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PubMed2003

Comparative in vitro activity of piperacillin, piperacillin-sulbactam and piperacillin-tazobactam against nosocomial pathogens isolated from intensive care patients.

We investigated the antimicrobial activity of piperacillin-tazobactam versus piperacillin-sulbactam against common nosocomial pathogens (n = 565) isolated from intensive care patients. For Gram-positive bacteria, antimicrobial susceptibilities to the two piperacillin-beta-lactamase inhibitor combinations were almost identical. For Gram-negative bacteria, piperacillin-tazobactam exhibited greater activity against Escherichia coli and Proteus vulgaris than piperacillin-sulbactam. Both combinations, however, were equally effective against the other Enterobacteriaceae and Pseudomonas aeruginosa isolates. Piperacillin-sulbactam exhibited better antimicrobial activity against Acinetobacter baumannii. Our findings might prove important for the appropriate choice of antibiotic therapy with beta-lactam-beta-lactamase inhibitor combinations.

Anti-Bacterial Agents↗
PubMed1995

In vitro pharmacodynamics of piperacillin, piperacillin-tazobactam, and ciprofloxacin alone and in combination against Staphylococcus aureus, Klebsiella pneumoniae, Enterobacter cloacae, and Pseudomonas aeruginosa.

The time-kill curve methodology was used to determine the pharmacodynamics of piperacillin, ciprofloxacin, piperacillin-tazobactam and the combinations piperacillin-ciprofloxacin and ciprofloxacin-piperacillin-tazobactam. Kill curve studies were performed for piperacillin, ciprofloxacin, and piperacillin-tazobactam at concentrations of 0.25 to 50 times the MICs for 13 strains of bacteria: four Pseudomonas aeruginosa, three Enterobacter cloacae, three Klebsiella pneumoniae, and three Staphylococcus aureus isolates (tazobactam concentrations of 0.5, 4, and 12 micrograms/ml). By using a sigmoid Emax model and nonlinear least squares regression, the 50% lethal concentrations and the maximum lethal rates of each agent were determined for each bacterial strain. For piperacillin-ciprofloxacin and ciprofloxacin-piperacillin-tazobactam, kill curve studies were performed with concentrations obtained by the fractional maximal effect method (R. C. Li, J. J. Schentag, and D. E. Nix, Antimicrob. Agents Chemother. 37:523-531, 1993) and from individual 50% lethal concentrations and maximum lethal rates. Ciprofloxacin-piperacillin-tazobactam was evaluated only against the four P. aeruginosa strains. Interactions between piperacillin and ciprofloxacin were generally additive. At physiologically relevant concentrations of piperacillin and ciprofloxacin, ciprofloxacin had the highest rates of killing against K. pneumoniae. Piperacillin-tazobactam (12 micrograms/ml) had the highest rate of killing against E. cloacae. Piperacillin-ciprofloxacin with relatively higher ciprofloxacin concentrations had the greatest killing rates against S. aureus. This combination had significantly higher killing rates than piperacillin (P < 0.002). For all the bacterial strains tested, killing rates by ciprofloxacin were significantly higher than those by piperacillin-tazobactam (4 and 12 micrograms/ml had significantly higher killing rates than piperacillin alone (P < 0.02 and P < 0.004, respectively). The effect of the combination of piperacillin-ciprofloxacin, in which piperacillin concentrations were relatively higher, was not statistically different from that of piperacillin alone (p > or = 0.71). The combination of ciprofloxacin-piperacillin-tazobactam achieved greater killing than other combinations or monotherapies against P. aeruginosa. The reduction in the initial inoculum was 1 to 4 logs greater with ciprofloxacin-piperacillin-tazobactam at 4 and 12 micrograms/ml than with any other agent or combination of agents. On the basis of the additive effects prevalently demonstrated in the in vitro study, the combinations of piperacillin-ciprofloxacin and piperacillin-tazobactam are rational therapeutic options. Greater killing of P. aeruginosa was demonstrated with ciprofloxacin-piperacillin--tazobactam. Since treatment failure of P. aeruginosa pneumonia is a significant problem, clinical studies are warranted.

