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PubMed1984

Clavulanic acid in combination with ticarcillin: an in-vitro comparison with other beta-lactams.

The in-vitro activity of ticarcillin in combination with clavulanic acid was compared with that of ticarcillin alone, piperacillin, cefotaxime and, where appropriate, other beta-lactams against a total of 301 recent clinical isolates and characterized beta-lactamase producers. An agar dilution procedure was used to determine MICs and two inocula (10(4) and 10(6) cfu) were used throughout. MICs of the combination of ticarcillin and clavulanic acid were expressed as MICs of ticarcillin in the presence of 5 or 10 mg/l of clavulanic acid. Against most members of the Enterobacteriaceae (Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Providencia stuartii and Serratia marcescens), ticarcillin plus clavulanic acid was as active as or more active than piperacillin. Against Staphylococcus aureus. Haemophilus influenzae and the Bacteroides fragilis group the combination was considerably more active than piperacillin. Piperacillin was more active than the ticarcillin/clavulanic acid combination against Pseudomonas aeruginosa.

Anti-Bacterial Agents↗
PubMed1989

A comparison of double beta-lactam combinations with netilmicin/ureidopenicillin regimens in the empirical therapy of febrile neutropenic patients.

In a randomized trial ceftazidime plus piperacillin or azlocillin, and netilmicin plus piperacillin or azlocillin were used as initial empirical therapy in 202 febrile neutropenic episodes. Netilmicin plus azlocillin was the most effective combination with a clinical response rate of 81% in clinically and microbiologically documented infections compared with 63% for ceftazidime plus piperacillin. All of the episodes of Gram-negative bacteraemia treated with azlocillin responded compared with 43% of those treated with piperacillin. Gram-positive organisms accounted for 52% of all bacteriologically documented infections and 40% of the febrile episodes were treated with vancomycin for presumptive or documented Gram-positive infection. Patients treated with netilmicin had significantly more nephrotoxicity than those given the double beta-lactam combinations (14.8% vs 3.5%; P less than 0.05). However, this difference was not shown in those patients who did not receive concurrent vancomycin or amphotericin. The double beta-lactam combinations were associated with more hypokalaemia (58.2% vs. 37.7%; P less than 0.05) and more colonization with yeasts (24% vs. 10.4%; P less than 0.05) but there was no evidence that their use was associated with prolongation of neutropenia. These results indicate that ceftazidime plus a ureidopenicillin would be adequate empirical therapy in situations where the concomitant use of nephrotoxic agents precludes the use of aminoglycoside containing combinations.

Adult↗
PubMed1991

Synergistic post-antibiotic effect of amikacin and beta-lactam antibiotics on Enterococcus faecalis.

The in-vitro post-antibiotic effect (PAE) of amikacin alone and in combination with ceftazidime, ceftriaxone and piperacillin was studied for two strains of Enterococcus faecalis using a bioluminescent assay of bacterial ATP. The two strains of E. faecalis were resistant to amikacin, ceftazidime and ceftriaxone but sensitive to piperacillin. The bacterial cultures were incubated with the beta-lactam antibiotics for 1 h and concentrations of amikacin between 2-64 mg/l were then added. Thereafter, incubation continued with the combinations for one more hour. After dilution, regrowth was monitored by measuring bacterial ATP every hour. Increasing concentrations of amikacin (2-64 mg/l), ceftazidime (8-32 mg/l) and ceftriaxone (32-128 mg/l) resulted in little or no PAE (0-0.3 h) on these strains. PAEs of 0.5 to 1.6 h resulted from exposure to piperacillin (4-32 mg/l). In combination amikacin and piperacillin increased the PAE to 5.5 h. A synergistic PAE was also seen when the enterococci were exposed to amikacin combined with ceftazidime or ceftriaxone in concentrations close to the MICs of the latter antibiotics.

Amikacin↗
PubMed1993

Safety profile of piperacillin/tazobactam in phase I and III clinical studies.

