Showing papers by "Donald E. Low published in 2015"

Pathway to Prevention of Nosocomial Clostridium difficile Infection

Abstract: Background To address the significant morbidity and mortality rates associated with nosocomial Clostridium difficile-associated diarrhea (CDAD), a series of recommendations and a pathway to prevention were developed. Methods An expert panel of infectious disease (ID) specialists participated in a modified Delphi process with specific objectives: (1) conduct a review for CDAD and prevention; (2) develop statements based upon panel members' opinions; (3) hold a panel meeting during the 2012 IDWeek; and (4) review the final recommendations and prevention pathway prior to submission for publication. Results The panel voted on (1) antibiotic stewardship (7 of 8 panelists); (2) reduction of other potentially modifiable risk factors (variable); (3) utilization of specific probiotics to prevent C. difficile overgrowth (8/8); (4) staff education regarding CDAD preventive measures (8/8); (5) appropriate hand hygiene for everyone (7/8); (6) environmental cleaning (8/8); (7) medical equipment disinfection (7/8); (8) early detection of CDAD in symptomatic patients (7/8); (9) usage of protective clothing/gloves (8/8); (10) proper measures during outbreak (8/8); and (11) surveillance to monitor efficacy data of preventive measures (8/8). Conclusions The panel members agreed with 11 of 17 recommendations presented. The additional recommendations by the panel were proton pump inhibitor use as a risk factor and the use of adjunctive therapy with specific probiotic, as it was approved by Health Canada for the risk reduction of CDAD in hospitalized patients.

Vancomycin-Variable Enterococci Can Give Rise to Constitutive Resistance during Antibiotic Therapy

Abstract: Vancomycin-resistant enterococci (VRE) are notorious clinical pathogens restricting the use of glycopeptide antibiotics in the clinic setting. Routine surveillance to detect VRE isolated from patients relies on PCR bioassays and chromogenic agar-based test methods. In recent years, we and others have reported the emergence of enterococcal strains harboring a “silent” copy of vancomycin resistance genes that confer a vancomycin-susceptible phenotype (vancomycin-susceptible enterococci [VSE]) and thus escape detection using drug sensitivity screening tests. Alarmingly, these strains are able to convert to a resistance phenotype (VSE→VRE) during antibiotic treatment, severely compromising the success of therapy. Such strains have been termed vancomycin-variable enterococci (VVE). We have investigated the molecular mechanisms leading to the restoration of resistance in VVE isolates through the whole-genome sequencing of resistant isolates, measurement of resistance gene expression, and quantification of the accumulation of drug-resistant peptidoglycan precursors. The results demonstrate that VVE strains can revert to a VRE phenotype through the constitutive expression of the vancomycin resistance cassette. This is accomplished through a variety of changes in the DNA region upstream of the resistance genes that includes both a deletion of a likely transcription inhibitory secondary structure and the introduction of a new unregulated promoter. The VSE→VRE transition of VVE can occur in patients during the course of antibiotic therapy, resulting in treatment failure. These VVE strains therefore pose a new challenge to the current regimen of diagnostic tests used for VRE detection in the clinic setting.

Genetic analysis of invasive pneumococcal isolates from children in Ontario, Canada, 2007-2012.

Abstract: Background Multilocus sequence typing (MLST) is commonly used to understand the genetic background of invasive pneumococcal disease (IPD) isolates. This study was conducted to identify serotype and genetic change among IPD isolates in Canadian children following vaccine use. Methods Clinical isolates collected from children ≤5 years old of Ontario, Canada with IPD during 2007-2012 were characterized with serotyping, multilocus sequence typing and antimicrobial susceptibility testing. Results One year after 13-valent pneumococcal conjugate vaccine (PCV13) implementation, a decline in 19A and 7F was observed in 2012, coincident with the rise of serogroup 15 and 22F. Clonal complex (CC) 199, CC320 and CC695 are 3 major CCs in 19A (74%). From 2007 to 2012, clonal shift was detected in the 19A population as CC320 and CC199 declined, whereas CC695 rose to a majority. Genetically, serogroup 15 was composed of 2 CCs and 7 sequence types (STs), making it more diverse than serotypes 3, 7F and 22F. Interestingly, 60% of 15C isolates were a novel ST, suggesting high single nucleotide polymorphism frequency in house-keeping genes of 15C. Several newly appeared STs found in 19A and 15 indicate the possibility of recent serotype switching events. Conclusion Genetic shift because of PCV13 impact may have resulted in the decline of 19A in IPD. Recent rise of serogroup 15 infections in children could be because of its selective advantage conferred by genetic diversity, frequent recombination in the population plus drug resistance potential related to CC63 genotype. Close monitoring of serotype replacement and genetic change in IPD among children post-PCV13 is warranted.