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In this prospective, observational, method comparison clinical study, the Xpert Xpress MVP test (MVP) was evaluated using both clinician-collected (CVS) and self-collected vaginal swabs (SVS) collected in a clinical setting. The study was conducted at 12 sites, including point-of-care (POC) settings, from geographically diverse locations in the United States.

Introduction Norovirus infections are common in the USA and worldwide. Detection of norovirus in fecal samples is now common in routine tests for enteric pathogens using molecular methods. We observed a change in positivity rates for norovirus after the beginning of the coronavirus disease 2019 (COVID-19) pandemic in our laboratory and performed a more detailed analysis of testing results. Methods We reviewed the positivity rates for detection of common enteric pathogens from stool samples submitted to an academic medical center laboratory pre (2016–2019) and post the start of the COVID-19 pandemic (2020). Results In contrast to other enteric pathogens, norovirus positivity rates dropped dramatically from a yearly average of 3.9% in 2016–2019 to 0.76% from March 2020 through the end of 2020. Conclusion A sustained reduction in norovirus positivity rates was temporally associated with COVID-19 mitigation processes in the Philadelphia area, while positivity rates for other common enteric pathogens were only intermittently reduced.

Introduction Blood cultures (BCs) frequently become contaminated during the pre-analytic phase of collection leading to downstream ramifications. We present a summary of performance improvement (PI) interventions provided by four hospital systems and common factors that contributed to decreased blood culture contamination (BCC) rates. Methods Each hospital independently formed a multidisciplinary team and action plan for implementation of their intervention, focusing on the use of educational and training tools. Their goal was to significantly decrease their BCC rates. Pre- and post-intervention data were compared during the sustainment period to determine their success. Results All hospitals met their goals of post-intervention BCC rates and with most achieving and sustaining BCC rates ≤ 1.0–2.0%. Conclusion Our report highlights how four hospitals independently achieved their objective to decrease their BCC rate with the support of a multidisciplinary team. We propose a benchmark for BCC rates of 1.5 to

Introduction H. pylori (HP) resistance is increasing in the US. Guidelines suggest treatment based on local resistance patterns, yet are poorly studied. We describe resistance patterns of the Delaware Valley. Methods A retrospective study of patients referred to the Hospital of the University of Pennsylvania, between 2009-2019 who underwent endoscopy for culture. Chart review identified demographics, history, endoscopic and culture results, treatment, and follow up. Results Of 109 patients referred for refractory HP, 90 had identified HP. Median age was 53.2 years and the majority was female (74%), with median 2 previous antibiotic courses for HP. Gastric erythema was the most common endoscopic abnormality. 65 (72.2%) were culture positive, and 45 (69.2%) were resistant to levofloxacin, 27 (41.5%) to metronidazole, and 39 (43.3%) to clarithromycin.Being resistant to any one of the 3 antibiotics was associated with resistance to either of the other two. There was an association with number of previous antibiotics with resistance (OR 1.74, p

It has been suggested that pets play a critical role in the maintenance of methicillin-resistant (MR) and multidrug-resistant (MDR) Staphylococcus spp. in the household. We examined risk factors for carriage of antimicrobial-resistant coagulase-positive staphylococci, with particular attention to Staphylococcus aureus and Staphylococcus pseudintermedius isolated from pets living in households of people diagnosed with methicillin-resistant S. aureus (MRSA) skin or soft-tissue infection. We analyzed data collected cross-sectionally from a study conducted in 2012 that evaluated the transmission of MRSA and other staphylococci from humans, their pets and the environment (Pets and Environmental Transmission of Staphylococci [PETS] study). We used unadjusted and adjusted stratified logistic regression analyses with household-clustered standard errors to evaluate the association between demographic, healthcare-related, contact-related and environmental risk factors and MDR Staphylococcus spp. isolated from dogs and cats. Staphylococcal isolates obtained from dogs (n = 63) and cats (n = 47) were included in these analyses. The use of oral or injectable antimicrobials by the pets during the prior year was the main risk factor of interest. Based on our results, 50% (12/24) of S. aureus, 3.3% (1/30) of S. pseudintermedius and 25% (14/56) of other coagulase-positive staphylococci (CPS) were determined to be MDR. S. aureus isolates were more likely to be MDR compared with S. pseudintermedius. We did not find a significant statistical association between the use of oral or injectable antimicrobials in the prior year and the presence of MDR bacteria. The results suggest that drivers of antimicrobial resistance in household staphylococci may vary by bacterial species, which could have implications for one health intervention strategies for staphylococci and inform the investigation of other reverse zoonoses, such as COVID-19.

The MORDOR I trial1, conducted in Niger, Malawi and Tanzania, demonstrated that mass azithromycin distribution to preschool children reduced childhood mortality1. However, the large but simple trial design precluded determination of the mechanisms involved. Here we examined the gut microbiome of preschool children from 30 Nigerien communities randomized to either biannual azithromycin or placebo. Gut microbiome γ-diversity was not significantly altered (P = 0.08), but the relative abundances of two Campylobacter species, along with another 33 gut bacteria, were significantly reduced in children treated with azithromycin at the 24-month follow-up. Metagenomic analysis revealed functional differences in gut bacteria between treatment groups. Resistome analysis showed an increase in macrolide resistance gene expression in gut microbiota in communities treated with azithromycin (P = 0.004). These results suggest that prolonged mass azithromycin distribution to reduce childhood mortality reduces certain gut bacteria, including known pathogens, while selecting for antibiotic resistance. Mass antibiotic administration to preschool children in Nigerien communities alters the relative abundances of 35 bacterial species in the gut microbiome, including enteric pathogens, but also increases expression of macrolide resistance genes.

