivity is presented. The information contained in this review allows for the evolving paradigm that permits the prescribing of selective cephalosporins to patients with a history of penicillin allergy as long as the allergic symptoms were not serious or life-threatening. PMID:19017859

Smith, Robert G



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

PubMed Central

Resistance to expanded-spectrum cephalosporins commonly develops in Enterobacter aerogenes during therapy due to selection of mutants producing high levels of the chromosomal Bush group 1 ?-lactamase. Recently, resistant strains producing plasmid-mediated extended-spectrum ?-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 susceptibility to expanded-spectrum cephalosporins and a positive double-disk potentiation test. Antibiotic susceptibility was determined by standard disk diffusion and agar dilution procedures. ?-Lactamases were investigated by an isoelectric focusing overlay technique which simultaneously determined isoelectric points (pIs) and substrate or inhibitor profiles. Decreased susceptibility to cefotaxime, ceftazidime, and aztreonam (MIC range, 1 to 64 ?g/ml) was detected and associated with resistance to gentamicin and trimethoprim-sulfamethoxazole. All strains produced an inducible Bush group 1 ?-lactamase (pI 8.3). Twenty-nine of the 31 isolates also produced an enzyme similar to SHV-4 (pI 7.8), while 1 isolate each produced an enzyme similar to SHV-3 (pI 6.9) and to SHV-5 (pI 8.2). The three different SHV-derived ESBLs were transferred by transconjugation to Escherichia coli C600N and amplified by PCR. Plasmid profiles of the clinical isolates showed a variety of different large plasmids. Because of the linkage of resistance to aminoglycosides and trimethoprim-sulfamethoxazole with ESBL production, it is possible that the usage of these drugs was responsible for selecting plasmid-mediated resistance to extended-spectrum cephalosporins in E. aerogenes. Furthermore, it is important that strains such as these be recognized, because they can be responsible for institutional spread of resistance genes.

Pitout, Johann D. D.; Thomson, Kenneth S.; Hanson, Nancy D.; Ehrhardt, Anton F.; Coudron, Philip; Sanders, Christine C.



Production of penicillins and cephalosporins in an immobilized enzyme reactor  

Microsoft Academic Search

Four enzymes required for the biosynthesis of pencillins and cephalosporins by Streptomyces clavuligerus have been immobilized on an anion exchange resin. The capabilities of the system have been studied by circulation of reaction mixtures through the immobilized enzyme reactor. Within 30 min, all of the substrate d-(l-a-aminoadipyl)-l-cysteinyl-d-valine is consumed and converted to a mixture of penicillins and cephalosporins. After 60

Susan E. Jensen; Donald W. S. Westlake; Saul Wolfe



Antibiotic Safety  


... drug allergies you have had in the past. • Antibiotic resistance Antibiotic resistance has become a very big problem in the ... too often or inappropriately for viral infections. When resistance develops, the antibiotic is not able to kill the germs causing ...


[Patterns of resistance of Staph aureus and gram-negative bacteria to aminoglycosides and cephalosporins].  


The sensitivity to 4 aminoglycoside antibiotics (gentamicin, tobramycin, netilmycin and amicacin) and 5 cephalosporins (cefradine, cefamandol, cefotaxime, cefoperazone and ceftriaxone) was determined in 700 bacterial strains isolated from clinical materials in the years 1986-1987. The most frequent coexistent resistance was observed to gentamicin and tobramycin in S. aureus (30%), Klebsiella (30%), Proteus mirabilis (28%) and Enterobacter (23%). Resistance to 5 cephalosporins was found in Enterobacter (28%), Proteus spp (18%), Klebsiella (10%). Resistance to cefradine only was found in 13% of E. coli and 27% of Proteus mirabilis strains, and resistance to cefradine and cefamandol in 30% of Proteus ssp strains S. aureus strains were resistant to cefradine, cefotaxime, cefoperazone and ceftriaxone in 28% of cases. Multiple resistance was found in the strains of Enterobacter, Proteus, Pseudomonas and S. aureus which were isolated mainly in intense therapy, surgery and haematology departments. Among aminoglycosides netilmycin and amicacin were most active, among cefalosporins ceftriaxone was most effective against Gram-negative bacteria, and cefamandol against S. aureus. PMID:2629327

Ruczkowska, J; Dolna, I



Improvement of cephalosporin C production by recombinant DNA integration in Acremonium chrysogenum.  


Cephalosporins are widely used as anti-infectious beta-lactam antibiotics in clinic. For the purpose of increasing the yield of cephalosporin C (CPC) fermentation, especially in an industrial strain, A. chrysogenum genes cefEF and cefG, which encode the ultimate and penultimate steps in CPC biosynthesis, cefT, which encodes a CPC efflux pump, and vgb, which encodes a bacterial hemoglobin gene were transformed in various combinations into an industrial strain of A. chrysogenum. Both PCR and Southern blotting indicated that the introduced genes were integrated into the chromosome of A. chrysogenum. Carbon monoxide difference spectrum absorbance assay was performed and the result showed that Vitreoscilla hemoglobin was successfully expressed in A. chrysogenum and had biological activity. HPLC analysis of fermentation broth of recombinant A. chrysogenum showed that most transformants had a higher CPC production level than the parental strain. Multiple transformants containing an additional copy of cefG showed a significant increase in CPC production. However, cefT showed little effect on CPC production in this high producer. The highest improvement of CPC titer was observed in the mutant with an extra copy of cefG + cefEF + vgb whose CPC production was increased by 116.3%. This was the first report that three or more genes were introduced simultaneously into A. chrysogenum. Our results also demonstrated that the combination of these genes had a synergy effect in a CPC high producer. PMID:19787461

Liu, Yan; Gong, Guihua; Xie, Liping; Yuan, Ning; Zhu, Chunbao; Zhu, Baoquan; Hu, Youjia



Gentamicin Nephrotoxicity: Failure of Three Cephalosporins to Potentiate Injury in Rats  

PubMed Central

The possibility that gentamicin and cephalosporin antibiotics may act synergistically to produce nephrotoxicity was evaluated in an experimental model. Necrosis of the proximal tubules occurred when rats were treated with 60 to 120 mg/kg of gentamicin for 5 days but not when 15 to 20 mg/kg per day was given for up to 4 weeks. In all gentamicin-treated animals lysosomes of proximal tubules were increased in size and number and the lumens of many tubules contained a granular deposit. Examination by electron microscopy revealed that the abnormal lysosomes contained membranous whorls. The luminal deposits consisted of similar material; identical bodies were also present in the urinary sediment. To determine whether concurrent administration of a cephalosporin would augment the nephrotoxic potential of gentamicin, additional rats were treated for 4 weeks with daily injections of gentamicin (20 mg/kg) and either cephaloridine, cephalothin, or cefazolin (500 mg/kg). None of the combination regimens produced any more injury than did gentamicin alone. Images

Harrison, William O.; Silverblatt, Fredric J.; Turck, Marvin



A Retrospective Comparative Study of 2-Drug Oral and Intramuscular Cephalosporin Treatment Regimens for Pharyngeal Gonorrhea  

PubMed Central

Background.?The Centers for Disease Control and Prevention guidelines for pharyngeal gonorrhea treatment recommend dual therapy with intramuscular ceftriaxone and either azithromycin or doxycycline. Few clinical data exist to support this recommendation. Methods.?We conducted a retrospective analysis of patients diagnosed with pharyngeal gonorrhea during 1993–2011, at a sexually transmitted disease clinic in Seattle, Washington, and compared the proportion of repeat positive tests for pharyngeal gonorrhea 7–180 days following treatment among persons receiving different drug regimens. Associations of treatment regimens were assessed using relative risks through Poisson regression models with log link and robust standard errors. Results.?A total of 1440 cases of pharyngeal gonorrhea were diagnosed during the study period, 25% of which (n = 360) underwent retesting. Among retested patients, the risk of repeat positive test was lowest among persons receiving an oral cephalosporin and azithromycin (7%, reference group), and highest among those receiving an oral cephalosporin alone (30%; relative risk [RR], 3.98; 95% confidence interval [CI], 1.70–9.36) or in combination with doxycycline (33%; RR, 4.18; 95% CI, 1.64–10.7). The risk of repeat test positivity did not significantly differ between persons treated with an oral cephalosporin and azithromycin and those treated with ceftriaxone alone (9.1%; RR, 0.81; 95% CI, .18–3.60) or ceftriaxone combined with azithromycin or doxycycline (11.3%; RR, 1.20; 95% CI, .43–3.33). Conclusions.?In this retrospective study, dual therapy with an oral third-generation cephalosporin and azithromycin was comparable to ceftriaxone-based regimens in the treatment of pharyngeal gonorrhea. Combination oral therapy with doxycycline was associated with an elevated risk of persistent or recurrent infection.

Barbee, Lindley A.; Kerani, Roxanne P.; Dombrowski, Julia C.; Soge, Olusegun O.; Golden, Matthew R.



beta-lactamase stability of HR 756, a novel cephalosporin, compared to that of cefuroxime and cefoxitin.  


The stability to beta-lactamase hydrolysis of HR 756, a new cephalosporin antibiotic, was compared to the beta-lactamase stability of cefoxitin and cefuroxime. HR 756, cefoxitin, and cefuroxime were not hydrolyzed by Richmond type I, III, IV, and V beta-lactamases. Antibacterial activity of HR 756 correlated well with resistance to beta-lactamase hydrolysis except against Pseudomonas aeruginosa. HR 756, cefoxitin, and cefuroxime inhibited type I beta-lactamases, but not type III, IV, or V enzymes. HR 756 was the most active inhibitor. PMID:101128

Fu, K P; Neu, H C



Susceptibility of Polish clinical strains of Yersinia enterocolitica serotype O3 to antibiotics.  


A total of 199 clinical strains of Yersinia enterocolitica serotype O3, biotype 4 were tested for their susceptibility to antibiotics (158 strains carried the virulence plasmid pYV and 41 strains did not). A total of 114 isolates were tested by a standard disk diffusion method for 21 antibiotics. Almost all strains tested were resistant to ampicillin and cefazolin and susceptible to amoxycillin/clavulanate, cefaclor, cefamandole, cefuroxime, cefotaxime, ceftriaxone, aztreonam, imipenem, gentamicin, amikacin, netilmicin, tetracycline, doxycycline, chloramphenicol, ciprofloxacin, sulphamethoxazole, trimethoprim, co-trimoxazole and furazolidone. In addition, minimal inhibitory concentrations of 15 antibiotics were determined by the agar dilution method for all 199 strains (158 carrying plasmid pYV and 41 strains that did not). Third-generation cephalosporins such as cefotaxime and ceftriaxone and a fluoroquinolone (ciprofloxacin) were the most active antimicrobial agents tested followed by aztreonam, imipenem, trimethoprim, tetracycline, gentamicin, chloramphenicol, amoxycillin/clavulanate, cefaclor, cefuroxime, amikacin, furazolidone and sulphamethoxazole. The present study demonstrated a high susceptibility of clinical strains of Y. enterocolitica to most of the tested antibiotics. In general there was no significant difference between susceptibility to antibacterial agents of strains with or without plasmid pYV. PMID:10755244

Rastawicki, W; Gierczy?ski, R; Jagielski, M; Ka?uzewski, S; Jeljaszewicz, J



Mutational biosynthesis—a tool for the generation of structural diversity in the biosynthesis of antibiotics  

Microsoft Academic Search

Natural products represent an important source of drugs in a number of therapeutic fields, e.g. antiinfectives and cancer therapy. Natural products are considered as biologically validated lead structures, and evolution of compounds with novel or enhanced biological properties is expected from the generation of structural diversity in natural product libraries. However, natural products are often structurally complex, thus precluding reasonable

S. Weist; R. D. Süssmuth



New antibiotics for bad bugs: where are we?  

PubMed Central

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



Surveillance of antibiotic resistance in Neisseria gonorrhoeae in the WHO Western Pacific and South East Asian Regions, 2010.  


The World Health Organization (WHO) Gonococcal Antimicrobial Surveillance Programme (GASP) has conducted continuous surveillance of antimicrobial resistance in Neisseria gonorrhoeae in the WHO Western Pacific Region (WPR) to optimise antibiotic treatment and control of gonococcal disease since 1992. From 2007, this has been enhanced by the inclusion of data from the WHO South East Asian Region (SEAR). Over time, there has been recruitment of additional centres in both regions. This report provides an analysis of antimicrobial resistance in N. gonorrhoeae in the WHO WPR and SEAR derived from results of the 2010 GASP surveillance. In 2010 there were 9,744 N. gonorrhoeae isolates examined for their susceptibility to one or more of the antibiotics used for the treatment of gonorrhoea, incorporating External Quality Assurance controlled methods, from reporting centres in 19 countries and/or jurisdictions. A high proportion of penicillin and quinolone resistance was again detected amongst isolates tested in the 'Asian' countries of WHO WPR and SEAR. In contrast, lower levels of penicillin and quinolone resistance were reported from the Pacific Islands of Fiji and New Caledonia. The proportion of gonococci reported as having 'decreased susceptibility' to the third-generation cephalosporin antibiotic ceftriaxone varied widely, ranging from 1.3% to 55.8%. There is a continued need for revision and clarification of some of the in vitro criteria that are currently used to categorise the clinical importance of gonococci with different ceftriaxone and oral cephalosporin MIC levels, and to relate these to treatment outcome. Azithromycin resistance was very low in most countries reporting, except in Mongolia where it was 34%. The number of instances of spectinomycin resistance remained low. A high proportion of strains tested continued to exhibit high-level plasmid mediated resistance to tetracyclines. The continuing emergence and spread of antibiotic resistant gonococci in and from the WHO WPR and SEAR underlines the importance of the maintenance and expansion of surveillance programs such as GASP, which are essential for disease control. PMID:23153085

Lahra, Monica M



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



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


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

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



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



Severe cutaneous adverse reactions related to systemic antibiotics.  


Background.?Systemic antibiotics are a major cause of severe cutaneous adverse reactions (SCARs). The selection of alternative antibiotics and management for SCARs patients with underlying infections can be challenging. Methods.?We retrospectively analyzed 74 cases of SCARs, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), related to use of systemic antibiotics in Taiwan from January 2006 to January 2012. We analyzed the causative antibiotics, clinical features, organ involvements, and mortality. We also assessed patient tolerability to alternative antibiotics after the development of antibiotic-related SCARs. Results.?The most common causes of SCARs were penicillins and cephalosporins for SJS/TEN and AGEP; glycopeptides for DRESS. Fatality was more frequent in the SJS/TEN group. In patients with SJS/TEN, higher mortality was associated with old age and underlying sepsis before the development of SCARs. The majority of patients with penicillin- or cephalosporin-related SCARs were able to tolerate quinolones, glycopeptides, and carbapenems. Conclusions.?Complicated underlying conditions and infections may increase mortality in patients with antibiotic-related SCARs. The selection of structurally different alternative drugs is important to avoid recurrence. PMID:24599767

Lin, Ying-Fang; Yang, Chih-Hsun; Sindy, Hu; Lin, Jing-Yi; Rosaline Hui, Chung-Yee; Tsai, Yun-Chen; Wu, Ting-Shu; Huang, Ching-Tai; Kao, Kuo-Chin; Hu, Han-Chung; Chiu, Cheng-Hsun; Hung, Shuen-Iu; Chung, Wen-Hung



Influence of hybrid inorganic/organic mesoporous and nanostructured materials on the cephalosporins' efficacy on different bacterial strains.  


The aim of this study was to investigate the effect of different hybrid inorganic-organic micro- and nanomaterials (Fe(3)O(4)/PEG(600), Fe(3)O(4)/C(12), ZSM-5) on the antibacterial activity of different cephalosporins against Gram-positive and Gram-negative bacterial strains. The synergic effect of the studied materials was demonstrated by the increase in the growth inhibition zones diameter. All tested hybrid micro- and nanomaterials increased the activity of cefotaxime against Staphylococcus aureus. ZSM-5 increased the activity of cefotaxime and ceftriaxone and Fe(3)O(4)/C(12) that of ceftriaxone against Pseudomonas aeruginosa and S. aureus. The anti-Pseudomonas, anti-Klebsiella pneumoniae and anti-Bacillus subtilis activity of cefoperazone was increased by Fe(3)O(4)/C(12) nanoparticles, while the ZSM-5 improved its anti-Escherichia coli, K. pneumoniae, S. aureus and B. subtilis activity, whereas Fe(3)O(4)/PEG(600) against K. pneumoniae. The anti-K. pneumoniae activity of cefepime was increased by all tested nanoparticles, whereas its anti-B. subtilis and anti-E. coli activity was improved by Fe(3)O(4)/C(12) and Fe(3)O(4)/PEG(600) nanoparticles. In conclusion, both magnetic Fe(3)O(4) nanoparticles, charged outside as extra-shell with the antibiotic as well as ZSM-5 microparticles carrying the antibiotic inside the pores, significantly and specifically improved cephalosporin efficacy. A probable explanation for the increase in the antibiotic efficiency is the better penetration through the cellular wall of the antibiotic charged nanoparticles. PMID:23101869

Carmen Chifiriuc, M; Mihaiescu, D; Ilinca, E; Marutescu, L; Mihaescu, G; Mihai Grumezescu, A



Reasons for choice of antibiotic for the empirical treatment of CAP by Canadian infectious disease physicians  

PubMed Central

BACKGROUND: Previous studies have documented substantial variation in physician prescribing practices for the treatment of community-acquired pneumonia. Much of this variation is the result of empirical treatment, in which physicians must choose antibiotics in the a8bsence of culture and sensitivity data. OBJECTIVE: To explore the factors that influence antibiotic choice for the empirical treatment of community-acquired pneumonia. MATERIALS AND METHODS: Case-based questionnaires were mailed to all 157 members of the Canadian Infectious Disease Society in June 1996. The questionnaires presented three clinical cases and asked respondents which antibiotics they would most likely prescribe. Half the questionnaires were closed-ended, and half were open-ended. In the former, respondents were asked to explain their antibiotic choice by assigning weights to a list of clinical factors. In the latter, respondents were asked to explain their antibiotic choice by providing a short written answer. Respondents were grouped by the class of antibiotics they selected. These groups were then compared with regards to respondent characteristics (age, years of infectious disease experience, adult versus pediatric practice, country of training, province of practice) and rationale for the treatment chosen. Rationale for drug choice was analyzed statistically for the closed-ended questionnaires and qualitatively for the open-ended questionnaires. RESULTS: A response rate of 84.6% was obtained. For the first clinical case, in which the patient was young and had no underlying illness, the majority of respondents chose a macrolide (74.7%). In the second case, in which the patient was older and had evidence of comorbidity, the most common choice of antibiotic was a penicillin (40.8%). In the third case, in which the patient had intensive care unit-requiring pneumonia, the most popular choice was combination therapy of a third-generation cephalosporin and a macrolide (43.2%). There was decreasing consensus regarding the choice of antibiotics as the complexity of the cases increased. There was evidence that prescribing variation could occasionally be attributed to both respondent characteristics and the use of different decision-making strategies. CONCLUSIONS: Despite the relative homogeneity of the physicians studied, considerable variation in antibiotic choice was observed. In the first case, this variation was based on the issue of whether the patient had a typical or atypical infection. In the second case, the choice of antibiotic was related to the issue of infection by Haemophilus influenzae, although the results of the Gram stain suggested a pneumococcal infection. In the third case, variance appeared to be based more on the respondent’s age and province of practice than on any difference in decision-making strategy.

Pendergrast, Jacob; Marrie, Thomas



[Susceptibility to selected antibiotics of Yersinia enterocolitica 03 strains, carrying and not carrying plasmid pYV].  


A total of 199 clinical strains of Yersinia enterocolitica serotype O3, biotype 4 were tested for their susceptibility to antibiotics (158 strains carried the virulence plasmid pYV and 41 strains did not). 114 isolates were tested by standard disk diffusion method for 21 antibiotics. Almost all tested strains were resistant to ampicillin and cefazolin and susceptible to amoxycillin/clavulanate, cefaclor, cefamandole, cefuroxime, cefotaxime, ceftriaxone, aztreonam, imipenem, gentamicin, amikacin, netilmicin, tetracycline, doxycycline, chloramphenicol, ciprofloxacin, sulphamethoxazole, co-trimoxazole, trimethoprim and furazolidone. In addition minimal inhibitory concentrations (MICs) of 15 antibiotics were determined by agar dilution method for all 199 strains (158 plasmid positive and 41 strains plasmid negative). Third-generation cephalosporins such as cefotaxime and ceftriaxone and a fluoroquinolone (ciprofloxacin) were the most active antimicrobial agents, tested followed by aztreonam, imipenem, trimethoprim, tetracycline, gentamicin, chloramphenicol, amoxycillin/clavulanate, cefaclor, cefuroxime, amikacin, furazolidone and sulphamethoxazole. The present study demonstrated a high susceptibility of clinical strains of Y. enterocolitica to most of the tested antibiotics. In general, there was no significant difference between susceptibility of virulence plasmid pYV positive and virulence plasmid negative strains to antibacterial agents. PMID:10803262

Rastawicki, W; Gierczy?ski, R; Jagielski, M; Ka?uzewski, S; Jeljaszewicz, J



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

PubMed Central

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.

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



Hospital Acquired Antibiotic-Resistant Acinetobacter Baumannii Infections in a 400-Bed Hospital in Tehran, Iran  

PubMed Central

Objectives: Acinetobacter baumannii is an omnipresent pathogen known as a major agent in healthcare and nosocomoal-associated infections. Its ability to develop resistant pattern to the major and broad spectrum antibiotics is an important issue to be studied. Methods: In this study, 101 strains of Acinetobacter baumannii were isolated from the hospitalized patients during July 2007 to June 2009 in one teaching hospital in the southern Tehran. The identification of Acinetobacter baumannii and resistant pattern was performed by using conventional bacteriological methods and Clinical Laboratory and Standards Institute (CLSI). Results: Respiratory tract specimens were the most common place of Acinetobacter isolation. The organism was resistant to ceftazidime (96%), ceftizoxime (95%), ceftriaxone (93%), amikacin (58%), gentamicin (68%), co-terimoxazole (85%), and ciprofloxacin (85%). This pattern also pointed that imipenem had the lowest resistance rate (9%). Conclusions: Susceptibility rates of Acinetobacter baumannii isolates to third-generation cephalosporins, fluoroquinolones, amikacin, gentamicin, and trimethoprim/sulfamethoxazole (SXT) were very low and the rate of resistant Acinetobacter baumannii to imipenem was significant. It would be a good idea to consider surveillance of antibiotic usage and restriction of using broad spectrum antibiotics before development of resistance to these agents.

Vahdani, Parviz; Yaghoubi, Tofigh; Aminzadeh, Zohreh



Comparative in vitro activities of aztreonam, ciprofloxacin, norfloxacin, ofloxacin, HR 810 (a new cephalosporin), RU28965 (a new macrolide), and other agents against enteropathogens.  

PubMed Central

The in vitro activity of drugs currently used in the treatment of diarrhea against 595 enteropathogens from worldwide sources was compared with that of six newly developed antibiotics, ciprofloxacin; norfloxacin; ofloxacin; aztreonam; HR810, an expanded-spectrum cephalosporin; and RU28965, a new macrolide. In contrast with ampicillin and chloramphenicol, trimethoprim-sulfamethoxazole showed an excellent activity against all of the enteropathogens tested, except Campylobacter species. Ciprofloxacin had the highest activity, with an overall 90% MIC of less than or equal to 0.097 micrograms/ml, except for Campylobacter species (0.39 micrograms/ml). Unlike other cephalosporins, HR810 showed a satisfactory activity against Campylobacter species (90% MIC of 3.12 micrograms/ml). RU28965 was three times less active than erythromycin against Campylobacter species.

Goossens, H; De Mol, P; Coignau, H; Levy, J; Grados, O; Ghysels, G; Innocent, H; Butzler, J P



[Potential nephrotoxicity of 2nd generation cephalosporins: cefuroxime versus cefotiam].  


Forty-one hospitalized patients were randomized to be treated with cefuroxime (4.05 g/die) or cefotiam (5.30 g/die). Several patients received additionally furosemide (0.5 mg/kg body weight) intravenously. Serum creatinine and creatinine clearance did not show significant differences during versus after treatment in any of the groups. Cefotiam or cefotiam/furosemide treated patients displayed higher proteinuria and higher urinary excretion of lysosomal enzymes (leucine aminopeptidase) than patients treated with cefuroxime or cefuroxime/furosemide. Our data indicate higher tubulotoxicity of cefotiam compared to cefuroxime. PMID:8314287

Riegel, W; Hörl, W H




Microsoft Academic Search

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)

R. Saravanane; M. Lavanya



Role of Preoperative Antibiotic Prophylaxis in Preventing Postoperative Peritonitis in Newly Placed Peritoneal Dialysis Catheters  

Microsoft Academic Search

The role of vancomycin and other antibiotics in the treatment of acute peritonitis in peritoneal dialysis (PD) patients is well established. However, the role of preoperative vancomycin or cephalosporins in preventing early infection in newly placed PD catheters remains controversial. We performed a prospective randomized study to examine the role of vancomycin or cefazolin prophylaxis in decreasing the incidence of

Merit F. Gadallah; Garfield Ramdeen; Joseph Mignone; Dipal Patel; Levonne Mitchell; Sandra Tatro



Pharmacokinetics of newer cephalosporins after subconjunctival and intravitreal injection in rabbits.  


Pharmacologic considerations suggest that third-generation cephalosporins might penetrate the vitreous humor better after periocular injection and might be eliminated less readily after intravitreous injection than older agents. We studied the sodium salts of ceftizoxime, ceftriaxone, and ceftazidime, and of an investigational cephalosporin, cefepime, in rabbits. After a single subconjunctival injection in animals with normal eyes, vitreous levels ranged from 3 to 13 mg/L. After five subconjunctival injections in rabbits with infected eyes, vitreous concentrations ranged from 12 to 34 mg/L. These concentrations are not appreciably greater than those found with older beta-lactams. The vitreous half-life of the four drugs after intravitreous injection varied from 5.7 to 20 hours in rabbits with uninflamed eyes and from 9.4 to 21.5 hours in rabbits with infected eyes. Except for ceftizoxime, the half-lives were substantially longer than those for older beta-lactams and suggest predominantly anterior route elimination. Vitreous penetration of these new agents after subconjunctival injection does not appear to be sufficient to overcome the need for intravitreous injections in the treatment of endophthalmitis. However, the longer vitreous half-lives of some of the newer agents may be useful if the drugs are to be given intravitreally. PMID:8424709

Barza, M; Lynch, E; Baum, J L



Role of cephalosporins in gonorrhoea and other sexually transmitted diseases.  


Cephalosporins have a role in the treatment of gonorrhoea, and especially infections caused by strains that are penicillin-resistant, either because they produce plasmid-mediated beta-lactamase or they have chromosomally mediated diminished permeability or modified penicillin-binding proteins. Although none of the oral or Group I agents are useful, most of the Group II, III and IV agents are, and especially cefuroxime, cefotaxime, ceftriaxone and cefoxitin. In addition to uncomplicated urethral, cervical or rectal infections, appropriate regimens are also effective for the treatment of pharyngeal infections, disseminated infections and gonococcal ophthalmia. The cephalosporins have no clear role in the treatment of syphilis, granuloma inguinale, Mycoplasma or chlamydial infections or bacterial vaginosis, but ceftriaxone may be effective in chancroid, and cefoxitin in combination with an antichlamydial agent (such as a tetracycline) might be used for the treatment of pelvic inflammatory disease. PMID:3319500

Phillips, I



[Cephalosporin C production by solid state fermentation with rice grains].  


The purpose of the present study was to investigate the production of cephalosporin C in solid state fermentation with rice as a basal substrate. Among the various grains as basal substrates tested, rice was the best one and the worst one was soyflour . Among the varieties of rice examined, Tsailai rice was the best. The proposed best formula for the fermentation medium on the basis of 10 g rice grain consists the following % of the ingredients, 0.65, peptone, 0.65, ammonium sulfate, 0.26, inositol, 1.3 (v/w), trace element solution, 0.65 calcium carbonate, 0.65 calcium sulfate, 0.065, potasium sulfate, 1.3, sucrose, 0.13, DL-methionine and 2.6, methyl oleate. Of the strains of C. acremonium used, strain M8650 -R-3 was superior to strain ATCC 14553. The optimum inoculum density was 2.8 X 10(8) spores of C. acremonium M8650 -R-3 per g substrate. The initial moisture content of the medium at 49-51%, the water activity at 0.985, and the fermentation temperature at 25 degrees C were found as the optimun . After 7 days of fermentation, the maximum yield of cephalosporin C was 6420 micrograms per g substrate and the total cephalosporin C equivalent potency was 11,000 micrograms per g substrate. PMID:6540160

Wang, H H; Chiou, J Y; Wang, J Y; Hong, C Y; Tsen, W C



The emergence of Clostridium difficile PCR ribotype 027 in Denmark--a possible link with the increased consumption of fluoroquinolones and cephalosporins?  


Increasing rates of Clostridium difficile infection (CDI) with an unusual, severe course have been reported in several countries; this rise has partly been ascribed to the emergence of a virulent strain, C. difficile PCR ribotype 027 (CD027). An intriguing question is whether this could be related to increasing consumption of broadspectrum antibiotics. From 1997 to 2007, the number of hospital discharges in Denmark with the diagnosis enterocolitis caused by C. difficile increased from eight to 23 per 100,000 hospital discharges. This increase was proportional to a concomitant rise in the consumption of fluoroquinolones and cephalosporins. The first outbreak of CD027 in Denmark occurred from October 2006 to August 2007 and included 13 patients, most of them elderly, admitted to three hospitals in the same region. Most of the patients had overlapping periods of admission. All patients had been treated with broadspectrum antibiotics, in particular cephalosporins and fluoroquinolones, prior to positive culture of CD027. 30 days after confirmation of diagnosis, three of the 13 patients had died. Taken together, the data support the hypothesis that the increasing use of certain broadspectrum antibiotics may be related to a possible increase of C. difficile infection, and show that the specific contribution by CD027 in its emergence needs to be determined. PMID:19371514

Søes, L; Mølbak, K; Strøbaek, S; Truberg Jensen, K; Torpdahl, M; Persson, S; Kemp, M; Olsen, K E



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

PubMed Central

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

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



beta-Lactamase stability and in vitro activity of oral cephalosporins against strains possessing well-characterized mechanisms of resistance.  


