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PubMed1987

Piperacillin and a combination of clindamycin and gentamicin for the treatment of hospital and community acquired acute pelvic infections including pelvic abscess.

Therapy for acute polymicrobial pelvic infections is empiric and must include predictable anaerobic coverage. Single agent therapy, if effective, is advantageous for the patient, nurses, pharmacy and hospital. Piperacillin sodium was compared with a combination of clindamycin and gentamicin as therapy for 63 female patients who were hospitalized with acute pelvic infections including pelvic abscess complicating community acquired salpingitis. Over-all clinical efficacy with piperacillin was 96.8 per cent and 90.3 per cent for clindamycin and gentamicin. Fewer bacteria demonstrated in vitro resistance to piperacillin (p = 0.008) and the cost of treatment for these infections was significantly less with piperacillin (p less than 0.05). Serious adverse reactions were not observed with either regimen. Piperacillin provides effective, cost-efficient therapy for women with acute polymicrobial pelvic infections.

Abscess↗
PubMed1986

A comparison of piperacillin and clindamycin plus gentamicin in women with pelvic infections.

The efficacy and safety of piperacillin were compared with those of clindamycin plus gentamicin in 74 women with obstetric or gynecologic infections (such as endometritis, salpingitis and septic abortion). Thirty-five of the patients in the group treated with piperacillin and 33 of the patients in the group treated with clindamycin plus gentamicin were clinically cured. Clinical failure occurred in two patients in the group treated with piperacillin (salpingitis in one and endometritis in the other patient) and relapse of salpingitis occurred in one. Three patients who were given clindamycin plus gentamicin (all with salpingitis) did not respond to therapy. The most frequently isolated organisms were Neisseria gonorrhea and Bacteroides species. Adverse clinical experiences and the results of laboratory tests were fewer in the group treated with piperacillin than in the patients who received the combination regimen; in neither instance was treatment discontinued because of these effects. Thus, piperacillin was as safe and effective as a combination of clindamycin plus gentamicin.

Abortion, Septic↗
PubMed1982

Piperacillin and gentamicin v carbenicillin and gentamicin for treatment of serious gram-negative infections.

Piperacillin sodium, a new penicillin with remarkable in vitro activity against Pseudomonas aeruginosa and other Gram-negative bacilli, and gentamicin sulfate were compared with carbenicillin disodium and gentamicin in a prospective, randomized, double-blind comparison for treating serious Gram-negative infections. Of the 32 patients whose courses were "evaluable" for efficacy, 12 of 14 who received piperacillin and gentamicin and 13 of 18 who received carbenicillin and gentamicin had favorable outcomes. Of the 99 patients whose courses were evaluable for toxicity, nine of 51 recipients of piperacillin and gentamicin and 15 of 48 recipients of carbenicillin and gentamicin suffered clinical reactions possibly, probably, or definitely related to the penicillin. No statistically significant differences were found in the two groups in the frequencies of biochemical abnormalities, including hypokalemia, that occurred in 19 or 44 recipients of piperacillin and gentamicin and 16 of 45 recipients of carbenicillin and gentamicin. Thus, this study did not prove differences in efficacy of toxicity for piperacillin and gentamicin plus carbenicillin and gentamicin for serious Gram-negative infections.

Bacterial Infections↗
PubMed1982

Piperacillin v Carbenicillin in the therapy for serious infections.

One hundred seven patients were treated with either piperacillin (56) or carbenicillin (51) in an open randomized trial of hospitalized patients with pleuropulmonary (40), urinary tract (26), gynecologic (21), skin and soft-tissue (eight), joint (five), bone (three), and miscellaneous other infections (four). Patients with urinary tract infections were given 150 mg/kg/day of piperacillin sodium or 200 mg/kg/day or carbenicillin sodium in divided doses every six hours intravenously. Patients with other infections were given 250 mg/kg/day of piperacillin sodium and 450 mg/kg/day of carbenicillin sodium; 53/56 (95%) patients treated with piperacillin and 45/51 (88%) patients treated with carbenicillin were cured clinically. In general, the drugs were well tolerated. There were, however, more adverse experiences in the groups taking carbenicillin. Of special interest was the finding of liver function test abnormalities in 17/78 (21%) carbenicillin recipients (evaluative and nonevaluative cases). We concluded that piperacillin was effective and safe. It has potential for use in a great variety of infections.

Adult↗
PubMed1980

In vitro activity of piperacillin compared with that of ampicillin, ticarcillin, azlocillin, and mezlocillin.