INTRODUCTION: H. pylori (HP) resistance is increasing in the US. Guidelines suggest treatment based on local resistance patterns, yet are poorly studied. We describe resistance patterns of the Delaware Valley. METHODS: A retrospective study of patients referred to the Hospital of the University of Pennsylvania, between 2009–2019 who underwent endoscopy for culture. Chart review identified demographics, history, endoscopic and culture results, treatment, and follow up. RESULTS: Of 109 patients referred for refractory HP, 90 had identified HP. Median age was 53.2 years and the majority was female (74%), with median 2 previous antibiotic courses for HP. Gastric erythema was the most common endoscopic abnormality. 65 (72.2%) were culture positive, and 45 (69.2%) were resistant to levofloxacin, 27 (41.5%) to metronidazole, and 39 (43.3%) to clarithromycin. Being resistant to any one of the 3 antibiotics was associated with resistance to either of the other two. There was an association with number of previous antibiotics with resistance (OR 1.74, p

At the time of percutaneous coronary intervention, participants were randomly assigned to prospective rapid point-of-care genotyping ofA total of 504 participants were randomized, 249 to the genotyped and 255 to the usual care group. The participants were primarily men (73%); age, 63±10 years; and 50% had acute coronary syndromes. In the genotyped group, 28% were carriers of loss-of-function alleles (*2, *3). The use of prasugrel or ticagrelor was significantly higher in the genotyped group compared with the usual care group (30% versus 21%; odds ratio, 1.60 [95% CI, 1.07-2.42];In a randomized controlled trial of clinicalURL: http://www.clinicaltrials.gov. Unique Identifier: NCT02508116.

ObjectiveResistance to extended-spectrum cephalosporins (ESC) among Enterobacteriaceae (EB) is increasingly prevalent. We sought to determine the clinical outcomes associated with community-onset ESC-resistant (ESC-R) EB urinary tract infections (UTIs) in a US health system.DesignRetrospective cohort study.PatientsAll patients presenting to the emergency departments (EDs) or outpatient practices with EB UTIs between 2010 and 2013 were included. Exposed patients had ESC-R EB UTIs. Unexposed patients had ESC-susceptible EB UTIs and were matched to exposed subjects 1:1 on study year. Multivariable logistic regression analyses were performed to evaluate the association between ESC-R EB UTI and the outcomes of clinical failure and inappropriate initial antibiotic therapy (IIAT).ResultsA total of 302 patients with community-onset EB UTI were included, with 151 exposed and unexposed. On multivariable analyses, UTI due to an ESC-R EB was significantly associated with clinical failure (odds ratio [OR], 7.07; 95% confidence interval [CI], 3.16–15.82; PCitrobacter spp and need for hemodialysis. UTI due to an ESC-R EB was also significantly associated with IIAT (OR, 4.40; 95% CI, 2.64–7.33; PConclusionsCommunity-onset UTI due to an ESC-R EB organism is significantly associated with clinical failure, which may be due in part to IIAT. Further studies are needed to determine which patients in the community are at high risk for drug-resistant infection to help inform prompt diagnosis and appropriate antibiotic prescribing for ESC-R EB.

Objectives Sepsis is associated with high early and total in-hospital mortality. Despite recent revisions in the diagnostic criteria for sepsis that sought to improve predictive validity for mortality, it remains difficult to identify patients at greatest risk of death. We compared the utility of nine biomarkers to predict mortality in subjects with clinically suspected bacterial sepsis. Design Cohort study. Setting The medical and surgical ICUs at an academic medical center. Subjects We enrolled 139 subjects who met two or more systemic inflammatory response syndrome (systemic inflammatory response syndrome) criteria and received new broad-spectrum antibacterial therapy. Interventions We assayed nine biomarkers (α-2 macroglobulin, C-reactive protein, ferritin, fibrinogen, haptoglobin, procalcitonin, serum amyloid A, serum amyloid P, and tissue plasminogen activator) at onset of suspected sepsis and 24, 48, and 72 hours thereafter. We compared biomarkers between groups based on both 14-day and total in-hospital mortality and evaluated the predictive validity of single and paired biomarkers via area under the receiver operating characteristic curve. Measurements and main results Fourteen-day mortality was 12.9%, and total in-hospital mortality was 29.5%. Serum amyloid P was significantly lower (4/4 timepoints) and tissue plasminogen activator significantly higher (3/4 timepoints) in the 14-day mortality group, and the same pattern held for total in-hospital mortality (Wilcoxon p ≤ 0.046 for all timepoints). Serum amyloid P and tissue plasminogen activator demonstrated the best individual predictive performance for mortality, and combinations of biomarkers including serum amyloid P and tissue plasminogen activator achieved greater predictive performance (area under the receiver operating characteristic curve > 0.76 for 14-d and 0.74 for total mortality). Conclusions Combined biomarkers predict risk for 14-day and total mortality among subjects with suspected sepsis. Serum amyloid P and tissue plasminogen activator demonstrated the best discriminatory ability in this cohort.

