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PubMed1983

Broad-spectrum beta-lactam resistance in Enterobacter: emergence during treatment and mechanisms of resistance.

Of three patients with Enterobacter mediastinitis treated with cefamandole, two failed initial treatment due to emergence of strains resistant to cefamandole and third generation cephalosporins. Extracts of the sensitive strains showed inducible hydrolysis of cephalothin; resistant strains (wild and laboratory derived) showed constitutive hydrolysis of cephalothin and cefamandole and bound but did not hydrolyze cefotaxime and latamoxef (moxalactam). In one mutant, increased latamoxef resistance appeared due to non-enzymatic mechanism(s). The Enterobacter strain from the patient who was treated successfully with cefamandole yielded only low level resistant mutants with lower cephalosporin binding than obtained with the other strains.

Anti-Bacterial Agents↗
PubMed1983

Cefotetan: comparative study in vitro against 226 Gram-negative clinical isolates.

The activity in vitro of the new cephamycin, cefotetan, was compared with that of cephalothin, cefoxitin, cefuroxime and cefotaxime against 226 recently isolated Gram-negative pathogens (207 Enterobacteriaceae and 19 Acinetobacter). Cefotetan was consistently more potent than cephalothin, cefoxitin and cefuroxime. Cefotaxime and cefotetan were essentially similar in activity against the Enterobacteriaceae with the singular exception of Enterobacter spp. which were markedly more susceptible to the former drug. None of the five agents was especially active against acinetobacter but cefotaxime was the best. Limited tests of bactericidal activity showed that the MBC differed from the MIC by a factor of 4 at most. Increasing the inoculum tested from 10(2) to 10(8) per ml had little adverse effect on the MIC of cefotetan. If the recommendations of the National Committee for Clinical Laboratory Standards for susceptibility to cephalosporins are applicable to cefotetan and the breakpoint criteria of less than or equal to 10 mg/l (sensitive) and greater than or equal to 32 mg/l (resistant) are acceptable, then only a few of the Enterobacteriaceae in this study were resistant. These resistant organisms were amongst Enterobacter spp. and Citrobacter spp.

Anti-Bacterial Agents↗
PubMed1984

Antimicrobial tolerance in group C and group G streptococci.

The in-vitro activity of various antimicrobial agents against 61 clinical isolates (35 group G streptococci and 26 group C streptococci) was studied. Penicillin, cephalothin and vancomycin were the most active agents with MIC90 values of 0.03, 0.06 and 0.12 mg/l respectively. Tolerance, defined as an MIC to MBC ratio of 32 or greater, was observed in six isolates (four group G--11.4% and two group C-7.7%). Two isolates were tolerant to penicillin alone and one each to cephalothin, vancomycin, latamoxef (moxalactam) and cefotaxime. No cross-tolerance was observed. The addition of gentamicin to the beta-lactam agents and of gentamicin or rifampicin to vancomycin resulted in bactericidal activity. None of the combinations were antagonistic. Our results demonstrate that various bactericidal antimicrobial combinations are available for therapy against tolerant organisms.

Anti-Bacterial Agents↗
PubMed1984

Effectiveness of cefamandole against methicillin-resistant strains of Staphylococcus aureus in vitro and in experimental infections.

An investigation was carried out into the effectiveness of cefamandole as compared to that of cephalothin against methicillin-sensitive and methicillin-resistant strains of Staphylococcus aureus both in vitro and in mice with the experimental peritonitis-induced septicaemia as a model for a generalized infection. In the agar-diffusion test 95% of 118 and in the broth-dilution test 80% of 30 methicillin-resistant strains were sensitive to cefamandole. In experimental infections the ED50 with methicillin-resistant strains was 20 times greater than that required for the methicillin-sensitive strain although the MIC was only twice that for the latter. Doses of cephalothin required for treatment of infections due to methicillin-resistant strains were also twenty times greater than for those due to the methicillin-sensitive strain. But these differences were consistent with those in MIC (by factors of 16-32). Thus, the results of in-vitro testing of cefamandole are not predictive for its therapeutic efficacy in staphylococcal infections with methicillin-resistant strains. Therefore, rather than relying on inhibition zone diameter and MIC, the information that a staphylococcal strain is methicillin-resistant should be used as an indication not to choose cefamandole for chemotherapy.

Animals↗
PubMed1984

Survey of the phenotypes of susceptibility to beta-lactams in Enterobacteriaceae at the Pitie-Salpetriere Hospital.