The safety of piperacillin/tazobactam was investigated in Phase I and Phase III clinical studies. In 22 Phase I pharmacokinetic studies, 242 healthy subjects and 232 patients were given single and multiple doses of piperacillin/tazobactam, piperacillin alone, tazobactam alone, and/or placebo. Interaction with tobramycin and vancomycin was also studied. Of 1201 patients enrolled in Phase III trials, 944 received piperacillin 4 g plus tazobactam 500 mg every 8 h for lower respiratory tract infections, complicated urinary tract infections, skin and soft tissue infections, and intra-abdominal infections, or piperacillin 2 g plus tazobactam 500 mg 8 hourly for less severe infections; 90 patients received imipenem/cilastatin as a comparative regimen. Piperacillin 4 g and tazobactam 500 mg were also administered every 6 h with an aminoglycoside to 167 patients with pulmonary infection or neutropenia and bacterial infection. In all trials, piperacillin/tazobactam was found to be safe and well tolerated. One death was deemed possibly drug-related. Thirty-eight patients were withdrawn from the trials because of adverse experiences, most often diarrhoea and allergic skin reactions. The commonest laboratory abnormalities related to liver function. The safety of piperacillin/tazobactam appears similar to that of other beta-lactam/beta-lactamase inhibitor combinations.

Bacterial Infections↗
PubMed2003

Efficacy of ertapenem in the treatment of serious infections caused by Enterobacteriaceae: analysis of pooled clinical trial data.

OBJECTIVE: The efficacy of ertapenem, 1 g once a day, for treatment of adults with serious infections caused by Enterobacteriaceae was compared with ceftriaxone 1 g once a day [complicated urinary tract infection (CUTI) and community-acquired pneumonia (CAP)] or piperacillin-tazobactam, 3.375 g every 6 h (complicated intra-abdominal, complicated skin/skin structure and acute pelvic infections). PATIENTS AND METHODS: This combined analysis included the subgroup of all 1167 treated patients infected with Enterobacteriaceae from seven randomized double-blind studies. RESULTS: Escherichia coli was the most common pathogen, accounting for 65.3% of all Enterobacteriaceae. Among evaluable patients with deep tissue (intra-abdominal, skin and pelvic) infections, the combined clinical cure rates were 84.8% (223 of 263) for ertapenem and 82.9% (194 of 234) for piperacillin-tazobactam [95% confidence interval (CI) for the difference, adjusting for infection, -4.9% to 8.9%]. Cure rates by infection for ertapenem and piperacillin-tazobactam, respectively, were: intra-abdominal, 85.1% (143 of 168) and 79.9% (119 of 149); pelvic, 86.8% (46 of 53) and 94% (47 of 50); skin/skin structure, 81% (34 of 42) and 80% (28 of 35). Among patients with CUTI, microbiological cure rates were 90.5% (220 of 243) for ertapenem and 92% (196 of 213) for ceftriaxone (95% CI for the difference, -7.1% to 4.1%). In patients with CAP, clinical cure rates were 95% (19 of 20) for ertapenem and 88.9% (16 of 18) for ceftriaxone. CONCLUSION: Ertapenem therapy was as effective as either piperacillin-tazobactam or ceftriaxone for serious infections caused by Enterobacteriaceae.

Adult↗
PubMed2005

Post-antibiotic effect induced by an antibiotic combination: influence of altered susceptibility to individual components.

OBJECTIVES: The impact of altered susceptibility of an organism to the components of an antibiotic combination on post-antibiotic effect (PAE) was studied. METHODS: The baseline PAEs expressed by Pseudomonas aeruginosa ATCC 27853 were recorded following 1 h of exposure to piperacillin and gentamicin, alone and in combination. Similar PAE assessments were made after resistance to the individual antibiotics was induced over 0.5-2x of their respective MIC. RESULTS: Before any induction, the PAE produced by piperacillin alone was negligible and that by the combination was synergistic. After piperacillin resistance was induced, PAE exhibited by the beta-lactam remained negligible, and comparable PAEs were observed for gentamicin and the combination, suggesting an additive interaction with a dominant effect from gentamicin. When resistance was induced against gentamicin, progressively shorter PAE was expressed by the aminoglycoside alone and the combination at increasing levels of resistance. In addition, a measurable PAE was unexpectedly observed for piperacillin, whereas the interaction also became additive. CONCLUSIONS: In summary, the PAE expressed by the test combination was highly dependent on the status of gentamicin resistance. The resistance profile exhibited by the organism against individual antibiotics of the combination showed an impact on the type of interaction expressed.

