Typing and susceptibility of bacterial isolates from the fidaxomicin (OPT-80) phase II study for C. difficile infection |
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| Institution: | 1. RM Alden Research Lab, Culver City, CA, USA;2. Optimer Pharmaceuticals, Inc., 10110 Sorrento Valley Road Ste. San Diego, CA 92121, USA;3. Edward Hines Jr. Veterans Affairs Hospital, Hines, IL, USA;4. Loyola University Chicago Stritch School of Medicine, Maywood, IL, USA;1. Department of Animal Health, Faculty of Veterinary, Universidad Complutense de Madrid, Madrid, Spain;2. Department of Medical Microbiology, Center of Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands;1. University of Ljubljana, Veterinary Faculty, Gerbičeva 60, SI-1000 Ljubljana, Slovenia;2. Institute of Public Health Maribor, Prvomajska 1, SI-2000 Maribor, Slovenia;3. University of Maribor, Faculty of Medicine, Slomškov trg 15, SI-2000 Maribor, Slovenia;4. Centre of Excellence for Integrated Approaches in Chemistry and Biology of Proteins, Jamova 39, SI-1000 Ljubljana, Slovenia;1. Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain;2. Instituto de Investigación Sanitaria del Hospital Gregorio Marañón, Madrid, Spain;3. Department of Animal Health, Faculty of Veterinary, UCM, Madrid, Spain;4. Department of Medicine, Faculty of Medicine, UCM, Madrid, Spain;5. Department of Animal Health, Faculty of Veterinary, University of Córdoba, Cordoba, Spain;6. Department of Medical Microbiology, Center of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands;1. University of Houston College of Pharmacy, Houston, TX, USA;2. Microbiota-Host Interactions and Clostridia Research Group, Facultad de Ciencias de La Vida, Universidad Andrés Bello, Santiago, Chile;3. ANID – Millennium Science Initiative Program - Millennium Nucleus in the Biology of the Intestinal Microbiota, Santiago, Chile;4. Department of Biology, Texas A&M University, College Station, TX, 77843, USA;1. Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, MA 02115, USA;2. School of Chemistry, University of Wollongong, NSW 2522, Australia;1. Institute of Medical Microbiology and Hygiene, National Reference Laboratory for Clostridium difficile, Saarland University, Kirrberger Straße, Building 43, 66421 Homburg/Saar, Germany;2. Center for Infectious Diseases Research, American University of Beirut Medical Center, Riad El-Solh 1107, 2020, Beirut, Lebanon;3. Department of Experimental Pathology, Immunology, and Microbiology, American University of Beirut Medical Center, Riad El-Solh 1107, 2020, Beirut, Lebanon;4. Department of Pathology and Lab Medicine, American University of Beirut Medical Center, Riad El-Solh 1107, 2020, Beirut, Lebanon;5. Department of Internal Medicine, American University of Beirut Medical Center, Riad El-Solh 1107, 2020, Beirut, Lebanon;6. Center for Infectious Diseases Research, American University of Beirut Medical Center, Riad El-Solh 1107, 2020 Beirut, Lebanon;7. Swiss Tropical and Public Health Institute, P.O. Box, CH-4002 Basel, Switzerland;8. University of Basel, P.O. Box, CH-4003 Basel, Switzerland;9. Institute for Laboratory Medicine, Microbiology and Hygiene, Christophorus Kliniken, Südwall 22, 48653, Coesfeld, Germany |
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| Abstract: | BackgroundClostridium difficile infection (CDI) has been increasing in incidence and severity in recent years, coincident with the spread of a “hypervirulent” strain, REA type BI (ribotype 027, PFGE NAP 1). Exacerbating the problem has been the observation that metronidazole may be showing decreased effectiveness, particularly in the more severe cases. Fidaxomicin is an 18-membered macrocycle currently in phase 3 trials for the treatment of C. difficile infection (CDI). An open-label, phase II study in CDI patients has been completed and the clinical results published. C. difficile organisms were isolated from patient stool specimens and typed by restriction endonuclease analysis (REA) in order to determine the frequency and susceptibility of the C. difficile isolates and their response to treatment.MethodsFecal samples were plated on CCFA agar for isolation of C. difficile. These isolates were tested for susceptibility to fidaxomicin, vancomycin, and metronidazole using CLSI agar dilution methods and were typed by REA.ResultsC. difficile was isolated from 38 of 49 subjects and 16 (42%) were the epidemic C. difficile BI group. The BI strain was distributed approximately equally in the three dosing groups. Overall antibiotic susceptibilities were consistent with the previously reported MIC90 values for the three antibiotics tested, but the MIC90 of BI strains was two dilutions higher than non-BI strains for metronidazole and vancomycin (for both antibiotics, MIC90 was 2 μg/mL vs. 0.5 μg/mL, P < 0.01 for metronidazole, P = NS for vancomycin). Clinical cure for BI isolates (11/14, 79%) was not significantly different from non-BI isolates (21/22, 95%).ConclusionThese results underscore the high prevalence of the BI epidemic strain and demonstrate that mild to moderate CDI infection as well as severe disease can be caused by these strains. Fidaxomicin cure rates for subjects with BI and with non-BI strains are similar, although the small numbers of subjects preclude a robust statistical comparison. |
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