The in vitro activity of four oral cephalosporins was assessed in dilution tests with 50 isolates of the family Enterobacteriaceae possessing well-characterized mechanisms of resistance to beta-lactam antibiotics. The interaction of the drugs with a broad array of beta-lactamases was also determined in spectrophotometric assays and tests for enzyme induction. Overall, the percentages of strains susceptible to each of the study drugs were 82% for cefixime, 62% for cefuroxime, 58% for cephalexin, and 44% for cefaclor. The poor activity of the older cephalosporins was due to a high degree of susceptibility to hydrolysis by both plasmid-mediated and chromosomally mediated beta-lactamases. For cefaclor, higher MICs were associated with higher levels of plasmid-mediated beta-lactamases in the strains. Resistance to cefuroxime was seen primarily among strains expressing high levels of class I or IV beta-lactamase. Resistance to cefixime was seen only among strains expressing high levels of class I enzymes. Neither cefixime nor cefuroxime was a strong inducer of class I beta-lactamases, although enzyme induction did appear to play a role in cefuroxime resistance in a strain of Serratia marcescens. The consistently greater activity of cefixime over cefuroxime was found not to be due to greater drug permeation into the cell. Rather, it appeared to result from the high affinity of the drug for target enzymes. PMID:2802558

Sanders, C C



The use and resistance to antibiotics in the community.  


The frequency of resistance to antibiotics among common community-acquired pathogens, and the number of drugs to which they are resistant have been increasing worldwide. The relationship between antibiotic usage and resistance is strongly supported by data from several studies. Countries with the highest per capita antibiotic consumption have the highest resistance. The emergence of penicillin-resistant Streptococcus pneumoniae is related to high consumption of antibiotics in general, as well as to increased use of aminopenicillins and/or probably to wider use of oral cephalosporins. Increased consumption of macrolides, especially the long-acting ones, correlates significantly with the level of macrolide resistance of group A streptococci and S. pneumoniae while increased use of oral cephalosporins might be associated with the increase of beta-lactamase-producing strains of Moraxella catarrhalis. Trimethoprim/sulphamethoxazole resistance is strongly associated with resistance to penicillin. A rise in consumption of fluoroquinolones is consonant with a higher rate of resistance to quinolones of S. pneumoniae, Escherichia coli and other Gram-negative bacteria. Paediatric bacterial isolates are more often resistant to various antimicrobial agents than isolates from adult patients; this higher resistance rate may be due to more frequent antimicrobial treatments in children, and extensive child to child transmission. Reliable data on antimicrobial consumption and resistance should form a basis for national policies devised to reduce the resistance of microorganisms to antibiotics. PMID:12672574

Cizman, Milan



Escherichia coli resistant to cephalosporins and quinolones is still susceptible to the cephalosporin-quinolone ester Ro 23-9424.  

PubMed Central

Ro 23-9424 is a broad-spectrum antibacterial agent consisting of a cephalosporin (desacetylcefotaxime) linked through an ester bond to a fluoroquinolone (fleroxacin). Its activity against mutants of Escherichia coli TE18 resistant to both antibacterial components was examined. E. coli TE18 overproduces the AmpC beta-lactamase and is resistant to several cephalosporins, including desacetylcefotaxime (MIC, 50 micrograms/ml), although it is still susceptible to Ro 23-9424 (MIC, 0.2 microgram/ml). Thirty-five spontaneous, two-step mutants of E. coli TE18 which were resistant to fleroxacin (MIC, 50 micrograms/ml) were isolated. In the mutants, replicative DNA biosynthesis (permeabilized cells) was resistant to fleroxacin, and some mutants had porin abnormalities. However, all remained susceptible to Ro 23-9424 (MIC, 0.5 microgram/ml). Examination of beta-lactamase activity in the parent strain revealed that it hydrolyzes desacetylcefotaxime more rapidly than it does Ro 23-9424. Thus, Ro 23-9424 may be less susceptible to the gram-negative, chromosomal beta-lactamases that hydrolyze several broad-spectrum cephalosporins and may be effective in cases in which neither of its two components is active. Images

Pace, J; Bertasso, A; Georgopapadakou, N H



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

PubMed Central

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

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



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



A Comprehensive Insight into Tetracycline Resistant Bacteria and Antibiotic Resistance Genes in Activated Sludge Using Next-Generation Sequencing  

PubMed Central

In order to comprehensively investigate tetracycline resistance in activated sludge of sewage treatment plants, 454 pyrosequencing and Illumina high-throughput sequencing were used to detect potential tetracycline resistant bacteria (TRB) and antibiotic resistance genes (ARGs) in sludge cultured with different concentrations of tetracycline. Pyrosequencing of 16S rRNA gene revealed that tetracycline treatment greatly affected the bacterial community structure of the sludge. Nine genera consisting of Sulfuritalea, Armatimonas, Prosthecobacter, Hyphomicrobium, Azonexus, Longilinea, Paracoccus, Novosphingobium and Rhodobacter were identified as potential TRB in the sludge. Results of qPCR, molecular cloning and metagenomic analysis consistently indicated that tetracycline treatment could increase both the abundance and diversity of the tet genes, but decreased the occurrence and diversity of non-tetracycline ARG, especially sulfonamide resistance gene sul2. Cluster analysis showed that tetracycline treatment at subinhibitory concentrations (5 mg/L) was found to pose greater effects on the bacterial community composition, which may be responsible for the variations of the ARGs abundance. This study indicated that joint use of 454 pyrosequencing and Illumina high-throughput sequencing can be effectively used to explore ARB and ARGs in the environment, and future studies should include an in-depth investigation of the relationship between microbial community, ARGs and antibiotics in sewage treatment plant (STP) sludge.

Huang, Kailong; Tang, Junying; Zhang, Xu-Xiang; Xu, Ke; Ren, Hongqiang



A comprehensive insight into tetracycline resistant bacteria and antibiotic resistance genes in activated sludge using next-generation sequencing.  


In order to comprehensively investigate tetracycline resistance in activated sludge of sewage treatment plants, 454 pyrosequencing and Illumina high-throughput sequencing were used to detect potential tetracycline resistant bacteria (TRB) and antibiotic resistance genes (ARGs) in sludge cultured with different concentrations of tetracycline. Pyrosequencing of 16S rRNA gene revealed that tetracycline treatment greatly affected the bacterial community structure of the sludge. Nine genera consisting of Sulfuritalea, Armatimonas, Prosthecobacter, Hyphomicrobium, Azonexus, Longilinea, Paracoccus, Novosphingobium and Rhodobacter were identified as potential TRB in the sludge. Results of qPCR, molecular cloning and metagenomic analysis consistently indicated that tetracycline treatment could increase both the abundance and diversity of the tet genes, but decreased the occurrence and diversity of non-tetracycline ARG, especially sulfonamide resistance gene sul2. Cluster analysis showed that tetracycline treatment at subinhibitory concentrations (5 mg/L) was found to pose greater effects on the bacterial community composition, which may be responsible for the variations of the ARGs abundance. This study indicated that joint use of 454 pyrosequencing and Illumina high-throughput sequencing can be effectively used to explore ARB and ARGs in the environment, and future studies should include an in-depth investigation of the relationship between microbial community, ARGs and antibiotics in sewage treatment plant (STP) sludge. PMID:24905407

Huang, Kailong; Tang, Junying; Zhang, Xu-Xiang; Xu, Ke; Ren, Hongqiang



Study on the resonance Rayleigh scattering spectra of the interactions of palladium (II)-cephalosporins chelates with 4,5-dibromofluorescein and their analytical applications.  


In pH 2.8-3.8 BR buffer medium, the third generation cephalosporin antibiotics (TGCs) such as ceftazidime (CZD), ceftriaxone (CTRX), cefoperazone (CPZ), and cefotaxime (CFTM) react with palladium(II) (Pd(II)) to form 1:2 yellowish-brown cationic chelates, which further react with 4,5-dibromofluorescein (DBF) to form 1:3 brown ion-association complexes. As a result, not only the spectra of absorption and fluorescence are changed, but also the resonance Rayleigh scattering (RRS) is enhanced greatly and the new RRS spectra are observed. The four TGCs products have similar spectral characteristics and their maximum RRS wavelengths are all located at 291 nm. The quantitative determination ranges and the detection limits of the four TGCs are 0.0065-1.0 microg mL(-1) and 2.0 ng mL(-1) for CZD, 0.0070-1.1 microg mL(-1) and 2.2 ng mL(-1) for CTRX, 0.0090-1.6 microg mL(-1) and 2.7 ng mL(-1) for CPZ, and 0.014-2.2 microg mL(-1) and 4.2 ng mL(-1) for CFTM, respectively. The optimum conditions of the reactions and the effects of foreign substances are investigated, and the composition of ion-association complexes is discussed also. Based on the ion-association reaction, a highly sensitive, simple and rapid method has been proposed to the determination of TGCs. PMID:17870290

Fu, Shenghui; Liu, Zhongfang; Liu, Shaopu; Liu, Jangtao; Yi, Aoer



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



Lipophilicity study of some non-steroidal anti-inflammatory agents and cephalosporin antibiotics: A review  

Microsoft Academic Search

Lipophilicity properties have long been considered a vital component of drug discovery and development, providing insight into the role of molecular properties in the biological activity of known and new compounds. An extensive survey of the literature published in analytical and pharmaceutical chemistry journals has been conducted. Separation, optical, electrochemical and calculation methods which were developed and used for determination

Monika D?browska; Ma?gorzata Starek; Jerzy Skuci?ski



Analysis of some common pathogens and their drug resistance to antibiotics  

PubMed Central

Objective: To investigate the common bacterial resistance of clinical isolates in our hospital in the second half of 2011. Methodology: Pathogens isolated from clinical samples in the second half of 2011 were analyzed and categorized to perform susceptibility tests. Results: In the gram-negative bacteria, Enterobacteriaceae and non-fermenting gram-negative bacilli accounted for 55.89% and 34.51%. In the gram-positive bacteria, Staphylococcus aureus, Coagulase-negative staphylococci, Enterococcus, Strptococcus pneumonia accounted for 32.85%, 40.39%, 12.41% and 10.22%, respectively. Other species accounted for 4.14%. Klebsiella pneumonia and Pseudomonas aeruginosa were sensitive to cepoperazon, cefepime and imipenem. However,Acinetobacter baumannii was more sensitive to carbapenems antibiotics, which was followed by fourth generation cephalosporins. Klebsiella pneumoniae was extremely sensitive to amikacin, cefepime and imipenem, but was resistant to ampicillin. The detection rates of the broad-spectrum Escherichia coli, Pseudomonasaeruginosa and Klebsiella pneumoniae were 54.51%, 52.08% and 38.65%. The gram negative bacilli were the prevalent clinical pathogens in our hospital in the second half of 2011. Conclusion: The drug resistance of pathogenic bacteria has increased significantly recently, thus the surveillance of antibacterial agents is necessary, and rational use of antibiotic will be urgently needed to reduce the production and dissemination of drug resistant strains.

Bao, Lidao; Peng, Rui; Ren, Xianhua; Ma, Ruilian; Li, Junping; Wang, Yi



Pharmacokinetics of some cephalosporins in normal and nephrectomized rabbits.  


We made a pharmacokinetic study of the cephalosporins cephazolin, cephaloridine, cefoperazone, and cefuroxime in the rabbit. We computed the pharmacokinetic parameters of a two-compartment open model from the plasma concentration time curves obtained at different increasing doses. Cephazolin, cephaloridine and cefoperazone demonstrated a dose dependent kinetics since the constants of apparent rate of elimination and apparent volume of distribution varied with the doses. In order to evaluate the extra-renal of elimination, we performed pharmacokinetic analysis on the same animals after nephrectomy. While cephazolin, cephaloridine and cefuroxime were eliminated primarily through the kidneys, cefoperazone was largely eliminated by extrarenal pathways. PMID:7121129

Eandi, M; Viano, I; Santiano, M



Emergence of a pneumococcal clone with cephalosporin resistance and penicillin susceptibility.  


We report two South African serotype 6B pneumococcal isolates with cephalosporin resistance, yet with susceptibility to penicillin. DNA fingerprinting revealed that they were clonal in origin. pbp 2X and 1A genes showed major alterations typical of cephalosporin-resistant pneumococci. The pbp 2B gene was completely unaltered, explaining the penicillin susceptibility of the isolates. PMID:11502545

Smith, A M; Botha, R F; Koornhof, H J; Klugman, K P



Emergence of a Pneumococcal Clone with Cephalosporin Resistance and Penicillin Susceptibility  

PubMed Central

We report two South African serotype 6B pneumococcal isolates with cephalosporin resistance, yet with susceptibility to penicillin. DNA fingerprinting revealed that they were clonal in origin. pbp 2X and 1A genes showed major alterations typical of cephalosporin-resistant pneumococci. The pbp 2B gene was completely unaltered, explaining the penicillin susceptibility of the isolates.

Smith, Anthony M.; Botha, Roelof F.; Koornhof, Hendrik J.; Klugman, Keith P.



Neisseria gonorrhoeae Strain with Reduced Susceptibilities to Extended-Spectrum Cephalosporins  

PubMed Central

The spread of Neisseria gonorrhoeae strains with reduced susceptibility to extended-spectrum cephalosporins is an increasing public health threat. Using Etest and multiantigen sequence typing, we detected sequence type 1407, which is associated with reduced susceptibilities to extended-spectrum cephalosporins, in 4 major populated regions in California, USA, in 2012.

Gose, Severin; Castro, Lina; Chung, Kathleen; Bernstein, Kyle; Samuel, Micheal; Bauer, Heidi; Pandori, Mark



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

PubMed Central

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

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



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


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

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



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. PMID:22991324

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



[Cefuroxim, a new beta-lactamase stable cephalosporin].  


In vitro activity of cefuroxime, a new cephalosporin stable to bacterial beta-lactamases, was compared with that of cefalothin and other cephalosporins by serial dilution test in more than 600 bacterial strains. Cefuroxime was more active than cefalothin on most strains of Gram negative bacilli (except Salmonella species) and also on most strains of cefalothin-resistant bacteria. In comparison to cefalothin, cefoxitin and cefamandol, cefuroxime exerted the strongest activity on meningococci, streptococci of group A and B and also on Citrobacter freundii. It was as active as cefamandol and more active than cefalothin and cefoxitin on Haemophilus influenzae (also in ampicillin-resistant strains). Pharmacokinetic studies were performed in 10 healthy adult volunteers after i.v. injection of 0.75 g, 1 g, and 1.5 g cefuroxime and of 1 g cefalothin. Cefuroxime was superior to cefalothin by slower renal excretion, longer half-life, lesser or no metabolization and better tissue penetration. Cefuroxime is well tolerated and should be administered in adequate doses corresponding to the severity of the disease and the susceptibility of the causative agent. PMID:309178

Simon, C



In vitro antibiotic activity of 11 beta-lactam antibiotics in a cancer center.  


Two-thousand, five-hundred and twenty-four bacterial isolates were tested against 11 new beta-lactam antibiotics in a prospective study conducted in a cancer center. E. coli, P. aeruginosa, and K. pneumoniae were the most common gram-negative organisms isolated, while S. aureus and Enterococcus were the most common organisms among the gram-positive. The new cephalosporins were more active than the semisynthetic penicillins against E. coli, P. aeruginosa, and K. pneumoniae (p less than 0.001). Mezlocillin had better activity than the other semisynthetic penicillins against most of the gram-negative organisms as well as the enterococci. As a result, mezlocillin was preferred as a beta-lactam agent to be employed with an aminoglycoside as empiric antibiotics for febrile patients with neoplasia. PMID:3935872

Landoy, Z; Roisilin, C; Surgalla, M J; Botzer, R; Fitzpatrick, J E; Blumenson, L E



[In vitro antibacterial activity of cefpirome: a new cephalosporin; results of a multicenter study].  


The in vitro activity of cefpirome, a new injectable cephalosporin was studied against 1,082 clinical isolates in a multicentre study. Minimum inhibitory concentrations were determined using an agar dilution method. Cefpirome was active against Enterobacteriaceae. On naturally non-producing beta-lactamase species, cefpirome was active on most of the strains with MICs < or = 0.5 mg/l, including strains producing an acquired penicillinase: E. coli 0.03-0.06, P. mirabilis 0.06-0.12, Salmonella spp. 0.06-0.06, Shigella spp. 0.016-0.03. MICs of K. pneumoniae (0.06-4) ranged from 0.016 to 32:MICs were high against expanded-spectrum betalactamase producers strains. Against species producing cephalosporinase, cefpirome was also active on most of the strains with MICs < or = 0.5: E. cloacae 0.06-2, Citrobacter spp. 0.03-1, S. marcescens 0.06-0.5, P. indol + 0.06-0.25, P. stuartii 0.12-0.5. Cefpirome was less active on Pseudomonas aeruginosa, (8-32) and on A. baumanii (16-32). MICs of cefpirome were low against Haemophilus spp. betalactamase producing or not (0.01-0.03) and M. catarrhalis (0.6-4). Activity of cefpirome on methicillin-sensitive staphylococci, was higher than other third generation cephalosporins (0.25-2) comparable to that of cephalotin and cefamandol. Methicillin-resistant strains should be considered as resistant. Pneumococci (0.01-0.03), except for penicillin-R strains, and streptococci A, B, C, G (0.01-0.06) were very susceptible. Enterococci were of low sensitivity or resistant. Among anaerobes, C. perfringens appeared often susceptible, and Bacteroides spp. resistant. PMID:7724247

Soussy, C J; Chanal, M; Derlot, E; Goldstein, F; Duval, J



Natural antibiotic susceptibility of Ewingella americana strains.  


The natural susceptibility of 20 Ewingella americana strains to 72 antibiotics was examined. MIC values were determined using a microdilution procedure in cation-adjusted Mueller-Hinton broth. Evaluation of natural antibiotic susceptibility was performed applying the German standard (where applicable). Beta-lactamases were examined with a conventional nitrocefin colony testing procedure, activity and induction assays, and SDS-PAGE. Ewingella strains were naturally resistant or of intermediate susceptibility to cefaclor, loracarbef, cefazoline, cefuroxime, cefoxitin, benzylpenicillin, oxacillin, fosfomycin, erythromycin, roxithromycin, clarithromycin, lincosamides, dalfopristin-quinupristin, ketolides, linezolid, glycopeptides, fusidic acid and rifampicin. Uniform natural sensitivity was found with acylureidopenicillins except for azlocillin, ticarcillin, several cephalosporins, carbapenems, aztreonam, tetracyclines, aminoglycosides, quinolones, azithromycin, folate-pathway inhibitors and chloramphenicol. Strains of E. americana were naturally sensitive or of intermediate susceptibility to aminopenicillins (with and without beta-lactamase inhibitors), azlocillin and nitrofurantoin. All ewingellae yielded beta-lactamases; testing of representative strains revealed that these enzymes belong to Ambler class C. Inducibility of beta-lactamase was shown for E. americana ATCC 33852T, CCUG 35675 and CCUG 42782. The present study describes a database concerning the natural susceptibility of E. americana strains to a range of antibiotics, which can be applied to validate forthcoming antibiotic susceptibility tests of these bacteria. It enlarges the number of Enterobacteriaceae expressing naturally-occurring AmpC beta-lactamases. PMID:14598935

Stock, I; Sherwood, K J; Wiedemann, B



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

PubMed Central

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



Cefoxitin, a Semisynthetic Cephamycin Antibiotic: Resistance to Beta-Lactamase Inactivation  

PubMed Central

Cefoxitin is a new, cephalosporin-like antibiotic which is highly resistant to hydrolysis by ?-lactamase. Ninety-one cultures were selected either for their general resistance to cephalosporin antibiotics or for their ability to produce ?-lactamase. Some of these cultures were resistant to cefoxitin. The capacity of each of the 91 strains to hydrolyze cefoxitin with ?-lactamase was determined. Only seven of the cultures degraded the antibiotic as determined by a general assay for ?-lactamase. Several others were able to hydrolyze cefoxitin after enzyme was induced by low concentrations of the antibiotic. The role of the constitutive and inducible enzyme in bacterial resistance to the antibiotic was investigated. Enzymatic destruction of cefoxitin was found to be an important factor contributing to bacterial resistance. However, the complete and rapid degradation of cefoxitin is not essential to resistance since one strain, Enterobacter cloacae 1316, hydrolyzed the antibiotic very slowly but was able to grow unaffected in the presence of cefoxitin. The presence of the enzyme is not necessarily sufficient to confer resistance since another culture, Klebsiella D535, readily hydrolyzed the antibiotic but was susceptible to it.

Onishi, H. Russell; Daoust, Donald R.; Zimmerman, Sheldon B.; Hendlin, David; Stapley, Edward O.



Evaluation of the Uro-Quick, a new rapid automated system, for the detection of well-characterized antibiotic-resistant bacteria.  


The Uro-Quick system has been employed to detect antibiotic resistance in genotypically and/or phenotypically well-characterized bacterial species including those that might not be easily identified by routine procedure. In order to achieve full agreement between the antibiotic susceptibility results obtained by the reference method (NCCLS) and the Uro-Quick system, the optimal experimental conditions (inoculum size, time of incubation and antibiotic concentration) for each strain to be used by the automatic system were determined. The shorter time periods for generation of correct susceptibility results were 180 min for ampicillin- and ciprofloxacin-resistant Escherichia coli and for ESBL- and Inhibitor-resistant TEM (IRT)-producing E. coli; 360 min for penicillin-susceptible Streptococcus pneumoniae, as well as for strains with reduced susceptibility to this antibiotic (both intermediate, and resistant isolates). The same time was required to detect erythromycin-resistant pneumococci irrespective of their mechanism of resistance (ribosomal methylation and efflux-mediated), Streptococcus pyogenes exhibiting the three erythromycin-resistance phenotypes (constitutive, inducible and M-type) and Klebsiella pneumoniae, Enterobacter aerogenes, Enterobacter cloacae, Serratia marcescens, Proteus mirabilis and Moraxella morganii refractory to third-generation cephalosporins, aminoglycosides, ciprofloxacin and other classes of antimicrobial agents; 480 min for penicillin-resistant, constitutive and inducible oxacillin-resistant (OXA-R) Staphylococcus aureus and OXA-R Staphylococcus epidermidis. The same period of time was also necessary to find the great majority of drug-resistance exhibited by Pseudomonas aeruginosa. Teicoplanin-resistant Staphylococcus haemolyticus, vancomycin-resistant (VanA, VanB, VanC) high-level aminoglycoside-resistant (HLAR) Enterococcus spp, and imipenem-resistant P. aeruginosa required longer incubation (24 h) to be detected. The results obtained indicate that Uro-Quick might be a reliable and promising instrument for the correct detection of the above antibiotic resistance markers. PMID:15216942

Roveta, S; Marchese, A; Debbia, E A



Contribution of BlaA and BlaB ?-Lactamases to Antibiotic Susceptibility of Yersinia enterocolitica Biovar 1B?  

PubMed Central

Highly pathogenic Yersinia enterocolitica biovar 1B produces two distinct ?-lactamases, BlaA and BlaB. Mutants of a representative biovar 1B isolate were constructed and evaluated to determine the extent of limitation of susceptibility to broad-spectrum ?-lactam antibiotics by BlaA and BlaB. The results demonstrated that BlaA, a class A enzyme, plays a significant role in limiting susceptibility to penicillins and cephalosporins. The contribution of BlaB, a class C enzyme, was less profound and was limited primarily to cephalosporin susceptibility.

Bent, Zachary W.; Young, Glenn M.



A comparative in vitro study of cephalosporin/beta-lactamase inhibitor combinations against gram negative bacilli.  


The present study aims at comparing the in-vitro susceptibility of six commercially available cephalosporin--BLI combinations with cephalosporins alone against hospital isolates of Gram negative bacilli. Gram negative bacilli, numbering 500, isolated from various clinical samples, were included in the study. The isolates were also screened for ESBL production by the methods recommended by CLSI. Susceptibility pattern of six Cephalosporins/Betalactamase inhibitor (BLI) combinations were compared with their partner cephalosporins. Overall, 29.6% of Gram negative bacilli were susceptible to the five Cephalosporins (IIIrd & IVth gen); the highest activity being shown by cefepime. Susceptibility was much higher (more than double) to the Cephalosporin combinations containing Tazobactam (TZB) & sulbactam (SLB) (62.7%). However such enhanced susceptibility was completely lacking with combinations containing clavulanate (29.1%). Gram negative bacilli, as a group, exhibited very high resistance to the new cephalosporins (IIIrd & IVth gen). When these agents were tested as fixed-dose combinations with TZB & SLB, the overall susceptibility was enhanced by more than 100%. Such an enhancement was absent with clavulanate combinations. Cefepime/TZB revealed the highest activity against ESBL producing GNB. Further studies are needed in the clinical settings as they can play an important role as good alternatives to carbapenems. PMID:24968582

Susan, M; Hariharan, T S; Sonya, J



Antibiotic prophylaxis in pulmonary surgery. A prospective randomized double-blind trial of flash cefuroxime versus forty-eight-hour cefuroxime.  


The aim of this study was to determine whether a 48-hour antibiotic prophylaxis regimen with a second-generation cephalosporin was more efficient than a flash antibiotic prophylaxis regimen in pulmonary operations. All the included patients underwent lung resection. Patients with preoperative infection were excluded. All the patients were given cefuroxime (1.5 gm intravenously) at the time of the anesthetic induction and again 2 hours later. The randomization was done postoperatively: group 1 was given placebo intravenously (n = 102) and group 2 was given cefuroxime intravenously (n = 101), each every 6 hours for 48 hours. The overall rate of infections was 46% in the 48-hour cefuroxime group versus 65% in the flash group (p = 0.005). The difference remained significant even after an adjustment with prognosis variables (p = 0.01). Six empyemas (6%) in the flash group were noted versus one (1%) in the 48-hour group (p = 0.03). From day 3 to day 8 after the operation, chest x-rays films were more often assessed as being normal in the flash group than in the 48-hour group (p = 0.005). On day 3 after operation, white blood cell counts were 13,020 +/- 1,220 elements/mm3 in the flash group versus 11,620 +/- 1,220 elements/mm3 in the 48-hour group (p = 0.03). A 48-hour antibiotic prophylaxis regimen decreases the rate of deep infections and particularly the rate of empyemas. PMID:8127120

Bernard, A; Pillet, M; Goudet, P; Viard, H



Nephrotoxicity of Cephalosporin-Gentamicin Combinations in Rats  

PubMed Central

To study the possibility that cephalosporins augment the nephrotoxicity of gentamicin, groups of rats were given four hourly subcutaneous doses of: gentamicin (5 mg/kg), gentamicin plus cephalothin (100 mg/kg), gentamicin plus cefazolin (20 mg/kg), gentamicin plus cefazolin (50 mg/kg), gentamicin plus cephaloridine (50 mg/kg), or saline diluent for 15 days. Periodic measurements were made of urine volume, urine osmolality, urine protein excretion and lysosomal enzymuria, as well as blood urea nitrogen, creatinine clearance, and drug concentrations in renal cortex and medulla. Tissue was examined by light and electron microscopy. Enzymuria and proteinuria increased early in the course of all treatment groups, whereas urine osmolality declined. No distinct patterns of these variables were discernable among the groups. Gentamicin alone, gentamicin plus cephalothin, and gentamicin plus cefazolin (20 mg/kg) caused the same significant fall in glomerular filtrate rate from control values by day 15 (P < 0.05). Gentamicin plus cefazolin (50 mg/kg) and gentamicin plus cephaloridine failed to cause a decline in glomerular filtration rate compared with controls (P > 0.05). Gentamicin concentrations in renal cortex were 5 to 10 times higher than those in medulla in all groups. Cephaloridine and cefazolin (50 mg/kg) also displayed a gradient pattern in renal cortex, whereas cephalothin and cefazolin (20 mg/kg) did not. Cytosegrosomes with myeloid figures were characteristic ultra-structural changes seen in all groups; however, they tended to be smaller with less numerous myeloid bodies in the groups receiving gentamicin plus cephalothin, cefazolin (50 mg/kg), or cephaloridine. Cephalosporins did not augment gentamicin toxicity. High doses of cefazolin and cephaloridine protected kidneys from gentamicin nephrotoxicity. The protection may involve intracellular drug interaction within the renal cortex. Images

Luft, Friedrich C.; Patel, Vimal; Yum, Moo Nahm; Kleit, Stuart A.



