A randomized prospective study of ceftazidime versus ceftazidime plus flucloxacillin in the empiric treatment of febrile episodes in severely neutropenic patients.

In a prospective, randomized study, ceftazidime monotherapy was compared with a combination of ceftazidime and flucloxacillin in 100 febrile neutropenic patients. Thirty-four bacteriologically documented infections, of which 26 were bacteremias, in 51 patients were treated with ceftazidime alone. Thirty-four bacteriologically proven infections, of which 29 were bacteremias, in 49 patients were treated with a combination of ceftazidime and flucloxacillin. The clinical response rate for ceftazidime monotherapy was 80%; the bacteriological cure rate was 90%. Efficacy against gram-negative pathogens appeared to be excellent, achieving a 100% cure rate. The clinical response and bacteriological cure rates for the combination were 76 and 86%, respectively. Three superinfections were registered in the ceftazidime group, and four, involving six pathogens, were registered in the combination group. Other side effects of ceftazidime were minimal. It is concluded that ceftazidime is an effective drug for the empiric treatment of febrile neutropenic patients. It offers the opportunity to avoid the aminoglycosides in first-line treatment. It may be appropriate to combine ceftazidime with cephalothin or vancomycin or to modify therapy if resistant gram-positive strains are encountered.     

Vancomycin is not an essential component of the initial empiric treatment regimen for febrile neutropenic patients receiving ceftazidime: a randomized prospective study.

The use of vancomycin as part of the initial antibiotic therapy of febrile neutropenic patients has become a controversial issue. Some studies support its incorporation in the initial regimen, and others suggest that vancomycin can be added later. We examined this issue in a prospective, randomized trial. We randomized 127 febrile neutropenic patients to receive either ceftazidime alone or ceftazidime plus vancomycin as the initial empiric antibiotic treatment. We added vancomycin to the ceftazidime arm of the study when fever persisted after 96 h of monotherapy, when new fever occurred after this time, or when a moderately ceftazidime-resistant gram-positive bacterium was isolated. Each of these regimens had similar initial response rates, similar durations of initial fever, similar frequencies of new fever during therapy, similar microbiological cure rates, similar superinfection rates, and similar survival rates. We observed more renal and cutaneous toxicities in patients receiving vancomycin and ceftazidime as initial therapy. We conclude that ceftazidime is appropriate as initial therapy for febrile neutropenic patients and that the addition of vancomycin is appropriate when fever persists after 4 days of monotherapy or when fever recurs following an initial response.     

Piperacillin-tazobactam plus amikacin versus ceftazidime plus amikacin as empiric therapy for fever in granulocytopenic patients with cancer. The International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer.

Gram-positive bacteria have become the predominant infecting organisms in granulocytopenic cancer patients. Empiric antibiotic regimens used in febrile neutropenic patients often include an extended-spectrum cephalosporin, but the response to therapy in gram-positive coccal bacteremia has been unsatisfactory. Thus, new antibiotics with better activity against gram-positive bacteria should be tested. The objective of this prospective randomized controlled study was to evaluate and compare the efficacy and tolerance of piperacillintazobactam plus amikacin with that of ceftazidime plus amikacin, the standard regimen of the International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer, in the empiric treatment of febrile granulocytopenic cancer patients. A total of 858 episodes were eligible for this study, and 706 episodes were assessable for efficacy. The antibiotic treatment was successful in 210 (61%) of 342 episodes in the piperacillin-tazobactam-amikacin group compared with 196 (54%) of 364 episodes treated with ceftazidime plus amikacin (P = 0.05). The time to defervescence was significantly shorter (P = 0.01) and the time to failure was significantly longer (P = 0.02) in the piperacillin-tazobactam-amikacin group. A significant difference in response to bacteremic infections between the two patient groups was found: piperacillin-tazobactam plus amikacin was successful in 40 of 80 episodes (50%), and ceftazidime plus amikacin was successful in 35 of 101 episodes (35%) (P = 0.05). A multivariate analysis showed that the probability of failure was significantly greater with ceftazidime plus amikacin than with piperacillin-tazobactam plus amikacin (P = 0.02). This trial suggests that piperacillin-tazobactam plus amikacin is more effective than ceftazidime plus amikacin for the empiric treatment of fever and bacteremia in granulocytopenic cancer patients. Although cutaneous reaction was more frequently associated with piperacillin-tazobactam plus amikacin than with ceftazidime-amikacin, this unwanted effect was relatively mild and its incidence was comparable to that of other penicillin compounds.     

