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PubMed1995

[Bactericidal activity of combinations of ticarcillin-clavulanic acid or other beta-lactams (amoxicillin, piperacillin-tazobactam, ticarcillin) with gentamicin against Enterococcus faecalis and E. faecium].

MICs of amoxicillin, piperacillin-tazobactam, ticarcillin and ticarcillin-clavulanic acid were determined against 52 clinical strains of E. faecalis and E. faecium. Modal MICs (mg/l) of these antibiotics were 1, 4, 64 and 64, respectively. Bactericidal activity of the beta-lactams was tested at two concentrations (1/2 MIC and 100 mg/l) alone or combined with gentamicin (4 mg/l) against 10 clinical strains of Enterococcus spp. Activity of ticarcillin was not modified by the addition of clavulanic acid (4 mg/l). Time-kill curves showed that all beta-lactams at 100 mg/l were bactericidal after 18 h of incubation (decrease in bacterial counts > or = 3 log10 CFU/ml) against 6 strains of E. faecalis, with MICs of amoxicillin at 1 mg/l and 2 strains of E. faecium with MICs of amoxicillin at 1 and 2 mg/l. Addition of gentamicin resulted in a bactericidal effect at 3 or 6 hours for the great majority of the combinations studied, except against the two strains highly resistant to gentamicin. Combination of every beta-lactam at 1/2 MIC with gentamicin was synergistic (except in case of high level resistance to gentamicin) and prevented bacterial growth but was not bactericidal. Against two strains of E. faecium with high MICs of amoxicillin (8 mg/l), piperacillin-tazobactam (64 mg/l) and ticarcillin-clavulanic acid (512 mg/l), only combinations of amoxicillin 100 mg/l and gentamicin were always bactericidal. In conclusion, against E. faecalis strains, ticarcillin-clavulanic acid tested at 100 micrograms/ml had a bactericidal activity similar to that of the other beta-lactams tested, alone or combined with gentamicin.(ABSTRACT TRUNCATED AT 250 WORDS)

Amoxicillin↗
PubMedDate not supplied

Piperacillin-tazobactam treatment for severe intra-abdominal infections.

In this limited series of 23 patients suffering from severe or life-threatening intra-abdominal infection, piperacillin + tazobactam, together with adequate surgical drainage and resections, cured 78% of our patients and eradicated almost all the pathogens. Side effects included essentially eosinophilia and elevation of transaminases but was never severe. Piperacillin + tazobactam seem thus to be an acceptable treatment, associated with correct surgical drainage. This regimen has to be compared in appropriate trial versus gold standard therapy, such as imipenem, a beta-lactam with aminoglucoside and imidazole or clindamycin or with broad spectrum beta-lactam and other inhibitors or beta-lactamases, but our rate of cure is impressive in such a population.

Abdomen↗
PubMed1993

[The use of piperacillin in the preoperative prophylaxis of colorectal surgery].

The authors present a prospective trial in 34 patients undergoing elective colo-rectal surgery. Seventeen patients received 2 g of piperacillin; intravenously, 30' min before surgery, and again 5 times, postoperatively, every 6 hours. The other 17 patients received 2 g of the same drug, intravenously, every 12 hours, immediately after surgery, at least for 5 days. The first group showed postoperative wound infections, with a rate of 11.75%. In the second group 5 patients showed postoperative infection, with a rate of 29.41%. There were 3 wound infections, one urinary tract infection and two pleuropolmonitis (a patient had two infections simultaneously). No side effects were registered. The better results registered in the first group, suggest the use of piperacillin in shortterm prophylaxis. This choice is attractive because of the comparison with other antibiotics, used in a similar way, shows similar results.

Adult↗
PubMed1998

Aztreonam plus piperacillin--empiric treatment of neutropenic fever in gynecology-oncology patients receiving cisplatin-based chemotherapy.

Antibiotic therapy must be instituted promptly and on an empiric basis in neutropenic patients. We evaluated the efficacy of a combined antibiotic regimen of monobactam (aztreonam) and antipseudomonal penicillin (piperacillin) in treating neutropenic fever episodes in gynecologic-oncology patients receiving cisplatin-based chemotherapy. A retrospective analysis of response to this regimen was performed. The rationale of this combination is the lack of nephrotoxicity and ototoxicity in patients who are or were previously treated with other nephrotoxic/ototoxic agents like cisplatin. A total of 19 courses of this regimen was administered to 13 patients with neutropenic fever following a complete fever work-up. Aztreonam (1-2gr q8h) plus piperacillin (4gr q8h) were administered intravenously for 6-8 days. Blood cultures were positive in four febrile episodes, and urine cultures were positive in seven. Gram negative organisms accounted for all positive cultures. The cultured organism showed in-vitro sensitivity to at least one of the drugs in all positive isolates. Clinical response with defervescence was noted during therapy in 18/19 courses (94.7%). Although the two drugs share a common bactericidal mechanism they were found to be highly active in this subgroup of patients. A double blind prospective evaluation of this empiric combination is warranted.

