UNLABELLED Piperacillin/tazobactam is a beta-lactam/beta-lactamase inhibitor combination with a broad spectrum of antibacterial activity against most Gram-positive and Gram-negative aerobic bacteria and anaerobic bacteria. Piperacillin/tazobactam is effective and well-tolerated in patients with lower respiratory tract infections (LRTI), intra-abdominal infections, skin and soft tissue infections, and febrile neutropenia. In comparative clinical trials against various other antibacterial regimens, piperacillin/tazobactam has shown higher clinical success rates, particularly in the treatment of patients with intra-abdominal infections and febrile neutropenia. Cost analyses of piperacillin/tazobactam have been variable, in part, because of differences in specific costs included. Three US cost analyses found that piperacillin/tazobactam had lower total medical costs than clindamycin plus gentamicin or imipenem/cilastatin in intra-abdominal infections, and ticarcillin/ clavulanic acid in community-acquired pneumonia. Piperacillin/tazobactam plus amikacin had lower total costs than ceftazidime plus amikacin in another cost analysis of patients with febrile neutropenic episodes modelled in nine European countries. However, piperacillin/tazobactam plus tobramycin was more costly than ceftazidime plus tobramycin in hospital-acquired pneumonia in a US cost analysis. In cost-effectiveness analyses, all studies of intra-abdominal infections, pneumonia and febrile neutropenic episodes consistently reported lower costs per unit of effectiveness versus comparators. Piperacillin/tazobactam was dominant (greater efficacy and lower costs) versus imipenem/cilastatin in intra-abdominal infections and ceftriaxone, ciprofloxacin or meropenem in pneumonia. Piperacillin/tazobactam plus amikacin was dominant over ceftazidime plus amikacin in the treatment of febrile neutropenic episodes. In a cost-effectiveness analysis of skin and soft tissue infection, piperacillin/tazobactam had lower costs per successfully treated patient than ceftriaxone or cefotaxime, but a slightly higher cost-effectiveness ratio than amoxicillin/clavulanic acid. All cost-effectiveness analyses were based on decision-analytical models. CONCLUSIONS Piperacillin/tazobactam is likely to reduce overall treatment costs of moderate to severe bacterial infections by increasing initial treatment success, thereby reducing the length of hospital stay and the use of additional antibacterials. Piperacillin/tazobactam has shown clinical and economic advantages over standard antibacterial regimens in the treatment of intra-abdominal infections, LRTIs, febrile episodes in patients with neutropenia, and skin and soft tissue infections, although more complete published data are needed to confirm these results. Present data regarding clinical efficacy, bacterial resistance and costs would support the use of piperacillin/tazobactam as an empirical first-line option in moderate to severe bacterial infections.

Piperacillin/tazobactam: a pharmacoeconomic review of its use in moderate to severe bacterial infections.

Background: The degree of penetration of an antibiotic into the site of infection is an important factor in its therapeutic efficacy, particularly in bone and joint infections. Piperacillin/tazobactam, a β-lactam/β-lactamase inhibitor combination, has been widely used in the treatment of serious infections, including bone infections, but few studies have examined the bone diffusion of these antibiotics. Objective: The purpose of this study was to quantify the bone tissue penetration of piperacillin/tazobactam into cancellous and cortical bone tissue and, from these results, estimate the efficacy of this antibiotic combination against microorganisms commonly encountered in bone infections. Methods: In this open-label, single-arm, noncomparative study, subjects of similar age, body weight, height, and creatinine clearance who were undergoing elective total hip replacement received a single, parenteral 4 g/500 mg dose of piperacillin/tazobactam. Approximately 1.5 hours later, plasma and bone tissue samples were collected and analyzed by a validated high-pressure liquid chromatography method. Results: Twelve patients (3 men and 9 women; mean age, 73.5 years; mean body weight, 52.2 kg) were enrolled. The mean concentrations of piperacillin and tazobactam were 18.9 ± 2.3 μg/g and 2.0 ± 0.3 μg/g, respectively, in cancellous bone tissue and 15.1 ± 2.0 μg/g and 2.0 ± 0.3 μg/g in cortical bone tissue. The bone tissue/plasma ratios for piperacillin and tazobactam were both 0.3 in cancellous bone tissue and 0.2 and 0.3, respectively, in cortical bone tissue. The piperacillin/tazobactam concentration ratio was 9.3:1 in cancellous bone tissue and 7.8:1 in cortical bone tissue. Conclusions: The concentrations achieved in both cancellous and cortical bone tissue were greater than the minimum concentrations required to inhibit the growth of 50% of strains (MIC 50 ) of most of the susceptible pathogens commonly involved in bone infections.

