Piperacillin/tazobactam versus cefepime as initial empirical antimicrobial therapy in febrile neutropenic patients: a prospective randomized pilot study. Piperacillin-tazobactam versus carbapenem therapy with and without amikacin as empirical treatment of febrile neutropenia in cancer patients: results of an open randomized trial at a university hospital. Piperacillin/tazobactam plus amikacin versus carbapenem monotherapy as empirical treatment of febrile neutropenia in childhood hematological malignancies. A randomized, open-label, multicenter comparative study of the efficacy and safety of piperacillin-tazobactam and cefepime for the empirical treatment of febrile neutropenic episodes in patients with hematologic malignancies. Monotherapy with piperacillin/tazobactam versus cefepime as empirical therapy for febrile neutropenia in pediatric cancer patients: a randomized comparison. Piperacillin/tazobactam versus cefepime for the empirical treatment of pediatric cancer patients with neutropenia and fever: a randomized and open-label study. Piperacillin-tazobactam is more effective than ceftriaxone plus gentamicin in febrile neutropenic patients with hematological malignancies: a randomized comparison. Piperacillin/tazobactam in comparison with clindamycin plus gentamicin in the treatment of intra-abdominal infections. Randomized trial of beta-lactam regimens in febrile neutropenic cancer patients.
The objective of the presented prospective, randomized study was to compare the efficacy of empirical antimicrobial monotherapy with piperacillin/tazobactam (PIP/TAZ) to cefepime (CEFP) for treatment of infections in neutropenic patients. From a total of 102 febrile episodes 100 were evaluable. The most frequent microorganisms were gram-negative, documented in 22% vs. 24% of the febrile episodes (gram-positives 18% vs. 16%, fungi 2% vs. 4%). The response rate was similar with 22/51 (43%) of episodes treated with PIP/TAZ vs. 19/49 (39%) with CEFP. Of the different infection types classified at the end of the febrile episodes, patients with fever of unknown origin (FUO) and primary bacteremias showed the best initial responses with 25/44 (57%) and 11/22 (50%). Lower initial response rates were found in pneumonias with totally 3/13 (23%) and other clinically documented infections with 2/21 (10%), without any difference between both groups. Gram positive infections showed a higher response with PIP/TAZ than with CEFP (4/9 vs. 0/8), gram negative responded less frequently (3/11 vs. 7/13). The median time until persistent defervescence was equal in both groups (2.5 vs. 2 days), likewise the response rates after the different steps of therapy modifications (change to imipenem or ceftazidim, or addition of gentamycin, vancomycin or amphotericin B). Totally, 96% of febrile episodes responded in both therapy arms. Overall, we found no significant differences in efficacy between the two therapeutic regimens. In conclusion, PIP/TAZ as well as CEFP might be a sufficient initial therapy for febrile neutropenia, but further randomized trials with larger patient numbers are necessary. Empirical beta-lactam monotherapy has become the standard therapy in febrile neutropenia. The aim of this study was to compare the efficacy and safety of piperacillin-tazobactam versus carbapenem therapy with or without amikacin in adult patients with febrile neutropenia.
                In this prospective, open, single-center study, 127 episodes were randomized to receive either piperacillin-tazobactam (4 x 4.5 g IV/day) or carbapenem [meropenem (3 x 1 g IV/day) or imipenem (4 x 500 mg IV/day)] with or without amikacin (1 g IV/day). Doses were adjusted according to renal function. Clinical response was determined during and at completion of therapy.
                One hundred and twenty episodes were assessable for efficacy (59 piperacillin-tazobactam, 61 carbapenem). Mean duration of treatment was 14.8 +/- 9.6 days in the piperacillin-tazobactam group and 14.7 +/- 8.8 days in the carbapenem group (P > 0.05). Mean days of fever resolution were 5.97 and 4.48 days for piperacillin-tazobactam and carbapenem groups, respectively (P > 0.05). Similar rates of success without modification were found in the piperacillin-tazobactam (87.9%) and in the carbapenem groups (75.4%; P > 0.05). Fungal infection occurrence rates were 30.5 and 18% in piperacillin-tazobactam and carbapenem groups, respectively (P = 0.05). Antibiotic modification rates were 30.5 and 13.1% (P = 0.02) and the addition of glycopeptides to empirical antibiotic regimens rates were 15.3 and 44.3% for piperacillin-tazobactam and carbapenem groups, respectively (P = 0.001). The rude mortality rates were 14% (6/43) and 29.3% (12/41) in piperacillin-tazobactam and carbapenem groups, respectively (P = 0.08).