Campylobacteriosis is the most common bacterial foodborne illness in the United States and is frequently associated with foods of animal origin. The goals of this study were to compare clinical and non-clinical Campylobacter populations from Tennessee (TN) and Pennsylvania (PA), use phylogenetic relatedness to assess source attribution patterns, and identify potential outbreak clusters. Campylobacter isolates studied (n = 3080) included TN clinical isolates collected and sequenced for routine surveillance, PA clinical isolates collected from patients at the University of Pennsylvania Health System facilities, and non-clinical isolates from both states for which sequencing reads were available on NCBI. Phylogenetic analyses were conducted to categorize isolates into species groups and determine the population structure of each species. Most isolates were C. jejuni (n = 2132, 69.2%) and C. coli (n = 921, 29.9%), while the remaining were C. lari (0.4%), C. upsaliensis (0.3%), and C. fetus (0.1%). The C. jejuni group consisted of three clades, most non-clinical isolates were of poultry (62.7%) or cattle (35.8%) origin, and 59.7 and 16.5% of clinical isolates were in subclades associated with poultry or cattle, respectively. The C. coli isolates grouped into two clades, most non-clinical isolates were from poultry (61.2%) or swine (29.0%) sources, and 74.5, 9.2, and 6.1% of clinical isolates were in subclades associated with poultry, cattle, or swine, respectively. Based on genomic similarity, we identified 42 C. jejuni and one C. coli potential outbreak clusters. The C. jejuni clusters contained 188 clinical isolates, 19.6% of the total C. jejuni clinical isolates, suggesting that a larger proportion of campylobacteriosis may be associated with outbreaks than previously determined.

Fecal samples submitted to our clinical microbiology laboratory from patients in the Philadelphia region were prospectively analyzed for Campylobacter species other than C. jejuni and C. coli using a filtration method and microaerobic conditions with increased H 2 concentrations. Of 225 samples tested, 13 (5.8%) yielded Campylobacter species, with frequent isolation of C. concisus . The majority of Campylobacter species were not clinically significant. Additional studies in U.S. populations are warranted.

A new US Food and Drug Administration-cleared needleless blood collection device (PIVO; Velano Vascular, San Francisco, CA) for short peripheral catheters was compared with conventional venipuncture for collecting blood samples for routine laboratory analysis from adult healthy volunteers. The PIVO device was comparable with venipuncture in terms of providing high-integrity samples (no hemolysis or clotting), equivalent laboratory values, and better patient experience as assessed by pain scores. Further studies to assess the overall utility of the PIVO device are warranted.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an antibiotic resistance threat of the highest priority. Given the limited treatment options for this multidrug-resistant organism (MDRO), there is an urgent need for targeted strategies to prevent transmission. Here, we applied whole-genome sequencing to a comprehensive collection of clinical isolates to reconstruct regional transmission pathways and analyzed this transmission network in the context of statewide patient transfer data and patient-level clinical data to identify drivers of regional transmission. We found that high regional CRKP burdens were due to a small number of regional introductions, with subsequent regional proliferation occurring via patient transfers among health care facilities. While CRKP was predicted to have been imported into each facility multiple times, there was substantial variation in the ratio of intrafacility transmission events per importation, indicating that amplification occurs unevenly across regional facilities. While myriad factors likely influence intrafacility transmission rates, an understudied one is the potential for clinical characteristics of colonized and infected patients to influence their propensity for transmission. Supporting the contribution of high-risk patients to elevated transmission rates, we observed that patients colonized and infected with CRKP in high-transmission facilities had higher rates of carbapenem use, malnutrition, and dialysis and were older. This report highlights the potential for regional infection prevention efforts that are grounded in genomic epidemiology to identify the patients and facilities that make the greatest contribution to regional MDRO prevalence, thereby facilitating the design of precision interventions of maximal impact.

The evidence base for the optimal laboratory diagnosis of Clostridioides (Clostridium) difficile in adults is currently unresolved due to the uncertain performance characteristics and various combinations of tests. This systematic review evaluates the diagnostic accuracy of laboratory testing algorithms that include nucleic acid amplification tests (NAATs) to detect the presence of C. difficile., SUMMARY The evidence base for the optimal laboratory diagnosis of Clostridioides (Clostridium) difficile in adults is currently unresolved due to the uncertain performance characteristics and various combinations of tests. This systematic review evaluates the diagnostic accuracy of laboratory testing algorithms that include nucleic acid amplification tests (NAATs) to detect the presence of C. difficile. The systematic review and meta-analysis included eligible studies (those that had PICO [population, intervention, comparison, outcome] elements) that assessed the diagnostic accuracy of NAAT alone or following glutamate dehydrogenase (GDH) enzyme immunoassays (EIAs) or GDH EIAs plus C. difficile toxin EIAs (toxin). The diagnostic yield of NAAT for repeat testing after an initial negative result was also assessed. Two hundred thirty-eight studies met inclusion criteria. Seventy-two of these studies had sufficient data for meta-analysis. The strength of evidence ranged from high to insufficient. The uses of NAAT only, GDH-positive EIA followed by NAAT, and GDH-positive/toxin-negative EIA followed by NAAT are all recommended as American Society for Microbiology (ASM) best practices for the detection of the C. difficile toxin gene or organism. Meta-analysis of published evidence supports the use of testing algorithms that use NAAT alone or in combination with GDH or GDH plus toxin EIA to detect the presence of C. difficile in adults. There is insufficient evidence to recommend against repeat testing of the sample using NAAT after an initial negative result due to a lack of evidence of harm (i.e., financial, length of stay, or delay of treatment) as specified by the Laboratory Medicine Best Practices (LMBP) systematic review method in making such an assessment. Findings from this systematic review provide clarity to diagnostic testing strategies and highlight gaps, such as low numbers of GDH/toxin/PCR studies, in existing evidence on diagnostic performance, which can be used to guide future clinical research studies.