Penetration of piperacillin/tazobactam into cancellous and cortical bone tissue

The degree of penetration of an antibiotic into the infected site is an important criterion for therapeutic success. This is particularly true for bone and joint infections. The association of piperacillin and tazobactam has been widely used in the treatment of serious infections including bone infections, but no study has been devoted to the subject of its diffusion into synovial tissue. Our objective was to quantify piperacillin/tazobactam synovial tissue penetration and to estimate the efficacy of the association against the microorganisms usually encountered in joint infections. In an open-label study, 6 subjects with similar age, weight, height and creatinine clearance, who were undergoing elective total hip replacement, received a single, parenteral, 4 g/500 mg dose of piperacillin/tazobactam. Plasma and synovial tissue samples were collected and analyzed by a validated HPLC method. The mean concentrations of piperacillin and tazobactam 1.5 h after the initiation of infusion were 69.9 +/- 4.9 microg/mL and 7.7 +/- 0.3 microg/mL, respectively, in plasma and 37.1 +/- 2.1 microg/g and 2.8 +/- 0.4 microg/g, respectively, in synovial tissue. The synovial tissue/plasma ratios were 0.5 +/- 0.0 for piperacillin and 0.4 +/- 0.0 for tazobactam. The piperacillin/tazobactam ratios were 9.1:1 in plasma and 13.5:1 in synovial tissue. The concentrations achieved in synovial tissue are above the MICs of most of the susceptible pathogens usually involved in joint infections, which suggests that the piperacillin/tazobactam combination should be effective in the treatment of most joint infections caused by susceptible microorganisms.

Penetration of piperacillin/tazobactam (4 g/500 mg) into synovial tissue.

Neutropenic patients with cancer are a heterogeneous group of patients who carry a variable risk for infection. When such patients present with fever, appropriate empiric antibiotic therapy is initiated and continued until

Current treatments for infection in neutropenic patients with hematologic malignancy.

Potency and antimicrobial spectrum update for piperacillin/tazobactam (2000): emphasis on its activity against resistant organism populations and generally untested species causing community-acquired respiratory tract infections.

Resistance of bacteria to antibiotics is an increasing problem in many countries. Accurate locally relevant information is essential for detection and control of emerging resistance and to facilitate choice of empirical antibiotic therapy in the immediate management of seriously ill patients. We have determined the minimum inhibitory concentration of piperacillin/tazobactam for 97 strains of bacteria (55 Enterobacteriaceae, 13 non-fermentative Gram-negative bacilli, 22Staphylococcus aureus), 6Enterococcus faecalis and 1Bacillus cereus) isolated from blood cultures and compared its activity to that of amoxycillin, co-amoxiclav, cephalothin, cefotaxime, ceftazidime, ciprofloxacin, gentamicin, piperacillin, cefotaxime. The strains were consecutive non-fastidious isolates with the following qualifications: coagulase negative staphylococci and diphtheroids were excluded and the number of Staphylococcus aureus isolates was limited to 12 methicillin-resistant and 10 methicillin-sensitive strains. Multiple isolates of the same species from individual patients were not included. The minimum inhibition concentrations of methicillin, penicillin, teichoplanin and vancomycin were also determined for specific groups of organisms. MICs were determined by the Etest method (AB Biodisk, Solna, Sweden) on Mueller Hinton agar. The MICs of appropriate American Type Culture Collection control strains were determined. Based on the interpretative criteria of the National Committee for Clinical Laboratory Standards (USA), 87 per cent of Gram-negative bacilli were susceptible to piperacillin/tazobactam compared with amoxycillin 26 per cent, cephalothin 35 per cent, co-amoxiclav 54 per cent, piperacillin 56 per cent, cefotaxime 69 per cent, ceftazidime 84 per cent, gentamicin 85 per cent and ciprofloxacin 91 per cent. Of all isolates 75 per cent were sensitive to piperacillin/tazobactam, compared with amoxycillin 22 per cent, cephalothin 35 per cent, piperacillin 41 per cent, co-amoxiclav 52 per cent, cefotaxime 59 per cent, ceftazidime 60 per cent, gentamicin 74 per cent and ciprofloxacin 77 per cent. Two isolates (1E. coli and 1Klebsiella pneumoniae) with antibiograms consistent with the relatively new resistance phenomenon of extended spectrum beta-Iactamase production were identified. The spectrum of activity of piperacillin-tazobactam for empirical antibiotic therapy is significantly greater than that of piperacillin alone and is similar to that of ciprofloxacin and gentamicin.

In-vitro activity of piperacillin/tazobactam relative to other antibiotics against blood culture isolates.

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In-vitro activity of piperacillin/tazobactam relative to other antibiotics against blood culture isolates.