Randomized comparison of sulbactam/cefoperazone with imipenem as empirical monotherapy for febrile granulocytopenic patients. Meropenem versus ceftazidime as empirical monotherapy for febrile neutropenic cancer patients. A comparative study of cefepime versus ceftazidime as empiric therapy of febrile episodes in neutropenic patients. Experience with cefepime versus meropenem as empiric monotherapy for neutropenia and fever in pediatric patients with solid tumors. Randomized trial of beta-lactam regimens in febrile neutropenic cancer patients. A comparison of imipenem to ceftazidime with or without amikacin as empiric therapy in febrile neutropenic patients. Empirical monotherapy with meropenem versus imipenem/cilastatin for febrile episodes in neutropenic patients. Cefepime vs. Meropenem as empirical therapy for neutropenic fever in children with lymphoma and solid tumours. Cefepime or carbapenem treatment for febrile neutropenia as a single agent is as effective as a combination of 4th-generation cephalosporin + aminoglycosides: comparative study. A comparison of aztreonam plus vancomycin and imipenem plus vancomycin as initial therapy for febrile neutropenic cancer patients. Cefepime versus ceftazidime as empirical therapy for fever in neutropenic patients with haematological malignancies. Meropenem versus ceftazidime as empirical monotherapy in febrile neutropenia of paediatric patients with cancer. Randomized comparison of cefepime versus ceftazidime monotherapy for fever and neutropenia in children with solid tumors. Treatment of febrile neutropenic patients with cancer who require hospitalization: a prospective randomized study comparing imipenem and cefepime. Imipenem-cilastatin versus piperacillin-tazobactam as monotherapy in febrile neutropenia. Beta-lactam regimens for the febrile neutropenic patient. Comparative study of cefepime versus ceftazidime in the empiric treatment of pediatric cancer patients with fever and neutropenia. Imipenem or cefoperazone-sulbactam combined with vancomycin for therapy of presumed or proven infection in neutropenic cancer patients. A prospective, randomized study comparing cefepime and imipenem-cilastatin in the empirical treatment of febrile neutropenia in patients treated for haematological 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. Empirical antimicrobial monotherapy in patients after high-dose chemotherapy and autologous stem cell transplantation: a randomised, multicentre trial. Panipenem versus cefepime as empirical monotherapy in adult cancer patients with febrile neutropenia: a prospective randomized trial. Cefepime versus imipenem-cilastatin as empirical monotherapy in 400 febrile patients with short duration neutropenia. CEMIC (Study Group of Infectious Diseases in Cancer). Piperacillin/tazobactam vs ceftazidime in the treatment of neutropenic fever in patients with acute leukemia or following autologous peripheral blood stem cell transplantation: a prospective randomized trial. Cefepime versus ceftazidime as empiric monotherapy for fever and neutropenia in children with cancer. Meropenem versus ceftazidime in the treatment of cancer patients with febrile neutropenia: a randomized, double-blind trial. 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 versus cefepime for the empirical treatment of pediatric cancer patients with neutropenia and fever: a randomized and open-label study. Equivalent efficacies of meropenem and ceftazidime as empirical monotherapy of febrile neutropenic patients. The Meropenem Study Group of Leuven, London and Nijmegen. Randomised comparison of ceftazidime and imipenem as initial monotherapy for febrile episodes in neutropenic cancer patients. [Comparative study of piperacillin/tazobactam versus imipenem/cilastatin in febrile neutropenia (1994-1996)]. Monotherapy for fever and neutropenia in cancer patients: a randomized comparison of ceftazidime versus imipenem. Empiric monotherapy for febrile neutropenia--a randomized study comparing meropenem with ceftazidime. Piperacillin/tazobactam versus cefepime as initial empirical antimicrobial therapy in febrile neutropenic patients: a prospective randomized pilot study. Ceftazidime versus imipenem-cilastatin as initial monotherapy for febrile neutropenic patients. Cefepime versus ceftazidime as empiric therapy for fever in neutropenic patients with cancer. Monotherapy with piperacillin/tazobactam versus cefepime as empirical therapy for febrile neutropenia in pediatric cancer patients: a randomized comparison.