Anti-Infective Agents↗
PubMed2002

Ciprofloxacin plus piperacillin compared with tobramycin plus piperacillin as empirical therapy in febrile neutropenic patients. A randomized, double-blind trial.

BACKGROUND: Therapy with an aminoglycoside and a beta-lactam remains common empirical therapy for febrile neutropenic patients. Concerns of aminoglycoside-induced ototoxicity and nephrotoxicity have led to studies of alternate regimens. OBJECTIVE: To determine whether ciprofloxacin-piperacillin is equivalent to tobramycin-piperacillin as empirical therapy for neutropenic fever. DESIGN: Randomized, double-blind multicenter trial. SETTING: Seven U.S. university-affiliated hospitals and one private research center. PATIENTS: Febrile (temperature >/= 38 degrees C), neutropenic (neutrophil level < 1 x 10(9) cells/L) hospitalized patients who had leukemia, lymphoma, or solid tumors, or were undergoing bone marrow transplantation. INTERVENTIONS: Patients received piperacillin, 50 mg/kg of body weight intravenously every 4 hours, and ciprofloxacin, 400 mg intravenously every 8 hours, or tobramycin, 2 mg/kg intravenously every 8 hours. MEASUREMENTS: Success was defined as resolution of infection and previously positive cultures without the need to give additional antimicrobial agents. RESULTS: 543 febrile episodes were evaluated, of which 471 were clinically evaluable (234 in the ciprofloxacin-piperacillin group and 237 in the tobramycin-piperacillin group). Success rates in the ciprofloxacin-piperacillin group (63 of 234 febrile episodes) and tobramycin-piperacillin group (52 of 237 episodes) were similar (27% vs. 22%, respectively; difference, 5.0 percentage points [95% CI, -2.3 to 12.8 percentage points]), as was survival (96.2% of patients receiving ciprofloxacin-piperacillin versus 94.1% of patients receiving tobramycin-piperacillin; difference, 2.1 percentage points [CI, -2.2 to 6.4 percentage points]). Additions to the initial antimicrobial regimen were the most common reason for treatment failure in both groups (accounting for 67% of failures in the ciprofloxacin-piperacillin group and 72% in the tobramycin-piperacillin group; difference, 5.0 percentage points [CI, -13.8 to 3.7 percentage points]). Fevers resolved faster in patients receiving ciprofloxacin-piperacillin than in patients receiving tobramycin-piperacillin (mean, 5 vs. 6 days) (P = 0.005). No significant differences in adverse events or toxicity were noted (P = 0.083). CONCLUSION: Ciprofloxacin-piperacillin is as safe and effective as tobramycin-piperacillin for empirical therapy of neutropenic fever.

Adult↗
PubMed1994

Pharmacodynamics of piperacillin alone and in combination with tazobactam against piperacillin-resistant and -susceptible organisms in an in vitro model of infection.

