Skip to main content
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1992 Apr;36(4):801–807. doi: 10.1128/aac.36.4.801

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

J J Cornelissen 1, A de Graeff 1, L F Verdonck 1, T Branger 1, M Rozenberg-Arska 1, J Verhoef 1, A W Dekker 1
PMCID: PMC189424  PMID: 1503442

Abstract

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.

Full text

PDF
801

Selected References

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

  1. Bodey G. P., Elting L., Jones P., Alvarez M. E., Rolston K., Fainstein V. Imipenem/cilastatin therapy of infections in cancer patients. Cancer. 1987 Jul 15;60(2):255–262. doi: 10.1002/1097-0142(19870715)60:2<255::aid-cncr2820600224>3.0.co;2-l. [DOI] [PubMed] [Google Scholar]
  2. Boyce J. M., Papa E., Dickenson R., Medeiros A. A. Failure of routine susceptibility tests to detect imipenem resistance among strains of methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 1991 Jul;35(7):1495–1497. doi: 10.1128/aac.35.7.1495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cohen J., Donnelly J. P., Worsley A. M., Catovsky D., Goldman J. M., Galton D. A. Septicaemia caused by viridans streptococci in neutropenic patients with leukaemia. Lancet. 1983 Dec 24;2(8365-66):1452–1454. doi: 10.1016/s0140-6736(83)90799-7. [DOI] [PubMed] [Google Scholar]
  4. Dekker A. W., Rozenberg-Arska M., Sixma J. J., Verhoef J. Prevention of infection by trimethoprim-sulfamethoxazole plus amphotericin B in patients with acute nonlymphocytic leukaemia. Ann Intern Med. 1981 Nov;95(5):555–559. doi: 10.7326/0003-4819-95-5-555. [DOI] [PubMed] [Google Scholar]
  5. Dekker A. W., Rozenberg-Arska M., Verhoef J. Infection prophylaxis in acute leukemia: a comparison of ciprofloxacin with trimethoprim-sulfamethoxazole and colistin. Ann Intern Med. 1987 Jan;106(1):7–11. doi: 10.7326/0003-4819-106-1-7. [DOI] [PubMed] [Google Scholar]
  6. Dickinson G. M., Bisno A. L. Infections associated with indwelling devices: concepts of pathogenesis; infections associated with intravascular devices. Antimicrob Agents Chemother. 1989 May;33(5):597–601. doi: 10.1128/aac.33.5.597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fan W., del Busto R., Love M., Markowitz N., Cendrowski C., Cardenas J., Quinn E., Saravolatz L. Imipenem-cilastatin in the treatment of methicillin-sensitive and methicillin-resistant Staphylococcus aureus infections. Antimicrob Agents Chemother. 1986 Jan;29(1):26–29. doi: 10.1128/aac.29.1.26. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hughes W. T., Armstrong D., Bodey G. P., Feld R., Mandell G. L., Meyers J. D., Pizzo P. A., Schimpff S. C., Shenep J. L., Wade J. C. From the Infectious Diseases Society of America. Guidelines for the use of antimicrobial agents in neutropenic patients with unexplained fever. J Infect Dis. 1990 Mar;161(3):381–396. doi: 10.1093/infdis/161.3.381. [DOI] [PubMed] [Google Scholar]
  9. Karp J. E., Merz W. G., Hendricksen C., Laughon B., Redden T., Bamberger B. J., Bartlett J. G., Saral R., Burke P. J. Oral norfloxacin for prevention of gram-negative bacterial infections in patients with acute leukemia and granulocytopenia. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1987 Jan;106(1):1–7. doi: 10.7326/0003-4819-106-1-1. [DOI] [PubMed] [Google Scholar]
  10. Kern W., Kurrle E., Vanek E. High risk of streptococcal septicemia after high dose cytosine arabinoside treatment for acute myelogenous leukemia. Klin Wochenschr. 1987 Aug 17;65(16):773–780. doi: 10.1007/BF01743253. [DOI] [PubMed] [Google Scholar]
  11. Klastersky J., Vamecq G., Cappel R., Swings G., Vandenborre L. Effects of the combination of gentamicin and carbenicillin on the bactericidal activity of serum. J Infect Dis. 1972 Feb;125(2):183–186. doi: 10.1093/infdis/125.2.183. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Meyer R. D. Risk factors and comparisons of clinical nephrotoxicity of aminoglycosides. Am J Med. 1986 Jun 30;80(6B):119–125. doi: 10.1016/0002-9343(86)90489-4. [DOI] [PubMed] [Google Scholar]
  14. Morrison A. J., Jr, Hoffmann K. K., Wenzel R. P. Associated mortality and clinical characteristics of nosocomial Pseudomonas maltophilia in a university hospital. J Clin Microbiol. 1986 Jul;24(1):52–55. doi: 10.1128/jcm.24.1.52-55.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mortimer J., Miller S., Black D., Kwok K., Kirby W. M. Comparison of cefoperazone and mezlocillin with imipenem as empiric therapy in febrile neutropenic cancer patients. Am J Med. 1988 Jul 25;85(1A):17–20. doi: 10.1016/0002-9343(88)90170-2. [DOI] [PubMed] [Google Scholar]
  16. Norrby S. R., Vandercam B., Louie T., Runde V., Norberg B., Anniko M., Andrien F., Baudrihaye M., Bow E., Burman L. A. Imipenem/cilastatin versus amikacin plus piperacillin in the treatment of infections in neutropenic patients: a prospective, randomized multi-clinic study. Scand J Infect Dis Suppl. 1987;52:65–78. [PubMed] [Google Scholar]
  17. Nováková I., Donnelly J. P., De Pauw B. Ceftazidime as monotherapy or combined with teicoplanin for initial empiric treatment of presumed bacteremia in febrile granulocytopenic patients. Antimicrob Agents Chemother. 1991 Apr;35(4):672–678. doi: 10.1128/aac.35.4.672. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Pizzo P. A., Commers J., Cotton D., Gress J., Hathorn J., Hiemenz J., Longo D., Marshall D., Robichaud K. J. Approaching the controversies in antibacterial management of cancer patients. Am J Med. 1984 Mar;76(3):436–449. doi: 10.1016/0002-9343(84)90663-6. [DOI] [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. Rubin M., Hathorn J. W., Marshall D., Gress J., Steinberg S. M., Pizzo P. A. Gram-positive infections and the use of vancomycin in 550 episodes of fever and neutropenia. Ann Intern Med. 1988 Jan;108(1):30–35. doi: 10.7326/0003-4819-108-1-30. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Schoch P. E., Cunha B. A. Pseudomonas maltophilia. Infect Control. 1987 Apr;8(4):169–172. doi: 10.1017/s019594170006584x. [DOI] [PubMed] [Google Scholar]
  23. Shenep J. L., Hughes W. T., Roberson P. K., Blankenship K. R., Baker D. K., Jr, Meyer W. H., Gigliotti F., Sixbey J. W., Santana V. M., Feldman S. Vancomycin, ticarcillin, and amikacin compared with ticarcillin-clavulanate and amikacin in the empirical treatment of febrile, neutropenic children with cancer. N Engl J Med. 1988 Oct 20;319(16):1053–1058. doi: 10.1056/NEJM198810203191604. [DOI] [PubMed] [Google Scholar]
  24. Visser M. R., Rozenberg-Arska M., Beumer H., Hoepelman I. M., Verhoef J. Comparative in vitro antibacterial activity of sparfloxacin (AT-4140; RP 64206), a new quinolone. Antimicrob Agents Chemother. 1991 May;35(5):858–868. doi: 10.1128/aac.35.5.858. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES