Cefepime/Enmetazobactam vs Piperacillin/Tazobactam and Complicated Urinary Tract Infection or Acute Pyelonephritis
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To the Editor A recent trial1 comparing the effect of cefepime/enmetazobactam vs piperacillin/tazobactam on complicated urinary tract infection or acute pyelonephritis found that patients receiving cefepime/enmetazobactam had a better primary outcome. We have some concerns about this study.Keywords:
Cefepime
Piperacillin/tazobactam
Tazobactam
The pharmacokinetics of tazobactam (500 mg) administered intravenously alone were compared with the pharmacokinetics of tazobactam coadministered with piperacillin (4 g), and the penetration into an inflammatory exudate in six healthy males was studied. Piperacillin influenced the pharmacokinetics of tazobactam. The mean levels of tazobactam in plasma at 4 h were 0.6 microgram/ml when it was given alone and 1.2 micrograms/ml when it was given with piperacillin (P = 0.0003). The mean total clearances of tazobactam were 203.5 and 134.2 ml/min (P = 0.035) when it was given alone and with piperacillin, respectively There were no significant differences in the elimination half lives, areas under the concentration-time curve from 0 h to infinity, or volumes of distribution. Inflammatory exudate penetration was rapid, and the mean maximum levels of tazobactam attained were 6.4 and 11.3 micrograms/ml when it was given alone or with piperacillin, respectively (P less than 0.06). The mean percent penetration of tazobactam and the area under the concentration-time curve from 0 h to infinity in inflammatory exudate were greater when tazobactam was given with piperacillin. The mean 24-h urinary recoveries of tazobactam were 63.7% +/- 7.9% when it was given alone and 56.8% +/- 2.7% when it was given with piperacillin. The explanation for the differences in the pharmacokinetics of tazobactam when it was administered alone compared with those when it was given with piperacillin was unclear.
Tazobactam
Piperacillin/tazobactam
Beta-Lactamase Inhibitors
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Background: Cefepime, piperacillin-tazobactam and meropenem are among the broadest-spectrum and most expensive antimicrobials. Aim: To evaluate guidelines for appropriate use of these drugs. Methods: We developed guidelines for use of these antibiotics, and conducted a two-phase drug utilization evaluation. We included all patients who received one of the study drugs during two 3-month periods, with an educational intervention in the intervening period. Appropriateness was determined for initiation of treatment, and for adaptation or continuation of established treatment. Results: Overall, 205 patients received 271 courses with one of these antibiotics, for a total of 709 defined daily doses (DDD) of cefepime, 543 of piperacillin-tazobactam, and 680 of meropenem (8.3, 6.3 and 7.9 DDD/1000 admission days, respectively). Of these 271 courses, 234 were appropriate (86%). Treatment was continued for ⩾5 days in 60%, of which 88% were appropriate (NS). Of the 271 courses, 210 (77%) were empirical (83% appropriate), while 61 (23%) were based on a relevant culture result (97% appropriate) ( p < 0.001). Appropriateness differed significantly between departments ( p < 0.001), and between the two phases ( p < 0.001). The major difference between the two surveys was a decrease in meropenem usage ( p < 0.05). Discussion: The vast majority of courses with cefepime, piperacillin-tazobactam and meropenem are empirically selected and continued, underlying the importance of an optimal initial choice. Antibiotic guidelines, in conjunction with formal infectious disease consultation, can contribute to more appropriate use of these drugs.
