Ceftazidime versus imipenem-cilastatin as initial monotherapy for febrile neutropenic patients. Monotherapy for fever and neutropenia in cancer patients: a randomized comparison of ceftazidime versus imipenem. Comparison of imipenem and ceftazidime as therapy for severe melioidosis. Oral ceftibuten switch therapy for acute pyelonephritis in children. Two randomized controlled trials of ceftazidime alone versus ceftazidime in combination with trimethoprim-sulfamethoxazole for the treatment of severe melioidosis. Comparative study of cefepime versus ceftazidime in the empiric treatment of pediatric cancer patients with fever and neutropenia. A comparison of imipenem to ceftazidime with or without amikacin as empiric therapy in febrile neutropenic patients. Cefazolin plus ceftazidime versus imipenem/cilastatin monotherapy for treatment of CAPD peritonitis--a randomized controlled trial. Ceftriaxone once daily for four weeks compared with ceftriaxone plus gentamicin once daily for two weeks for treatment of endocarditis due to penicillin-susceptible streptococci. Endocarditis Treatment Consortium Group. Open-label randomized trial of oral trimethoprim-sulfamethoxazole, doxycycline, and chloramphenicol compared with trimethoprim-sulfamethoxazole and doxycycline for maintenance therapy of melioidosis. Efficacy and tolerability of imipenem-cilastatin versus ceftazidime plus tobramycin as empiric therapy of presumed bacterial infection in neutropenic cancer patients.
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 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. An open, prospective, randomized, comparative treatment trial was conducted to compare the therapeutic efficacy of high-dose intravenous imipenem and ceftazidime for acute severe melioidosis. Adult Thai patients with suspected acute, severe melioidosis were randomized to receive either imipenem, at a dosage of 50 mg/(kg x d), or ceftazidime, at a dosage of 120 mg/(kg x d), for a minimum of 10 days. The main outcome measures were death or treatment failure. Of the 296 patients enrolled, 214 had culture-confirmed melioidosis, and 132 (61.7%) of them had positive blood cultures. Mortality among patients with melioidosis was 36.9% overall. There were no differences in survival overall (P = .96) or after 48 hours (P = .3). Treatment failure after 48 hours was more common among patients treated with ceftazidime (P = .011). Both treatments were well tolerated. Imipenem is a safe and effective treatment for acute severe melioidosis and may be considered an alternative to ceftazidime. The available oral third generation of cephalosporin, "ceftibuten" was used to substitute the intravenous drug after defervescence in acute pyelonephritis in children. This randomized controlled study compared the efficacy of an oral ceftibuten switch therapy with a ceftriaxone in both short-term and long-term outcomes. 36 99mTc-dimercaptosuccinic acid (DMSA) scan proved pyelonephritis patients were randomized into the study group, "ceftibuten" (N=18) and the control group, "ceftriaxone" (N=18). Ceftriaxone (75 mg/kg/day) was the initial antibiotic in both groups. After defervescence for 24-48 hours, oral ceftibuten (9 mg/kg/day) was substituted in the study group and continued for 10 days. The subject characteristics and laboratory data were not different between the two groups. The urine culture at D14 was sterilized in both groups. The incidence of renal scarring was 66.6 per cent and 61.1 per cent in the study group and the control group respectively. The rate of recurrent infection showed no statistical significance. The duration of hospitalization was shorter in the study group than in the control. In conclusion, oral ceftibuten switch therapy can be recommended as a safe and effective treatment for acute pyelonephritis in children. The use of oral therapy may result in a significant reduction of health care expenditure. Two antibiotic regimens are used commonly in Thailand for the initial treatment of severe melioidosis: ceftazidime in combination with trimethoprim-sulfamethoxazole (TMP-SMX) and ceftazidime monotherapy. It is not known whether TMP-SMX provides an additional benefit.
                Two prospective, randomized trials that compared these regimens for patients presenting with acute severe melioidosis were started independently at tertiary care hospitals in Ubon Ratchathani and Khon Kaen (in northeastern Thailand), and the results were analyzed together as a prospective, individual-patient data meta-analysis. The primary end point was in-hospital mortality rate.
                The in-hospital mortality rate among all enrolled patients (n=449) was not significantly different between those randomized to ceftazidime alone (25.1%; 56 of 223 subjects) and those randomized to ceftazidime with TMP-SMX (26.6%; 60 of 226 subjects; odds ratio [OR], 1.08; 95% confidence interval [CI], 0.7-1.7; stratified P=.73). Of the 241 patients with culture-confirmed melioidosis, 51 (21.2%) died. Of these 241 patients, 31 (12.9%) died > or =48 h after the time of study entry. Among patients with melioidosis, there was no difference in death rate between the 2 treatment groups for either all deaths (OR, 0.88; 95% CI, 0.48-1.6; stratified P=.70) or for deaths that occurred > or =48 h after hospital admission (OR, 0.88; 95% CI, 0.41-1.9; stratified P=.73). Conditional logistic regression analysis revealed that bacteremia, respiratory failure, and renal failure were independently associated with death and treatment failure. Drug regimens were not associated with death or treatment failure in this model.
                We conclude that the addition of TMP-SMX to ceftazidime therapy during initial treatment of severe melioidosis does not reduce the acute mortality rate. 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. 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. Peritonitis is a serious complication of peritoneal dialysis (PD). We studied the efficacy of imipenem/cilastatin monotherapy in the treatment of PD-related peritonitis.