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


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 understand the potential contamination of the antibiotic in the environment, the degradation kinetics and mechanisms of ceftiofur in solutions blended with and without the recycled water derived from a beef farm were investigated. The transformation of ceftiofur in aqueous solutions in the presence of the CAFO recycled water was the combined process of hydrolysis and biodegradation. The total degradation rates of ceftiofur at 15 °C, 25 °C, 35 °C, and 45 °C varied from 0.4-2.8×10(-3), 1.4-4.4×10(-3), 6.3-11×10(-3), and 11-17×10(-3) h(-1), respectively, in aqueous solutions blended with 1 to 5% CAFO recycled water. Hydrolysis of ceftiofur increased with incubation temperature from 15 to 45 °C. The biodegradation rates of ceftiofur were also temperature-dependent and increased with the application amounts of the recycled CAFO water. Cef-aldehyde and desfuroylceftiofur (DFC) were identified as the main biodegradation and hydrolysis products, respectively. This result suggests that the primary biodegradation mechanism of ceftiofur was the cleavage of the ?-lactam ring, while hydrolytic cleavage occurred at the thioester bond. Unlike DFC and ceftiofur, cef-aldehyde does not contain a ?-lactam ring and has less antimicrobial activity, indicating that the biodegradation of ceftiofur in animal wastewater may mitigate the potentially adverse impact of the antibiotic to the environment. PMID:21863813

Li, Xiaolin; Zheng, Wei; Machesky, Michael L; Yates, Scott R; Katterhenry, Michael



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

PubMed Central

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

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



[Synthesis and antibacterial activity of 7 beta-[2-(2-substituted aminothiazol-4-yl)-(Z)-2-methoxyiminoacetylamido]-3-quaternaryammoniummethyl-cephalosporins].  


In order to find new cephalosporin with more and more potent antibacterial activity, nine new fourth-generation cephalosporins (N1-N9) were synthesized from ethyl 2-(2-aminothiazol-4-yl)-(Z)-2-methoxyiminoacetate (1) via acylation, substitution, hydrolysis, active esterification, condensation and salt formation. The structures of compounds (N1-N9) were confirmed by IR, MS, 1H NMR and elemental analysis. The target compounds possess different antimicrobial activities against Gram-positive and Gram-negative bacteria. The preliminary results of antibacterial activities revealed that they showed better antibacterial activities against Gram-positive bacteria than cefpirome sulfate. In particular, their activities against Staphylococcus aureus and Streptococcus albus are better. PMID:19545053

Chen, Guo-hua; Yang, Yang; Ren, Zhong; Zhong, Qi-xing



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


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.



OH.-generation by adriamycin semiquinone and H2O2; an explanation for the cardiotoxicity of anthracycline antibiotics.  


Anthracycline-induced cardiomyopathy is still a matter of discussion. The many mechanisms proposed cannot explain a selective sensitivity of the heart to these antitumor drugs. The present paper provides experimental evidence which shows that heart tissue has special biochemical conditions which favour an anthracycline-catalysed electron shuttle to H2O2. This results in the generation of highly reactive OH.-radicals, instead of O-.2-radicals, which are expected to be formed in tissues also supplemented with anthracycline-activating microsomal enzyme systems. PMID:6309165

Nohl, H; Jordan, W



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

Federal Register 2010, 2011, 2012, 2013

...FDA-2008-N-0326] New Animal Drugs; Cephalosporin Drugs...lactamases in Bacteria of Animal Origin. Veterinary Microbiology...Typhimurium Isolated from Food Animals. Microbial Drug Resistance...Antimicrobial Susceptibility Testing: Sixteenth Informational...



Cross-reactivity between a penicillin and a cephalosporin with the same side chain  

Microsoft Academic Search

BACKGROUND: The cross-reactivity between penicillins and cephalosporins can be influenced by different factors, which are not all well known. The chemical structure of the side chain may contribute to the cross-reactivity. OBJECTIVE: The study was carried out in allergic subjects who are selectively responsive to amoxicillin to determine allergenic cross-reactivity with a cephalosporin containing a side chain identical to that

Alfonso Miranda; Miguel Blanca; Jose M. Vega; Felisa Moreno; Maria J. Carmona; Juan J. García; Elisardo Segurado; Jose L. Justicia; Carlos Juarez



Risk factors and treatment outcomes of bloodstream infection caused by extended-spectrum cephalosporin-resistant Enterobacter species in adults with cancer.  


Treatment of Enterobacter infection is complicated due to its intrinsic resistance to cephalosporins. Medical records of 192 adults with cancer who had Enterobacter bacteremia were analyzed retrospectively to evaluate the risk factors for and the treatment outcomes in extended-spectrum cephalosporin (ESC)-resistant Enterobacter bacteremia in adults with cancer. The main outcome measure was 30-day mortality. Of the 192 patients, 53 (27.6%) had bloodstream infections caused by ESC-resistant Enterobacter species. Recent use of a third-generation cephalosporin, older age, tumor progression at last evaluation, recent surgery, and nosocomial acquisition were associated with ESC-resistant Enterobacter bacteremia. The 30-day mortality rate was significantly higher in the resistant group. Multivariate analysis showed that respiratory tract infection, tumor progression, septic shock at presentation, Enterobacter aerogenes as the culprit pathogen, and diabetes mellitus were independent risk factors for mortality. ESC resistance was significantly associated with mortality in patients with E. aerogenes bacteremia, although not in the overall patient population. PMID:24321352

Huh, Kyungmin; Kang, Cheol-In; Kim, Jungok; Cho, Sun Young; Ha, Young Eun; Joo, Eun-Jeong; Chung, Doo Ryeon; Lee, Nam Yong; Peck, Kyong Ran; Song, Jae-Hoon



Stability and activity improvement of cephalosporin esterase EstB from Burkholderia gladioli by directed evolution and structural interpretation of muteins.  


Esterase EstB from Burkholderia gladioli, which belongs to a family of esterases related to beta-lactamases and DD-peptidases was evolved for increased stability and simultaneously maintaining high cephalosporin C deacetylation activity. Random mutagenesis PCR was used to generate up to 5 aa substitutions per gene. A newly designed colony filter-screening assay, which was based on pH change after deacetylation of cephalosporin C in presence of DMF was established. In a first evolution round employing random mutagenesis, which included about 10(6) mutants, a set of interesting mutants was isolated. Distinct mutations identified as significant for stability were combined by a rational recombination step and the resulting recombinant was further evolved by an additional random mutagenesis round. After screening an additional 10(5) clones, it was possible to isolate a variant of EstB having more than 100-fold better activity in reactions containing 35% DMF. This mutant also showed a high increase in temperature stability (T(m) was raised by 13 degrees C) and retained high activity towards cephalosporin C under standard assay conditions. The molecular effects of mutations found in random mutants are discussed in view of the three-dimensional structure of wild-type EstB. PMID:17137667

Valinger, Goran; Hermann, Manuela; Wagner, Ulrike G; Schwab, Helmut



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



Pharmacokinetics of cephalosporins in normal and septicemic rabbits.  

PubMed Central

The differences in the pharmacokinetics of cefotaxime, moxalactam, and CPW 86-363, a new expanded-spectrum cephalosporin, were studied in healthy rabbits and in rabbits infected intravenously with Streptococcus pneumoniae. The pharmacokinetic analysis of concentration-time courses in the sera of infected animals according to a two compartment-model evidenced a clear decrease of drug fractions in the central compartment but enhanced drug fractions in the peripheral compartment. The shift was more pronounced in animals which received CPW 86-363 (60%; P less than 0.05) than in those which received cefotaxime (20%) or moxalactam (5%). Corresponding increases in drug concentration were observed in soft tissue interstitial fluid; therefore, the areas under the curve and mean residence times in the soft tissue interstitial fluid of infected rabbits were prolonged. The shift of drug fractions from the central compartment to other body fluid compartments during infection was thought to be due to cardiovascular changes associated with fever. No changes in serum binding of the three drugs were found during the course of the infection. The quantitative differences in the extent of altered distribution properties of the drugs might be due to variations in the physicochemical properties of the drugs.

Ganzinger, U; Haslberger, A



Microbiological effects of sublethal levels of antibiotics.  


The widespread use of antibiotics results in the generation of antibiotic concentration gradients in humans, livestock and the environment. Thus, bacteria are frequently exposed to non-lethal (that is, subinhibitory) concentrations of drugs, and recent evidence suggests that this is likely to have an important role in the evolution of antibiotic resistance. In this Review, we discuss the ecology of antibiotics and the ability of subinhibitory concentrations to select for bacterial resistance. We also consider the effects of low-level drug exposure on bacterial physiology, including the generation of genetic and phenotypic variability, as well as the ability of antibiotics to function as signalling molecules. Together, these effects accelerate the emergence and spread of antibiotic-resistant bacteria among humans and animals. PMID:24861036

Andersson, Dan I; Hughes, Diarmaid



Antibiotic sensitivity pattern and cost-effectiveness analysis of antibiotic therapy in an Indian tertiary care teaching hospital  

PubMed Central

Objective: The purpose of this study is to analyze the antibiotic sensitivity pattern of microorganisms, to study the antibiotic usage pattern, and to conduct a cost-effectiveness analysis (CEA) for the antibiotics prescribed in a tertiary care teaching hospital in south India. Methods: This prospective study was carried out in the General Medicine and Pulmonology departments of the hospital for a period of 6 months. The study was carried out in three phases: A prospective analysis to check the sensitivity pattern of microorganisms to various antibiotics, data extraction and determining the cost of antibiotics and finally evaluation of the sensitivity pattern of microorganisms and the antibiotic usage. A total of 796 documented records were analyzed. Findings: It was found that Escherichia coli was the major organism identified in 36.4% of the isolated specimens, followed by Klebsiella sp. (18.9%), Streptococcus pneumoniae (15.8%), Staphylococcus aureus (12.4%), and Pseudomonas (9.3%). The sensitivity pattern data of the prospective study revealed that E. coli was highly sensitive to Amikacin (99.3%), Klebsiella to Amikacin (93.8%), Pseudomonas to Meropenem (97.6%), and S. pneumoniae to Ofloxacin (93.8%). In the prescribing pattern study, it was found that the most common disease (21.2%) was found to be lower respiratory tract infection in 51 patients. Cephalosporins (73%), in particular Ceftriaxone (63.5%) was highly prescribed, followed by fluoroquinolones (53.9%). In the CEA, it was revealed that Ceftriaxone was the cost-effective antibiotic with a cost-effectiveness ratio (CER) of 78.27 compared to Levofloxacin, which had a CER of 95.13. Conclusion: Continuous surveillance of susceptibility testing is necessary for cost-effective customization of empiric antibiotic therapy. Furthermore, reliable statistics on antibiotic resistance and policies should be made available.

Sriram, Shamungum; Aiswaria, Varghese; Cijo, Annie Eapen; Mohankumar, Thekkinkattil



[Molecular mechanisms of cephalosporin resistance in Gram-negative bacteria of the Enterobacteriaceae family].  


Extended spectrum beta lactamase genes were detected by the PCR in 87.6% of 231 Enterobacteriaceae strains isolated in medical institutions of Moscow, St. Petersburg, Tomsk and Nazran that showed a decrease in their susceptibility to 3rd generation cephalosporins. Alone or in various combinations TEM type beta lactamases were detected in 43.3% of the isolates, 46.8 and 51.2% of the isolates produced SHV type and CTX type beta lactamases respectively. Combinations of 2 and 3 different determinants were detected in 40 and 14% of the isolates respectively. Production of class C beta lactamases was suspected in 28% of the isolates by their resistance to cefoxitin. The gene of ACT type beta lactamase was detected in 1 strain of Klebsiella pneumoniae and the gene of CMY type beta lactamase was detected in 1 strain of Proteus mirabilis. By the NCCLS 100% of the isolates was susceptible to meropenem, 14% was susceptible to cefotaxime, 64% was susceptible to cefepime, 81% was susceptible to cefoperazone/sulbactam, 47% was susceptible to gentamicin, 57% was susceptible to amikacin and 36% was susceptible to ciprofloxacin. PMID:15344391

Sidorenko, S V; Berezin, A G; Ivanov, D V



Impact of treatment strategies on cephalosporin and tetracycline resistance gene quantities in the bovine fecal metagenome.  


The study objective was to determine the effects of two treatment regimens on quantities of ceftiofur and tetracycline resistance genes in feedlot cattle. The two regimens were ceftiofur crystalline-free acid (CCFA) administered to either one or all steers within a pen and subsequent feeding/not feeding of therapeutic doses of chlortetracycline. A 26-day randomized controlled field trial was conducted on 176 steers. Real-time PCR was used to quantify blaCMY-2, blaCTX-M, tet(A), tet(B), and 16S rRNA gene copies/gram of feces from community DNA. A significant increase in ceftiofur resistance and a decrease in tetracycline resistance elements were observed among the treatment groups in which all steers received CCFA treatment, expressed as gene copies/gram of feces. Subsequent chlortetracycline administration led to rapid expansion of both ceftiofur and tetracycline resistance gene copies/gram of feces. Our data suggest that chlortetracycline is contraindicated when attempting to avoid expansion of resistance to critically important third-generation cephalosporins. PMID:24872333

Kanwar, Neena; Scott, H Morgan; Norby, Bo; Loneragan, Guy H; Vinasco, Javier; Cottell, Jennifer L; Chalmers, Gabhan; Chengappa, Muckatira M; Bai, Jianfa; Boerlin, Patrick



Improved cross-linked enzyme aggregates for the production of desacetyl beta-lactam antibiotics intermediates.  


Cross-linked enzyme aggregates (CLEAs) are reported for the first time for a recombinant acetyl xylan esterase (AXE) from Bacillus pumilus. With this enzyme, CLEAs production was most effective using 3.2M (80%-saturation) ammonium sulfate, followed by cross-linking for 3h with 1% (v/v) glutaraldehyde. Particle size was a key determinant of the CLEAs activity. The usual method for generating particles, by short-time vortexing was highly inefficient in terms of enzyme activity yields. In contrast, the use of long-time vortexing increased activity recovery, and a novel approach consisting in the utilization of a commercial mechanical cell disruptor which is based on a reciprocating movement recovered all the enzyme activity in few seconds. In the CLEAs thus produced, the enzyme was much more resistant to shear, heat and extreme pH values than the soluble enzyme. The CLEAs were highly effective in transforming fully 7-amino cephalosporanic acid and cephalosporin C into their corresponding desacetyl derivatives, which are important advanced intermediates in the production of semisynthetic beta-lactam antibiotics. The operational stability of such CLEAs was remarkable, with a half life of 45 cycles. Therefore, the new methodology used here should decrease the industrial cost of the CLEAs, both in terms of biocatalyst production and reusability. PMID:19733060

Montoro-García, Silvia; Gil-Ortiz, Fernando; Navarro-Fernández, José; Rubio, Vicente; García-Carmona, Francisco; Sánchez-Ferrer, Alvaro



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

PubMed Central

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

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



Antibiotic usage in 2013 on a dairy CAFO in NY State, USA  

PubMed Central

Antimicrobial resistance is threatening humans and animals worldwide. Biosecurity and 1-year usage of antibiotics on a dairy concentrated animal feeding operation (CAFO) in NY State, USA, were mapped: how much antibiotics were used, for what purpose, and whether any decrease could be warranted. Approximately 493 kg antibiotics was used, of which 376 kg was ionophores (monensin and lasalocides), 79 kg penicillin, 16.5 kg lincosamides, 8.0 kg aminoglycosides, 7.7 kg sulfamides, 3.4 kg cephalosporin, 2 kg macrolides, 0.7 kg amphenicols, and 0.1 kg fluoroquinolones. Usage reduction by 84% was realistic without compromising the animal welfare. Further reduction could be possible by improving the biosecurity and by utilizing antibiotic sensitivity testing.

Doane, Marie; Sarenbo, Sirkku



Relationship between structure and convulsant properties of some beta-lactam antibiotics following intracerebroventricular microinjection in rats.  

PubMed Central

The epileptogenic activities of several beta-lactam antibiotics were compared following their intracerebroventricular administration in rats. Different convulsant potencies were observed among the various beta-lactam antibiotics tested, but the epileptogenic patterns were similar. The patterns consisted of an initial phase characterized by wet-dog shakes followed by head tremor, nodding, and clonic convulsions. After the largest doses of beta-lactam antibiotics injected, clonus of all four limbs and/or the trunk, rearing, jumping, falling down, escape response, transient tonic-clonic seizures, and sometimes generalized seizures were observed, followed by a postictal period with a fatal outcome. At a dose of 0.033 mumol per rat, cefazolin was the most powerful epileptogenic compound among the drugs tested. It was approximately three times more potent than benzylpenicillin in generating a response and much more potent than other cephalosporins, such as ceftriaxone, cefoperazone, and cefamandole. No epileptogenic signs were observed with equimolar doses of cefotaxime, cefonicid, cefixime, and ceftizoxime in this model. The more convulsant compounds (i.e., cefazolin and ceftezole) are both characterized by the presence of a tetrazole nucleus at position 7 and show a marked chemical similarity to pentylenetetrazole. Imipenem and meropenem, the two carbapenems tested, also showed epileptogenic properties, but imipenem was more potent than meropenem, with a convulsant potency similar to those of ceftezole and benzylpenicillin. In addition, the monobactam aztreonam possessed convulsant properties more potent than those of cefoperazone and cefamandole. This suggest that the beta-lactam ring is a possible determinant of production of epileptogenic activity, with likely contributory factors in the substitutions at the 7-aminocephalosporanic or 6-aminopenicillanic acid that may increase or reduce the epileptogenic properties of the beta-lactam antibiotics. While the structure-activity relationship was also investigated, there seem to be no convincing correlations among the rank order of lipophilicities and the convulsant potencies of the compounds studied. The lack of marked convulsant properties of cefixime, cefonicid, cefuroxime, and cephradine suggests that these antibiotics may interact with a binding site which is different from that by which the beta-lactam antibiotics exert their convulsant effects or may demonstrate a reduced affinity for the relevant site(s).

De Sarro, A; Ammendola, D; Zappala, M; Grasso, S; De Sarro, G B



Trends in Antibiotic Treatment of Acute Otitis Media and Treatment Failure in Children, 2000-2011  

PubMed Central

Objectives Guidelines to treat acute otitis media (AOM) were published in 2004. Initial declines in prescribing were shown, but it's unknown if they were sustained. We examine trends in antibiotic dispensing patterns to treat AOM among a large population of children. We also document trends in antibiotic failure. Study Design Children aged 3 months to 12 years with an AOM diagnosis, enrolled in a commercial claims database between January 1, 2000-December 31, 2011 were included. Pharmacy claims within 7 days of diagnosis were searched for antibiotic prescriptions. Antibiotic failure was defined as a dispensing of a different antibiotic class within 2-18 days after the first prescription. We analyzed trends in antibiotic use and failure by class of antibiotic and year. Results We identified over 4 million children under 13 years with AOM. The proportion of antibiotic dispensing decreased from 66.0% in 2005 to 51.9% in 2007, after which the instances of dispensing rebounded to pre-guideline levels. However, levels began decreasing again in 2010 and the antibiotic use rate in 2011 was 57.6%. Cephalosporin prescriptions increased by 41.5% over eleven years. Antibiotic failure decreased slightly, and macrolides had the lowest proportion of failures, while all other classes had failure rates around 10%. Conclusions In recent years, antibiotic dispensing to treat AOM remains high. In addition, the use of broad-spectrum antibiotics is increasing despite having a high rate of treatment failure. Overprescribing of antibiotics and use of non-penicillin therapy for AOM treatment could lead to the development of antibiotic-resistant infections.

McGrath, Leah J.; Becker-Dreps, Sylvia; Pate, Virginia; Brookhart, M. Alan



Spectrophotometric determination of certain cephalosporins using molybdophosphoric acid. Part II. Determination of cefadroxil, cefapirin, ceforanide and cefuroxime.  


The use of molybdophosphoric acid as an oxidising agent for the spectrophotometric determination of four cephalosporin derivatives, viz., cefadroxil monohydrate (I), cefapirin sodium (II), ceforanide L-lysine (III) and cefuroxime sodium (IV), either in the pure form or in pharmaceutical formulations is described. Beer's law is obeyed up to 100 micrograms ml-1 for I, up to 60 micrograms ml-1 for II and IV and up to 80 micrograms ml-1 for III. The molar absorptivities were 4.58 X 10(3), 11.3 X 10(3), 9.8 X 10(3) and 10.9 X 10(3) l mol-1 cm-1 and the Sandell sensitivities were 83.3, 39.3, 53.0 and 41.0 ng cm-2 for I, II, III and IV, respectively. The slopes and intercepts of the equations of the regression line were calculated for each of these drugs with the following correlation coefficients: I, 0.9993; II, 0.9999; III, 1.000; and IV, 0.9999. These antibiotics were determined successfully both in the pure form and in pharmaceutical preparations. The results demonstrated that the proposed procedure is at least as accurate, precise and reproducible as the official methods, while being simpler and less time consuming. A statistical analysis indicated that there was no significant difference between the results obtained by the proposed procedure and those of the official methods. PMID:2712321

Issopoulos, P B



Porin Involvement in Cephalosporin and Carbapenem Resistance of Burkholderia pseudomallei  

PubMed Central

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

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



Comparison of the pharmacokinetics of cefamandole and other cephalosporin compounds.  


The pharmacokinetic properties of cefamandole were determined and compared with the properties of other cephalosporin agents. Cefamandole was found to be approximately 70% bound to protein. The mean peak concentration in serum after intramuscular (im) injection of 1 g of cefamandole was 20 microgram/ml at 0.5 hr, whereas the level at 6 hr was 1 microgram/ml. After intravenous (iv) infusion of 1 g of cefamandole, levels in serum ranged from 68 to 147 microgram/ml depending on the period of infusion. At 4 hr after infusion, levels were less than 1 microgram/ml. Probenecid elevated serum levels and prolonged excretion. The half-life (t1/2) of cefamandole after im injection ranged from 1 to 1.5 hr and from 0.45 to 1.2 hr after iv injection. Rates of serum and renal clearance of cefamandole ranged from 210 to 300 microliter/min per 1.73 m2. The apparent volume of distribution ranged from 12.4 to 17.9 liters/1.73 m2. Urinary excretion was rapid, with 60% of a dose excreted in the first 2 hr after injection. In 6 hr 90% of a dose was excreted. The pharmacokinetic properties of cefamandole were similar to those of cephalothin and cefoxitin, but the serum t1/2 was shorter than that reported for cefazolin and cefuroxime. Correlation of in vitro studies with pharmacokinetic properties revealed that cefamandole would inhibit most susceptible gram-positive and gram-negative bacteria if given by suggested im or iv regimens. PMID:650006

Neu, H C



Evaluation of separation and purification processes in the antibiotic industry  

SciTech Connect

The different separation and purification processes for three major types of antibiotics, Penicillins, Cephalosporins and Tetracyclines will be discussed. All antibiotic, processing plants contain two majors sections, a relatively small and highly specialized fermentation section and a very large (60-80% of the plant) separation and purification section. The fermentation sections for the different antibiotics are essentially identical, except for differences in growth media and operating variables, but there are vast differences in the separation and purification sections. Several different separation methods are used including filtration, ultrafiltration, centrifugation, precipitation, extraction, chromatography and various membrane methods. Variables affecting the specific separation and purification configurations include final fermentation broth concentration, by-product formed during fermentation, the physical properties and molecular structure of the various antibiotics and special purification requirements. Necessary reductions in the separation and purification processes required for rebuilding the antibiotic industry after a national emergency are discussed along with several relatively new separation/purification methods that hold great promise for effecting these reductions, chromatography, supercritical fluid extraction (SCF), and membranes. 35 refs., 10 figs., 2 tabs.

Bienkowski, P.R.; Lee, D.D.; Byers, C.H.



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



Indicators show differences in antibiotic use between general practitioners and paediatricians.  


The purpose of this investigation was to adapt to an individual physician level and to the paediatric context a set of drug-specific indicators of outpatient antibiotic use developed by the European Surveillance of Antimicrobial Consumption (ESAC) project, and to describe the differences in antibiotic prescriptions between general practitioners (GPs) and paediatricians. We conducted a retrospective cross-sectional study analysing antibiotic prescriptions in 2009 for children below 16 years of age in south-eastern France, using the National Health Insurance (NHI) outpatient reimbursement database. A generalised linear model adjusted on physicians' characteristics and patient population characteristics was used to compare indicators between GPs and paediatricians. We included 4,921 self-employed GPs and 301 paediatricians. Penicillins accounted for 47% and 45% of all antibiotics prescribed by GPs and paediatricians, respectively, followed by cephalosporins (33% and 39%) and macrolides (14% and 9%). In both specialties, there were around 70% more antibiotic prescriptions during the winter quarters compared to the summer quarters. The 13 indicators we calculated showed wide variations in antibiotic prescriptions among GPs, among paediatricians, and between GPs and paediatricians. In an adjusted econometric model, GPs were found to issue 54% more antibiotic prescriptions than paediatricians, whereas paediatricians used a significantly higher proportion of co-amoxiclav (18% vs. 12%) and cephalosporins (39% vs. 33%) and a significantly lower proportion of macrolides (9% vs. 14%) compared to GPs. A set of 13 indicators may be calculated using reimbursement data to describe outpatient antibiotic use at the physician level. We observed very different prescribing profiles between GPs and paediatricians. PMID:23361400

Pulcini, C; Lions, C; Ventelou, B; Verger, P



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

Microsoft Academic Search

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

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



Trend of antibiotic resistance in children with first acute pyelonephritis.  


There have been many recent reports of increasing antimicrobial resistance among uropathogens. In this study, we reviewed medical records of children (<18 yr age) with first acute pyelonephritis admitted to our Institution between January 2005 to December 2009. 411 children (189 girls) were studied and increasing trend in bacterial resistance toward co-trimoxazole, 2nd and 3rd generation cephalosporins and gentamicin were observed. PMID:22080687

Amira, Peco-Antic; Dusan, Paripovic; Brankica, Spasojevic-Dimitrijeva; Svetlana, Buljugic



Prediction of major antibiotic resistance in Escherichia coli and Klebsiella pneumoniae in Singapore, USA and China using a limited set of gene targets.  


Antibiotic resistance in Gram-negative bacteria, especially Enterobacteriaceae, can be conferred by a large number of different acquired resistance genes, although it appears that relatively few dominate. A previous survey of Escherichia coli and Klebsiella pneumoniae isolates from Sydney, Australia, revealed that a limited set of genes could reliably predict resistance to third-generation cephalosporins (3GCs) and aminoglycosides. Here we tested E. coli and K. pneumoniae isolates with a cefotaxime, ceftriaxone and/or ceftazidime minimum inhibitory concentration of ?2?g/mL from China and Singapore, with significantly higher resistance rates than Australia, as well as the USA. Few targets were needed to predict non-susceptibility to 3GCs (95/95; 100%) and gentamicin (47/51; 92%). The gene types detected here are consistent with previous surveys in similar countries with similar resistance rates, where the majority of 3GC resistance can be explained by blaCTX-M genes. This study identified a limited set of genes capable of predicting resistance to 3GC and aminoglycoside antibiotics and implies a restriction in the global resistance gene pool that can be exploited for diagnostic purposes. PMID:24721234

Ginn, Andrew N; Wiklendt, Agnieszka M; Zong, Zhiyong; Lin, Raymond T P; Teo, Jeanette W P; Tambyah, Paul A; Peterson, Lance R; Kaul, Karen; Partridge, Sally R; Iredell, Jonathan R



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



Antimicrobial activities of BMY-28142, cefbuperazone, and cefpiramide compared with those of other cephalosporins.  

PubMed Central

The antimicrobial activities of BMY-28142, cefbuperazone (BMY-25182; formerly T-1982), and cefpiramide (WY-44635; formerly SM-1652) were compared with those of cefmenoxime, cefoperazone, cefotaxime, ceftizoxime, and moxalactam. BMY-28142 was the most active cephalosporin against the majority of aerobic and facultatively anaerobic microorganisms studied. Its spectrum of activity was very similar to that of cefotaxime. However, BMY-28142, cefbuperazone, cefmenoxime, cefotaxime, ceftizoxime, and moxalactam were equivalent in activity and rate of killing against members of the family Enterobacteriaceae. Cefpiramide was considerably less active than the other cephalosporins against the Enterobacteriaceae.

Khan, N J; Bihl, J A; Schell, R F; LeFrock, J L; Weber, S J



[Synthesis of 7-(4,7-di-substituted coumarin-3-acetamido)cephalosporins].  


Seventeen derivatives of 7-(4,7-di-substituted coumarin-3-acetamido)cephalosporins were synthesized with acid chloride method, Vilsmeier reagent method and mixed anhydride method. Isolation and purification were fulfilled with Sephadex LH-20 column chromatography and centrifugal-TLC technique. Their chemical structures were identified by elemental analysis, IR and 1HNMR spectrum. The preliminary antibacterial activity tests showed that these cephalosporin derivatives exhibited good activity against Gram-positive bacteria and individual Gram-negative bacteria. Further experiments in pharmacology will be made. PMID:2816372

Fan, H J; Duan, T H; Li, M H



Antibiotic-Resistant Gonorrhea (ARG)  


... Clifton Rd. NE, Mailstop A12, Atlanta, GA 30333. Trends In 1993, ciprofloxacin (a fluoroquinolone) and cephalosporins (ceftriaxone ... were the only remaining recommended treatments. Similar to trends observed elsewhere in the world, CDC has observed ...


Tetracycline antibiotics and resistance mechanisms.  


Abstract The ribosome and protein synthesis are major targets within the cell for inhibition by antibiotics, such as the tetracyclines. The tetracycline family of antibiotics represent a large and diverse group of compounds, ranging from the naturally produced chlortetracycline, introduced into medical usage in the 1940s, to second and third generation semi-synthetic derivatives of tetracycline, such as doxycycline, minocycline and more recently the glycylcycline tigecycline. Here we describe the mode of interaction of tetracyclines with the ribosome and mechanism of action of this class of antibiotics to inhibit translation. Additionally, we provide an overview of the diverse mechanisms by which bacteria obtain resistance to tetracyclines, ranging from efflux, drug modification, target mutation and the employment of specialized ribosome protection proteins. PMID:24497223

Nguyen, Fabian; Starosta, Agata L; Arenz, Stefan; Sohmen, Daniel; Dönhöfer, Alexandra; Wilson, Daniel N



[Sensitivity and resistance of aerobic bacteria isolated from patients with periodontitis towards antibiotics and bacteriophages (comparative analysis)].  


