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PubMed1991

In-vitro and in-vivo antimicrobial activities of a novel cephalosporin derivative, CP6162, possessing a dihydroxypyridone moiety at the C-3 side chain.

The antibacterial activity of a novel cephalosporin derivative, CP6162, possessing a dihydroxypyridone moiety at the C-3 side chain, was evaluated in vitro and in vivo, with ceftazidime, aztreonam and cefoperazone as the reference antibiotics. CP6162 showed weak or little activity against Gram-positive bacteria, but potent activity against clinical isolates of the Gram-negative species including strains of Pseudomonas aeruginosa, Ps. cepacia, Acinetobacter sp., Xanthomonas maltophilia, Serratia marcescens, Enterobacter cloacae and Citrobacter freundii, which were resistant to the reference antibiotics. The MICs of CP6162 were only slightly affected by the high producers of beta-lactamases except for cephalosporinase-producing C. freundii. It was, however, affected by the presence of ferric ion. CP6162 showed in-vivo activity paralleling the in-vitro activity, and also showed pharmacokinetic parameters similar to those of ceftazidime in mice and rats.

Animals↗

PubMed1991

Concomitant dissemination of three extended-spectrum beta-lactamases among different Enterobacteriaceae isolated in a French hospital.

From January 1988 to August 1989, 267 non-repetitive strains of Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBla) derived from TEM (CTX-1/TEM-3, CAZ-6) or SHV (CAZ-5) were isolated from 219 colonized or infected patients. ESBlas were characterized by analytical isoelectric focusing. Biotypes, resistance phenotypes and plasmid patterns were determined in order to differentiate the isolates in each species. Among the 116 CTX-1-producing Enterobacteriaceae, 48 strains were differentiated: 27 from 74 Klebsiella pneumoniae isolates, seven from 22 Enterobacter aerogenes isolates, and 14 from a combined total of seven K. oxytoca, five Serratia marcescens, six Escherichia coli, 1 Enterobacter cloacae and 1 Citrobacter freundii. CAZ-5 has been isolated since January 1988 in 16 different strains among 101 K. pneumoniae isolates. CAZ-6 was first identified in K. pneumoniae (January 1988). Among the 48 Enterobacteriaceae producing CAZ-6, 12 strains were differentiated: four from 39 E. aerogenes isolates, three from four K. pneumoniae, and five from a combined total of two S. marcescens, two E. coli and one E. cloacae. During this outbreak, CTX-1 was found to be encoded by 85 kb (Inc 7/M) or greater than or equal to 150 kb (Inc 6/C) plasmids. CAZ-6 was always encoded by an 85 kb (Inc 7/M) plasmid and CAZ-5 by a greater than 150 kb plasmid. These results show that strain epidemics and plasmid dissemination occurred mainly in K. pneumoniae and E. aerogenes for CTX-1, in E. aerogenes for CAZ-6, and in K. pneumoniae for CAZ-5. They also suggest that the bla(tem) gene (CTX-1) has spread between different plasmids present in the same ecosystem.

Cross Infection↗

PubMed1991

beta-Lactamase expression and outer membrane protein changes in cefpirome-resistant and ceftazidime-resistant gram-negative bacteria.

Twenty-five strains of Enterobacteriaceae (five each of Enterobacter cloacae, Citrobacter freundii, Serratia marcescens, Morganella morganii, and Providencia stuartii) and five strains of Pseudomonas aeruginosa were exposed to various concentrations of cefpirome or ceftazidime in agar. Mutants with a greater than four-fold increase in the MIC were examined for changes in beta-lactamase expression and outer membrane protein (OMP) profile. Both agents selected mutants with decreased susceptibility to the selecting antibiotic and other beta-lactams at a frequency of 10(-7)-10(-8). The MICs of all beta-lactams were higher for the resistant mutants of E. cloacae and P. aeruginosa than for the other species. Both agents selected mutants expressing derepressed class I beta-lactamase, but this was more common with ceftazidime. Only a few mutants of P. aeruginosa and E. cloacae had an MIC of cefpirome that was above the recommended breakpoint concentration. Some mutant strains of Enterobacteriaceae lacked an OMP of molecular size similar to OmpF, but the MIC of cefpirome was below the breakpoint concentration for all these strains.

