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PubMed1986

In vitro studies of the synergism of piperacillin and netilmicin against blood culture isolates.

The purpose of this study was to evaluate the in vitro synergism between piperacillin and netilmicin against microorganisms isolated from Danish patients with septicemia and to examine the influence of inactivation of piperacillin among these bacteria on the synergy results. A total of 132 stains was examined: Escherichia coli 20, indole-positive Proteus 17, Klebsiella pneumoniae 18, Enterobacter cloacae 20, Pseudomonas aeruginosa 20, Staphylococcus aureus 20, and coagulase-negative staphylococci 17. Synergy testing was performed by checkerboard titration in microtiter trays. The ability of the strains to inactivate piperacillin was examined by the clover-leaf test. Synergism was found for 52% of the strains and partial synergism for 32%. Antagonism was not found. Of the piperacillin-resistant strains synergism could be demonstrated in 80% compared with 33% of the piperacillin-susceptible strains (p less than 0.001). No significant correlation was seen between the results of the synergy test and the results of the susceptibility test to netilmicin. The frequency of piperacillin inactivation according to the clover-leaf test was significantly higher among the strains with synergism than among all the others (p less than 0.02). The combination of piperacillin and netilmicin gave good results concerning the in vitro synergism. This synergism was probably sometimes caused by netilmicin disturbing the bacterial production of piperacillin-inactivating proteins.

Bacteria↗
PubMed1990

Turbidimetric and microscopic analysis of Bacteroides fragilis exposed to tazobactam and piperacillin alone and in combination.

Tazobactam, a non-amino penicillanic acid sulfone, is a new beta-lactamase inhibitor and acts synergistically with piperacillin against clinical isolates of beta-lactamase-producing Bacteroides fragilis. The effectiveness of this inhibitor has been demonstrated by reduction of piperacillin MIC values and growth curves in two combinations (ratio 8:1 and 4:1). Tazobactam has an intrinsic activity against B. fragilis (MIC = 4-8 micrograms/ml). Phase contrast microscopy of treated cells showed cell-wall-deficient bacteria, predominantly filaments for piperacillin and spheric bodies for tazobactam. The combination of these two drugs induced large bulging filaments. This would suggest that with this organism, tazobactam binds to PBP2 while piperacillin binds to PBP3. The growth curves obtained with the MS-2 system showed: (1) a significant deviation (lower OD value) from the control curve with piperacillin at 1/4 MIC and numerous irregularities as compared to the control, due to the presence of filament clusters; (2) a deviation from the control curves without irregularities, quite different than these observed with piperacillin while using tazobactam at 1/8 MIC, and (3) a deviation from the control curve for lower piperacillin values in piperacillin-tazobactam combinations (8:1-4:1). In conclusion, the synergistic efficiencies of piperacillin/tazobactam against B. fragilis act in two ways, inhibition of beta-lactamase and a probable competition of PBPs.

Bacteroides fragilis↗
PubMed1984

Comparative efficacy of piperacillin versus carbenicillin for complicated urinary tract infections.

In this controlled, randomized clinical trial we compared piperacillin and carbenicillin in the treatment of complicated urinary tract infections. 24 patients received piperacillin 150 mg/kg/day for 7.2 +/- 2.75 days and 17 patients received carbenicillin 200 mg/kg/day for 7.5 +/- 2.90 days. Patients were evaluated for clinical and bacteriologic responses and tolerance to therapy. Although the clinical cure rate significantly favored carbenicillin treatment (p less than 0.01), the sum of the percentages of cases with clinical cure and clinical improvement were similar between groups: 91.6% for piperacillin and 88.2% for carbenicillin. The bacteriologic cure rates for piperacillin and carbenicillin patients (54.1 and 47.0%, respectively) were not significantly different (p greater than 0.05). The low cure rates in our study were probably the result of uncorrected/uncorrectable genitourinary tract abnormalities. Superinfections developed in 12.5 and 17.6% of piperacillin and carbenicillin patients, respectively, and were due to Klebsiella pneumonia, Proteus mirabilis, Citrobacter diversus, and Pseudomonas aeruginosa. Overall, side effects were mild, reversible, and did not require discontinuation of treatment. However, carbenicillin caused elevations in liver enzymes more frequently than piperacillin (p less than 0.05). Based on our data, we recommend reserving piperacillin monotherapy for patients who are poor candidates for aminoglycosides, or are on severe sodium restriction, and have serious complicated urinary tract infections due to susceptible organisms. We do not recommend piperacillin alone for empiric treatment of complicated urinary tract infections.