Anti-Bacterial Agents↗
PubMed1987

Ceftazidime monotherapy vs. combined therapy in Pseudomonas pulmonary infections in cystic fibrosis.

To evaluate whether the addition of an aminoglycoside might enhance the clinical efficacy of ceftazidime in cystic fibrosis patients with acute exacerbations of chronic Pseudomonas lung infections we carried out a prospective, comparative, randomized blind study with three schedules: ceftazidime vs. ceftazidime plus sisomicin (C/S) vs. piperacillin plus sisomicin, for a total of 60 courses of 14 days of treatment. Each treatment led to clinical and radiologic improvement with marked reduction of signs of acute infection. Statistically there was no significant difference in clinical responses among the schedules. No side effect appeared during treatments with ceftazidime or C/S. Hyperpyrexia was seen in 35% of patients receiving piperacillin. Decrease in Pseudomonas aeruginosa count to less than 10(5) colony-forming units/ml of sputum was achieved in 60% of patients treated with C/S and in 30% of patients who received ceftazidime or piperacillin plus sisomicin (statistically not significant). A transient increase in mean geometric minimal inhibitory concentrations for ceftazidime and piperacillin was observed at the end of the combined therapies. A larger percentage of persistent resistant strains of P. aeruginosa was seen after the combined therapies. We conclude that ceftazidime as monotherapy may be an effective alternative in Pseudomonas lung infections in cystic fibrosis patients. Its clinical efficacy seems not to be enhanced by the addition of an aminoglycoside, although reduction of Pseudomonas in the sputum was better achieved by the combination of C/S.

Adolescent↗
PubMed1981

In vitro and in vivo antibacterial effects of combinations of beta-lactam antibiotics.

The effects of combining the new broad-spectrum penicillins piperacillin and mezlocillin with cefoxitin, cefamandole, or cephalothin on the antibacterial activities of these antibodies were determined in vitro against 50 to 109 bacterial strains and in six experimental infections in mice. Against strains of Escherichia coli, Klebsiella, Proteus mirabilis, Salmonella, Acinetobacter, Enterococcus, and Staphylococcus, the combinations exhibited synergistic, indifferent, or additive effects, but no antagonism. Against strains of four groups of organisms (Pseudomonas, Serratia, Enterobacter, and indole-positive Proteus), a high incidence of antagonism was observed, particularly with combinations containing cefoxitin (60 to 100%). The penicillins were antagonized by the cephalosporin antibiotics. In vitro effects were reflected in vivo. Mice infected with cultures associated with synergistic or additive in vitro effects were protected with lower doses of piperacillin when this antibiotic was administered with ineffective doses of cefoxitin than when piperacillin was used alone. Infections with cultures associated with in vitro antagonism required two- to eightfold higher doses of piperacillin and mezlocillin when these antibiotics were used in combination with the cephalosporins. The clinical implications of these effects should be considered.

Animals↗
PubMed1990

Beta-lactamase production in members of the family Enterobacteriaceae and resistance to beta-lactam-enzyme inhibitor combinations.

Recent reports that members of the family Enterobacteriaceae that produce high levels of certain beta-lactamases are often resistant to ticarcillin-clavulanate prompted this study to assess the relationship between type and amount of enzyme produced and susceptibility to ticarcillin-clavulanate, piperacillin-tazobactam, and cefoperazone-sulbactam. Agar dilution MICs were determined by using 73 strains of Enterobacteriaceae that produced a single beta-lactamase that had been characterized and quantified and a beta-lactamase-negative control strain of Escherichia coli. For E. coli and Klebsiella pneumoniae, MICs of each combination increased as levels of TEM, SHV-1, or class IV enzymes increased. However, the percentage of strains that were resistant was highest for ticarcillin-clavulanate (32%), with only 18 and 6% resistant to piperacillin-tazobactam and cefoperazone-sulbactam, respectively. Strains producing PSE-1, regardless of level, were resistant or moderately susceptible to ticarcillin-clavulanate but were susceptible to piperacillin-tazobactam and cefoperazone-sulbactam. HMS-1 and OHIO-1 beta-lactamases were associated with resistance to ticarcillin-clavulanate and piperacillin-tazobactam, respectively. High levels of class IV enzymes in Klebsiella oxytoca were associated with resistance to all three combinations. These results indicate that the level and type of beta-lactamase produced by members of the family Enterobacteriaceae are important determinants of susceptibility to beta-lactam-inhibitor combinations, especially ticarcillin-clavulanate.

