Archive for April 10, 2016

Evaluation of Oxacillin and Cefoxitin Disk and MIC Breakpoints for Prediction of Methicillin Resistance in Human and Veterinary Isolates of Staphylococcus intermedius Group

Journal of Clinical Microbiology March 2016 V.54 N.3 P.535-542


T. Wu, C.-A. D. Burnham, L. F. Westblade, J. Dien Bard, S. D. Lawhon, M. A. Wallace, T. Stanley, E. Burd, J. Hindler, and R. M. Humphries

aUCLA David Geffen School of Medicine, Los Angeles, California, USA

bLandstuhl Regional Medical Center, Landstuhl, Germany

cWashington University School of Medicine, St. Louis, Missouri, USA

dWeill Cornell Medical College, New York, New York, USA

eChildren’s Hospital of Los Angeles, Los Angeles, California, USA

fVeterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA

gEmory University School of Medicine, Atlanta, Georgia, USA

hEmory Antibiotic Resistance Center, Atlanta, Georgia, USA

  1. M. Humphries,

Staphylococcus pseudintermedius is a coagulase-positive species that colonizes the nares and anal mucosa of healthy dogs and cats.

Human infections with S. pseudintermedius range in severity from bite wounds and rhinosinusitis to endocarditis; historically, these infections were thought to be uncommon, but new laboratory methods suggest that their true incidence is underreported.

Oxacillin and cefoxitin disk and MIC tests were evaluated for the detection of mecA- or mecC-mediated methicillin resistance in 115 human and animal isolates of the Staphylococcus intermedius group (SIG), including 111 Staphylococcus pseudintermediusand 4 Staphylococcus delphini isolates, 37 of which were mecA positive.

The disk and MIC breakpoints evaluated included the Clinical and Laboratory Standards Institute (CLSI) M100-S25 Staphylococcus aureus/Staphylococcus lugdunensis oxacillin MIC breakpoints and cefoxitin disk and MIC breakpoints, the CLSI M100-S25 coagulase-negative Staphylococcus (CoNS) oxacillin MIC breakpoint and cefoxitin disk breakpoint, the CLSI VET01-S2 S. pseudintermedius oxacillin MIC and disk breakpoints, and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) S. pseudintermedius cefoxitin disk breakpoint.

The oxacillin results interpreted by the VET01-S2 (disk and MIC) and M100-S25 CoNS (MIC) breakpoints agreed with the results of mecA/mecC PCR for all isolates, with the exception of one false-resistant result (1.3% of mecA/mecC PCR-negative isolates). In contrast, cefoxitin tests performed poorly, ranging from 3 to 89% false susceptibility (very major errors) and 0 to 48% false resistance (major errors).

BD Phoenix, bioMérieux Vitek 2, and Beckman Coulter MicroScan commercial automated susceptibility test panel oxacillin MIC results were also evaluated and demonstrated >95% categorical agreement with mecA/mecC PCR results if interpreted by using the M100-S25 CoNS breakpoint. The Alere penicillin-binding protein 2a test accurately detected all mecA-positive isolates, although for four isolates, cefoxitin induction was required prior to testing.

These data demonstrate that the cefoxitin surrogate test does not reliably detect the presence of mecA in S. pseudintermedius isolates and that laboratories should perform oxacillin disk or MIC tests of these isolates when they are encountered.




April 10, 2016 at 7:52 pm

What’s in a Name? The Impact of Accurate Staphylococcus pseudintermedius Identification on Appropriate Antimicrobial Susceptibility Testing

Journal of Clinical Microbiology March 2016 V.54 N.3 P.516-517


Brandi M. Limbago

Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia, USA

Bacteria in the Staphylococcus intermedius group, including Staphylococcus pseudintermedius, often encode mecA-mediated methicillin resistance.

Reliable detection of this phenotype for proper treatment and infection control decisions requires that these coagulase-positive staphylococci are accurately identified and specifically that they are not misidentified as S. aureus.

