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PubMed2001

Cholangiopathy after short-term administration of piperacillin and imipenem/cilastatin.

We describe a patient who suffered from intestinal perforation after abdominal trauma. Perioperatively, he was treated with a single dose of piperacillin and 9 doses of imipenem/cilastatin over 3 days. The patient was discharged 5 days after surgery in good clinical condition and with normal liver values except for a marginal elevation of alanine aminotransferase. Two weeks after discharge, he developed fatigue, fever and pruritus, necessitating rehospitalization. He was jaundiced and had elevated alkaline phosphatase and transaminases. After exclusion of an intra-abdominal fluid collection, a vascular problem, and infectious or autoimmune liver disease, a liver biopsy was performed. The biopsy revealed centrizonal bilirubinostasis, a portal infiltrate rich in eosinophils and cholangitis. Lymphocyte transformation tests for piperacillin and imipenem/cilastatin were positive, suggesting an immunological mechanism for the observed hepatopathy. Cholestasis gradually decreased but was detectable for several weeks. The patient had a full clinical and biochemical recovery after 3 months. We conclude that short-term therapy with piperacillin, imipenem/cilastatin or the combination of these drugs can lead to the same type of hepatopathy as described for amoxycillin/clavulanic acid or antistaphylococcal penicillins. Liver biopsy and positive lymphocyte transformation are compatible with an immunological mechanism.

Adult↗
PubMed2003

Piperacillin plus aztreonam for treatment of neutropenic fever.

BACKGROUND: A combination of beta-lactam plus an aminoglycoside is the most frequently used regimen for febrile episodes in neutropenic cancer patients. However, aminoglycoside-related toxicity occasionally makes this regimen difficult to use as the first-line drug therapy. In the present study, we chose aztreonam as the alternative to aminoglycoside in combination with piperacillin for neutropenic fever in pediatric patients and we evaluated its effectiveness. METHODS: A total of 31 febrile episodes in 16 patients with malignant neoplasms were evaluted. Piperacillin (200 mg/kg per day) plus aztreonam (150 mg/kg per day) were administered intravenously following a routine fever work-up. RESULTS: The overall response rate was 67%. The response rate when neutrophil count was less than 100/mm3 was 63%. The side effects were mild and rare. In three patients, all of the microbiologically documented infections were caused by alpha-streptococcus, which required a change in the regimen. CONCLUSIONS: A combination of piperacillin and aztreonam provides an effective and non-toxic regimen for first-line therapy in febrile patients with neutropenia. In contrast, the results of the present study suggest the need for caution with regard to alpha-streptococcus infections.

Adolescent↗
PubMed2006

[Antibiotic prophylaxis in cesarean section -- piperacillin versus piperacillin/tazobactam in 300 cesarean sections].

INTRODUCTION: Antibiotic prophylaxis is a standard procedure in obstetric surgery and has been discussed in various investigations. Use of treatment is judged by high efficacy and good tolerance. METHOD: In 300 patients undergoing cesarean sections we compared results of application of Piperacillin 4 g and Piperacillin/Tazobactam 4.5 g after cut of umbilical cord. Tazobactam/Piperacillin is a combination of a broad-spectrum penicillin and a beta-lactamase inhibitor with increased toxicity against staph. aureus, enterobacter, and other germs responsible for local and systemic infections in obstetric surgery. RESULTS: We did not observe any severe adverse effects. Rate of severe wound infections was 1.3 % (Tazobactam/Piperacillin) and 2 % (Piperacillin alone). The difference showed no statistic significance (p > 0.01). During postoperative course we found a higher increase of CRP (p < 0.01) in the Piperacillin group. CRP proved to be a useful objective parameter to distinguish between patients with or without postoperative infections. No differences were found in the number of leucocytes, time in hospital and other parameters.

Anti-Bacterial Agents↗
PubMed1989

Piperacillin alone vs triple antibiotic combination in gynecological infections.

Forty hospitalized adult patients with gynecological infections were randomly assigned to treatment either with piperacillin alone (22 patients) or with the combination of gentamicin, clindamycin and penicillin G (18 patients). The aim of the study was to investigate the possibility of replacing a triple combination therapy with a single-agent broad spectrum antibiotic. Penicillin G was added for the coverage of enterococci. The median duration of treatment was 8 days for both groups. The daily dose for the administered drugs was 12g for piperacillin, 4mg/kg for gentamicin, 1.8g for clindamycin and 20 million units for penicillin G. The cure-improvement rate in the single agent therapy group was 90.9% and in the combination therapy group 94.4%. These differences were not statistically significant. No side effects were reported. It is concluded that single agent piperacillin is as effective as the combination therapy used in this study for the treatment of hospitalized gynecological infections.

