1491. Standard- vs. High-dose Trimethoprim-Sulfamethoxazole for Stenotrophomonas maltophilia pneumonia

Abstract

Background Stenotrophomonas maltophilia is a multidrug-resistant pathogen known to cause pneumonia with associated mortality rates up to 44%.1,2 Trimethoprim-sulfamethoxazole (TMP-SMX) is the drug of choice based on available clinical evidence and excellent in-vitro susceptibility rates.3 High-dose TMP-SMX strategies recommend between 15-20mg/kg/day of the TMP component, however this has been associated with increased adverse drug events (ADE).4,5 The optimal dosing strategy remains unclear and it is unknown whether lower doses of TMP-SMX would achieve similar outcomes. Methods Patients with positive respiratory cultures for S. maltophilia who received at least 72 hours of TMP-SMX therapy for hospital-acquired or ventilator-associated pneumonia from January 2010 to March 2020 were included. Doses were categorized as standard-dose (SD) TMP-SMX (< 15 mg/kg/day TMP) or high-dose (HD) TMP-SMX (≥ 15 mg/kg/day TMP) after adjusting for renal function. The primary outcome was clinical success, defined as the composite of resolution of signs/symptoms of pneumonia, in-hospital survival, and no escalation of care. Secondary outcomes included hospital length of stay (LOS), 30-day mortality, 30-day readmission, and ADE. Results Of the 44 patients meeting inclusion criteria for the study, 27 received SD and 17 received HD TMP-SMX therapy. Patients received 12 mg/kg/day (IQR 11-14) and 16 mg/kg/day (IQR 16-19) in the SD and HD groups, respectively. There was no difference in clinical success between the SD and HD group (41% vs 59%, p=0.24). Secondary outcomes were similar between both groups except for 30-day hospital readmission; the SD group had significantly lower readmission rates (6% vs 69%, p < 0.01). Rates of adverse events were not statistically different between the two groups. Conclusion This study provides evidence that SD TMP-SMX may achieve similar clinical efficacy to HD TMP-SMX. We found no significant difference in clinical success, LOS, 30-day mortality, or adverse events between groups. Although HD TMP-SMX is the current recommendation for S. maltophilia infections, concerns about tolerability and adverse effects suggest that further clinical and pharmacodynamic research is needed. Disclosures All Authors: No reported disclosures