A comparative study of cefepime versus ceftazidime as empiric therapy of febrile episodes in neutropenic patients.

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 comparative study of meropenem and ceftazidime in the treatment of patients hospitalized with community-acquired pneumonia

This multicenter, open-label, randomized clinical trial compared the efficacy and tolerability of intravenous (IV) meropenem 0.5 g every 8 hours (n = 147) and IV ceftazidime 1 g every 8 hours (n = 148) as empiric monotherapy for 295 patients hospitalized with community-acquired pneumonia. Seventy-four meropenem recipients and 81 ceftazidime recipients with pneumonia were assessable both clinically and bacteriologically. In these patients, no statistically significant differences were reported in the satisfactory clinical (95% with meropenem vs 90% with ceftazidime) or bacteriologic (95% with meropenem vs 93% with ceftazidime) response rates with the two agents at the end of treatment. High satisfactory clinical (95% with meropenem vs 92% with ceftazidime) and bacteriologic (97% with meropenem vs 89% with ceftazidime) response rates were maintained at follow-up (2 to 4 weeks later). In 90 patients who were clinically assessable but bacteriologically unassessable (no pretreatment pathogen isolated), both agents produced a satisfactory clinical response rate of 87% at the end of therapy. Streptococcus pneumoniae was the most frequently isolated pretreatment pathogen (28%), but nosocomial-type pathogens such as Escherichia coli (5%), Pseudomonas aeruginosa (11%), and Klebsiella pneumoniae (6%) were also frequently isolated. Both medications were well tolerated, and the types of treatment-related adverse events were similar in the two treatment groups. These findings indicate that meropenem 0.5 g every 8 hours is a useful option for the empiric treatment of patients hospitalized with community-acquired pneumonia.     

Prospective randomized clinical trial of teicoplanin for empiric combined antibiotic therapy in febrile, granulocytopenic acute leukemia patients.

The increasing prevalence of bacteremia caused by gram-positive bacteria in granulocytopenic acute leukemia patients prompted us to evaluate, in a prospective randomized trial, the role of teicoplanin, a new glycopeptide antibiotic, when it was added to amikacin plus ceftazidime, as an empiric therapy of fever in these patients. Of 47 evaluable episodes, 22 were treated with the teicoplanin regimen and 25 were treated with the combination of amikacin and ceftazidime. The overall response to therapy of patients treated with teicoplanin was slightly better (82% improvement) than that obtained with amikacin plus ceftazidime (52%). The response rate of patients with gram-positive bacteremias was 80% (4 of 5) to the regimen that included teicoplanin; 25% (1 of 4) of the patients treated with amikacin plus ceftazidime responded to treatment; and for patients with gram-negative bacteremias, the response rates were, respectively, 100% (4 of 4) and 70% (7 of 10). The better results obtained with amikacin-ceftazidime-teicoplanin treatment were most evident in patients with profound (less than 100/mm3) and persistent neutropenia (83 versus 30% improvement). Furthermore, a good response rate of patients with gram-positive bacteremias (seven of eight; 87% improvement) was achieved in a small group of bone marrow transplant patients who were all treated with amikacin-ceftazidime-teicoplanin. No severe side effects were documented in any patient. Teicoplanin, as a drug administered as a single daily dose, seems to be a safe and useful anti-gram-positive agent when used in combination with amikacin-ceftazidime as an empiric therapy of febrile episodes in granulocytopenic acute leukemia patients.     

Effects of teicoplanin and those of vancomycin in initial empirical antibiotic regimen for febrile, neutropenic patients with hematologic malignancies. Gimema Infection Program.