The antibacterial activity of ampicillin, ticarcillin, azlocillin, mezlocillin and piperacillin was investigated in 1112 fresh clinical isolates using the microdilution technic. Ampicillin was the most active agent against enterococci and ticarcillin against Staphylococcus aureus, 91% of the latter being inhibited by 32 mg/l. 95% of strains of Pseudomonas aeruginosa were susceptible to piperacillin and 90% to ticarcillin and azlocillin. Piperacillin was still active against half of the azlocillin-resistant strains of Pseudomonas aeruginosa. Against the Enterobacteriaceae, mezlocillin and piperacillin were equally active: 31% of these strains were resistant to both drugs. Amongst the various strains the percentage of resistance was highest in Klebsiella (60%). Analysis of resistance patterns of Enterobacteriaceae showed almost completely parallel resistance between these two drugs the difference being less than 3%. Piperacillin, however, had the broadest spectrum of all the penicillins tested.

Ampicillin↗
PubMed1981

Evaluation of cefmetazole and piperacillin with or without tobramycin for infections in patients with hematological disorders.

The combination of cefmetazole and piperacillin was compared with the combination of cefmetazole, piperacillin and tobramycin in the treatment of 20 patients with hematological disorders. The response rate was similar for both treatments (90% vs. 80%), and the difference was not statistically significant. The rate of serum glutamic pyruvic transaminase elevation was higher in patients treated with cefmetazole, piperacillin and tobramycin than in those treated with cefmetazole and piperacillin. Cefmetazole and piperacillin without tobramycin appear to be an effective combination with acceptable toxicity for empirical therapy of febrile episodes occurring in patients with hematological disorders.

Adolescent↗
PubMed1983

Comparative study of parenteral piperacillin and cefoxitin in the treatment of surgical infections of the abdomen.

Patients who had contaminated traumatic perforations of the gastrointestinal tract and those with acute peritonitis resulting from acute surgical inflammatory conditions were treated with piperacillin or cefoxitin infused intravenously as single therapy for a minimum of five days. Thirty-four patients were given 4.5 grams of piperacillin every six hours and 26 patients, 2.0 grams of cefoxitin every six hours. In the piperacillin group, 63 organisms (34 aerobes and 29 anaerobes) were isolated from pretreatment cultures, while in the cefoxitin group, 73 organisms (35 aerobes and 38 anaerobes) were isolated. Clinical recovery was achieved in 31 of 34 patients receiving piperacillin therapy and in 24 of 26 patients receiving cefoxitin therapy. Organisms were found to be resistant to the respective drug in two piperacillin-treated patients and in one cefoxitin-treated patient, and the patients were given other antibacterial treatment. One patient from each treatment group died of causes unrelated to septic conditions. No serious adverse effects occurred from either antibiotic.

Abdomen↗
PubMedDate not supplied

Piperacillin-tazobactam pharmacokinetics in patients with intraabdominal infections.

STUDY OBJECTIVE: To determine the appropriate compartmental and noncompartmental pharmacokinetic parameters for intravenous piperacillin and tazobactam. DESIGN: Sequential selection of patients entered into a randomized, open-label clinical efficacy trial. SETTING: Los Angeles County-University of Southern California Medical Center. PARTICIPANTS: Sequential sample of 18 patients admitted for intraabdominal infections and consented into a comparative antibiotic trial. INTERVENTIONS: Patients received piperacillin 4 g plus tazobactam 500 mg by intravenous intermittent infusion every 8 hours. MEASUREMENTS AND MAIN RESULTS: The estimated noncompartmental pharmacokinetic parameters (mean +/- SD) for piperacillin and tazobactam, respectively, were as follows: maximum concentration in plasma 218.7 +/- 48.9 micrograms/ml and 27.8 +/- 9.1 micrograms/ml; half-life 1.07 +/- 0.22 hours and 1.00 +/- 0.27 hours; elimination rate constant 0.67 +/- 0.13 hr-1 and 0.73 +/- 0.18 hr-1; area under the concentration-time curve from zero hour to infinity 288.5 +/- 71.25 mg.hr/L and 36.3 +/- 9.55 mg.hr/L; total plasma clearance 14.75 +/- 3.93 L/hour and 14.78 +/- 4.39 L/hour; renal clearance 5.69 +/- 1.94 L/hour and 7.85 +/- 3.37 L/hour; volume of distribution at steady state 21.00 +/- 4.18 L and 22.47 +/- 8.27 L; and mean residence time 1.72 +/- 0.29 hours and 1.79 +/- 0.35 hours. CONCLUSION: Our findings were similar to those in other surgical patient models. The two-compartmental model best described piperacillin and tazobactam disposition in our patients. Bayesian analyses of the two-compartment models of piperacillin and tazobactam were able to predict trough, peak, and 2-hour postadministration levels without bias.