Background Bacterial resistance to first line antibiotics used to treat community-onset urinary tract infections (UTIs) continues to increase. We sought to create a clinical prediction tool for community-onset UTIs due to extended-spectrum cephalosporin-resistant (ESC-R) Enterobacterales (formerly Enterobacteriaceae, EB). Methods A case-control study was performed. The source population included patients presenting to an emergency department (ED) or outpatient practice with an EB UTI between 2010 and 2013. Case patients had ESC-R EB UTIs. Control patients had ESC-susceptible EB UTIs and were matched to cases 1:1 on study year. Multivariable conditional logistic regression was performed to develop the predictive model by maximizing the area under the receiver-operating curve (AUC). Internal validation was performed via bootstrapping. Results A total of 302 patients with a community-onset EB UTI were included, with 151 cases and 151 controls. After multivariable analysis, we found that presentation with an ESC-R EB community-onset UTI could be predicted by the following: (1) a history of malignancy; (2) a history of diabetes; (3) recent skilled nursing facility or hospital stay; (4) recent trimethoprim-sulfamethoxazole exposure; and (5) pyelonephritis at the time of presentation (AUC 0.73, Hosmer-Lemeshow goodness-of-fit P value 0.23). With this model, each covariate confers a single point, and a patient with ≥ 2 points is considered high risk for ESC-R EB (sensitivity 80%, specificity 54%). The adjusted AUC after bootstrapping was 0.71. Conclusions Community-onset ESC-R EB UTI can be predicted using the proposed scoring system, which can help guide diagnostic and therapeutic interventions., Bacterial resistance continues to increase in the community. We found that community-onset urinary tract infections due to extended-spectrum cephalosporin-resistant Enterobacterales (formerly Enterobacteriaceae) could be predicted with knowledge of 5 clinical factors.

OBJECTIVETo determine the impact of total household decolonization with intranasal mupirocin and chlorhexidine gluconate body wash on recurrent methicillin-resistant Staphylococcus aureus (MRSA) infection among subjects with MRSA skin and soft-tissue infection.DESIGNThree-arm nonmasked randomized controlled trial.SETTINGFive academic medical centers in Southeastern Pennsylvania.PARTICIPANTSAdults and children presenting to ambulatory care settings with community-onset MRSA skin and soft-tissue infection (ie, index cases) and their household members.INTERVENTIONEnrolled households were randomized to 1 of 3 intervention groups: (1) education on routine hygiene measures, (2) education plus decolonization without reminders (intranasal mupirocin ointment twice daily for 7 days and chlorhexidine gluconate on the first and last day), or (3) education plus decolonization with reminders, where subjects received daily telephone call or text message reminders.MAIN OUTCOME MEASURESOwing to small numbers of recurrent infections, this analysis focused on time to clearance of colonization in the index case.RESULTSOf 223 households, 73 were randomized to education-only, 76 to decolonization without reminders, 74 to decolonization with reminders. There was no significant difference in time to clearance of colonization between the education-only and decolonization groups (log-rank P=.768). In secondary analyses, compliance with decolonization was associated with decreased time to clearance (P=.018).CONCLUSIONSTotal household decolonization did not result in decreased time to clearance of MRSA colonization among adults and children with MRSA skin and soft-tissue infection. However, subjects who were compliant with the protocol had more rapid clearanceTrial registration. ClinicalTrials.gov identifier: NCT00966446Infect Control Hosp Epidemiol 2016;1–8

Two screening methods to detect staphylococcal colonization in humans were compared. Direct plating to CHROMagar (BD Diagnostics) was compared to a broth preenrichment followed by plating to Baird-Parker agar. The broth-enrichment method was comparable to CHROMagar for methicillin-resistant Staphylococcus aureas (MRSA) detection, but the enrichment method was optimum for recovery of coagulase-positive Staphylococcus spp.

ObjectiveTo describe the pattern of blood culture utilization in an academic university hospital setting.DesignRetrospective cohort study.SettingA 789-bed tertiary-care university hospital that processes 40,000+blood cultures annually.MethodsWe analyzed blood cultures collected from adult inpatients at the Hospital of the University of Pennsylvania between July 1, 2014, and June 30, 2015. Descriptive statistics and regression models were used to analyze patterns of blood culture utilization: frequency of blood cultures, use of repeat cultures following a true-positive culture, and number of sets drawn per day.ResultsIn total, 38,939 blood culture sets were drawn during 126,537 patient days (incidence rate, 307.7 sets per 1,000 patient days). The median number of blood culture sets drawn per hospital encounter was 2 (range, 1–76 sets). The median interval between blood cultures was 2 days (range, 1–71 days). Oncology services and cultures with gram-positive cocci were significantly associated with greater odds of having repeat blood cultures drawn the following day. Emergency services had the highest rate of drawing single blood-culture sets (16.9%), while oncology services had the highest frequency of drawing ≥5 blood culture sets within 24 hours (0.91%). Approximately 10% of encounters had at least 1 true-positive culture, and 89.2% of those encounters had repeat blood cultures drawn. The relative risk of a patient having repeat blood cultures was lower for those in emergency, surgery, and oncology services than for those in general medicine.ConclusionsOrdering practices differed by service and culture results. Analyzing blood culture utilization can contribute to the development of guidelines and benchmarks for appropriate usage.

Objective Despite numerous studies, the clinical value of sputum cultures in the management of pneumonia remains controversial; therefore, understanding the economic value of sputum cultures may help decision makers determine their appropriate use in patient management. Methods We developed a decision model to determine the economic and clinical value of using sputum cultures in the treatment of community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP) from the hospital perspective under various conditions. Results For both CAP and HCAP patients, obtaining sputum cultures resulted in similar costs compared to no culture, even if cultures cost $0. Given current clinical practices, obtaining cultures cost $539–631 more per CAP patient and $13–170 per HCAP patient compared to no culture use. However, cultures saved $8–202 per HCAP patient with a 40% probability the pathogen was the true cause (75% reduction in adverse outcomes, greater length of hospital stay (LOS) increase) to a 70% probability the pathogen was the true cause (25% reduction in outcomes and greater LOS increase and a 75% reduction in outcomes and all LOS increases). Additionally, obtaining sputum cultures had no impact on the number of adverse outcomes (i.e., adverse drug events, Clostridium difficile infection, pneumonia readmissions, additional hospitalization days). When all patients were treated with antibiotics empirically, obtaining cultures saved $4–342. Conclusions Overall, obtaining sputum cultures does not provide significant clinical or economic benefits for CAP or HCAP patients; however, it can reduce costs and shorten overall LOS under some circumstances. Clinicians should consider their local conditions when making decisions about sputum culture use.