Bacterial Outer Membrane Proteins↗

PubMed1991

In-vitro activity and beta-lactamase stability of SR 44337, a new long acting cephalosporin.

The in-vitro activity of SR 44337 was compared with that of other broad-spectrum parenteral cephalosporins, plus imipenem and co-amoxiclav. SR 44337 showed good activity against the Enterobacteriaceae, with MIC90s of less than 0.5 mg/L against all species tested, with the exception of Citrobacter spp. (MIC90 2 mg/L) and Serratia spp. (MIC90 4 mg/L). Of the agents tested, only ceftriaxone showed consistently greater activity against this family of organisms. SR 44337 had higher activity than ceftriaxone against Acinetobacter spp. and Pseudomonas aeruginosa, and was the most active agent tested against Neisseria meningitidis (MIC90 0.004 mg/L). All strains of N. gonorrhoeae, Haemophilus influenzae and the streptococci (excluding the enterococci) were susceptible to less than or equal to 0.25 mg/L of SR 44337, which was also the most active cephalosporin tested against Staphylococcus aureus. SR 44337 was stable to hydrolysis by the TEM-1, SHV-1 and P99 beta-lactamases, and was more stable than ceftriaxone to the K-1 beta-lactamase.

Amoxicillin↗

PubMed1991

Characterization of FCE 22101-resistant Enterobacteriaceae and the effect of FCE 22101 upon the activity of anti-pseudomonal beta-lactams for Pseudomonas aeruginosa.

Twenty-five strains of Enterobacteriaceae (five each of Enterobacter cloacae, Citrobacter freundii, Serratia marcescens, Morganella morganii, and Providencia stuartii) were exposed to FCE 22101 in agar containing 3, 5, or 10 x the MIC. Any putative mutant with a greater than or equal to four-fold increase in the MIC was examined for beta-lactamase expression and outer membrane protein (OMP) profile. Mutant colonies were selected at a frequency of 10(-7)-10(-11) with decreased susceptibility to FCE 22101 and other beta-lactams, but after one subculture on antibiotic-free agar the mutants from 13 of the 25 strains reverted to wild-type. Only 19 stable mutants were selected from the other 12 wild-type strains, of which 15 lacked an OMP of similar molecular size to OmpF, and/or a low size OMP of approximately 18 kDa. None of the mutants had a significant alteration in expression of Richmond & Sykes class I beta-lactamase. In a separate section of the study in which 50 strains of Pseudomonas aeruginosa were examined, it was found that FCE 22101, at a concentration of 4 mg/L, induced beta-lactamase expression such that, after 24 h exposure, 24 of the 50 strains had a greater than or equal to four-fold rise in the MIC of several anti-pseudomonal beta-lactams.

Anti-Bacterial Agents↗

PubMed1991

Selection and characterization of cefepime-resistant gram-negative bacteria.

The NCTC type strains and four clinical isolates of Enterobacter cloacae, Citrobacter freundii, Serratia marcescens, Morganella morganii, Providencia stuartii and Pseudomonas aeruginosa were exposed, in agar, to cefepime at 3, 5, and 10 x MIC and a breakpoint concentration of 16 mg/L. Mutants were selected at a frequency of approximately 10(-8) that had decreased susceptibility to cefepime and cefpirome, and species-dependent resistance to other beta-lactams. Any putative mutant with a greater than four-fold increase in the MIC was examined to determine its beta-lactamase expression and outer membrane protein (Omp) profile. Mutant strains of P. stuartii and M. morganii lacked an Omp of molecular mass similar to that of OmpF, and were cross-resistant to nalidixic acid. Mutant strains of E. cloacae had derepressed class I beta-lactamase production and lacked an Omp corresponding to OmpF, suggesting that in this species both parameters are necessary for decreased susceptibility. Derepressed beta-lactamases purified from mutant strains of E. cloacae, C. freundii and P. stuartii was able to hydrolyse cefepime, but not as quickly as TEM-10.