Cefepime
Piperacillin/tazobactam
Tazobactam
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Background: While certain extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae may appear susceptible to piperacillin-tazobactam in the laboratory, controversy exists regarding its appropriateness to treat serious infections. The Clinical and Laboratory Standards Institute (CLSI) recommends that piperacillin-tazobactam susceptibility be reported as tested, and that ESBL screening is not required in Enterobacteriaceae. We evaluated a sequential group of patients with ESBL Escherichia coli bacteremia to determine the factors associated with piperacillin-tazobactam use despite this controversy. Methods: This was a retrospective observational study at the McGill University Health Center (832 beds) in Montréal, Canada, from April 2010 to June 2015, examining patients with positive blood cultures that grew E. coli. Pediatric, untreated, and duplicate cultures within 14 days were excluded. Antimicrobial susceptibility testing was determined in accordance with CLSI guidelines. Definitive therapy was defined as antibiotics given after susceptibility results became available. Results: There were 845 E. coli bacteremias in the data set, with a median patient age of 68 years (IQR 57–81.25) and a 30-day in-hospital mortality of 12.1%. Overall, there were 44 ceftriaxone-resistant, piperacillin-tazobactam-susceptible bloodstream infections (BSI), and 41 received definitive therapy. Of these, 14/41 (34.1%) received piperacillin-tazobactam and 30 had an infectious disease consult performed. Consult with infectious disease was associated with less use of piperacillin-tazobactam as definitive therapy (7/30 [23%] versus 7/11 [64%]; OR 0.17; 95% CI 0.03–0.96; p = 0.02). Conclusion: Piperacillin-tazobactam definitive therapy was used in approximately one-third of ceftriaxone-resistant E. coli bacteremias. Given a risk of increased mortality with the use of beta-lactam/beta-lactamase inhibitors for treating serious ESBL infections, microbiology laboratories should consider withholding piperacillin-tazobactam susceptibility results in such cases pending definitive evidence of clinical efficacy.
Piperacillin/tazobactam
Tazobactam
Bacteremia
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OBJECTIVE:To evaluate the efficacy of Piperacillin/Tazobactam versus Ciprofloxacin plus Metronidazole for complicated intraabdominal infection. METHODS: 192 patients whose bacterial culture test on intraoperative-resected samples indicated growth of at least one pathogen were treated with Piperacillin/Tazobactam versus Ciprofloxacin plus Metronidazole for complicated intraabdominal infection. The drug resistance of the pathogens isolated form intraoperative-resected samples and the parameters including the clinical effective rate etc were compared between the two groups excluding the resistant cases. RESULTS: 85 case received Piperacillin/Tazobactam versus 107 cases received Ciprofloxacin plus Metronidazole,and the resistance rates of the pathogens isolated from the intraoperative-resected samples were 5.9% (5/85) and 21.5% (23/107),respectively. The clinical effective rates in the two groups excluding the resistant cases were 92.5% (74/80) and 77.4%(65/84),respectively,showing significant difference (P0.05). CONCLUSION: Whether being used as empiric drug or confirmed drug for complicated intraabdominal infection,the efficacy of Piperacillin/Tazobactam is significantly superior to Ciprofloxacin plus Metronidazole,thus Piperacillin/Tazobactam should be used as the first line therapy for complicated intraabdominal infection.
Tazobactam
Piperacillin/tazobactam
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Objective:To evaluate clinical efficacy and safety of piperacillin tazobactam treatment in acute bacterial infections.Methods:In this study 131 patients were randomized to receive either piperacillin tazobactam 8～12g/d or ticarcillin clavulanate 9.6～12.8g/d for 7～14 days.Sixty seven patients received piperacillin tazobactam and 64 patients received ticarcillin clavnlanate.Results:The cure rates in piperacillin tazobactom and ticarcillin clavulanate groups were 62.7% and 60.9% respectively and the efficary rates 89.6% and 84.4% respectively.Bacterial eradication rates were 91.5% and 89.1% respectively.The side effect rates were 11.9% and 6.25% respectively.There were no significant differences between two groups.Conclusion:Piperacillin tazobactam is a kind of safe and effective anti infection medicine.
