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PubMed2003

In vitro activity of combination therapy with cefepime, piperacillin-tazobactam, or meropenem with ciprofloxacin against multidrug-resistant Pseudomonas aeruginosa strains.

The prevalence of multidrug-resistant Pseudomonas aeruginosa strains has been increasing every year, and treatment with various antimicrobial combinations has been offered alternatively in the clinical practice. The aim of this study was to evaluate the in vitro effects of combinations of meropenem, cefepime, or piperacillin-tazobactam with ciprofloxacin against multidrug-resistant P. aeruginosa strains by the time-kill method. The results show that both the combination of two beta lactams with ciprofloxacin and three beta lactams with ciprofloxacin against 4 of 5 multidrug-resistant P. aeruginosa strains has no effect in vitro. The combination of one beta lactam (meropenem, cefepime, piperacillin-tazobactam) with ciprofloxacin has a synergistic effect against one strain of multidrug-resistant P. aeruginosa that is ciprofloxacin susceptible and resistant to meropenem, cefepime, and piperacillin-tazobactam. None of the combinations had an antagonistic effect against these multidrug-resistant strains.

Anti-Bacterial Agents↗
PubMed2006

Impact of a piperacillin-tazobactam shortage on antimicrobial prescribing and the rate of vancomycin-resistant enterococci and Clostridium difficile infections.

UNLABELLED: States in 2002 on antimicrobial prescribing and associated rates of vancomycin-resistant enterococci (VRE) and Clostridium difficile infections.Design. Retrospective chart review.Setting. University-affiliated medical center. Measurements and Main Results. Microbiologic reports, patient demographics, and antimicrobial utilization were evaluated for patients admitted 6 months before the shortage (March 1-August 31, 2001) and for 6 months during the shortage (March 1-August 31, 2002). Significant increases in usage of alternative mu-lactamase inhibitor combinations, cefepime, levofloxacin, vancomycin, clindamycin, and metronidazole were observed during the shortage; in contrast, a significant decrease in the use of ceftriaxone took place. No change in the rate of VRE infection was observed from before to during the piperacillin-tazobactam shortage. However, a paradoxical 47% decrease in the rate of C. difficile colitis was documented during the shortage. Subsequent multivariate analyses suggested the reduced use of ceftriaxone and increased use of levofloxacin, but not the reduced use of piperacillin-tazobactam, correlated with the decreased rate of C. difficile infections. CONCLUSION: The piperacillin-tazobactam shortage was associated with significant changes in antimicrobial prescribing, which resulted in a significant reduction in the rate of C. difficile but not VRE infections.

Anti-Bacterial Agents↗
PubMed2002

[Second multicenter study of the in vitro susceptibility to piperacillin-tazobactam].

A study was conducted in 1999 on the activity of piperacillin-tazobactam on 1349 strains collected in a Spanish multicenter study involving 10 hospitals. A total of 897 Gram-negative bacteria of the following genuses were collected: Escherichia coli (169), Klebsiella spp. (112), Pseudomonas spp. (122), Enterobacter spp. (92), Serratia spp. (44), Citrobacter spp. (37), Proteus spp. (114), Morganella spp. (49), Acinetobacter spp. (47), Stenotrophomonas spp. (47), Haemophilus spp. (45), Moraxella spp. (19). The Gram-positive bacteria included Staphylococcus aureus (116), Streptococcus pneumoniae (92), and Enterococcus spp. (114). Piperacillin-tazobactam activity against different anaerobic bacteria was also determined: Bacteroides spp. (88), Clostridium spp. (25), Prevotella spp. (5), Fusobacterium spp. (3) and Peptosteptococcus spp. (9). The piperacillin-tazobactam combination was found to maintain its activity against the isolated microorganisms with regard to the previous study.

Drug Therapy, Combination↗
PubMed1994

Compatibility of piperacillin sodium plus tazobactam with selected drugs during simulated Y-site injection.