Sepsis remains a diagnostic challenge in the intensive care unit (ICU), and the use of biomarkers may help in differentiating bacterial sepsis from other causes of systemic inflammatory syndrome (SIRS). The goal of this study was to assess test characteristics of a number of biomarkers for identifying ICU patients with a very low likelihood of bacterial sepsis. A prospective cohort study was conducted in a medical ICU of a university hospital. Immunocompetent patients with presumed bacterial sepsis were consecutively enrolled from January 2012 to May 2013. Concentrations of nine biomarkers (α-2 macroglobulin, C-reactive protein [CRP], ferritin, fibrinogen, haptoglobin, procalcitonin [PCT], serum amyloid A, serum amyloid P, and tissue plasminogen activator) were determined at baseline and at 24 h, 48 h, and 72 h after enrollment. Performance characteristics were calculated for various combinations of biomarkers for discrimination of bacterial sepsis from other causes of SIRS. Seventy patients were included during the study period; 31 (44%) had bacterial sepsis, and 39 (56%) had other causes of SIRS. PCT and CRP values were significantly higher at all measured time points in patients with bacterial sepsis. A number of combinations of PCT and CRP, using various cutoff values and measurement time points, demonstrated high negative predictive values (81.1% to 85.7%) and specificities (63.2% to 79.5%) for diagnosing bacterial sepsis. Combinations of PCT and CRP demonstrated a high ability to discriminate bacterial sepsis from other causes of SIRS in medical ICU patients. Future studies should focus on the use of these algorithms to improve antibiotic use in the ICU setting.

Patients with community-onset (CO) methicillin-resistant Staphylococcus aureus (MRSA) infections contribute to MRSA contamination of the home environment and may be reexposed to MRSA strains from this reservoir. This study evaluates One Health risk factors, which focus on the relationship between humans, animals, and the environment, for the increased prevalence of multiple antimicrobial-resistant MRSA isolates in the home environment. During a trial of patients with CO-MRSA infection, MRSA was isolated from the household environment at the baseline and 3 months later, following randomization of patients and household members to mupirocin-based decolonization therapy or an education control group. Up to two environmental MRSA isolates collected at each visit were tested. MRSA isolates were identified in 68% (65/95) of homes at the baseline ( n = 104 isolates) and 51% (33/65) of homes 3 months later ( n = 56 isolates). The rates of multidrug resistance (MDR) were 61% among isolates collected at the baseline and 55% among isolates collected at the visit 3 months later. At the baseline, 100% (14/14) of MRSA isolates from rural homes were MDR. While antimicrobial use by humans or pets was associated with an increased risk for the isolation of MDR MRSA from the environment, clindamycin use was not associated with an increased risk for the isolation of MDR MRSA. Incident low-level mupirocin-resistant MRSA strains were isolated at 3 months from 2 (5%) of 39 homes that were randomized to mupirocin treatment but none of the control homes. Among patients recently treated for a CO-MRSA infection, MRSA and MDR MRSA were common contaminants in the home environment. This study contributes to evidence that occupant use of antimicrobial drugs, except for clindamycin, is associated with MDR MRSA in the home environmental reservoir. (This study has been registered at ClinicalTrials.gov under registration no. NCT00966446.) IMPORTANCE MRSA is a common bacterial agent implicated in skin and soft tissue infections (SSTIs) in both community and health care settings. Patients with CO-MRSA infections contribute to environmental MRSA contamination in these settings and may be reexposed to MRSA strains from these reservoirs. People interact with natural and built environments; therefore, understanding the relationships between humans and animals as well as the characteristics of environmental reservoirs is important to advance strategies to combat antimicrobial resistance. Household interactions may influence the frequency and duration of exposure, which in turn may impact the duration of MRSA colonization or the probability for recurrent colonization and infection. Therefore, MRSA contamination of the home environment may contribute to human and animal recolonization and decolonization treatment failure. The aim of this study was to evaluate One Health risk factors that may be amenable to intervention and may influence the recovery of MDR and mupirocin resistance in CO-MRSA isolates.

As part of the American Society for Microbiology (ASM) Evidence-Based Laboratory Medicine Practice Guidelines Committee of the Professional Practice Committee, an ad hoc committee was formed in 2014 to assess guidelines published by the committee using an assessment tool, Appraisal of Guidelines for Research Evaluation II (AGREE II). The AGREE II assessment helps reviewers determine whether published guidelines are robust, transparent, and clear in presenting practice recommendations in a standardized manner. Identifying strengths and weaknesses of practice guidelines by ad hoc assessments helps with improving future guidelines through the participation of key stakeholders. This minireview describes the development of the ad hoc committee and results from their review of several ASM best practices guidelines and a non-ASM practice guideline from the Emergency Nurses Association.