Abdomen↗
PubMed1994

Stability of piperacillin sodium-tazobactam sodium and ranitidine hydrochloride in 0.9% sodium chloride injection during simulated Y-site administration.

The stability of piperacillin sodium plus tazobactam sodium and ranitidine hydrochloride in 0.9% sodium chloride injection during simulated Y-site administration was studied. Triplicate test solutions of piperacillin 40 mg/mL plus tazobactam 5 mg/mL (as the sodium salts) or piperacillin 80 mg/mL plus tazobactam 10 mg/mL (as the sodium salts) were mixed 1:1 with ranitidine 0.5 and 2.0 mg/mL (as the hydrochloride salt). The solutions were stored at 23 degrees C, and samples were removed at zero, one, two, and four hours for measurement of drug concentration by stability-indicating high-performance liquid chromatography. At the time of sampling and before any dilution, each sample was visually inspected for color and precipitation, and pH was determined. At all sampling times, the concentrations of piperacillin, tazobactam, and ranitidine were > 90% of initial concentrations. There were no substantial changes in pH or color. Tazobactam 5 mg/mL (as the sodium salt) and ranitidine 0.5 and 2 mg/mL (as the hydrochloride salt) in 0.9% sodium chloride injection were stable for up to four hours during simulated Y-site administration. Piperacillin 80 mg/mL plus tazobactam 10 mg/mL (as the sodium salts) and ranitidine 0.5 and 2 mg/mL (as the hydrochloride salt) were stable for up to four hours during simulated Y-site administration.

Chromatography, High Pressure Liquid↗
PubMed1993

Use of pharmacodynamic concepts in developing a cost-effective dosing method for piperacillin.

Because they were almost always used in combination with an aminoglycoside, piperacillin and mezlocillin were considered therapeutic alternatives at Hartford Hospital, a 900-bed teaching facility. To determine an appropriate comparative dose, the bactericidal activities of 5 gm of mezlocillin and 4 gm and 3 gm of piperacillin were compared. The results demonstrated that 4 gm of piperacillin possessed stronger bactericidal activity than either 3 gm of piperacillin or 5 gm of mezlocillin. Hartford Hospital has since approved an antibiotic management program using 4 gm of piperacillin every 8 hours, thereby reducing the daily cost of antibiotic therapy. The modified program offers the hospital measurable cost savings without jeopardizing the quality of care.

Cost-Benefit Analysis↗
PubMed1997

Pharmacokinetic-pharmacodynamic modelling of the in vitro antiinfective effect of piperacillin-tazobactam combinations.

PURPOSE: The aim of the study was to investigate the in vitro antiinfective effect of piperacillin-tazobactam (PIP-TZB) combinations on Escherichia coli in simulations of free concentration time profiles of both drugs, similar to those obtained in human tissue after i.v. bolus administrations. METHODS: An in vitro dilution model was used to expose E. coli ATCC 35218 (beta-lactamase producer) to various piperacillin-tazobactam concentration profiles obtained after i.v. bolus multiple dose, using different dose ratio combinations (1:4, 1:8, 1:16) and dosing regimens, ranging from once-a-day to 4 times a day. The antimicrobial effect was evaluated by determination of the number of bacteria over time. The concentration of PIP in the model was determined by HPLC. RESULTS: A modified Emax model was used to describe the pharmacodynamic effect. The model was linked with the piperacillin concentrations determined experimentally to provide a pharmacokinetic-pharmacodynamic (PK-PD) model. The EC50 for piperacillin alone averaged 5.66 +/- 0.29 micrograms/ml. The EC50 for all doses of piperacillin combined with 0.5 g of tazobactam were dose-dependent and averaged 1.70 +/- 0.56, 3.95 +/- 1.02, and 6.14 +/- 1.24 micrograms/ml for PIP 2, 4, and 8 g, respectively. By increasing the dose of TZB in combination with a fixed dose of PIP, a decreased EC50 was observed. CONCLUSIONS: The PK-PD model allowed a detailed evaluation of the dosing regimens investigated. The results suggested that for these combinations, 3 times a day administration is as effective as 4 times a day. Pharmacodynamic activity of the combinations can be prolonged by sufficiently high inhibitor concentrations.

Colony-Forming Units Assay↗
PubMed1979

In vitro activity of furazlocillin (Bay k 4999) compared with those of mezlocillin, piperacillin, and standard beta-lactam antibiotics.