The efficacy and toxicity of teicoplanin and vancomycin in the initial empirical antibiotic regimen in febrile, neutropenic patients with hematologic malignancies were compared in a prospective, randomized, unblinded, multicenter trial in the setting of 29 hematologic units in tertiary-care or university hospitals. A total of 635 consecutive febrile patients with hematologic malignancies and chemotherapy-induced neutropenia were randomly assigned to receive intravenously amikacin plus ceftazidime plus either teicoplanin at 6 mg/kg of body weight once daily or vancomycin at 1 g twice daily. An efficacy analysis was done for 527 evaluable patients: 275 treated with teicoplanin and 252 treated with vancomycin. Overall, successful outcomes were recorded for 78% of patients who received teicoplanin and 75% of those who were randomized to vancomycin (difference, 3%; 95% confidence interval [CI], -10 to 4%; P = 0.33). A total of 102 patients presented with primary, single-agent, gram-positive bacteremia. Coagulase-negative staphylococci accounted for 42%, Staphylococcus aureus accounted for 27%, and streptococci accounted for 21% of all gram-positive blood isolates. The overall responses to therapy of gram-positive bacteremias were 92 and 87% for teicoplanin and vancomycin, respectively (difference, 5%; CI, -17 to 6%; P = 0.22). Side effects, mainly represented by skin rash, occurred in 3.2 and 8% of teicoplanin- and vancomycin-treated patients, respectively (difference, -4.8%; CI, 0.7 to 8%; P = 0.03); the rate of nephrotoxicity was 1.4 and 0.8% for the teicoplanin and vancomycin groups, respectively (difference, 0.6%; CI, -2 to 1%; P = 0.68). Further infections were caused by gram-positive organisms in two patients (0.7%) treated with teicoplanin and one patient (0.4%) who received vancomycin (difference, 0.3%; CI, -0.9 to 1.0%; P = 0.53). Overall mortalities were 8.5 and 11% for teicoplanin- and vancomycin-treated patients, respectively (difference, -2.5%; CI, - 2 to 7%; P = 0.43); death was caused by primary gram-positive infections in three patients (1%) in each treatment group. When used for initial empirical antibiotic therapy in febrile, neutropenic patients, teicoplanin was at least as efficacious as vancomycin, but it was associated with fewer side effects.     

Monotherapy with piperacillin/tazobactam versus combination therapy with ceftazidime plus amikacin as an empiric therapy for fever in neutropenic cancer patients

Between July 1993 and September 1996, 107 consecutive febrile episodes in 83 neutropenic cancer patients with a median age of 41 years were randomized to treatment either with piperacillin/tazobactam 4.5 g every 8 h i.v. or ceftazidime 2 g every 8 h plus amikacin 15 mg/kg i.v. per day. In the case of fever >38° C 48 h after initiation of the antibiotic therapy, vancomycin 500 mg every 6 h i.v. was added. The study population was at serious risk of a poor outcome, since 67% of the patients had leukemia or lymphoma, 19% of the febrile events occurred after autologous bone marrow or blood stem cell transplantation, the median total duration of neutropenia was 16 days, and the median neutrophil count at study inclusion was 0.09 × 10⁹/l. The two patient groups were comparable in terms of risk factors. Bacteremia was found in 37%, other microscopically documented infections in 16%, and clinically documented infections in 26% of the febrile episodes. Most (96) febrile episodes were evaluable for response. No significant difference was found between piperacillin/ tazobactam and ceftazidime plus amikacin in terms of success rate (81% versus 83%), empirical addition of vancomycin (42% versus 38%), median time to fever defervescence (3.3 versus 2.9 days) or median duration of antibiotic therapy (7.2 versus 7.4 days). No patient died from the infection. Both antibiotic regimens were well tolerated, the study treatment being stopped only in 1 patient because of toxicity (cutaneous allergy to piperacillin/tazobactam). On the basis of the 107 febrile events encountered, we conclude that piperacillin/tazobactam is a safe and effective monotherapy. To define the definitive value of piperacillin/ tazobactam as a monotherapy for febrile neutropenic patients a large randomized trial is warranted.     

A comparison of double beta-lactam combinations with netilmicin/ureidopenicillin regimens in the empirical therapy of febrile neutropenic patients

In a randomized trial ceftazidime plus piperacillin or azlocillin, and netilmicin plus piperacillin or azlocillin were used as initial empirical therapy in 202 febrile neutropenic episodes. Netilmicin plus azlocillin was the most effective combination with a clinical response rate of 81% in clinically and microbiologically documented infections compared with 63% for ceftazidime plus piperacillin. All of the episodes of Gram-negative bacteraemia treated with azlocillin responded compared with 43% of those treated with piperacillin. Gram-positive organisms accounted for 52% of all bacteriologically documented infections and 40% of the febrile episodes were treated with vancomycin for presumptive or documented Gram-positive infection. Patients treated with netilmicin had significantly more nephrotoxicity than those given the double beta-lactam combinations (14.8% vs 3.5%; P less than 0.05). However, this difference was not shown in those patients who did not receive concurrent vancomycin or amphotericin. The double beta-lactam combinations were associated with more hypokalaemia (58.2% vs. 37.7%; P less than 0.05) and more colonization with yeasts (24% vs. 10.4%; P less than 0.05) but there was no evidence that their use was associated with prolongation of neutropenia. These results indicate that ceftazidime plus a ureidopenicillin would be adequate empirical therapy in situations where the concomitant use of nephrotoxic agents precludes the use of aminoglycoside containing combinations.     