Bacterial Infections↗
PubMed1986

Multiple-dose pharmacokinetics of piperacillin and azlocillin in 12 healthy volunteers.

The pharmacokinetic profile of piperacillin and azlocillin after multiple-dose administration to healthy volunteers was studied. Twelve healthy volunteers received either piperacillin 4 g (as the sodium salt) or azlocillin 4 g (as the sodium salt) as a 20-minute infusion every six hours for five doses. After a one-week washout period, subjects received identical treatment with the alternate drug. Serum and urine concentrations of piperacillin and azlocillin were measured using a reversed-phase high-performance liquid chromatographic assay, and the pharmacokinetic analysis of serum concentration-versus-time data was performed using a computerized program. A standard open-model equation for i.v. infusions was used. Mean serum concentrations of piperacillin and azlocillin after dose 5 were 344 +/- 66 micrograms/mL and 414 +/- 86 micrograms/mL, respectively. The terminal elimination half-life of azlocillin (1.1 +/- 0.2 hr) was significantly longer than that of piperacillin (0.75 +/- 0.13 hr) (p less than 0.05). Total body clearance of azlocillin (125 +/- 25 mL/min) was significantly less than that of piperacillin (226 +/- 43 mL/min) after dose 5. Azlocillin showed accumulation between the first and fifth doses. Twelve hours after administration of dose 5, 75% of azlocillin and 57% of piperacillin were excreted unchanged into the urine. In healthy volunteers, azlocillin produced higher and more prolonged serum concentrations than piperacillin after administration of equivalent i.v. doses. Further studies are needed to determine the clinical importance of these observations.

Adult↗
PubMed1994

Biliary elimination and hepatic disposition of an association of piperacillin and tazobactam: experimental evaluation.

Biliary elimination and hepatic disposition of tazocillin, an association of a highly bile-excreted ureido-penicillin, piperacillin, with a beta-lactamase inhibitor, tazobactam, have been assessed applying an isolated perfused rabbit liver experimental model. Six investigations were performed, each during a 3 h period, using reconstituted blood circulating in a closed circuit. Piperacillin and tazobactam concentration in all specimens were determined by high performance liquid chromatography. Blood samples and cumulative bile secretion were collected every 30 min, and liver fragments were isolated at the end of each experiment for dosage purposes. Following the simultaneous administration of piperacillin 80 mg and tazobactam 10 mg (dose ratio 8/1) in the perfusion device, theoretical initial serum concentrations were respectively 414 micrograms/ml and 32.1 micrograms/ml. Maximal biliary concentrations of 4431 +/- 1541 (s.d.) of piperacillin and 21.3 +/- 7.8 micrograms/ml of tazobactam were reached between 0.5-1 h and 2.5-3 h, respectively. Cumulative biliary excretion (0-3 h) amounted to 37.6 +/- 17.7% of the administered dose for piperacillin and 1.5% for tazobactam. At the end of the perfusion, respectively 22.1% and 50.7% of piperacillin and tazobactam doses remained in the circulating blood, while 1.1% and 5.6% were found in the liver. On the basis of these data, the calculated percentages of piperacillin and tazobactam doses having undergone hepatic biotransformation, were 6.5% and 1.2%, respectively. Under such experimental conditions, concentrations and excretion of piperacillin in bile prove to be substantial. Of note, tazobactam concentrations turn out to be stable both in serum and in bile whereas they stay at a relatively constant level of 20 micrograms/ml during nearly all the perfusion time.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Disposition kinetics and bioavailability of piperacillin and cephapirin in mares.