The pharmacodynamics of dosage regimens of piperacillin alone or in combination with tazobactam against piperacillin-resistant or -susceptible bacteria were studied in an in vitro model of infection. Experiments were conducted by using a fixed daily exposure of 12 g of piperacillin, given as 3 g alone or in combination with tazobactam at 0.375 g every 6 h, or the same total dose of the combination given as 4 g of piperacillin plus 0.5 g of tazobactam every 8 h. The addition of tazobactam to piperacillin, irrespective of the dosing interval, did not alter the killing of piperacillin-susceptible organisms (Escherichia coli J53 and Pseudomonas aeruginosa ATCC 27853). In contrast, experiments with an isogenic TEM-3-containing transconjugant of E. coli J53 (E. coli J53.2-TEM-3) that was resistant to piperacillin (MIC, 128 micrograms/ml) showed that the addition of tazobactam resulted in bacterial killing similar to that observed with the wild-type strain. Although tazobactam concentrations fell to less than 4 mg/liter (the concentration associated with a reduction in the piperacillin MIC from 128 to 2 mg/liter) 2 to 3 h after a dose, a similar degree of bacterial killing was observed when the same total 24-h dose of piperacillin-tazobactam was fractionated into dosing intervals of every 6 or 8 h. Investigations with Staphylococcus aureus 7176 (piperacillin MIC, 128 micrograms/ml) showed that the addition of tazobactam, again irrespective of dosing interval, also resulted in net bacterial killing which was not seen with piperacillin alone. These data support the use of extended dosing intervals (every 8 h) of piperacillin-tazobactam in the treatment of infections caused by piperacillin-resistant bacteria.

Bacteria↗
PubMed2003

Comparison of four antimicrobial susceptibility testing methods to determine the in vitro activities of piperacillin and piperacillin-tazobactam against clinical isolates of Enterobacteriaceae and Pseudomonas aeruginosa.

Susceptibility to piperacillin was similar to that to piperacillin-tazobactam (<1% difference) for 6,938 isolates of Enterobacter aerogenes and 13,954 isolates of Enterobacter cloacae tested using a Vitek system; for the same species, in contrast, susceptibility rates to piperacillin-tazobactam were 5.9 to 13.9% higher than to piperacillin using disk diffusion, MicroScan, and Vitek 2 testing. Unprecedented phenotypes (piperacillin susceptible and piperacillin-tazobactam intermediate; piperacillin intermediate and piperacillin-tazobactam resistant; piperacillin susceptible and piperacillin-tazobactam resistant) accounted for 6.1% of the results for E. aerogenes isolates and 6.0% of the results for E. cloacae isolates tested with the Vitek system.

Drug Resistance, Bacterial↗
PubMed1988

Comparison of piperacillin alone versus piperacillin plus tobramycin for treatment of respiratory infections in children with cystic fibrosis.

Seventeen patients with cystic fibrosis (CF) and pulmonary exacerbations were randomly assigned to two treatment groups: piperacillin 600 mg/kg/day (P), and piperacillin 600 mg/kg/day plus tobramycin (PT), in order to determine the safety and pharmacokinetics of high-dose piperacillin and whether piperacillin alone was effective for the treatment of Pseudomonas infections. The mean half-life of piperacillin was 0.54 hours, with a peak concentration of 232 micrograms/ml. No differences between P and PT groups were noted in clinical assessment, as judged by Shwachman scores, pulmonary function testing, or weight gain. However, during the course of treatment, quantitative sputum cultures decreased by greater than 10(2) colony-forming units in only 5 out of 19 Pseudomonas isolates from the P group, compared with 12 of 19 isolates from the PT group (P less than 0.03, Chi-square). Although emergence of resistance was not seen, one isolate had an increase in minimum inhibitory concentration from 8 to 128 micrograms/ml. There were no serious adverse reactions to piperacillin; only one patient developed fever possibly related to piperacillin. Therapy with high-dose piperacillin was safe in children with CF. Treatment with piperacillin alone was less effective than combination therapy with gentamicin for reduction in titer of Pseudomonas in sputum. However, the role of antimicrobial agents in the treatment of CF remains undefined. A double-blind placebo-controlled trial is indicated.

Child↗
PubMed1997

Importance of beta-lactamase inhibitor pharmacokinetics in the pharmacodynamics of inhibitor-drug combinations: studies with piperacillin-tazobactam and piperacillin-sulbactam.