Anti-Bacterial Agents↗
PubMed1997

In vitro activities of beta-lactam-beta-lactamase inhibitor combinations against Stenotrophomonas maltophilia: correlation between methods for testing inhibitory activity, time-kill curves, and bactericidal activity.

The activities of ampicillin, ampicillin-sulbactam, amoxicillin, amoxicillin-clavulanic acid, ticarcillin, ticarcillin-clavulanic acid, piperacillin, piperacillin-tazobactam, aztreonam, and aztreonam-clavulanic against Stenotrophomonas maltophilia strains for which the MICs of penicillins and commercially available beta-lactam-beta-lactamase inhibitor combinations were higher than the breakpoints usually recommended for Pseudomonas aeruginosa in commercially available broth microdilution methods were tested by the agar diffusion, agar dilution, and broth microdilution methods. Time-kill curve studies were performed when discrepancies between these methods were observed. The MICs obtained by the commercially available broth microdilution method, the agar dilution method, and the broth microdilution method were almost identical. Twenty-five percent of the strains tested showed inhibition diameters of > or =15 mm for ticarcillin-clavulanic acid, and 43.7% of the strains tested showed inhibition diameters of > or =18 mm for piperacillin-tazobactam by the agar diffusion method. The time-kill curves for these strains confirmed the results obtained by dilution methods. Aztreonam-clavulanic acid (2:1) at concentrations of < or =16 microg/ml inhibited all of these strains (MIC range, 1 to 16 microg/ml). The time-kill curves confirmed this activity. The addition of piperacillin to this combination did not modify the MICs. The combination aztreonam-clavulanic acid-ticarcillin was two- to fourfold more active than aztreonam-clavulanic acid alone. We studied the inhibitory and bactericidal activities of the two most active combinations (aztreonam-clavulanic acid and aztreonam-clavulanic acid-ticarcillin) against the standard inoculum and 10 and 50 times the standard inoculum. Inoculum modifications did not modify the MICs. Both combinations showed good bactericidal activity against the standard inoculum. With 10 times the standard inoculum, minimum bactericidal concentration (MBC) results were heterogeneous (for 55% of the strains, MBCs were between the MIC and 4-fold the MIC, and for 45% of the strains MBCs were between 8- and >32-fold the MIC). With 50 times the standard inoculum, MBCs were at least 32-fold the MICs for all the strains tested.

Amoxicillin↗
PubMed2002

Single-dose intraperitoneal magainins improve survival in a gram-negative-pathogen septic shock rat model.

The therapeutic efficacies of three polycationic peptides selected among the class of the magainins (magainin I, magainin II, and magainin II amide), alone and combined with piperacillin, were investigated in a rat model of septic shock. Rats were given an intraperitoneal injection of 2 x 10(10) CFU of Escherichia coli and randomized to receive intraperitoneally isotonic sodium chloride solution, 60 mg of piperacillin per kg of body weight, and 1 mg of each magainin per kg alone and combined with 60 mg of piperacillin per kg. The main outcome measures were bacterial growth in abdominal exudate and plasma, endotoxin and tumor necrosis factor alpha (TNF-alpha) concentrations in plasma, and lethality. Treatments with the magainins achieved significant reductions of bacterial growth and plasma endotoxin and TNF-alpha concentrations. In general, treatments with the combinations of magainins and piperacillin demonstrated the highest efficacies.

Animals↗
PubMedDate not supplied

In vitro activity of piperacillin/tazobactam against 615 Pseudomonas aeruginosa strains isolated in intensive care units.