In a prospective, randomized, controlled trial, we compared sulbactam/cefoperazone with imipenem as empirical monotherapy for febrile, granulocytopenic patients; 101 patients received sulbactam/cefoperazone (2 g/4 g every 12 hours) and 102 patients received imipenem (500 mg every 6 hours). Documented infections were present in 40% of patients treated with sulbactam/cefoperazone (40 of 101) and in 39% of patients receiving imipenem (40 of 102). The number of pretherapy gram-positive pathogens (52 isolates) was twice the number of pretherapy gram-negative pathogens (26 isolates). The overall favorable clinical response rates for sulbactam/cefoperazone (91 of 103 patients, or 88%) and imipenem (84 of 104 patients, or 81%) were similar. Both drugs were generally well tolerated. However, diarrhea occurred more often in patients treated with sulbactam/cefoperazone (31 of 101 patients, or 31%, vs. 15 of 102 patients, or 15%; P = .007), while seizures developed only in patients receiving imipenem (0 of 101 patients vs. 3 of 102 patients, or 3%). Superinfections developed in 16% of patients in both study groups but were infrequently caused by beta-lactam-resistant gram-negative bacilli (two cases with sulbactam/cefoperazone therapy and six cases with imipenem). These results support the efficacy and safety of either sulbactam/cefoperazone or imipenem as empirical monotherapy for febrile granulocytopenic patients. A total of 101 cancer patients with 121 febrile neutropenia episodes were randomised to receive empirical treatment with i.v. meropenem (1g/8 h) or ceftazidime (2 g/8 h). After 3 days, 89% of patients were on unmodified therapy in the meropenem group, compared with 83% in the ceftazidime group. Of the evaluable episodes (n = 106), the success rate with unmodified empirical therapy until the end of the treatment course was slightly higher with meropenem than with ceftazidime (48% vs 38%, P=0.39). Furthermore, initial success with further infections was observed in 22% of episodes treated with meropenem and in 13% of episodes treated with ceftazidime. Glycopeptides were used as first modification in 28% and 39% of meropenem and ceftazidime recipients, respectively. Both treatments were well tolerated and there were no reports of drug-related nausea/vomiting or seizures. No significant differences in response rate or in tolerability were observed when analysing only the first febrile episodes. In conclusion, meropenem seems to be as efficacious and well tolerated as ceftazidime and may be associated with a lesser requirement for the addition of glycopeptides. An open-label, randomized comparative study was conducted to evaluate the efficacy and safety of cefepime (2.0 g q. 8 h) and ceftazidime (2.0 g q. 8 h) in the empiric therapy of febrile neutropenic patients. A total of 45 eligible febrile episodes were randomized (1:1) to be treated with the study regimen. Nineteen febrile episodes treated with cefepime and 22 febrile episodes treated with ceftazidime were evaluable for efficacy. The two groups were comparable in terms of age, sex, height, weight, underlying neoplasm, number of pretherapy neutrophil, duration of neutropenia and types of infections. The overall therapeutic success rate of the cefepime group (53%) was comparable to the ceftazidime group (50%). It did not differ significantly (95% confidence interval: -0.28 to 0. 34, p = 0.85). Eighty-eight percent of pathogens in each group were bacteriologically eradicated. The safety profile was similar in both groups. No patients in either group discontinued the therapy because of adverse events. None (0%) of the cefepime patients and 2 (9%) of the ceftazidime patients died of infection. The results of this study suggest that cefepime is an effective and safe agent in the empiric therapy of febrile episodes in neutropenic patients. A prospective, open-label, randomized, comparative study in pediatric cancer patients was conducted to evaluate the efficacy and safety of cefepime and meropenem in the empiric therapy of febrile neutropenic patients. Febrile episodes were classified as microbiologically documented infection, clinical documented infection, or fever of unknown origin. Clinical response to therapy was classified as success or failure. In this period 37 children with solid tumors including lymphoma, 25 males, 12 females, had neutropenia on 65 occasions. Microbiologically documented infections occurred in 21 episodes (32.31%). Frequency of positive bacteria isolated was higher than gram-negative bacteria. There was no infection-related death. There were no statistical differences between the cefepime and meropenem groups for duration of fever or neutropenia, response rate, and necessity for modification. Cefepime appears to be as effective and safe as meropenem for empiric treatment of febrile episodes in neutropenic pediatric cancer patients. 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. Neutropenic patients with cancer are traditionally treated with empiric antibiotic combinations when they become febrile. The availability of broad-spectrum antibiotics such as ceftazidime and imipenem has made it possible to initiate therapy with a single agent (monotherapy). The objectives of this trial were to compare ceftazidime and imipenem as single agents for the therapy of febrile episodes in neutropenic patients and to ascertain whether the addition of an aminoglycoside (amikacin) to either of these agents would provide an advantage.
                A prospective clinical trial was conducted in which eligible neutropenic patients with cancer were randomized to one of four treatment arms: ceftazidime alone; imipenem alone; ceftazidime plus amikacin; and imipenem plus amikacin. Efficacy analysis was done for 750 assessable episodes. A multivariate logistic-regression analysis was also performed to examine the unique contribution of various prognostic factors.
                The overall response rates were 76% with imipenem plus amikacin, 72% with imipenem, 71% with ceftazidime plus amikacin, and 59% with ceftazidime alone. Single-organism gram-positive infections occurred in 101 of 750 episodes. Without a change in antibiotics, the response rates were 50% with imipenem, 40% with imipenem plus amikacin, 39% with ceftazidime plus amikacin, and 38% with ceftazidime. Most responded to vancomycin or other antibiotics, and the mortality associated with gram-positive infections was only 5%. Regardless of the antibiotic regimen, the majority of uncomplicated gram-negative infections responded to therapy and the majority of complicated gram-negative infections failed to respond. Multivariate logistic-regression analysis showed that recovery of the neutrophil count was the most favorable prognostic factor in a patient's response to infection, whereas the presence of gram-positive infection, acute leukemia, pulmonary or enteric infection, and therapy with ceftazidime were unfavorable factors.
