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. 1996 May;40(5):1108–1115. doi: 10.1128/aac.40.5.1108

Monotherapy with meropenem versus combination therapy with 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 and the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto Infection Program.

A Cometta 1, T Calandra 1, H Gaya 1, S H Zinner 1, R de Bock 1, A Del Favero 1, G Bucaneve 1, F Crokaert 1, W V Kern 1, J Klastersky 1, I Langenaeken 1, A Micozzi 1, A Padmos 1, M Paesmans 1, C Viscoli 1, M P Glauser 1
PMCID: PMC163274  PMID: 8723449

Abstract

Combinations of beta-lactams plus aminoglycosides have been standard therapy for suspected infections in granulocytopenic cancer patients, especially those with profound long-lasting granulocytopenia. With the advent of new broad-spectrum bactericidal antibiotics such as extended-spectrum cephalosporins or carbapenems, the need to combine beta-lactams with aminoglycosides became more controversial. The objective of this prospective randomized multicenter study was to compare the efficacy, safety, and tolerance of meropenem monotherapy with those of the combination of ceftazidime plus amikacin for the empirical treatment of fever in granulocytopenic cancer patients. Of 1,034 randomized patients, 958 were assessable in the intent-to-treat analysis for response to antibacterial therapy, including 483 in the meropenem group and 475 in the ceftazidime-plus-amikacin group. The median durations of neutropenia were 16 and 17 days, respectively. A successful outcome was reported in 270 of 483 (56%) patients treated with monotherapy compared with 245 of 475 (52%) patients treated with the combination group (P = 0.20). The success rates in the monotherapy group and the combination group were similar by type of infection (single gram-negative bacteremia, single gram-positive bacteremia, clinically documented infection, and possible infection). The occurrence of further infections assessed in patients for whom the allocated regimen was not modified did not differ between the two groups (12% in both groups). Mortality due to the presenting infection or further infection was relatively low (8 patients treated with the monotherapy compared with 13 patients treated with the combination). A total of 1,027 patients were evaluable for adverse events; the proportion of those who developed adverse effects was similar between the two groups (29% in both groups), and only 19 (4%) patients in the monotherapy group and 31 (6%) in the combination group experienced an adverse event related or probably related to the study drug. Allergic reactions were the only reason for stopping the protocol antibiotic(s) (3 and 5 patients, respectively). This study confirms that monotherapy with meropenem is as effective as the combination of ceftazidime plus amikacin for the empiric treatment of fever in persistently granulocytopenic cancer patients, and both regimens were well tolerated.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Blaser J., König C., Fatio R., Follath F., Cometta A., Glauser M. Multicenter quality control study of amikacin assay for monitoring once-daily dosing regimens. International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer. Ther Drug Monit. 1995 Apr;17(2):133–136. doi: 10.1097/00007691-199504000-00005. [DOI] [PubMed] [Google Scholar]
  2. Calandra T., Cometta A. Antibiotic therapy for gram-negative bacteremia. Infect Dis Clin North Am. 1991 Dec;5(4):817–834. [PubMed] [Google Scholar]
  3. Cometta A., Baumgartner J. D., Lew D., Zimmerli W., Pittet D., Chopart P., Schaad U., Herter C., Eggimann P., Huber O. Prospective randomized comparison of imipenem monotherapy with imipenem plus netilmicin for treatment of severe infections in nonneutropenic patients. Antimicrob Agents Chemother. 1994 Jun;38(6):1309–1313. doi: 10.1128/aac.38.6.1309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cometta A., Zinner S., de Bock R., Calandra T., Gaya H., Klastersky J., Langenaeken J., Paesmans M., Viscoli C., Glauser M. P. 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. Antimicrob Agents Chemother. 1995 Feb;39(2):445–452. doi: 10.1128/aac.39.2.445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. De Jongh C. A., Joshi J. H., Newman K. A., Moody M. R., Wharton R., Standiford H. C., Schimpff S. C. Antibiotic synergism and response in gram-negative bacteremia in granulocytopenic cancer patients. Am J Med. 1986 May 30;80(5C):96–100. [PubMed] [Google Scholar]
  6. De Pauw B. E., Deresinski S. C., Feld R., Lane-Allman E. F., Donnelly J. P. Ceftazidime compared with piperacillin and tobramycin for the empiric treatment of fever in neutropenic patients with cancer. A multicenter randomized trial. The Intercontinental Antimicrobial Study Group. Ann Intern Med. 1994 May 15;120(10):834–844. doi: 10.7326/0003-4819-120-10-199405150-00004. [DOI] [PubMed] [Google Scholar]