The compatibility of piperacillin sodium plus tazobactam with selected drugs during simulated Y-site administration was studied. A 5-mL sample of piperacillin sodium 40 mg/mL plus tazobactam 5 mg/mL (Zosyn) in 5% dextrose injection was combined with a 5-mL sample of each of 75 other drugs at concentrations used clinically. Each combination was prepared in duplicate in glass culture tubes, with the order of mixing being reversed between the duplicates; storage was in constant fluorescent light at 22 degrees C. The admixtures were examined visually in normal fluorescent light and in high-intensity light zero, one, and four hours after preparation. A turbidimeter was used to measure the turbidity of each drug combination at the same intervals. Samples showing visual or turbidimetric evidence of incompatibility were subjected to particle sizing and counting. The majority of the drugs tested were compatible with Zosyn injection; most combinations had a turbidity of less than 0.1 nephelometric turbidity unit. However, 24 drugs exhibited various incompatibilities, including increased turbidity, particulate formation and precipitation, and color change. Piperacillin sodium 40 mg/mL plus tazobactam in 5% dextrose injection was visually compatible with the majority of the drugs tested for up to four hours at 22 degrees C but incompatible with 24 drugs.

Drug Incompatibility↗
PubMedDate not supplied

Piperacillin-Tazobactam: a new beta-lactam-beta-lactamase inhibitor combination.

We reviewed the spectrum of activity, pharmacokinetics, clinical efficacy, adverse effects, and relative advantages of piperacillin-tazobactam, a new beta-lactam-beta-lactamase inhibitor. Piperacillin-tazobactam has a wide spectrum of activity that includes gram-positive organisms such as staphylococci and streptococci, as well as many gram-negative aerobic and anaerobic bacteria. The combination distributes rapidly after parenteral administration and penetrates well into skin, lung, and intestinal mucosa. Compared with other beta-lactam-beta-lactamase inhibitor combinations, piperacillin-tazobactam has comparable efficacy in the treatment of intraabdominal infections, skin and soft tissue infections, and upper and lower respiratory tract infections. It may have better in vitro activity than the currently available combinations against selective bacteria that produce class I beta-lactamases (Richmond-Sykes classification). The combination is well tolerated, with diarrhea being the most common reported adverse effect. Additional controlled trials and clinical experience are required to define its role in clinical practice.

Drug Interactions↗
PubMed1998

Ciprofloxacin plus piperacillin is an equally effective regimen for empiric therapy in febrile neutropenic patients compared with standard therapy.

The purpose of this study was to test the comparative efficacy and toxicity of empiric gentamicin and ciprofloxacin, in combination with piperacillin, in febrile patients with treatment-induced neutropenia. Fifty patients were prospectively randomized to receive piperacillin plus gentamicin (PG), and 46 were randomized to receive piperacillin plus ciprofloxacin (PC). The groups were similar in age, sex, diagnosis, duration of neutropenia, and incidence of positive cultures. The two antibiotic regimens were associated with comparable rates of defervescence in the patients with gram-positive bacteremia. In the patients with gram-negative bacteremia and those with negative cultures, however, defervescence was more prompt in the PC group. In particular, 27% of the culture-negative patients on PC, compared to only 5% of those on PG, defervesced within 72 hr (P = 0.015). Because of the more prompt defervescence in the PC group, amphotericin B was used less frequently; 78% of the patients on PG compared with only 56% of those on PC were started on amphotericin B (P = 0.025). PC is an effective alternative to the more traditional PG for treatment of febrile neutropenic hosts who have not been given prophylactic quinolones. More important, PC appears to hasten defervescence compared with PG, especially in culture-negative patients and those with gram-negative bacteremia, and may decrease the necessity of additional antimicrobial agents such as amphotericin B.

Adult↗
PubMed1983

The effect of piperacillin dose on elimination kinetics in renal impairment.

The effect of drug dose on piperacillin elimination kinetics was examined in 27 adult subjects with varying renal function. Piperacillin, 15 mg/kg or 60 mg/kg, was given by bolus intravenous injection. The elimination half-life (t1/2) increased five-fold and plasma clearance (Clp) decreased by 80% in patients with renal failure. Both parameters were dose dependent in patients with normal renal function, but not in patients with renal insufficiency. Piperacillin dose dependent elimination is due primarily to capacity limited renal excretion.