Adult↗
PubMed1979

Piperacillin kinetics.

Piperacillin was administered to normal, healthy volunteers by an intravenous infusion over 30 min at dosage regimens of 12 gm daily (4 gm every 8 hr) and 24 gm daily (6 gm every 6 hr) for 5 consecutive days. Mean peak serum level after 12 gm daily was 244 +/- 24 (SE) microgram/ml and after 24 gm daily, 353 +/- 7 microgram/ml. After infusion the serum level declined monoexponentially in most subjects. On the 12-gm daily dosage mean values were 60 min for half-life (t1/2), 16 1 for volume of distribution, 188 ml/min for body clearance, and 139 ml/min for renal clearance. The same values on day 4 were 47 min, 12 1, 181 ml/min, and 125 ml/min; the volume of distribution was lower than on day 1. On the 24-gm daily dosage regimen, t1/2 was 60 min; volume of distribution, 16 1; body clearance, 183 ml/min; and renal clearance, 101 ml/min on day 1 compared to 68 min, 15 1, 148 ml/min, and 71 ml/min on day 4, the last 2 being significantly lower than on day 1. High renal clearance values were observed at low serum concentrations and vice versa, suggesting saturation of the tubular secretion process at high piperacillin concentrations in serum.

Adolescent↗
PubMed1986

In-vitro antibacterial activity of imipenem compared with four other beta-lactam antibiotics (ceftazidime, cefotaxime, piperacillin and azlocillin) against 828 separate clinical isolates from a Portuguese hospital.

An agar dilution technique was used to determine the MIC50 and MIC90 of imipenem in comparison with ceftazidime, cefotaxime, piperacillin and azlocillin. Eight hundred and eighteen of the 828 (98.8%) unselected Gram-positive cocci and Gram-negative bacilli were inhibited by imipenem at a concentration of 8 mg/l or less. Imipenem was shown to be superior to the other four beta-lactam antibiotics against Acinetobacter calcoaceticus (40 strains), all the Staphylococcus aureus (80 strains, 10 of them penicillin- and methicillin-resistant), Streptococcus faecalis (20 strains) and Salmonella spp. (50 strains). Imipenem and cefotaxime were the most active against Str. pneumoniae (20 strains). Against Escherichia coli (52 strains) the activity of imipenem was similar to that of ceftadizime and superior to the other three antibiotics. Imipenem was two-fold inferior to cefotaxime and four-fold inferior to ceftazidime against Serratia marcescens (52 strains) and superior to piperacillin and azlocillin. Against Pseudomonas aeruginosa (300 strains), Ps. cepacia (104 strains) and indole positive Proteus (52 strains), only ceftazidime was better than imipenem. This study confirms published results that point to the impressive spectrum of activity offered by imipenem.

Anti-Bacterial Agents↗
PubMed1998

Diffusion of piperacillin, cefotiam, minocycline, amikacin and ofloxacin into the prostate.

BACKGROUND: The successful treatment of bacterial prostatitis depends on an effective antimicrobial concentration in prostatic tissue against the infecting organism. In this study we compared the diffusion of 5 types of antimicrobials into the prostate. METHODS: The concentrations of piperacillin, cefotiam, minocycline, amikacin, and ofloxacin were determined in prostatic fluid, prostatic tissue, and serum 2.5 to 3 hours after a single administration from 55 patients with benign prostatic hypertrophy. RESULTS: Although amikacin showed the highest mean concentration both in prostatic tissue and prostatic fluid, the prostatic tissue/serum ratio was significantly higher (P < 0.01) for ofloxacin (1.49 +/- 0.80) and minocycline (0.94 +/- 0.39) compared with those for amikacin (0.49 +/- 0.21) and piperacillin (0.21 +/- 0.15). Also, the prostatic fluid/serum ratio was lower than the prostatic tissue/serum ratio for each drug, however, the prostatic fluid/serum ratio of ofloxacin was significantly higher than that of other antimicrobials tested (P < 0.01). CONCLUSION: These results support earlier studies demonstrating that fluoroquinolones are a useful class of antimicrobials for the treatment of chronic bacterial prostatitis. They also suggest that in view of the pharmacokinetic properties and antimicrobial activities, amikacin and minocycline may be alternate antimicrobial options for selected patients with bacterial infections of the prostate.