The phenotypes of susceptibility to ampicillin, carbenicillin, cephalothin, cefamandole, cefoxitin and cefotaxime were determined by the disc-diffusion method in 10,994 Enterobacteriaceae consecutively isolated from in-patients during 18 months. The susceptible phenotypes were much more frequent among Escherichia coli, Proteus mirabilis and Klebsiella (67.4 to 84.8%) than among Serratia, Enterobacter and Citrobacter (8.8 to 35.5%). In all species the most common resistance phenotypes were to ampicillin and carbenicillin: E. coli (28%), Pr. mirabilis (15.2%), Klebsiella (23.8%), indole-positive Proteus (33.3%), Serratia (74.4%), Enterobacter (61.4%) and Citrobacter (74.8%). Among E. coli 4.6% of the strains were resistant to ampicillin and cephalothin but susceptible to carbenicillin. Among E. coli, Pr. mirabilis and Klebsiella the strains susceptible only to cefotaxime represented 0.3 to 5% and no cefotaxime-resistant strain was isolated; whereas among Serratia, Enterobacter and Citrobacter the former represented 28.3 to 58.3% and the latter 7.5 to 18.5%. Some important differences in the distribution of the phenotypes according to the type of ward were observed.

Anti-Bacterial Agents↗
PubMed1985

Evaluation of the in-vivo efficacy of Sch 34343.

Sch 34343 showed a linear dose response (with respect to AUCs) in mice following both intravenous and subcutaneous administration. It was 100% bioavailable following subcutaneous administration. Peak serum levels, AUCs, beta-phase half-life and recovery of Sch 34343 from the urine of mice indicated that it was similar to cephalothin and cefamandole. In experimental mouse infections, against Gram-negative strains, Sch 34343 was more active than cephalothin, equal to or more active than cefamandole and cefoxitin, but less active than latamoxef (moxalactam) and cefotaxime following single or multiple dose therapy. It was the most active compound against Staphylococcus. Sch 34343 was equally active against strains sensitive to beta-lactams and strains producing beta-lactamases. In an anaerobic abscess model in mice, Sch 34343 was more active than cefoxitin and clindamycin against Bacteroides fragilis. In Escherichia coli meningitis in rabbits, it cured rabbits with a single intravenous dose of 50 mg/kg.

Animals↗
PubMed1986

Comparative in-vitro activity of antibiotics incorporated in acrylic bone cement.

We compared the persistence of antibacterial activity around antibiotic-impregnated acrylic bone cement discs which were serially transferred on seeded agar plates. On plates inoculated with Staphylococcus aureus ATCC 25923, CMW1 discs containing 2.5% by dry weight of cephalothin, coumermycin or fusidic acid (as diethanolamine fusidate) produced zones of inhibition for four to eight weeks when transferred daily. In contrast, ceftriaxone, cotrimoxazole, rifampicin and vancomycin ceased to be inhibitory within a week. Discs made of 'Palacos-R with Garamycin,' which contains gentamicin 1.25%, had an intermediate duration of activity. When Escherichia coli ATCC 25922 was used as the test organism, ceftriaxone and 'Palacos-R with Garamycin' showed activity for almost three weeks, cephalothin and cotrimoxazole were briefly inhibitory and the remainder not at all. When discs were transferred each week instead of daily, the ranking of antibiotics was similar but antibacterial activity persisted for longer. A combination of gentamicin plus fusidic acid in CMW1 was active for a much shorter time than either fusidic acid alone or 'Palacos-R with Garamycin'. We conclude that coumermycin is a promising new agent for incorporation in acrylic cement.

Acrylates↗
PubMed1992

Characterization of chromosomally encoded penicillinases in clinical isolates of Klebsiella pneumoniae.

Four Klebsiella pneumoniae strains, isolated in two geographically distant French hospitals, were found to produce constitutive beta-lactamases with an unusual isoelectric point for this species (8.1). The four enzymes were chromosomally encoded and related to the Ambler's class A plasmid-mediated SHV-type enzymes. The four enzymes were predominantly penicillinases, with good activity against amino- and ureidopenicillins. They poorly hydrolysed cephalothin, cephaloridine and cefoperazone and did not hydrolyse third-generation cephalosporins and aztreonam. The four enzymes were susceptible to the inhibitory effect of clavulanic acid. Finally, the strains were all found to produce an acetyl-esterase. The acetyl-esterases catalysized hydrolysis of the acetoxy group of cephalothin and cefotaxime although this did not affect their antibacterial activities. These esterases were not susceptible to the inhibitory effect of clavulanic acid and EDTA.

Chromosomes, Bacterial↗
PubMed1997

Comparison of the effect of cefepime with four cephalosporins against pneumococci with various susceptibilities to penicillin, in vitro and in the mouse peritonitis model.