                Single-agent therapy with imipenem is as effective as more conventional combination antibiotic therapy for the empirical treatment of febrile episodes in neutropenic patients with cancer. In a nonblind, randomised, parallel-group study, initial empirical monotherapy with meropenem 1 g intravenously every 8 h was compared to an identical dosage of imipenem/cilastatin for the treatment of 66 febrile episodes in 61 adult neutropenic patients. 25/31 episodes treated with meropenem and 24/30 imipenem/cilastatin-treated episodes were still receiving unmodified therapy at 72 h (primary endpoint); this difference was not statistically significant. By the end of the treatment courses, 18/31 meropenem-treated episodes had responded clinically (cured or improved) compared with 18/30 episodes treated with imipenem/cilastatin. Another ten episodes initially treated with meropenem and six episodes treated with imipenem/cilastatia were cured after an additional antimicrobial agent had been administered (cured with modification). Satisfactory bacteriological responses (eradication plus presumed eradication) at the end of unmodified therapy was 9/11 in the meropenem group and 14/16 in the comparator group. Both regimes were well tolerated; however, there were more reports of nausea and/or vomiting in the impenem/cilastatin group (7/33 vs. 2/33 in the meropenem group). The carbapenems meropenem and imipenem/cilastatin appear to be suitable agents for empirical monotherapy of febrile episodes in neutropenic patients. Meropenem may be better tolerated than imipenem/cilastatin, allowing optimal dosing in this patient population. nan 1998, a consensus meeting was held in Miyazaki, Japan, to develop an approach to management of febrile neutropenia (FN). The K-HOT study group decided to examine whether this proposal was applicable to clinical practice in a multicenter study. Patients who developed fever with neutrophil counts <1,000/microL were randomized to receive either a single antibiotic, cefepime or one of the carbapenems, or a combination of cefepime and an aminoglycoside. Patients who became afebrile within the first 3 days were continued on the same treatment. Patients who remained febrile were switched to a combination regimen if they were randomized to receive a single agent, and patients on combination medication were changed from cefepime to another cephalosporin. A total of 165 patients were entered into the trial. One hundred fifty-three patients were evaluable for response. The average age was 52 years, and 70% of the patients had acute leukemia. Severe neutropenia, defined as <100/microL at the time of FN, was seen in 62% of the patients on entry and during the course of treatment 71% of patients experienced neutrophil counts of <100/microL. Microbiologically documented infection was seen in 6.5% for monotherapy, and 10.5% for a combination treatment, and fever of unknown origin occurred in 75.3% and 59.2% of the patients in each regimen, respectively. Excellent to good response was seen in two-thirds of the patients in all treatment groups. Adverse events were minimal, and three early deaths were observed at days 9, 16, and 16 among patients treated with a single antibiotic and three in the combination regimen group at days 14, 15, and 20. These results indicate that cefepime or a carbapenem alone is as effective as a combination of cefepime and an aminoglycoside for treating FN.
                Copyright 2002 Wiley-Liss, Inc. The improved efficacy of imipenem over other beta-lactam antibiotics in the treatment of febrile neutropenic patients has been attributed to its broad spectrum of activity.
                A prospective, randomized, clinical trial was performed comparing vancomycin 1 g every 12 hours plus imipenem/cilassatin 500 mg every 6 hours and the same dose of vancomycin plus aztreonam 2 g every 6 hours for empiric treatment of febrile episodes in neutropenic patients with cancer.
                The imipenem regimen cured 76% of the 148 evaluable episodes compared with a 67% cure rate for the 152 episodes treated with the aztreonam regimen (p = 0.1). Most of the polymicrobial infections (77% or 10/13) treated with the imipenem responded, whereas only 38% (5/13) of these infections responded to the aztreonam regimen. Although the cost of the imipenem regimen was less than the cost of the aztreonam regimen, it was associated significantly more with skin rashes (12/194 vs 3/189, p = 0.02). In a multivariate analysis, a poor outcome was independently associated in both instances with the persistence of neutropenia and the presence of pneumonia (p < 0.001).
                Overall, in a multifactorial analysis that included efficacy, toxicity, and cost, the imipenem and aztreonam regimens were comparable. An open randomized comparative study was conducted to evaluate the efficacy of Cefepime (2 gm iv. 8 hr.) vs. ceftazidime (2 gm iv. every 8 hr.) in empirical therapy of febrile neutropenic patients. A total of 40 eligible febrile episodes were randomized to be treated with study regimen. Twenty febrile episodes were treated with cefepime and 20 were treated with ceftazidime. The two groups were comparable in terms of age, sex, height, underlying neoplasm, number of pretherapy neutrophils, duration of neutropenia. The overall therapeutic success rate of cetepime group (60%) was comparable to that of ceftazidime group (55%). The results of this study suggest that cefepime is an effective and safe agent in empirical therapy of febrile episode in neutropenic patient and its efficacy is comparable with that of ceftazidime. This trial assessed the efficacy and safety of meropenem versus ceftazidime as empirical monotherapy for febrile neutropenia in paediatric cancer patients. In a prospective randomized study, 172 evaluable febrile episodes in the meropenem arm and 170 episodes in the ceftazidime arm were analysed for the clinical and microbiological response dependent on the kind of infection. About half the episodes were classified as fever of unknown origin (FUO) and the remainder as microbiologically or clinically documented infections. The most frequently documented infections in both arms were bacteraemias (22.1 versus 26.5%), predominantly caused by Gram-positive organisms (57.9 versus 71.1%). The success rate of the initial monotherapy differed significantly between the two arms and was 55.8% in the meropenem and 40.0% in the ceftazidime arm (P = 0.003). In addition, a significantly longer duration of fever and of antimicrobial therapy was observed in the ceftazidime arm than in the meropenem arm (median 5 versus 4 days, P = 0.022, and 7 versus 6 days, P = 0.009, respectively). With respect to the kind of infection, differences between the two arms were significant only in episodes classified as FUO but not in documented infections. In both arms, side effects were minimal. Despite the greater response rate for meropenem in FUO, the fact that ceftazidime has been proven to be as effective as meropenem in documented infections in the present study suggests that both drugs are useful as empirical monotherapy in febrile paediatric cancer patients. With the availability of new broad-spectrum antibiotics, initial therapy with a single agent has become an alternative to classic combinations, especially beta-lactam antibiotics plus aminoglycosides, in the management of febrile neutropenic cancer patients.
