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

Antimicrobial Agents and Chemotherapy (Impact Factor: 4.48). 03/2014; 58(3). DOI: 10.1128/AAC.01908-13


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.

Download full-text


Available from: Eili Y Klein, Jul 31, 2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: Methicillin-resistant Staphylococci (MRS), methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE) have become a challenging problem in nosocomial infections and are connected with high morbidity and mortality rates. This is due to the increasing incidence of resistance to virtually all β-lactams and a wide variety of antimicrobials. The spread of MRS severely limits therapeutic options and generates the need for novel antibiotics that are able to combat MRS infections. One method of inhibiting bacterial growth is by blocking the expression of conserved bacterial genes and provides potential new avenues for generating a new generation of antimicrobials. The mecA gene is highly conserved among Staphylococcal species, and this makes it an ideal target for antisense inhibition. We had identified a target sequence (854-871 nt) within the mecA mRNA coding region that is particularly sensitive to antisense inhibition. The anti-mecA PS-ODN04 oligonucleotide was encapsulated into an anionic liposome. MRSA01 and MRSE01 clinical strains treated with this antisense sequence became susceptible to existing β-lactam antibiotics, and their growth was inhibited by oxacillin in vitro and in vivo. PS-ODN04 reduced the bacterial titers in the blood of mice infected with MRSA01 and MRSE01 and significantly improved their survival rate. Our data offer a possible new strategy for treating MRS infections.The Journal of Antibiotics advance online publication, 1 October 2014; doi:10.1038/ja.2014.132.
    No preview · Article · Oct 2014 · The Journal of Antibiotics
  • [Show abstract] [Hide abstract]
    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.
    No preview · Article · Feb 2015 · Antimicrobial Agents and Chemotherapy
  • [Show abstract] [Hide abstract]
    ABSTRACT: It is unknown if vancomycin minimal inhibitory concentrations (MICs) have increased in coagulase-negative staphylococci (CoNS) or whether vancomycin remains appropriate empiric therapy. We performed a retrospective study at a single tertiary care center over 8 years. Adult inpatients with ≥2 positive blood cultures for CoNS within a 48-hour period were eligible. Susceptibilities were performed by automated broth based-microdilution. Changes in antimicrobial susceptibility were analyzed using logistic regression. The clinical characteristics and outcomes of patients with bloodstream infections (BSI) were compared by MIC. Of 308 episodes of possible CoNS bacteremia, the vancomycin MIC was ≤1μg/mL in 80 (26%) isolates, 2μg/mL in 223 (72.4%) isolates and 4μg/mL in 5 (1.6%) isolates. No isolates were resistant. We observed an 11-fold increased chance of having an isolate with a vancomycin MIC ≤1μg/mL in 2009-2011 compared with 2004-2008 (OR 10.8, 95%CI 6.0-19.5, p<0.05). In 152 patients with BSI, the median days of bacteremia, hospital mortality and readmissions at 30 days were similar in BSI caused by isolates with high vancomycin MICs (2-4μg/mL) and low vancomycin MICs (≤1μg/mL). We conclude vancomycin is still appropriate empiric therapy for CoNS BSIs. CoNS vancomycin MICs decreased over the study period despite widespread use of vancomycin. Copyright © 2015. Published by Elsevier Ltd.
    No preview · Article · Feb 2015 · Journal of Infection
Show more