The purpose of this study was to compare the effect, both in vitro and in vivo, of cefepime with those of four other cephalosporins, namely ceftriaxone, cefotaxime, cefuroxime and cephalothin, against penicillin-resistant pneumococci. One hundred pneumococcal strains, 31 penicillin-susceptible, 30 penicillin-intermediate-resistant and 39 penicillin-resistant pneumococci, were used in MIC studies. Time-kill experiments were carried out for four strains. In the mouse peritonitis model, the dose that gave protection to 50% of mice challenged with a lethal dose of pneumococci (ED50) was determined for three pneumococci and five cephalosporins. The MICs of all five cephalosporins and penicillin correlated significantly with each other. In vitro, the most potent cephalosporins against pneumococci were cefotaxime, ceftriaxone and cefepime, followed by cefuroxime and cephalothin. In time-kill experiments, carried out for four pneumococci, no differences were found in the killing effect of these five cephalosporins in relation to MICs. In the mouse peritonitis model, there was no significant correlation between log(MIC) and log(ED50) for the five cephalosporins against three pneumococci (Spearman's rho = 0.39, P = 0.16). However, if the values for cefepime against the three pneumococci were excluded, there was a significant correlation for the remaining four cephalosporins (Spearman's rho = 0.62, P = 0.04). For all three pneumococci, the ED50s of cefepime were lower than expected from the MICs. It was not possible to explain this beneficial difference in the effect of cefepime in terms of in-vitro bactericidal activities, serum protein binding or pharmacodynamic parameters.

Animals↗
PubMedDate not supplied

Methicillin-resistant Staphylococcus aureus bacteriuria.

Methicillin-resistant Staphylococcus aureus (MRSA) bacteriuria was detected in 11 of 41 patients colonized or infected with MRSA. The patients with bacteriuria generally were older than 40 years of age, five were diabetic, seven had prior indwelling uretheral catheters, two had undergone other urologic manipulations, and only one was clinically symptomatic. Eight patients received variable combinations of antibiotic therapy prior to the diagnosis of MRSA bacteriuria, and seven were still on antibiotic therapy at the time the bacteriuria was detected. Bacteriuria lasted four days to 14 weeks, and was eradicated promptly with cephalosporin therapy in five six patients. Bacteriuria in the untreated patients cleared spontaneously in one month. A single MRSA serotype (83A) predominated. The MRSA isolates were resistant in vitro to most antibiotics except vancomycin. Resistant colonies were observed within cephalothin disc zones of inhibition at 30C (resistance was confirmed by microtube-dilution sensitivity testing). MRSA disc sensitivity testing for cephalothin may be unreliable when performed at 35C.

Adult↗
PubMedDate not supplied

Septicemia due to coagulase-negative staphylococci in a neonatal intensive care unit: clinical and bacteriological features and contaminated parenteral fluids as a source of sepsis.

During the years 1979 to 1981 we experienced an increasing incidence of septicemia due to coagulase-negative staphylococci in the neonatal intensive care unit (NICU). A detailed analysis was performed for the 1981 NICU population. More than 90% of cases occurred in premature infants of low birth weight (less than 2500 g). All septicemic infants were receiving intravenous therapy and total parenteral nutrition (TPN) solutions had been administered to nearly 80% just before or during the septic episode. A case-control study performed for the 1981 NICU population, which included 26 proved cases of coagulase-negative staphylococcal septicemia and 26 matched controls, did not uncover any differences in underlying diseases or modes of treatment between cases and controls. However, the infusion of contaminated TPN fluids was identified as a significant risk factor. Random bacteriological checks of TPN fluids revealed that nearly 20% of these solutions were contaminated, mainly with coagulase-negative staphylococci. The incidence of staphylococcal septicemia in infants who had received contaminated TPN fluids was 10-fold higher than in infants who had received sterile solutions (P less than 0.0005). The majority of coagulase-negative staphylococci isolated from the blood cultures from the NICU were multiply resistant to antibiotics although all isolates were susceptible to cephalothin. Treatment, consisting of removal or replacement of the intravenous devices and the administration of cephalothin and fresh plasma, was universally successful.

Humans↗
PubMed1985

Cephalosporins for surgical prophylaxis: computer projections of intraoperative availability.

