Efficacy of combination therapy with minocycline for treating Stenotrophomonas maltophilia infections.

BACKGROUND

Stenotrophomonas maltophilia is a multidrug-resistant opportunistic pathogen associated with substantial in-hospital mortality. However, data supporting the efficacy of treating S. maltophilia infections using a combination of antimicrobials remain inconclusive.

OBJECTIVES

To assess whether adjunctive minocycline improves clinical outcomes of S. maltophilia infections compared with standard monotherapy.

METHODS

This randomized, double-blind, placebo-controlled trial was conducted at Siriraj Hospital, Thailand. Adults with confirmed S. maltophilia infections were randomized to receive minocycline or a matching placebo in addition to monotherapy with either levofloxacin or trimethoprim/sulfamethoxazole.

RESULTS

This trial enrolled 112 patients (71.4% [n = 80/112] of patients requiring an intensive care unit [ICU] and 66.1% [n = 74/112] of patients were diagnosed with ventilator-associated pneumonia [VAP]). Baseline demographic and clinical characteristics were balanced between intervention and control groups. Adjunctive minocycline did not significantly reduce 28-day-mortality (n = 24/55[43.6%] vs n = 22/57[38.6%], P = 0.590) but did achieve significantly higher microbiological response rates at early assessment (n = 25/55[45.5%] vs n = 8/57[14.0%], P < 0.001) and the end of treatment (n = 44/55[80.0%] vs n = 32/57[56.1%], P = 0.023). In contrast, clinical response rates did not differ between groups at either 72 h after the start of study treatment or the end of study treatment. In multivariable analysis, two factors were independently associated with 28-day mortality: history of antibiotic use before admission (adjusted odds ratio [aOR]: 7.65, 95% confidence interval [CI]: 2.04-28.76; P = 0.030) and septic shock (aOR: 7.24, 95% CI: 2.75-19.23; P < 0.001).

CONCLUSIONS

Although adding minocycline to either levofloxacin or trimethoprim/sulfamethoxazole therapy enhanced microbiological eradication, it did not confer a measurable survival or clinical advantage. Combination therapy was well tolerated. This study is potentially of interest to those treating ICU patients, as the majority of infections were VAP.