                Since January 1994, monotherapy has been used for empiric initial treatment at our center. The aim of this prospective randomized study is to compare the efficacy of cefepime (CFP), a new fourth-generation cephalosporin, and ceftazidime (CFZ) as empirical monotherapy of febrile neutropenic patients with solid tumors. From January 1998 to November 1998, 63 episodes of fever and neutropenia occurring in 33 children with solid tumors including lymphomas, were randomized to receive treatment with either CFP or CFZ. The patients were analyzed for leukocyte count and absolute neutrophil count (ANC) at entry, days in fever, neutropenia and hospitalization, and side effects of drugs. Success with or without modifications of the initial antibiotic was defined as survival through neutropenia; failure was death due to infection.
                In our study group, with a median age of 7 [(1/12)-14] years, CFP was administered in 32, and CFZ in 31 episodes. An infection was documented microbiologically in eight episodes (25%) in the CFP arm and in nine episodes (29%) in the CFZ arm. The success rate with initial empiric monotherapy was 62.5% in the CFP arm and 61.3% in the CFZ arm respectively (P > 0.05). The total success rate (success with or without modification) was 100% in both arms. No major adverse effects were observed in either groups.
                CFP is as effective and safe as CFZ for the empirical treatment of febrile episodes in neutropenic patients with solid tumors.
                Copyright 2001 Wiley-Liss, Inc. The objective of the current study was to compare the efficacy and safety of imipenem and cefepime in the treatment of adult patients with cancer who had fever and neutropenia requiring hospitalization according to Infectious Disease Society of America criteria.
                In the current prospective randomized clinical trial at a university-affiliated tertiary cancer center, adult patients with cancer who had fever (> or = 38.3 degrees C or > or = 38.0 degrees C for > 2 hours) and neutropenia (< or = 500/mm(3) or < 1000/mm(3) but declining) requiring hospitalization were randomized to receive either cefepime or imipenem. Vancomycin or amikacin was added on suspicion of gram-positive or gram-negative bacterial infection, respectively.
                Patients who received an imipenem regimen or a cefepime regimen were comparable in terms of age, gender, underlying malignancy, prior transplantation, degree and trend of neutropenia, and presence of central venous catheters (P > or = 0.3). An intent-to-treat analysis showed a 68% response rate to the imipenem regimen, compared with a 75% response rate to the cefepime regimen (P = 0.2). The rates of antibiotic-related adverse events and superinfections also were comparable (P = 0.6). There was no difference in response among patients who received imipenem or cefepime alone compared with patients who also received vancomycin or amikacin (P = 1.0). Leukemia was the only independent risk factor associated with a poor outcome (odds ratio, 4.6; 95% confidence interval, 1.9-10.7; P < 0.0001).
                Imipenem and cefepime had similar efficacy and safety profiles in the treatment of adult cancer patients with fever and neutropenia who required hospitalization. The addition of either vancomycin or amikacin may not be necessary.
                Copyright 2003 American Cancer Society. In view of the recent trend toward monotherapy in the treatment of febrile neutropenia, we evaluated the clinical efficacy and safety of imipenem-cilastatin versus piperacillin-tazobactam as an empiric therapy for febrile neutropenia in children with malignant diseases.
                Febrile neutropenic patients received either imipenem-cilastatin or piperacillin-tazobactam randomly. Improvement without any changes in the initial antibiotic treatment was defined as "success" and improvement with modification of the initial treatment and death was defined as "failure".
                Over 12 months, 99 febrile neutropenic episodes were treated with monotherapy in 63 patients with a median age of 5 years. At admission, median absolute neutrophil count was 50/mm(3) and in 67% of episodes, neutrophil count was under 100/mm(3). Median duration of neutropenia was 5 days. In 22% of episodes, neutropenia persisted for more than 10 days. Piperacillin-tazobactam was used in 52 episodes and imipenem-cilastatin was used in 47 episodes. There was no difference between groups in terms of age, sex, primary diseases, neutrophil count or duration of neutropenia. In the whole group, the success rate was 67% and the failure rate was 33%, whereas in the piperacillin-tazobactam group, the rates were 71% and 29%; and in the imipenem-cilastatin group they were 62% and 38%, respectively (P > 0.05). There were no deaths. No major adverse effects were seen in either group.
                Although failure was slightly higher in the imipenem-cilastatin group, this was statistically insignificant. Both of these antibiotics can be used safely for initial empirical monotherapy of febrile neutropenia. A total of 535 evaluable febrile episodes in neutropenic patients were randomly assigned to treatment with ticarcillin-clavulanate plus vancomycin (TV), ceftazidime plus vancomycin (CV), or all three antibiotics (TCV). The TCV regimen was significantly more effective than TV, considering all evaluable episodes, documented infections, gram-negative infections, and infections in patients with persistent severe neutropenia (less than 100 neutrophils/mm3). The results with CV were intermediate between TV and TCV. The toxicities were similar with all three regimens and consisted primarily of skin rashes. The TCV regimen is effective for empiric therapy of fever in neutropenic patients and probably should be utilized in preference to CV or TV, although its superiority over CV in this study was inconclusive. In view of the recent trend toward monotherapy in the treatment of bacterial infection, we evaluate the clinical efficacy and safety of cefepime vs. ceftazidime for the empiric treatment of febrile episodes in neutropenic pediatric cancer patients.