Adult↗
PubMedDate not supplied

In vitro comparison of aminoglycoside activities and their synergistic action with piperacillin.

The antimicrobial activity of six aminoglycosides against 927 clinical isolates was compared. Gentamicin and netilmicin were most active against Enterobacteriaceae, followed by tobramycin greater than dibekacin greater than amikacin greater than kanamycin. Tobramycin was most active against Pseudomonas aeruginosa, both mucoid and non-mucoid strains, followed by dibekacin greater than gentamicin greater than netilmicin greater than amikacin greater than kanamycin. Piperacillin-aminoglycoside combinations acted (partially) synergistically against 33-40% of the Enterobacteriaceae, 34-58% of non-mucoid strains of P. aeruginosa and 63-84% of the mucoid strains of P. aeruginosa (p less than 0.01). Piperacillin + gentamicin was the most synergistic combination against Enterobacteriaceae and non-mucoid strains of P. aeruginosa (p less than 0.05). The action against Staphylococcus aureus and Streptococcus faecalis was mostly indifferent. Antagonism was not observed. In treating gram-negative infections where tissue concentrations are less important, every aminoglycoside combination may be effective; for Pseudomonas lung infections in cystic fibrosis, piperacillin + gentamicin or tobramycin will remain the drugs of first choice.

Aminoglycosides↗
PubMedDate not supplied

Piperacillin and netilmicin combination therapy for febrile episodes in neutropenic patients.

We assessed the efficacy of a piperacillin (3 x 4 g/d) and netilmicin (5 mg/kg/d) combination therapy for infections in febrile neutropenic patients. The study was conducted over a 30-month period and 203 patients were included. Bone marrow transplant recipients were not included in this study. Origin of infection was documented in 101 (50%) episodes: 33 fungal, viral or parasitic infections and 68 bacterial infections mainly composed of septicemia. Of the 169 evaluable patients with proved bacterial infections or non-documented infections, 129 (76%) recovered with the piperacillin and netilmicin combination treatment. All gram-positive bacterial infections failing first line therapy were cured after the addition of vancomycin. Piperacillin and netilmicin appeared very effective in this large monocentric prospective study. It does not seem necessary to include vancomycin in first line therapy of infections of the neutropenic patients in our institution; however, vancomycin must be added early in the case of suspected or documented staphylococcal infection failing empiric treatment.

Acute Disease↗
PubMed1989

[Acute interstitial nephritis following piperacillin].

A 75-year-old woman developed fever, exanthema and nonoliguric renal failure 16 days after the beginning of Piperacillin treatment. Renal biopsy revealed lympho-plasma-cellular acute interstitial nephritis (AIN). A lymphocyte-transformation-test showed significant stimulation of patient's lymphocytes by Piperacillin. Corticosteroid-therapy correlated to clinical and renal improvement. Nevertheless the patient died of foudroyant septicemia caused by E. coli. Our report describes the first immunologically documented case of AIN following Piperacillin treatment.

Aged↗
PubMed1983

Effect of azlocillin and piperacillin in subinhibitory and inhibitory concentrations on Staphylococcus aureus and Pseudomonas aeruginosa in broth, in serum and in the presence of human polymorphonuclear leukocytes.

The bactericidal activity of azlocillin and piperacillin was tested at concentrations of 1/4 the MIC, the MIC and four-fold the MIC agents a serum-resistant Staphylococcus aureus and a serum-resistant Pseudomonas aeruginosa strain in broth, in serum and in the presence of leukocytes. The antibacterial activity of azlocillin and piperacillin in serum against Staphylococcus aureus was slightly better than in broth (p greater than 0.05); both compounds were distinctly less active against Pseudomonas aeruginosa in serum than in broth (p less than 0.05). Both antibiotics enhanced susceptibility of Pseudomonas aeruginosa to leukocyte killing without serum (p less than 0.05), whereas leukocyte killing of Staphylococcus aureus was hardly improved even at the MIC and four-fold the MIC of both compounds. The antibacterial activity of azlocillin and piperacillin against both bacterial strains was most pronounced in the presence of leukocytes and serum. A marked bactericidal effect was achieved at 1/4 the MIC, the effect not being further significantly enhanced (p greater than 0.05) at the MIC or four-fold the MIC.