Ceftazidime as monotherapy or combined with teicoplanin for initial empiric treatment of presumed bacteremia in febrile granulocytopenic patients.

In a prospective randomized study, 120 febrile, granulocytopenic patients received as initial therapy ceftazidime with or without teicoplanin. At the onset of fever, patients had no obvious infectious focus. For 103 assessable episodes, initial bacteremias were detected in 18 of 51 patients (35%) given ceftazidime and 20 of 52 patients (38%) given the combination; 13 and 17 bacteremias caused by gram-positive bacteria occurred in these groups, respectively. There was no difference in terms of the final response (25 of 51 patients [49%] treated with ceftazidime alone versus 33 of 52 patients [63%] given the combination), and the morbidity was comparable for both treatment groups. The duration of fever and of total antibiotic therapy were similar in both groups. Initial therapy was modified in 26 patients (51%) treated with ceftazidime, with 20 surviving the infection, and in 19 patients (37%) treated with the combination, with 15 surviving. Persistent fever was the main reason for changing treatment, and no patient died of a gram-positive infection. Subsequent infective events occurred in 16 patients (31%) given ceftazidime and in 25 patients (48%) given the combination. Lung infiltrates developed in 12 and 13 patients, respectively, but more new infections occurred in the combination group. Allergic skin reactions were also more frequent in this group. Thus, while teicoplanin provides simple, reliable, and safe treatment of patients with presumed gram-positive infections, it is not useful when given empirically to this patient population, and treatment may result in more infective complications and adverse events.     

Pharmacokinetics of ceftazidime, alone or in combination with piperacillin or tobramycin, in the sera of cancer patients.

We administered 2 g of ceftazidime intravenously every 8 h to cancer patients for the empiric therapy of febrile episodes. Ceftazidime was administered as monotherapy for patients with granulocyte counts in excess of 1,000/microliter. Febrile, neutropenic patients were randomized to also receive either piperacillin or tobramycin. The pharmacokinetic profile of ceftazidime during a steady-state dosing interval was ascertained in 21 patients. No differences were seen between groups for any of the pharmacokinetic parameters examined. As expected, the observed half-life was longer, the serum clearance was smaller, and the volumes of distribution were larger than in previously reported studies of volunteers. Serum concentrations remained above the MIC for inhibition of 90% of strains of the most common bacteremic pathogens seen in our cancer center for the entire 8-h dosing interval.     

An open, randomized, multicentre study comparing the use of low-dose ceftazidime or cefotaxime, both in combination with netilmicin, in febrile neutropenic patients. German Multicentre Study Group.

To reduce drug acquisition costs, the clinical and bacteriological efficacy of low-dose ceftazidime i.v. (1 g tid) was compared with cefotaxime i.v. (2 g tid). Both regimens were combined with netilmicin i.v. (2 mg/kg bodyweight tid), in an open, randomized, multicentre trial in febrile neutropenic patients. The addition of antibiotics for gram-positive coverage was part of the protocol; alteration in the antibiotics for gram-negative cover or premature discontinuation of the study antibiotics were judged as failure. One hundred and eighty six patients were randomized by nine German centres, the patients matched for age, underlying diseases and duration of neutropenia (median duration 14 days) in both treatment arms. Infections were documented microbiologically in 29% of the patients, clinically in 16% and suspected (fever of unknown origin) in 102/186 patients (55%). The 82 pathogens isolated were predominantly gram-positive bacteria. In an intent-to-treat analysis, the overall response rate without modification at the final evaluation was 58% in the ceftazidime group and 34% in the cefotaxime group (P < 0.01). The success rates with modification were 84% and 64%, respectively. The failure rate in a highly immunosuppressed subgroup of the patients (bone marrow transplant recipients) was higher for cefotaxime (53%) than for the ceftazidime arm (14%) (P < 0.001). Response rates were significantly higher in the ceftazidime group for patients with microbiologically documented and possible infections. No major bacterial superinfections occurred in the low-dose treatment arm. The tolerability was good for both regimens. Low-dose ceftazidime combined with netilmicin proved to be superior to recommended doses of cefotaxime/netilmicin in febrile neutropenic patients.     

