[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE We aimed to determine the frequency of qacA/B chlorhexidine tolerance genes and high-level mupirocin resistance among MRSA isolates before and after the introduction of a chlorhexidine (CHG) daily bathing intervention in a surgical intensive care unit (SICU). DESIGN Retrospective cohort study (2005���2012) SETTING A large tertiary-care center PATIENTS Patients admitted to SICU who had MRSA surveillance cultures of the anterior nares METHODS A random sample of banked MRSA anterior nares isolates recovered during (2005) and after (2006���2012) implementation of a daily CHG bathing protocol was examined for qacA/B genes and high-level mupirocin resistance. Staphylococcal cassette chromosome mec (SCCmec) typing was also performed. RESULTS Of the 504 randomly selected isolates (63 per year), 36 (7.1%) were qacA/B positive (+) and 35 (6.9%) were mupirocin resistant. Of these, 184 (36.5%) isolates were SCCmec type IV. There was a significant trend for increasing qacA/B (P=.02; highest prevalence, 16.9% in 2009 and 2010) and SCCmec type IV (P<.001; highest prevalence, 52.4% in 2012) during the study period. qacA/B(+) MRSA isolates were more likely to be mupirocin resistant (9 of 36 [25%] qacA/B(+) vs 26 of 468 [5.6%] qacA/B(���); P=.003). CONCLUSIONS A long-term, daily CHG bathing protocol was associated with a change in the frequency of qacA/B genes in MRSA isolates recovered from the anterior nares over an 8-year period. This change in the frequency of qacA/B genes is most likely due to patients in those years being exposed in prior admissions. Future studies need to further evaluate the implications of universal CHG daily bathing on MRSA qacA/B genes among hospitalized patients. Infect. Control Hosp. Epidemiol. 2016;1���8.
Preview · Article · Feb 2016 · Infection Control and Hospital Epidemiology
[Show abstract][Hide abstract] ABSTRACT: Despite appropriate therapy, Candida bloodstream infections are associated with a mortality rate of approximately 40 %. In animal models, impaired immunity due to T cell exhaustion has been implicated in fungal sepsis mortality. The purpose of this study was to determine potential mechanisms of fungal-induced immunosuppression via immunophenotyping of circulating T lymphocytes from patients with microbiologically documented Candida bloodstream infections.
Patients with blood cultures positive for any Candida species were studied. Non-septic critically ill patients with no evidence of bacterial or fungal infection were controls. T cells were analyzed via flow cytometry for cellular activation and for expression of positive and negative co-stimulatory molecules. Both the percentages of cells expressing particular immunophenotypic markers as well as the geometric mean fluorescence intensity (GMFI), a measure of expression of the number of receptors or ligands per cell, were quantitated.
Twenty-seven patients with Candida bloodstream infections and 16 control patients were studied. Compared to control patients, CD8 T cells from patients with Candidemia had evidence of cellular activation as indicated by increased CD69 expression while CD4 T cells had decreased expression of the major positive co-stimulatory molecule CD28. CD4 and CD8 T cells from patients with Candidemia expressed markers typical of T cell exhaustion as indicated by either increased percentages of or increased MFI for programmed cell death 1 (PD-1) or its ligand (PD-L1).
Circulating immune effector cells from patients with Candidemia display an immunophenotype consistent with immunosuppression as evidenced by T cell exhaustion and concomitant downregulation of positive co-stimulatory molecules. These findings may help explain why patients with fungal sepsis have a high mortality despite appropriate antifungal therapy. Development of immunoadjuvants that reverse T cell exhaustion and boost host immunity may offer one way to improve outcome in this highly lethal disorder.