Cephalosporin antibiotics are the most frequently used agents for surgical prophylaxis. Within this class are considerable pharmacokinetic variations that could have significant implications. We used a computer simulation of cephalosporin serum levels to describe concentrations achieved and maintained intraoperatively when the agents are given intravenously "on call" to the operating room or with induction of anesthesia. Intraoperative serum concentrations fall below 1 microgram/ml if an operation lasts longer than 2.3, 2.7, 3.8, or 4.0 hours when cephalothin, cephapirin, cefamandole, or cefoxitin, respectively, is given in usual doses upon induction of anesthesia. When the same agents are given intravenously on call to the operating room, intraoperative serum concentrations fall below 1 microgram/ml for operations lasting longer than 1.1, 1.5, 2.6, or 2.8 hours, respectively. If cephalothin, cephapirin, cefamandole, or cefoxitin is used, it should be given at induction of anesthesia to provide maximal intraoperative serum concentrations. The longer half-life of cefazolin, ceforanide, cefonicid, and cefuroxime is a potential advantage because serum concentrations of these agents are well above 1 microgram/ml for as long as eight to 22 hours even after on-call administration.

Anesthesia, General↗
PubMed1994

Phylogeny of Helicobacter isolates from bird and swine feces and description of Helicobacter pametensis sp. nov.

Previously, nine fecal isolates from wild birds and a domestic swine were identified as helicobacters by phenotypic characterization and reaction with a helicobacter genus-specific DNA probe. These isolates fell into three biotypes by analysis of phenotypic traits. To further characterize these isolates, full 16S rRNA sequences were determined for strains representing each biotype, and sequence comparison indicated that the strains represented three novel, phylogenetically defined Helicobacter species. Three 16S rRNA-based DNA probes were designed and used to identify the remaining strains. Probe reactivity divided the strains into the same three groups identified phenotypically. Six of the isolates represented a new species of the genus Helicobacter for which we propose the name Helicobacter pametensis sp. nov. The following phenotypic features distinguished H. pametensis from other Helicobacter and Campylobacter species: positive tests for oxidase, catalase, alkaline phosphatase, nitrate reduction, growth at 42 degrees C, and growth in the presence of 1% glycine; negative tests for urease, gamma glutamyl transpeptidase, indoxyl acetate hydrolysis, and hippurate hydrolysis; and susceptibility to nalidixic acid and cephalothin. H. pametensis cells were motile and possessed one subterminal sheathed flagellum at each end. The two additional Helicobacter species were similar to H. pametensis except that they were urease positive, hydrolyzed indoxyl acetate, and were resistant to cephalothin. Because these two additional species are phenotypically similar and are represented by only two isolates for one species and one isolate for the other, they are not formally named but are referred to as Helicobacter sp. "Bird-B" and Helicobacter sp. "Bird-C."(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2005

Impact of remote mutations on metallo-beta-lactamase substrate specificity: implications for the evolution of antibiotic resistance.

Metallo-beta-lactamases have raised concerns due to their ability to hydrolyze a broad spectrum of beta-lactam antibiotics. The G262S point mutation distinguishing the metallo-beta-lactamase IMP-1 from IMP-6 has no effect on the hydrolysis of the drugs cephalothin and cefotaxime, but significantly improves catalytic efficiency toward cephaloridine, ceftazidime, benzylpenicillin, ampicillin, and imipenem. This change in specificity occurs even though residue 262 is remote from the active site. We investigated the substrate specificities of five other point mutants resulting from single-nucleotide substitutions at positions near residue 262: G262A, G262V, S121G, F218Y, and F218I. The results suggest two types of substrates: type I (nitrocefin, cephalothin, and cefotaxime), which are converted equally well by IMP-6, IMP-1, and G262A, but even more efficiently by the other mutants, and type II (ceftazidime, benzylpenicillin, ampicillin, and imipenem), which are hydrolyzed much less efficiently by all the mutants. G262V, S121G, F218Y, and F218I improve conversion of type I substrates, whereas G262A and IMP-1 improve conversion of type II substrates, indicating two distinct evolutionary adaptations from IMP-6. Substrate structure may explain the catalytic efficiencies observed. Type I substrates have R2 electron donors, which may stabilize the substrate intermediate in the binding pocket. In contrast, the absence of these stabilizing interactions with type II substrates may result in poor conversion. This observation may assist future drug design. As the G262A and F218Y mutants confer effective resistance to Escherichia coli BL21(DE3) cells (high minimal inhibitory concentrations), they are likely to evolve naturally.

Biological Evolution↗
PubMed2005

Dissemination of transferable CTX-M-type extended-spectrum beta-lactamase-producing Escherichia coli in Korea.