In order to examine sensitivity and resistance of isolated aerobic bacteria from periodontitis materials towards antibiotics and bacteriophages, there has been studied exudations taken from 737 patients' periodontic pockets or the tissue taken from curettage. According to the rate of identified microorganisms, they have been arranged as follows: S. epidermidis 39,34+/-1,56%; S. pyogenes 18,84+/-1,25%; M. catarrhalis 17,09+/-1,2%; S. aureus 10,71+/-0,99%; E.coli-5,66+/-0,74%; Diphtheroids in 1,13+/-0,33%; S. Mucilaginosus 1,02+/-0,32%, proteus vulgaris - 0,72+/-0,27%; H. parainfluenzae - 0,72+/-0,27%; S. intermedium 0,61+/-0,24%; P. aeruginosa - 0,61+/-0,24%; H. influenzae - 0,51+/-0,22%, S. saprophiticus - 0,51+/-0,22%; S. viridans - 0,51+/-0,22%; S. pneumoniae - 0,41+/-0,2%; K. pneumoniae - 0,41+/-0,22%; S. haemoliticus - 0,41+/-0,2%; B. adolescentics - 0,3+/-0,17%; L. acidophilus -0,3+/-0,17%; S. salivarius-0,1+/-0,1%. It has been stated that percentage of polyresistant strains is growing. While having aerobic infections of periodontitis, kefzol, cephazolin, cephamezin, zinaceph, klaphoran, cephdazidim (cephalosporins I, II, II generation); tetracycline, doxycycline, (tetracyclines); 5-noks, cyprophloxacyne (chinolons I, II generation); ryphamphcyne (rymphamicynes); but standby medicines may be also considered: penicillin G, procaine penicillin (penicillines); streptomycin, kanamicin, gentamicin (aminoglycosides); lincomycin, clindamycin, (lincosamides); eritromycin, macropen (macrolides); chloramphenicol. Since the resistance of microbial strains was not developed towards bacteriophages during the treatment it is considerable to apply simultaneously the bacteriophages and standby antibiotics. PMID:16636376

Nemsadze, T D; Mshvenieradze, D D; Apridonidze, K G



LC determination of cephalosporins in in vitro rat intestinal sac absorption model  

Microsoft Academic Search

Cefotaxime sodium (CX) and Ceftazidime pentahydrate (CZ) are peptidomimetic cephalosporins (CPS) which exist as zwitterionic compounds at physiological pH and because of this reason they are not absorbed appreciably on peroral administration. The permeability of these compounds can be increased transiently by altering membrane characteristics of absorptive epithelium by use of sorption promoters (SPs). In present work a simple validated

P. Sharma; H. P. S Chawla; R. Panchagnula



In Vitro and In Vivo Activities of LB 10827, a New Oral Cephalosporin, against Respiratory Pathogens  

Microsoft Academic Search

The in vitro antibacterial activities of LB 10827, a new oral cephalosporin, against common respiratory tract pathogens were compared with those of six b-lactams (cefdinir, cefuroxime, cefprozil, penicillin G, amoxicillin- clavulanate, and ampicillin), two quinolones (trovafloxacin and ciprofloxacin), and one macrolide (clarithro- mycin). The MIC of LB 10827 at which 90% of the penicillin-resistant strains of Streptococcus pneumoniae tested were




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



Susceptibility of Respiratory Tract Anaerobes to Orally Administered Penicillins and Cephalosporins  

PubMed Central

Anaerobic bacteria recovered from airway-related infections were tested by agar dilution against selected penicillins and cephalosporins available for oral administration. Against 136 isolates, penicillins G and V showed comparable activity, particularly when pharmacological differences were considered. Although many isolates were exquisitely susceptible to the penicillins, only 55% of the Bacteroides species and 72% of all isolates were inhibited at 0.5 ?g of penicillin G per ml. Results for penicillin V at 1 ?g/ml were similar (59 and 73%). The two cephalosporins were more active at achievable levels, inhibiting 94 to 95% of Bacteroides and 95 to 96% of all isolates at 8 ?g/ml. These levels represent approximately 50% of the reported peak serum levels after oral administration of 625 mg of the penicillins and 500 mg of the cephalosporins. Dicloxacillin and nafcillin were tested against 50 isolates. The two were comparably active on a weight basis; dicloxacillin was more active when pharmacological differences were considered, but did not match the other penicillins or the cephalosporins.

Busch, David F.; Kureshi, Lubna Afzal; Sutter, Vera L.; Finegold, Sydney M.



Conjunctivitis Caused by Neisseria gonorrhoeae Isolates with Reduced Cephalosporin Susceptibility and Multidrug Resistance  

PubMed Central

We report two cases of conjunctivitis caused by Neisseria gonorrhoeae with reduced cephalosporin susceptibility. Patients showed no response to cefmenoxime eye drops and intravenous ceftriaxone administration. The patients' condition improved after the addition of oral minocycline. The isolates contained the mosaic penA for reduction of ?-lactam susceptibility.

Kitagawa, Yutaka; Maruyama, Yosuke; Yamaguchi, Satoshi; Sakane, Yuri; Miyamoto, Hitoshi; Ohashi, Yuichi



Characteristics of Demand for Pharmaceutical Products: An Examination of Four Cephalosporins  

Microsoft Academic Search

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

Sara Ellison Fisher; Iain Cockburn; Zvi Griliches; Jerry Hausman



Certain attributes of the sexual ecosystem of high-risk MSM have resulted in an altered microbiome with an enhanced propensity to generate and transmit antibiotic resistance.  


Surveillance data from a number of countries have indicated that antibiotic resistance in Neisseriagonorrhoea is strongly associated with men who have sex with men (MSM). This manuscript advances the hypothesis that certain features of the MSM sexual ecosystem may be responsible for this association. It is argued that in comparison with heterosexuals, high-risk MSM (hrMSM) have a higher prevalence of oro-penile, oro-rectal and anal sex which facilitates an enhanced mixing of the pharyngeal, rectal and penile microbiomes. In addition, hrMSM have an increased number of sexual partners per unit time and an increased prevalence of sexual relationships overlapping in time. The increased flux of microbiomes between different body habitats between sexual partners, in combination with the increased connectivity of the sexual network, serve to create a novel high-risk MSM sexual ecosystem with important consequences for the genesis and spread of antibiotic resistance. PMID:24857261

Kenyon, C; Osbak, K



Metabolism of oral cephalothin and related cephalosporins in the rat  

PubMed Central

The fate of orally administered [14C]cephalothin has been studied in the rat. This antibiotic undergoes degradation in the gut followed by the subsequent absorption of a portion of the degradation products. About 50% of the administered radioactivity appears in the urine as a mixture of thienylacetylglycine, thienylacetamidoethanol and an unidentified polar metabolite. Evidence is presented indicating that thienylacetamidoethanol arises by the enzymic reduction of a metabolic intermediate, thienylacetamidoacetaldehyde. The metabolic fate of cephalothin is very similar to that of cephaloram reported earlier. The fate of [14C]cephaloridine and 7-phenoxy[1-14C]acetamidocephalosporin was also investigated. In addition to the expected metabolites, about 5% of the cephaloridine dose is absorbed unchanged. With 7-phenoxy[1-14C]acetamidocephalosporin, 15% of the dose is recovered in urine as deacetyl-7-phenoxy[1-14C]acetamidocephalosporin.

Sullivan, H. R.; McMahon, R. E.



TB and Antibiotic Resistance  

NSDL National Science Digital Library

How does the development of antibiotic resistant strains of TB influence modern healthcare practices? We will consider genetic, environmental, epidemiological, and social perspectives of this renewed threat to public health. The TB simulation allows us to experiment with several TB strains and the antibiotics used to treat TB as we explore antibiotic resistance. * use sequence information to develop a protocol for treating antibiotic resistant TB

Marion Fass (Beloit College;Biology)



Outpatient intravenous antibiotic therapy.  


Outpatient intravenous antibiotic therapy is a cost-effective modality to shorten hospital stays and provide continued care to patients with infections. The recent availability of tamper-proof pumps that can deliver multiple antibiotics on independently timed regimens will further expand the use of home intravenous antibiotics. Problems with reimbursement remain, and new classes of oral antibiotics may provide alternatives to parenteral medications. PMID:2801460

Brown, R B; Sands, M



Reversibility of antibiotic resistance.  


Abstract Although theoretically attractive, the reversibility of resistance has proven difficult in practice, even though antibiotic resistance mechanisms induce a fitness cost to the bacterium. Associated resistance to other antibiotics and compensatory mutations seem to ameliorate the effect of antibiotic interventions in the community. In this paper the current understanding of the concepts of reversibility of antibiotic resistance and the interventions performed in hospitals and in the community are reviewed. PMID:24836051

Sundqvist, Martin



Reversibility of antibiotic resistance  

PubMed Central

Although theoretically attractive, the reversibility of resistance has proven difficult in practice, even though antibiotic resistance mechanisms induce a fitness cost to the bacterium. Associated resistance to other antibiotics and compensatory mutations seem to ameliorate the effect of antibiotic interventions in the community. In this paper the current understanding of the concepts of reversibility of antibiotic resistance and the interventions performed in hospitals and in the community are reviewed.



[Studies on the simultaneous measurement of several cephalosporins by RP-HPLC (I)].  


This paper reported the research on the simultaneous separation and determination of six cephalosporins by RP-HPLC. Six cephalosporins are cefalcor, cefalexin, cefradine, cefadroxil, cefominox and cefoxitin. The analytical conditions for this method were as follows: a Hypersil ODS C18(200 mm x 4.6 mm i.d., 5 microns), detection wavelength: 254 nm; a mobile phase solution of 50 mmol/L monopotassium phosphate (pH 3.4)-acetonitrile (87.5:12.5) and DAD detector. The flow rate was 1.0 mL/min. The calibration curves of the six compounds were linear, the correlation coefficients were 0.9951 for cefominox, 0.9999 for the others, the range were 164 ng-16.4 micrograms for cefominox, 99 ng-9.934 micrograms for cefadroxil, 104 ng-10.358 micrograms for cefalcor, 122 ng-12.224 micrograms for cefalexin, 107 ng-10.702 micrograms for cefradine and 115 ng-11.506 micrograms for cefoxitin. The recovery rates were 103.5% for cefominox, 99.3% for cefadroxil, 101.4% for cefalcor, 101.5% for cefalexin, 98.7% for cefradine and 97.6% for cefoxitin. Six cephalosporins were all stable in 50 mmol/L monopotassium phosphate (pH 3.4-4.6). When preparations of these cephalosporins were determined, it is indicated there were no difference between the results by using this method and the pharmacopoeia methods. The total separation time of these cephalosporins was within fifteen minutes. This method is simple, sensitive, rapid and accurate. PMID:12552680

Wu, Z J; Guo, W B; Zhang, Q G; Ni, K Y; Lin, Y S



Evaluation of active designs of cephalosporin C acylase by molecular dynamics simulation and molecular docking.  


Optimization to identify the global minimum energy conformation sequence in in silico enzyme design is computationally non-deterministic polynomial-time (NP)-hard, with the search time growing exponentially as the number of design sites increases. This drawback forces the modeling of protein-ligand systems to adopt discrete amino acid rotamers and ligand conformers, as well as continuum solvent treatment of the environment; however, such compromises produce large numbers of false positives in sequence selection. In this report, cephalosporin acylase, which catalyzes the hydrolytic reaction of cephalosporin C to 7-aminocephalosporanic acid, was used to investigate the dynamic features of active-site-transition-state complex structures using molecular dynamics (MD) simulations to potentially eliminate false positives. The molecular docking between cephalosporin C and wild type acylase N176 and its eight mutants showed that the rate-limiting step in the hydrolytic reaction of cephalosporin C is the acylation process. MD simulations of the active-site-transition-state complex structures of the acylation processes for N176 and its eight mutants showed that the geometrical constraints between catalytic residues and small molecule transition states are always well maintained during the 20 ns simulation for mutants with higher activities, and more hydrogen bonds between binding residues and functional groups of the ligand side chain in the active pocket are formed for mutants with higher activities. The conformations of the ligand transition states were changed greatly after the simulation. This indicates that the hydrogen bond network between the ligand and protein could be improved to enhance the activity of cephalosporin C acylase in subsequent design. PMID:24935111

Li, Qing; Huang, Xiaoqiang; Zhu, Yushan



Efficacy evaluation of some antibiotics against syrian brucella spp isolates, in vitro.  


Brucellosis is an endemic zoonosis in Syria, affecting large numbers of animals and there are an increasing number of cases in humans. The aim of this study is to investigate the in vitro efficacy of various traditional and new antibiotics against 89 Brucella isolates (isolated from domestic animals) collected from different Syrian regions. Minimum inhibitory concentrations (MICs) of seventeen antibiotics were determined. Ciprofloxacin and ofloxacin were the most effective antibiotics, whereas sparfloxacin, levofloxacin, doxycycline and tetracycline had a moderate activity. In contrast, moxifloxacin and rifampicin had a low activity, while streptomycin, spiramycin and cephalosporines were ineffective. As a result, we come to the conclusion that a combination between one effective quinolone and doxycycline has a good efficacy against Brucella. Further in vivo studies are necessary to support this suggestion. PMID:24031952

Safi, Mazen; Al-Mariri, Ayman



Antibiotic Susceptibility of Streptococcus Pyogenes Isolated from Respiratory Tract Infections in Dakar, Senegal  

PubMed Central

Group A Streptococcus (GAS) is one of the major causes of respiratory tract infections. The objectives of this study were to identify isolates of S. pyogenes obtained from respiratory tract infections, and to assess their susceptibility to several antibiotics. A total of 40 strains were isolated and their susceptibility to 17 antibiotics was tested using a standard disk diffusion method. The minimum inhibitory concentrations (MICs) were determined using the E-test. All isolates were sensitive to ?-lactam antibiotics including penicillin, amoxicillin, and cephalosporins. Macrolides remain active with the exception of spiramycin, which showed reduced susceptibility. Out of the 40 isolates, 100% of the isolates were resistant to tetracycline. Interestingly, isolates were sensitive to chloramphenicol, teicoplanin, vancomycine, and levofloxacin, providing potential alternative choices of treatment against infections with S. pyogenes.

Camara, Makhtar; Dieng, Assane; Boye, Cheikh Saad Bouh



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

PubMed Central

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

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



Efficacy evaluation of some antibiotics against syrian brucella spp isolates, in vitro  

PubMed Central

Brucellosis is an endemic zoonosis in Syria, affecting large numbers of animals and there are an increasing number of cases in humans. The aim of this study is to investigate the in vitro efficacy of various traditional and new antibiotics against 89 Brucella isolates (isolated from domestic animals) collected from different Syrian regions. Minimum inhibitory concentrations (MICs) of seventeen antibiotics were determined. Ciprofloxacin and ofloxacin were the most effective antibiotics, whereas sparfloxacin, levofloxacin, doxycycline and tetracycline had a moderate activity. In contrast, moxifloxacin and rifampicin had a low activity, while streptomycin, spiramycin and cephalosporines were ineffective. As a result, we come to the conclusion that a combination between one effective quinolone and doxycycline has a good efficacy against Brucella. Further in vivo studies are necessary to support this suggestion.

Safi, Mazen; Al-Mariri, Ayman



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



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 0.9 mM using 10mM phosphate buffer at pH 8 as the optimum condition for the aqueous solution. The applied methodology, named salting-out assisted liquid/liquid extraction (SALLE) involves the use of 1.25 g of ammonium sulfate as salting-out agent. The separation of cephalosporins using a Luna C18 (150 mm × 0.3mm, 5 µm, 100 Å) column was achieved under the following conditions: a gradient program combining solvent A (0.1% formic acid in water, pH 4) and solvent B (acetonitrile-methanol (50:50, v/v)), at a flow rate of 20 µl min(-1), column temperature 35°C and injection volume 7 µl with UV detection at 250 nm. The limits of quantification for the studied compounds were between 4.3 and 22.7 ?g/L for water samples and 4.1 and 73.3 ?g/kg in the case of beef samples, lower than the maximum residue limits permitted by the EU for this kind of food. The developed methodology has demonstrated its suitability for the analysis of these widely applied antibiotics in environmental water and meat samples, including beef and pork muscle, with high sensitivity, precision and satisfactory recoveries. PMID:24054686

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



Analysis of antibiotics in fish samples.  


The use of antibiotics in food-producing animals has generated considerable interest because the widespread administration of these drugs may lead to the development of resistant human pathogens. A large increase in the demand for seafood products has occurred in the last century. This has led to a concomitant increase in high-intensity aquaculture methods, characterized by high stock density and volume, and the heavy use of formulated feeds containing antibiotics, among other substances. Therefore, accurate and sensitive determination of antibiotic residues is now a necessity. In order to protect human health, the European Union and other regulatory authorities worldwide have established maximum residue limits (MRL) for antibiotic residues in animal products entering the human food chain. This paper reviews the most recent methods for analysis of antibiotic residues in fish. PMID:19533104

Cañada-Cañada, F; Muñoz de la Peña, A; Espinosa-Mansilla, A



Inpatient antibiotics pharmacology and physiological use in Hayatabad medical complex, Pakistan  

PubMed Central

Antibiotics are used commonly and as powerful medicines, it well known that they affect the variety and composition of the microflora which has important physiological roles, therefore and for other health complications, the aim of the current study was to evaluate and estimate the appropriateness of antimicrobial drugs use in Hayatabad Medical Complex (HMC), Peshawar, Pakistan. The present work is based on the hospitalized patient’s case studies. Individual patients were interviewed using the prepared questionnaire for the study. All hospitalized patients who received antibiotics were evaluated by a cross-sectional study. The total number of patients interviewed was 270 in medical department. According to our study in medical department, for prophylaxis 64.3% of antibiotic was used, whereas, an empirical use was 35.7%. Prodigious double regimen of antibiotics was observed throughout the study. The most prescribed antimicrobial group is penicillin and followed by tetracycline, macrolides, quinolones, and cephalosporin. Furthermore, 14.56% antibiotics were prescribed on generic name and 85.43% were prescribed on the basis of brand names. Taken together, the antibiotic use in medical department was unsatisfactory and irrational. In summary, in order to protect the physiological functions of flora microorganisms, a combination of both limitation, continuous education of physicians and elaboration of local guidelines appear to be necessary to improve rational antibiotic use.

Khan, Salman; Shehzad, Adeeb; Shehzad, Omer; Al-Suhaimi, Ebtesam A



Consumption of antibiotics in Sweden, 1975 to 1992: pharmacoeconomic and clinical aspects.  


Using official statistics for the consumption of antibiotics in Sweden during the period 1975 to 1991, the pharmacoeconomic consequences were analysed. An increase of more than 25% in Swedish consumption of antibiotics during the study period was found. There is no obvious clinical explanation; indeed, improved hospital hygiene as well as decreased frequencies of some common bacterial infections should have resulted in a decrease in total consumption. Overconsumption was most marked for oral antibiotics. In 1991 the most often used antibiotic, phenoxymethylpenicillin, was given in about 20 million defined daily doses (DDD), corresponding to 2.4 DDDs per member of the population per year. From a pharmacoeconomic viewpoint, this overconsumption is acceptable because the drug has a low price and causes a minimum of severe adverse reactions. More serious is the marked misuse of tetracyclines (12 million DDDs in 1991) and macrolides (5.3 million DDDs in 1991), with which adverse reactions are more common, and where the high consumption has led to increasing frequencies of resistance among common bacterial pathogens. This emergent resistance often leads to a need to use newer more expensive antibiotics, in addition to the costs resulting from therapeutic failures of the initial treatment. Of the parenteral antibiotics, the cephalosporins, particularly cefuroxime, dominate in Sweden. The introduction of 'diagnosis-related groups' (DRGs) for reimbursement of hospitals for in-patient care is likely to result in the development of antibiotic use in 'intensive home care' as has occurred in the US.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:10147013

Norrby, S R



Genotypic-Phenotypic Discrepancies between Antibiotic Resistance Characteristics of Escherichia coli Isolates from Calves in Management Settings with High and Low Antibiotic Use ? †  

PubMed Central

We hypothesized that bacterial populations growing in the absence of antibiotics will accumulate more resistance gene mutations than bacterial populations growing in the presence of antibiotics. If this is so, the prevalence of dysfunctional resistance genes (resistance pseudogenes) could provide a measure of the level of antibiotic exposure present in a given environment. As a proof-of-concept test, we assayed field strains of Escherichia coli for their resistance genotypes using a resistance gene microarray and further characterized isolates that had resistance phenotype-genotype discrepancies. We found a small but significant association between the prevalence of isolates with resistance pseudogenes and the lower antibiotic use environment of a beef cow-calf operation versus a higher antibiotic use dairy calf ranch (Fisher's exact test, P = 0.044). Other significant findings include a very strong association between the dairy calf ranch isolates and phenotypes unexplained by well-known resistance genes (Fisher's exact test, P < 0.0001). Two novel resistance genes were discovered in E. coli isolates from the dairy calf ranch, one associated with resistance to aminoglycosides and one associated with resistance to trimethoprim. In addition, isolates resistant to expanded-spectrum cephalosporins but negative for blaCMY-2 had mutations in the promoter regions of the chromosomal E. coli ampC gene consistent with reported overexpression of native AmpC beta-lactamase. Similar mutations in hospital E. coli isolates have been reported worldwide. Prevalence or rates of E. coli ampC promoter mutations may be used as a marker for high expanded-spectrum cephalosporin use environments.

Davis, Margaret A.; Besser, Thomas E.; Orfe, Lisa H.; Baker, Katherine N. K.; Lanier, Amelia S.; Broschat, Shira L.; New, Daniel; Call, Douglas R.



Changes in Bacterial Species and Antibiotic Sensitivity in Intensive Care Unit: Acquired Urinary Tract Infection during 10 Years Interval (2001-2011).  


Purpose: Patients in the intensive care unit (ICU) are usually at greater risk for acquiring urinary tract infections (UTIs). Few studies have focused on UTIs specifically acquired within the ICU. We studied the change in bacterial species causing UTIs in ICU admitted patients in 2001 and 2011. Materials and Methods: We reviewed the medical records of a total of 2,890 ICU patients who had undergone urine culture in 2001 and 2011 at the Yeouido and Bucheon St. Mary's hospitals. Changes in causative organisms and their antibiotic sensitivity between the years 2001 and 2011 were analyzed. Results: Escherichia coli (E. coli) was the most common organism in ICU-acquired UTIs in 2001 and 2011 in our study. The pathogens that significantly increased in 2011 compared to 2001 were Pseudomonas, and Klebsiella species (P < .05). In 2011gram-negative organisms showed relatively higher sensitivities to amikacin, imipenem, and tazocin (72.0%, 77.5% and 76.1%, respectively), whereas they showed relatively lower sensitivities to third-generation cephalosporins and ciprofloxacin (55.2% and 45.0%, respectively). In 2011gram-positive organisms showed high sensitivities to teicoplanin and vancomycin (91.1% and 87.9%, respectively), whereas they showed low sensitivities to ampicillin and ciprofloxacin (24.1% and 25.5%, respectively). The antibiotic resistance rate of Pseudomonas species was nearly doubles that of E. coli. Conclusion: Infections caused by Pseudomonas and Klebsiella species were found to have increased significantly in 2011. Pseudomonas species had a significantly lower susceptibility to antibiotic sensitivity than other identified organisms.  PMID:24807764

Yoon, Byung Il; Kim, Hyo Sin; Kim, Sung Dae; Cho, Kang Jun; Kim, Sun Wook; Ha, U-Syn; Cho, Yong-Hyun; Sohn, Dong Wan



Emergence of high ampicillin-resistant Enterococcus faecium isolates in a kidney transplant ward: role of antibiotic pressure and cross transmission.  


The epidemiology of patients associated with ampicillin-resistant Enterococcus faecium (ARE) was investigated by combining both clinical approach and molecular analysis in a kidney transplant patient's ward. A case-control study was performed to identify risk factors for ARE by matching each patient with ARE with two control patients without any isolated E. faecium strain. ARE isolates were characterized by pulsed-field gel electrophoresis. From June 2004 to May 2006, 18 cases with clinical ARE samples were detected and compared with 35 control patients. By univariate analysis, recurrent urinary tract infections (UTIs) (odds ratio [OR], 4.9; 95% confidence interval [CI], 1.0-25.6), mean number of hospitalization days in the last year (p < 0.003), pyelonephritis or UTI (OR, 9.6; 95% CI, 2.2-46.1), oral third-generation cephalosporin use (OR, 12.42; 95% CI, 2.04-109.1), and fluoroquinolone use (OR, 4.4; 95% CI, 1.1-18.2) were significantly associated with ARE urinary tract colonization. By conditional logistic regression, hospitalization >21 days within 1 year (adjusted OR [aOR], 6.9; 95% CI, 1.0-46.5), recent medical history of pyelonephritis or UTI (aOR, 8.6; 95% CI, 1.5-49.1), and prior oral third-generation cephalosporin use (aOR, 13.1; 95% CI, 1.2-142.6) were identified as independent factors associated with ARE urinary tract colonization. Genotyping revealed a heterogeneous epidemiological situation with two major clones in patients hospitalized in successive rooms and 10 different single pulsotypes. Emergence of highly resistant enterococcal strains is a collateral damage from antibiotic prescription and represents a potential source of patient-to-patient transmission. Combining epidemiological approach and molecular analysis is a powerful tool to delineate mechanisms of emerging resistance. Improving our knowledge on ARE emergence in high antibiotic pressure hospital wards is a key factor to better control these colonizations/infections and to prevent the emergence of vancomycin-resistant E. faecium. PMID:20370509

Maillard, Olivier; Corvec, Stéphane; Dantal, Jacques; Reynaud, Alain; Lucet, Jean-Christophe; Bémer, Pascale; Lepelletier, Didier



Health Economics of Antibiotics  

PubMed Central

Antibiotics have made a significant contribution to improving patient health, but policy makers and health care payers are concerned about the costs of antibiotics in addition to their effectiveness. This paper aims to assess the value of antibiotics by examining incremental cost-utility ratios of antibiotics. Evidence was derived from cost-utility analyses of antibiotics included in the Tufts-New England Center Cost-Effectiveness Analysis Registry through September 2009. The analysis included 85 incremental cost-utility ratios from 23 cost-utility analyses. The findings showed that 38.8% of incremental cost-utility ratios related to dominant antibiotics (i.e., more effective and less costly than the comparator); 45.9% referred to antibiotics that improved effectiveness, but also increased costs; and 15.3% related to dominated antibiotics (i.e., less effective and more costly than the comparator). The median ratio was 748 € per quality-adjusted life year. Using threshold values of 20,000 € per quality-adjusted life year and 50,000 € per quality-adjusted life year, the probability that an antibiotic provides value for money was 64% and 67%, respectively. The current evidence base suggests that the majority of antibiotics provide value for money and that antibiotics can aid decision makers to attain further population health improvements, whilst containing pharmaceutical expenditures.

Simoens, Steven



Genetic Architecture of Intrinsic Antibiotic Susceptibility  

PubMed Central

Background Antibiotic exposure rapidly selects for more resistant bacterial strains, and both a drug's chemical structure and a bacterium's cellular network affect the types of mutations acquired. Methodology/Principal Findings To better characterize the genetic determinants of antibiotic susceptibility, we exposed a transposon-mutagenized library of Escherichia coli to each of 17 antibiotics that encompass a wide range of drug classes and mechanisms of action. Propagating the library for multiple generations with drug concentrations that moderately inhibited the growth of the isogenic parental strain caused the abundance of strains with even minor fitness advantages or disadvantages to change measurably and reproducibly. Using a microarray-based genetic footprinting strategy, we then determined the quantitative contribution of each gene to E. coli's intrinsic antibiotic susceptibility. We found both loci whose removal increased general antibiotic tolerance as well as pathways whose down-regulation increased tolerance to specific drugs and drug classes. The beneficial mutations identified span multiple pathways, and we identified pairs of mutations that individually provide only minor decreases in antibiotic susceptibility but that combine to provide higher tolerance. Conclusions/Significance Our results illustrate that a wide-range of mutations can modulate the activity of many cellular resistance processes and demonstrate that E. coli has a large mutational target size for increasing antibiotic tolerance. Furthermore, the work suggests that clinical levels of antibiotic resistance might develop through the sequential accumulation of chromosomal mutations of small individual effect.

Tavazoie, Saeed



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

PubMed Central

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

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



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

PubMed Central

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

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



Neonatal septicaemia in Ilorin: bacterial pathogens and antibiotic sensitivity pattern.  