                The effect of empirical regimen of piperacillin-tazobactam regimen is equivalent to carbapenem in adult febrile neutropenic patients. A prospective, randomized clinical trial was conducted to compare the efficacy of piperacillin/tazobactam and amikacin combination with carbapenem monotherapy for the empirical treatment of febrile neutropenic episodes of children with acute lymphoblastic leukemia or acute myeloblastic leukemia. Patients aged 2-16 years with hematological malignancies who had febrile neutropenia were randomly assigned to receive piperacillin/tazobactam (80 mg/kg piperacillin/10 mg/kg tazobactam, q6h) combined with amikacin (PTA) (7.5 mg/kg, q12h) or meropenem or imipenem (20 mg/kg, q8h) (C). Response to antimicrobial therapy, evaluated for etiological agents, was measured. Duration of fever, neutropenia, and hospitalization, mortality, and the need for additional antibiotics or antifungal drugs were compared for the treatment success between the two groups. Out of 87 febrile neutropenic episodes that were evaluable for comparison, 46 patients received PTA and 41 patients were treated with carbapenems (imipenem or meropenem). Overall, the microbiologically documented infection rate was 21.9%, with Staphylococcus epidermidis as the most common cause of bacteremia. The rate of treatment modification was 56.5% in the PTA group and 53.6% in the carbapenem group with no statistical difference (p > .05). There was no infection-related mortality during the study period. There was no difference between the two regimens for durations of fever, neutropenia, and hospitalization (p > .05 for all categories). PTA was as effective as carbapenem monotherapy as an initial empirical regimen in febrile neutropenic episodes of pediatric hematological malignancies. The empirical treatment of febrile, neutropenic patients with cancer requires antibacterial regimens active against both gram-positive and gram-negative pathogens. This study was performed to demonstrate the noninferiority of monotherapy with piperacillin-tazobactam, compared with cefepime.
                We conducted a randomized-controlled, open-label, multicenter clinical trial among high-risk patients from 34 university-affiliated tertiary care medical centers in the United States, Canada, and Australia who were undergoing treatment for leukemia or hematopoietic stem cell transplantation and were hospitalized for empirical treatment of febrile neutropenic episodes. Patients received piperacillin-tazobactam (4.5 g every 6 h) or cefepime (2 g every 8 h) intravenously. The primary outcome was success (defined by defervescence without treatment modification) at 72 h of treatment, end of treatment, and test of cure in the modified intent-to-treat analysis. Secondary outcomes included time to defervescence, microbiological efficacy, the additional use of glycopeptide antibiotics, emergence of resistant bacteria, and safety.
                For 528 subjects (265 received piperacillin-tazobactam and 263 received cefepime), success rates were 57.7% and 48.3%, respectively (P = .04) at the 72-h time point, 39.6% and 31.6% (P = .06) at end of treatment, and 26.8% and 20.5% (P = .11) at the test-of-cure visit. The analyses demonstrated noninferiority for piperacillin-tazobactam at all time points (P< or = .0001). Treatment with piperacillin-tazobactam was independently associated with treatment success in multivariate analysis (odds ratio, 1.65; 95% confidence interval, 1.04-2.64; P = .035). Both regimens were well tolerated.
                This study demonstrates the noninferiority and safety of piperacillin-tazobactam monotherapy, compared with cefepime, for the empirical treatment of high-risk febrile neutropenic patients with cancer. The purpose of this study was to compare the efficacy, safety, and cost of piperacillin/tazobactam with cefepime monotherapy in children with febrile neutropenia. A prospective randomized study in children and adolescent with cancer was conducted. Patients were randomly assigned to receive either 80 mg/kg piperacillin/10 mg/kg tazobactam every 6 h (maximum 4.5 g/dose) or cefepime 50 mg/kg every 8 h (maximum 2 g/dose). Treatment modification was defined as all the changes in the empirical antimicrobials after the first 96 h. Overall treatment success was defined as cure of febrile episode with or without modification. Cost of hospitalization, antimicrobial drugs, and supportive therapy were calculated. Fifty febrile neutropenic episodes (25 in the piperacillin/tazobactam group, 25 in the cefepime group) in 27 pediatric cancer patients were evaluated. The groups were comparable in terms of age, gender, body weight, primary diagnosis, disease status, initial neutrophil count, and duration of neutropenia. Microbiologically and clinically documented infection rate was 46%. There was no infection-related mortality in the study period. The treatment success of initial empirical therapy without modification was not different in the 2 groups (56% in piperacillin/tazobactam group and 48% in cefepime group). Anti-anaerobic drugs were added more frequently in the cefepime group. Duration of fever, neutropenia, treatment, and cost of therapy were not different in the treatment groups. Piperacillin/tazobactam monotherapy is as effective as cefepime monotherapy in febrile neutropenia of pediatric cancer patients. This is a prospective, randomized, and open-label clinical trial that examines the efficiency and safety of PIP/TAZO monotherapy in comparison to cefepime (CEF), for the empirical treatment of pediatric cancer patients with neutropenia and fever.