[Show abstract][Hide abstract] ABSTRACT: Importance
Many preschool children develop recurrent, severe episodes of lower respiratory tract illness (LRTI). Although viral infections are often present, bacteria may also contribute to illness pathogenesis. Strategies that effectively attenuate such episodes are needed.Objective
To evaluate if early administration of azithromycin, started prior to the onset of severe LRTI symptoms, in preschool children with recurrent severe LRTIs can prevent the progression of these episodes.Design, Setting, and Participants
A randomized, double-blind, placebo-controlled, parallel-group trial conducted across 9 academic US medical centers in the National Heart, Lung, and Blood Institute’s AsthmaNet network, with enrollment starting in April 2011 and follow-up complete by December 2014. Participants were 607 children aged 12 through 71 months with histories of recurrent, severe LRTIs and minimal day-to-day impairment. Intervention
Participants were randomly assigned to receive azithromycin (12 mg/kg/d for 5 days; n = 307) or matching placebo (n = 300), started early during each predefined RTI (child’s signs or symptoms prior to development of LRTI), based on individualized action plans, over a 12- through 18-month period.Main Outcomes and Measures
The primary outcome measure was the number of RTIs not progressing to a severe LRTI, measured at the level of the RTI, that would in clinical practice trigger the prescription of oral corticosteroids. Presence of azithromycin-resistant organisms in oropharyngeal samples, along with adverse events, were among the secondary outcome measures.Results
A total of 937 treated RTIs (azithromycin group, 473; placebo group, 464) were experienced by 443 children (azithromycin group, 223; placebo group, 220), including 92 severe LRTIs (azithromycin group, 35; placebo group, 57). Azithromycin significantly reduced the risk of progressing to severe LRTI relative to placebo (hazard ratio, 0.64 [95% CI, 0.41-0.98], P = .04; absolute risk for first RTI: 0.05 for azithromycin, 0.08 for placebo; risk difference, 0.03 [95% CI, 0.00-0.06]). Induction of azithromycin-resistant organisms and adverse events were infrequently observed.Conclusions and Relevance
Among young children with histories of recurrent severe LRTIs, the use of azithromycin early during an apparent RTI compared with placebo reduced the likelihood of severe LRTI. More information is needed on the development of antibiotic-resistant pathogens with this strategy.Trial Registration
clinicaltrials.gov Identifier: NCT01272635
No preview · Article · Nov 2015 · JAMA The Journal of the American Medical Association
[Show abstract][Hide abstract] ABSTRACT: Norovirus is the most common cause of sporadic gastroenteritis and outbreaks worldwide. The rapid identification of norovirus has important implications for infection prevention measures, and may reduce the need for additional diagnostic testing. The Xpert Norovirus Assay recently received FDA clearance for the detection and differentiation of norovirus genogroups I and II (GI and GII), which account for the vast majority of infections. In this study, we evaluated the performance of the Xpert Norovirus Assay with both fresh, prospectively collected (n=914) and frozen, archived (n=489) fecal specimens. A Centers for Disease Control (CDC) composite reference method was used as the gold standard for comparison. For both prospective and frozen specimens, the Xpert Norovirus Assay showed a positive percent agreement (PPA) and negative percent agreement (NPA) of 98.3% and 98.1% for GI, and 99.4% and 98.2% for GII, respectively. Norovirus prevalence in the prospective specimens (collected from March to May of 2014) was 9.9% (n=90), with the majority of positives caused by genogroup II (82%, n=74). The positive predictive value (PPV) of the Xpert Norovirus Assay was 75% for GI whereas it was 86.5% for GII positive specimens. The negative predictive value (NPV) for GI and GII was 100% and 99.9%, respectively.
Full-text · Article · Nov 2015 · Journal of clinical microbiology
[Show abstract][Hide abstract] ABSTRACT: Historically, a number of typing methods have been evaluated for Staphylococcus aureus strain characterization. The emergence of contemporary strains of community-associated S. aureus, and the ensuing epidemic with a predominant strain type (USA300), necessitates re-evaluation of the discriminatory power of these typing methods for discerning molecular epidemiology and transmission dynamics, essential to investigations of hospital and community outbreaks. We compared the discriminatory index of 5 typing methods for contemporary S. aureus strain characterization.
Children presenting to St. Louis Children's Hospital and community pediatric practices in St. Louis, Missouri (MO), with community-associated S. aureus infections were enrolled. Repetitive sequence-based PCR (repPCR), pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), staphylococcal protein A (spa), and staphylococcal cassette chromosome (SCC) mec typing were performed on 200 S. aureus isolates. The discriminatory index of each method was calculated using the standard formula for this metric, where a value of 1 is highly discriminatory and a value of 0 is not discriminatory.