The activity of furazlocillin (Bay k 4999) was compared with those of mezlocillin, piperacillin, and standard beta-lactam antibiotics against a number of gram-positive and gram-negative organisms. These new expanded-spectrum penicillins were less active than penicillin G against most gram-positive organisms. Furazlocillin, mezlocillin, and piperacillin showed activity comparable to ampicillin and penicillin G against Haemophilus influenzae and penicillin-susceptible neisseriae, respectively. None of the drugs tested was effective against penicillin-resistant gonococci. The activity of furazlocillin was greater than that of mezlocillin, piperacillin, ampicillin, or carbenicillin against many Enterobacteriaceae. However, certain beta-lactam-resistant strains among these organisms were not highly susceptible to any of the three new penicillins. Furazlocillin was less active than piperacillin against Pseudomonas aeruginosa but was more active than carbenicillin or mezlocillin. Inoculum effects and discrepancies between minimal inhibitory concentrations and minimal bactericidal concentrations were observed with furazlocillin, mezlocillin, and piperacillin against several genera. The kinetics of bacterial killing by the new penicillins were often slow and incomplete over 24 h, especially in tests with Enterobacter and P. aeruginosa. Synergy was demonstrated between furazlocillin and aminoglycosides against a variety of gram-negative bacilli and Streptococcus faecalis.

Aminoglycosides↗
PubMed1977

Piperacillin (T-1220), a new semisynthetic penicillin: in vitro antimicrobial activity comparison with carbenicillin, ticarcillin, ampicillin, cephalothin, cefamandole and cefoxitin.

Piperacillin (T-1220) is a new semisynthetic penicillin with an unusually broad spectrum of antimicrobial activity. In vitro comparisons of this drug with 6 other beta-lactam antimicrobics (ticarcillin, carbenicillin, ampicillin, cephalothin, cefamandole and cefoxitin) were conducted. These included minimal inhibitory concentrations (MIC) against 394 bacterial isolates, the minimal lethal concentrations (MLC) against 79 of those, as well as the effect of inoculum size on the MIC and MLC of the drugs. Piperacillin had significantly greater activity than did the other penicillins against Pseudomonas species and Klebsiella pneumoniae. Against P. aeruginosa piperacillin was 8- and 16-fold more active than ticarcillin and carbenicillin, respectively. The MLC of piperacillin rarely differed from the MIC by more than one log2 dilutions except against P. aeruginosa in which the MLC was 4-fold greater or more than the MIC of 45% of isolates tested. Ticarcillin, carbenicillin and cefoxitin showed minimal inoculum size effects. Cefamandole results showed the greatest inoculum size variation with 55% and 37% of isolates showing an 8-fold increase in MIC and MLC respectively by increasing inoculum from 10(5) to 10(7) CFU/ml. Piperacillin was intermediately effected having 25% of strains greater than 8-fold increase in MIC.

Ampicillin↗
PubMed1979

Piperacillin (T-1220), a new semisynthetic penicillin. II. In vitro antimicrobial activity and synergy comparison with carbenicillin and gentamicin.

Piperacillin, a new semisynthetic penicillin, was found to have potent antimicrobial activity against nearly all (405) tested bacterial species. Piperacillin was consistently 4 approximately 16-fold more active than carbenicillin against the Enterobacteriaceae, 16 approximately 32-fold against Pseudomonas aeruginosa and Pseudomonas species, and 16-fold against Streptococcus faecalis. Carbenicillin and piperacillin were equally effective against Staphylococcus aureus, but inactivated by beta-lactamase. A 38% overall synergy rate for the piperacillin-gentamicin combination was identified, a finding similar to that for carbenicillin-gentamicin. Highest incidences of synergy were found for both antibiotic pairs tested on gentamicin-resistant isolates (Ps. aeruginosa and Providencia). In vitro findings suggest that piperacillin alone or in combination with aminoglycosides may be highly efficacious in the treatment of most serious bacterial infections.

Bacteria↗
PubMed1994

Comparative in-vitro activity of piperacillin-tazobactam against recent clinical isolates, a Dutch national multicentre study.

In this Dutch national survey piperacillin-tazobactam had a MIC90 of < or = 8 mg/L for Enterobacteriaceae (Enterobacter cloacae excluded) and Pseudomonas aeruginosa, 64 mg/L for E. cloacae, and 4 mg/L for Acinetobacter spp. The corresponding MIC90 values for piperacillin alone were < or = 256 mg/L, 256 mg/L, 16 mg/L and 32 mg/L. Only 15 of 93 piperacillin-tazobactam resistant E. cloacae strains were sensitive for ceftazidime, whereas 41 of 93 ceftazidime-resistant E. cloacae were sensitive to piperacillin-tazobactam.

