Work

A 2012–2014 Global Antimicrobial Surveillance of Iclaprim Against Clinical Strains Causing Hospital-Associated Bacterial Pneumonia (HABP) and Skin and Skin Structure Infections (SSSI)

Year: 2016

Type: article

Abstract: Background. ICL, a new generation diaminopyrimidine compound, is a dihydrofolate reductase inhibitor antibiotic in phase 3 clinical development. An in vitro retrospective surveillance study on the antimicrobial spectrum and activity of iclaprim was performed against clinical isolates causing HABP and SSSI. Methods. A total of 1636 clinical gram-positive isolates causing HABP (601) and SSSI (577) were collected from the US, Europe, Latin America, and Asia Pacific during 2012–2014. Reference broth microdilution tests were conducted according to the Clinical and Laboratory Standards Institute (CLSI M07-A10, 2015) methods. Quality control (QC) ranges and interpretive criteria for comparator compounds were as published in (CLSI M100-S25, 2015). QC ranges for iclaprim were those approved by CLSI and published in M100-S25. Results. The MIC distributions of iclaprim, trimethoprim, trimethoprim-sulfamethoxazole and comparator antimicrobials for all S. aureus, including methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) strains, beta-hemolytic streptococci, and S. pneumoniae are shown in the table. Globally, ICL MIC50/90s for S. aureus including MRSA were l6-fold lower than those for TMP and similar to TMP/SMX. ICL MIC 50/90s for beta-hemolytic streptococci were 8-fold lower than for TMP and 2-fold lower than for TMP/SMX. ICL 50/90 were 32-fold lower than TMP and 4-fold lower than TMP/SMX for S. pneumoniae. ICL MIC 50/90 were 0.06/0.12, 0.06/0.25, and 0.06/2 for US S. aureus, beta-hemolytic Streptococcus, and S. pneumoniae, respectively; corresponding values for European isolates were 0.6/0.12, 0.12/0.25, and 0.6/4, respectively. Conclusion. ICL was potently active against all S. aureus, beta-hemolytic streptococcus, and S. pneumoniae clinical SSSI and HABP isolates globally from 2012 to 2014. ICL could be an important new therapeutic option for the treatment of SSSI and HABP, especially cases caused by multidrug resistant gram-positive bacteria. Pivotal clinical trials are warranted to evaluate ICL for the indications of SSSI and HABP. Disclosures. D. Huang, Motif BioSciences: Employee, Salary T. M. File Jr, Motif BioSciences: Scientific Advisor, Consulting fee M. Wilcox, Merck: Grant Investigator, Scientific Advisor and Speaker's Bureau, Consulting fee, Research support and Speaker honorarium Pfizer: Grant Investigator, Scientific Advisor and Speaker's Bureau, Consulting fee, Research support and Speaker honorarium Summit: Grant Investigator and Scientific Advisor, Consulting fee and Research support Seres: Grant Investigator, Scientific Advisor and Speaker's Bureau, Consulting fee, Research support and Speaker honorarium Da Volterra: Grant Investigator and Scientific Advisor, Consulting fee and Research support bioMérieux: Investigator and Scientific Advisor, Consulting fee and Research support Alere: Grant Investigator, Scientific Advisor and Speaker's Bureau, Consulting fee, Research support and Speaker honorarium Actelion: Grant Investigator and Scientific Advisor, Consulting fee and Research support M. Dryden, Motif BioSciences: Scientific Advisor, Consulting fee R. Shukla, Motif BioSciences: Employee, Salary

Source: Open Forum Infectious Diseases

DOI: 10.1093/ofid/ofw172.1384

Authors: David Huang, Thomas M. File, Mark Wilcox, Matthew Dryden, G Corey, Rajesh Shukla