Causes and Implications of the Disappearance of Rifampin Resistance in a Rat Model of Methicillin-Resistant Staphylococcus aureus Foreign Body Osteomyelitis.
|
| Abstract |
Orthopedic foreign body-associated infections are often treated with rifampin-based combination antimicrobial therapy. We previously observed that rifampin-resistant and methicillin-resistant Staphylococcus aureus (MRSA) isolates were present 2 days after cessation of rifampin therapy in experimental foreign body osteomyelitis. Unexpectedly, only rifampin-susceptible isolates were detected 14 days after the completion of treatment. We studied two rifampin-resistant isolates recovered 2 days after treatment and one rifampin-susceptible isolate recovered 14 days after treatment. Growing these isolates alone in vitro or in vivo demonstrated no fitness defects; however, in mixed culture, rifampin-susceptible bacteria outcompeted rifampin-resistant bacteria. In vivo, two courses of rifampin treatment (25 mg/kg of body weight every 12 h for 21 days) yielded a greater decrease in bacterial quantity in the bones of treated animals 14 days following treatment than that in animals receiving a single course of treatment (P = 0.0398). In infections established with equal numbers of rifampin-resistant and rifampin-susceptible bacteria, one course of rifampin treatment did not affect bacterial quantities. Rifampin-resistant and rifampin-susceptible isolates were recovered both 2 days and 14 days following treatment completion; however, the proportion of animals with rifampin-resistant isolates was lower at 14 days than that at 2 days following treatment completion (P = 0.024). In untreated animals infected with equal numbers of rifampin-resistant and rifampin-susceptible bacteria for 4 weeks, rifampin-susceptible isolates were exclusively recovered, indicating the outcompetition of rifampin-resistant by rifampin-susceptible isolates. The data presented imply that although there is no apparent fitness defect in rifampin-resistant bacteria when grown alone, they are outcompeted by rifampin-susceptible bacteria when the two are present together. The findings also suggest that selected rifampin resistance may not persist in initially rifampin-susceptible infections following the discontinuation of rifampin.
|
|---|---|
| Authors | Cassandra L Brinkman, Harmony L Tyner, Suzannah M Schmidt-Malan, Jayawant N Mandrekar, Robin Patel |
| Journal | Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 59 Issue 8 Pg. 4481-8 (Aug 2015) ISSN: 1098-6596 [Electronic] United States |
| PMID | 25987614 (Publication Type: Journal Article, Research Support, N.I.H., Extramural) |
| Copyright | Copyright © 2015, American Society for Microbiology. All Rights Reserved. |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!