title: A comparison of double beta-lactam combinations with netilmicin/ureidopenicillin regimens in the empirical therapy of febrile neutropenic patients.
abstract: 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.
authors.affiliation: Department of Microbiology, Royal Free Hospital, London, UK.
authors.forename: C C
authors.initials: CC
authors.lastname: Kibbler
authors.forename: H G
authors.initials: HG
authors.lastname: Prentice
authors.forename: R J
authors.initials: RJ
authors.lastname: Sage
authors.forename: A V
authors.initials: AV
authors.lastname: Hoffbrand
authors.forename: M K
authors.initials: MK
authors.lastname: Brenner
authors.forename: P
authors.initials: P
authors.lastname: Mannan
authors.forename: P
authors.initials: P
authors.lastname: Warner
authors.forename: A
authors.initials: A
authors.lastname: Bhamra
authors.forename: P
authors.initials: P
authors.lastname: Noone
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001390:Azlocillin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D001424:Bacterial Infections / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D005334:Fever / Q000150:complications; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D009428:Netilmicin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D009503:Neutropenia / Q000150:complications; D010400:Penicillin G / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010878:Piperacillin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D011897:Random Allocation
chemical_list: D000900:Anti-Bacterial Agents; D009428:Netilmicin; D001390:Azlocillin; D010400:Penicillin G; D010878:Piperacillin