Bacterial Outer Membrane Proteins↗

PubMed1992

Survey of the prevalence of beta-lactamases amongst 1000 gram-negative bacilli isolated consecutively at the Royal London Hospital.

beta-Lactamase expression was examined in 1000 consecutive Gram-negative bacilli isolated from urine, wound swab, sputum or blood specimens received at the Microbiology Laboratory of the Royal London Hospital. This survey, performed between January and April, 1991, followed a similar study undertaken in early 1982. The distribution of species was similar in the two surveys, except that the proportion of Pseudomonas aeruginosa isolates had increased from 11% in 1982 to 17.5% in the present study. This increase was balanced by a decreased proportion of enterobacteria. Amongst plasmid-mediated beta-lactamases, TEM-1 (especially), TEM-2, SHV-1 and OXA types continued to predominate in enterobacteria. Their frequency in Escherichia coli was unchanged (46% in 1991 compared with 43% in 1982), but had increased from 5 to 22% amongst Proteus mirabilis isolates. An apparent decrease in their frequency amongst Enterobacter cloacae isolates, from 48% in 1982 to 17% in 1991, probably reflected changes to strain prevalence rather than enzyme prevalence. Plasmid type beta-lactamases were present in fewer than 2% of P. aeruginosa isolates in both surveys. In the present study, chromosomal beta-lactamase derepression (constitutive hyperproduction) was detected in 10/76 isolates of E. cloacae, Enterobacter aerogenes, Citrobacter freundii, Serratia spp. and Morganella morganii, and in 2/170 P. aeruginosa isolates. These proportions were increased, compared with those seen the 1982 survey, though the significance was borderline (P approximately 0.05; chi 2 test). Extended-spectrum plasmid mediated beta-lactamases, unknown in 1982, were found in 11/70 Klebsiellae pneumoniae isolates in the present study. Ten of these organisms, representing at least five distinct strains, produced TEM-10 enzyme, encoded by a plasmid of c. 90 kb; the remaining organism had an unidentified SHV-derived enzyme.

Anti-Bacterial Agents↗

PubMed1993

The activity of cefpirome and ten other antibacterial agents against 2858 clinical isolates collected from 20 centres.

Two thousand eight hundred and fifty-eight aerobic clinical isolates of Enterobacteriaceae, Pseudomonas species, staphylococci, streptococci and Haemophilus species were collected in 19 geographically separated centres in the UK and one in Ireland. The identity of each isolate was confirmed at Southmead Hospital and the MIC of cefpirome, cefotaxime, ceftazidime, cefuroxime, cephradine, amoxycillin, piperacillin, imipenem, gentamicin, ciprofloxacin and trimethoprim was determined by an agar dilution method. Against species of Enterobacteriaceae not associated with producing an inducible cephalosporinase, cefpirome had a similar degree of activity to cefotaxime and was more active than ceftazidime and earlier cephalosporins. Against species with a high prevalence of inducible beta-lactamase production, cefpirome was superior to other cephalosporins; imipenem was also active against these isolates. Cefpirome was active against Pseudomonas aeruginosa, methicillin-sensitive staphylococci, non-enterococcal streptococci and Haemophilus spp. When the isolates were exposed to 0.1 mg/L of imipenem in agar plus the test agent, cefpirome had superior activity compared with the other cephalosporins tested for the Enterobacteriaceae, except Proteus vulgaris and Proteus penneri. 8.7% of Enterobacter spp., 7% of Citrobacter spp. and 6.7% of Morganella morganii had susceptibilities to beta-lactams suggesting constitutive hyperproduction of chromosomal cephalosporinase; cefpirome, unlike the other cephalosporins tested, was active against these isolates, although to a lesser degree than against the wild-type inducible isolates. No isolates were thought to produce an extended-spectrum beta-lactamase.