Piperacillin/tazobactam
Ticarcillin
Tazobactam
Beta-Lactamase Inhibitors
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To determine effectiveness and safety of generic piperacillin/tazobactam (Astaz-P) that has been available as a substitute for original piperacillin/tazobactam (Tazocin) in Siriraj Hospital since October 2011.Medical records of hospitalized adult patients who received piperacillin/tazobactam for at least 48 hours from January 2011 to June 2012 were reviewed. The data on demographics, clinical features of infections, antibiotic treatments, clinical courses and outcomes of the patients who received original piperacillin/tazobactam and generic piperacillin/ tazobactam were analyzed and compared.The medical records of 300 patients who received original piperacillin/tazobactam and 300 patients who received generic piperacillin/tazobactam were included. The characteristics of the patients and clinical and microbiological features of infections of the patients in both groups were not significantly different. Overall favorable clinical outcome and overall mortality were comparable between generic and original groups (74.0% vs. 74.7%, p = 0.93; 18.3% vs. 18.0%, p = 1.00, respectively). No significant difference of adverse effect was found between two groups. The non-inferiority test indicated that the clinical outcome and overall mortality of the patients who received generic piperacillin/tazobactam were not inferior to those who received original piperacillin/tazobactam (p = 0.004 and p = 0.001, respectively).Generic piperacillin/tazobactam (Astaz-P) was not inferior to original piperacillin/tazobactam (Tazocin) for therapy of infections in the hospitalized patients at Siriraj Hospital.
Piperacillin/tazobactam
Tazobactam
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To evaluate clinically the efficacy and safety in northern India of cefepime monotherapy versus piperacillin-tazobactam in patients of paediatric age group with febrile neutropenia.Children aged ≤18 years admitted febrile with chemotherapy-induced neutropenia were randomised into two groups comprising 20 cases in each group viz. CEF (receiving cefepime only) and PIP-TAZO (receiving piperacillin-tazobactam). Based on clinical and laboratory tests, patients were classified into: microbiologically documented infections (MDI); clinically documented infections (CDI); and unexplained fever (UF). They were assessed for clinical signs and symptoms as well as laboratory parameters at the time of enrolment and subsequently on days 3 and 7.Incidence of MDI, CDI and UF were 22.5%, 47.5% and 30%, respectively. The mean duration of neutropenia (in days) was 5.45 ± 2.1 in the PIP-TAZO group and 5.5 ± 1.5 in the CEF group (P = 0.305). The success rate defined as clearing infection effectively and improvement of neutropenia was comparable (P = 0.705). There was a mortality rate of 20% in the PIP-TAZO group as compared to 10% in the CEF group.We conclude that cefepime monotherapy and piperacillin-tazobactam are equally efficacious and safe in treating patients with febrile neutropenia. Empirical monotherapy with cefepime would prevent an unnecessary extra economic burden as well as avoiding the serious adverse or toxic effects of multi-drug regimes, especially in low- and middle-income countries.
Cefepime
Piperacillin/tazobactam
Tazobactam
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Piperacillin-tazobactam is a commonly used antibiotic that belongs to penicillin and beta-lactam inhibitors, which has a wide range of gram-negative bacteria and limited gram-positive activity. This case report presents one of the rare ADR of piperacillin–tazobactam –thrombocytopenia where a dramatic improvement within 24hrs in platelet count was observed after withdrawing the drug. Few cases of piperacillin tazobactam-induced thrombocytopenia have been reported.
Piperacillin/tazobactam
Tazobactam
Beta-Lactamase Inhibitors
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Piperacillin/tazobactam
Tazobactam
Pharmacodynamics
Beta-Lactamase Inhibitors
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We evaluated the in vitro activity of piperacillin alone or in combination with the beta-lactamase inhibitor tazobactam against clinical isolates of Legionella species. At an inoculum of approximately 10(4) CFU, tazobactam, piperacillin, and the 8:1 combination had equivalent activities against Legionella spp. At an approximately 10-fold higher inoculum, the following results were obtained, expressed as MICs for 50 and 90% of strains tested (MIC range): piperacillin, 4 and 16 (0.25 to 32) micrograms/ml; tazobactam, 0.5 and 1 (0.125 to 2) micrograms/ml; and piperacillin-tazobactam (expressed in terms of MIC of piperacillin) 0.5 and 1 (0.03 to 2) micrograms/ml. Tazobactam alone and the combination with piperacillin were more active than piperacillin alone at the higher inoculum.
Piperacillin/tazobactam
Tazobactam
Legionella
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