The pharmacokinetics of piperacillin (430 mg/kg.b.wt.) and cephapirin (20 mg/kg.b.wt.) were investigated following a single intravenous and intramuscular injection in normal mares. The serum concentration-time curve following a single intravenous injection of both antibiotics obeyed a two-compartment open model. After intravenous dose, piperacillin and cephapirin were transferred from central to peripheral compartment (k12) with values 0.46 and 0.52 h-1, while their passages from peripheral to central compartment (k21) were equal to 0.56 and 0.49 h-1, respectively. The elimination half-lives [t0.5(beta)] following intravenous injection were 6.94 and 3.82 h for piperacillin and cephapirin, respectively. Piperacillin and cephapirin were cleared after intravenous injection by all clearance processes in the body (CItot.) at rates of 5.52 and 0.67 ml/min., respectively. The absorption half-lives [t0.5(ab)] of piperacillin and cephapirin following a single intramuscular injection were 0.46 and 0.88 h., respectively. The calculated maximum [Cmax.] and minimum [Cmin.] serum concentrations to establish a proper multiple dosage regimen were 52.94, 4.50 micromilligrams (for piperacillin) and 10.18, 2.20 micromilligrams (for cephapirin), respectively. The mean systemic bioavailabilities of piperacillin and cephapirin following a single intramuscular injection were 85.47% and 67.89%, respectively. The in-vitro protein binding percent was 19.23% for piperacillin and 52.62% for cephapirin.

Animals↗
PubMed2005

Acquisition of resistant bowel flora during a double-blind randomized clinical trial of ertapenem versus piperacillin-tazobactam therapy for intraabdominal infections.

Bowel colonization with resistant bacteria can develop in patients receiving broad-spectrum antimicrobial therapy. We compared the impact of two antimicrobial regimens often used to treat intraabdominal infections on susceptibility patterns of bowel flora at the end of therapy. In a double-blind clinical trial, adults with complicated intraabdominal infection requiring surgery were randomized to receive piperacillin-tazobactam (3.375 g every 6 h) or ertapenem (1 g once a day) for 4 to 14 days. Rectal swabs were obtained at baseline and at the end of study therapy to determine the acquisition rates of Enterobacteriaceae resistant to the study drug, extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli or Klebsiella species, Pseudomonas aeruginosa resistant to imipenem or piperacillin-tazobactam, and vancomycin-resistant Enterococcus faecalis or Enterococcus faecium. Treated patients were assessable for the acquisition of resistant bacteria if appropriate specimens were obtained at both time points. Enterobacteriaceae resistant to the treatment received were acquired during study therapy by 8/122 assessable piperacillin-tazobactam recipients (6.6%) compared to 0/122 assessable ertapenem recipients (P = 0.007). Neither ESBL-producing E. coli or Klebsiella species nor P. aeruginosa resistant to piperacillin-tazobactam was isolated from patients in either treatment group. Imipenem-resistant P. aeruginosa was acquired by two of the ertapenem recipients (1.6%) versus zero of the piperacillin-tazobactam recipients (P = 0.50). Vancomycin-resistant enterococci were acquired during therapy by 8/125 assessable ertapenem recipients (6.4%) versus 2/123 assessable piperacillin-tazobactam recipients (1.6%; P = 0.10). In this study, the acquisition of resistant Enterobacteriaceae occurred significantly more often in patients treated with piperacillin-tazobactam than in those treated with ertapenem.

Abdominal Abscess↗
PubMed1997

Piperacillin-tazobactam as empiric monotherapy in febrile neutropenic patients with haematological malignancies.