Anti-Bacterial Agents↗

PubMed1993

Use of the polymerase chain reaction (PCR) for the detection of aacA genes encoding aminoglycoside-6'-N-acetyltransferases in reference strains and gram-negative clinical isolates from two Belgium hospitals.

Genes encoding aminoglycoside 6'-N-acetyltransferases, were identified using the polymerase chain reaction (PCR). Four sets of primers delineating DNA fragments of 209 bp, 250 bp, 260 bp and 347 bp, specific for the four known aacA genes, and probes within these fragments, were constructed based on the nucleotide sequences of the aacA genes. The specificity of the primers was evaluated using reference strains encoding various aminoglycoside-modifying enzymes. The primers reacted with their corresponding aacA genes and did not cross-react with genes coding for other aminoglycoside-modifying enzymes. One hundred and sixty-one aminoglycoside resistant clinical isolates showing AAC(6')I activity were tested using the PCR assays. The gene described by Tran Van Nhieu & Collatz (1987) was the most frequently identified aacA gene. One strain of Citrobacter freundii contained two distinct aacA genes. However, in 46% of the strains, the majority being Serratia spp. and Acinetobacter spp. none of the specific amplified DNA fragments for any of the known aacA genes could be detected.

Acetyltransferases↗

PubMed1993

Multicentre survey of the comparative in-vitro activity of piperacillin/tazobactam against bacteria from hospitalized patients in the British Isles.

Twenty-nine British and Irish hospitals each collected up to 300 bacterial isolates from in-patients. The organisms were identified by an appropriate API system or, for staphylococci, by their Gram and coagulase reactions. Disc susceptibility tests were performed. Isolates that gave zones < or = 25 mm to piperacillin/tazobactam (75 micrograms + 10 micrograms) discs were sent to a central laboratory for re-examination and determination of MIC, together with a sample of the more susceptible organisms. Results were evaluated for 6724 isolates. Over 95% of the isolates of Escherichia coli, klebsiellae, Proteus mirabilis, Pseudomonas aeruginosa, Haemophilus, Moraxella and Bacteriodes, spp. streptococci, pneumococci and Enterococcus faecalis were susceptible to piperacillin/tazobactam (defined as giving a zone > or = 22 mm to a 75 micrograms + 10 micrograms disc), as were 86% of Acinetobacter spp. and 82% of the Citrobacter, Enterobacter, Morganella and Serratia group. Tazobactam particularly extended the activity of piperacillin against E. coli isolates (96% susceptible cf. 61% to piperacillin alone) klebsiellae (95% cf. 70%), P. mirabilis (99% cf. 86%), and Acinetobacter spp. (86% cf. 53%). Occasional (18%) resistance in Enterobacter, Serratia and Citrobacger spp. was probably caused by stable depression of Class I beta-lactamases, which are inhibited poorly by tazobactam. High resistance frequencies (> 25%) were found for Enterococcus faecium and Xanthomonas maltophilia. Tazobactam potentiated piperacillin against beta-lactamase-producing methicillin-susceptible Staphylococcus aureus, but the mode inhibition zone of piperacillin/tazobactam discs was only 26 mm, compared to 38 mm for beta-lactamase-negative isolates. Nevertheless, fewer than 5% of the enzyme producers appeared resistant to 8 + 4 mg/L piperacillin/tazobactam in MIC tests. Similar behaviour was noted for coagulase-negative staphylococci. Amongst the eleven comparator drugs, ceftazidime, gentamicin and ciprofloxacin were as active as piperacillin/tazobactam against most enterobacteria. However, Acinetobacter and Bacteroides spp. and enterococci were resistant to ceftazidime, and Bacteroides spp., enterococci, pneumococci and other streptococci were inherently resistant to ciprofloxacin and gentamicin. Cefuroxime, ampicillin and co-amoxiclav had narrower spectra. Only imipenem showed a consistently wider spectrum and lower frequency of resistance than piperacillin/tazobactam.