Overall, we identified 26 distinct strain types by repPCR, 17 strain types by PFGE, 30 strain types by MLST, 68 strain types by spa typing, and 5 strain types by SCCmec typing. RepPCR had the highest discriminatory index (D) of all methods (D = 0.88), followed by spa typing (D = 0.87), MLST (D = 0.84), PFGE (D = 0.76), and SCCmec typing (D = 0.60). The method with the highest D among MRSA isolates was repPCR (D = 0.64) followed by spa typing (D = 0.45) and MLST (D = 0.44). The method with the highest D among MSSA isolates was spa typing (D = 0.98), followed by MLST (D = 0.93), repPCR (D = 0.92), and PFGE (D = 0.89). Among isolates designated USA300 by PFGE, repPCR was most discriminatory, with 10 distinct strain types identified (D = 0.63). We identified 45 MRSA isolates which were classified as identical by PFGE, MLST, spa typing, and SCCmec typing (USA300, ST8, t008, SCCmec IV, respectively); within this collection, there were 5 distinct strain types identified by repPCR.
The typing methods yielded comparable discriminatory power for S. aureus characterization overall; when discriminating among USA300 isolates, repPCR retained the highest discriminatory power. This property is advantageous for investigations conducted in the era of contemporary S. aureus infections.
[Show abstract][Hide abstract] ABSTRACT: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most prevalent multidrug-resistant pathogens worldwide, exhibiting increasing resistance to the latest antibiotic therapies. Here we show that the triple β-lactam combination meropenem-piperacillin-tazobactam (ME/PI/TZ) acts synergistically and is bactericidal against MRSA subspecies N315 and 72 other clinical MRSA isolates in vitro and clears MRSA N315 infection in a mouse model. ME/PI/TZ suppresses evolution of resistance in MRSA via reciprocal collateral sensitivity of its constituents. We demonstrate that these activities also extend to other carbapenem-penicillin-β-lactamase inhibitor combinations. ME/PI/TZ circumvents the tight regulation of the mec and bla operons in MRSA, the basis for inducible resistance to β-lactam antibiotics. Furthermore, ME/PI/TZ subverts the function of penicillin-binding protein-2a (PBP2a) via allostery, which we propose as the mechanism for both synergy and collateral sensitivity. Showing in vivo activity similar to that of linezolid, ME/PI/TZ demonstrates that combinations of older β-lactam antibiotics could be effective against MRSA infections in humans.
Full-text · Article · Sep 2015 · Nature Chemical Biology
[Show abstract][Hide abstract] ABSTRACT: Clostridium difficile infections (CDI) are the most common cause of healthcare-associated infections (HAI) in the USA, accounting for 12 % of all HAIs . Reasons for such an increase are unknown but may relate to antibiotic use and evolution of a new, pathogenic strain, NAP1/BI/027. The Centers for Disease Control and Prevention (CDC) identifies C. difficile as one of only three organisms to be assigned a designation of an "urgent" threat level. Asymptomatic colonization with C. difficile is much more common than symptomatic CDI and has been documented to contribute to new cases of CDI. Despite this knowledge, approaches to managing and preventing transmission from asymptomatically colonized patients are lacking. Enhanced cleaning, avoidance of unnecessary antimicrobials, and use of gowns and gloves for patients with CDI are the cornerstone of C. difficile management in patients with known disease. Infection control interventions to prevent transmission from asymptomatically colonized patients have not been determined.
[Show abstract][Hide abstract] ABSTRACT: Nasopharyngeal (NP) pneumococcal carriage predisposes children to pneumococcal infections. Defining the proportion of pneumococcal isolates that are antibiotic-resistant enables the appropriate choice of empiric therapies. The antibiogram of NP carriage isolates derived from a pediatric population following the introduction of the 13-valent pneumococcal conjugate vaccine was defined in this study. (C) 2015 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license.