                In a single site, open label study, 104 neutropenic pediatric cancer patients [96% with absolute neutrophil count (ANC) of <500 neutrophils/mm3] with a median age of 6 years were randomized (1:1) to receive either intravenous cefepime or ceftazidime (50 mg/kg/dose every 8 h; < or = 6 g/day) for empiric treatment of fever (temperature >38.0 degrees C occurring at least twice in 24 h, or single >38.5 degrees C). Febrile episodes were classified as either microbiologically or clinically documented infection or fever of unknown origin. Therapy continued until the ANC was > or = 1,000 neutrophils/mm3 or there was an increasing ANC in low risk patients (maximum duration of treatment, 8 weeks). The primary efficacy endpoints assessed were clinical and microbiologic response to assigned drug therapy. Secondary outcome measures were rate of early discontinuation of study drug and use of concomitant antibiotic therapy to modify initial study drug regimen.
                Of 68 patients who could be evaluated for efficacy, 74% (26 of 35) of cefepime-treated patients and 70% (23 of 33) of ceftazidime-treated patients responded to treatment. The small number of study patients precluded statistical analysis of results. In a modified intent-to-treat analysis, 59% of the patients treated with cefepime and 47% of ceftazidime-treated patients responded to therapy. Cefepime patients developed fewer new infections than ceftazidime patients (9% vs. 21%, respectively) and early discontinuation of study drug therapy occurred slightly more often in the ceftazidime group. Further, the use of concomitant systemic antimicrobial therapy (mostly vancomycin) occurred less often in the cefepime-treated patients, as compared with the ceftazidime group [35% [17 of 49] vs. 44% (24 of 55), respectively]. No deaths or serious adverse events were considered to be related to study therapy. The most frequent adverse event was rash that was moderate in severity, and it occurred equally in both groups.
                Cefepime appears to be safe and effective compared with ceftazidime for initial empiric therapy of febrile episodes in neutropenic pediatric cancer patients. The purpose of this prospective randomized study was to compare the efficacy and safety of imipenem and cefoperazone-sulbactam combined with vancomycin for the treatment of fever in neutropenic cancer patients. Patients were assigned to either imipenem 500 mg/m2 (500 mg for bone marrow transplant recipients) every 6 h or cefoperazone (2 g)-sulbactam (1 g) every 8 h All patients received vancomycin 1 g every 12 h. A total of 457 febrile or infectious episodes occurring in 407 patients were entered in the study. The response rate was 73% for imipenem plus vancomycin and 74% for cefoperazone-sulbactam plus vancomycin among the 369 episodes that could be evaluated. Response rates were comparable for the two regimens with regard to infecting organism, administration of antimicrobial prophylaxis, and neutrophil count and trend. The frequency of side-effects was significantly higher for imipenem plus vancomycin (11% vs.5%, p = 0.02), due to therapy-associated nausea and vomiting (5.3% vs. 0%, p = 0.0004). The overall frequency of superinfections was similar with both regimens, but Clostridium difficile colitis occurred significantly more often in patients receiving imipenem plus vancomycin (5 vs. 0, p = 0.02). In this study cefoperazone-sulbactam plus vancomycin was an effective alternative to imipenem plus vancomycin for initial therapy of fever in neutropenic patients. A prospective, open label, randomized, multicentre study was conducted, comparing the efficacy and safety of cefepime with that of imipenem-cilastatin for the management of febrile neutropenia in patients with haematological malignancies. Furthermore, the safety of early discontinuation of antibiotic therapy in patients with fever of undetermined origin (FUO) was assessed. A total of 180 patients with 207 febrile episodes were randomized at start of fever (105 episodes for cefepime and 102 episodes for imipenem). The 2 groups were comparable in terms of age, gender, underlying malignancy, prior transplantation, and presence of central venous catheters. All patients were neutropenic at inclusion with median absolute neutrophil count (ANC) 0.1 x 10(9)/l(range 0-1 x 10(9)/l), and ANC < or = 0.1 x 10(9)/l in 77% of included patients. The mean duration of neutropenia, with ANC < 0.5 x 10(9)/l was 6.2 d. Febrile episodes were classified as microbiologically documented infection (47%), FUO (43%), or clinically documented infection (10%). At final evaluation 1-2 weeks after completion of antibiotic therapy, monotherapy success rates were 40% and 51% in the cefepime and imipenem-cilastatin groups respectively (p = 0.33). The 4-week overall mortality rate was 5%. Three (2%) of the cefepime treated patients and 4 (3%) of the imipenem-cilastatin treated patients died as a result of infection. Adverse events directly related to antibiotic treatment were uncommon and did not differ between groups. Early discontinuation of antibiotic therapy in 31 patients with FUO 48 h after defervescence was not associated with an increased rate of fever relapse or mortality compared with a subgroup of 29 patients where therapy was continued. 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. We report on 232 patients undergoing autologous haematopoietic stem cell transplantation (ASCT) entered into a multicentre, randomised trial comparing the efficacy and tolerability of meropenem (MPM) with that of piperacillin/tazobactam (P/T) as empirical antimicrobial first-line therapy for febrile neutropenia. In 27.6% of patients in the MPM group and 22.4% in the P/T group, therapy was initially supplemented with a glycopeptide for venous catheter infection or bacteraemia because of coagulase-negative staphylococci. Complete response rate after 72 h was 63.8% in the MPM group and 49.6% in the P/T group (P = 0.034). Overall complete response rate after treatment modification was 94.0% in the MPM group and 93.1% in the P/T group. Median time to defervescence was 2 d in the MPM group and 3 d in the P/T group. The most frequently isolated pathogens were Gram-positive cocci. Treatment was well tolerated in both groups. One patient (0.4%) died from infection. Empirical first-line therapy with MPM as well as with P/T is safe and effective in febrile episodes emerging after ASCT. Higher response rates to primary treatment can be achieved with MPM. To compare the efficacy and safety of panipenem/betamipron with cefepime as empirical monotherapy for adult cancer patients with febrile neutropenia, a randomized, open-label, comparative trial was performed.