An in vitro pharmacokinetic model was used to study the pharmacodynamics of piperacillin-tazobactam and piperacillin-sulbactam against gram-negative bacilli producing plasmid-encoded beta-lactamases. Logarithmic-phase cultures were exposed to peak antibiotic concentrations observed in human serum after the administration of intravenous doses of 3 g of piperacillin and 0.375 g of tazobactam or 0.5 g of sulbactam. Piperacillin and inhibitor were either dosed simultaneously or piperacillin was dosed sequentially 0.5 h after dosing with the inhibitor. In studies with all four test strains, the pharmacodynamics observed after simultaneous dosing were similar to those observed with the sequential regimen. Since the ratio between piperacillin and tazobactam was in constant fluctuation after sequential dosing, these data suggest that the pharmacodynamics of the piperacillin-inhibitor combinations were not dependent upon maintenance of a critical ratio between the components. Furthermore, when regrowth was observed, the time at which bacterial counts began to increase was similar between the simultaneous and sequential dosing regimens. Since the pharmacokinetics of the inhibitors were the same for all regimens, these data suggest that the length of time that the antibacterial activity was maintained over the dosing interval with these combinations was dictated by the pharmacokinetics of the beta-lactamase inhibitor in the combination. The antibacterial activity of the combination appeared to be lost when the amount of inhibitor available fell below some critical concentration. This critical concentration varied depending upon the type and amount of enzyme produced, as well as the specific inhibitor used. These results indicate that the antibacterial activity of drug-inhibitor combinations, when dosed at their currently recommended ratios, is more dependent on the pharmacokinetics of the inhibitor than on those of the beta-lactam drug.

Bacteria↗
PubMed1982

Comparative synergistic activity of netilmicin-piperacillin versus gentamicin-piperacillin.

The synergistic action of the combination netilmicin-piperacillin in comparison to gentamicin-piperacillin was studied in 206 clinical isolates of staphylococci, enterococci, Enterobacteriaceae and Pseudomonas aeruginosa by means of the checkerboard technique. Overall, netilmicin-piperacillin acted synergistically against 31% and gentamicin-piperacillin against 14% of the 206 strains. In particular, synergism was more frequently observed with netilmicin-piperacillin against Escherichia coli, Citrobacter spp., indole-positive Proteus spp. and Pseudomonas aeruginosa. Synergy was uncommon with either combination against enterococci, Staphylococcus epidermidis and Serratia spp. Only partial synergy or indifference was seen with both combinations against Klebsiella spp. The interaction of netilmicin would appear to be superior to that of gentamicin in combination with piperacillin.

Bacteria↗
PubMed2004

Serum bactericidal activity of piperacillin/tazobactam against Staphylococcus aureus, piperacillin-susceptible and piperacillin-resistant Escherichia coli and Pseudomonas aeruginosa.

BACKGROUND: The serum bactericidal test measures the highest level of an antibiotic-containing serum dilution at which 99.9% of bacteria are killed. In this study the serum bactericidal activity of piperacillin/tazobactam was determined for bacteria often involved in severe infections. In earlier studies titres >/=1:8 in the serum bactericidal tests correlated well with clinical success in the treatment of endocarditis and osteomyelitis as well as bacterial eradication. METHODS: Blood samples of 6 healthy volunteers were taken before and 1 and 4 h after piperacillin/tazobactam (4.5 g) administration. Serum concentrations and serum bactericidal activity were determined for 10 strains each of Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli, both piperacillin-resistant and piperacillin-susceptible according to NCCLS guidelines. RESULTS: 100% of S. aureus and piperacillin-susceptible E. coli, 90% of piperacillin-resistant E. coli and 80% of P. aeruginosa were killed 1 h after drug administration. 4 h after drug administration serum bactericidal activity decreased to 60% for S. aureus, 90% for piperacillin-susceptible E. coli, 80% for piperacillin-resistant E. coli and 30% for P. aeruginosa. CONCLUSIONS: Excellent serum bactericidal activity of piperacillin/tazobactam was recorded 1 h after drug administration for S. aureus, E. coli and P. aeruginosa. After 4 h limited killing rates for P. aeruginosa could be detected, which supports the idea of a combination therapy.