All cases of septicemia among neonates admitted to the neonatal intensive care unit of the University of Ilorin Teaching Hospital, Ilorin, Nigeria between Jan 1995 and Dec 1996 were studied. Our aims were (1) to assess the incidence and microbial epidemiology of neonatal sepsis, (2) to generate baseline data and necessary research question for a proposed study on predictors of neonatal sepsis in our centre. Microbiology records of patients with confirmed septicemia was reviewed. Each of these babies had a single venous blood sample from a peripheral vein taken under aseptic conditions and before commencement of antibiotics. The needed data were entered into a proforma. Of the 198 neonates screened for sepsis, there were 61 (30.8%) positive blood cultures. Twenty-nine (48%) of these were inborn. The total number of live births in the hospital during the study period was 4118, thus giving a hospital-based incidence of neonatal sepsis of 7.04/1000 for in-born patients. The male:female ratio was 1.2:1. Overall Staphylococcus aureus was the commonest pathogen, accounting for 18 (29.5%) of the total isolates. Other pathogens were as follows; coagulase negative Saphylococcus albus 15 (24.6%), Klebsiella spp 10 (16.4%) and unclassified Coliforms 9 (14.8%). The predominant organisms in the first 48 hours were Gram negative bacilli; accounting for (70%) of the 10 isolates. Between 3 and 7 days of life the Gram positive cocci accounted for 12 (60%) of the 20 isolates while the Gram negative bacilli represented 40%. After 7 days, the predominant organism was Staphylococcus aureus (38.8%) while coagulase-negative Staphylococci were isolated in 7 of 31 isolates (22.6%). The sensitivity pattern showed that 94% of the organisms were sensitive to azythromicin, 77.8% to streptomycin, 73.3% to gentamicin and 69.2% to ampicillin-sulbactam. For the cephalosporins the isolates showed a sensitivity rate of 69% to ceftriaxone, 66.7% to ceftazidime and 58.3% to cefuroxime. As a group the Gram positive organisms had 100% sensitivity to Azythromcin, 85% to ampicillin-sulbactam, 63% to ceftazidime and 62.5% to gentamicin. In the Gram negative group, the best overall sensitivity was to ceftriaxone (86.4%). Gentamicin had 85.7% while sensitivity to ceftazidime was 60%. The distribution of the organisms causing early and late onset sepsis were different. For early onset sepsis, the Gram negative bacilli as a group were the commonest organisms while Staphylococcus aureus was the commonest cause of late onset sepsis. There was a lower incidence of sepsis compared to reports from other parts of the country. This, in addition to differences in antibiotic sensitivity pattern call for more multi-centre studies on predictors of neonatal sepsis. The antibiotic sensitivity profiles suggest that the initial empirical choice of ampicillin-sulbactam and gentamicin appears to be the most rational for our environment. PMID:12518907

Mokuolu, A O; Jiya, N; Adesiyun, O O



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.



A novel sensor for cephalosporins based on electrocatalytic oxidation by poly(o-anisidine)/SDS/Ni modified carbon paste electrode.  


In this work for first time, the electrocatalytic oxidations of some cephalosporins were carried out by poly(o-anisidine)/SDS/Ni modified carbon paste electrode using cyclic voltammetry, chronoamperometry and chronocoulometry methods. At first, poly(o-anisidine) was formed by cyclic voltammetry in monomer solution containing sodium dodesyl sulfate (SDS), on carbon paste electrode surface. Then, Ni(II) ions were incorporated to electrode by immersion of the polymeric modified electrode having amine group in 0.1molL(-1) Ni(II) ion solution. A good redox behavior was observed for the Ni(OH)(2)/NiOOH couple on the surface of this electrode. Cephalosporins were successfully oxidized on the surface of this nickel ions dispersed poly(o-anisidine) modified carbon paste electrode. The electrocatalytic oxidation peak currents of cephalosporins were linearly dependent on their concentration. Electrode was successfully applied to determine cephalosporins in pharmaceutical preparations. PMID:20441933

Ojani, Reza; Raoof, Jahan-Bakhsh; Zamani, Saeed



Antibiotics in the environment.  


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

Larsson, D G Joakim



Antibiotics in the environment  

PubMed Central

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



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



Evolution of plasmid-coded resistance to broad-spectrum cephalosporins.  

PubMed Central

A clinical isolate of Klebsiella ozaenae with transferable resistance to broad-spectrum cephalosporins produces a beta-lactamase determined by plasmid pBP60. The beta-lactamase had the same isoelectric point as SHV-1 (7.6). From heteroduplex analysis, an extensive homology between the two bla genes could be deduced; therefore, the new beta-lactamase was designated SHV-2. Enzymatic studies revealed that SHV-2 was able to hydrolyze broad-spectrum cephalosporins due to an increased affinity of these compounds for the enzyme. The assumption that SHV-2 is a natural mutant of SHV-1 was strongly supported by the isolation of a laboratory mutant of SHV-1 that showed activities similar to those of SHV-2. Images

Kliebe, C; Nies, B A; Meyer, J F; Tolxdorff-Neutzling, R M; Wiedemann, B



Pemphigus vulgaris after coxsackievirus infection and cephalosporin treatment: a paraviral eruption?  


Pemphigus is an autoimmune disease that results from the interaction between predisposing genetic factors and exogenous agents, mainly drugs and viruses. Herein we report the case of a 66-year-old woman referred to our department for the onset of painful oral erosions and bullous lesions on the torso. Clinical, laboratory and histopathological investigations led to the diagnosis of pemphigus vulgaris. Two weeks before the outbreak of the lesions, the patient had suffered from a viral pharyngitis, subsequently diagnosed as herpangina, and had been taking an oral cephalosporin (cefixime) for 1 week to prevent possible bacterial complications. A relationship between the onset of pemphigus and coxsackievirus infection or cefixime administration or both was supposed. The case may represent a peculiar paraviral eruption, where a predisposing pemphigus-prone genetic background paved the way for the acantholytic autoimmune disorder as a consequence of the combined effect of the coxsackievirus infection and the cephalosporin treatment. PMID:18230979

Ruocco, E; Lo Schiavo, A; Baroni, A; Sangiuliano, S; Puca, R V; Brunetti, G; Ruocco, V



Antibiotic compared with antiseptic prophylaxis for prostatic surgery.  


Two different regimens of cephalosporin antibiotic prophylaxis were compared with antiseptic lubricating jelly to try to prevent infection and complications in 196 men after prostatic surgery. Pre-operative urine was cultured and prostatic chips (170 cases) were also cultured to define the source of any infection. The use of antibiotics was associated with a reduced risk of postoperative bacteriuria. No serious complications occurred, although 1 patient in the antiseptic treated group developed rigors; 79 of 170 patients (46%) had positive prostatic chip cultures, of whom 74 had sterile pre-operative urine. There was no association between the result of chip culture and the presence of a pre-operative catheter. Culture positive patients had an increased risk of post-operative urine infection, although the same organism was found in the prostate and urine in only 36% of cases of post-operative bacteriuria and in 43 (54%) the organism cultured from the prostate was Staphylococcus albus. This study provides further evidence of the benefit of true prophylactic antibiotic therapy for transurethral prostatic surgery and the prostatic chip data suggest that some of the risk is due to pre-operative contamination of the prostate in the absence of per-operative urinary infection or catheterisation. PMID:2249121

Prescott, S; Hadi, M A; Elton, R A; Ritchie, A W; Foubister, G C; Gould, J C; Hargreave, T B



Visible spectrophotometric determination of cephalosporins and penicillins by indophenol derivatization with and without alkaline degradation to ammonia.  


Cephalosporins and penicillins give reproducible yields of ammonia on degradation in 0.5 M sodium hydroxide solution at 100 degrees C: the ammonia formed was determined in the degraded solutions using the indophenol reaction. In another approach the ammonia driven off on refluxing alkaline solutions of the cephalosporin or penicillin was collected in dilute hydrochloric acid solution and determined using the indophenol reaction. For eight of the fourteen cephalosporins and penicillins studied identical yields were recorded using the two procedures: these varied from 29% for penicillin G to 137% for cephalonium based on the production of one ammonia molecule per beta-lactam molecule. For six other cephalosporins the distillation method gave substantially higher yields of ammonia than did the direct determination. Eight cephalosporins and penicillins were found to give substantial indophenol-type reactions without prior hydrolysis of the beta-lactam, but the sensitivities were usually lower than for the hydrolysis method. Manual spectrophotometric procedures for the determination of cephalosporins and penicillins based on these reactions have been developed. PMID:16867666

Fogg, A G; Abdalla, M A



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.



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 and In Vivo Activities of a New Cephalosporin, FR264205, against Pseudomonas aeruginosa  

Microsoft Academic Search

FR264205 is a novel parenteral 3-aminopyrazolium cephalosporin. This study evaluated the in vitro and in vivo activities of FR264205 against Pseudomonas aeruginosa. The MIC of FR264205 at which 90% of 193 clinical isolates of P. aeruginosa were inhibited was 1 g\\/ml, 8- to 16-fold lower than those of ceftazidime (CAZ), imipenem (IPM), and ciprofloxacin (CIP). FR264205 also exhibited this level

Shinobu Takeda; Toru Nakai; Yoshimi Wakai; Fumiaki Ikeda; Kazuo Hatano



Flow-injection spectrophotometric determination of certain cephalosporins based on the formation of dyes  

Microsoft Academic Search

A flow-injection spectrophotometric method is described for the determination of cefadroxil (I) and cefotaxime (II). The method is based on the hydrolysis of the cephalosporin with sodium hydroxide whereby the sulfide ion is produced. The latter is allowed to react with N,N-diethyl-p-phenylenediamine sulfate (N,N-DPPD) and Fe (III), and the blue color produced is measured at 670 nm (method A). Linear

Fadia H. Metwally; Abdulrahman A. Alwarthan; Salma A. Al-Tamimi



In vitro susceptibility of recent clinical isolates of pneumococci to the investigational cephalosporin cefditoren  

Microsoft Academic Search

From February to June 2000, 2,597 isolates of Streptococcus pneumoniae were prospectively collected from 146 clinical laboratories across the United States (US) and tested to evaluate the in vitro activity of cefditoren, an investigational oral cephalosporin. In all, 2,492 isolates (96.0%) had a cefditoren MIC of 0.5 ?g\\/mL or less, 74 isolates (2.8%) had an MIC of 1 ?g\\/mL, 30

James A Karlowsky; Mark E Jones; Deborah C Draghi; Ian A Critchley; Clyde Thornsberry; Daniel F Sahm



An artificial pathway to 3,4-dihydroxybenzoic acid allows generation of new aminocoumarin antibiotic recognized by catechol transporters of E. coli.  


An artificial operon was synthesized, consisting of the genes for chorismate pyruvate-lyase of E. coli and for 4-hydroxybenzoate 3-hydroxylase of Corynebacterium cyclohexanicum. This operon, directing the biosynthesis of 3,4-dihdroxybenzoate, was expressed in the heterologous expression host Streptomyces coelicolor M512, together with a modified biosynthetic gene cluster for the aminocoumarin antibiotic clorobiocin. The resulting strain produced a clorobiocin derivative containing a 3,4-dihdroxybenzoyl moiety. Its structure was confirmed by MS and NMR analysis, and it was found to be a potent inhibitor of the gyrases from Escherichia coli and Staphylococcus aureus. Bioassays against different E. coli mutants suggested that this compound is actively imported by catechol siderophore transporters in the cell envelope. This study provides an example of the structure of a natural product that can be rationally modified by synthetic biology. PMID:21439475

Alt, Silke; Burkard, Nadja; Kulik, Andreas; Grond, Stephanie; Heide, Lutz



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



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.



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



On the use of antibiotics to reduce rhizoplane microbial populations in root physiology and ecology investigations  

NASA Technical Reports Server (NTRS)

No straightforward method exists for separating the proportion of ion exchange and respiration due to rhizoplane microbial organisms from that of root ion exchange and respiration. We examined several antibiotics that might be used for the temporary elimination of rhizoplane bacteria from hydroponically grown wheat roots (Triticum aestivum cv. Veery 10). Each antibiotic was tested for herbicidal activity and plate counts were used to enumerate bacteria and evaluate antibiotic kinetics. Only lactam antibiotics (penicillins and cephalosporins) did not reduce wheat growth rates. Aminoglycosides, the pyrimidine trimethoprim, colistin and rifampicin reduced growth rates substantially. Antibiotics acted slowly, with maximum reductions in rhizoplane bacteria occurring after more than 48 h of exposure. Combinations of nonphytotoxic antibiotics reduced platable rhizoplane bacteria by as much as 98%; however, this was generally a reduction from about 10(9) to 10(6) colony forming units per gram of dry root mass, so that many viable bacteria remained on root surfaces. We present evidence which suggests that insufficient bacterial biomass exists on root surfaces of nonstressed plants grown under well-aerated conditions to quantitatively interfere with root nitrogen absorption measurements.

Smart, D. R.; Ferro, A.; Ritchie, K.; Bugbee, B. G.



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

PubMed Central

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

Greenwood, D.; O'Grady, F.



Secular trends in antibiotic consumption in the adult population in Emilia-Romagna, Italy, 2003-2009.  


Antibiotic resistance is closely related to antibiotic use and Italy is a country with high levels of both antibiotic use and antimicrobial resistance. We analysed the trend in antibiotic use in the community among adults (?15 years) and elderly, in the period 2003-2009, in Emilia-Romagna, Italy, a region with over 4 000 000 inhabitants. Data regarding antibiotic use were obtained from the regional public health system databases. Between 2003 and 2009 the antibiotic consumption increased from 15.4 to 18.7 defined daily doses/1000 inhabitants per day (DID) (+21.4%, p <0.0001). The prescription rate in 2009 was 2.19 prescriptions/1000 inhabitants per day, an increase of 13.8% compared with 2003. The highest increase in antibiotic use was observed among persons aged 20-59 years (+24.7%). The proportion of inhabitants receiving at least one antibiotic treatment was 36.4% in 2003 and 39.7% in 2009, and the proportions receiving at least three antibiotic treatments were 3.5% and 4.2%, respectively. The H1N1 pandemic was associated, in October and November 2009, with a 37-90% increase in antibiotic use among the 15-19-year and 20-59-year age groups compared with 2007 and 2008. No other difference was observed in any other age group. The analysis per antibiotic class showed increases for penicillin + beta-lactamase inhibitor (from 3.6 to 6.3 DID), quinolones (from 2.6 to 3.0 DID) and macrolides (from 3.1 to 3.7 DID), whereas cephalosporin use was stable (1.4 DID). A steady increase in antibiotic use in the adult population has been observed in the Emilia-Romagna: public health interventions are mandatory to counteract this trend. PMID:21595784

Pan, A; Buttazzi, R; Marchi, M; Gagliotti, C; Resi, D; Moro, M L



Access to antibiotics in New Delhi, India: implications for antibiotic policy  

PubMed Central

Objective The present survey was conducted to investigate the price and availability of a basket of 24 essential antibiotics and eight high-end antibiotics at various levels of health care in public and private sector in National Capital Territory of Delhi, India using standardized WHO/HAI methodology. Methods Data on procurement price and availability was collected from three public healthcare providers in the state: the federal (central) government, state government and Municipal Corporation of Delhi (MCD). Overall a total of 83 public facilities, 68 primary care, 10 secondary cares and 5 tertiary care facilities were surveyed. Data was also collected from private retail (n?=?40) and chain pharmacies (n?=?40) of a leading corporate house. Prices were compared to an international reference price (expressed as median price ratio-MPR). Results Public sector: Delhi state government has its essential medicine list (Delhi state EML) and was using Delhi state EML 2007 for procurement; the other two agencies had their own procurement list. All the antibiotics procured including second and third generation antibiotics except for injections were available at primary care facilities. Antibiotic available were on the basis of supply rather than rationality or the Delhi state EML and none was 100% available. There was sub-optimal availability of some essential antibiotics while other non-essential ones were freely available. Availability of antibiotics at tertiary care facilities was also sub-optimal. Private sector: Availability of antibiotics was good. For most of the antibiotics the most expensive and popular trade names were often available. High-end antibiotics, meropenam, gemifloxacin, and moxifloxacin were commonly available. In retail pharmacies some newer generation non-essential antibiotics like gemifloxacin were priced lower than the highest-priced generic of amoxicillin?+?clavulanic acid, azithromycin, and cefuroxime aexitl. Conclusions Inappropriate availability and pricing of newer generation antibiotics, which may currently be bought without prescription, is likely to lead to their over-use and increased resistance. All providers should follow the EML of whichever of the three concerned Delhi public sector agencies that it is under and these EMLs should follow the essential medicine concept. The Indian regulatory authorities need to consider urgently, drug schedules and pricing policies that will curtail inappropriate access to new generation antibiotics.



Prescription antibiotics for outpatients in Bangladesh: a cross-sectional health survey conducted in three cities  

PubMed Central

Background Antibiotics prescribing by physicians have gained due importance across the globe, mainly because of an increase in antibiotic usage, prevalence of infections and drug resistances. The present study is aimed to evaluate the physicians prescribing pattern of antibiotics, their usages by outpatients and disease conditions for which the antibiotics are prescribed in three cities of Bangladesh. Methods This cross sectional health survey was carried out with a self designed standard questionnaire by manual data collection over a three months period (20.03.2013 to 20.06.2013) at three adjacent cities Jessore Sadar, Monirampur and Keshabpur upazila respectively. The data were collected from the patient’s prescription and by directly interviewing the patients who were prescribed at least one antibiotic during the study period. WHO Anatomical Therapeutic Chemical (ATC) classifications for antibiotics was used and descriptive statistics were applied to the collected data and analyzed using Microsoft Excel software. Modified Wald method was applied to calculate 95% CI. Results A total of 900 prescriptions were analyzed during the study period. It was found that the prescriber prescribed antibiotics to the patients who were suffering mainly from cold and fever, infections, diarrhea and gonorrhea. The highest prescribed antibiotic groups were cephalosporins (31.78%), macrolides (27.33%), quinolones (16.33%), penicillins (7.11%), and metronidazoles (6.78%) respectively. Two or more antibiotics were prescribed in 25.44% of prescriptions. A total of 66.89% prescriptions had complete information on dosage form, 57% had complete direction for antibiotics use and 64.22% patients completed full course of antibiotics. Although 83% prescriptions have no clinical test for using antibiotics, even though the percentages of patients’ disease recovery were 61.78% and incompliance were 38.22%. Conclusion From this research, it is observed that physicians prescribed antibiotics rationally in some cases but needs to ensure in all cases of prescription. Because irrational use leads to the spread of bacterial resistance to antibiotics and related health problems, our findings have important implications for public education and the enforcement of regulations regarding the prescription of antibiotics in Bangladesh.



?-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-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: When Do They Help  


... Antibiotics: When Do They Help select new symptom Antibiotics: When Do They Help Definition When To Call ... viral or bacterial. Consider their perspective. Bacterial Infections: Antibiotics can help and will be prescribed Bacterial infections ...


Automation of a Technique for Determining Bacterial Sensitivity to Antibiotics, Volume I.  

National Technical Information Service (NTIS)

Several hundred bacterial growth curves were generated by the Lindberg-Reese automated instrument for testing sensitivity to antibiotics. The instrument monitors 24-hour growth in liquid media in the presence of graded levels of antibiotics. The curves, c...

L. T. Carleton C. M. Miller G. Reese



Acquisition of Resistance to Extended-Spectrum Cephalosporins by Salmonella enterica subsp. enterica Serovar Newport and Escherichia coli in the Turkey Poult Intestinal Tract  

PubMed Central

Salmonella enterica subsp. enterica serovar Newport resistant to the extended-spectrum cephalosporins (ESCs) and other antimicrobials causes septicemic salmonellosis in humans and animals and is increasingly isolated from humans, animals, foods, and environmental sources. Mechanisms whereby serovar Newport bacteria become resistant to ESCs and other classes of antimicrobials while inhabiting the intestinal tract are not well understood. The present study shows that 25.3% of serovar Newport strains isolated from the turkey poult intestinal tract after the animals were dosed with Escherichia coli harboring a large conjugative plasmid encoding the CMY-2 ?-lactamase and other drug resistance determinants acquired the plasmid and its associated drug resistance genes. The conjugative plasmid containing the cmy-2 gene was transferred not only from the donor E. coli to Salmonella serovar Newport but also to another E. coli serotype present in the intestinal tract. Laboratory studies showed that the plasmid could be readily transferred between serovar Newport and E. coli intestinal isolates. Administration of a single dose of ceftiofur, used to prevent septicemic colibacillosis, to 1-day-old turkeys did not result in the isolation of ceftiofur-resistant E. coli or Salmonella serovar Newport. There was a remarkable association between serotype, drug resistance, and plasmid profile among the E. coli strains isolated from the poults. This study shows that Salmonella serovar Newport can become resistant to ESCs and other antibiotics by acquiring a conjugative drug resistance plasmid from E. coli in the intestines.

Poppe, C.; Martin, L. C.; Gyles, C. L.; Reid-Smith, R.; Boerlin, P.; McEwen, S. A.; Prescott, J. F.; Forward, K. R.



Ro 22-5417, a new clavam antibiotic from Streptomyces clavuligerus. I. Discovery and biological activity.  


Streptomyces clavuligerus NRRL 3585, a culture which produces a variety of beta-lactam antibiotics in the penicillin, cephalosporin and clavam families, was found to produce a new beta-lactam antibiotic, Ro 22-5417. The compound, which was neither a substrate for nor inhibitor of several beta-lactamases, showed antimicrobial activity in defined minimal medium but little or no inhibitory activity in nutrient-rich medium. The activity was bacteriostatic against Bacillus species ATCC 27860 and was antagonized by D- and L-methionine, L-cystathionine, L-homocystine and O-acetyl-L-homoserine but not by L-homoserine, L-aspartate, L-cysteine or other common amino acids, vitamins and nucleosides. Our results are consistent with Ro 22-5417 acting as an inhibitor in methionine biosynthesis. PMID:6833140

Pruess, D L; Kellett, M



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

SciTech Connect

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 {beta}-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 structures of three mutant enzymes were determined. These structures suggest that activity gain and stability loss is related to an enlarged active site cavity in the mutant enzymes. In several clinically isolated mutant enzymes, a secondary substitution is observed far from the active site (Met182 {yields} Thr). This substitution had little effect on enzyme activity but restored stability lost by substitutions near the active site. This regained stability conferred an advantage in vivo. This pattern of stability loss and restoration may be common in the evolution of new enzyme activity.

Wang, Xiaojun; Minasov, George; Shoichet, Brian K. (NWU)



Analysis of 12 beta-lactam antibiotics in human plasma by HPLC with ultraviolet detection.  


A simple and economical high performance liquid chromatography method was developed and validated for routine analysis of 12 Penicillin, Cephalosporin and Carbapenem antibiotics in 200 microL of human plasma. Antibiotics determined were Ceftazidime, Meropenem, Ceftriaxone, Ampicillin, Cefazolin, Ertapenem, Cephalothin, Benzylpenicillin, Flucloxacillin, Dicloxacillin, Piperacillin and Ticarcillin. There was a common sample preparation approach involving precipitation of proteins with acetonitrile and removal of lipid-soluble components by a chloroform wash. Separations were performed on a Waters X-bridge C18 column with, depending on analytes, one of three acetonitrile-phosphate buffer mobile phases. Detection was by UV at 210, 260 and 304 nm. Validation has demonstrated the method to be linear, accurate and precise. The method has been used in a pathology laboratory for therapeutic drug monitoring (TDM) of beta-lactams in critically ill patients. PMID:20561826

McWhinney, Brett C; Wallis, Steven C; Hillister, Tara; Roberts, Jason A; Lipman, Jeffrey; Ungerer, Jacobus P J



Selectively Guanidinylated Aminoglycosides as Antibiotics  

PubMed Central

The emergence of virulent, drug-resistant bacterial strains coupled with a minimal output of new pharmaceutical agents to combat them makes this a critical time for antibacterial research. Aminoglycosides are a well-studied, highly potent class of naturally occurring antibiotics with scaffolds amenable to modification, and therefore, they provide an excellent starting point for the development of semisynthetic, next-generation compounds. To explore the potential of this approach, we synthesized a small library of aminoglycoside derivatives selectively and minimally modified at one or two positions with a guanidine group replacing the corresponding amine or hydroxy functionality. Most guanidino-aminoglycosides showed increased affinity for the ribosomal decoding rRNA site, the cognate biological target of the natural products, when compared with their parent antibiotics, as measured by an in vitro fluorescence resonance energy transfer (FRET) A-site binding assay. Additionally, certain analogues showed improved minimum inhibitory concentration (MIC) values against resistant bacterial strains, including methicillin-resistant Staphylococcus aureus (MRSA). An amikacin derivative holds particular promise with activity greater than or equal to the parent antibiotic in the majority of bacterial strains tested.

Fair, Richard J.; Hensler, Mary E.; Thienphrapa, Wdee; Dam, Quang N.



Comparative kinetic analysis on thermal degradation of some cephalosporins using TG and DSC data  

PubMed Central

Background The thermal decomposition of cephalexine, cefadroxil and cefoperazone under non-isothermal conditions using the TG, respectively DSC methods, was studied. In case of TG, a hyphenated technique, including EGA, was used. Results The kinetic analysis was performed using the TG and DSC data in air for the first step of cephalosporin’s decomposition at four heating rates. The both TG and DSC data were processed according to an appropriate strategy to the following kinetic methods: Kissinger-Akahira-Sunose, Friedman, and NPK, in order to obtain realistic kinetic parameters, even if the decomposition process is a complex one. The EGA data offer some valuable indications about a possible decomposition mechanism. The obtained data indicate a rather good agreement between the activation energy’s values obtained by different methods, whereas the EGA data and the chemical structures give a possible explanation of the observed differences on the thermal stability. A complete kinetic analysis needs a data processing strategy using two or more methods, but the kinetic methods must also be applied to the different types of experimental data (TG and DSC). Conclusion The simultaneous use of DSC and TG data for the kinetic analysis coupled with evolved gas analysis (EGA) provided us a more complete picture of the degradation of the three cephalosporins. It was possible to estimate kinetic parameters by using three different kinetic methods and this allowed us to compare the Ea values obtained from different experimental data, TG and DSC. The thermodegradation being a complex process, the both differential and integral methods based on the single step hypothesis are inadequate for obtaining believable kinetic parameters. Only the modified NPK method allowed an objective separation of the temperature, respective conversion influence on the reaction rate and in the same time to ascertain the existence of two simultaneous steps.



Non-Steroidal Anti-Inflammatory Drugs and Antibiotics Prescription Trends at a Central West Bank Hospital  

PubMed Central

Objectives: We aimed to reliably describe the pattern of outpatient prescription of non-steroidal anti-inflammatory drugs (NSAIDs) and antibiotics (ATBs) at a central hospital in the West Bank, Palestine. Methods: This was a retrospective, cross-sectional study investigating a cohort of 2,208 prescriptions ordered by outpatient clinics and the emergency room over one year in Beit Jala Hospital in Bethlehem, West Bank. The orders were analysed for the rate and types of NSAIDs and ATBs utilised, and the appropriateness of these drugs to the diagnosis. Results: Of the total prescriptions, 410 contained NSAIDs (18.6%), including diclofenac (40.2%), low dose aspirin (23.9%), ibuprofen (17.8%) and indomethacin (15.1%). A minority of these prescriptions contained a combination of these agents (2.5%). Only one prescription contained cyclooxyeganse-2 inhibitors (0.2%). The appropriateness of NSAID use to the diagnosis was as follows: appropriate (58.3%), inappropriate (14.4%) and difficult to tell (27.3%). The rate of ATB use was 30.3% (669 prescriptions). The ATBs prescribed were amoxicillin (23.3%), augmentin (14.3%), quinolones (12.7%), first and second generation cephalosporins (9.4% and 12.7%, respectively) and macrolides (7.2%). ATB combinations were identified in 9.4%, with the most common being second-generation cephalopsorins and metronidazole (4.3%). Regarding the appropriateness of prescribing ATBs according to the diagnosis, it was appropriate in 44.8%, inappropriate in 20.6% and difficult to tell in 34.6% of the prescriptions. Conclusion: These findings revealed a relatively large number and inappropriate utilisation of ATBs and NSAIDs. An interventional programme needs to be adopted to reinforce physicians’ knowledge of the rational prescription of these agents.

Tayem, Yasin I.; Qubaja, Marwan M.; Shraim, Riyad K.; Taha, Omar B.; Abu Shkheidem, Imadeddin A.; Ibrahim, Murad A.



Risk of clinical blood dyscrasia in a cohort of antibiotic users.  


Blood dyscrasias, although rare, can be fatal. Many drugs, including antibiotics, are associated with these dyscrasias. We conducted a cohort study with a nested case-control analysis using data from the General Practice Research Database to estimate incidence rates of clinical blood dyscrasias in the general population and to examine their association with use of antibiotic drugs. The study population consisted of patients aged 5-69 years receiving at least one antibiotic prescription from January 1994-September 1998. The final cohort consisted of 822,048 persons who received 1,507,307 antibiotic prescriptions during the study period. The main outcome measure was a diagnosis of neutropenia, agranulocytosis, hemolytic anemia, thrombocytopenia, bicytopenia, pancytopenia, or aplastic anemia. We confirmed 122 patients who developed clinical blood dyscrasias. The incidence was 3.3/100,000 person-years in the general population. Patients older than 60 years (relative risk [RR] 2.8, 95% confidence interval [CI] 1.6-5.0) and those who took phenothiazines (RR 49.0, 95% CI 4.9-488.2) had an increased risk of blood dyscrasia. Users of antibiotics had an RR of 4.4 (95% CI 2.6-7.5), and patients taking more than one class of antibiotics had an RR of 29.1 (95% CI 9.1-92.8). Among individual antibiotic classes, the greatest risk was with cephalosporins (RR 13.8, 95% CI 3.6-52.6). Although uncommon, our study supports an association between blood dyscrasias and antibiotics. PMID:12013362

Huerta, Consuelo; García Rodríguez, Luis Alberto



Prepositioning Antibiotics for Anthrax.  

National Technical Information Service (NTIS)

Rapid access to antibiotics can prevent people who are exposed to aerosolized Bacillus anthracis from developing anthrax; once symptoms of anthrax emerge, the disease progresses rapidly and can prove fatal. Since the anthrax attack in 2001, the nations pu...



Antibiotic-Induced Anaphylaxis  

Microsoft Academic Search

\\u000a An antibiotic allergic reaction represents one of the side effects of drugs and is a daily worry for the clinician. If urticaria\\u000a and maculo–papular eruptions are the most frequent manifestations, then anaphylaxis can occur. The tools allowing a definite\\u000a diagnosis are validated for some antibiotics and include the following procedures: a thorough clinical history, standardized\\u000a skin tests, reliable biological tests,

Pascal Demoly; Philippe Jean Bousquet; Antonino Romano


Aspergillomarasmine A overcomes metallo-?-lactamase antibiotic resistance.  


