Publications (117)571.83 Total impact
- [Show abstract] [Hide abstract] ABSTRACT: Objectives: To describe the strengths and limitations of the available influenza diagnostics, with a focus on rapid antigen detection assays and nucleic acid detection assays. Methods: A case-based presentation is used to illustrate the potential limitations of rapid antigen detection assays for influenza. Results: Influenza is a seasonal illness; estimates attribute influenza to approximately 200,000 hospitalizations and 41,000 deaths in the United States annually. Antigen detection assays for influenza are rapid and convenient, and thus are widely used in a variety of health care settings, even though the sensitivity of these assays may be suboptimal. The United States Food and Drug Administration has recently created new guidelines intended to improve the oversight and performance characteristics of influenza antigen detection assays. Molecular assays, although more costly and complex, are more sensitive and may be designed to simultaneously detect multiple respiratory pathogens within a single assay. Conclusions: Diagnostic assays for influenza can vary greatly with regards to analytical performance characteristics, complexity, turnaround time and cost. This can have important patient care and infection prevention implications.
- [Show abstract] [Hide abstract] ABSTRACT: Background: Sexually transmitted infections (STIs) are spread primarily through sexual contact and are a major cause of morbidity and mortality worldwide. Once identified, some STIs can be cured following appropriate therapy; for others, suppressive regimens and approaches to prevent ongoing transmission are important. The incidence of many common STIs is increasing in the US as well as worldwide, and hundreds of millions of people are currently infected. Laboratory testing plays a major role in the diagnosis and treatment of STIs, and clinical laboratorians should be familiar with the current guidelines and methods for testing. Content: Accurate and sensitive methods to diagnose STIs are essential to direct appropriate antimicrobial therapy and interrupt the cycle of disease transmission. This review summarizes laboratory testing for common bacterial, viral, and parasitic causes of STIs. Disease manifestations reviewed include cervicitis and urethritis, genital ulcerative disease, human immunodeficiency virus, viral hepatitis, human papilloma virus, and vaginitis. Recent advancements in the recognition and management of STIs, including updates to diagnostic algorithms, advances in testing methods, and emerging challenges with antimicrobial resistance, are summarized. Summary: Diagnostic methods and therapeutic guidelines for STIs are rapidly evolving. In combination with changing epidemiology, the development of novel therapeutics, and advancements in diagnostic methods, this has resulted in changing practices in laboratory testing and, subsequently, management of disease. Molecular methods have facilitated personalized therapy and follow-up regimens targeted for individual types or strains of some STIs.
- [Show abstract] [Hide abstract] ABSTRACT: Methicillin-resistant Staphylococcus aureus (MRSA) infections cause significant morbidity and mortality in neonatal intensive care units (NICUs). We characterized the clinical and molecular epidemiology of MRSA strains colonizing NICU patients. Nasal MRSA isolates (n=250, from 96 NICU patients) recovered through active surveillance from 2009-2014 were characterized with Staphylococcal cassette chromosome mec (SCCmec) typing and detection of mupA (marker of high-level mupirocin resistance) and qacA/B (marker associated with chlorhexidine resistance). Factors associated with community-associated (CA-) or healthcare-associated (HA-) MRSA were evaluated. The overall prevalence of MRSA nasal colonization was 3.9%. Of 96 neonates in our retrospective cohort, 60 (63%) were colonized with CA-MRSA strains and 35 (36%) were colonized with HA-MRSA strains. Patients colonized with HA-MRSA were more likely to develop MRSA infections than patients colonized with CA-MRSA (13/35 [37%] vs. 8/60 [13%], p=0.007), although the interval from colonization to infection was shorter in CA-MRSA-colonized infants (0 days [range -1 to 4] versus HA-MRSA-colonized infants, 7 days [-1 to 43], p=0.005). Maternal peripartum antibiotics were associated with CA-MRSA colonization (adjusted odds ratio [aOR] 8.7; 95% confidence interval [CI] 1.7, 45.0); intubation and surgical procedures were associated with HA-MRSA colonization (aOR 7.8; 95% CI 1.3, 47.6 and aOR 6.0; 95% CI 1.4, 24.4, respectively). Mupirocin- and chlorhexidine-resistant MRSA was isolated from 4 and 8 patients, respectively; carriage of a mupirocin-resistant strain precluded decolonization. CA-MRSA strains are prominent in the NICU and associated with distinct risk factors. Given community reservoirs for MRSA acquisition and transmission, novel infection prevention strategies are needed.