Imipenem versus gentamicin combined with either cefuroxime or cephalothin as initial therapy for febrile neutropenic patients.

A prospective randomized study was conducted to determine the efficacy of imipenem-cilastatin (hereafter referred to as imipenem) (500 mg four times daily) versus combination therapy for febrile neutropenic patients receiving either no prophylaxis or ciprofloxacin for prevention of infections. Combination therapy consisted of gentamicin (80 mg every 8 h) plus either cefuroxime (1,500 mg every 8 h) or cephalothin (1,000 mg every 4 h) for suspected catheter-related infections. Ninety-four neutropenic fever episodes in 87 patients were evaluable for efficacy. The overall clinical rate of response to imipenem was significantly higher than that to combination therapy (91 versus 74%; P = 0.05). The difference in efficacy was most pronounced in patients with microbiologically documented infections (89 versus 53%; P = 0.025), which were predominantly caused by gram-positive bacteria. Differences in susceptibility may have caused the better rate of response to imipenem. Two of 29 gram-positive bacteria were imipenem resistant, whereas 10 were resistant to cephalothin and cefuroxime and 12 were resistant to gentamicin. No causative gram-negative bacterium and 24 gram-positive bacteria were isolated in 61 fever episodes with ciprofloxacin prophylaxis (oral). In contrast, nine causative gram-negative and five gram-positive bacteria were isolated in 33 episodes without prophylaxis. The difference in distribution proved to be statistically significant for gram-negative (P = 0.0001) as well as gram-positive (P = 0.025) bacteria, indicating that ciprofloxacin effectively prevented the occurrence of gram-negative bacteria and may have contributed to the relatively large number of gram-positive bacteria isolated. Empirical initial therapy with imipenem may be a valuable alternative to combination therapy for neutropenic fever episodes.     

Piperacillin/tazobactam plus tobramycin versus ceftazidime plus tobramycin as empiric therapy for fever in severely neutropenic patients

The objective of this trial was to evaluate the potential advantages of the combination of piperacillin and tazobactam in the control of fever in neutropenic patients. In this single-center study, patients who experienced a total of 247 febrile episodes were prospectively randomized to receive either our standard regimen, ceftazidime 3 g/day (1 g t.i.d.) plus tobramycin 3 mg/kg per day (1.5 mg/kg b.i.d.), or piperacillin 12 g/day plus tazobactam 1.5 g/day (4 g+0.5 g t.i.d.) plus tobramycin 3 mg/kg per day (1.5 mg/kg b.i.d.). Vancomycin was added in all cases of persistent fever in the ceftazidime arm, but only when there was microbiologically documented resistance in the piperacillin/tazobactam arm. All 247 episodes were evaluable by "intent-to-treat" analysis. The two populations were well matched in terms of age, gender, underlying disease, chemotherapy received, oral decontamination, clinical and bacterial documentation, and severity and duration of neutropenia. Initial antibacterial therapy was successful (apyrexia at 72 h, without antibiotic change) more frequently (P=0.008) with the regimen containing piperacillin/tazobactam (54.4%) than with the one including ceftazidime (37.6%). Fewer (P=0.02) major infectious events (infectious death or delay in treatment of underlying disease due to infection) were observed during piperacillin/ tazobactam treatment (2.6%) than with the ceftazidime regimen (11.3%), despite a lower frequency of glycopeptide addition when piperacillin/tazobactam was used (54.4% versus 77.4%) according to the rules adopted. This trial confirmed the efficacy of the piperacillin/tazobactam combination for empirical treatment of febrile neutropenic patients. This antibiotic combination permitted a dramatic decrease in empiric glycopeptide antibiotic administration in such patients. Electronic publication: 12 January 1999     

Ceftazidime versus imipenem-cilastatin as initial monotherapy for febrile neutropenic 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.     

A comparative study of imipenem versus piperacillin plus gentamicin in the initial management of febrile neutropenic patients with haematological malignancies.

Three-hundred and twelve episodes of fever in 234 neutropenic patients with haematological malignancies were treated empirically with either imipenem or a combination of piperacillin and gentamicin. There were no significant differences in the percentages of patients responding to therapy at either 72 h (59% and 56% of assessable episodes in the imipenem and combination groups respectively) or at the end of treatment (55% and 53% of assessable episodes in the imipenem and combination groups respectively). Patients in the piperacillin plus gentamicin group experienced significantly more renal tubular damage whereas those who received imipenem suffered more nausea or vomiting. We conclude that imipenem monotherapy represents an acceptable alternative to piperacillin plus gentamicin as empirical therapy of the febrile neutropenic patient.     

