Mortality due to severe LD remains high with 20-25% of patients requiring mechanical ventilation. TG, a minocycline derivative, is active against L. pneumophila in animal and cell models, achieves high concentrations intracellularly and demonstrated minimal in vitrosynergy with levofloxacin (LVX). Clinical data on TG for LD are limited to two case reports in immunocompromised hosts. We describe our experience with TG as salvage therapy in severely ill patients with LD.
Patient demographics, clinical data and treatment details were collected retrospectively. Clinical failure was defined based on vital signs (temperature ≥37.2 C, heart rate ≥100 beats/min, respiratory rate ≥24 breath/min, systolic ≤100 mm Hg, oxygen saturation on room air <90%) and/or physician-documented deterioration in clinical parameters or death.
At our University Medical Center 12 patients with severe LD (positive Legionella urinary antigen n=8, elevated L. pneumophiliaantibody n=4) received TG salvage therapy after failure of initial treatment with azithromycin (AZ) n=6 or LVX and AZ n=6 between 1/2008 and 2/2016. Median age of these patients was 81 (37-90) years. More than half had ≥2 comorbidities, with cardiovascular and pulmonary being more common. Two patients were immunocompromised due to active chemotherapy. PSI score on admission was 130 (97-223); at the time of switch to TG, SOFA score was 6 (1-9) with respiratory worsening present in 11/12 patients after median of 4 (2-8) days of initial therapy. Seventy percent of patients required intensive care unit stay for 12 (1-18) days, 42% (5/12) had septic shock and were intubated for 10 (1-22) days.
These patients received salvage therapy with TG 100 mg x 1 dose, followed by 50 mg IV q12h in addition to LVX n=5, AZ n=3, LVX and AZ n=3, or as monotherapy n=1 for median of 8 (4-17) days. After TG salvage therapy, clinical improvement was seen in 67% (8/12). Two patients died and 2 were made comfort care. No patients experienced adverse events attributable to TG salvage therapy. Total duration of therapy was 18 (9-24) days.
This small cohort of patients provides evidence that TG can be considered for salvage therapy in patients failing macrolide or fluoroquinolone therapy.
Y. Dubrovskaya, None
E. Louie, None
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