No preview · Article · Aug 2015 · International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases
[Show abstract][Hide abstract] ABSTRACT: This was a randomized controlled pilot study of Lactobacillus rhamnosus GG versus standard of care to prevent gastrointestinal multidrug-resistant organism colonization in intensive care unit patients. Among 70 subjects, there were no significant differences in acquisition or loss of any multidrug-resistant organisms (P>.05) and no probiotic-associated adverse events. Infect. Control Hosp. Epidemiol. 2015;00(0):1���4.
No preview · Article · Aug 2015 · Infection Control and Hospital Epidemiology
[Show abstract][Hide abstract] ABSTRACT: Infections cause morbidity and mortality in neonatal intensive care units (NICUs). The association between nursery design and nosocomial infections is unclear.
To determine whether rates of colonization by methicillin-resistant
(MRSA), late-onset sepsis, and mortality are reduced in single-patient rooms.
Retrospective cohort study.
NICU in a tertiary referral center.
Our NICU is organized into single-patient and open-unit rooms. Clinical data sets including bed location and microbiology results were examined over 29 months. Differences in outcomes between bed configurations were determined by χ
and Cox regression.
All NICU patients.
Among 1,823 patients representing 55,166 patient-days, single-patient and open-unit models had similar incidences of MRSA colonization and MRSA colonization-free survival times. Average daily census was associated with MRSA colonization rates only in single-patient rooms (hazard ratio, 1.31;
039), whereas hand hygiene compliance on room entry and exit was associated with lower colonization rates independent of bed configuration (hazard ratios, 0.834 and 0.719 per 1% higher compliance, respectively). Late-onset sepsis rates were similar in single-patient and open-unit models as were sepsis-free survival and the combined outcome of sepsis or death. After controlling for demographic, clinical, and unit-based variables, multivariate Cox regression demonstrated that bed configuration had no effect on MRSA colonization, late-onset sepsis, or mortality.
MRSA colonization rate was impacted by hand hygiene compliance, regardless of room configuration, whereas average daily census affected only infants in single-patient rooms. Single-patient rooms did not reduce the rates of MRSA colonization, late-onset sepsis, or death.
Infect Control Hosp Epidemiol
No preview · Article · Jun 2015 · Infection Control and Hospital Epidemiology
[Show abstract][Hide abstract] ABSTRACT: To characterize the genomic context of New Delhi metallo-β-lactamase-1 (NDM-1) and Klebsiella pneumoniae carbapenemase (KPC), we sequenced 78 Enterobacteriaceae isolates from Pakistan and the United States encoding KPC, NDM-1, or no carbapenemase. High similarities of the results indicate rapid spread of carbapenem resistance between strains, including globally disseminated pathogens.
Preview · Article · Jun 2015 · Emerging infectious diseases
[Show abstract][Hide abstract] ABSTRACT: Background:
The reservoir of pathogenic ciprofloxacin-resistant Escherichia coli remains unknown.
We conducted a prospective cohort study of 80 healthy twins and their mothers to determine the frequency of excretion of ciprofloxacin-resistant, potentially pathogenic E. coli. Stool specimens were cultured selectively for ciprofloxacin-resistant gram-negative bacteria. Isolates were categorized on the basis of additional resistance and virulence profiles. We also prospectively collected clinical metadata.
Fifteen children (19%) and 8 mothers (20%) excreted ciprofloxacin-resistant E. coli at least once. Overall, 33% of 40 families had at least 1 member whose stool specimen yielded ciprofloxacin-resistant E. coli on culture. Fifty-seven submitted stool specimens (2.8%) contained such organisms; clones ST131-H30 and ST405 accounted for 52 and 5 of the positive specimens, respectively. Length of hospital stay after birth (P = .002) and maternal colonization (P = .0001) were associated with subsequent childhood carriage of ciprofloxacin-resistant E. coli; antibiotic use, acid suppression, sex, mode of delivery, and maternal perinatal antibiotic use were not. Ciprofloxacin-resistant E. coli were usually resistant to additional antibiotic classes, and all had virulence genotypes typical of extraintestinal pathogenic E. coli.
Healthy children and their mothers commonly harbor ciprofloxacin-resistant E. coli with pathogenic potential.
Preview · Article · May 2015 · The Journal of Infectious Diseases