As correct species level bacterial identification becomes more commonplace in clinical laboratories, one can expect to see changes in guidance for antimicrobial susceptibility testing and interpretation.

The study by Wu et al. in this issue (M. T. Wu, C.-A. D. Burnham, L. F. Westblade, J. Dien Bard, S. D. Lawhon, M. A. Wallace, T. Stanley, E. Burd, J. Hindler, R. M. Humphries, J Clin Microbiol 54:535–542, 2016, highlights the impact of robust identification of S. intermedius group organisms on the selection of appropriate antimicrobial susceptibility testing methods and interpretation.


April 10, 2016 at 7:49 pm

Clustering of Antimicrobial Resistance Outbreaks Across Bacterial Species in the Intensive Care Unit

Clinical Infectious Diseases July 1, 2013 V.57 N.1 P.65-76

Editor’s Choice

Anne L. M. Vlek, Ben S. Cooper, Theodore Kypraios, Andy Cox, Jonathan D. Edgeworth, and Olga Tosas Auguet

1Centre for Clinical Infection and Diagnostics Research, Department of Infectious Diseases, King’s College London and Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom

2Medical Microbiology, University Medical Centre Utrecht, the Netherlands

3Centre for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, United Kingdom

4Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand

5School of Mathematical Sciences, University of Nottingham

6Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom


here are frequent reports of intensive care unit (ICU) outbreaks due to transmission of particular antibiotic-resistant bacteria. Less is known about the burden of outbreaks of resistance due to horizontal transfer of mobile genetic elements between species. Moreover, the potential of existing statistical software as a preliminary means for detecting such events has never been assessed. This study uses a software package to determine the burden of species and resistance outbreaks in 2 adjacent ICUs and to look for evidence of clustering of resistance outbreaks consistent with interspecies transmission of resistance elements.


A retrospective analysis of data from 2 adjacent 15-bed adult ICUs between 2002 and 2009 was undertaken. Detection of bacterial species-groups and resistance outbreaks was conducted using SaTScan and WHONet-SaTScan software. Resampling and permutation methods were applied to investigate temporal clustering of outbreaks.


Outbreaks occurred for 69% of bacterial species-groups (18/26), and resistance outbreaks were detected against 63% of antibiotics (10/16). Resistance outbreaks against 7 of 10 antibiotics were observed in multiple species-groups simultaneously and there was evidence of inter–species-group dependence for 4 of 7 antibiotics; background temporal changes in resistance did not explain the temporal aggregation of outbreaks in 3 of 7 antibiotics.


Species outbreaks occurred for the majority of bacteria commonly identified in the ICU. There was evidence for frequent temporal clustering of resistance outbreaks consistent with interspecies transmission of resistance elements. Wider application of outbreak detection software combined with targeted sequencing of bacterial genomes is needed to understand the contribution of interspecies gene transfer to resistance emergence. Outbreaks of bacterial species occur for the majority of bacteria commonly identified in the intensive care unit. This study provides evidence for frequent temporal clustering of resistance outbreaks consistent with interspecies transmission of resistance elements.



April 10, 2016 at 12:58 pm

Protective Effect of Contemporary Pertussis Vaccines: A Systematic Review and Meta-analysis

Clinical Infectious Diseases May 1, 2016 V.62 N.9 P.1100-1110

Editor’s Choice

Roice Fulton, Varun K. Phadke, Walter A. Orenstein, Alan R. Hinman, Wayne D. Johnson, and Saad B. Omer

1Department of Global Health

2Department of Epidemiology, Rollins School of Public Health, Emory University

3Division of Infectious Diseases, Emory University School of Medicine

4Emory Vaccine Center

5Department of Pediatrics, Emory University School of Medicine, Atlanta

6The Task Force for Global Health, Decatur, Georgia


Acellular pertussis (aP) and whole-cell (wP) pertussis vaccines are presumed to have similar short-term (<3 years after completion of the primary series) efficacy. However, vaccine effect varies between individual pertussis vaccine formulations, and many originally studied formulations are now unavailable. An updated analysis of the short-term protective effect of pertussis vaccines limited to formulations currently on the market in developed countries is needed.