From May 1996 to September 1997, 615 Pseudomonas aeruginosa strains isolated from patients in intensive care units collected from different Italian laboratories were studied. The susceptibility of piperacillin/tazobactam, in comparison with other antipseudomonal antibiotics, to their NCCLS breakpoints was evaluated: amikacin 79. 6%, carbenicillin 67.0%, ceftazidime 73.4%, ciprofloxacin 55.8%, imipenem 64.1%, piperacillin 88.1%, piperacillin/tazobactam 92.4% and ticarcillin/clavulanic acid 69.0%. Seventy-three strains were selected because of their resistance to piperacillin and the mechanisms underlying such a resistance were investigated. Isoelectric focusing and hydrolysis assays revealed the presence of 15 plasmid-mediated beta-lactamases. Chromosomal beta-lactamase derepression was demonstrated in 34 isolates. The remaining 24 piperacillin-resistant strains did not produce beta-lactamases and an 'intrinsic mechanism' of resistance was inferred. The piperacillin/tazobactam combination restored resistance in 25 piperacillin strains. Nine of these were derepressed for chromosomal beta-lactamase, 8 showed impermeability and 8 showed plasmid enzymes.

Drug Therapy, Combination↗
PubMed1990

In vitro effect of YTR (tazobactam) on plasmid and chromosomally mediated beta-lactamases.

The effect of tazobactam on the piperacillin susceptibility and on the beta-lactamase activity of different strains and species was evaluated. A synergistic effect was observed on the piperacillin susceptibility for all microorganisms tested, irrespective of the type and/or amount of beta-lactamase produced. Addition of gentamicin resulted in a further reduction of the piperacillin MIC. The enzyme activity after induction with piperacillin alone or in combination with tazobactam (4 mg/l) was quite similar.

Chromosomes↗
PubMedDate not supplied

Cost of antibiotic prophylaxis in cesarean section.

Two hundred sixty-three patients were randomly assigned to receive either piperacillin or cefoxitin for prophylaxis in cesarean section. Although both drugs were considered effective, piperacillin achieved a level of 98 percent satisfactory prophylaxis compared with only 91 percent for cefoxitin. Costs of prophylactic failure in cesarean section were calculated and then assessed for four different antibiotic regimens (based on 100 patients). Because of its high failure rate, ampicillin was the most expensive antibiotic; piperacillin was the least expensive. It was suggested that highly effective prophylaxis with an antibiotic agent such as piperacillin can result in significant cost savings when used for high-risk patients undergoing cesarean section.

Cefoxitin↗
PubMedDate not supplied

Economic evaluation of pharmacologic therapy.

Cost-benefit and cost-effectiveness analyses are defined and described, particularly as they apply to evaluating costs in pharmacologic therapy. The cost-benefit analysis (CBA) approach is used to compare dissimilar alternatives, whereas the cost-effectiveness (CEA) approach compares similar alternatives with similar objectives. A CBA, for instance, will demonstrate the economic effects of a program and can thus be used as a tool to compare the outcomes of several programs. A CEA, on the other hand, can help determine which of several alternatives is the least costly in achieving a stated objective. A CEA approach was used to examine results of clinical trials with cefoxitin or piperacillin in 86 patients undergoing intraabdominal surgery at two institutions. Results of multivariate analysis showed that patients who had received piperacillin had significantly shorter hospital stays (1.59 days) than those who had received cefoxitin. Based on national average hospital per diem rates, piperacillin patients were said to have saved $680 compared with patients treated with cefoxitin. Moreover, piperacillin was less expensive than cefoxitin.

Cefoxitin↗
PubMed2001

[Use of the Etest method for antimicrobial susceptibility testing of obligate anaerobes].

The aim of this study was to evaluate Etest usefulness for antimicrobial susceptibility testing of obligate anaerobes and to compare the activity of five antibacterial drugs against clinical strains of anaerobes. One hundred strains of obligate anaerobes were tested: 2 reference strains (B. fragilis ATCC 25285 and B. thetaiotaomicron ATCC 29741) and 98 clinical strains isolated from patients of the Infant Jesus Clinical Hospital--Center for Trauma Treatment in Warsaw during the last three years (1997-1999). Strains of seven genera of obligate nonsporeforming anaerobes (Bacteroides, Prevotella, Porphyromonas, Fusobacterium, Peptostreptococcus, Propionibacterium and Actinomyces) and strains of two sporeforming species (C. perfringens and C. difficile) were examined. The MIC values were determined by the gradient diffusion method Etest (AB BIODISK, Sweden). Wilkins-Chalgren solid medium supplemented with 5% of sheep blood was used. Test plates were incubated at 35 degrees C for 48 hours in glove-box (85% N2, 10% H2, 5% CO2). The MIC values for each strain and antimicrobial agent, and the MIC ranges for bacteria of the same species were established. Ten strains resistant to clindamycin, ten resistant to piperacillin, and ten resistant to imipenem were detected. Seven strains were resistant to metronidazole and two strains to piperacillin combined with tazobactam. Tazobactam restored the susceptibility of eight strains to piperacillin. Obtained results confirm that Etest method is useful for antimicrobial susceptibility testing of obligate anaerobes. Older (clindamycin and metronidazole) and newer (piperacillin, piperacillin/tazobactam and imipenem) antimicrobial agents revealed high and comparable activity against clinical strains of obligate anaerobes. The percentage of strains susceptible to tested antimicrobials was > or = 90. These antimicrobials may be still useful in the empiric treatment of infections caused by medically important anaerobes.