Adult↗
PubMed1997

Tazobactam-piperacillin compared with sulbactam-ampicillin, clavulanic acid-ticarcillin, sulbactam-cefoperazone, and piperacillin for activity against beta-lactamase-producing bacteria isolated from patients with complicated urinary tract infections.

The antibacterial activity of tazobactam-piperacillin was compared with that of sulbactam-ampicillin, clavulanic acid-ticarcillin, sulbactam-cefoperazone and piperacillin against beta-lactamase-producing bacteria isolated from patients with complicated urinary tract infections. Tazobactam-piperacillin showed a broad antibacterial spectrum against gram-negative and gram-positive bacteria. The minimum inhibitory concentrations (MIC90) of tazobactam-piperacillin were 6.25 micrograms/ml against Escherichia coli, 1.56 micrograms/ml against Proteus mirabilis, 3.13 micrograms/ml against Proteus vulgaris, 6.25 micrograms/ml against methicillin-susceptible Staphylococcus aureus, and 6.25 micrograms/ml coagulase-negative methicillin-susceptible staphylococci. Against all beta-lactamase-producing bacteria tested the antibacterial activity of tazobactam-piperacillin was at least 4- to 64-fold stronger than that of piperacillin, clavulanic acid-ticarcillin, and sulbactam-ampicillin, and similar to or greater than that of sulbactam-cefoperazone except for E. coli.

Ampicillin↗
PubMed1991

Beta-lactam antibiotic therapy in febrile granulocytopenic patients. A randomized trial comparing cefoperazone plus piperacillin, ceftazidime plus piperacillin, and imipenem alone.

OBJECTIVE: To compare the efficacy, toxicity, and cost-effectiveness of double beta-lactam therapy with monotherapy. DESIGN: A randomized, controlled trial. PATIENTS: Febrile, granulocytopenic patients (429). INTERVENTIONS: Patients were randomly assigned to receive iv cefoperazone (3 g every 12 hours) plus piperacillin (75 mg/kg body weight every 6 hours), ceftazidime (2 g every 8 hours) plus piperacillin (75 mg/kg every 6 hours), or imipenem alone (1.0 g or 0.5 g every 6 hours). Patients also received prophylactic vitamin K. MEASUREMENTS: Clinical improvement, eradication of the infecting organism, and toxicity in 403 evaluable patients with one or more infections. MAIN RESULTS: Cefoperazone and ceftazidime, when given in combination with piperacillin, were equally effective (response rates of 75% (104 of 138 patients) and 74% (101 of 137 patients), respectively). Monotherapy with imipenem had a response rate of 82% (111 of 136 patients) and was as effective as double beta-lactam therapy. Overall antibiotic-related toxicity was minimal, although seizures were associated with high doses of imipenem. Seizures occurred in 3 of 29 patients (10.3%) who were receiving 4 g/d of imipenem, in 3 of 136 patients (2.2%) who were receiving cefoperazone plus piperacillin, in 0 of the 132 patients who were receiving ceftazidime plus piperacillin, and in 1 of 106 patients (0.9%) who were receiving 2 g/d of imipenem (P less than 0.005). The 2-g daily dose of imipenem was as effective as the 4-g daily dose. Diarrhea was more frequent in patients receiving cefoperazone, whereas nausea occurred more often with imipenem. No antibiotic-related hemorrhage or nephrotoxicity was observed. Superinfections caused by beta-lactam-resistant, gram-negative bacilli were uncommon but occurred more frequently with double beta-lactam therapy than with imipenem monotherapy (11 of 268 patients compared with 1 of 135 patients; P = 0.06). Xanthomonas maltophilia superinfections occurred only in patients receiving imipenem (3 of 135 patients compared with 0 of 268 patients; P = 0.03). Imipenem monotherapy was the least expensive therapy. CONCLUSIONS: Cefoperazone and ceftazidime were equally effective when used in combination antibiotic therapy with piperacillin. Twice-daily cefoperazone is less expensive than ceftazidime given three times daily. Monotherapy with imipenem, at a daily dose of 2 g, is as efficacious as double beta-lactam therapy and costs less than combination therapy.

