Alternating First-Line Antibiotics Increases Heterogeneity Without Increasing Mortality in Febrile Neutropenia

Rising antibiotic resistance presents a challenge for managing febrile neutropenia in patients with hematologic malignancies receiving chemotherapy. Assessing the alternation of first-line antibiotics to avoid antibiotic resistance, researchers have determined that the strategy results in an increase in heterogeneity without increasing mortality.

The strategy, also called heterogenous antibiotic use, is 1 of 2 strategies often touted as a way to avoid antibiotic resistance, the other being antibiotic cycling. As heavy use of an antibiotic over a long period of time will likely promote resistance to that antibiotic, an antibiotic cycling strategy operates on the hypothesis that a scheduled withdrawal of the antibiotic—or all in its classes—for a set period of time should re-establish susceptibility to that antibiotic. While that antibiotic is restricted, a suitable alternative is used. However, results of this strategy have been mixed.

To determine the impact of heterogenous antibiotic use, researchers implemented the strategy in their tertiary hospital in 2013. Data and Antibiotic Heterogeneity Index (AHI) for 2012 (pre-strategy implementation) and 2014 (post-strategy implementation) were compared.

“After a consensus meeting comprising hematologists and infectious disease physicians, it was decided that that choice of empiric antibiotic for febrile neutropenia would be piperacillin-tazobactam (PTZ) on odd dates and cefepime-amikacin (CEF-AMK) combination on even dates,” explained the researchers. “If the patient was still febrile after 48 hours, and cultures remained negative, physicians had several options, including continuing the originally prescribed antibiotics, adding vancomycin, or switching to a broad-spectrum carbapenem.”

There were 2012 admissions in 2012 and 1843 admissions in 2014, with no significant baseline characteristics between the 2 groups. During the study period, the defined daily doses of CEF fell from 235.22/1000 patient days in 2012 to 108.82/1000 patient days in 2014, and the defined daily doses of vancomycin fell from 116.62/1000 patient days to 70.82/1000 patient days. Meanwhile, the defined daily doses of PTZ rose from 20.73/1000 patient days to 86.05/1000 patient days. The rate of other antibiotic use was not statistically different.

Between 2012 and 2014, the AHI increased from 0.466 to 0.582. All-cause mortality was not significantly different between the 2 periods, decreasing slightly from 11% to 9%.

The researchers also observed no difference in rates of bacteremia with CEF-resistant, PTZ-resistant, and carbapenem-resistant gram-negative organisms in the 2 groups. There was no change in the rates of new cases of Methicillin-resistant Staphylococcus aureus or Vancomycin-resistant Enterococcus. Between 2012 and 2014, the AHI increased from 0.466 to 0.582.

Reference:

Tan B, Guzman M, Donato L, Kalimuddin S, et al. Impact of an alternation first-line antibiotics strategy in febrile neutropenia [published online November 28, 2018]. PLOS One. doi: 10.1371/journal.pone.0208039.