- [Show abstract] [Hide abstract] ABSTRACT: Objectives: As individuals may be colonized with multiple strains of Staphylococcus aureus at different body sites, the objectives of this study were to determine whether S. aureus polyclonal colonization exists within one body niche and the optimal sampling sites and culture methodology to capture the diversity of S. aureus strains in community-dwelling individuals. Methods: Swabs were collected from the nares, axillae, and inguinal folds of 3 children with community-associated S. aureus infections and 11 household contacts, all with known S. aureus colonization. S. aureus isolates were recovered from each body niche using 4 culture methods and evaluated for polyclonality using phenotypic and genotypic strain characterization methodologies. Results: Within individuals, the mean (range) number of phenotypes and genotypes was 2.4 (1-4) and 3.1 (1-6), respectively. Six (43%) and 10 (71%) participants exhibited phenotypic and genotypic polyclonality within one body niche, respectively. Broth enrichment yielded the highest analytical sensitivity for S. aureus recovery, while direct plating to blood agar yielded the highest genotypic strain diversity. Conclusions: This study revealed S. aureus polyclonality within a single body niche. Culture methodology and sampling sites influenced the analytical sensitivity of S. aureus colonization detection and the robustness of phenotypic and genotypic strain recovery.
- [Show abstract] [Hide abstract] ABSTRACT: Minimum inhibitory concentration (MIC) results for 115 Staphylococcus intermedius group isolates are presented. 33% were methicillin resistant, among which 51.4% were susceptible to doxycycline, 29.7% to clindamycin and 21.6% to trimethoprim-sulfamethoxazole. All isolates were susceptible to ceftaroline, daptomycin, linezolid, nitrofurantoin, quinupristin-dalfopristin, rifampin, tigecycline, and vancomycin. 82.6%, 67.8% and 23.5% of all isolates were susceptible to ciprofloxacin, erythromycin, and penicillin. No isolates harbored mupA or qacA/B genes, suggestive of no resistance to mupirocin or chlorhexidine.
- [Show abstract] [Hide abstract] ABSTRACT: The objective of this study was to investigate an apparent increase in linezolid non-susceptible staphylococci and enterococci following a laboratory change in antimicrobial susceptibility testing from disk diffusion to an automated susceptibility testing system. Non-susceptible results (n = 27) from Vitek2 were subjected to a battery of confirmatory testing which included disk diffusion, Microscan broth microdilution, Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution, gradient diffusion (Etest), 23S rRNA gene sequencing, and cfr PCR. Our results show that there is poor correlation between methods and that only 70-75% of isolates confirmed as linezolid resistant with alternative phenotypic testing methods (disk diffusion, Microscan broth microdilution, CLSI broth microdilution, Etest). 23S rRNA gene sequencing identified mutations previously associated with linezolid resistance in 16 (59.3%) of isolates and the cfr gene was detected in 3 (11.1%) of isolates. Mutations located at positions 2576 and 2534 of the 23S rRNA gene were most common. In addition, two previously undescribed variants (positions 2083 and 2345 of the 23S rRNA gene) were also identified and may suggest that they could contribute to linezolid resistance.
- [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.
- [Show abstract] [Hide abstract] ABSTRACT: We performed a retrospective analysis of a simple modification to MALDI-TOF MS for microorganism identification to accurately improve the turnaround time (TAT) for identification of Enterobacteriaceae recovered in blood cultures. Relative to standard MALDI-TOF MS procedures, we reduced TAT from 28.3 (n=90) to 21.2h (n=107).
- [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
- [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.
- [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.
- [Show abstract] [Hide abstract] ABSTRACT: No laboratory test can diagnose Clostridium difficile infection (CDI). Rather, CDI is a clinical diagnosis that can be supported by laboratory data. While a diagnostic assay may indicate the absence or presence of the organism or its toxins, the test by itself does not determine who does or does not have CDI.One of the challenges in diagnosing CDI is that there are more asymptomatic C difficile carriers than there are people with CDI in the community and in the hospital. It is estimated 3% to 7% of the healthy adult population are colonized with C difficile.1 Asymptomatic colonization is more common among individuals with inpatient health care exposures. Between 4.4% and 15% of people are colonized with C difficile on admission to the hospital, with as many as 50% of persons living in long-term care facilities colonized.1 To add to the dilemma, diarrhea is frequent among those with health care exposures. Although C difficile is the most common health care–associated pathogen in the United States and CDI is a major cause of morbidity and mortality, it typically affects less than 1% of hospitalized patients and is the cause of diarrhea in only 5% to 10% of hospitalized people who have diarrhea and are tested for C difficile.1
- [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.
- [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.
- [Show abstract] [Hide abstract] ABSTRACT: Ceftolozane/tazobactam (C/T) is approved for treatment of complicated intra-abdominal and urinary tract infections; C/T has variable activity against anaerobic bacteria. Here, we evaluate the activity of C/T against a phylogenetically diverse collection of C. difficile isolates, and report uniformly high minimum inhibitory concentrations (≥256 μg/mL) to C/T. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
Washington University in St. Louis
San Luis, Missouri, United States
- Department of Pathology and Immunology
Washington & Lee UniversityЛексингтон, Virginia, United States
University of Alberta
Edmonton, Alberta, Canada
- Department of Laboratory Medicine and Pathology