Adolescent↗
PubMed1991

In vitro activity and stability against novel beta-lactamases of investigational beta-lactams (cefepime, cefpirome, flomoxef, SCE2787 and piperacillin plus tazobactam) in comparison with established compounds (cefotaxime, latamoxef and piperacillin).

The therapeutic perspectives of flomoxef, SCE 2787, cefpirome, cefepime, latamoxef, cefotaxime and of piperacillin plus tazobactam were comparatively evaluated by their in vitro activity against 1119 clinical isolates of 83 bacterial species. Escherichia coli, Klebsiella spp. Enterobacter sakazakii, Proteus spp. and Shigella spp. were about equally susceptible to the cephalosporins (MIC90: 0.06 to 0.5 mg/l), while the MIC90 for piperacillin plus tazobactam was between 2 and 16 mg/l. Enterobacter cloacae, Enterobacter aerogenes and Serratia spp. were most susceptible to SCE 2787, cefpirome and cefepime (MIC90: 0.06 to 2 mg/l) followed by latamoxef, cefotaxime, flomoxef and piperacillin plus tazobactam. For Citrobacter spp., Providencia spp. and Yersinia enterocolitica MIC90 were between 0.06 and 0.5 mg/l. Flomoxef was between 2 to 4 log2 less active against these species but more active than piperacillin plus tazobactam (MIC90: 2 and 8 mg/l). Morganella morganii and Hafnia alvei were most susceptible to cefepime, cefpirome and latamoxef (MIC90: 0.13 to 0.5 mg/l) while cefotaxime (MIC90: 8 mg/l) and piperacillin plus tazobactam (MIC90: 8 and greater than 64 mg/l) were the least active compounds. SCE 2787, cefepime and cefpirome were the most potent beta-lactams against the majority of the 13 species of non-fermentative bacilli (NFB) investigated (MIC90: 0.5 to 16 mg/l). The oxacephems were the least active compounds against NFB. Cefepime was the most active of the compounds included against Pseudomonas aeruginosa (MIC90: 16 mg/l). Haemophilus spp., Neisseria gonorrhoeae and Bordetella pertussis were most susceptible to cefotaxime (MIC90: 0.03 to 0.06 mg/l). Latamoxef had the lowest activity of all compounds against gram-positive cocci. Flomoxef was the most active compound against penicillinase producing Staphylococcus aureus and about equally active as the other betalactams against methicillin susceptible staphylococci of other staphylococcal species.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗
PubMed1998

[A national multicenter study of the in-vitro activity of piperacillin-tazobactam. The Spanish Piperacillin-Tazobactam Group].

The action of piperacillin-tazobactam on 4,137 of the 4,364 strains collected in a Spanish multicenter study involving 46 participating hospitals was studied. The samples were from the following: 41% urine, 18% exuded from wound abscesses, 13% respiratory, 9% blood, 3% peritoneal liquid, and the remainder from other various sources. The gram-negative bacteria included 2,778 strains from 13 genera: Escherichia (1,289), Pseudomonas (451), Proteus (230), Klebsiella (203), Haemophilus (172), Enterobacter (145), Acinetobacter (88), Salmonella (60), Bacteroides (57), Morganella (53), Serratia (46), Citrobacter (46), Stenotrophonomas (23) and Moraxella (21). The gram-positive bacteria were S. aureus (316), E. faecalis (239), S. epidermis (130), S. pneumoniae (115) and Clostridium spp. (12). The global susceptibility of the gram-negatives to piperacillin-tazobactam was 94%: E. coli 98%, P. aeruginosa 92%, and P. mirabilis, Morganella, K. pneumoniae, Serratia and Salmonella spp. all greater than 94%. The susceptibility of other bacteria was as follows: 91% Citrobacter, 77% E. cloacae, 42% A. baumannii, 61% S. maltophilia, 97% E. faecalis, 93% S. epidermidis, 100% M. catarrhalis, 99% H. influenzae and 100% anaerobic bacteria. The action on S. pneumoniae and S. aureus varied according to the susceptibility or lack there of to penicillin or methicillin. In comparison to other antibiotics (piperacillin, cefoxitin, cefotaxime, ceftazidime, cefepime, imipenem and ciprofloxacin), piperacillin-tazobactam was far better than piperacillin alone and better or similar to the others.