The emergence and spread of carbapenem-resistant Gram-negative pathogens is a global public health problem. The acquisition of metallo-?-lactamases (MBLs) such as NDM-1 is a principle contributor to the emergence of carbapenem-resistant Gram-negative pathogens that threatens the use of penicillin, cephalosporin and carbapenem antibiotics to treat infections. To date, a clinical inhibitor of MBLs that could reverse resistance and re-sensitize resistant Gram-negative pathogens to carbapenems has not been found. Here we have identified a fungal natural product, aspergillomarasmine A (AMA), that is a rapid and potent inhibitor of the NDM-1 enzyme and another clinically relevant MBL, VIM-2. AMA also fully restored the activity of meropenem against Enterobacteriaceae, Acinetobacter spp. and Pseudomonas spp. possessing either VIM or NDM-type alleles. In mice infected with NDM-1-expressing Klebsiella pneumoniae, AMA efficiently restored meropenem activity, demonstrating that a combination of AMA and a carbapenem antibiotic has therapeutic potential to address the clinical challenge of MBL-positive carbapenem-resistant Gram-negative pathogens. PMID:24965651

King, Andrew M; Reid-Yu, Sarah A; Wang, Wenliang; King, Dustin T; De Pascale, Gianfranco; Strynadka, Natalie C; Walsh, Timothy R; Coombes, Brian K; Wright, Gerard D



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.



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, João Lúcio de; Araújo, Janete Magali de



Activity of a new antipseudomonal cephalosporin, CXA-101 (FR264205), against carbapenem-resistant and multidrug-resistant Pseudomonas aeruginosa clinical strains.  


The activity of the new cephalosporin CXA-101 (CXA), previously designated FR264205, was evaluated against a collection of 236 carbapenem-resistant P. aeruginosa isolates, including 165 different clonal types, from a Spanish multicenter (127-hospital) study. The MICs of CXA were compared to the susceptibility results for antipseudomonal penicillins, cephalosporins, carbapenems, aminoglycosides, and fluoroquinolones. The MIC of CXA in combination with tazobactam (4 and 8 microg/ml) was determined for strains with high CXA MICs. The presence of acquired beta-lactamases was investigated by isoelectric focusing and PCR amplification followed by sequencing. Additional beta-lactamase genes were identified by cloning and sequencing. The CXA MIC50/MIC90 for the complete collection of carbapenem-resistant P. aeruginosa isolates was 1/4 microg/ml, with 95.3% of the isolates showing an MIC of antibiotics tested was not observed; the MIC50/MIC90 of CXA-101 was still 1/4 when multidrug-resistant (MDR) strains (42% of all tested isolates) or AmpC-hyperproducing clones (53%) were analyzed. Almost all (10/11) of the strains showing a CXA MIC of >8 microg/ml produced a horizontally acquired beta-lactamase, including the metallo-beta-lactamase (MBL) VIM-2 (one strain), the extended-spectrum beta-lactamase (ESBL) PER-1 (one strain), several extended-spectrum OXA enzymes (OXA-101 [one strain], OXA-17 [two strains], and a newly described OXA-2 derivative [W159R] designated OXA-144 [four strains]), and a new BEL variant (BEL-3) ESBL (one strain), as identified by cloning and sequencing. Synergy with tazobactam in these 11 strains was limited, although 8 microg/ml reduced the mean CXA MIC by 2-fold. CXA is highly active against carbapenem-resistant P. aeruginosa isolates, including MDR strains. Resistance was restricted to still-uncommon strains producing an acquired MBL or ESBL. PMID:19933793

Juan, Carlos; Zamorano, Laura; Pérez, José L; Ge, Yigong; Oliver, Antonio



Overcoming Resistance to ?-Lactam Antibiotics  

PubMed Central

?-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 perspective 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.

Worthington, Roberta J.; Melander, Christian



Antibiotic therapy for ocular infection.  

PubMed Central

Infections of the eye can rapidly damage important functional structures and lead to permanent vision loss or blindness. Broad-spectrum antibiotics should be administered to the appropriate site of infection as soon as a diagnosis is made. Topical drops are preferred for corneal and conjunctival infections. Intravitreal antibiotics, and possibly subconjunctival and parenteral antibiotics, are preferred for endophthalmitis. Parenteral antibiotics are recommended for infection in deep adnexal structures. We review specific aspects of antibiotic therapy for ocular and periocular infection.

Snyder, R W; Glasser, D B



In Vitro Activities of BAL9141, a Novel Broad-Spectrum Pyrrolidinone Cephalosporin, against Gram-Negative Nonfermenters  

PubMed Central

The activities of BAL9141 (formerly Ro 63-9141), a novel pyrrolidinone-3-ylidenemethyl cephalosporin, against 244 strains of gram-negative nonfermenters were evaluated. The overall MIC at which 50% of isolates are inhibited (MIC50) and the overall MIC90 were 2 and 64 ?g/ml, respectively, which are similar to those of imipenem, lower than those of the other cephalosporins tested, amoxicillin, and the ticarcillin-clavulanic acid combination, and much higher than those of ciprofloxacin. BAL9141 shows species-dependent activity in vitro against a variety of gram-negative nonfermentative pathogens.

Zbinden, R.; Punter, V.; von Graevenitz, A.



Cloning and characterization of the genes for two distinct cephalosporin acylases from a Pseudomonas strain.  

PubMed Central

Pseudomonas sp. strain SE83 converts cephalosporin C and 7 beta-(4-carboxybutanamido)cephalosporanic acid (GL-7ACA) to 7-aminocephalosporanic acid (7ACA). A DNA library of this strain was constructed in Escherichia coli and screened for the ability to deacylate GL-7ACA to 7ACA. Apparently, two distinct genes, designated acyI and acyII, were cloned on 4.8- and 6.0-kilobase-pair BglII fragments, respectively. The enzymes encoded by the two genes showed different substrate specificities, and the acyII-encoded enzyme was found to yield 7ACA from cephalosporin C by direct deacylation. Expression of the two genes in E. coli was strongly dependent on a promoter of the vector. The coding regions for acyI and acyII were localized on the 2.5- and 2.8-kilobase-pair fragments, respectively, by subcloning experiments, and high expression of both genes was obtained by placing them under the control of the lacUV5 promoter. The acyII-encoded enzyme was purified and shown to be composed of two nonidentical subunits with molecular weights of 26,000 and 57,000. Maxicell analysis revealed three acyII-specific polypeptides, two of which corresponded to the above subunits. The third polypeptide with a molecular weight of 83,000 was suggested to be the precursor of both subunits. Images

Matsuda, A; Matsuyama, K; Yamamoto, K; Ichikawa, S; Komatsu, K



In vitro evaluation of E1077, a new cephalosporin with a broad antibacterial spectrum.  

PubMed Central

E1077 is a novel parenteral cephalosporin with a wide spectrum of potent antibacterial activity against aerobic and anaerobic gram-positive and gram-negative bacteria. Against methicillin-susceptible Staphylococcus aureus, E1077 was twice as active as cefpirome, with an MIC for 90% of strains tested (MIC90) of 0.78 micrograms/ml. Methicillin-resistant S. aureus was moderately to highly resistant to E1077, but E1077 was at least twice as active as other beta-lactams tested. Against Enterococcus faecalis, E1077 was the most active of the cephalosporins tested (MIC90, 12.5 micrograms/ml) and was at least fourfold more active than cefpirome and ceftazidime. At concentrations of less than or equal to 0.78 micrograms/ml, E1077 inhibited 90% of streptococci and most of the members of the family Enterobacteriaceae tested, with the exceptions of Serratia marcescens and Proteus vulgaris, for which the MIC90s of E1077 were both 3.13 micrograms/ml. Against Pseudomonas aeruginosa, E1077 was two- to fourfold more active than cefpirome and ceftazidime. For the anaerobes, E1077 was as active against Bacteroides fragilis as was cefuzonam, and its activity was fourfold higher than those of cefpirome and ceftazidime. E1077 was at least as resistant as cefpirome to hydrolysis by various beta-lactamases, and these enzymes had a low affinity for E1077.

Watanabe, N; Hiruma, R; Katsu, K



Beta-lactamase stability of cefpirome (HR 810), a new cephalosporin with a broad antimicrobial spectrum.  

PubMed Central

Cefpirome was highly stable to hydrolysis by various beta-lactamases, although it was hydrolyzed to some extent by R plasmid-mediated penicillinase of Richmond-Sykes type Va/b and by chromosomal cephalosporinases from Bacteroides species. The compound had a very low affinity for cephalosporinases from Enterobacter cloacae, Citrobacter freundii, Serratia marcescens, and Proteus vulgaris. Cefpirome showed strong antimicrobial activity against eight beta-lactamase (cephalosporinase)-producing strains which have become resistant to broad-spectrum cephalosporins; especially against E. cloacae and C. freundii, it had the highest activity among the cephalosporins used. Its activity against ampicillin-resistant R plasmid-containing transconjugant isolates of Escherichia coli was as high as that against the recipient strain E. coli chi 1037. The inducer activity of cefpirome in S. marcescens and P. vulgaris increased dose dependently, whereas cephamycin derivatives showed high inducer activity at low concentrations. A relatively low affinity of cefpirome for beta-lactamases is considered to be one of the reasons for its high antimicrobial activity against such enzyme-producing strains. In addition, other factors such as good penetration through the outer membrane and affinity for the target sites may also be involved in the high activity of cefpirome.

Kobayashi, S; Arai, S; Hayashi, S; Fujimoto, K



Occurrences and fate of selected human antibiotics in influents and effluents of sewage treatment plant and effluent-receiving river Yamuna in Delhi (India).  


Antibiotics consumption has increased worldwide, and their residues are frequently reported in aquatic environments. It is believed that antibiotics reach aquatic water bodies through sewage. Medicine consumed for healthcare practices are often released into sewage, and after sewage treatment plant, it reaches the receiving water bodies of lakes or rivers. In the present study, we determined the fate of some commonly used antibiotics in a sewage treatment plant (STP) located in Delhi and the environmental concentration of these antibiotics in the Yamuna River, which receives the sewage and industrial effluent of Delhi. There are many reports on antibiotics occurrences in STP and river water worldwide, but monitoring data from the Indian subcontinent is sparse. Samples were taken from a STP and from six sampling sites on the Yamuna River. Several antibiotics were tested for using offline solid-phase extraction followed by high-performance liquid chromatography equipped with photodiode array analysis. Recoveries varied from 25.5-108.8 %. Ampicillin had the maximum concentration in wastewater influents (104.2?±?98.11 ?g l(-1)) and effluents (12.68?±?8.38 ?g l(-1)). The fluoroquinolones and cephalosporins had the lower concentrations. Treatment efficiencies varied between 55 and 99 %. Significant amounts of antibiotics were discharged in effluents and were detected in the receiving water body. The concentration of antibiotics in the Yamuna River varied from not detected to 13.75 ?g l(-1) (ampicillin) for the compounds investigated. PMID:24085621

Mutiyar, Pravin K; Mittal, Atul K



Antibiotic treatment of sepsis.  


Early, appropriate antibiotic therapy is critical to the treatment of the septicemic patient. The degree of organ dysfunction, underlying medical conditions, and physiologic abnormalities are important prognostic factors but are not important in initial antibiotic selection. Initial empiric therapy should be directed against the resident flora of the organ, which is primarily involved in the infectious process. Blood cultures should be obtained in all patients for the initiation of antibiotic therapy, and methods should be employed for the early detection of septicemia. Other conditions that mimic sepsis, e.g., pseudosepsis, should be ruled out initially to avoid an incorrect diagnosis and unnecessary antibiotic therapy. Monotherapy and fully recommended doses of antimicrobial drugs delivered by the intravenous route as soon as the diagnosis is established remain the cornerstone of therapy in treating the septic patient. Monotherapy with an antibiotic of the appropriate spectrum is more than adequate to treat the great majority of septicemic patients. Double-drug therapy is recommended to treat febrile leukopenic compromised hosts, serious P. aeruginosa infections, and selected cases of intra-abdominal sepsis. At the present time, corticosteroids and mediator therapy have no place in the treatment of the septic patient. PMID:7752728

Cunha, B A



Antibiotics after rattlesnake envenomation.  


To record the outcome, with regard to infection rate, of patients with rattlesnake bites (RSBs) who do not receive prophylactic antibiotics, a prospective observational study was performed of patients with RSBs treated at our institution during a consecutive 18-month period. The inclusion criteria were RSBs <24 h old and completion of follow-up (telephone call, mail reply, medical toxicologist, or private physician examination) 7-10 days following envenomation. Fifty-six consecutive patients (Median age: 32.8 years [range 4-67 years]) were enrolled. One patient was excluded because of presentation 38 h after envenomation and two patients failed to complete the required follow-up. One patient received a dose of antibiotics before transfer. Antibiotics were discontinued upon arrival. Of the total 56 RSB patients, 34 (61%) RSBs involved the upper extremity and 22 (39%) involved the lower extremity. Six patients (11%) applied ice and two (4%) used a tourniquet before evaluation. The mean arrival time was 2.7 h (Range <1-24 h). Forty-three patients (81%) received antivenin. Fifty-three patients (100%) had extremity swelling and 38 patients (72%) had tender proximal lymph nodes. Of the 53 patients who completed the study, 3 (6%) received antibiotics from their primary care physicians at 7-10 day follow-up, with no cases (0%) of documented infection. Prophylactic antibiotics are not indicated in patients with rattlesnake bites. PMID:12480007

LoVecchio, Frank; Klemens, Jane; Welch, Sharon; Rodriguez, Ron



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



Analysis of macrolide antibiotics.  


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 separation and quantitative analysis of the macrolides in fermentation media, purity assessment of raw materials, assay of pharmaceutical dosage forms and the measurement of clinically useful macrolide antibiotics in biological samples such as blood, plasma, serum, urine and tissues. Data relating to the chromatographic behaviour of some macrolide antibiotics as well as the various detection methods used, such as bioautography, UV spectrophotometry, fluorometry, electrochemical detection, chemiluminescence and mass spectrometry techniques are also included. PMID:9691324

Kanfer, I; Skinner, M F; Walker, R B



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



Natural evolution of skin-test sensitivity in patients with IgE-mediated hypersensitivity to cephalosporins.  


There are studies demonstrating that skin-test sensitivity to penicillins can decrease over time and that allergic patients may lose sensitivity if the responsible compounds are avoided. With regard to subjects with IgE-mediated hypersensitivity to cephalosporins, however, such studies are lacking. We evaluated prospectively in a 5-year follow-up 72 cephalosporin-allergic patients. After the first evaluation, patients were classified into two groups according to their patterns of allergologic-test positivity: to both penicillins and cephalosporins (group A), or only to cephalosporins (group B). Skin tests and serum-specific IgE assays were repeated 1 year later and, in case of persistent positivity, 3 and 5 years after the first allergologic examination. Seven (43.7%) of the 16 subjects of group A and 38 (67.8%) of the 56 patients of group B became negative; one was lost to follow-up. Patients of group B became negative sooner and more frequently than group A subjects. PMID:24673580

Romano, A; Gaeta, F; Valluzzi, R L; Zaffiro, A; Caruso, C; Quaratino, D



Antibiotic bonding to polytetrafluoroethylene with tridodecylmethylammonium chloride  

SciTech Connect

Polytetrafluoroethylene (PTFE) treated with the cationic surfactant, triodecylmethylammonium chloride (TDMAC), binds /sup 14/C-penicillin (1.5 to 2 mg antibiotic/cm graft), whereas untreated PTFE or PTFE treated with anionic detergents shows little binding of antibiotic. TDMAC-treated PTFE concomitantly binds penicillin and heparin, generating a surface that potentially can resist both infection and thrombosis. The retention of these biologically active molecules is not due to passive entrapment in the PTFE but reflects an ionic interaction between the anionic ligands and surface-bound TDMAC. Penicillin bound to PTFE is not removed by exhaustive washing in aqueous buffers but is slowly released in the presence of plasma or when the PTFE is placed in a muscle pouch in the rat. Muscle tissue adjacent to the treated PTFE shows elevated levels of antibiotic following implantation. PTFE treated with TDMAC and placed in a muscle pouch binds /sup 14/C-penicillin when it is locally irrigated with antibiotic or when penicillin is administered intravenously. Thus, the TDMAC surface treated either in vitro or in vivo with penicillin provides an effective in situ source for the timed release of antibiotic.

Harvey, R.A.; Alcid, D.V.; Greco, R.S.



Tackling antibiotic resistance.  


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 gathered at the Banbury Conference Centre in Cold Spring Harbor, New York, USA, from 16 to 18 May 2011. From these discussions there emerged a priority list of steps that need to be taken to resolve this global crisis. PMID:22048738

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



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

Falcão, Amílcar C.


Pharmacokinetics of cephem antibiotics in exudate of pelvic retroperitoneal space after radical hysterectomy and pelvic lymphadenectomy.  

PubMed Central

Many cephalosporin antibiotics have recently been invented and attempts have been made to use them clinically. The choice of which of these drugs should be used has been difficult in gynecology. The efficacies of these drugs depend on their antibacterial spectra, potencies, and concentrations in tissues. This study was designed to investigate the pharmacokinetics of various cephem antibiotics in the exudate of the retroperitoneal space that is formed after radical hysterectomy and pelvic lymphadenectomy. These cephem antibiotics were cefoxitin, cefotiam, cefotetan, cefpiramide, cefminox, cefotaxime, ceftizoxime, cefoperazone, cefmenoxime, cefbuperazone, ceftazidime, cefpimizole, flomoxef, and cefuzonam. The maximum concentrations after administration of a 1-g dose in the exudate of the pelvic retroperitoneal space were 37.9 micrograms/ml with cefminox, 30.3 micrograms/ml with cefpimizole, 21.6 micrograms/ml with flomoxef, 21.5 micrograms/ml with ceftazidime, and 17.6 micrograms/ml with cefbuperazone, which were relatively high. When selecting antibiotics for prophylactic use against infections in the retroperitoneal space after radical hysterectomy and pelvic lymphadenectomy, on the basis of drug transfer, flomoxef, cefminox, cefbuperazone, ceftazidime, and cefpimizole were considered to be the drugs of first choice at a dose of 1 g.

Ito, K; Hayasaki, M; Tamaya, T



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



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



Insight into autoproteolytic activation from the structure of cephalosporin acylase: A protein with two proteolytic chemistries  

PubMed Central

Cephalosporin acylase (CA), a member of the N-terminal nucleophile hydrolase family, is activated through sequential primary and secondary autoproteolytic reactions with the release of a pro segment. We have determined crystal structures of four CA mutants. Two mutants are trapped after the primary cleavage, and the other two undergo secondary cleavage slowly. These structures provide a look at pro-segment conformation during activation in N-terminal nucleophile hydrolases. The highly strained helical pro segment of precursor is transformed into a relaxed loop in the intermediates, suggesting that the relaxation of structural constraints drives the primary cleavage reaction. The secondary autoproteolytic step has been proposed to be intermolecular. However, our analysis provides evidence that CA is processed in two sequential steps of intramolecular autoproteolysis involving two distinct residues in the active site, the first a serine and the second a glutamate.

Kim, Jin Kwang; Yang, In Seok; Shin, Hye Jeong; Cho, Ki Joon; Ryu, Eui Kyung; Kim, Sun Hwa; Park, Sung Soo; Kim, Kyung Hyun



Degradation of ? ?-lactam antibiotics  

Microsoft Academic Search

?- lactam antibiotics which culminated with the intro- duction of several clinically useful classical and non - classical ? ?-lactams have been most thrilling and highly rewarding. While this review touches upon the his- torical development of ? ?-lactams and their reactivity in a nutshell, it provides an overview of various aspects of chemical and enzymatic degradation of ? ?-lactams,

A. D. Deshpande; K. G. Baheti; N. R. Chatterjee


Chasing after antibiotic leads.  


The emergence of drug-resistant pathogens has prompted the search for new antibacterials. In this issue of Chemistry & Biology, Starosta et al. identify specific thiopeptide-antibiotic precursor lead compounds using three complementary high-throughput translation machinery assays. PMID:19875074

Geiermann, Anna-Skrollan; Micura, Ronald



Minocycline: far beyond an antibiotic  

PubMed Central

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.

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



Resistance to antibiotics: are we in the post-antibiotic era?  


Serious infections caused by bacteria that have become resistant to commonly used antibiotics have become a major global healthcare problem in the 21st century. They not only are more severe and require longer and more complex treatments, but they are also significantly more expensive to diagnose and to treat. Antibiotic resistance, initially a problem of the hospital setting associated with an increased number of hospital-acquired infections usually in critically ill and immunosuppressed patients, has now extended into the community causing severe infections difficult to diagnose and treat. The molecular mechanisms by which bacteria have become resistant to antibiotics are diverse and complex. Bacteria have developed resistance to all different classes of antibiotics discovered to date. The most frequent type of resistance is acquired and transmitted horizontally via the conjugation of a plasmid. In recent times new mechanisms of resistance have resulted in the simultaneous development of resistance to several antibiotic classes creating very dangerous multidrug-resistant (MDR) bacterial strains, some also known as "superbugs". The indiscriminate and inappropriate use of antibiotics in outpatient clinics, hospitalized patients and in the food industry is the single largest factor leading to antibiotic resistance. In recent years, the number of new antibiotics licensed for human use in different parts of the world has been lower than in the recent past. In addition, there has been less innovation in the field of antimicrobial discovery research and development. The pharmaceutical industry, large academic institutions or the government are not investing the necessary resources to produce the next generation of newer safe and effective antimicrobial drugs. In many cases, large pharmaceutical companies have terminated their anti-infective research programs altogether due to economic reasons. The potential negative consequences of all these events are relevant because they put society at risk for the spread of potentially serious MDR bacterial infections. PMID:16216651

Alanis, Alfonso J



What Can Be Done about Antibiotic Resistance?  


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


Danger of Antibiotic Overuse (For Parents)  


... antibiotic treatment. This is called bacterial resistance or antibiotic resistance. Treating these resistant bacteria requires higher doses of ... some of the most powerful antibiotics available today. Antibiotic resistance is a widespread problem, and one that the ...


Antibiotic prophylaxis in dermatologic surgery  

Microsoft Academic Search

Antibiotic prophylaxis is generally administered either to prevent wound infection or to hinder the development of endocarditis. Although the use of antibiotics in certain circumstances to prevent wound infection can be straightforward, there are other circumstances in which the decision to use antibiotics is much less clear. Endocarditis prophylaxis has traditionally been based on the American Heart Association's guidelines, which

Ann F Haas; Roy C Grekin



Immobilization of microbial cells in crosslinked, prepolymerized, linear polyacrylamide gels: antibiotic production by immobilized Streptomyces clavuligerus cells  

SciTech Connect

A mild method for the immobilization of whole microbial cells has been developed. Cells were suspended in a solution of preformed, linear, water-soluble polyacrylamide chains, partially substituted with acylhydrazide groups. The prepolymerized backbone polymer was crosslinked, in the presence of viable cells, by stoichiometric amounts of dialdehydes such as glyoxal, glutardialdehyde, and periodate-oxidized polyvinyl alcohol. The crosslinking reaction, carried out in cold, neutral physiological conditions resulted in cells entrapped in gels with physical properties similar to those of the common polyacrylamide gels. However, cell damage generally caused by the acrylamide monomer was avoided. Resting Streptomyces clavuligerus cells, possessing a high capacity for antibiotic production, were entrapped according to this procedure. These immobilized cells produced cephalosporins continuously for 96 hours with yields similar to those of free resting cells. The same cells, when immobilized by direct polymerization of acrylamide monomers, yielded significantly lower amounts of antibiotics. (Refs. 19).

Freeman, A.; Aharonowitz, Y.



Structure-activity relationship of carbacephalosporins and cephalosporins: antibacterial activity and interaction with the intestinal proton-dependent dipeptide transport carrier of Caco-2 cells.  


An intestinal proton-dependent peptide transporter located on the lumenal surface of the enterocyte is responsible for the uptake of many orally absorbed beta-lactam antibiotics. Both cephalexin and loracarbef are transported by this mechanism into the human intestinal Caco-2 cell line. Forty-seven analogs of the carbacephalosporin loracarbef and the cephalosporin cephalexin were prepared to evaluate the structural features necessary for uptake by this transport carrier. Compounds were evaluated for their antibacterial activities and for their ability to inhibit 1 mM cephalexin uptake and, subsequently, uptake into Caco-2 cells. Three clinically evaluated orally absorbed carbacephems were taken up by Caco-2 cells, consistent with their excellent bioavailability in humans. Although the carrier preferred the L stereoisomer, these compounds lacked antibacterial activity and were hydrolyzed intracellularly in Caco-2 cells. Compounds modified at the 3 position of cephalexin and loracarbef with a cyclopropyl or a trifluoromethyl group inhibited cephalexin uptake. Analogs with lipophilic groups on the primary amine of the side chain inhibited cephalexin uptake, retained activity against gram-positive bacteria but lost activity against gram-negative bacteria. Substitution of the phenylglycl side chain with phenylacetyl side chains gave similar results. Compounds which lacked an aromatic ring in the side chain inhibited cephalexin uptake but lost all antibacterial activity. Thus, the phenylglycl side chain is not absolutely required for uptake. Different structural features are required for antibacterial activity and for being a substrate of the transporter. Competition studies with cephalexin indicate that human intestinal Caco-2 cells may be a useful model system for initially guiding structure-activity relationships for the rational design of new oral agents. PMID:9257735

Snyder, N J; Tabas, L B; Berry, D M; Duckworth, D C; Spry, D O; Dantzig, A H



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




NSDL National Science Digital Library

This page contains an article from The Science Creative Quarterly on acquired antibiotic resistance in bacteria. Topics covered include the discovery of antibiotics, the history and scope of antibiotic use and antibiotic resistance, mechanisms of antibiotic activity and antibiotic resistance, molecular biology of acquiring antibiotic resistance, and possible solutions to the antibiotic resistance problem. This article would be accessible to middle school or higher level students and teachers.

Yim, Grace; Quarterly, The S.


A systematic review and meta-analysis of the effects of antibiotic consumption on antibiotic resistance  

PubMed Central

Background Greater use of antibiotics during the past 50 years has exerted selective pressure on susceptible bacteria and may have favoured the survival of resistant strains. Existing information on antibiotic resistance patterns from pathogens circulating among community-based patients is substantially less than from hospitalized patients on whom guidelines are often based. We therefore chose to assess the relationship between the antibiotic resistance pattern of bacteria circulating in the community and the consumption of antibiotics in the community. Methods Both gray literature and published scientific literature in English and other European languages was examined. Multiple regression analysis was used to analyse whether studies found a positive relationship between antibiotic consumption and resistance. A subsequent meta-analysis and meta-regression was conducted for studies for which a common effect size measure (odds ratio) could be calculated. Results Electronic searches identified 974 studies but only 243 studies were considered eligible for inclusion by the two independent reviewers who extracted the data. A binomial test revealed a positive relationship between antibiotic consumption and resistance (p?generated a significant pooled odds ratio of 2.3 (95% confidence interval 2.2 to 2.5) with a meta-regression producing several significant predictors (F(10,77)?=?5.82, p?antibiotic consumption is associated with the development of antibiotic resistance. A subsequent meta-analysis, with a subsample of the studies, generated several significant predictors. Countries in southern Europe produced a stronger link between consumption and resistance than other regions so efforts at reducing antibiotic consumption may need to be strengthened in this area. Increased consumption of antibiotics may not only produce greater resistance at the individual patient level but may also produce greater resistance at the community, country, and regional levels, which can harm individual patients.



Antibiotic alternatives: the substitution of antibiotics in animal husbandry?  

PubMed Central

It is a common practice for decades to use of sub-therapeutic dose of antibiotics in food-animal feeds to prevent animals from diseases and to improve production performance in modern animal husbandry. In the meantime, concerns over the increasing emergence of antibiotic-resistant bacteria due to the unreasonable use of antibiotics and an appearance of less novelty antibiotics have prompted efforts to develop so-called alternatives to antibiotics. Whether or not the alternatives could really replace antibiotics remains a controversial issue. This review summarizes recent development and perspectives of alternatives to antibiotics. The mechanism of actions, applications, and prospectives of the alternatives such as immunity modulating agents, bacteriophages and their lysins, antimicrobial peptides, pro-, pre-, and synbiotics, plant extracts, inhibitors targeting pathogenicity (bacterial quorum sensing, biofilm, and virulence), and feeding enzymes are thoroughly discussed. Lastly, the feasibility of alternatives to antibiotics is deeply analyzed. It is hard to conclude that the alternatives might substitute antibiotics in veterinary medicine in the foreseeable future. At the present time, prudent use of antibiotics and the establishment of scientific monitoring systems are the best and fastest way to limit the adverse effects of the abuse of antibiotics and to ensure the safety of animal-derived food and environment.

Cheng, Guyue; Hao, Haihong; Xie, Shuyu; Wang, Xu; Dai, Menghong; Huang, Lingli; Yuan, Zonghui



Selection of antibiotic resistance at very low antibiotic concentrations.  


