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

Does aminoglycoside therapy cause significant acute kidney injury in febrile neutropenia?

“…The rate was similar to those in the studies included in the meta-analysis by Paul et al [1] that used once-daily dosing of aminoglycosides [6,[8][9][10][11], with the exception of Esteve et al [2] who found an unusually high incidence of renal toxicity. This outlying study accounted for the observation in the meta-analysis of increased renal toxicity where once-daily dosing was used.…”

“…Most other studies, including the meta-analysis [1], have either not defined renal failure or have used a single abnormal serum creatinine level as an endpoint for analysis. The use of the newer AKIN definitions of AKI demonstrated 24 additional episodes that resulted in AKIN stage 1 AKI compared with older definitions of AKI in the febrile neutropenia literature.…”

“…A meta-analysis of 68 trials from 1983-2007 demonstrated a trend towards reduced mortality with monotherapy [relative risk (RR) = 0.87; 95% confidence interval (CI) 0.75-1.02] [1]. ␤-Lactam monotherapy was also associated with a decreased incidence of any nephrotoxicity in the six trials in the meta-analysis that used once-daily aminoglycoside dosing (RR = 0.29; 95% CI 0.13-0.63).…”

“…However, one study with an unusually high incidence of acute kidney injury (AKI) was responsible for this effect [2]. Furthermore, treatment failure was significantly more common in monotherapy trials that compared the same ␤-lactam agent (RR = 1.11; 95% CI 1.02-1.21) [1]. The meta-analysis did not define renal impairment and the individual studies subjected to meta-analysis used variable definitions of AKI and did not differentiate between a transient rise in serum creatinine as opposed to long-term loss of renal function.…”

Combination Therapy for Treatment of Infections with Gram-Negative Bacteria

“…As there have been a number of studies conducted to assess the appropriateness of combination therapy for infections caused by Gram-negative organisms, several meta-analyses have been compiled to summarize these data (Table 1) (23,67,68,80,161,194,(196)(197)(198)(199)212). In general, meta-analyses of observational studies have shown a benefit of combination therapy, while those including RCTs have not demonstrated such a benefit (161).…”