Bacteria↗
PubMed1984

Isolation and identification of piperacillin amide as an impurity in piperacillin.

Piperacillin amide (IV) was successfully identified as the predominant impurity in commercial lots of piperacillin monohydrate (III). The impurity was isolated via a preparative liquid chromatographic scheme utilizing Florisil as the adsorbent and a mobile phase of water-acetonitrile (4:96, v/v). The isolated component had nearly the same reverse-phase HPLC properties as piperacillin and was chemically and thermally unstable. This labile impurity was spectroscopically identified by field desorption (FD), fast atom bombardment (FAB) with collision activation decomposition (CAD), and desorption chemical ionization (DCI) mass spectrometries , and NMR and IR spectrometries . Identity was confirmed on comparison of the chromatographic and spectrometric data of the impurity with an independently synthesized sample of piperacillin amide.

Chemical Phenomena↗
PubMed1990

Comparative in-vitro activity of piperacillin and piperacillin plus tazobactam towards beta-lactamase producing clinical isolates.

The authors evaluated the in-vitro antibacterial activity of piperacillin alone and of piperacillin combined with tazobactam, a new beta-lactamase inhibitor, on 398 clinical isolates, both Gram-positive and Gram-negative. The piperacillin/tazobactam combination was evaluated in the fixed ratio 8:1. The vast majority of the microorganisms tested had reduced susceptibility to piperacillin (minimum inhibitory concentration (MIC) range 0.12- greater than 256 mg/l) due to beta-lactamase production. The following results were obtained: against Haemophilus influenzae, tazobactam was effective in reducing the MICs of piperacillin by 512 fold. The activity of piperacillin/tazobactam was lower against Pseudomonas sp., while some activity was demonstrated against some strains of Klebsiella. Good activity was seen not only against methicillin-susceptible (MS) staphylococci but also against some methicillin-resistant (MR) strains. In the latter, the combination of piperacillin/tazobactam was active only if the strains showed beta-lactamase production. These findings are interesting above all in regard to the synergistic effect demonstrated against MR beta-lactamase producing staphylococci and the Klebsiella-Enterobacter-Serratia (KES) group.

Drug Synergism↗
PubMed1993

Susceptibilities of 428 gram-positive and -negative anaerobic bacteria to Bay y3118 compared with their susceptibilities to ciprofloxacin, clindamycin, metronidazole, piperacillin, piperacillin-tazobactam, and cefoxitin.