Adult↗
PubMed1992

Aztreonam plus vancomycin versus gentamicin plus piperacillin as empirical therapy for the treatment of fever in neutropenic patients: a randomised controlled study.

The efficacy of aztreonam in combination with vancomycin was compared with that of gentamicin plus piperacillin as empirical antibiotic treatment for fever in 61 neutropenic patients. Aztreonam plus vancomycin was as effective, but no more effective, than gentamicin plus piperacillin. Aztreonam showed excellent clinical and in vitro efficacy against Gram-negative pathogens. Failure to respond to aztreonam plus vancomycin was, in most cases, due to presumed or documented fungal infection; by contrast, failure to respond to gentamicin plus piperacillin was frequently to be due to resistant or superadded infection with Gram-positive bacteria.

Adult↗
PubMed2002

Ertapenem once daily versus piperacillin-tazobactam 4 times per day for treatment of complicated skin and skin-structure infections in adults: results of a prospective, randomized, double-blind multicenter study.

We conducted a prospective, randomized, double-blind trial comparing ertapenem (1 g once daily) with piperacillin-tazobactam (3.375 g every 6 h) as parenteral treatment for 540 adults with complicated skin and skin-structure infections. The most common diagnoses were skin or soft-tissue abscesses and lower-extremity infections associated with diabetes. The mean duration (+/- standard deviation) of therapy was 9.1+/-3.1 days for ertapenem and 9.8+/-3.3 days for piperacillin-tazobactam. At the assessment of primary efficacy end point, 10-21 days after treatment, 82.4% of those who received ertapenem and 84.4% of those who received piperacillin-tazobactam were cured. The difference in response rates, adjusting for the patients' assigned strata, was -2.0% (95% confidence interval, -10.2% to 6.2%), indicating that the response rates in the 2 treatment groups were equivalent. Cure rates for the 2 treatment groups were similar when compared by stratum, diagnosis, and severity of infection. The frequency and severity of drug-related adverse events were similar in the treatment groups.

Adult↗
PubMedDate not supplied

The acylampicillins: mezlocillin, piperacillin, and azlocillin.

The new acylampicillin derivatives azlocillin, mezlocillin, and piperacillin have an increased activity against many gram-negative bacilli, especially Klebsiella pneumoniae, Serratia marcescens, and Pseudomonas aeruginosa, when compared with the carboxypenicillins carbenicillin and ticarcillin. The new penicillins show synergistic activity in combination with aminoglycosides but, when combined with other beta-lactams, may be synergistic (piperacillin and moxalactam; mezlocillin and cefoperazone), indifferent, or antagonistic (azlocillin, mezlocillin, or piperacillin and cefoxitin or cefamandole). The in vitro activity of these agents, either alone or in combination, appears to correlate with in vivo efficacy in animal models. The new penicillins are clinically effective for a very broad range of infections, including life-threatening nosocomial infections. Adverse effects with these, as with other semisynthetic penicillins, are minimal. Attention must be paid to the potential for infection by naturally resistant, gram-negative bacilli such as beta-lactamase-producing Escherichia coli and for the emergence of resistance during therapy. The granulocytopenic patient should receive these agents only in conjunction with another agent, such as an aminoglycoside; this combination will often result in a synergistic effect when tested in vitro. The carboxypenicillins and the newer penicillins have substantial similarities, and prospective, comparative studies have so far failed to demonstrate significant clinical superiority. However, the increased activity of the acylampicillins may be advantageous for the treatment of infections due to K. pneumoniae and P. aeruginosa.

Agranulocytosis↗
PubMed1985

Mutation of Pseudomonas aeruginosa to piperacillin resistance mediated by beta-lactamase production.

Piperacillin-resistant mutants were detected in each of ten strains of Pseudomonas aeruginosa. The resistance was associated with constitutive production by the strains of high levels of beta-lactamase which was similar in character to the induced chromosomal Id beta-lactamase of the parent strains. This type of mutation to piperacillin-resistance occurred at a low frequency. The beta-lactamase production and piperacillin-resistance were stable on repeated subculture and prolonged storage of the strains.

Mutation↗
PubMed1986

Effect on growth curves and killing curves of brief exposure of Escherichia coli to imipenem and piperacillin.

Escherichia coli was exposed to various concentrations of imipenem and piperacillin. As with the majority of beta-lactam antibiotics, the kinetic turbidometric growth curves showed, during the first few hours, an increase in optical density (OD) before lysis. This increase in OD depended on the concentration of imipenem and was independent of the concentration of piperacillin. A good correlation was found between the pre-lytic increase in OD and the killing curve. The bactericidal activity rate of imipenem was concentration-dependent. Imipenem was rapidly bactericidal, in contrast to piperacillin.