Anti-Bacterial Agents↗
PubMed2002

[Piperacillin/tazobactam--Tazocin. A penicillin-based alternative to 3rd generation cephalosporins and carbapenems].

The antibiotic piperacillin/tazobactam has recently been licensed for use in Denmark. Piperacillin/tazobactam combines a well known beta-lactam antibiotitic, piperacillin, and an inhibitor of bacterial beta-lactamase, tazobactam. The combination of piperacillin and tazobactam compared to piperacillin alone has an expanded antimicrobial spectrum, which includes Klebsiellae, Escherichia coli, and Proteus vulgaris resistant to ampicillin, as well as beta-lactamase-producing Staphylococcus aureus. As piperacillin in itself possesses antimicrobial activity against streptococci, enterococci, and Pseudomonas aeruginosa, the antimicrobial activity of piperacillin/tazobactam indicates that the combination may constitute an alternative to third generation cephalosporins and carbapenems in the treatment of complicated intra-abdominal infections infections in critically ill patients and for the empirical treatment of acute neutropenic febrile patients, as indicated by clinical studies.

Anti-Bacterial Agents↗
PubMed2006

[The rate of isolation of Klebsiella pneumoniae producing extended-spectrum beta-lactamases and resistance to antibiotics].

OBJECTIVE: To determine the relationship between the production of extended-spectrum beta-lactamases (ESBLs) in Klebsiella pneumoniae (K. pneumoniae) strains resistant to third-generation cephalosporins and resistance of these strains to antibiotics used. MATERIAL AND METHODS: A total of 157 cultures of K. pneumoniae resistant to third-generation cephalosporins were obtained from bronchial secretions of patients treated in intensive care units (ICUs) at Kaunas University of Medicine Hospital (KUMH). The secretions were cultured, and antibacterial susceptibility was tested in the Laboratory of Microbiology at KUMH according to the recommendations of the National Committee for Clinical Laboratory Standards (NCCLS). Using a method of double-disc synergy test, K. pneumoniae strains possibly producing ESBL were considered for further testing by means of E-tests. The resistance to carbapenems, piperacillin, gentamycin, amikacin, and ciprofloxacin was compared between ESBL-producing and non-ESBL-producing K. pneumoniae strains resistant to third-generation antibiotics. RESULTS: Almost one-third of K. pneumoniae strains (n=28, 32.8%) were resistant to third-generation cephalosporins in 2001 and 50.0% (n=36)--in 2004 (p<0.05). Half of the strains (n=7, 50%) were producing ESBLs in 2001 and 50% (n=12)--in 2004. All strains of K. pneumoniae were susceptible to carbapenems. Resistance rates to piperacillin and gentamicin were higher in ESBL-producing strains compared with non-ESBL-producing strains (94.7% (n=18) vs. 15.8% (n=3) (p<0.05) for gentamicin and 100% (n=19) vs. 36.8% (n=7) (p<0.001) for piperacillin, respectively). No significant differences were found in the resistance rates to amikacin and ciprofloxacin. CONCLUSIONS: The resistance of K. pneumoniae strains, isolated from bronchial secretions of patients treated in ICUs at KUMH, to third-generation cephalosporins increased significantly during the period of 2001-2004. However, the proportion of ESBL-producing strains remained unchanged. Resistance to certain antibacterials could be suspected if ESBL production is present - higher rates of resistance to piperacillin and gentamicin were found in the group of ESBL-producing K. pneumoniae strains.

Amikacin↗