Azlocillin↗
PubMed1982

In vitro activity of ceftazidime, cefotaxime and piperacillin against multi-resistant gram-negative bacteria tested with a modified agar dilution method.

The minimum inhibitory concentrations of ceftazidime, cefotaxime and piperacillin were determined for 870 multi-resistant gram-negative bacterial strains by means of a modified agar dilution technique using dishes with 25 compartments. This technique facilitates the reading of the MICs, reduces the risk of inoculation errors, and eliminates interference of interaction of bacterial strains. Ceftazidime and cefotaxime inhibited 90% of the Enterobacteriaceae strains at concentrations of 3.12 mg/l and 1.56 mg/l respectively. Ceftazidime and piperacillin inhibited 90% of the Pseudomonas aeruginosa strains at concentrations of 6.25 mg/l and 12.5 mg/l respectively. Mucoid Pseudomonas aeruginosa strains were more susceptible to the antibiotics tested, especially piperacillin, than non-mucoid strains.

Anti-Bacterial Agents↗
PubMed1985

Antibiotics and immunomodulation: effects of cefotaxime, amikacin, mezlocillin, piperacillin and clindamycin.

The effects of 7 days' chemotherapy on the humoral and cellular parameters of the host immune system are described. In Balb/c mice the effects of cefotaxime, amikacin, mezlocillin, piperacillin and clindamycin were examined. The delayed-type hypersensitivity reaction, as well as the IgM and IgG responses, were suppressed by four of the five drugs tested: cefotaxime, amikacin, mezlocillin and piperacillin. One to two weeks after completion of chemotherapy with cefotaxime and amikacin, these parameters returned to normal values, whereas the mezlocillin- or piperacillin-modified reactions were still suppressed after 20 days. The concanavalin A and lipopolysaccharide-induced proliferative activities of mouse spleen cells were suppressed, especially by mezlocillin. The possible consequences of the immunomodulating effects of antibiotics for antimicrobial chemotherapy are discussed.

Amikacin↗
PubMed2003

Piperacillin-tazobactam is more effective than ceftriaxone plus gentamicin in febrile neutropenic patients with hematological malignancies: a randomized comparison.

GOALS: Efficacy and costs of empirical antibacterial therapy in febrile neutropenic patients are important issues. Several strategies have been reported to be similarly effective: monotherapy with cefepime, ceftazidime or a carbapenem or duotherapy with an antipseudomonal beta-lactam antibiotic or ceftriaxone in combination with an aminoglycoside. Piperacillin-tazobactam monotherapy is promising, but its role in this setting still has to be defined. PATIENTS AND METHODS: Of 212 consecutive febrile episodes in 130 neutropenic patients with hematological malignancies randomized to receive either piperacillin-tazobactam (4.5 g every 8 h; group A) or ceftriaxone (2 g once daily plus gentamicin 5 mg/kg once daily; group B), 183 episodes (98 group A, 85 group B) were evaluable for response. RESULTS: Defervescence within 72 h without modification of the antibiotic therapy was achieved in 56/98 episodes (57.1%) in group A and in 30/85 (35.3%) in group B (P=0.0047). If fever persisted, teicoplanin plus gentamicin (group A) or teicoplanin plus ciprofloxacin (group B) were added. All patients still febrile then received meropenem, teicoplanin and amphotericin B. With these modifications of antibiotic therapy, 89.8% of patients in group A had responded at 21 days but only 71.8% in group B (P=0.005). The mean total antibiotic drug cost in group A was only 39.4% of that in group B (euro 445 versus euro 1129; P=0.010). CONCLUSION: Piperacillin-tazobactam monotherapy is significantly more effective and cost-efficient than ceftriaxone plus gentamicin as first-line therapy in febrile neutropenic patients with hematological malignancies.