Bacterial Proteins↗
PubMed1988

Bactericidal activity and killing rate of serum in volunteers receiving pefloxacin alone or in combination with ceftazidime, piperacillin or mezlocillin against Pseudomonas aeruginosa.

The activity of the combination of pefloxacin with ceftazidime, piperacillin, or mezlocillin was compared to the activity of the same antibiotics given alone, by measurement of serum bactericidal titres and the rate of killing of ten strains of Pseudomonas aeruginosa. Three groups of five volunteers each received pefloxacin (12 mg/kg iv) with or without ceftazidime, piperacillin or mezlocillin (25 mg/kg iv). Serum samples were obtained at the end of the infusion. The mean serum concentration of pefloxacin at this time was 13.9 mg/l (3.2, S.D.). The activity of each of the three combinations was identical to the corresponding activity of the beta-lactam alone. However, the emergence of resistance to pefloxacin was prevented by ceftazidime (five out of five strains), and piperacillin (two out of five strains). We conclude that combinations of pefloxacin with beta-lactam antibiotics may not increase efficacy against P. aeruginosa.

Anti-Bacterial Agents↗
PubMed1990

Inhibition of beta-lactamases by tazobactam and in-vitro antibacterial activity of tazobactam combined with piperacillin.

The in-vitro synergistic activity of tazobactam, a new beta-lactamase inhibitor, combined with piperacillin was tested against various beta-lactamase-producing strains. The beta-lactamase inhibitory activity of tazobactam against various known types of beta-lactamase was also tested in comparison with clavulanic acid or sulbactam. Tazobactam caused a remarkable reduction of the piperacillin MICs for penicillinase- and oxyiminocephalosporinase-producing strains and also showed a moderate synergistic effect against cephalosporinase-producing strains. The bactericidal activity of piperacillin was enhanced in combination with tazobactam. Tazobactam inhibited the penicillinases, and the oxyiminocephalosporinase produced by Proteus vulgaris, at low concentration. In these cases its activity was comparable with that of clavulanic acid and stronger than that of sulbactam. Tazobactam demonstrated a better inhibitory capability than sulbactam against the cephalosporinases tested. Tazobactam was able to inactivate intracellular beta-lactamase in Prot. vulgaris and Morganella morganii, confirming its ability to penetrate the cell membrane of these species.

Bacteria↗
PubMed1992

A comparative study of imipenem versus piperacillin plus gentamicin in the initial management of febrile neutropenic patients with haematological malignancies.

Three-hundred and twelve episodes of fever in 234 neutropenic patients with haematological malignancies were treated empirically with either imipenem or a combination of piperacillin and gentamicin. There were no significant differences in the percentages of patients responding to therapy at either 72 h (59% and 56% of assessable episodes in the imipenem and combination groups respectively) or at the end of treatment (55% and 53% of assessable episodes in the imipenem and combination groups respectively). Patients in the piperacillin plus gentamicin group experienced significantly more renal tubular damage whereas those who received imipenem suffered more nausea or vomiting. We conclude that imipenem monotherapy represents an acceptable alternative to piperacillin plus gentamicin as empirical therapy of the febrile neutropenic patient.

Adolescent↗
PubMed1993

Susceptibility survey of piperacillin alone and in the presence of tazobactam.

Among 325 fresh isolates of bacteria from 153 hospital patients with serious infections, 142 were susceptible to piperacillin, 129 were resistant and a further 54 exhibited a marked inoculum effect. Tazobactam restored the susceptibility of resistant isolates of Staphylococcus aureus and Staphylococcus epidermidis (except methicillin-resistant isolates), Haemophilus influenzae, Moraxella catarrhalis, Acinetobacter spp. and Bacteroides fragilis. Among 87 Enterobacteriaceae that were resistant to piperacillin, or showed an inoculum effect, 78 (89%) were restored to susceptibility by tazobactam. Pseudomonas spp. resistant to piperacillin were mostly resistant to the combination.

Bacteria↗
PubMed1988

Alterations in lower reproductive tract flora after single-dose piperacillin and triple-dose cefoxitin at vaginal and abdominal hysterectomy.

There are no current data regarding the effect of a newer, broad-spectrum penicillin on lower reproductive flora at hysterectomy. To identify any existing differential effect on species and their susceptibilities, we obtained pre- and postoperative lower reproductive tract culture material from 209 women who were given single-dose piperacillin, then placebo or triple-dose cefoxitin, intravenously for prophylaxis at vaginal and abdominal hysterectomy in a prospective, randomized, blinded clinical trial. Significantly more preoperative endocervical bacteria were susceptible to piperacillin. Piperacillin caused less alteration in the numbers of lower reproductive tract flora when preoperative species were compared with postoperative species. More resistance to cefoxitin was identified postoperatively in bacteria recovered from the vaginal cuff of women who remained uninfected.