                All enrolled patients were randomly assigned to receive either panipenem or cefepime. All febrile episodes were classified as microbiologically defined infection (MDI), clinically defined infection (CDI) or unexplained fever (UF). Clinical responses to antibiotic therapy were defined as success, initial response but regimen modified or failure.
                A total of 116 patients were enrolled: 55 patients in the panipenem group and 61 patients in the cefepime group. Demographic and clinical characteristics were similar in the two groups (P > 0.05). In the final evaluation, the success rate for the panipenem group (89.1%) was similar to that of the cefepime group (91.8%) (non-inferiority, P = 0.002, 95% confidence interval: -13.48%, 10.35%). Of the 18 bacterial isolates, nine (50%) were gram-positive and nine (50%) were gram-negative. The prevalence of adverse events in the panipenem group (23.6%) were similar to those in the cefepime group (23.0%) (P = 0.93). All of the adverse events were well tolerated and transient.
                Although larger studies are necessary, panipenem appeared to be as effective and safe as cefepime for empirical monotherapy in the treatment of adult cancer patients with febrile neutropenia. This open, comparative, randomized, multicentre equivalence study compared cefepime 2 g bd and imipenem-cilastatin 1 g tds (50 mg/kg/day) as empirical monotherapy for febrile episodes in a homogeneous cohort of cancer patients with short duration neutropenia following chemotherapy for solid tumour, lymphoma or myeloma. The study was conducted in 17 French anti-cancer centres in 1995 and 1996. Response to monotherapy was assessed 7 days after treatment and was based on resolution of fever and signs and symptoms, eradication of pathogens, absence of new infection, relapse, and death of infectious origin, without addition of other antibiotics. Patients were treated for a minimum of 4 days. Of the 400 episodes randomized, 344 (86%) were evaluable for efficacy. Patient characteristics were comparable between treatment groups. Success of monotherapy was observed in 79% of episodes with cefepime and 72% with imipenem-cilastatin (equivalence, P <0.0001). The response rate for microbiologically documented infections was 66% with cefepime and 61% with imipenem-cilastatin (bacteraemic episodes: 63% for cefepime; 44% for imipenem-cilastatin). A second antibiotic (usually a glycopeptide) was added in 20% and 21% of the cases, respectively. Overall, the response to therapy, with or without an additional antibiotic, was 95% (cefepime) and 90% (imipenem-cilastatin). Survival was similar in both groups (95% and 98%, respectively). Cefepime treatment was better tolerated, with 9% of the patients experiencing related intercurrent events compared with 19% in the imipenem-cilastatin group (P = 0.003). Nausea/vomiting was significantly more frequent in the imipenem-cilastatin group (15%) than in the cefepime group (5%; P = 0.001). Cefepime monotherapy was as effective as, and better tolerated than, imipenem-cilastatin in the empirical treatment of fever during short duration neutropenia. Piperacillin/tazobactam was compared with ceftazidime for the empirical treatment of febrile neutropenia in patients with acute leukemia or following autologous peripheral blood stem cell transplantation. Owing to inclusion criteria, it was possible for the same patient to be randomized several times. A total of 219 individual patients were admitted to a prospective randomized clinical study: 24 patients were included twice. Patients (23.5%) remained afebrile. Patients who developed febrile neutropenia were randomized to receive intravenous ceftazidime (n = 74 patients, group I) or piperacillin/tazobactam (n = 87 patients, group II). Response to first-line antibiotic treatment was seen in 55% (group I) and 53% (group II). After the addition of vancomycin, a further 19% (group I) and 24% (group II) of the patients became afebrile. Causes of fever were: microbiologically documented infection in 36 and 34 patients of group I and II; Clostridium difficile in eight and 12 patients of group I and II, and fever of unknown origin in 30 and 41 patients of group I and II. One patient died in each group. Single-agent therapy with piperacillin/tazobactam is as effective as ceftazidime in the treatment of neutropenic fever and is well tolerated. Direct and indirect costs of both treatment regimes are equivalent. Monotherapy with cefepime or ceftazidime is an effective alternative to combination therapy for the treatment of febrile neutropenic adult cancer patients. We compared the efficacy and safety of cefepime and ceftazidime as empiric monotherapy of febrile neutropenia in children with cancer.
                A prospective, open label, randomized, comparative study in pediatric cancer patients was conducted at Chang Gung Children's Hospital from January 1, 2000, to April 15, 2001. Patients with fever and neutropenia (absolute neutrophil count of < or = 500/mm3) were randomized to receive either intravenous cefepime or ceftazidime (50 mg/kg/dose as two or three doses daily). Febrile episodes were classified as microbiologically documented infection, clinically documented infection or unexplained fever. Clinical response to therapy was classified as success and failure.