Bacteria, Anaerobic↗

PubMed1993

In-vitro activities of cefepime against Enterobacter cloacae, Serratia marcescens, Pseudomonas aeruginosa and other aerobic gram-negative bacilli.

Infections caused by resistant bacterial pathogens such as Citrobacter freundii, Enterobacter cloacae, Serratia marcescens and Pseudomonas aeruginosa have become an increasing problem with respect to therapy in large medical centres in Korea. The MICs of cefepime for aerobic Gram-negative bacilli isolated during 1991, mostly from in-patients in a hospital in Seoul, were determined by the agar dilution method and compared with those of several other antimicrobials. Of the agents tested, cefepime had the lowest MIC90s for C. freundii and E. cloacae (0.12 and 8 mg/L, respectively). The MIC90s of cefepime and amikacin (both 8 mg/L) were the lowest for S. marcescens. The MIC90s of cefepime, ceftazidime and doxycycline (all 32 mg/L) were the lowest for Acinetobacter anitratus. For P. aeruginosa, the MIC90 was relatively high (32 mg/L) but still the lowest of the antimicrobials tested. Of the cefotaxime-resistant E. cloacae isolates studied, only 7% were resistant to cefepime, while 100%, 96% and 89% were resistant to ceftazidime, ceftizoxime and cefuzonam, respectively. Similarly, only 6% of gentamicin-resistant isolates were resistant to cefepime, compared with 91%, 72%, 69% and 63% to ceftazidime, ceftizoxime, cefuzonam and cefotaxime, respectively. In conclusion, isolates from Korean patients are often resistant to several antimicrobial agents. However, based on the results of this study, cefepime may be very useful as treatment for patients with nosocomial infections caused by aerobic Gram-negative bacilli, including those which are resistant to most of the third-generation cephalosporins and gentamicin.

Aminoglycosides↗

PubMed1993

In-vitro activity of cefepime and other antimicrobials: survey of European isolates.

Cefepime, a new cephalosporin which has a broad-spectrum of activity was tested in vitro against 1961 Gram-positive and Gram-negative clinical isolates obtained from European hospitals. Cefepime was highly active against Gram-negative organisms, inhibiting over 94% of strains tested. The overall susceptibility rate for cefepime against all isolates was 81%. Cefepime was more active than any of the third-generation cephalosporins tested against species capable of producing type I beta-lactamases, e.g. Enterobacter cloacae, Citrobacter freundii, and Enterobacter aerogenes. The activity of cefepime against Pseudomonas aeruginosa was similar to that of ceftazidime and substantially greater than those of cefotaxime and ceftriaxone. All cephalosporins except ceftazidime exhibited high activity against methicillin-susceptible Staphylococcus aureus but poor activity was observed against methicillin-resistant strains. Overall susceptibility to cefepime is lower in Europe than it is in North America.

Anti-Bacterial Agents↗

PubMed1994

Comparative in-vitro activity of biapenem against enterobacteria with beta-lactamase-mediated antibiotic resistance.

The effects of enterobacterial beta-lactamases were studied for biapenem (L627), a new carbapenem. Susceptibility tests were performed for isogenic mutant series of Citrobacter freundii, Enterobacter cloacae, Morganella morganii, Serratia marcescens and Proteus vulgaris which varied only in chromosomal beta-lactamase expression. beta-Lactamase-derepressed organisms in these series were as susceptible as beta-lactamase-inducible strains to biapenem; beta-lactamase-basal mutants were up to eight-fold more susceptible. Similar patterns of relative activity against the different expression types were noted for imipenem and biapenem. These data were related to direct induction and hydrolysis assays: biapenem, like imipenem, was a strong inducer of several Class I enzymes and of the P. vulgaris cefuroximase and, like the other carbapenems, was only very slowly hydrolysed by these enzymes. Moreover, like meropenem, biapenem reversibly deactivated these beta-lactamases. Piperacillin and the cephalosporins, tested as comparators, were more labile than carbapenems to the Class I enzymes, were weak inducers below their MICs and lacked deactivator function. In consequence their MICs were higher for derepressed organisms than for those with inducible or basal beta-lactamase expression. Unlike the carbapenems, they selected derepressed mutants from inducible populations. Biapenem, like imipenem and meropenem, retained full activity against most transconjugants of Escherichia coli K-12 that produced plasmid-mediated beta-lactamases, including extended-spectrum TEM mutants. Only production of OXA-10 (previously PSE-2) enzyme gave a slight reduction in susceptibility to the new carbapenem. Biapenem resistance (MIC 16 mg/L) did, however, occur in S. marcescens S6, which produced a chromosomal carbapenemase. This enzyme hydrolysed biapenem. Overall, our findings indicate that biapenem shares the favourable properties of imipenem and meropenem in its interactions with the most important beta-lactamases of enterobacteria.