  7. Edwards J. R., Turner P. J., Wannop C., Withnell E. S., Grindey A. J., Nairn K. In vitro antibacterial activity of SM-7338, a carbapenem antibiotic with stability to dehydropeptidase I. Antimicrob Agents Chemother. 1989 Feb;33(2):215–222. doi: 10.1128/aac.33.2.215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Eliopoulos G. M., Eliopoulos C. T. Antibiotic combinations: should they be tested? Clin Microbiol Rev. 1988 Apr;1(2):139–156. doi: 10.1128/cmr.1.2.139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Francioli P. B., Glauser M. P. Synergistic activity of ceftriaxone combined with netilmicin administered once daily for treatment of experimental streptococcal endocarditis. Antimicrob Agents Chemother. 1993 Feb;37(2):207–212. doi: 10.1128/aac.37.2.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Freedman L. S., White S. J. On the use of Pocock and Simon's method for balancing treatment numbers over prognostic factors in the controlled clinical trial. Biometrics. 1976 Sep;32(3):691–694. [PubMed] [Google Scholar]
  11. Freifeld A. G., Walsh T., Marshall D., Gress J., Steinberg S. M., Hathorn J., Rubin M., Jarosinski P., Gill V., Young R. C. Monotherapy for fever and neutropenia in cancer patients: a randomized comparison of ceftazidime versus imipenem. J Clin Oncol. 1995 Jan;13(1):165–176. doi: 10.1200/JCO.1995.13.1.165. [DOI] [PubMed] [Google Scholar]
  12. Gribble M. J., Chow A. W., Naiman S. C., Smith J. A., Bowie W. R., Sacks S. L., Grossman L., Buskard N., Growe G. H., Plenderleith L. H. Prospective randomized trial of piperacillin monotherapy versus carboxypenicillin-aminoglycoside combination regimens in the empirical treatment of serious bacterial infections. Antimicrob Agents Chemother. 1983 Sep;24(3):388–393. doi: 10.1128/aac.24.3.388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Klastersky J., Cappel R., Daneau D. Clinical significance of in vitro synergism between antibiotics in gram-negative infections. Antimicrob Agents Chemother. 1972 Dec;2(6):470–475. doi: 10.1128/aac.2.6.470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Klastersky J., Daneau D., Swings G., Weerts D. Antibacterial activity in serum and urine as a therapeutic guide in bacterial infections. J Infect Dis. 1974 Feb;129(2):187–193. doi: 10.1093/infdis/129.2.187. [DOI] [PubMed] [Google Scholar]
  15. Klastersky J., Meunier-Carpentier F., Prevost J. M. Significance of antimicrobial synergism for the outcome of gram negative sepsis. Am J Med Sci. 1977 Mar-Apr;273(2):157–167. doi: 10.1097/00000441-197703000-00005. [DOI] [PubMed] [Google Scholar]
  16. Klastersky J., Zinner S. H. Synergistic combinations of antibiotics in gram-negative bacillary infections. Rev Infect Dis. 1982 Mar-Apr;4(2):294–301. doi: 10.1093/clinids/4.2.294. [DOI] [PubMed] [Google Scholar]
  17. Leyland M. J., Bayston K. F., Cohen J., Warren R., Newland A. C., Bint A. J., Cefai C., White D. G., Murray S. A., Bareford D. A comparative study of imipenem versus piperacillin plus gentamicin in the initial management of febrile neutropenic patients with haematological malignancies. J Antimicrob Chemother. 1992 Dec;30(6):843–854. doi: 10.1093/jac/30.6.843. [DOI] [PubMed] [Google Scholar]
  18. Liang R., Yung R., Chiu E., Chau P. Y., Chan T. K., Lam W. K., Todd D. Ceftazidime versus imipenem-cilastatin as initial monotherapy for febrile neutropenic patients. Antimicrob Agents Chemother. 1990 Jul;34(7):1336–1341. doi: 10.1128/aac.34.7.1336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Pizzo P. A., Hathorn J. W., Hiemenz J., Browne M., Commers J., Cotton D., Gress J., Longo D., Marshall D., McKnight J. A randomized trial comparing ceftazidime alone with combination antibiotic therapy in cancer patients with fever and neutropenia. N Engl J Med. 1986 Aug 28;315(9):552–558. doi: 10.1056/NEJM198608283150905. [DOI] [PubMed] [Google Scholar]
  20. Pizzo P. A. Management of fever in patients with cancer and treatment-induced neutropenia. N Engl J Med. 1993 May 6;328(18):1323–1332. doi: 10.1056/NEJM199305063281808. [DOI] [PubMed] [Google Scholar]
  21. Rolston K. V., Berkey P., Bodey G. P., Anaissie E. J., Khardori N. M., Joshi J. H., Keating M. J., Holmes F. A., Cabanillas F. F., Elting L. A comparison of imipenem to ceftazidime with or without amikacin as empiric therapy in febrile neutropenic patients. Arch Intern Med. 1992 Feb;152(2):283–291. [PubMed] [Google Scholar]
  22. Schimpff S., Satterlee W., Young V. M., Serpick A. Empiric therapy with carbenicillin and gentamicin for febrile patients with cancer and granulocytopenia. N Engl J Med. 1971 May 13;284(19):1061–1065. doi: 10.1056/NEJM197105132841904. [DOI] [PubMed] [Google Scholar]
  23. Winston D. J., Ho W. G., Bruckner D. A., Champlin R. E. Beta-lactam antibiotic therapy in febrile granulocytopenic patients. A randomized trial comparing cefoperazone plus piperacillin, ceftazidime plus piperacillin, and imipenem alone. Ann Intern Med. 1991 Dec 1;115(11):849–859. doi: 10.7326/0003-4819-115-11-849. [DOI] [PubMed] [Google Scholar]

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