Background Suboptimal clinical response to fluoroquinolone (FQ) therapy has been clearly documented in patients with Salmonella typhi infection with reduced FQ susceptibility. However, the clinical impact of reduced FQ susceptibility on other infections including E. coli urinary tract infections (UTIs) has never been evaluated. Methods We conducted a retrospective cohort study of female patients with fluoroquinolone susceptible E. coli (FQSEC) UTIs who received FQ therapy at outpatient services within University of Pennsylvania Health System, Philadelphia. Exposed patients were those with high MIC-FQSEC UTIs (the levofloxacin MIC > 0.12 but ≤ 2 mg/L) while unexposed patients were those with low MIC-FQSEC UTIs (the levofloxacin MIC ≤ 0.12 mg/L). The primary treatment outcome was treatment failure within 10 weeks after initiation of FQ therapy. Results From May 2008 to April 2011, we enrolled 29 exposed patients and 246 unexposed patients. Two patients in each group experienced treatment failure; exposed vs. unexposed (6.9 vs. 0.8%; p = 0.06). Risk difference and risk ratio (RR) for treatment failure were 0.06 [95% CI −0.03–0.15; exact-p = 0.06] and 8.48 [95% CI 1.24–57.97; exact-p = 0.06], respectively. After adjusting for underlying cerebrovascular disease, the RR was 7.12 (95% CI 1.20–42.10; MH-p = 0.04). Conclusion Our study demonstrated the negative impact of reduced FQ susceptibility on the treatment response to FQ therapy in FQSEC UTIs. This negative impact may be more intensified in other serious infections. Future studies in other clinical situations should be conducted to fill the gap of knowledge.

SUMMARYWe conducted a prospective cohort study between 1 January 2010 and 31 December 2012 at five adult and paediatric academic medical centres to identify factors associated with persistent methicillin-resistantStaphylococcus aureus(MRSA) colonisation. Adults and children presenting to ambulatory settings with a MRSA skin and soft tissue infection (i.e. index cases), along with household members, performed self-sampling for MRSA colonisation every 2 weeks for 6 months. Clearance of colonisation was defined as two consecutive negative sampling periods. Subjects without clearance by the end of the study were considered persistently colonised and compared with those who cleared colonisation. Of 243 index cases, 48 (19·8%) had persistent colonisation and 110 (45·3%) cleared colonisation without recurrence. Persistent colonisation was associated with white race (odds ratio (OR), 4·90; 95% confidence interval (CI), 1·38–17·40), prior MRSA infection (OR 3·59; 95% CI 1·05–12·35), colonisation of multiple sites (OR 32·7; 95% CI 6·7–159·3). Conversely, subjects with persistent colonisation were less likely to have been treated with clindamycin (OR 0·28; 95% CI 0·08–0·99). Colonisation at multiple sites is a risk factor for persistent colonisation and may require more targeted decolonisation efforts. The specific effect of clindamycin on MRSA colonisation needs to be elucidated.

Background We evaluated the importance of measuring early vaginal levels of eight BV-associated bacteria, at two points in pregnancy, and the risk of spontaneous preterm delivery (SPTD) among pregnant women and the subgroup of pregnant women with a history of preterm delivery (PTD).

Optimal strategies for limiting the transmission of extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella spp (ESBL-EK) in the hospital setting remain unclear. The objective of this study was to evaluate the impact of a urine culture screening strategy on the incidence of ESBL-EK.Prospective quasi-experimental study.Two intervention hospitals and one control hospital within a university health system from 2005 to 2009.All clinical urine cultures with E. coli or Klebsiella spp were screened for ESBL-EK. Patients determined to be colonized or infected with ESBL-EK were placed in a private room with contact precautions. The primary outcome of interest was nosocomial ESBL-EK incidence in nonurinary clinical cultures (cases occurring more than 48 hours after admission). Changes in monthly ESBL-EK incidence rates were evaluated with mixed-effects Poisson regression models, with adjustment for institution-level characteristics (eg, total admissions).The overall incidence of ESBL-EK increased from 1.42/10,000 patient-days to 2.16/10,000 patient-days during the study period. The incidence of community-acquired ESBL-EK increased nearly 3-fold, from 0.33/10,000 patient-days to 0.92/10,000 patient-days (P.001). On multivariable analysis, the intervention was not significantly associated with a reduction in nosocomial ESBL-EK incidence (incidence rate ratio, 1.38 [95% confidence interval, 0.83-2.31]; P - .21).Universal screening of clinical urine cultures for ESBL-EK did not result in a reduction in nosocomial ESBL-EK incidence rates, most likely because of increases in importation of ESBL-EK cases from the community. Further studies are needed on elucidating optimal infection control interventions to limit spread of ESBL-producing organisms in the hospital setting.

The objective of this study was to characterize the temporal variability of fluoroquinolone resistance mechanisms among Escherichia coli colonizing the gastrointestinal tract of hospitalized patients. Patients with new fluoroquinolone-resistant E. coli (FQREC) colonization were followed with serial fecal sampling until discharge or death. Genetic mechanism(s) of resistance for all FQREC isolates was characterized, including mutations in gyrA and parC and efflux pump overexpression. Of 451 subjects, 73 (16.2%) became newly colonized with FQREC. There was significant variability in regard to temporal changes in resistance mechanisms and levofloxacin MICs among isolates from individual patients. Compared to patients with transient colonization, patients with persistent colonization were more likely to have a urinary catheter (P = 0.04), diarrhea (P = 0.04), and a longer duration of hospitalization (22 and 9.0 mean days, respectively; P = 0.01) prior to sampling. Our data demonstrate the significant variability of resistance mechanisms in colonizing E. coli isolates among hospitalized patients.

We describe the prevalence of and risk factors for colonization with extended-spectrum β-lactamase (ESBL)–producing Escherichia coli and Klebsiella species (ESBL-EK) in hospitalized patients. The prevalence of colonization with ESBL-EK was 2.6%. Colonization was associated with cirrhosis, longer duration of hospital stay prior to surveillance, and prior exposure to clindamycin or meropenem.