Drug Resistance, Microbial↗

PubMed1995

Molecular epidemiology of ceftazidime resistant Enterobacteriaceae from patients on a paediatric oncology ward.

Between the autumn of 1989 and January 1990, 21 of the 44 children on the paediatric oncology ward of St. James's University Hospital, Leeds, UK were infected or colonised with Enterobacteriaceae producing extended-spectrum beta-lactamases. This represents 48% of the patients on the ward. Only six patients (14%) had microbiologically proven septicaemia caused by such bacteria during this period. Eighty-one isolates of Enterobacteriaceae producing extended-spectrum beta-lactamases derived from blood culture (7 isolates from 6 patients) or faecal samples (74 isolates) were available for examination. These comprised 28 Escherichia coli, 28 Klebsiella oxytoca, 11 Klebsiella pneumoniae, 10 Citrobacter freundii, 3 Enterobacter spp. and 1 Serratia marcescens. Clinical isolates were resistant to penicillins and to ceftazidime. Strains isolated in this study also showed multiple resistance to a range of antimicrobial agents. Transfer to a nalidixic acid resistant laboratory strain of E. coli UB5201 was attempted, but transfer of the ceftazidime resistance determinant was only successful in 25 isolates (31%). Examination of plasmid DNA revealed sequences in each isolate that hybridised with the TEM beta-lactamase gene probe used on a variety of plasmids ranging in size from 2.5- > 150 kb, sometimes found on several replicons in a single isolate. The TEM gene probe also hybridised with chromosomal DNA in a large number of isolates. Nucleotide sequence analysis demonstrated the presence of three extended-spectrum beta-lactamases: TEM-10B produced by two isolates, TEM-12B produced by 37 isolates and TEM-26B produced by 40 isolates. In two cases, isolates produced two beta-lactamases, and it proved impossible to identify these enzymes unequivocally. The genes encoding TEM-10B and TEM-26B both differ from TEM-12B by single nucleotide substitutions. Analysis of the ribotype patterns derived from the clinical isolates provided evidence for cross-colonisation between patients, and this was confirmed by analysis of the plasmid profiles. Four years after discontinuing ceftazidime and other extended-spectrum cephalosporins on this ward, patients were still colonised with bacteria that produced extended-spectrum beta-lactamases.

Base Sequence↗

PubMed1995

Activity of cefepime against nosocomial blood culture isolates.

Cefepime is a new aminothiazolylacetamido cephalosporin with a wider spectrum and greater potency than many currently available cephalosporins. Since the blood culture isolates from patients of the study centre in Saudi Arabia are significantly more resistant to antimicrobial agents in clinical practice, we evaluated the in-vitro activity of cefepime and six other beta-lactam antibodies against 390 and 273 isolates of Gram-negative and Gram-positive bacteria, respectively. Cefepime had a broad spectrum of activity against the Enterobacteriaceae (MIC50 < 0.12 mg/L), Pseudomonas aeruginosa, Acinetobacter spp. and methicillin susceptible Staphylococcus aureus (MIC50 2.0 mg/L). The activity of cefepime was generally two-to four-fold greater than that of ceftazidime. Resistance to cefepime was most often encountered with Serratia spp. (45%), Citrobacter spp. (25%), Enterobacter cloacea (22%), and Stenotrophomonos mattophilia (45%). It had little or no activity against methicillin-resistant S. aureus and enterococci. Cefepime was highly active, with a spectrum better than ceftazidime against Gram-negative, and better than cephalothin against Gram-positive blood culture isolates.