AIMS: Among 365 Escherichia coli isolated in 2003, 31 cefotaxime-resistant isolates were obtained from clinical specimens taken from adults hospitalized in Busan, Korea. Six extended-spectrum beta-lactamase (ESBL)-producing isolates were investigated further to determine the mechanism of resistance. METHODS AND RESULTS: These isolates were analysed by antibiotic susceptibility testing, pI determination, plasmid profiles, transconjugation test, PCR-restriction fragment length polymorphism (RFLP), enterobacterial repetitive consensus (ERIC)-PCR and DNA sequencing. All six of these isolates were found to contain the CTX-M-type ESBL genes. Five clinical isolates and their transconjugants produced CTX-M-3. One clinical isolate (K17391) and its transconjugant (trcK17391) produced CTX-M-15. Five clinical isolates also produced another TEM-1. One clinical isolate (K12776) also contained another TEM-52. CTX-M-3 ESBL gene was responsible for the resistance to piperacillin, cephalothin, cefotaxime, cefepime and aztreonam. CTX-M-15 or TEM-52 was especially responsible for the resistance to ceftazidime. CONCLUSIONS: These results appear to represent the in vivo evolution of CTX-M-type beta-lactamase genes (bla(CTX-M-3) --> bla(CTX-M-15)) under the selective pressure of antimicrobial therapy (especially ceftazidime). PCR-RFLP is a reliable method to discriminate CTX-M-15 gene from CTX-M-3 gene. ERIC-PCR analysis revealed that dissemination of CTX-M-3 was not due to a clonal outbreak of a resistant strain but to the intra-species spread of resistance to piperacillin, cephalothin, cefotaxime, cefepime and aztreonam in Korea. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report of the occurrence of CTX-M-1 cluster ESBLs in Korea. A more comprehensive survey of these ESBL types from Korea is urgently needed because of the in vivo evolution of CTX-M-15 from CTX-M-3. The emergence of these CTX-M-type ESBLs suggests that diagnostic laboratories should screen for ESBLs with ceftazidime as well as cefotaxime; they should still perform clavulanate synergy tests on resistant isolates.

Adult↗
PubMed1996

Antibiotic sensitivity of Staphylococcus aureus and Staph. intermedius of canine and feline origin.

Disc agar diffusion testing was performed on 547 isolates (two common pathogens) to determine if the site of isolation influenced the antimicrobial susceptibility results for a given bacterium. The most statistically significant results (P < 0.05) included cephalothin (ear) against Staphylococcus aureus and cephalothin (ear), lincomycin (ear), trimethoprim sulpha (ear), and amoxycilin and clavulanic acid (nose) against Staph. intermedius. Although the impact of these results (empirical treatment) is unknown, it is hypothesized that the site of isolation of Staph. aureus and Staph. intermedius may influence the choice of antimicrobial therapy in the dog and cat.

Animals↗
PubMed1981

Passage of cephalosporins and amoxicillin into the breast milk.

The concentrations of five cephalosporins and amoxicillin in breast milk were studied in 42 voluntarily participating lactating mothers using standard assay methods. Each mother received one single dose of 1 g of either an orally or intravenously administered antibiotic. Amoxicillin, cephalexin, and cefadroxil were given orally, and peak milk concentrations averaged 0.81 +/- 0.33 microgram/ml at 5 hours, 0.50 +/- 0.23 microgram/ml at 4 hours, and 1.64 +/- 0.73 microgram/ml at 6 hours, respectively. Cephalothin, cephapirin and cefotaxime were given as an i.v. bolus injection, and peak milk concentrations at 2 hours averaged 0.47 +/- 0.14 microgram/ml, 0.43 +/- 0.16 microgram/ml and 0.32 +/- 0.09 microgram/ml, respectively. The high concentrations of cefadroxil can be explained by its low rate of elimination and higher fat solubility. Milk/serum ratios for all antibiotics were increasing as serum concentrations were diminishing, especially with cephalothin and cephapirin whose serum concentrations are rapidly declining. The significance of bactericidal concentrations in breast milk remains to be evaluated.

Administration, Oral↗
PubMed1983

Population analysis in strains of Staphylococcus aureus and Staphylococcus epidermidis. II. Cefuroxime and cefotaxime.

Population analyses of susceptibility to cefuroxime and cefotaxime in penicillin-susceptible, penicillin-resistant, and methicillin-resistant strains of Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis (S. epidermidis) were carried out. All strains were clinical isolates. Both antibiotics were shown to be more penicillinase-stable than cephalothin in studies of the penicillin-resistant strains of S. aureus, but less stable than methicillin. The studies of penicillin-resistant strains of S. epidermidis showed no differences in penicillinase-stability between cephalothin and the new cephalosporins. From the methicillin-resistant strains of S. aureus and S. epidermidis it was possible to select highly-resistant mutants against both antibiotics with a frequency of c. 10(-5) although MIC determinations had shown the strains to be susceptible.

Cefotaxime↗