Abstract Human use of antibiotics has driven the selective enrichment of pathogenic bacteria resistant to clinically used drugs. Traditionally, the selection of resistance has been considered to occur mainly at high, therapeutic levels of antibiotics, but we are now beginning to understand better the importance of selection of resistance at low levels of antibiotics. The concentration of an antibiotic varies in different body compartments during treatment, and low concentrations of antibiotics are found in sewage water, soils, and many water environments due to natural production and contamination from human activities. Selection of resistance at non-lethal antibiotic concentrations (below the wild-type minimum inhibitory concentration) occurs due to differences in growth rate at the particular antibiotic concentration between cells with different tolerance levels to the antibiotic. The minimum selective concentration for a particular antibiotic is reached when its reducing effect on growth of the susceptible strain balances the reducing effect (fitness cost) of the resistance determinant in the resistant strain. Recent studies have shown that resistant bacteria can be selected at concentrations several hundred-fold below the lethal concentrations for susceptible cells. Resistant mutants selected at low antibiotic concentrations are generally more fit than those selected at high concentrations but can still be highly resistant. The characteristics of selection at low antibiotic concentrations, the potential clinical problems of this mode of selection, and potential solutions will be discussed. PMID:24694026

Sandegren, Linus



Selection of antibiotic resistance at very low antibiotic concentrations  

PubMed Central

Human use of antibiotics has driven the selective enrichment of pathogenic bacteria resistant to clinically used drugs. Traditionally, the selection of resistance has been considered to occur mainly at high, therapeutic levels of antibiotics, but we are now beginning to understand better the importance of selection of resistance at low levels of antibiotics. The concentration of an antibiotic varies in different body compartments during treatment, and low concentrations of antibiotics are found in sewage water, soils, and many water environments due to natural production and contamination from human activities. Selection of resistance at non-lethal antibiotic concentrations (below the wild-type minimum inhibitory concentration) occurs due to differences in growth rate at the particular antibiotic concentration between cells with different tolerance levels to the antibiotic. The minimum selective concentration for a particular antibiotic is reached when its reducing effect on growth of the susceptible strain balances the reducing effect (fitness cost) of the resistance determinant in the resistant strain. Recent studies have shown that resistant bacteria can be selected at concentrations several hundred-fold below the lethal concentrations for susceptible cells. Resistant mutants selected at low antibiotic concentrations are generally more fit than those selected at high concentrations but can still be highly resistant. The characteristics of selection at low antibiotic concentrations, the potential clinical problems of this mode of selection, and potential solutions will be discussed.



Prospective audit and feedback on antibiotic prescription in an adult hematology-oncology unit in Singapore.  


We evaluated the impact of a prospective audit and feedback antimicrobial stewardship program (ASP) on antibiotic prescription and resistance trends in a hematology-oncology unit in a university hospital (National University Cancer Institute, Singapore [NCIS]). A prospective interrupted time-series study comprising 11-month pre-intervention (PIP) and intervention evaluation phases (IEP) flanking a one-month implementation phase was carried out. Outcome measures included defined daily dose per 100 (DDD/100) inpatient-days of ASP-audited and all antibiotics (encompassing audited and non-audited antibiotics), and the incidence-density of antibiotic-resistant microorganisms at the NCIS. Internal and external controls were DDD/100 inpatient-days of paracetamol at the NCIS and DDD/100 inpatient-days of antibiotics prescribed in the rest of the hospital. There were 580 ASP recommendations from 1,276 audits, with a mean monthly compliance of 86.9%. Significant reversal of prescription trends towards reduced prescription of audited (coefficient?=?-2.621; 95% confidence interval [CI]: -4.923, -0.319; p?=?0.026) and all evaluated antibiotics (coefficient?=?-4.069; 95% CI: -8.075, -0.063; p?=?0.046) was observed. No changes were seen for both internal and external controls, except for the reversal of prescription trends for cephalosporins hospital-wide. Antimicrobial resistance did not change over the time period of the study. Adverse outcomes-the majority unavoidable-occurred following 5.5% of accepted ASP recommendations. Safe and effective ASPs can be implemented in the complex setting of hematology-oncology inpatients. PMID:21845470

Yeo, C-L; Chan, D S-G; Earnest, A; Wu, T-S; Yeoh, S-F; Lim, R; Jureen, R; Fisher, D; Hsu, L-Y



Bacterial vaccines and antibiotic resistance  

PubMed Central

Spread of antibiotic resistance is mediated by clonal lineages of bacteria that besides being resistant also possess other properties promoting their success. Some vaccines already in use, such as the pneumococcal conjugate vaccines, have had an effect on these successful clones, but at the same time have allowed for the expansion and resistance evolution of previously minor clones not covered by the vaccine. Since resistance frequently is horizontally transferred it will be difficult to generate a vaccine that covers all possible genetic lineages prone to develop resistance unless the vaccine target(s) is absolutely necessary for spread and/or disease development. Targeting the resistance mechanism itself by a vaccine is an interesting but hitherto unexplored approach.

Normark, Staffan



Bacterial vaccines and antibiotic resistance.  


Abstract Spread of antibiotic resistance is mediated by clonal lineages of bacteria that besides being resistant also possess other properties promoting their success. Some vaccines already in use, such as the pneumococcal conjugate vaccines, have had an effect on these successful clones, but at the same time have allowed for the expansion and resistance evolution of previously minor clones not covered by the vaccine. Since resistance frequently is horizontally transferred it will be difficult to generate a vaccine that covers all possible genetic lineages prone to develop resistance unless the vaccine target(s) is absolutely necessary for spread and/or disease development. Targeting the resistance mechanism itself by a vaccine is an interesting but hitherto unexplored approach. PMID:24694025

Henriques-Normark, Birgitta; Normark, Staffan



Antagonism by chloramphenicol of broad-spectrum beta-lactam antibiotics against Klebsiella pneumoniae.  

PubMed Central

Chloramphenicol combined with cefotaxime, moxalactam, cefoperazone, aztreonam, or imipenem was tested in vitro against clinical isolates of Klebsiella pneumoniae. By time-kill cultures (killing curves), chloramphenicol interfered with activity of all five beta-lactams. When chloramphenicol was added before the beta-lactams, the action of cefotaxime, moxalactam, or cefoperazone against all isolates was antagonized at all times tested. The action of aztreonam was antagonized against four of six isolates. With imipenem, antagonism occurred against half of the isolates at some time during 24 h when chloramphenicol was added simultaneously, provided that a sufficient inoculum of K. pneumoniae was employed. Generally, less antagonism resulted when chloramphenicol was added after the cephalosporins. Interference of bactericidal activity of three new cephalosporins by chloramphenicol has potential clinical relevance to the therapy of gram-negative bacillary meningitis. The lesser antagonism of aztreonam and imipenem by chloramphenicol is of uncertain clinical relevance but indicates that this in vitro phenomenon may apply to a wide range of beta-lactam antibiotics.

Brown, T H; Alford, R H



The Comprehensive Antibiotic Resistance Database  

PubMed Central

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.

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



Diverse antibiotic resistance genes in dairy cow manure.  


Application of manure from antibiotic-treated animals to crops facilitates the dissemination of antibiotic resistance determinants into the environment. However, our knowledge of the identity, diversity, and patterns of distribution of these antibiotic resistance determinants remains limited. We used a new combination of methods to examine the resistome of dairy cow manure, a common soil amendment. Metagenomic libraries constructed with DNA extracted from manure were screened for resistance to beta-lactams, phenicols, aminoglycosides, and tetracyclines. Functional screening of fosmid and small-insert libraries identified 80 different antibiotic resistance genes whose deduced protein sequences were on average 50 to 60% identical to sequences deposited in GenBank. The resistance genes were frequently found in clusters and originated from a taxonomically diverse set of species, suggesting that some microorganisms in manure harbor multiple resistance genes. Furthermore, amid the great genetic diversity in manure, we discovered a novel clade of chloramphenicol acetyltransferases. Our study combined functional metagenomics with third-generation PacBio sequencing to significantly extend the roster of functional antibiotic resistance genes found in animal gut bacteria, providing a particularly broad resource for understanding the origins and dispersal of antibiotic resistance genes in agriculture and clinical settings. IMPORTANCE The increasing prevalence of antibiotic resistance among bacteria is one of the most intractable challenges in 21st-century public health. The origins of resistance are complex, and a better understanding of the impacts of antibiotics used on farms would produce a more robust platform for public policy. Microbiomes of farm animals are reservoirs of antibiotic resistance genes, which may affect distribution of antibiotic resistance genes in human pathogens. Previous studies have focused on antibiotic resistance genes in manures of animals subjected to intensive antibiotic use, such as pigs and chickens. Cow manure has received less attention, although it is commonly used in crop production. Here, we report the discovery of novel and diverse antibiotic resistance genes in the cow microbiome, demonstrating that it is a significant reservoir of antibiotic resistance genes. The genomic resource presented here lays the groundwork for understanding the dispersal of antibiotic resistance from the agroecosystem to other settings. PMID:24757214

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



Antibiotics and preterm labor.  


In summary, a definite association has been demonstrated between preterm labor and genital tract infection. Conclusions regarding the true benefits of antibiotics as adjunctive therapy in treatment of preterm labor are inconsistent. Whereas some of the studies were able to demonstrate significant prolongation of pregnancy, no consistent reduction in either maternal or neonatal morbidity has been demonstrated. However, because the actual incidental morbidity rate is low in the populations studied, the power of this finding is also low. The potential risks for using antimicrobials has yet to be adequately addressed. It has been shown that bacterial resistance can develop when antibiotics are used without specific aim or when a specific bacteria is undertreated. It has been recently shown that prenatal and intrapartum antibiotic use is associated with an increased risk for antibiotic resistant neonatal sepsis if infection occurs. Because of these reasons, we discourage the administration of antibiotic treatment to women in preterm labor for the purpose of pregnancy prolongations. Treatment should be directed towards those with specific indications for treatment (e.g., intrapartum, group B streptococci prophylaxis, urinary tract infection, etc). The primary flaw in these many evaluations of preterm labor is the true incidence of preterm birth. The clinical diagnosis of preterm labor is a difficult one. Approximately one-half of those individuals with preterm contractions will not deliver until term. So, the use of antibiotics for all women in idiopathic preterm labor is destined to treat many women who are unlikely to benefit. If we were able to truly identify those who were in "true" labor, perhaps we could be more selective in determining who may benefit from antibiotics. Biochemical markers such as onco-fetal fibronectin could well-be a helpful marker. Goldberg et al evaluated FFN in vaginal and cervical secretions while attempting to better-predict who would have upper genital tract infection. In this large, multicenter trial, patients were tested for FFN every 2 weeks from 23 to 30 weeks gestation. In those patients who proceeded to deliver before 32 weeks gestation, increased levels of cervical FFN (> 50 ng/ml) were identified in approximately one-quarter. Fetal fibronectin was positive in 4% of their samples and was found to be twice as likely in one with bacterial vaginosis. They showed that the presence of increased FFN was associated with upper genital tract infection (clinical and histologic chorioamnionitis) as a main reason for preterm labor and delivery (increased risk 16-20-fold). Those with increased FFN levels were also shown to have an increased incidence of neonatal sepsis as well. Peaceman et al used FFN to attempt to identify those at risk for preterm delivery among women with contractions between 24 and 34 6/7 weeks gestation. Those with negative FFN were less likely to deliver within 7 days of the test. The negative predictive value was 99.7%, suggesting that this test may be helpful in identifying women who would not benefit from antibiotic treatment. However, if in the absence of prospective clinical trials demonstrating the efficacy of this approach, we discourage the use of FFN screening for this indication. PMID:11100298

Stetzer, B P; Mercer, B M



Antibiotic-associated neutropenia.  


Neutropenia is an uncommon but potentially serious complication of drug therapy. Many drugs, especially antibiotics, can produce this untoward effect. Typically, drug-induced neutropenia occurs in a patient receiving a semisynthetic penicillin for two weeks or more. The cause is believed to be either a hypersensitivity reaction or a toxic dose-related suppression of white blood cell precursors. Most patients improve after discontinuation of the drug. PMID:1575118

Walbroehl, G S; John, P G



Pneumococcal resistance to antibiotics.  

PubMed Central

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

Klugman, K P



Characteristics of Plasmid-Mediated Quinolone Resistance Genes in Extended-Spectrum Cephalosporin-Resistant Isolates of Klebsiella pneumoniae and Escherichia coli in Korea  

Microsoft Academic Search

Background: Quinolone resistance is frequently associated with extended-spectrum cephalosporin resistance in Enterobacteriaceae. Methods: The characteristics of plasmid-mediated quinolone resistance (PMQR) genes [qnr genes, aac(6?)-Ib-cr and qepA] in clinical isolates of Klebsiella pneumoniae and Escherichia coli resistant to extended-spectrum cephalosporin were studied. Results: 5 and 4 of 95 E. coli isolates but 46 (86\\/187) and 6% (12\\/187) of K. pneumoniae had

Mi-Ran Seo; Yoon Soo Park; Hyunjoo Pai



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



Prescribing for children - taste and palatability affect adherence to antibiotics: a review.  


The taste of an antibiotic is often not taken into account by practitioners, although there is significant evidence to show palatability correlates strongly with adherence. Many parents will be familiar with the difficulties of convincing young children to take bitter, unfamiliar medicine. Certain drugs, for example flucloxacillin, are so unpalatable that they should not be prescribed as syrups without prior 'taste testing' in an individual child, while others, such as oral cephalosporins, are accepted very well although they are more expensive with a broader antimicrobial spectrum than may be strictly necessary. Palatability is important in the broader context of global child health as regards the successful treatment of malaria, HIV and dehydration. The hidden cost of poor adherence resulting treatment failure, complications and the development of drug resistance cannot be over emphasised. Prescribing should involve parents, children and practitioners in an open discussion around the most suitable, palatable formulations for successful treatment outcomes. PMID:22088684

Baguley, Dave; Lim, Emma; Bevan, Amanda; Pallet, Ann; Faust, Saul N



Developments in liquid membrane separation of beta-lactam antibiotics.  


This paper presents an overview on the developments in liquid membrane separation and purification of commercially important beta-lactam antibiotics. Reactive extraction via liquid-liquid ion exchange or ion-pair extraction mechanism can be exploited to develop liquid membrane processes for separation and concentration of penicillins and cephalosporins. Because of high selectivity and flux, liquid membrane processes can be adopted for direct extraction of beta-lactams from fermentation broth. Other advantages of liquid membrane technologies are low capital and operating costs, compact unit installation in commercial plants, low material inventory, etc. Both emulsion liquid membrane and supported liquid membrane techniques can be effective under the reactive extraction conditions. However, the stability problems of liquid membrane should be resolved before commercial application can be established. Alternately, reactive extraction in non-dispersive mode with hollow fiber membranes can be an attractive and viable strategy for practical application. Applicability of the liquid membrane processes has been discussed from process engineering and design considerations. PMID:8818264

Ghosh, A C; Bora, M M; Dutta, N N



Comparative in vitro activity and the inoculum effect of ertapenem against Enterobacteriaceae resistant to extended-spectrum cephalosporins  

Microsoft Academic Search

The in vitro activity and the inoculum effect of ertapenem were evaluated against a total of 70 Enterobacteriaceae isolates resistant to extended-spectrum cephalosporins. The extended-spectrum ?-lactamase phenotypic confirmatory disk diffusion test was performed and AmpC-inducible species were detected using cefoxitin\\/cefotaxime disk antagonism tests. ?-Lactamases were characterised by isoelectric focusing and TEM-specific polymerase chain reaction. Minimum inhibitory concentrations (MICs) were determined

Carmen Betriu; Santiago Salso; Aida Sánchez; Esther Culebras; María Gómez; Iciar Rodríguez-Avial; Juan J. Picazo



In vitro and in vivo evaluation of Ro 09-1428, a new parenteral cephalosporin with high antipseudomonal activity.  

PubMed Central

Ro 09-1428, a new parenteral cephalosporin with a catechol moiety attached at position 7 of the cephalosporin ring, showed high in vitro activity against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, and Streptococcus pyogenes, with MICs for 90% of strains tested (MIC90s) of less than or equal to 0.39 micrograms/ml. Morganella morganii, Providencia rettgeri, Citrobacter freundii, Haemophilus influenzae, Staphylococcus aureus, and Streptococcus pneumoniae were inhibited with MIC90s of less than or equal to 3.13 micrograms/ml. Serratia marcescens was less susceptible to Ro 09-1428, with a MIC90 of 25 micrograms/ml. The most distinctive feature of Ro 09-1428 was its potent activity against Pseudomonas aeruginosa and Acinetobacter calcoaceticus, with MIC90s of 0.39 and 6.25 micrograms/ml, respectively. Most of the ceftazidime-resistant strains of P. aeruginosa, E. cloacae, and C. freundii were inhibited by Ro 09-1428, while those of S. marcescens were resistant at a concentration of 12.5 micrograms/ml. Ro 09-1428 was more active than ceftazidime against staphylococci. PBP 3 was the most sensitive target in E. coli and P. aeruginosa. The response to ferric iron in growth medium suggests that Ro 09-1428 may be taken up by transport mechanisms similar to those of other catechol cephalosporins. In accordance with its in vitro activity, Ro 09-1428 activity was equal to or greater than ceftazidime activity in efficacy against experimental septicemias in mice. The results indicate that Ro 09-1428 is a broad-spectrum cephalosporin with advantages over ceftazidime in its activity against P. aeruginosa, staphylococci, and ceftazidime-resistant strains of C. freundii and E. cloacae.

Arisawa, M; Sekine, Y; Shimizu, S; Takano, H; Angehrn, P; Then, R L



BAL9141, a Novel Extended-Spectrum Cephalosporin Active against Methicillin-Resistant Staphylococcus aureus in Treatment of Experimental Endocarditis  

Microsoft Academic Search

The therapeutic efficacy of BAL9141 (formerly Ro 63-9141), a novel cephalosporin with broad in vitro activity that also has activity against methicillin-resistant Staphylococcus aureus (MRSA), was investigated in rats with experimental endocarditis. The test organisms were homogeneously methicillin-resistant S. aureus strain COL transformed with the penicillinase-encoding plasmid pI524 (COL Bla) and homogeneously methicillin-resistant, penicillinase-producing isolate P8-Hom, selected by serial exposure

J. M. Entenza; P. Hohl; I. Heinze-Krauss; M. P. Glauser; P. Moreillon



BEL-2, an Extended-Spectrum ?-Lactamase with Increased Activity toward Expanded-Spectrum Cephalosporins in Pseudomonas aeruginosa?  

PubMed Central

A Pseudomonas aeruginosa isolate recovered in Belgium produced a novel extended-spectrum ß-lactamase, BEL-2, differing from BEL-1 by a single Leu162Phe substitution. That modification significantly altered the kinetic properties of the enzyme, increasing its affinity for expanded-spectrum cephalosporins. The blaBEL-2 gene was identified from a P. aeruginosa isolate clonally related to another blaBEL-1-positive isolate.

Poirel, Laurent; Docquier, Jean-Denis; De Luca, Filomena; Verlinde, Annemie; Ide, Louis; Rossolini, Gian Maria; Nordmann, Patrice



BEL-2, an extended-spectrum beta-lactamase with increased activity toward expanded-spectrum cephalosporins in Pseudomonas aeruginosa.  


A Pseudomonas aeruginosa isolate recovered in Belgium produced a novel extended-spectrum ss-lactamase, BEL-2, differing from BEL-1 by a single Leu162Phe substitution. That modification significantly altered the kinetic properties of the enzyme, increasing its affinity for expanded-spectrum cephalosporins. The bla(BEL-2) gene was identified from a P. aeruginosa isolate clonally related to another bla(BEL-1)-positive isolate. PMID:19884378

Poirel, Laurent; Docquier, Jean-Denis; De Luca, Filomena; Verlinde, Annemie; Ide, Louis; Rossolini, Gian Maria; Nordmann, Patrice



Lysine biosynthesis in microbes: relevance as drug target and prospects for ?-lactam antibiotics production.  


Plants as well as pro- and eukaryotic microorganisms are able to synthesise lysine via de novo synthesis. While plants and bacteria, with some exceptions, rely on variations of the meso-diaminopimelate pathway for lysine biosynthesis, fungi exclusively use the ?-aminoadipate pathway. Although bacteria and fungi are, in principle, both suitable as lysine producers, current industrial fermentations rely on the use of bacteria. In contrast, fungi are important producers of ?-lactam antibiotics such as penicillins or cephalosporins. The synthesis of these antibiotics strictly depends on ?-aminoadipate deriving from lysine biosynthesis. Interestingly, despite the resulting industrial importance of the fungal ?-aminoadipate pathway, biochemical reactions leading to ?-aminoadipate formation have only been studied on a limited number of fungal species. In this respect, just recently an essential isomerisation reaction required for the formation of ?-aminoadipate has been elucidated in detail. This review summarises biochemical pathways leading to lysine production, discusses the suitability of interrupting lysine biosynthesis as target for new antibacterial and antifungal compounds and emphasises on biochemical reactions involved in the formation of ?-aminoadipate in fungi as an essential intermediate for both, lysine and ?-lactam antibiotics production. PMID:23504110

Fazius, Felicitas; Zaehle, Christoph; Brock, Matthias



Rapid screening of multiple antibiotic residues in milk using disposable amperometric magnetosensors.  


Disposable amperometric magnetosensors, involving a mixture of modified-magnetic beads (MBs), for the multiplex screening of cephalosporins (CPHs), sulfonamides (SAs) and tetracyclines (TCs) antibiotic residues in milk are reported for the first time in this work. The multiplexed detection relies on the use of a mixture of target specific modified magnetic beads (MBs) and application of direct competitive assays using horseradish peroxidase (HRP)-labeled tracers. The amperometric responses measured at -0.20V vs. the Ag pseudo-reference electrode of screen-printed carbon electrodes (SPCE) upon the addition of H2O2 in the presence of hydroquinone (HQ) as redox mediator, were used to monitor the extent of the different affinity reactions. The developed methodology, involving a simple and short pretreatment, allowed discrimination between no contaminated UHT and raw milk samples and samples containing antibiotic residues at the maximum residue limits (MRLs). The usefulness of the multiplexed magnetosensor was demonstrated by analyzing spiked milk samples in only 5min. The results demonstrated that a clear discrimination of milk samples contaminated with antibiotics at their MRL level or their mixtures, allowing the identification of milk not complying with current legislation. These features make the developed methodology a promising alternative in the development of user-friendly devices for on-site analysis to ensure quality control for dairy products. PMID:24745735

Conzuelo, F; Ruiz-Valdepeñas Montiel, V; Campuzano, S; Gamella, M; Torrente-Rodríguez, R M; Reviejo, A J; Pingarrón, J M



Antibiotic resistance in pediatric urology  

PubMed Central

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

Copp, Hillary L.



Core-shell supramolecular gelatin nanoparticles for adaptive and "on-demand" antibiotic delivery.  


The treatment of bacterial infection is one of the most challenging tasks in the biomedical field. Antibiotics were developed over 70 years and are regarded as the most efficient type of drug to treat bacterial infection. However, there is a concern that the overuse of antibiotics can lead to a growing number of multidrug-resistant bacteria. The development of antibiotic delivery systems to improve the biodistribution and bioavailability of antibiotics is a practical strategy for reducing the generation of antibiotic resistance and increasing the lifespan of newly developed antibiotics. Here we present an antibiotic delivery system (Van?SGNPs@RBC) based on core-shell supramolecular gelatin nanoparticles (SGNPs) for adaptive and "on-demand" antibiotic delivery. The core composed of cross-linked SGNPs allows for bacterial infection-microenvironment responsive release of antibiotics. The shell coated with uniform red blood cell membranes executes the function of disguise for reducing the clearance by the immune system during the antibiotic delivery, as well as absorbs the bacterial exotoxin to relieve symptoms caused by bacterial infection. This approach demonstrates an innovative and biomimetic antibiotic delivery system for the treatment of bacterial infection with a minimum dose of antibiotics. PMID:24716550

Li, Li-Li; Xu, Jun-Hua; Qi, Guo-Bin; Zhao, Xingzhong; Yu, Faquan; Wang, Hao




PubMed Central

Strains of antibiotic-resistant staphylococci that develop in a hospital are becoming increasingly important as a cause of untoward complications of hospitalization. The hospital environment and hospital personnel present the chief reservoir of antibiotic-resistant strains; and they, as well as patients discharged after hospital stay, may represent the greatest source of antibiotic-resistant strains found in the community at large. Cross infection appears to be thwarted by rigid adherence to antiseptic techniques.

Kempe, C. Henry



Ultrathin antibiotic walled microcapsules.  


Ultrathin microcapsules comprised of anionic polyelectrolytes (PE) and a polycationic aminoglycoside (AmG) antibiotic drug were prepared by depositing PE/AmG multilayers on zinc oxide (ZnO) colloid particles using the layer-by-layer self-assembly technique and subsequently dissolving the ZnO templated cores. The polyelectrolytes, dextran sulfate sodium (DxS) and poly(styrenesulfonate) (PSS), were selected owing to their different backbone structure. An aminoglycoside, tobramycin sulfate (TbS), was used for studying DxS/TbS or PSS/TbS multilayer films. The multilayer growth on ZnO cores was characterized by alternating zeta potential values that were different for the DxS/TbS and PSS/TbS multilayers due to the PE chemistry and its interaction with Zn(2+) ions. Transmission and scanning electron microscopy provide evidence of PE/TbS multilayer coating on ZnO core particles. The slow acid-decomposition of the ZnO cores using weak organic acids and the presence of sufficient quantity of Zn(2+) in the dispersion were required to produce antibiotic multilayer capsules. There was no difference in the morphological characteristics of the two types of capsules; although, the yield for [PSS/TbS](5) capsules was significantly higher than for [DxS/TbS](5) capsules which was related to the physicochemical properties of DxS/TbS/Zn(2+) and PSS/TbS/Zn(2+) complexes forming the capsule wall. The TbS quantity in the multilayer films was determined using a quartz crystal microbalance and high performance liquid chromatography techniques which showed less TbS loading in both, capsules and multilayers on planar gold substrate, than the theoretical DxS:TbS or PSS:TbS stoichiometric ratio. The decomposition of the [PE/TbS](6) multilayers was fastest in physiological buffer followed by mannitol and water. The decomposition rate of the [PSS/TbS](6) multilayers was slower than [DxS/TbS](6) monolayers. The incomplete decomposition of DxS/TbS under saline conditions suggests the major role of hydrogen bonding for stability of DxS/TbS multilayers. A combination of hydrogen bonding and hydrophobic interaction between phenyl rings in PSS was responsible for PSS/TbS multilayer stability. In vivo studies in rabbits highlight the safety and sustained drug delivery potential of the PE/AmG microcapsules. The antibiotic walled ultrathin capsules presented here are suitable for sustained ophthalmic antibiotic delivery. PMID:15638525

Khopade, Ajay J; Arulsudar, N; Khopade, Surekha A; Hartmann, J



In vitro activity of RU 29246, the active compound of the cephalosporin prodrug ester HR 916.  


The in vitro activity of RU 29246 was compared with those of other agents against 536 recent clinical isolates. The MICs of RU 29246 for 90% of members of the family Enterobacteriaceae tested (MIC90s) were less than 2 micrograms/ml except those for Morganella spp. (16 micrograms/ml) and Proteus spp. (8 micrograms/ml). RU 29246 was active against Staphylococcus aureus (MIC90, < or = 8 micrograms/ml) and against Staphylococcus saprophyticus and coagulase-negative staphylococci (MIC90s, < or = 2 micrograms/ml). Streptococci and Neisseria gonorrhoeae were highly susceptible to RU 29246, and the activity of the agent against isolates of Streptococcus pneumoniae (MIC90, < or = 0.5 micrograms/ml), Haemophilus influenzae (MIC90, < or = 2 micrograms/ml), and Moraxella catarrhalis (MIC90, < or = 2 micrograms/ml) was comparable to those of the other cephalosporins tested. RU 29246 was insusceptible to hydrolysis by the common plasmid-mediated beta-lactamases (TEM-1 and SHV-1). However, hydrolysis by the new extended-spectrum beta-lactamases (TEM-3, TEM-5, and TEM-9) was detected. Results of the study suggested that RU 29246 should be investigated clinically for use in the treatment of a wide range of infections. PMID:1489178

Riess, G; Andrews, J; Thornber, D; Wise, R



Advanced treatment of cephalosporin pharmaceutical wastewater by nano-coated electrode and perforated electrode.  


The objective of this study was to investigate the degradation of nonbiodegradable organic pollutants in biologically cephalosporin pharmaceutical wastewater using different electrodes such as non-nano-scale electrode (traditional coated), nano-scale (nano-coated) electrode, and perforated electrode after biotreatment. The traditional coated electrode plate, nano-coated electrode plate, and two different perforated titanium dioxide (TiO2) electrode plates with an average pore size of 10 ?m and 20 ?m were chosen as the anode. The results demonstrated that traditional coated electrode, nano-scale electrode, and perforated electrode could effectively remove nonbiodegradable organic pollutants from pharmaceutical wastewater. The perforated electrode with an average pore size of 10 ?m exhibited the best degradation effect with a 90 % decrease in the chemical oxygen demand (COD) (COD content reduced from 320 mg L(-1) to 32 mg L(-1)). During catalytic degradation, the electrical conductivity of pharmaceutical wastewater increased and the pH increased and finally reached equilibrium. It was also found that the perforated TiO2 electrode produced relatively large amounts of dissolved oxygen during the catalytic oxidation process, reaching above 4 mg L(-1), whereas the nano-coated electrode produced little dissolved oxygen. The biotoxicities of all wastewater samples increased firstly then decreased slightly during the electrical catalytic oxidation, but the final biotoxicities were all higher than initial ones. PMID:24967559

Yang, Bo; Zuo, Jiane; Gan, Lili; Yu, Xin; Liu, Fenglin; Tang, Xinyao; Wang, Yajiao



Overexpression of synthesized cephalosporin C acylase containing mutations in the substrate transport tunnel.  


