Beta-lactam versus beta-lactam-aminoglycoside combination therapy in cancer patients with neutropaenia

Chemotherapy treated cancer patients are prone to neutropaenia and life-threatening infections. Early, empirical antibiotic treatment is therefore administered routinely to febrile neutropaenic patients. Currently, either beta-lactam-aminoglycoside combination treatment or beta-lactam monotherapy are recommended.

We compared beta-lactam monotherapy versus beta-lactam-aminoglycoside combination therapy for cancer patients with fever and neutroepaenia.

Cochrane Library (Issue 4,2001), the Cochrane Cancer Network Register of trials (July 2000), EMBASE (January 1980-2000), MEDLINE (1966-8/2001), and ICAAC conference proceedings (1995 onwards). We scanned references of all included studies, pertinent reviews, and contacted the first author of each included trial and the pharmaceutical companies.

Randomised controlled trials comparing any beta-lactam antibiotic monotherapy to any combination of a beta-lactam and an aminoglycoside antibiotic, for the initial, empirical treatment of febrile neutropaenic cancer patients.

Data concerning mortality, treatment failure (including treatment modifications), superinfections, adverse effects and study quality measures were extracted independently by two reviewers. Relative risks with their 95% confidence intervals (CI) were estimated. Outcomes were extracted by intention-to-treat analysis whenever possible.

Forty-six trials and 7642 patients were included. All cause mortality was the primary outcome assessed. For all mortality comparisons, no significant difference between monotherapy and combination therapy was seen, relative risk 0.85 (95% CI 0.72-1.02) for all studies combined. Treatment failure was the outcome reported in all included trials. No significant difference between study groups was shown for studies comparing the same beta-lactam, relative risk 1.12 (95% CI 0.96-1.29). A significant advantage to monotherapy was observed for studies comparing different beta-lactams, relative risk 0.86 (95% CI 0.80-0.93). Bacterial and fungal superinfections developed with similar frequencies in the monotherapy and combination treatment groups. Adverse events were significantly more common in the combination treatment group, relative risk 0.83, (95% CI 0.72-0.97). These included events associated with significant morbidity, primarily renal toxicity. Results were consistent for subgroup and sensitivity analyses.

We have shown an advantage to broad-spectrum beta-lactam monotherapy over beta-lactam-aminoglycoside combination therapy for febrile neutropaenia. This advantage comprises of 1) a similar, if not better, survival, 2) a significantly lower treatment failure rate, 3) comparable probability for secondary infections and, 4) most importantly, a lower rate of adverse events associated with significant morbidity. Monotherapy can be regarded, therefore, as the standard of care for febrile neutropaenic patients.