                We performed an open-label, randomized control study comparing imipenem/cilastatin monotherapy (treatment group) versus cefazolin plus ceftazidime (control group) in the treatment of PD peritonitis. The result was further compared to a historic group treated with cefazolin plus netilmycin. Outcome measures were primary response rate at day 10 and complete cure rate.
                We enrolled 51 patients in the treatment group, 51 in the control group, and identified 96 in the historic group. The primary response rate to the assigned antibiotics was 49.0%, 51.0%, and 49.0% for the treatment, control, and historic groups, respectively (p = 0.97). The primary response rate allowing for change in antibiotic was 82.4%, 90.2%, and 82.3%, respectively, for the three groups (p = 0.41). The complete cure rate was 72.5%, 80.4%, and 82.3%, respectively (p = 0.60). Tenckhoff catheter removal was needed in 6 cases in the treatment group, 6 cases in the control group, and 13 cases in the historic group (p = 0.90).
                We concluded that monotherapy of imipenem/cilastatin has similar efficacy compared to the two standard regimens of cefazolin plus ceftazidime or netilmycin in the treatment of PD peritonitis. This randomized, multicenter, open-label study compared the efficacy and safety of monotherapy with 2 g of intravenous ceftriaxone once daily for 4 weeks with those of combination therapy with 2 g of intravenous ceftriaxone and 3 mg of intravenous gentamicin/kg once daily for 2 weeks as therapy for endocarditis due to penicillin-susceptible streptococci. Sixty-one patients were enrolled in the study. Clinical cure was observed for 51 evaluable patients both at termination of therapy and at the 3-month follow-up: 25 (96.2%) of 26 monotherapy recipients and 24 (96%) of 25 combination therapy recipients. Of the 23 patients in each treatment group who were microbiologically evaluable, 22 (95.7%) in each group were considered cured. No patient had evidence of relapse. Fourteen patients (27.5%) required cardiac surgery after initiation of treatment, including five monotherapy recipients and nine combination therapy recipients. Adverse effects were minimal in both treatment groups. We conclude that 2 g of ceftriaxone once daily for 4 weeks and 2 g of ceftriaxone in combination with 3 mg of gentamicin/kg once daily for 2 weeks are both effective and safe for the treatment of streptococcal endocarditis. Melioidosis (infection caused by Burkholderia pseudomallei) requires a prolonged course of oral antibiotics following initial intravenous therapy to reduce the risk of relapse after cessation of treatment. The current recommendation is a four-drug regimen (trimethoprim [TMP], sulfamethoxazole [SMX], doxycycline, and chloramphenicol) and a total treatment time of 12 to 20 weeks. Drug side effects are common; the aim of this study was to compare the efficacy and tolerance of the four-drug regimen with a three-drug regimen (TMP-SMX and doxycycline). An open-label, randomized trial was conducted in northeast Thailand. A total of 180 adult Thai patients were enrolled, of which 91 were allocated to the four-drug regimen and 89 to the three-drug regimen. The trial was terminated early due to poor drug tolerance, particularly of the four-drug regimen. The culture-confirmed relapse rates at 1 year were 6.6% and 5.6% for the four- and three-drug regimens, respectively (P = 0.79). The three-drug regimen was better tolerated than the four-drug regimen; 36% of patients receiving four drugs and 19% of patients receiving three drugs required a switch in therapy due to side effects (P = 0.01). The duration of oral therapy was significantly associated with relapse; after adjustment for confounders, patients receiving less than 12 weeks of oral therapy had a 5.7-fold increase of relapse or death. A combination of TMP-SMX and doxycycline is as effective as and better tolerated than the conventional four-drug regimen for the oral treatment phase of melioidosis. The efficacy and tolerability of monotherapy with imipenem-cilastatin (I-C) were compared with that of ceftazidime plus full-course therapy with an aminoglycoside (tobramycin) (C&T) in the treatment of presumed bacterial infection in neutropenic cancer patients. A total of 106 adult patients diagnosed with presumed bacterial infection and an underlying malignancy with an absolute neutrophil count (ANC) < 500/mm3 were enrolled in this open-label study. A total of 131 febrile episodes occurred. Forty-five patients in the I-C group and 41 in the C&T group, who were well matched on demographic and baseline characteristics, were evaluable for efficacy and safety. Seventy-two hours after the start of therapy, no significant between-group differences in treatment outcomes, including withdrawals or deaths, were seen. Thirty-five (78%) of 45 patients in the I-C group and 29 (71%) of the 41 in the C&T group had successful outcomes at the final evaluation. Superinfection occurred in 8 (18%) I-C patients and 3 (7%) C&T patients. Within the subgroup of patients with an initial ANC < 100/mm3, the final evaluation showed no significant differences in treatment outcome between groups. Of the 131 in the safety population 30 (46%) I-C patients and 28 (42%) C&T patients had one or more adverse experiences; drug-related adverse events occurred in 25 (38%) patients in the I-C group and 11 (17%) patients in the C&T group. The data suggest that imipenem-cilastatin should be considered for initial empiric therapy of presumed bacterial infection in neutropenic cancer patients.
Regimens for the acute phase of illness should contain ceftazidime or imipenem. It is not yet clear if combinations of treatments in the early phase reduce relapse. For oral therapy after the acute phase of treatment, trials suggest that conventional four drug regimens can be used for treatment.