Aged↗
PubMed1978

Inhibition of cell division of Escherichia coli by a new synthetic penicillin, piperacillin.

The mechanism of the action of piperacillin against Escherichia coli was investigated. This drug converted cells to filaments, but did not show lytic action in a range of concentrations below 25 mug/ml. In some of the filaments, stretched constrictions with various diameters were observed. Addition of piperacillin to a synchronous culture inhibited cell division immediately at any stage of the cell cycle. The results of morphological examination of synchronous cultures show that the percentage of filaments with a stretched constriction corresponds to that of normally septated cells before addition of the drug. Furthermore, peptidoglycan synthesis and cross-linking were not inhibited by this drug. It is likely that this drug inhibits only septum formation, but not the growth of wall, and that stretched constrictions are a result of longitudinal growth of septation caused by the drug. Examination of affinity of the drug to penicillin-binding proteins shows that protein 3 is the most sensitive, proteins 2 and 7 are moderately so, and protein 1 is sensitive only to high concentrations of the drug.

Bacterial Proteins↗
PubMed1979

Comparison of the activities of the new ureidopenicillins piperacillin, mezlocillin, azlocillin, and Bay k 4999 against gram-negative organisms.

The in vitro activities of the new ureidopenicillins piperacillin, mezlocillin, azlocillin, and Bay k 4999 were compared with those of ampicillin and ticarcillin against 336 Enterobacteriaceae, 109 nonfermenters, 55 Neisseria, and 28 Haemophilus influenzae isolates. Bay k 4999 displayed the largest spectrum of activity and had lower minimal inhibitory concentrations than any of the other penicillins against all of the species tested. Piperacillin showed the same spectrum but was slightly less active than Bay k 4999; it was slightly more effective than mezlocillin against Enterobacteriaceae and fully as active as azlocillin against Pseudomonas. All ureidopenicillins were substantially more active than ampicillin and ticarcillin. Isolates highly resistant to ampicillin or ticarcillin were also less susceptible to the ureidopenicillins.

Ampicillin↗
PubMed1979

Agar disk diffusion susceptibility characteristics of azlocillin, carbenicillin, mezlocillin, piperacillin, and ticarcillin.

The agar disk diffusion susceptibility of Enterobacteriaceae to mezlocillin and piperacillin was correlated with agar minimal inhibitory concentrations and compared with the susceptibility to carbenicillin. The agar disk susceptibility of Pseudomonas aeruginosa to azlocillin, mezlocillin, and piperacillin was correlated with agar minimal inhibitory concentrations and compared with the susceptibility to carbenicillin and ticarcillin. Criteria are offered for the zones of inhibition to provide information about resistant and susceptible isolates that correlate with known serum levels.

Carbenicillin↗
PubMed2006

Efficacy and safety of ertapenem versus piperacillin-tazobactam for the treatment of intra-abdominal infections requiring surgical intervention.

Complicated intra-abdominal infections usually mandate prompt surgical intervention supplemented by appropriate antimicrobial therapy. The aim of this study was to demonstrate that ertapenem was not inferior to piperacillin-tazobactam for the treatment of community-acquired intra-abdominal infections. A randomized open-label active-comparator clinical trial was conducted at 48 medical centers on four continents from December 2001 to February 2003. Adult patients with intra-abdominal infections requiring surgery were randomized to receive either ertapenem 1 g daily or piperacillin/tazobactam 13.5 g daily in 3-4 divided doses. The primary analysis of efficacy was the clinical response rate in clinically and microbiologically evaluable patients at the test-of-cure assessment 2 weeks after completion of therapy. All treated patients were included in the safety analysis. Patient demographics, disease characteristics, and treatment duration in both treatment groups were generally similar. The most commonly isolated pathogens at baseline were E coli (greater than 50% of cases in each group) and B fragilis ( approximately 9%). Favorable clinical response rates were 107/119 (90%) for ertapenem recipients and 107/114 (94%) for piperacillin/tazobactam recipients. The frequencies of drug-related adverse events, most commonly diarrhea and elevated serum alanine aminotransferase levels, were similar in both treatment groups. Six of 180 ertapenem recipients (3%) and two of 190 piperacillin/tazobactam recipients (1%) had serious drug-related adverse experiences. In this study, ertapenem and piperacillin/tazobactam were comparably safe and effective treatments for adult patients with complicated intra-abdominal infections.

Abdomen↗
PubMed1998

Influence of pregnancy on the pharmacokinetic behaviour and the transplacental transfer of the piperacillin-tazobactam combination.