The efficacy of piperacillin-tazobactam as first line empiric therapy was assessed in 54 febrile neutropenic episodes in 42 patients (27 male, 15 female) with haematological malignancy. Nineteen (35%) episodes were bacteraemias (15 Gram-positive, 4 Gram-negative), 5 (9%) were clinically documented (Hickman line sites) and 30 (56%) were pyrexias of unknown origin. Study therapy was initiated after a median of 4 days of neutropenia (range 1-30). Eighteen (33%) episodes responded to piperacillin-tazobactam without a need for treatment modification. Four (7%) episodes initially responded to piperacillin-tazobactam but required treatment modification for fungal superinfection. Of the 19 bacteraemias, 6 (32%) were eradicated or presumed eradicated by piperacillin-tazobactam. Of the 32 (60%) episodes which failed to respond to piperacillin-tazobactam, 11 (34%) responded to anti-fungal therapy; 14 (44%) responded to a glycopeptide and 5 (16%) responded to a second-line broad spectrum antibacterial agent. Two (6%) patients died, both in the presence of progressive malignancy. There was no significant toxicity associated with piperacillin-tazobactam. We conclude that piperacillin-tazobactam is effective as empiric monotherapy in neutropenic fever and may reduce the requirement for glycopeptides.

Adolescent↗
PubMedDate not supplied

Comparative in vitro activities of amoxicillin-clavulanate, ampicillin-sulbactam and piperacillin-tazobactam against strains of Escherichia coli and proteus mirabilis harbouring known beta-lactamases.

Strains of Escherichia coli (N = 124) and Proteus mirabilis (N = 29) harboring known beta-lactamases were analyzed as to their susceptibility to ampicillin, amoxicillin, and piperacillin alone and in combination with sulbactam, clavulanate, and tazobactam. With TEM 1-producing E. coli, a correlation between specific beta-lactamase activity and the MIC of piperacillin and ampicillin-sulbactam was observed. These strains also showed significant differences in susceptibilities to the various combinations, suggesting that, at least in strains resistant to one combination, several beta-lactam/beta-lactamase inhibitor combinations should be tested in the laboratory. All combinations tested enhanced the activity of the beta-lactam towards TEM 1-producing E. coli, piperacillin-tazobactam being the most active. The drugs were less active to OXA 1 enzymes; solely with piperacillin-tazobactam 90% of strains were within the therapeutic range of the drug. Sulbactam acted synergistically to chromosomally encoded beta-lactamases, whereas amoxicillin-clavulanate was inactive. Piperacillin and piperacillin-tazobactam inhibited all strains producing chromosomally encoded beta-lactamases at concentrations within the therapeutic range of the drugs. In contrast, TEM 2 of P. mirabilis was not sensitive to ampicillin-sulbactam, but to the other combinations; here again piperacillin-tazobactam was the most active.

Amoxicillin↗
PubMed1992

Comparison of fixed concentration and fixed ratio options for testing susceptibility of gram-negative bacilli to piperacillin and piperacillin/tazobactam.

Piperacillin combined with tazobactam was tested at both a fixed ratio (8:1) and fixed tazobactam concentration (4 micrograms/ml) against 2,685 consecutively isolated gram-negative bacilli and 56 highly piperacillin-resistant isolates. Tazobactam significantly enhanced the spectrum of piperacillin activity. Overall, at a concentration of 16 micrograms/ml piperacillin alone inhibited 78.8% of the Enterobacteriaceae isolates compared to inhibition of 92.7% and 95.5% by the 8:1 ratio and fixed (4 micrograms/ml) tazobactam combinations, respectively. In MIC tests the two combination options performed comparably against both routine and highly piperacillin-resistant isolates. Synergistic inhibition was observed for comparable numbers of isolates with the two combination options, the most marked effect being seen in the more highly piperacillin-resistant isolates. Both testing options are supported by the available human pharmacokinetic data; however the 8:1 ratio of piperacillin to tazobactam may be preferable given that the clinical formulation contains the two compounds in an 8:1 ratio and this ratio is maintained in vivo.

Drug Synergism↗
PubMed1981

Piperacillin or ticarcillin plus amikacin. A double-blind prospective comparison of empiric antibiotic therapy for febrile granulocytopenic cancer patients.