Adolescent↗
PubMed2004

Piperacillin-tazobactam and netilmicin as a safe and efficacious empirical treatment of febrile neutropenic children.

GOALS OF WORK: We evaluated piperacillin-tazobactam in association with netilmicin (TN) in the early empirical treatment of neutropenic children, as data are limited in number. PATIENTS AND METHOD: In 1996, an observational study was initiated to assess the efficacy and safety of this association, with a glycopeptide (TNG) if needed. The impact on the bacterial ecology of our unit was also observed. Children were treated for hematological malignancy or solid tumor between September 1996 and December 1998 and presented a febrile neutropenia. RESULTS: There were 148 evaluable febrile neutropenic episodes in 104 patients. Median age was 7 years, 55% of the episodes were fever of unknown origin, 22% were clinically documented and 23% microbiologically documented (27 bacteriemia). A glycopeptide was added in 67 episodes. The initial unmodified treatment was successful in 114 episodes (77%): 75/81 episodes in the TN group and 39/67 in the TNG group. For successful episodes, median treatment duration was 6 days. There were 22 febrile recurrences. These patients, as well as initial failures, always responded to a second-line treatment. One child was considered a failure because he developed a skin rash probably due to piperacillin-tazobactam and required another beta-lactamase. CONCLUSION: This study suggests that piperacillin-tazobactam in association with netilmicin presents a satisfactory efficacy and a good tolerance as empirical therapy for febrile neutropenic children. It allowed us to maintain the bacterial ecology of our unit.

Adolescent↗
PubMed1994

A randomized prospective study of cefoxitin versus piperacillin in appendicectomy.

A randomized prospective study of antibiotic prophylaxis using a single dose of either cefoxitin or piperacillin is presented. The trial was carried out in Al Ain Hospital in the period 1989-1992 on 250 adult patients with non-perforated appendicitis. One group (124 patients) received 2 g cefoxitin, the other group (126 patients) 2 g piperacillin. Antibiotics were administered intravenously in the operating theatre immediately before surgery. Wound infection occurred in three patients, 2.4% of the cefoxitin group and in five patients (4%) of the second group (with no significant difference). The commonest infecting organisms were Escherichia coli (5 out of 8). Mean hospital stay for patients with wound infection was 15 days (range 12-21) compared with 6 days, (range 4-8) for non-infected cases. Prophylactic cefoxitin or piperacillin were each therefore similarly effective in minimizing the rate of wound infections in patients with non-perforated appendicitis.

Acute Disease↗
PubMed2004

Impact of tazobactam pharmacokinetics on the antimicrobial effect of piperacillin-tazobactam combinations.

Pharmacokinetic-pharmacodynamic (PK-PD) modelling was used to study the impact of the pharmacokinetics of tazobactam on the antimicrobial effect of piperacillin-tazobactam combinations. An in vitro experiment using a novel dilution system was performed to compare the effects of two conditions of the combination therapy against Escherichia coli ATCC35218, a beta-lactamase producing bacterium. Both conditions simulated the same initial concentrations of piperacillin and tazobactam, but different elimination half-lives for tazobactam. The killing and regrowth kinetics of E. coli clearly indicated that there is a difference in the antimicrobial effects when there is a difference in the pharmacokinetics of tazobactam in the combination therapy. The results show that for equal piperacillin exposure, different tazobactam half-lives will have a significant effect on antimicrobial outcome.

Anti-Bacterial Agents↗
PubMed2001

Study on fluorescent property of degrading products of piperacillin and its analytical application.

The fluorimetric property of the degrading products of piperacillin has been studied in detail. The studies on degrading pH, degrading time, detection alkalinity and other corresponding analytical parameters of acid degradation have been made. Then fluorometry of piperacillin was established by producing its stable fluorescent products. The detection limit for acid degradation analytical method is 2.34 ng/ml, the linear range is 7.80-4.0 x 10(2) ppb. The analytical sensitivity, precision and stability of degrading products of acid degradation are satisfactory, which has been used for the determination of the trace piperacillin in human serum and urine with satisfactory results.

Humans↗