Bacteria↗
PubMed2003

Treatment with a broad-spectrum cephalosporin versus piperacillin-tazobactam and the risk for isolation of broad-spectrum cephalosporin-resistant Enterobacter species.

Receipt of a broad-spectrum cephalosporin is a strong risk factor for isolation of broad-spectrum cephalosporin-resistant Enterobacter species, and yet the risk from other broad-spectrum beta-lactams hydrolyzed by group 1 beta-lactamases has not been well characterized. We compared the risk conferred by broad-spectrum cephalosporins to that conferred by piperacillin-tazobactam, alone or in combination with an aminoglycoside or a fluoroquinolone. A retrospective cohort was monitored from treatment onset until a broad-spectrum cephalosporin-resistant Enterobacter strain was isolated or the patient was discharged. There were 447 patients in the piperacillin-tazobactam group and 2,341 patients in the broad-spectrum cephalosporin group. Groups were similar in age (mean, 62.5 years). The piperacillin-tazobactam group had a smaller percentage of men (32% versus 44%, P < 0.001) and a lower rate of intensive care unit stay (25% versus 38%, P < 0.001) but a higher rate of surgery (41% versus 26%, P < 0.001). Groups differed in the distribution of comorbidities. Resistant Enterobacter strains were isolated from 62 patients, 2% in each group (hazard ratio [RR] = 1.02 [P = 0.95]). In multivariable analysis, risk was similar among treatment groups (RR = 0.71 [P = 0.32]). Intensive care unit stay and surgery were associated with increased risk (RR = 4.53 [P < 0.001] and RR = 1.97 [P = 0.015], respectively), fluoroquinolones were protective (RR = 0.24 [P = 0.003]), and aminoglycosides did not affect risk (RR = 0.98 [P = 0.95]). The protective effect of fluoroquinolones against isolation of broad-spectrum cephalosporin-resistant Enterobacter spp. and the equivalence in risk associated with piperacillin-tazobactam and broad-spectrum cephalosporins may have important clinical and epidemiologic implications.

Anti-Bacterial Agents↗
PubMed2004

Replacement of broad-spectrum cephalosporins by piperacillin-tazobactam: impact on sustained high rates of bacterial resistance.

We have previously observed a significant reduction of ceftriaxone resistance in Proteus mirabilis associated with an increase in the use of cefepime, along with a decrease in the consumption of broad-spectrum cephalosporins (CEP). However, we did not observe such a reduction with Klebsiella pneumoniae. Therefore, we sought to determine whether replacement of CEP by piperacillin-tazobactam might be useful in reducing sustained high rates of CEP resistance by this organism. We used a 6-month "before and after model"; during the second (intervention) period, most prescriptions of CEP were changed to piperacillin-tazobactam at the pharmacy. No additional barrier precautions were undertaken. During intervention, consumption of ceftazidime decreased from 17.73 to 1.14 defined daily doses (DDD) per 1,000 patient-days (P < 0.0001), whereas that of piperacillin-tazobactam increased from 0 to 30.57 DDD per 1,000 patient-days (P < 0.0001). The levels of resistance to CEP by K. pneumoniae and P. mirabilis decreased from 68.4 and 57.9% to 37.5 and 29.4%, respectively (P < 0.05). We conclude that replacement of ceftazidime by piperacillin-tazobactam might be a suitable strategy to decrease endemic CEP resistance by K. pneumoniae and P. mirabilis, even where there are high bacterial resistance rates and irrespective of any additional precautions for controlling nosocomial infection.

Anti-Bacterial Agents↗
PubMedDate not supplied

Suspected acute interstitial nephritis induced by piperacillin-tazobactam.

A 51-year-old woman developed an acute onset of renal dysfunction accompanied by rash, lumbar pain, arthralgias, fever, eosinophiluria, and an elevated serum creatinine after 6 days of intravenous piperacillin-tazobactam therapy. On discontinuing piperacillin-tazobactam and after a 21-day course of prednisone, the patient's constitutional symptoms dissipated and her renal function returned to baseline. Acute interstitial nephritis has been reported as an adverse effect of many drugs, including antibiotics, but not, to our knowledge, after piperacillin-tazobactam. The time course of events suggested that piperacillin-tazobactam was the cause of acute interstitial nephritis in this patient.

Acute Disease↗