Bacteremia↗

PubMed1995

Escherichia hermannii: susceptibility pattern to beta-lactams and production of beta-lactamase.

The susceptibility pattern of Escherichia hermannii, although closely related to Escherichia coli according to its biochemical patterns, was clearly distinguishable by its susceptibility to beta-lactams by both diffusion and dilution methods from E. coli penicillinase producing or non-producing strains, Citrobacter diversus, Klebsiella pneumoniae, and Klebsiella oxytoca. Beta-lactamase clavulanate-sensitive activity was localized with various isoelectric points from 7.0 to 8.5. No cross hybridization with DNA intragenic probes (blaTEM, blaSHV, blaCARB and blaOXY) was observed by dot blot procedure.

Anti-Bacterial Agents↗

PubMed1997

Antibacterial activity of T-5575, a novel 2-carboxypenam, and its stability to beta-lactamase.

The in-vitro activity of T-5575, 2-carboxypenam, a new parenteral antibiotic and its stability to beta-lactamases were compared with those of ceftazidime and imipenem. The activity of T-5575 was equal or superior to that of ceftazidime or imipenem against Gram-negative bacteria that produced penicillinase with the exception of the enzyme OXA-1. Against strains that produced Cephalosporinase and zinc-dependent beta-lactamase, the activity of T-5575 was superior to that of ceftazidime or imipenem. T-5575 was a poor substrate and had low affinity for beta-lactamases produced by Citrobacter freundii, Enterobacter cloacae and Pseudomonas aeruginosa. The activity of T-5575 was less influenced by the derepressed production of chromosomal enzymes than that of ceftazidime. Overall, T-5575 had excellent activity against Gram-negative pathogens that produced various types of beta-lactamases.

Anti-Bacterial Agents↗

PubMed1997

In-vitro pharmacodynamic studies of piperacillin/tazobactam with gentamicin and ciprofloxacin.

Six isolates each of Enterococcus faecium, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes, Stenotrophomonas maltophilia, Pseudomonas aeruginosa, Citrobacter spp., Serratia spp., Acinetobacter spp. and Enterobacter spp. (total 60 strains) were studied against the combination of piperacillin/tazobactam plus gentamicin or ciprofloxacin at physiological concentrations by the microtitre chequerboard method incorporating simultaneous time-kill curves. Tazobactam was fixed at 4 mg/L. Gentamicin plus piperacillin/tazobactam was a synergic combination against 28 strains at 2 h, 51 at 5 h and 54 at 24 h as assessed by time-kill curves and synergic or additive (FBC index < or = 1) against all 60 strains at 24 h by chequerboards. The corresponding figures for ciprofloxacin plus piperacillin/tazobactam were seven, 26, 52 and 58 respectively. Antagonism (FBC index > or = 4) was demonstrated for one strain to each combination at 24 h. There were no significant differences between FIC indices and FBC indices for each antibiotic combination. Gentamicin plus piperacillin/tazobactam gave > or = 3 log kill for 47 strains by 2 h, 56 by 5 h and 59 by 24 h. Ciprofloxacin plus piperacillin/tazobactam gave > or = 3 log kill for 22 strains by 2 h, 36 by 5 h and 56 by 24 h. In conclusion both antibiotic combinations at physiological concentrations were synergic or additive at 24 h for the majority of strains tested although notably gentamicin plus piperacillin/tazobactam gave faster kill. Antagonism was rarely seen. Both combinations are likely to prove beneficial for treatment of serious infections.

Anti-Bacterial Agents↗