OBJECTIVETo evaluate risk factors for and molecular characteristics of community-onset extended-spectrum cephalosporin-resistant (ESC-R) Enterobacteriaceae (EB) urinary tract infections (UTIs) in a US health system.DESIGNCase-control study.PARTICIPANTSAll patients presenting to the emergency department or outpatient practices with EB UTIs from December 21, 2010, through April 22, 2013, were included. Case patients had ESC-R EB UTIs. Control patients had ESC-susceptible EB UTIs and were matched 1:1 on study year.METHODSRisk factors for ESC-R EB UTI were assessed using multivariable conditional logistic regression. A subset of case isolates was evaluated for extended-spectrum beta-lactamases.RESULTSA total of 302 patients with community-onset EB UTI were included, of which 151 were cases. On multivariable analysis, risk factors for ESC-R EB UTI included trimethoprim-sulfamethoxazole use in the prior 6 months (odds ratio, 2.40 [95% CI, 1.22–4.70];P=.01), older age (1.03 [1.01–1.04];PP=.008), and presentation to the emergency department ( 2.42 [1.31–4.46];P=.005). The prevalence of extended-spectrum beta-lactamases among 120 case isolates was 52% CTX-M, 29% TEM, 20% OXA, and 13% SHV. The prevalence of AmpC was 25%. Pulsed-field gel electrophoresis of the CTX-MEscherichia coliisolates showed no distinct clusters.CONCLUSIONSUse of trimethoprim-sulfamethoxazole, older age, diabetes, and presentation to the emergency department were associated with community-onset ESC-R EB UTI. There was a high prevalence of CTX-M among our community isolates. Further studies are needed to determine strategies to limit emergence of these organisms in the community.Infect Control Hosp Epidemiol2016;1433–1439

Background. Biomarkers that identify critically ill children with systemic inflammatory response syndrome (SIRS) at low risk for bacterial infection may help clinicians reduce unnecessary antibiotic use. Methods. We conducted a prospective cohort study of children with SIRS and suspected infection admitted to a pediatric intensive care unit from January 5, 2012 to March 7, 2014. We enrolled patients upon initiation of new antibiotics (Time 0) and measured a panel of 8 serum biomarkers daily over 72 hours. Microbiology, imaging, and clinical data were reviewed to classify bacterial infections using Centers for Disease Control and Prevention definitions. We identified cut points of biomarker combinations to maximize the negative predictive value (NPV) and specificity for bacterial infection. Excess antibiotics were calculated as days of therapy beyond day 2 after SIRS onset in patients without bacterial infection. Results. Infections were identified in 46 of 85 patients: bacterial (n = 22) and viral (24), whereas 39 patients had no infection identified. At Time 0, C-reactive protein (CRP)

The use of culture-independent diagnostic tests (CIDTs), such as stool antigen tests, as standalone tests for the detection of Campylobacter in stool is increasing. We conducted a prospective, multicenter study to evaluate the performance of stool antigen CIDTs compared to culture and PCR for Campylobacter detection. Between July and October 2010, we tested 2,767 stool specimens from patients with gastrointestinal illness with the following methods: four types of Campylobacter selective media, four commercial stool antigen assays, and a commercial PCR assay. Illnesses from which specimens were positive by one or more culture media or at least one CIDT and PCR were designated “cases.” A total of 95 specimens (3.4%) met the case definition. The stool antigen CIDTs ranged from 79.6% to 87.6% in sensitivity, 95.9 to 99.5% in specificity, and 41.3 to 84.3% in positive predictive value. Culture alone detected 80/89 (89.9% sensitivity) Campylobacter jejuni/Campylobacter coli -positive cases. Of the 209 noncases that were positive by at least one CIDT, only one (0.48%) was positive by all four stool antigen tests, and 73% were positive by just one stool antigen test. The questionable relevance of unconfirmed positive stool antigen CIDT results was supported by the finding that noncases were less likely than cases to have gastrointestinal symptoms. Thus, while the tests were convenient to use, the sensitivity, specificity, and positive predictive value of Campylobacter stool antigen tests were highly variable. Given the relatively low incidence of Campylobacter disease and the generally poor diagnostic test characteristics, this study calls into question the use of commercially available stool antigen CIDTs as standalone tests for direct detection of Campylobacter in stool.

Fluoroquinolones (FQs) are among the most commonly prescribed antimicrobial agents in both inpatient and outpatient healthcare settings in the United States [1, 2]. The increasing prevalence of FQ resistance is of significant public health concern given the association between FQ resistance and poor clinical outcomes, including increased mortality [3, 4]. FQ resistance is of particular concern for Escherichia coli [1, 5], given it is the most common gram-negative pathogen in both hospital and community settings [6, 7]. In addition, FQ-resistant organisms are often resistant to other antimicrobial classes, thereby further limiting treatment options for associated infections [1, 8]. In the laboratory, resistance to FQs in E. coli has typically been demonstrated to arise in a stepwise fashion [9, 10]. In the clinical setting, this stepwise selection of resistance likely occurs at the level of gastrointestinal tract colonization (eg, as a result of antimicrobial selection pressure) [11, 12]. The primary mechanism of FQ resistance in E. coli is chromosomal mutation in one or more of the genes encoding the target bacterial enzymes DNA gyrase and topoisomerase IV [10]. These mutations occur predominantly in the gyrA and parC genes in the quinolone resistance-determining region (QRDR) [10]. Efflux-mediated antimicrobial resistance is also an important mechanism leading to FQ resistance in gram-negative bacteria. For example, overproduction of the AcrAB-TolC pump in E. coli has been shown to contribute to clinical FQ resistance through increased drug efflux [13]. A recent study demonstrated that of a total of 149 E. coli isolates with reduced FQ susceptibility (levofloxacin minimum inhibitory concentration [MIC], >0.125 μg/mL) identified via hospital-wide fecal surveillance, 59 (39.6%) isolates demonstrated efflux overexpression by organic solvent tolerance. Furthermore, the isolates that exhibited efflux overexpression were significantly more likely to demonstrate resistance to other antimicrobial agents [14]. Other studies have also confirmed an association between efflux overexpression in E. coli and increased rates of resistance to other antimicrobial agents [15, 16]. These findings have clear implications for the clinical setting given the large proportion of isolates that exhibit efflux overexpression. In addition, FQ-resistant E. coli (FQREC) isolates with efflux overexpression may present a significant therapeutic challenge given limitations in available antimicrobial treatment options. Along these lines, improved understanding of risk factors for efflux overexpression among FQREC would help elucidate the environmental pressures, including use of antimicrobial agents that can inhibit or activate expression of efflux pumps, which contribute to selection of this particular resistance mechanism. However, to our knowledge, only 2 studies have explored risk factors for efflux overexpression among FQREC [17, 18]. Furthermore, these studies demonstrated conflicting results and were characterized by small sample sizes [17], failure to conduct multivariable analyses [18], and a focus on only clinical urinary isolates [18]. Therefore, we conducted this study to determine risk factors for efflux overexpression as a mechanism of resistance among inpatients with FQREC gastrointestinal tract colonization.