                One hundred thirty-one consecutive febrile episodes in 70 neutropenic pediatric cancer patients received randomized treatment either with piperacillin/tazobactam (PIP/TAZO) 80 mg/kg piperacillin/10 mg/kg tazobactam every 6 hr or CEF 50 mg/kg every 8 hr. Clinical response was determined at completion of therapy. Duration of fever, neutropenia, hospitalization, the need for modification of the therapy, and mortality rates were compared between the two groups.
                One hundred twenty-seven episodes in 69 patients (35 females, 34 males) with a median age of 4.2 years were assessed for efficiency (65 PIP/TAZO, 62 CEF). The frequency of success without modification of treatment was nearly identical for both PIP/TAZO (60.0%) and CEF (61.3%) (P > 0.05). The overall response rate, with or without modification of assigned treatment, was 96.9% for PIP/TAZO and 98.4% for CEP (P > 0.05). Infection-related mortality at the end of the febrile episode was 2.4%. Duration of fever and hospitalization were not different between the treatment groups. No major side effects were observed in neither of the groups.
                PIP/TAZO treatment was as effective and safe as CEF monotherapy as an initial empirical regimen in pediatric cancer patients with fever and neutropenia. 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.
                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.
                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).
                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. Concerned about the inactivation of piperacillin by beta-lactamase and the risk of aminoglycoside-induced nephrotoxicity and clindamycin-induced enterocolitis, we conducted the following phase III clinical trial.
                Between November 1991 and March 1993, 77 surgical patients with intraabdominal infections were enrolled and randomly assigned in a 3:2 ratio to receive either piperacillin/tazobactam or clindamycin plus gentamicin to compare safety, tolerance and efficacy between both two treatment groups.
                There were 76 clinically and 50 bacteriologically evaluable patients with 80 isolated pathogens. The demographic data were comparable in both groups. There was no statistically significant difference of clinical response at any time-point of treatment, with 97.8% favorable clinical response rate in piperacillin tazobactam group and 96.6% in clindamycin plus gentamicin group at endpoint. The bacteriological eradication rates were similar, with 97.7% in piperacillin/tazobactam group and 94.4% in clindamycin plus gentamicin group at pathogen level, and 96.7% in piperacillin/tazobactam group and 95.0% in clindamycin plus gentamicin group at patient level. By susceptibility tests, only 3 (4%) isolated pathogens were resistant to piperacillin/tazobactam, which was much superior to the use of piperacillin, clindamycin or gentamicin alone in antimicrobial activity. The piperacillin tazobactam-related adverse experiences included 1 (2.1%) urticaria and 2 (4.3%) diarrhea. However, there were no significant differences in the adverse experiences between these two groups.
                This study has demonstrated that piperacillin/tazobactam is comparable with clindamycin plus gentamicin in efficacy, safety and tolerance in the treatment of surgical patients with intra-abdominal infections. The combination of piperacillin/tazobactam could potentially be the treatment of choice in adjunt to surgical management in intra-abdominal infection. A three-arm prospective randomized trial was designed to compare the efficacies of piperacillin plus vancomycin, ceftazidime plus vancomycin, or all three drugs as initial therapy for fever in neutropenic cancer patients. The objectives were to determine whether a broad-spectrum penicillin was as effective as a broad-spectrum cephalosporin and whether two beta-lactam antibiotics were more effective than one. Four hundred and seventy of the 519 febrile episodes entered in the study could be evaluated for response. Ceftazidime plus vancomycin was significantly more effective than piperacillin plus vancomycin, considering all febrile episodes (79 percent versus 61 percent, p = 0.001), documented infections (79 percent versus 57 percent, p = 0.004), gram-negative infections (88 percent versus 47 percent, p = 0.001), and bacteremias (81 percent versus 51 percent, p = 0.01). The addition of piperacillin to ceftazidime (piperacillin plus ceftazidime and vancomycin versus ceftazidime plus vancomycin) did not improve the response rate and was associated with a significantly higher incidence of skin rash. Vancomycin plus ceftazidime provides adequate antibiotic coverage for initial treatment of fever in neutropenic patients. This combination was equally effective, less expensive, and less toxic than the double beta-lactam combination used in this study.
Current evidence supports the use of piperacillin-tazobactam in locations where antibiotic resistance profiles do not mandate empirical use of carbapenems. Carbapenems result in a higher rate of antibiotic-associated and Clostridium difficile-associated diarrhea. There is a high level of evidence that all-cause mortality is higher with cefepime compared to other beta-lactams and it should not be used as monotherapy for patients with febrile neutropenia.