The susceptibilities of 428 gram-negative and gram-positive anaerobes (including selected cefoxitin-resistant strains) to Bay y3118 (a new fluoroquinolone), ciprofloxacin, clindamycin, metronidazole, cefoxitin, piperacillin, and piperacillin-tazobactam were tested. Organisms comprised 115 Bacteroides fragilis group, 116 non-B. fragilis Bacteroides, Prevotella, and Porphyromonas spp., 40 fusobacteria, 58 peptostreptococci, 48 gram-positive non-spore-forming rods, and 51 clostridia. beta-Lactamase production was demonstrated in 87% of the gram-negative rods but in none of the gram-positive organisms. Overall, Bay y3118 was the most active agent, with all organisms inhibited at an MIC of < or = 2.0 micrograms/ml (MICs for 50% [MIC50] and 90% [MIC90] of strains tested, 0.125 and 0.5 microgram/ml, respectively). By contrast, ciprofloxacin was much less active, with only 42% of strains susceptible at a breakpoint of 2.0 micrograms/ml (MIC50, 4.0 micrograms/ml; MIC90, 16.0 micrograms/ml). Metronidazole was active against all gram-negative rods, but 7% of peptostreptococci, 83% of gram-positive non-spore-forming rods, and 4% of non-Clostridium perfringens, non-Clostridium difficile clostridia were resistant to this agent (MICs, > 16.0 micrograms/ml). Clindamycin was active against 94% of Bacteroides, Prevotella, and Porphyromonas spp., 91% of peptostreptococci, and 100% of gram-positive non-spore-forming rods, but was active against only 70% of fusobacteria and 53% of clostridia. Cefoxitin was active against > or = 90% of all groups except the B. fragilis group and non-Propionibacterium acnes gram-positive non-spore-forming rods (both 85%) and C. difficile (20%). Significant enhancement of piperacillin by tazobactam was seen in all beta-lactamase-positive strains (99% susceptible; MIC90, 8.0 micrograms/ml), and all beta-lactamase-negative strains were susceptible to piperacillin (MIC90, 8.0 micrograms/ml). Clinical studies are required to delineate the role of Bay y3118 in the treatment of anaerobic infections.

Anti-Infective Agents↗
PubMed1994

Inoculum effects on Etests and agar dilution minimum inhibitory concentrations. Piperacillin and piperacillin-tazobactam against Staphylococcus aureus.

Inoculum effects notoriously occur with beta-lactamase-positive staphylococci in dilution susceptibility tests with substrate beta-lactams. Etests, like dilution experiments, demonstrated such effects with piperacillin and, to a lesser extent, with its tazobactam combinations. When Etests were used with the recommended inoculum of approximately 10(6) colony-forming units (CFU/plate, the minimum inhibitory concentrations (MICs) of piperacillin-tazobactam found for beta-lactamase-positive Staphylococcus aureus isolates resembled those found by agar dilution for inocula of 10(4) CFU/spot but were two- to eightfold below those found by agar dilution for inocula of 10(6) CFU/spot; MICs of piperacillin itself by Etest were about fourfold below even those found by agar dilution with inocula of 10(4) CFU/spot. Inoculum effects for beta-lactamase-negative S. aureus were minimal by both methods.

Bacteriological Techniques↗
PubMed1994

Activity of CP 99,219 compared with those of ciprofloxacin, grepafloxacin, metronidazole, cefoxitin, piperacillin, and piperacillin-tazobactam against 489 anaerobes.

Agar dilution was used to compare the in vitro activity of CP 99,219 with those of ciprofloxacin, grepafloxacin, metronidazole, cefoxitin, piperacillin, and piperacillin-tazobactam against 489 anaerobes. CP 99,219 yielded a MIC for 50% of the strains tested (MIC50) of 0.25 micrograms/ml and a MIC90 of 1.0 microgram/ml, with 99.6% of the strains susceptible at a breakpoint of 2.0 micrograms/ml. Ciprofloxacin and grepafloxacin were less active (MIC50, 4.0 micrograms/ml; MIC90, 32.0 micrograms/ml and 2.0 and 16.0 micrograms/ml, respectively). Metronidazole was active against all gram-negative rods (MIC90, 4.0 micrograms/ml), but 31% of the gram-positive anaerobes were resistant at > 8.0 micrograms/ml. Cefoxitin was active against 84% of all strains at < or = 16.0 micrograms/ml, with a MIC50 of 4.0 micrograms/ml and a MIC90 of 32.0 micrograms/ml. Tazobactam enhanced the activity of piperacillin against > 95% of the beta-lactamase-producing gram-negative anaerobic rods (MIC90, 16.0 micrograms/ml).

Anti-Infective Agents↗