Piperacillin plus amikacin was compared in a prospective randomized double-blind trial with our standard regimen of ticarcillin plus amikacin as empiric therapy of fever in patients with granulocytopenia. Profound persistent granulocytopenia (fewer than 100/microliter polymorphonuclear leukocytes without any rise during therapy) was present in 60 percent of the patient trials in both treatment groups. Of 38 microbiologically and clinically documented infections treated with piperacillin plus amikacin, 22 (58 percent) showed improvement. Of 34 microbiologically and clinically documented infections treated with ticarcillin plus amikacin, 19 (56 percent) showed improvement. There was no difference in response between groups according to the site of infection or infecting pathogen. Toxicity was minimal, with an equivalent incidence of immediate reactions, nephrotoxicity and superinfection. Patients receiving ticarcillin plus amikacin became colonized with more resistant gram-negative bacilli (17) than did those receiving piperacillin plus amikacin (3). Despite the monosodium structure of piperacillin, hypokalemia was not reduced for patients who received piperacillin plus amikacin. Although piperacillin has a wider in vitro antibacterial spectrum than ticarcillin, the clinical efficacy and toxicity of the combination of piperacillin plus amikacin were similar to those of ticarcillin plus amikacin as empiric therapy.

Adolescent↗
PubMed1985

Comparative study of ticarcillin plus clavulanate potassium versus piperacillin in the treatment of hospitalized patients with urinary tract infections.

The efficacy and safety of ticarcillin plus clavulanate potassium and piperacillin were compared in a clinical trial of 78 hospitalized patients with urinary tract infections. There were 37 evaluable patients in the ticarcillin plus clavulanate potassium-treated group and 39 in the piperacillin-treated group. The 43 infection sites in each group were primarily complicated pyelonephritis or complicated cystitis; six patients in the ticarcillin plus clavulanate potassium-treated group and four in the piperacillin-treated group also had septicemia. Both ticarcillin (3 g) plus clavulanate potassium (200 mg) and piperacillin (125 to 200 mg/kg per day) were administered intravenously. The 43 most common pathogens in each treatment group were Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa from the urinary tract and E. coli from the blood. Eight pathogens in the ticarcillin plus clavulanate potassium-treated group and 11 in the piperacillin-treated group were resistant to ticarcillin in vitro. Eradication was achieved for 39 of the 43 (91 percent) pathogens in the ticarcillin plus clavulanate potassium group, including all six organisms isolated from the blood and eight (89 percent) of the ticarcillin-resistant pathogens. In the piperacillin-treated group, 33 of the 43 (77 percent) pathogens were eradicated, including three of the four blood isolates but only eight (73 percent) of the ticarcillin-resistant pathogens. The rate of reinfection or relapse was similar in both groups. Clinical cure or improvement occurred in 97 percent of the patients in each group. Mild and transient increases in levels of liver enzymes or eosinophilia was reported for 11 patients in the ticarcillin plus clavulanate potassium-treated group and for seven in the piperacillin-treated group. In one patient in the ticarcillin plus clavulanate potassium-treated group, a drug-related rash and nausea developed, and treatment was discontinued.

Adult↗
PubMed1988

Cefoperazone plus piperacillin versus mezlocillin plus tobramycin as empiric therapy for febrile episodes in neutropenic patients.

