W. Terzian3, S. P. Stawicki3, L. E. Bratis2, M. Turki2, N. D. Civic1, C. V. Murphy4 1St. Luke’s University Health Network,Department Of Pharmacy,Bethlehem, PA, USA 2St. Luke’s University Health Network,Center For Critical Care,Bethlehem, PA, USA 3St. Luke’s University Health Network,Department Of Surgery,Bethlehem, PA, USA 4Ohio State University,Department Of Pharmacy,Columbus, OH, USA
Introduction: Continued increase of multi-drug resistant (MDR) gram-negative (GN) infections, including Pseudomonas spp and Acinetobacter spp, prompted re-examination of Colistin – an antibiotic abandoned in the 1970s due to nephro- and neurotoxicity – as an alternative for recalcitrant MDR-GN pneumonia. Colistin may be administered intravenously or as an inhaled-intravenous combination. Effectiveness of combination therapy has been examined previously; however, no definitive evidence exists to either support or refute this approach. The current meta-analysis examines potential benefits of combination intravenous-inhaled colistin (IVIC) regimen compared to intravenous colistin monotherapy (ICM) in patients with MDR-GN pneumonia.
Methods: An exhaustive English-language literature review was performed using Google™ Scholar, PubMed, and EBSCO Internet repositories. Out of 119 potential candidate studies, 6 retrospective reports met the inclusion criteria of: (a) directly comparing the two therapy groups (IVIC versus ICM); (b) sufficient scientific quality, including detailed descriptions of comparator groups and corresponding outcomes; and (c) describing similar microbiologic pathogen mix. Meta-analytic techniques were utilized to pool clinical results from the six studies, with selected clinical outcomes of mortality (6 studies), microbiologic cure (4 studies), and clinical cure (4 studies) being reported.
Results: The overall quality of data reporting for all three studies included was low. Combined data on microbiologic cure demonstrated no differences between IVIC and ICM regimens (OR 2.076, 95%CI 0.453-1.929, p=0.165). For clinical cure and mortality, pooled analyses demonstrate potential benefit to combined (IVIC) therapy. More specifically, IVIC colistin use is associated with both increased clinical cure (OR 2.857, 95%CI 1.385-5.890, p=0.004) and lower mortality (OR 0.603, 95%CI 0.384-0.949, p=0.029). Key study results are summarized in Table 1.
Conclusion: Addition of aerosolized Colistin to intravenous Colistin may improve clinical cure and mortality for patients with MDR-GN pneumonia. In terms of microbiologic cure, current results show a trend toward improved outcomes with the IVIC approach. Results of this exploratory meta-analysis support the use of IVIC as the primary therapeutic approach. Large, sufficiently powered prospective trials are needed to confirm the benefit of combination IVIC therapy for MDR-GN pneumonia, especially with regard to microbiologic cure.