                Ninety-five pediatric cancer patients with 120 febrile neutropenic episodes were randomized to receive empiric treatment with cefepime or ceftazidime. After 72 h of treatment, 82.8% (48 of 58) of the eligible patients in the cefepime group continued with unmodified therapy, compared with 87.9% (51 of 58) in the ceftazidime group. The neutrophil count was <100/mm3 at randomization for 76% of the patients in the cefepime group and 83% of those in the ceftazidime group; the median durations of neutropenia (<500/mm3) were 8.5 and 6.5 days, respectively. Of the 96 evaluable episodes the overall success rate with unmodified empiric therapy until the end of the treatment course in the cefepime group was comparable with that in the ceftazidime group (69% vs. 71%, P = 0.95). The response rate after glycopeptides were added to the regimens was 79.2% for the cefepime group and 77.1% for the ceftazidime group. The bacterial eradication rate was 33% for the cefepime group and 20% for the ceftazidime group (P = 0.85), and the rates of new infections were 10.4% vs. 4.2% (P = 0.67), respectively. Both study drugs were well-tolerated. Three (6.4%) patients in the cefepime group and 2 (4.3%) patients in the ceftazidime group died.
                Cefepime appeared to be as effective and safe as ceftazidime for empiric treatment of febrile episodes in neutropenic pediatric cancer patients. To compare meropenem, a carbapenem antibiotic, with ceftazidime for the empirical treatment of patients with febrile neutropenia.
                A prospective, double-blind, randomized clinical trial was conducted at medical centers in North America and the Netherlands. A total of 411 cancer patients (196 treated with meropenem and 215 treated with ceftazidime), who had 471 episodes of fever, participated in the trial. For each neutropenic episode, patients were allocated at random to receive intravenous administration of meropenem (1 g every 8 hours) or ceftazidime (2 g every 8 hours). Treatment could be modified at any time. Key end points were clinical and bacteriologic outcomes, eradication of infecting organism, and adverse events.
                The rate of successful clinical response at the end of therapy was significantly higher for patients treated with meropenem than for those on ceftazidime for all episodes (54% v 44%, respectively) and for episodes of fever of unknown origin (62% v 46%, respectively), but differences between groups were not statistically significant for clinically defined or microbiologically defined infections. Meropenem was significantly more effective than ceftazidime in severely neutropenic (</= 100 cells/microliter) patients (55% v 43%, respectively), bone marrow transplant patients (73% v 27%, respectively), and patients given antibiotic prophylaxis before study entry (71% v 52%, respectively). Common adverse effects of meropenem and ceftazidime therapy were rash, diarrhea, and nausea and vomiting.
                Monotherapy with meropenem represents a suitable choice for initial empirical antibiotic therapy for febrile episodes in neutropenic cancer patients. 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. 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. The efficacies of meropenem, a novel carbapenem, and ceftazidime, as empirical therapy of febrile neutropenic patients, were compared in a prospective, randomized clinical trial. One hundred and twelve adult patients were given meropenem 1 g tds iv for 153 episodes of fever, while 109 patients received ceftazidime 2 g tds iv for 151 episodes. All patients survived the first 3 days of therapy and, by the end of the treatment courses, 67 (44%) episodes had responded to meropenem, compared with 62 (41%) to ceftazidime. Eighty (53%) episodes initially treated with ceftazidime and 63 (41%) episodes treated with meropenem were considered to have failed treatment because it was thought necessary to administer additional antibacterial agents; however, modifications were made twice as often because of fever that persisted beyond 2-3 days than because of obvious causes of failure such as persistent infection. Three patients in the ceftazidime group and five in the meropenem group died. Meropenem was well tolerated, with no reports of nausea or toxicity to the central nervous system. Although ceftazidime was shown in the present study to be as effective as meropenem, the broader spectrum of activity of meropenem against Gram-positive cocci suggests that it might be more appropriate as empirical therapy of febrile neutropenic patients who are at high risk of acquiring infections caused by these bacteria. With the availability of new, broad-spectrum antibiotics, initial therapy with a single agent has become an alternative to classic combinations in the management of febrile, neutropenic cancer patients. The aims of this study were to compare the efficacy of ceftazidime and imipenem as empirical monotherapy of febrile episodes in neutropenic patients, and to examine the frequency with which second-line antibiotics (amikacin, vancomycin, or both) were required. A prospective clinical trial was carried out in a single centre. Eligible patients with solid tumours or lymphoma were randomised to receive monotherapy with ceftazidime or imipenem. In the event of no response, amikacin and/or vancomycin were added in 48-72 h intervals (sequentially, or according to clinical or microbiological data). Efficacy was evaluable for 111 assessable episodes. Median neutrophil count at entry was 100 cells/microliters and median duration of neutropenia was 4 days. Febrile episodes were classified as microbiologically (34%) or clinically documented (42%), and fever of unknown origin (24%). Gram-negative infections (57%) predominated over gram-positive isolates (30%). The overall success rate with monotherapy (69% versus 70%), or with modification (20% versus 23%) were equivalent for ceftazidime and imipenem (P = 0.75). The mortality in this series was 5%. Single-agent therapy with either ceftazidime or imipenem is effective for the empirical treatment of febrile episodes in neutropenic patients with solid tumours. Early addition of amikacin and/or vancomycin resolves most failures of the first step. We aimed at comparing the effectiveness and safety of piperacillin/tazobactam(PIP-TAZ) versus imipenem/cilastin (IMI) administered as empiric monotherapy in patients with febrile neutropenia.
                Patients with hematological diseases who were randomly assigned either PIP-TAZor IMI were enrolled in the study. A sequential strategy of antibiotic therapy addition was applied as long as fever persisted or microorganisms were isolated at 72 h. Moreover, if bacteriologically unconfirmed fever persisted after 5-7 days, an antifungal therapy was started. The treatment was considered successful if fever and clinical signs resolved and/or pathogens were cleared without adding further antibiotics at 72 h. Differences between percentages were analyzed using the *2test.