The double beta-lactam combination of cefoperazone plus piperacillin was compared with an aminoglycoside-containing regimen of mezlocillin plus tobramycin in a prospective, randomized trial of empiric therapy for febrile neutropenic patients (neutrophils no more than 1,000/mm3). Thirty febrile episodes were treated with cefoperazone plus piperacillin and mezlocillin plus tobramycin, respectively. There was no significant difference between the two groups with respect to age, sex, pretherapy neutrophil count, and mean duration of therapy. The majority of patients had neutrophil counts of no more than 200/mm3 at the initiation of therapy. Only microbiologically and clinically documented infections were evaluated for efficacy. The cefoperazone plus piperacillin regimen appeared to have a comparable response rate with the mezlocillin plus tobramycin regimen (20 of 24 patients [83 percent] versus 16 of 23 patients [70 percent]). Gram-positive micro-organisms were seen predominantly in this study, with the cefoperazone plus piperacillin regimen achieving a bacteriologic response in 84 percent, as opposed to 60 percent for those organisms treated with the mezlocillin plus tobramycin regimen. Neither regimen was totally effective against coagulase-negative staphylococci. Eight superinfections occurred in the cefoperazone plus piperacillin arm, whereas 11 superinfections occurred in the mezlocillin plus tobramycin arm. Although fungal superinfections were most common, the number of gram-positive superinfections in the mezlocillin plus tobramycin arm exceeded those seen in the cefoperazone plus piperacillin arm. The incidence of antibiotic-related side effects was similar in the two groups. Hypokalemia was most frequently seen. Both skin rashes and nephrotoxicity were more common with mezlocillin plus tobramycin. Cefoperazone plus piperacillin was found to be effective empiric therapy in febrile neutropenic patients. This double beta-lactam combination may be particularly useful for patients who have or are at high risk for the development of renal insufficiency.

Adolescent↗
PubMed1983

Comparative study of piperacillin versus cefoxitin in the treatment of obstetric and gynecologic infections.

Piperacillin sodium (Pipracil, Lederle Laboratories, Wayne, New Jersey), a new semisynthetic penicillin, demonstrated in vitro activity against a broad spectrum of clinical pathogens. It is active against most strains of the clinically important gram-negative aerobic or facultative bacteria and against virtually all the clinically important anaerobic organisms, including Bacteroides fragilis and Bacteroides bivius. This broad antibacterial spectrum suggested that piperacillin might be an effective single antimicrobial agent for the treatment of mixed aerobic/anaerobic infections in obstetric and gynecologic patients. In this study, the clinical efficacy and safety of piperacillin was compared with that of cefoxitin in the management of pelvic infections. There were 23 patients in the piperacillin group (acute salpingitis, 12; endomyometritis, 7; pelvic cellulitis, 2; tuboovarian abscess, 2) and 25 patients in the cefoxitin group (acute salpingitis, 13; endomyometritis, 10; tuboovarian abscess, 2). An average of six bacteria were isolated from each patient. Aerobic bacteria only were recovered from 12.5%, anaerobic bacteria only in 6.5%, and both aerobic and anaerobic bacteria were present in 82.5% of patients. Overall, 21 of 23 (91%) of the piperacillin treatment group and 23 of 25 (92%) of the cefoxitin group responded to therapy with antimicrobial agents alone. The major cause of failure was the presence of an abscess. Piperacillin was shown to be an effective single agent for the management of pelvic infections caused by mixed aerobic and anaerobic bacteria. In addition, piperacillin proved to be safe and well tolerated.

Adolescent↗
PubMed1989

Piperacillin for prophylaxis in gynecological surgery.

The effectiveness of perioperative Piperacillin for prevention of operative-site infection after gynaecological surgery was studied in a total of 100 patients. In an open randomized clinical trial of 52 women undergoing abdominal or vaginal hysterectomy Piperacillin was compared to the combination Gentamicin/Metronidazole. Piperacillin was well-tolerated. Surgical-site infection was diagnosed in the Piperacillin group in two patients and in the Gentamicin/Metronidazole group in one patient. The occurrence of postoperative febrile morbidity was also similar between the two group. In 48 patients undergoing complicated gynecological surgery of long duration, only Piperacillin was administered perioperatively. Thirty-five of these 48 women underwent oncological operations and the mean operative length was 3.3 h. One patient developed a transient rash after the administration of Piperacillin. No other adverse side-effects were observed. Nine of these 48 patients developed a surgical-site infection postoperatively, and this was found to be significantly more often than in the first group of 52 patients. It was concluded that Piperacillin seems to be a valuable alternative for perioperative prophylaxis in gynecological surgery. Its effectiveness in vaginal and abdominal hysterectomy is similar to the combination of Gentamicin/Metronidazole, but after complicated surgery of long duration a decreased effectiveness should be reckoned with.