In 2010, we surveyed 176 clinical laboratories in Pennsylvania regarding stool specimen testing practices for enteropathogens, including Campylobacter spp. Most (96.3%) routinely test for Campylobacter spp. In 17 (15.7%), a stool antigen test is the sole method for diagnosis. We recommend that laboratory practice guidelines for Campylobacter spp. testing be developed.

We conducted population-based surveillance for pneumococcal bacteremia within a 5-county region surrounding Philadelphia from October 2001 through September 2008, the period following introduction of the seven-valent pneumococcal conjugate vaccine. Erythromycin resistance increased from 14.7% in 2001-2002 to 20.3% in 2007-2008, while the resistance rate to penicillin (MIC, ≥2 μg/ml) decreased from 7.2% to 4.2% during the same period. The most predominant serotypes associated with erythromycin resistance in 2007-2008 included 19A (29.7%), 15A (29.2%), 6C (10.1%), 3 (5.6%), and 6A (4.5%). The molecular mechanisms for the increasing erythromycin resistance were mainly due to the growing presence of mef(A) negative erm (B) + and mef(A) + erm (B) + genotypes, which increased from 20.0% to 46.1% and from 1.8% to 19.1%, respectively, from 2001-2002 to 2007-2008. However, mef(A) -mediated erythromycin resistance decreased from 72.7% in 2001-2002 to 34.8% in 2007-2008. Serotypes related to the erm (B) gene were 15A (45.6%), 19A (20.9%), 3 (10.1%), and 6B (6.3%); serotypes related to the mef(A) gene were 6A (18.6%), 19A (15.0%), 6C (9.3%), and 14(8.4%); serotypes associated with the presence of both erm (B) and mef(A) were 19A (81.5%), 15A (7.7%), and 19F (6.2%). Pulsed-field gel electrophoresis analysis demonstrated that erythromycin-resistant isolates within the 19A serotype were genetically diverse and related to several circulating international clones. In contrast, erythromycin-resistant isolates within the 15A serotype consisted of clonally identical or closely related isolates.

This chapter mainly focuses on algorithms used for identification of curved and spiral-Shaped Gram-negative rods. Curved and spiral-shaped bacteria have a common microscopic morphology but represent diverse bacterial pathogens. Helicobacter cinaedi and Helicobacter fennelliae are two important Helicobacter species isolated from fecal specimens. Helicobacter pylori is the most common curved gram-negative rod isolated from gastric tissue, but other Helicobacter species have also been reported in this site. Other less commonly isolated curved gram-negative rods include the anaerobes Desulfovibrio spp., Sutterella wadswortkensis, Wolinella succinogenes, and Anaerobiospirillum succiniciproducens, which may be isolated from blood, abscess material, or other clinical samples. The spirochetes Borrelia spp. and Leptospira spp. cause systemic infections and are infrequently isolated in clinical laboratories, usually only with specialized media. Treponema spp. of clinical importance are diagnosed based on clinical and epidemiologic findings, as well as microscopic, serologic, and molecular test procedures. Various details about curved gram-negative bacilli that may be encountered in clinical specimens are described in the chapter.

Acute invasive fungal rhinosinusitis (AIFRS) most commonly occurs in immunosuppressed patients. The identification of fungal subtypes is important for management, and cultures can be negative. We studied 55 specimens from 23 patients with AIFRS (Rhizopus sp, 6; Aspergillus sp, 8; Fusarium sp, 1; Alternaria sp, 1; and culture negative, 7) using in situ hybridization (ISH) with biotin-labeled oligonucleotide probes targeting Aspergillus sp, Fusarium sp, Rhizopus sp, and a sequence identified in dematiaceous fungi. Ribosomal RNA preservation was established by using a pan-fungal probe. Nucleic acid preservation was seen in 18 patients (33 specimens [60%]). ISH using the specific fungal probes highlighted the respective fungal organisms in all culture-positive cases with adequate negative controls. Of the 7 culture-negative AIFRS cases, 4 had preserved fungal sequences. Of these cases, 2 additional cases of Aspergillus and 1 additional case of dematiaceous species were identified. In our study, 60% of AIFRS cases had fungal nucleic acid preservation. ISH can effectively identify fungi in AIFRS. ISH for specific fungal pathogens may aid in species identification in specimens with negative cultures.