Cephalosporin C (CPC) acylase converts CPC into 7-aminocephalosporanic acid (7-ACA) by single-step enzymatic catalysis. An optimized CPC acylase gene with substituted codons and a reduced GC content was artificially designed, synthesized and overexpressed in recombinant Escherichia coli. The synthetic CPC acylase (sCPCAcy) exhibited 2.3 times more CPC specific deacylation activity with substrate CPC than with substrate glutaryl-7-ACA (GL-7-ACA). Site-directed mutagenesis of the residues around the active center showed that not only the residues that were adjacent to the CPC D-?-aminoadipyl moiety, but also the residues that were in the substrate transport tunnel (Leu666, Ala675, Leu677), played crucial roles in catalysis as the ones locating in active center. Mutant sCPCAcy(Leu666Phe) and sCPCAcy(Leu677Ala) exhibited significantly reduced specific enzymatic activity, while mutant sCPCAcy(Ala675Gly) demonstrated enhanced activity. The specific activity of purified sCPCAcy and sCPCAcy(Ala675Gly) was 10.0 U/mg and 11.3 U/mg, respectively. The optimal CPC acylase productivity of mutant sCPCAcy(Ala675Gly) reached 5349 U/l after 24h in culture, which was a 35% increase over the activity of sCPCAcy. PMID:21968249

Wang, Ying; Yu, Huimin; Song, Wensi; An, Ming; Zhang, Jing; Luo, Hui; Shen, Zhongyao



Therapeutic effect of cefozopran (SCE-2787), a new parenteral cephalosporin, against experimental infections in mice.  

PubMed Central

The therapeutic effect of cefozopran (SCE-2787), a new semisynthetic parenteral cephalosporin, against experimental infections in mice was examined. Cefozopran was more effective than cefpiramide and was as effective as ceftazidime and cefpirome against acute respiratory tract infections caused by Klebsiella pneumoniae DT-S. In the model of chronic respiratory tract infection caused by K. pneumoniae 27, cefozopran was as effective as ceftazidime. The therapeutic effect of cefozopran against urinary tract infections caused by Pseudomonas aeruginosa P9 was superior to that of cefpirome and was equal to those of ceftazidime and cefclidin. In addition, cefozopran was more effective than ceftazidime and was as effective as flomoxef in a thigh muscle infection caused by methicillin-sensitive Staphylococcus aureus 308A-1. Against thigh muscle infections caused by methicillin-resistant S. aureus N133, cefozopran was the most effective agent. The potent therapeutic effect of cefozopran in those experimental infections in mice suggests that it would be effective against respiratory tract, urinary tract, and soft tissue infections caused by a variety of gram-positive and gram-negative bacteria in humans.

Iizawa, Y; Okonogi, K; Hayashi, R; Iwahi, T; Yamazaki, T; Imada, A





Groups naturally promote their strengths and prefer values and rules that give them an identity and an advantage. This shows up as generational tensions across cohorts who share common experiences, including common elders. Dramatic cultural events in America since 1925 can help create an understanding of the differing value structures of the Silents, the Boomers, Gen Xers, and the Millennials. Differences in how these generations see motivation and values, fundamental reality, relations with others, and work are presented, as are some applications of these differences to the dental profession. PMID:16623137

Chambers, David W



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


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

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



[Intraocular antibiotic administration for prevention of fibrin reaction after extracapsular cataract extraction? A randomized double-blind study].  


Postoperative fibrinoid reactions are regarded as a localized form of endophthalmitis caused by microbial contamination of the capsular bag during intraocular lens implantation. The incidence of early fibrinoid reactions within the first 6 postoperative days following extracapsular cataract extraction was examined after intraocular administration of antibiotics vs placebo. In a double-blind randomized trial, 2 mg cefamandol or a placebo was administered in a 0.4-ml volume at the end of the operation. A group of 28 patients received the antibiotic (mean age 74.6 years; 15 f, 13 m), while 33 patients received the placebo (mean age 72,1 years; 21 f, 12 m). Fibrinoid reactions were observed in 8 out of 61 patients during the first 6 postoperative days. There was no significant difference between the antibiotic group and the placebo group (P = 0.31). We were unable to reduce the incidence of fibrinoid reactions although we had selected a broad-spectrum cephalosporin for antibiotic treatment. The results give rise to the suspicion that most of the early postoperative fibrinoid reactions we observed were not caused by contamination with bacteria of low pathogenicity. PMID:1757024

Mittelviefhaus, H



Microbes: Too Smart for Antibiotics?  

NSDL National Science Digital Library

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

Peggy Deichstetter (St. Edward High School;)



Veterinary use and antibiotic resistance  

Microsoft Academic Search

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

Michael Teuber



Antibiotic Equisetin and Method of Production.  

National Technical Information Service (NTIS)

The patent application relates to a new antibiotic. More specifically, it relates to the antibiotic equisetin produced by Fusarium equiseti NRRL 5537. The antibiotic is active against gram-positive bacteria. Portions of this document are not fully legible...

H. R. Burmeister



Antibiotics, microbiota, and immune defense.  


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. PMID:22677185

Ubeda, Carles; Pamer, Eric G



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.



Axenomycins, New Cestocidal Antibiotics  

PubMed Central

Axenomycins are a new group of macrolide antibiotics isolated from the fermentation broth of Streptomyces lisandri n.sp. They exhibit anthelmintic activity against tapeworms (Cestoda). Three different fractions, A, B, and D, have been obtained, the most active fraction being axenomycin D. The activities of the axenomycin complex and axenomycin D against Hymenolepis nana in mice, Taenia pisiformis, Dipylidium caninum, and Diphyllobothrium sp. in dogs, and Moniezia expansa, M. benedeni, and Avitellina centripunctata in lambs were studied in experimentally and naturally infected animals. Axenomycins were effective and well tolerated by the oral route. Worm reduction rates after a single oral dose were 90 to 100% with 5 to 10 mg of axenomycin D/kg and 50 to 100% with 20 mg of axenomycin complex/kg.

Bruna, C. Della; Ricciardi, M. L.; Sanfilippo, A.



Multiresidue LC-MS/MS analysis of cephalosporins and quinolones in milk following ultrasound-assisted matrix solid-phase dispersive extraction combined with the quick, easy, cheap, effective, rugged, and safe methodology.  


A sensitive and selective confirmatory method for milk-residue analysis of ten quinolones and eight cephalosporins by LC-MS/MS has been developed herein. For the chromatographic separation of target analytes, a Perfectsil ODS-2 (250 × 4 mm, 5 ?m) analytical column was used and gradient elution was applied, using a mobile phase of 0.1% w/w TFA in water and 0.1% w/w TFA in ACN. Ultrasound-assisted matrix solid-phase dispersion procedure was applied for the extraction and clean-up procedure of antimicrobials agents from milk matrix using a mixture of Bond Elut Plexa sorbent and QuEChERS. The method was validated meeting the European Legislation determining selectivity, linearity response, trueness, precision (repeatability and between-day reproducibility), decision limit, detection capability, and ruggedness following the Youden approach. Recoveries of all antibiotics ranged from 81.7 to 117.9%, while RSD values were lower than 13.7%. Limits of quantification for all examined compounds ranged from 2.4 to 15.0 ?g/kg, substantially lower than the maximum residue limits established by the European Union (30-100 ?g/kg). PMID:23568854

Karageorgou, Eftichia; Myridakis, Antonis; Stephanou, Euripides G; Samanidou, Victoria



In vitro evaluation of HR810, a new wide-spectrum aminothiazolyl alpha-methoxyimino cephalosporin.  

PubMed Central

HR810 (Hoechst-Roussel Pharmaceuticals Inc., Somerville, N.J.) is a new, cyclical-pyridinium cephalosporin that appeared superior to numerous comparison drugs against 658 strains of aerobic and facultative anaerobic bacteria. Seventeen Enterobacteriaceae spp. were tested by broth microdilution methods, and the 50% MICs (MIC50S) and 90% MICs (MIC90s) were 0.03 to 0.12 and 0.03 to 2.0 micrograms/ml, respectively. Only one strain had an MIC greater than 8.0 micrograms/ml (99.6% is considered susceptible). HR810 inhibited 98% of Pseudomonas aeruginosa isolates at less than or equal to 16 micrograms/ml, and the MIC90 for Acinetobacter spp. was 4.0 micrograms/ml. It was also very active against Pseudomonas spp. and Staphylococcus aureus (MIC90, 0.5 micrograms/ml) but marginally active against methicillin-resistant staphylococcal strains (MIC90, 16 micrograms/ml) and enterococcus (MIC90, 32 micrograms/ml). Non-enterococcal streptococci had MIC50s ranging from 0.008 micrograms/ml for Streptococcus pyogenes to 0.12 micrograms/ml for pneumococci. All MICs of HR810 against Haemophilus and Neisseria spp. were less than or equal to 0.03 micrograms/ml (MIC50, 0.002 to 0.008 micrograms/ml). HR810 poorly inhibited beta-lactamases and was very stable against 11 tested beta-lactamases of plasmid (TEM, OXA, SHV-1, and PSE) and chromosomal (K1, K14, P99) types.

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



In vitro and in vivo antibacterial activities of E1077, a novel parenteral cephalosporin.  

PubMed Central

E1077, a new injectable cephalosporin with a broad antibacterial spectrum and potent antibacterial activity, was evaluated for its in vitro and in vivo antibacterial activities in comparison with those of cefpirome, cefuzonam, ceftazidime, and cefotaxime. E1077 showed broad in vitro antibacterial activity against gram-positive and gram-negative bacteria. Against methicillin-susceptible Staphylococcus aureus, E1077 was as active as cefpirome; the MIC for 90% of strains tested (MIC90) was 1.0 microgram/ml. Against methicillin-resistant S. aureus, E1077 was less active (MIC90, 64 micrograms/ml). For Enterobacter cloacae and Pseudomonas aeruginosa, E1077 was fourfold more active than cefpirome, with MIC90s of 1.0 and 16 micrograms/ml, respectively. For Proteus vulgaris, the MIC90 of E1077 was 32 micrograms/ml, which was fourfold greater than that of cefpirome. Against other gram-negative strains tested, the in vitro activity of E1077 was comparable to that of cefpirome. The broad antibacterial spectrum of E1077 was reflected by its in vivo efficacy against experimental septicemia caused by gram-positive and gram-negative bacteria. Against S. aureus 90 and P. aeruginosa E7, E1077 had activity superior to those of the reference compounds; against most other bacterial strains, the efficacy of E1077 was similar to that of cefpirome. Levels of E1077 in plasma and tissue of mice were studied. At 15 min after a single subcutaneous administration, E1077 displayed high peak levels (mean, 31.8 +/- 3.1 micrograms/ml). These results indicate that the in vitro and in vivo efficacies of E1077 are similar to those of cefpirome except against P. aeruginosa and P. vulgaris.

Toyosawa, T; Miyazaki, S; Tsuji, A; Yamaguchi, K; Goto, S



Gene cloning, nucleotide sequence, and expression of a cephalosporin-C deacetylase from Bacillus subtilis.  

PubMed Central

The gene encoding a cephalosporin-C deacetylase (CAH) from Bacillus subtilis SHS 0133 was cloned and sequenced. The nucleotide sequence contained an open reading frame encoding a polypeptide consisting of 318 amino acids, the molecular weight of which was in good agreement with the value obtained by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The deduced amino acid sequence contained the common sequence Gly-X-Ser-X-Gly found in many esterases, lipases, and serine proteases. This indicates that CAH is a serine enzyme. A possible promoter sequence which is very similar to the consensus sequences of -35 and -10 regions recognized by B. subtilis RNA polymerase utilizing sigma factor H was found in the 5'-flanking region of the CAH structural gene. Two repeated A+T-rich blocks consisting of 24 bp were also found in the upstream region of the initiation codon. We constructed a series of expression plasmids by inserting the CAH gene into Escherichia coli ATG vectors. The degree of CAH gene expression depended on promoters and vector plasmids, which have different replication origins. The expressed CAH protein was an active form in the soluble fraction obtained after cell disruption. The highest expression level was accomplished with an expression plasmid, pCAH400, which has the trp promoter and the replication origin derived from pAT153. In the fermentation using a 30-liter jar fermentor, the transformant E. coli JM103(pCAH400) produced 440 U of CAH per ml of culture during a 24-h incubation. This value corresponded to 2.1 g of CAH protein in 1 liter of culture broth.

Mitsushima, K; Takimoto, A; Sonoyama, T; Yagi, S



Resistance to selected beta-lactam antibiotics.  


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

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



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



Characterization of Neisseria gonorrhoeae isolates detected in Switzerland (1998-2012): emergence of multidrug-resistant clones less susceptible to cephalosporins  

PubMed Central

Background The spread of Neisseria gonorrhoeae (Ng) isolates resistant to the clinically implemented antibiotics is challenging the efficacy of treatments. Unfortunately, phenotypic and molecular data regarding Ng detected in Switzerland are scarce. Methods We compared the characteristics of Ng detected during 1998–2001 (n?=?26) to those detected during 2009–2012 (n?=?34). MICs were obtained with the Etest and interpreted as non-susceptible (non-S) according to EUCAST criteria. Sequence type (ST) was achieved implementing the NG-MAST. BlaTEM, ponA, penA, mtrR, penB, tet(M), gyrA, parC, mefA, ermA/B/C/F, rplD, rplV, and 23S rRNA genes were analyzed. Results The following susceptibility results were obtained (period: % of non-S, MIC90 in mg/L): penicillin (1998–2001: 42.3%, 3; 2009–2012: 85.3%, 16), cefixime (1998–2001: 0%, ?0.016; 2009–2012: 8.8%, 0.125), ceftriaxone (1998–2001: 0%, 0.004; 2009–2012: 0%, 0.047), ciprofloxacin (1998–2001: 7.7%, 0.006; 2009–2012: 73.5%, ?32), azithromycin (1998–2001: 11.5%, 0.25; 2009–2012: 23.6%, 0.38), tetracycline (1998–2001: 65.4%, 12; 2009–2012: 88.2%, 24), spectinomycin (1998–2001: 0%, 12; 2009–2012: 0%, 8). The prevalence of multidrug-resistant (MDR) isolates increased from 7.7% in 1998–2001 to 70.6% in 2009–2012. International STs and genogroups (G) emerged during 2009–2012 (G1407, 29.4%; G2992, 11.7%; G225, 8.8%). These isolates possessed distinctive mechanisms of resistance (e.g., G1407: PBP1 with L421, PBP2 pattern XXXIV, GyrA with S91F and D95G, ParC with S87R, PorB with G120K and A121N, mtrR promoter with A deletion). Conclusions The prevalence of penicillin- ciprofloxacin- and tetracycline-resistant Ng has reached dramatic levels, whereas cefixime and ceftriaxone show MICs that tend to increase during time. International MDR clones less susceptible to cephalosporins are rapidly emerging indicating that the era of untreatable gonococcal infections is close.



Bacterial evolution of antibiotic hypersensitivity  

PubMed Central

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.

Lazar, Viktoria; Pal Singh, Gajinder; Spohn, Reka; Nagy, Istvan; Horvath, Balazs; Hrtyan, Monika; Busa-Fekete, Robert; Bogos, Balazs; Mehi, Orsolya; Csorgo, Balint; Posfai, Gyorgy; Fekete, Gergely; Szappanos, Balazs; Kegl, Balazs; Papp, Balazs; Pal, Csaba



Liquid-chromatographic determination of five orally active cephalosporins--cefixime, cefaclor, cefadroxil, cephalexin, and cephradine--in human serum.  


We report an isocratic "high-performance" liquid-chromatographic (HPLC) procedure for measurement of five orally administered cephalosporins (cefixime, cefaclor, cefadroxil, cephalexin, and cephradine) in 0.1 mL of human serum. Serum protein is precipitated with acetonitrile, the sample is centrifuged, and the supernate is evaporated under nitrogen. The residue is reconstituted in 0.1 mL of mobile phase, and 50 to 80 microL of this is injected onto a reversed-phase Altex Ultrasphere Octyl (C8) column. The five cephalosporins are resolved by elution with a pH 2.6 mobile phase of methanol/monobasic phosphate buffer (20/80) by vol), flow rate 2 mL/min. The column effluent is monitored at 240 nm. Cefixime serves as the internal standard for the analysis of the four other compounds, cephalexin as the internal standard for cefixime. We used two standard curves for all compounds: a low-range curve for concentrations commonly observed clinically and a higher-range curve for higher concentrations. The former were linear from 1.0 to 10 mg/L for cefaclor, cefadroxil, cephalexin, and cephradine and from 0.1 to 1 mg/L for cefixime. The high-concentration curves were linear from 1 to 10 mg/L for cefixime and from 10 to 100 mg/L for the other compounds. The detection limits were 0.1 mg/L for cefixime, 1 mg/L for the other cephalosporins. Mean within-run and day-to-day CVs were always less than 15% for all compounds studied. PMID:3665031

McAteer, J A; Hiltke, M F; Silber, B M; Faulkner, R D



RU 29 246, the active compound of the cephalosporin-prodrug-ester HR 916. I. Antibacterial activity in vitro.  


The aminothiazolyl-cephalosporin RU 29 246 is the active metabolite of the prodrug-pivaloyl-oxyethyl-ester HR 916. RU 29 246 in vitro activity includes a wide range of clinically relevant bacterial pathogens. Against methicillin-sensitive Staphylococci RU 29 246 (MIC90 of 0.25 approximately 2 micrograms/ml) was clearly more active than cefaclor, cefuroxime, cefpodoxime, cefixime and ceftibuten, but slightly less active than cefdinir. RU 29 246 inhibited hemolytic Streptococci of the serogroups A, B, C and G as well as penicillin-sensitive Streptococcus pneumoniae at concentrations similar to cefdinir, cefpodoxime and cefuroxime (MIC90 less than or equal to 0.13 micrograms/ml), but less than the other oral cephalosporins investigated (cefixime, cefaclor and ceftibuten). MIC90s of RU 29 246 against Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Salmonella spp., Shigella spp., Proteus mirabilis and Haemophilus influenzae were less than or equal to 0.5 micrograms/ml. Only RU 29 246 and cefdinir demonstrated moderate activity against Acinetobacter baumannii (MIC90 greater than or equal to 4 micrograms/ml). Most strains of Pseudomonas spp., Serratia marcescens, Enterobacter spp., Hafnia alvei and Bacteroides spp. were resistant to RU 29 246. RU 29 246 killed Escherichia coli and Staphylococcus aureus at a rate of 99% to 99.9% at concentrations of two times MIC. The pH value of the medium (range 5.5 to 8.5) and the inoculum size (range 10(5) to 10(7) cfu/ml) had no or only low influence on the antibacterial activity of RU 29 246. RU 29 246 is a broad spectrum cephalosporin including in its activity both Gram-positive and Gram-negative pathogens and therefore--depending on the bioavailability of its prodrug--looks promising as to its therapeutic perspective. PMID:1592683

Bauernfeind, A; Jungwirth, R; Eberlein, E; Klesel, N; Adam, F; Isert, D; Limbert, M; Markus, A; Schrinner, E; Seibert, G



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.



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

PubMed Central

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

Blondeau, J M; Yaschuk, Y



Expression of the transporter encoded by the cefT gene of Acremonium chrysogenum increases cephalosporin production in Penicillium chrysogenum  

Microsoft Academic Search

By introduction of the cefEF genes of Acremonium chrysogenum and the cmcH gene of Streptomyces clavuligerus, Penicillium chrysogenum can be reprogrammed to form adipoyl-7-amino-3-carbamoyloxymethyl-3-cephem-4-carboxylic acid (ad7-ACCCA), a carbamoylated derivate of adipoyl-7-aminodeacetoxy-cephalosporanic acid. The cefT gene of A. chrysogenum encodes a cephalosporin C transporter that belongs to the Major Facilitator Superfamily. Introduction of cefT into an ad7-ACCCA-producing P. chrysogenum strain results

Jeroen G. Nijland; Andriy Kovalchuk; Marco A. van den Berg; Roel A. L. Bovenberg; Arnold J. M. Driessen



Antibiotic resistance in wild birds.  


Abstract Wild birds have been postulated as sentinels, reservoirs, and potential spreaders of antibiotic resistance. Antibiotic-resistant bacteria have been isolated from a multitude of wild bird species. Several studies strongly indicate transmission of resistant bacteria from human rest products to wild birds. There is evidence suggesting that wild birds can spread resistant bacteria through migration and that resistant bacteria can be transmitted from birds to humans and vice versa. Through further studies of the spatial and temporal distribution of resistant bacteria in wild birds, we can better assess their role and thereby help to mitigate the increasing global problem of antibiotic resistance. PMID:24697355

Bonnedahl, Jonas; Järhult, Josef D



Antibiotic resistance in wild birds  

PubMed Central

Wild birds have been postulated as sentinels, reservoirs, and potential spreaders of antibiotic resistance. Antibiotic-resistant bacteria have been isolated from a multitude of wild bird species. Several studies strongly indicate transmission of resistant bacteria from human rest products to wild birds. There is evidence suggesting that wild birds can spread resistant bacteria through migration and that resistant bacteria can be transmitted from birds to humans and vice versa. Through further studies of the spatial and temporal distribution of resistant bacteria in wild birds, we can better assess their role and thereby help to mitigate the increasing global problem of antibiotic resistance.

Bonnedahl, Jonas



Systemic antibiotic therapy in periodontics  

PubMed Central

Systemic antibiotics in conjunction with scaling and root planing (SRP), can offer an additional benefit over SRP alone in the treatment of periodontitis, in terms of clinical attachment loss (CAL) and pocket depth change, and reduced risk of additional CAL loss. However, antibiotics are not innocuous drugs. Their use should be justified on the basis of a clearly established need and should not be substituted for adequate local treatment. The aim of this review is to discuss the rationale, proper selection, dosage and duration for antibiotic therapy so as to optimize the usefulness of drug therapy.

Kapoor, Anoop; Malhotra, Ranjan; Grover, Vishakha; Grover, Deepak



Transport of beta-lactam antibiotics in kidney brush border membrane. Determinants of their affinity for the oligopeptide/H+ symporter.  

PubMed Central

This study was designed to determine whether beta-lactam antibiotics (cephalosporins and penicillins) are all substrates for the renal oligopeptide/H+ symporter and, if so, whether the transport system discriminates among the numerous beta-lactam antibiotics. We used [3H]glycylglutamine, [3H]cephalexin, and [3H]-ampicillin as probes for the transport of oligopeptides, cephalosporins, and penicillins in kidney brush border membrane vesicles, respectively. Among the beta-lactam antibiotics, only those with an alpha-amino group in the phenylacetamido moiety were found to interact with the oligopeptide/H+ symporter. Aminocephalosporins displayed high affinities (KiS generally < 250 microM), whereas aminopenicillins displayed low affinities (Ki 0.78-3.03 mM). These differences in affinities appeared to be a consequence of conformational features of the substrates, especially the sterical location of the carboxy group. The affinities of aminolactams for the oligopeptide/H+ symporter were, furthermore, related to the hydrophobicity of the phenylglycyl chains and the substituents attached to the thiazolidine and dihydrothiazine ring. In sharp contrast to the uptake of [3H]glycylglutamine and [3H]cephalexin, the uptake of [3H]ampicillin was not dependent on a pH gradient and was inhibited by various beta-lactam antibiotics, whether or not they contained an alpha-amino group. Our data suggest that: (a) the transport of aminocephalosporins is largely mediated by the oligopeptide/H+ symporter, which is highly influenced by the substrate structure; and (b) penicillins are transported by another system, which is less discriminative with respect to substrate structure.

Daniel, H; Adibi, S A



A method for determining the free (unbound) concentration of ten beta-lactam antibiotics in human plasma using high performance liquid chromatography with ultraviolet detection.  


With the clinical imperative to further research in the area of optimising antibiotic dosing in the intensive care setting, a simple high performance liquid chromatography method was developed and validated for routinely determining the free (unbound) concentration of ten beta-lactam antibiotics in 200 ?L of human plasma. Antibiotics determined include three cephalosporins (ceftriaxone, cephazolin and cephalotin); two carbapenems (meropenem and ertapenem); and five penicillins (ampicillin, piperacillin, benzylpenicillin, flucloxacillin and dicloxacillin). There was a single common sample preparation method involving ultracentrifugation and stabilisation. Chromatography was performed on a Waters XBridge C18 column with, depending on analytes, one of four acetonitrile-phosphate buffered mobile phases. Peaks of interest were detected via ultraviolet absorbance at 210, 260 and 304 nm. The method has been validated and used in a pathology laboratory for therapeutic drug monitoring in critically ill patients. The significant variability in the level of protein binding that is common with antibiotics traditionally considered to have high protein binding (e.g. ceftriaxone, cephazolin, ertapenem, flucloxacillin and dicloxacillin) suggests that this assay should be preferred for measuring the pharmacologically active concentration of beta-lactam antibiotics in a therapeutic drug monitoring programme. PMID:23026224

Briscoe, Scott E; McWhinney, Brett C; Lipman, Jeffrey; Roberts, Jason A; Ungerer, Jacobus P J



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



Activity of cephalosporins against methicillin-susceptible and methicillin-resistant, coagulase-negative staphylococci: minimal effect of beta-lactamase.  

PubMed Central

Eight cephalosporins were tested for their activity against methicillin-susceptible and methicillin-resistant, coagulase-negative staphylococci and for their resistance to beta-lactamase from methicillin-resistant, coagulase-negative staphylococci. Susceptibility testing by the agar plate method was evaluated for the effect of inoculum size and duration of incubation. Methicillin-susceptible, coagulase-negative staphylococci were highly susceptible to the cephalosporins, with cephapirin and cepahlothin showing the greatest activity, followed by cefazolin and cefamandole. Methicillin-resistant, coagulase-negative staphylococci displayed nearly total cross-resistance to the cephalosporins. Resistance increased with increasing inoculum size. Beta-Lactamases produced by methicillin-resistant, coagulase-negative staphylococci had a minimal hydrolytic effect on cepahlothin, cephapirin, cefazolin, and cefamandole and no measurable effect on cefoxitin. There was no correlation between the anti-staphylococcal activity and resistance to beta-lactamases.

John, J F; McNeill, W F



Validation of a microbiological method: the STAR protocol, a five-plate test, for the screening of antibiotic residues in milk.  


The results of an in-house laboratory validation of a microbiological method for the screening of antibiotic residues in milk are presented. The sensitivity of this five-plate test, called Screening Test for Antibiotic Residues (STAR), was established by the analysis of milk samples spiked with 66 antibiotics at eight different concentrations. Ten different groups of antibiotics were studied: macrolides, aminoglycosides, cephalosporins, penicillins, quinolones, tetracyclines, sulphonamides, lincosamides, phenicolated and miscellaneous drugs. It was shown that 21 antibiotics were detected by the STAR protocol at or below the maximum residue limit (MRL), and that a further 27 drugs could be detected at levels from the MRL up to four times the MRL. The sensitivity of the STAR protocol was at or below the MRL for three macrolides, one tetracycline, two aminoglycosides, some sulphonamides, half of the beta-lactams, quinolones, lincosamides, trimethoprim and baquiloprim. Moreover, the STAR protocol was at least twice as sensitive as conventional methods for macrolides, quinolones and tetracyclines. The other antibiotics had limits of detection between four and 150 times the MRL. Each plate was preferentially sensitive for one or two families of antibacterials: the plate Bacillus cereus for tetracyclines, the plate Escherichia coli for quinolones, the plate Basillus subtilis for aminoglycosides, the plate Kocuria varians for macrolides, and the plate Bacillus stearothermophilus for sulphonamides and beta-lactams. This method has been used routinely on a day-to-day basis to direct the physicochemical confirmation towards one or two families of antibiotics. Considering the high cost of liquid chromatography coupled with tandem mass spectrometry detection analyses, the reduction of the range of antibiotics to test for confirmation is a significant gain in time and money. PMID:15204543

Gaudin, V; Maris, P; Fuselier, R; Ribouchon, J-L; Cadieu, N; Rault, A



Multiple Antibiotic Resistance Operon Assays.  

National Technical Information Service (NTIS)

An isolated and cloned region of a bacterial chromosome containing a multiple antibiotic resistance operon is disclosed. A description of the structure and function of the operon is provided as are assorted recombinant DNA constructs involving the operon ...

S. B. Levy



Intravenous antibiotic therapy at home.  


Many patients who are hospitalized for intensive intravenous (IV) antibiotic therapy of serious infections are not disabled. Following a short period of treatment in the hospital and after their medical problem has stabilized, these patients can safety receive IV antibiotics at home. Patients who had osteomyelitis or infective endocarditis were selected for this study. Utilizing an IV nurse team, patients were instructed in the administration of the antibiotic. They returned to the hospital every 48 hours to have their IV catheter changed and to receive a new supply of antibiotic. There was a substantial monetary saving with each treatment course (at least $1,600 per patient), and, in addition, the patients were much more comfortable at home and some returned to work or to school. PMID:434994

Kind, A C; Williams, D N; Persons, G; Gibson, J A



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



Prophylactic antibiotics in orthopaedic surgery.  


The use of prophylactic antibiotics in orthopaedic surgery is effective in reducing surgical site infections in hip and knee arthroplasty, spine surgery, and open reduction and internal fixation of fractures. To maximize the beneficial effect of prophylactic antibiotics while minimizing adverse effects, the correct antimicrobial agent must be selected, the drug must be administered just before incision, and the duration of administration should not exceed 24 hours. PMID:18460689

Prokuski, Laura



Challenges and future prospects of antibiotic therapy: from peptides to phages utilization  

PubMed Central

Bacterial infections are raising serious concern across the globe. The effectiveness of conventional antibiotics is decreasing due to global emergence of multi-drug-resistant (MDR) bacterial pathogens. This process seems to be primarily caused by an indiscriminate and inappropriate use of antibiotics in non-infected patients and in the food industry. New classes of antibiotics with different actions against MDR pathogens need to be developed urgently. In this context, this review focuses on several ways and future directions to search for the next generation of safe and effective antibiotics compounds including antimicrobial peptides, phage therapy, phytochemicals, metalloantibiotics, lipopolysaccharide, and efflux pump inhibitors to control the infections caused by MDR pathogens.

Mandal, Santi M.; Roy, Anupam; Ghosh, Ananta K.; Hazra, Tapas K.; Basak, Amit; Franco, Octavio L.