Bacterial Infections↗
PubMed1990

In vitro comparison of mezlocillin and piperacillin plus tobramycin or gentamicin versus 100 gram-negative nosocomial bloodstream isolates.

We compared the in vitro activity of mezlocillin and piperacillin, alone and in combination with tobramycin or gentamicin, against clinical isolates of gram-negative bacilli from hospitalized patients with 100 distinct episodes of nosocomial bacteremia. The minimum inhibitory concentrations (MICs) necessary to inhibit 50% and 90% of isolates showed that piperacillin was most active against Pseudomonas aeruginosa. The MIC needed to inhibit 90% of isolates also showed that mezlocillin was more active against Enterobacter cloacae. Activities of the two acylaminopenicillins were comparable against the rest of the isolates. Combining the acylaminopenicillins with either gentamicin or tobramycin decreased the MICs fourfold or more for both combinations. Synergy occurred more frequently with mezlocillin-gentamicin (12%), followed by piperacillin-tobramycin (9%), mezlocillin-tobramycin (6%), and piperacillin-gentamicin (5%). Antagonism for Enterobacteriaceae isolates was observed most frequently with the combination of piperacillin plus tobramycin (20%), followed by mezlocillin plus tobramycin (17.6%), piperacillin plus gentamicin (12.9%), and mezlocillin plus gentamicin (8.2%). There are very few differences in the activities of mezlocillin and piperacillin combined with either gentamicin or tobramycin versus nosocomial gram-negative bloodstream isolates.

Drug Synergism↗
PubMed1992

Single-dose pharmacokinetics of piperacillin and tazobactam in patients with renal disease.

Tazobactam is an irreversible inhibitor of many beta-lactamases. In combination with piperacillin, tazobactam exhibits synergy against many beta-lactamase-producing bacteria. The pharmacokinetics of piperacillin and tazobactam were evaluated in eight normal volunteers and in 52 patients with renal dysfunction. Plasma and urine were obtained for up to 30 hours after an infusion of piperacillin and tazobactam (3 and 0.375 gm, respectively). Dialysate samples were collected from patients undergoing dialysis. Piperacillin and tazobactam concentrations were determined by high-performance liquid chromatography. Noncompartmental methods were used for pharmacokinetic analysis. Piperacillin and tazobactam total body clearance, area under the curve, and terminal elimination rate correlated with renal function. Hemodialysis removed 31% and 39% of piperacillin and tazobactam, respectively. During continuous ambulatory peritoneal dialysis, 5.5% of the piperacillin and 10.7% of the tazobactam was recovered in the dialysate over 28 hours. Peak plasma concentrations of both drugs increased minimally with decreasing creatinine clearance. Dosage alterations for creatinine clearance values less than 40 ml/min are recommended.

Adult↗
PubMed2001

Conjugative resistance to tazobactam plus piperacillin among extended-spectrum beta-lactamase-producing nosocomial Klebsiella pneumoniae.

We studied the genetic origins of piperacillin-tazobactam resistance among nosocomial Klebsiella pneumoniae strains. A total of 30 nosocomial isolates resistant to piperacillin-tazobactam were obtained from various regions of Turkey. Isoelectric focusing demonstrated at least 2 enzymes common to all strains: I at a pI of 8.0 and the other at 5.4. Piperacillin-tazobactam resistance was successfully transferred from all of the strains to Escherichia coli. Of the piperacillin-tazobactam-resistant transconjugates, 23 were also resistant to ceftazidime. However, 7 transconjugates were susceptible to ceftazidime but resistant to piperacillin-tazobactam, producing a single enzyme focusing at pI 5.4. Piperacillin resistance caused by this enzyme was reversed by clavulanate and by increased amounts of tazobactam, which indicates that this enzyme confers resistance due to its high amount. Sequence analysis revealed this enzyme to be TEM-1. This study demonstrates that transferable hyper-produced TEM-1 causes piperacillin-tazobactam resistance in Klebsiella strains in Turkish hospitals.

Base Sequence↗