Bacteria↗
PubMed1992

Pharmacokinetic study of piperacillin in newborns relating to gestational and postnatal age.

The pharmacokinetics of piperacillin after a single 75-mg/kg intravenous injection as analyzed in 28 neonates with gestational ages of 29 to 40 weeks (A = 29 to 31 weeks, B = 33 to 35 weeks, C = 38 to 42 weeks) and birth weights of 860 to 3900 g during 35 courses. Serum concentrations of piperacillin were determined by high pressure liquid chromatography. A one compartment open model characterized the disposition of piperacillin. Twenty courses were given between Day 3 and Day 5 of life. The elimination half-life and total body clearance were related to gestational age. Differences were significant between Groups A and B and Group C for half-life (4.3 +/- 1.9 and 3.35 +/- 0.75 vs. 2.47 +/- 0.72 hours) and for clearance (1.68 +/- 0.6 and 1.8 +/- 0.4 vs. 2.46 +/- 0.36 ml/min/kg). Volumes of distribution were similar in the 3 groups, from 516 +/- 108 to 633 +/- 226 ml/kg. Fourteen courses were given from Day 9 to Day 11 of life. The same differences were observed between Groups A and B and Group C. Elimination half-life was significantly reduced with simultaneous increase of the total body clearance. In clinical practice, 75-mg/kg intravenous injections every 12 hours during the first week of life and every 8 hours in the second week provide appropriate concentrations in infants of less than 36 weeks gestational age. In full term newborns the 75-mg dosage is appropriate but the number of injections must be increased to 3/24 h for the first week and 4 times daily thereafter.

Bacterial Infections↗
PubMed1983

Piperacillin therapy for Pseudomonas infections.

Piperacillin, a new broad spectrum semisynthetic penicillin derivative, was administered to 22 patients with 25 Pseudomonas aeruginosa infections. All initially responded favorably, although five complicated urinary tract infections and two infections involving prostheses relapsed. In 15 cases, microbiologic eradication of the Pseudomonas was achieved. Failure to achieve a clinical cure was correlated in all cases with the inability to eradicate the organism, which was the result of development of in vitro resistance to piperacillin during therapy (four cases) and of underlying disease impairing host responses. Adverse reactions to piperacillin included leukopenia (eight cases) and nephrotoxicity (two cases).

Adolescent↗
PubMed1987

Comparison of EMIT versus bioassay to evaluate inactivation of tobramycin by piperacillin.

We evaluated and compared the sensitivity of enzyme multiplied immunoassay (EMIT) and bioassay techniques in detecting the degree of inactivation of tobramycin by piperacillin in serum specimens. Specimens were prepared to contain initial tobramycin concentrations of 10 micrograms/ml and piperacillin concentrations of 62.5, 125.0, 250.0, and 500 micrograms/ml. The samples were stored at room temperature (25 degrees C), in the refrigerator (4 degrees C), and in the freezer (-10 degrees C) for up to 7 days. Tobramycin concentrations were determined by the two assay methods at the conclusion of 1, 3, and 6 h and 1, 3, 5, and 7 days of storage. The percentage of tobramycin activity as measured by EMIT and bioassay differed throughout the study period. Statistical analysis revealed that the assay method was the only significant variable to contribute to the variability observed in the differences of tobramycin concentration. Our results suggest that the bioassay technique is more sensitive than the EMIT assay for detecting the degree of inactivation of tobramycin by piperacillin. The EMIT assay overestimates tobramycin concentrations, which may be due to measurement of active and inactive tobramycin.

Analysis of Variance↗
PubMed2006

Determination of the biliary excretion of piperacillin in humans using a novel method.

AIM: To evaluate the applicability of a novel method to determine the biliary excretion of piperacillin. METHODS: Healthy volunteers were administered piperacillin i.v. Duodenal aspirates were collected via a custom-made oroenteric catheter; blood and urine also were collected. Gallbladder ejection fraction (EF) was determined by gamma scintigraphy and pharmacokinetic parameters were calculated using noncompartmental analysis. RESULTS: The fraction of the piperacillin dose excreted unchanged into bile was 1.1 +/- 0.3% (biliary clearance corrected for EF was 0.032 +/- 0.008 ml min(-1) kg(-1)). CONCLUSIONS: This methodology can be used to determine reliably the biliary clearance of drugs that are excreted only marginally into bile. Normalization of biliary clearance for EF significantly reduces intersubject variability of this parameter.

Adult↗