Successful Treatment of Multi-drug Resistant Acinetobacter baumannii Ventilator-Associated Pneumonia with a Novel Colistin and Fusidic Acid Combination Therapy
The treatment of Acinetobacter baumannii infections is increasingly challenging due to the success of multi-drug resistant (MDRAB) strains and the lack of new compounds in development. Combination therapies are increasingly employed although there is little data on the clinical efficacy and outcome of unorthodox regimens.
Here we describe successful treatment of a MDRAB ventilator-associated pneumonia (VAP) in a 19-year-old trauma patient with colistin and fusidic acid following identification of potent antimicrobial synergy in vitro.
Acinetobacter baumannii isolated from endotracheal aspirates on day 15 was found to be resistant to all agents tested with the exception of colistin (MIC 0.25 mg/l). Potential synergy between colistin and fusidic acid was identified in a double disc diffusion test and investigated further in microtitre checkerboard assays and a time-kill study using susceptible clinical breakpoint concentrations of colistin (2 mg/l) and fusidic acid (1 mg/l; for Staphylococcus spp). The patient was treated with intravenous colistimethate sodium (Colomycin¨) 2 million units 8 hourly and fusidic acid 500mg 8 hourly for a total of 16 days.
The MDRAB isolate was identified as a member of the UK OXA-23 clone 1 lineage by molecular typing. Synergy between colistin and fusidic acid in vitro was confirmed with a FICI of 0.5 and SBPI of 17 in checkerboard assays and an 8 log fold reduction in viable counts using the combination in time-kill studies (Figure 1).
Clinical response was rapid, with improvement in both systemic and biochemical markers of infection within 48h. Clinical cure and microbiological eradication was achieved after 16 days of treatment with surveillance cultures for MDRAB remaining consistently negative.
The combination of colistin and fusidic acid was identified as a highly active therapy for the treatment of MDRAB VAP. The regimen was well tolerated, efficacious and led to sustained microbiological and clinical cure. Further studies to determine and refine the role of colistin / fusidic acid therapy in the treatment of MDR Gram-negative infections are warranted.
Figure 1. Time-kill assay. COL 2mg/l – 8x MIC colistin sulfate. FD 1mg/l – 0.004x MIC fusidic acid.
D. W. Wareham, None