The safety/acceptability, blood pharmacokinetics and urinary excretion of the piperacillin-tazobactam (PPR-TZB) combination were studied in six patients between 25 1/7 and 31 5/7 weeks of amenorrhea. The combination was given for a materno-fetal infection due to susceptible organisms i.e. 4/0.5 g/6 h. Whenever possible, the trans-placental transfer (TPT) of the combination was assessed in several sub-compartments of the feto-placental unit i.e. maternal blood sample, cord blood, amniotic fluid, placenta tissue and fetal urine. Two series of nine blood samples were scheduled for each patient, i.e. on D1 (first dose) and D3 (at plateau). Samples were assayed by HPLC and data were analyzed by a non-compartmental method. Safety/acceptability of the treatment proved to be good. The kinetic behavior of both beta-lactams appeared to be identical. Evidence was found during pregnancy of an increase in Vss and Cl of the combination. These increases can be linked to a notable decrease in AUCs. The TPT of the combination was significant. Regarding other accessible compartments (i.e. placenta tissue, amniotic fluid and fetal urine), the ratio of PPR-TZB concentrations was invariably about 8. Maternal circulating levels of PPR-TZB were, by 4 h, less than the MIC of target organisms (i.e. < or = 8 micrograms/ml), both on D1 and at steady state. This raises the question of the pertinence of the dosage regimen. Regarding PPR, it is accepted that antibacterial protection is satisfactory when circulating concentrations are kept at a Css (steady state concentration) of the order of 20 micrograms/ml or more. PPR-TZB combination would be administered by continuous infusion i.e. 8 mg/min to obtain 3 h later a Css of more than 20 micrograms/ml. The daily dosage would then be 12/1.5 g instead of 16/2 g, which is also more satisfactory from a pharmaco-economic standpoint. This proposal must be validated in a sufficient number of patients and, could avoid disqualification of the combination PPR-TZB in the treatment of serious infections during certain pathological pregnancies.

Adult↗
PubMed2002

Development and optimization of a reversed-phase high-performance liquid chromatographic method for the determination of piperacillin and tazobactam in tazocin injectable powder.

A reversed phase high-performance liquid chromatographic method with detection at 220 nm was developed and validated for the determination of piperacillin, I, and tazobactam, II, in Tazocin injectable powder. Acetaminophen was used as internal standard. A Hypersil BDS RP-C(18) column (250 x 4.6 mm), 5 microm particle size, was equilibrated with a mobile phase composed of aqueous solution of sodium dihydrogenphosphate-dihydrate (20 mM)-acetonitrile-methanol (70:15:15, v/v/v) and pH 5.0. Its flow rate was 1.0 ml/min. Calibration curves were linear for I and II in the concentration ranges of 3.0 x 10(-7)-2.0 x 10(-4) M and 7.0 x 10(-7)-2.0 x 10(-4) M, respectively. Limits of detection and quantitation were 1 x 10(-7), 3 x 10(-7) M for I and 2 x 10(-7), 7 x 10(-7) M for II, respectively. Relative standard deviation, for I and II was less than 0.40 and 0.75%, respectively. Extensive recovery studies were also performed.

Chromatography, High Pressure Liquid↗
PubMed2004

False-positive galactomannan platelia Aspergillus test results for patients receiving piperacillin-tazobactam.

At the bone marrow transplantation center of the San Martino Hospital (Genoa), we observed an increase in the rate of patients with positive Platelia Aspergillus (PA; Bio-Rad) test results, from 10% (38 of 386 patients) in the period from January 1999 through January 2003 to 36% (21 of 59 patients) in the period from February 2003 through May 2003. Positivity was significantly (P<.001) associated with the administration of piperacillin-tazobactam (PT) (17 [74%] of 23 patients who received PT had positive results vs. 4 [11%] of 36 who did not receive PT). Multivariate analysis found administration of PT ( chi 2=34.7; P<.001) and underlying disease ( chi 2=21.14; P<.001) to be associated with PA positivity. Of 15 PT batches tested, 12 had positive PA test results.

Anti-Bacterial Agents↗
PubMed1998

Treatment of ventilator-associated pneumonia with piperacillin-tazobactam/amikacin versus ceftazidime/amikacin: a multicenter, randomized controlled trial. VAP Study Group.

