Active monotherapy and combination therapy for extensively drug-resistant Pseudomonas aeruginosa pneumonia

Abstract

Data on treatment regimens and outcomes of extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) pneumonia are currently limited. A 6-year retrospective cohort study of adult patients diagnosed with XDR-PA pneumonia was conducted between January 2011 and December 2016. All XDR-PA isolates were susceptible to colistin and/or fosfomycin alone. Some XDR-PA isolates, which had minimum inhibitory concentrations for doripenem of 4 or 8 mg/L, were considered to be susceptible to 4-h prolonged infusion therapy with high-dose doripenem. Definite treatment regimens were categorized into three groups: inactive therapy, active monotherapy and active combined two-drug therapy. Outcomes were compared between the three groups. In total, 136 patients were included, and 37% had ventilator-associated pneumonia. Twenty-two, 74 and 40 patients received inactive therapy, active monotherapy and active combined two-drug therapy, respectively. Demographic and clinical characteristics were comparable between the three groups. Rates of 28-day survival and microbiological cure were significantly higher in patients who received active combined two-drug therapy compared with those who received active monotherapy and inactive therapy [90% vs 51% vs 0% (P<0.001) and 90% vs 54% vs 0% (P<0.001), respectively]. Kaplan-Meier survival analysis demonstrated a survival benefit of those who received active combined two-drug therapy over those who received active monotherapy and inactive therapy. Predictors for 28-day mortality were no infectious diseases (ID) consultations [adjusted odds ratio (aOR) 10.93; P<0.001], and receipt of inactive therapy (aOR 42.07; P<0.001) or active monotherapy (aOR 6.63; P=0.002) compared with receipt of active combined two-drug therapy. Active combined two-drug therapy was associated with better survival compared with active monotherapy for XDR-PA pneumonia. ID consultation was associated with a reduction in mortality.

Keywords: Combination therapy; Extensively drug-resistant; Mortality; Pneumonia; Pseudomonas aeruginosa; Treatment.