Cefepime versus ceftazidime as empiric therapy for fever in neutropenic patients with cancer

OBJECTIVE: To compare the efficacies of cefepime and ceftazidime as empiric therapy during the management of fever in cancer patients with chemotherapy-induced neutropenia. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

Open randomized study of cefepime versus piperacillin-gentamicin for treatment of febrile neutropenic cancer patients.

An open-label randomized trial comparing the efficacy and safety of cefepime versus piperacillin plus gentamicin (P+G) given intravenously for the treatment of febrile episodes in neutropenic patients with underlying malignancy was conducted at two oncology centers. Over a 30-month period 111 patients were enrolled and 99 patients were found to be suitable for evaluation. At the 72-h time of evaluation, cefepime monotherapy and P+G combination therapy produced comparable clinical response rates (78% for both). P+G and cefepime produced comparable response rates in microbiologically documented (78 versus 71%), clinically documented (100 versus 100%), and possible (75 versus 79%) infections. The P+G and cefepime treatments achieved comparable microbiological eradication of gram-negative (100 versus 71%) (P = 0.09) and gram-positive (44 versus 70%) (P = 0.37) organisms. There were no statistically significant differences in the rates of superinfection between the groups; however, more superinfections of fungal origin were noted in the P+G group. Cefepime was demonstrated to be an effective and safe treatment for febrile episodes in neutropenic patients with malignancies, and its lack of nephrotoxicity compared to P+G was noteworthy. Cefepime appears to be a candidate for monotherapy in febrile neutropenic cancer patients.     

Intravenous fleroxacin versus ceftazidime for lower respiratory tract and skin and soft-tissue infections.

Fleroxacin, a new quinolone antimicrobial agent, was evaluated as part of a multicenter, comparative, open-label, randomized trial with ceftazidime in the treatment of lower respiratory tract infections and skin and soft-tissue infections. After written informed consent was obtained, 20 patients were entered at our center. Twelve patients were assigned to the fleroxacin group; 6 in each infection category. Of these 12 patients, 2 with pneumonia and 3 with skin and soft-tissue infection were not clinically evaluable. The mean duration of therapy was 5.7 +/- 3.0 days in the fleroxacin group versus 7.9 +/- 2.0 days in the ceftazidime group. The gram-positive organisms responsible for those infections not evaluable were methicillin-resistant Staphylococcus aureus, Streptococcus pneumoniae, and group F streptococcus, all of which were resistant to fleroxacin. In total, 6 gram-positive isolates were resistant to fleroxacin. All but 2 S aureus isolates were susceptible to ceftazidime. Adverse reactions in both groups were negligible. Fleroxacin was found to be as effective as ceftazidime against a variety of gram-negative pathogens, but local susceptibility patterns for quinolones should be checked before empiric use of fleroxacin against gram-positive pathogens such as streptococci.     

Ticarcillin in Combination with Cephalothin or Gentamicin as Empiric Antibiotic Therapy in Granulocytopenic Cancer Patients

Ticarcillin was used in combination with either cephalothin or gentamicin as initial empiric antibiotic therapy for 127 patient trials of suspected infection in granulocytopenic cancer patients. Bacteremia was present in 20%, nonbacteremic microbiologically documented infections in 21%, clinically documented infections in 23%, and possible infections in 5%; infection was doubtful in 31%. Although Staphylococcus aureus was the most common single organism isolated (23%), gram-negative bacilli accounted for 54% of all pathogens. Both antibiotic regimens were highly efficacious, with complete resolution in 46% of bacteremias, 88% of nonbacteremic microbiologically documented infections, and 95% of clinically documented infections. Among bacteremias, 8 of 9 caused by S. aureus but only 4 of 15 (27%) caused by gram-negative bacilli were completely resolved with these antibiotic combinations. Reasons for nonresponse in bacteremias were persistent granulocytopenia, mixed infection and, in two patients, antibiotic-resistant organisms. Toxicities other than hypokalemia were minimal. Although the rate of further infections was high overall (18/127), only one occurred among the 39 patients with <4 days of antibiotic therapy. Ticarcillin in combination with either cephalothin or gentamicin was effective as initial empiric therapy of suspected infection in granulocytopenic cancer patients.