Trends in Antibiotic Resistance in Coagulase-Negative Staphylococci in the United States, 1999 to 2012

Antimicrobial Agents and Chemotherapy (Impact Factor: 4.45). 03/2014; 58(3). DOI: 10.1128/AAC.01908-13

ABSTRACT Coagulase-negative staphylococci (CoNS) are important bloodstream pathogens that are typically resistant to multiple antibiotics. Despite the concern about increasing resistance, there have been no recent studies describing the national prevalence of CoNS pathogens. We used national resistance data over a period of 13 years (1999 to 2012) from The Surveillance Network (TSN) to determine the prevalence of and assess the trends in resistance for Staphylococcus epidermidis, the most common CoNS pathogen, and all other CoNS pathogens. Over the course of the study period, S. epidermidis resistance to ciprofloxacin and clindamycin increased steadily from 58.3% to 68.4% and from 43.4% to 48.5%, respectively. Resistance to levofloxacin increased rapidly from 57.1% in 1999 to a high of 78.6% in 2005, followed by a decrease to 68.1% in 2012. Multidrug resistance for CoNS followed a similar pattern, and this rise and small decline in resistance were found to be strongly correlated with levofloxacin prescribing patterns. The resistance patterns were similar for the aggregate of CoNS pathogens. The results from our study demonstrate that the antibiotic resistance in CoNS pathogens has increased significantly over the past 13 years. These results are important, as CoNS can serve as sentinels for monitoring resistance, and they play a role as reservoirs of resistance genes that can be transmitted to other pathogens. The link between the levofloxacin prescription rate and resistance levels suggests a critical role for reducing the inappropriate use of fluoroquinolones and other broad-spectrum antibiotics in health care settings and in the community to help curb the reservoir of resistance in these colonizing pathogens.


Available from: Eili Y Klein, Jul 31, 2014
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    ABSTRACT: S. aureus and coagulase-negative staphylococci (CoNS) are responsible for a wide variety of human infections. The investigational antibacterial Debio 1450 (previously AFN-1720), a prodrug of Debio 1452 (previously AFN-1252) specifically targets staphylococci without significant activity against other Gram-positive or Gram-negative species. Debio 1452 inhibits FabI, an enzyme critical to fatty acid biosynthesis in staphylococci. The activity of Debio 1452 against CoNS, methicillin-susceptible (MSSA) and -resistant (MRSA) S. aureus, including significant clones, was determined. A globally diverse collection of 574 patient isolates from 35 countries was tested that included CoNS (6 species, 103 strains), MSSA (154), MRSA (163) and molecularly characterized strains (including spa typed MRSA clones; 154). Isolates were susceptibility tested by CLSI broth microdilution methods against Debio 1452 and 10 comparators. Susceptibility rates for comparators were determined using CLSI and EUCAST breakpoint criteria. All S. aureus and CoNS were inhibited by Debio 1452 concentrations of ≤0.12 and ≤0.5 μg/mL, respectively. MIC50 values for MSSA, MRSA and molecularly characterized-MRSA strains were 0.004 μg/mL and MIC90 values ranged from 0.008 - 0.03 μg/mL. MIC values were higher for CoNS isolates (MIC50/90, 0.015/0.12 μg/mL). Among S. aureus, resistance was common for erythromycin (61.6%), levofloxacin (49.0%), clindamycin (27.6%), tetracycline (15.7%) and trimethoprim-sulfamethoxazole (7.0%). Debio 1452 demonstrated potent activity against MSSA, MRSA and CoNS. Debio 1452 showed significantly greater activity overall (MIC50, 0.004 μg/mL) when compared to other agents tested against these staphylococcal species that included dominant MRSA clones and strains resistant to currently utilized antimicrobial agents. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
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