Background: Trimethoprim-sulfamethoxazole (TS) is recommended for the treatment of Stenotrophomonas maltophilia infections due to high levels of in vitro susceptibility, but tolerability and increasing resistance may limit its utility. Studies have identified fluoroquinolones, tetracyclines, polymyxins, ceftazidime, and ticarcillin-clavulanate, as alternatives but clinical data are limited regarding the role of these agents and their role in combination therapy (CT).
Methods: Retrospective cohort study of adult patients at NewYork-Presbyterian Hospital with S. maltophilia pneumonia defined by CDC/NHSN criteria from 2009-2015. Patients were excluded if treatment was initiated > 5 days after the index culture (IC), they received <48 hours of therapy, resistance to both TS and levofloxacin were identified, or the patient died within 3 days of IC. The primary outcome was 30-day mortality. Secondary outcomes included clinical response (CR) at end of therapy (EOT), microbiologic eradication (ME) at EOT, and the development of resistance (DOR) within 90 days. Outcomes were compared between monotherapy (MT) and CT as well as TS-containing and -sparing regimens.
Results: 106 patients were included (Figure 1). Patients were 50% male with median age of 64 years and 47% were immunosuppressed. Compared to MT, patients with CT had higher median Charlson Comorbidity Index (2 vs. 4; p=0.014), higher median modified APACHE II scores (13 vs. 14; p<0.001), and were more often in severe sepsis/septic shock (38% vs. 62%; p=0.021). CT was associated with increased mortality (16% vs. 40%; p=0.012), decreased CR at EOT (72% vs. 49%; p=0.025), and increased DOR (26% vs. 65%; p=0.012) with no difference in ME. On multivariable analysis only the modified APACHE II score (p=0.001) and continuous renal replacement therapy (p=0.008) were associated with increased risk of mortality. No difference in mortality (22% vs. 29%; p=0.547), CR (56% vs. 66%; p=0.404), ME (63% vs. 72%; p=0.455), or DOR (52% vs. 37%; p=0.467) was identified between TS-sparing (n=41) and TS-containing (n=65) regimens.
Conclusion: Combination therapy for S. maltophilia pneumonia did not improve outcomes and outcomes may be driven more by severity of illness than susceptible drug therapy. No differences were identified for TS-containing or -sparing regimens. Additional data are needed to identify optimal therapy.
C. J. Kubin, None