In a randomized trial conducted in 27 intensive care units, we compared the clinical efficacy and safety of piperacillin-tazobactam (TAZ; 4 g/0.5 g q.i.d.) and of ceftazidime (CAZ; 1 g q.i.d.), both combined with amikacin (7.5 mg/kg b.i.d.), as therapy for ventilator-associated pneumonia (VAP; acquired after > or =48 hours of mechanical ventilation). VAP was diagnosed with use of protected samples and quantitative cultures, and outcome was assessed blindly from treatment. Of 204 patients suspected of having VAP and randomized to a treatment arm of the study, 127 (64%) had bacteriologically confirmed infections, of which 37% were polymicrobial and 32% involved Pseudomonas aeruginosa; 115 patients (51 TAZ and 64 CAZ recipients) remained evaluable as per protocol. Clinical/bacteriologic cure rates (TAZ vs. CAZ, 51% vs. 36%; 95% confidence interval of difference, -0.2% to 30.2%), and 28-day mortality rates (16% vs. 20%) were similar; however, fewer bacteriologic failures occurred with TAZ (33% vs. 51%; P = .05). We conclude that the two regimens were of equivalent clinical efficacy in therapy for confirmed VAP.

Amikacin↗
PubMed2002

Surgical infections with enterococcus: outcome in patients treated with ertapenem versus piperacillin-tazobactam.

BACKGROUND: The pathogenicity of Enterococcus in polymicrobial surgical infections is controversial. The objective of this analysis was two-fold. The impact of Enterococcus on clinical outcome was assessed in adults with complicated intra-abdominal (IAI), complicated skin and skin structure (CSSSI), or acute pelvic (PI) infection treated with ertapenem or piperacillin-tazobactam, which is more active in vitro against enterococci than ertapenem. Baseline characteristics were identified that were associated with Enterococcus infection and with treatment failure. METHODS: This analysis included 1,558 patients treated in three randomized, triple-blind studies. Of these patients, 223 had Enterococcus in initial cultures: 125 of 623 (20%) with IAI, 28 of 529 (5%) with CSSSI, and 70 of 406 (17%) with PI. Logistic regression models were fit to assess each objective. RESULTS: The cure rates for the two treatment groups were similar in each of the three studies, regardless of the presence or absence of Enterococcus. Cure rates for both treatment groups combined were significantly lower in patients with Enterococcus than without Enterococcus for IAI (76% [69/91] versus 87% [264/305], OR 2.3 [95% CI, 1.2-4.1], P = 0.009) and CSSSI (58% [11/19] versus 84% [241/287], OR 3.8 [95% CI, 1.5-10.0], P = 0.010); but for PI, rates were similar (96% [50/52] versus 92% [188/205], OR 0.4 [95% CI, 0.1-1.9], P = 0.220). Characteristics predictive of the presence of Enterococcus were Pseudomonas aeruginosa as a baseline pathogen for IAI, older age, and the presence of a complicating underlying disease for CSSSI, and infection severity rated moderate rather than severe for PI. The strongest predictors of treatment failure were >2 days postoperative infection at study entry for patients with IAI and older age for patients with CSSSI. CONCLUSION: Choice of antimicrobial therapy did not affect cure rates in patients with or without Enterococcus. The strongest predictors of failure were postoperative infection at study entry in patients with IAI and older age in patients with CSSSI.

Abdomen↗
PubMed2006

Endocarditis caused by extended-spectrum-beta-lactamase-producing Klebsiella pneumoniae: emergence of resistance to ciprofloxacin and piperacillin-tazobactam during treatment despite initial susceptibility.

Three episodes of bacteremia occurred in the course of prosthetic valve endocarditis caused by an extended-spectrum-beta-lactamase (ESBL)-producing Klebsiella pneumoniae strain. The second isolate developed resistance to ciprofloxacin and the third isolate to piperacillin-tazobactam (PIP-TZ) following sequential therapy with each agent. The first isolate was resistant to PIP-TZ only at high inocula, the second isolate acquired increased transcription of the acrA gene, and the third isolate became resistant to PIP-TZ due to loss of beta-lactamase inhibition by TZ. We question if and how PIP-TZ susceptibility should be reported for ESBL-producing Enterobacteriaceae.

Ciprofloxacin↗
PubMed2006

Clinical correlation of the CLSI susceptibility breakpoint for piperacillin- tazobactam against extended-spectrum-beta-lactamase-producing Escherichia coli and Klebsiella species.

We assessed infections caused by extended-spectrum-beta-lactamase-producing Escherichia coli or Klebsiella spp. treated with piperacillin-tazobactam to determine if the susceptibility breakpoint predicts outcome. Treatment was successful in 10 of 11 nonurinary infections from susceptible strains and in 2 of 6 infections with MICs of >16/4 mug/ml. All six urinary infections responded to treatment regardless of susceptibility.

Aged↗