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

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.