                137 patients were evaluated. The successful response rate of PIP-TAZ after 72 h was similar to IMI (32.2 and 35.2%). The defervescence time was shorter (3.6 and 4.2 days) and the bacterial response more favourable with PIP-TAZ than with IMI, but statistically significant differences were not reached. The overall response in both groups was 91%.18.2% of episodes were bacteriologically confirmed. The most frequent isolated microorganism was Staphylococcus coagulase-negative(48.8%). There was one only case of septic shock, within the IMI group, and the overall mortality of the group was 8.7%. The occurrence of vomiting in the IMI group was significantly higher than in the PIP-TAZ group (39.9 and 5.6%; p < 0.0001).
                PIP-TAZ is as effective as IMI and it constitutes a good choice as an initial empiric monotherapy of febrile neutropenia. To compare the efficacy of ceftazidime and imipenem monotherapy for fever and neutropenia, and to determine whether fewer antimicrobial modifications (additions or changes) are required by the broader-spectrum agent, imipenem.
                Adult and pediatric patients undergoing chemotherapy for solid tumors, leukemias, or lymphomas were randomized to receive open-label ceftazidime or imipenem on presentation with fever and neutropenia. Success with or without modifications of the initial antibiotic was defined as survival through neutropenia; failure was death due to infection. Comparisons were based on numbers of modifications made to each monotherapy during the course of neutropenia, in patients stratified as having unexplained fever or a documented infection.
                Among 204 ceftazidime and 195 imipenem recipients, the overall success rate with or without modification was more than 98%, regardless of initial antibiotic regimen. Modifications occurred in half of all episodes, primarily in patients with documented infections on either monotherapy. Antianaerobic agents were more frequently added to ceftazidime (P < .001), but addition of other antibiotics, including vancomycin and aminoglycosides, was similar between the two monotherapy groups. Imipenem therapy was associated with significantly greater toxicity, manifested by Clostridium difficile-associated diarrhea and by nausea and vomiting, which required discontinuation of imipenem in 10% of recipients.
                Ceftazidime and imipenem are both effective in the management of fever and chemotherapy-related neutropenia, provided that modifications are made in response to clinical and microbiologic data that emerge during the course of neutropenia. Imipenem, despite its broader antimicrobial spectrum, does not significantly decrease the overall need for antibiotic modifications and is more often complicated by gastrointestinal toxicity. In this Swedish multicentre study we compared the efficacy of meropenem with ceftazidime for treatment of febrile neutropenia. 192 patients were randomized and the number of evaluable patients was 92 in the meropenem group and 95 in the ceftazidime group. 40 (43%) patients in the meropenem arm and 49 (52%) in the ceftazidime arm had acute leukaemia. 56 (61%) and 52 (55%) patients respectively had a neutrophil count of < 0.1 x 10(9)/l at randomization and the median duration of neutropenia was 6.5 and 8 d, respectively. Thirty-one (34%) and 28 (29%) patients had a microbiologically defined infection, 14 (15%) and 17 (18%) a clinically defined infection and the remaining 47 (51%) and 50 (53%) had unexplained fever. After 72 h of treatment, 46 (50%) patients in the meropenem arm and 53 (56%) patients in the ceftazidime arm were alive on unmodified monotherapy. 42 (46%) and 47 (49%) of these completed the study on monotherapy alone. Only 2 patients (2%) in each arm had to stop treatment owing to allergic reactions. None of the observed differences were statistically significant and we therefore conclude that meropenem was an effective and safe alternative to ceftazidime for empiric treatment of fever during neutropenia. 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. One hundred febrile episodes in 89 neutropenic patients after cytotoxic chemotherapy were randomized to be treated with either ceftazidime or imipenem as initial monotherapy. The clinical characteristics of the two groups of patients were comparable. The response of the fever in patients who received imipenem was significantly better than that in those who received ceftazidime (77 versus 56%, respectively; P = 0.04), especially in those with microbiologically documented infection (81 versus 33%, respectively; P = 0.02). The in vitro susceptibilities and the clinical responses suggested that, with the possible exception of Pseudomonas spp., imipenem was more effective than ceftazidime in treating neutropenic infections caused by both gram-positive and -negative organisms. An additional 23 and 21% of the patients in the ceftazidime and imipenem groups, respectively, responded to the addition of cloxacillin and amikacin following failure of monotherapy. The majority of the treatment failures, relapses, and superinfections were related to resistant infective organisms such as methicillin-resistant Staphylococcus spp. and Pseudomonas spp. or disseminated fungal infections. To compare the efficacies of cefepime and ceftazidime as empiric therapy during the management of fever in cancer patients with chemotherapy-induced neutropenia.
                A prospective, double-blind, randomized study of cefepime 2 g every eight hours and ceftazidime 2 g every eight hours was performed in 276 adult neutropenic (absolute neutrophil count < 500/mm3) cancer patients with fever.
                Median duration of neutropenia was five days. Sixty-one percent (n = 188) of the patients were evaluable. Treatment was successful in 57% (58/101) of cefepime-treated patients and 60% (52/87) of ceftazidime-treated patients (95% CI -18 to 12; p = 0.77). Bacteremic clearance occurred in 71% (12/17) of cefepime-treated patients and 40% (6/15) of ceftazidime-treated patients (p = 0.3). Both drugs were well tolerated.
                Cefepime appears to be as effective as ceftazidime in the initial treatment of febrile episodes in adult cancer patients with chemotherapy-associated neutropenia of modest duration. 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.
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.