We conducted a systematic review and meta-analysis of published studies that evaluated pertussis vaccine efficacy or effectiveness within 3 years after completion (>3 doses) of a primary series of a currently available aP or wP vaccine formulation. The primary outcome was based on the World Health Organization (WHO) clinical case definitions for pertussis. Study quality was assessed using the approach developed by the Child Health Epidemiology Research Group. We determined overall effect sizes using random-effects meta-analyses, stratified by vaccine (aP or wP) and study (efficacy or effectiveness) type.


Meta-analysis of 2 aP vaccine efficacy studies (assessing the 3-component GlaxoSmithKline and 5-component Sanofi-Pasteur formulations) yielded an overall aP vaccine efficacy of 84% (95% confidence interval [CI], 81%–87%). Meta-analysis of 3 wP vaccine effectiveness studies (assessing the Behringwerke, Pasteur/Mérieux, and SmithKline Beecham formulations) yielded an overall wP vaccine effectiveness of 94% (95% CI, 88%–97%) (both I2 = 0%).


Although all contemporary aP and wP formulations protect against pertussis disease, in this meta-analysis the point estimate for short-term protective effect against WHO-defined pertussis in young children was lower for currently available aP vaccines than wP vaccines.



April 10, 2016 at 12:56 pm

Effect of Previous-Year Vaccination on the Efficacy, Immunogenicity, and Safety of High-Dose Inactivated Influenza Vaccine in Older Adults

Clinical Infectious Diseases May 1, 2016 V.62 N.9 P.1092-1099

Carlos A. DiazGranados, Andrew J. Dunning, Corwin A. Robertson, H. Keipp Talbot, Victoria Landolfi, and David P. Greenberg

1Sanofi Pasteur, Swiftwater, Pennsylvania

2Vanderbilt University Medical Center, Nashville, Tennessee

3Department of Pediatrics, University of Pittsburgh School of Medicine, Pennsylvania


High-dose inactivated influenza vaccine (IIV-HD) is an alternative to the standard-dose inactivated influenza vaccine (IIV-SD) in the United States for influenza prevention in older adults. IIV-HD improved efficacy relative to IIV-SD in a randomized controlled trial. Recent observational studies suggest that previous influenza vaccination may influence the immunogenicity and effectiveness of current-season vaccination.


The original study was a double-blind, randomized trial comparing IIV-HD to IIV-SD in adults aged ≥65 years over 2 influenza seasons. A subset of year 1 (Y1) participants reenrolled in year 2 (Y2), receiving vaccine by random assignment in both years. We evaluated the effect of Y1 vaccination on Y2 relative vaccine efficacy (VE), immunogenicity (hemagglutination inhibition [HAI] titers), and safety among reenrolled participants.


Of 14 500 Y1 participants, 7643 reenrolled in Y2. Relative to participants who received IIV-SD both seasons, VE was higher for IIV-HD vaccinees in Y2 (28.3% overall; 25.1% for Y1 IIV-HD, Y2 IIV-HD; and 31.6% for Y1 IIV-SD, Y2 IIV-HD). In multivariate logistic regression models, Y1 vaccine was not a significant modifier of Y2 VE (P = .43), whereas Y2 IIV-HD remained significantly associated with lower influenza risk (P = .043). Compared to administration of IIV-SD in both years, postvaccination HAI titers were significantly higher for patterns that included IIV-HD in Y2. No safety concerns were raised with IIV-HD revaccination.


IIV-HD is likely to provide clinical benefit over IIV-SD irrespective of previous-season vaccination with IIV-HD or IIV-SD. IIV-HD consistently improved immune responses, and no safety concerns emerged in the context of IIV-HD revaccination.



April 10, 2016 at 12:55 pm


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