A Clinical Prediction Tool for Extended-Spectrum Cephalosporin Resistance in Community-Onset Enterobacterales Urinary Tract Infection.

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.

Blood culture utilization at an academic hospital: Addressing a gap in benchmarking.

OBJECTIVE: To describe the pattern of blood culture utilization in an academic university hospital setting. DESIGN: Retrospective cohort study. SETTING: A 789-bed tertiary-care university hospital that processes 40,000+blood cultures annually. METHODS: We 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. RESULTS: In 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. CONCLUSIONS: Ordering practices differed by service and culture results. Analyzing blood culture utilization can contribute to the development of guidelines and benchmarks for appropriate usage.

Combined Biomarkers Predict Acute Mortality Among Critically Ill Patients With Suspected Sepsis.

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.

Comparison of Culture-Based Methods for Identification of Colonization with Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus in the Context of Cocolonization.

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.

Occupational Exposure to Swine, Poultry, and Cattle and Antibody Biomarkers of Campylobacter jejuni Exposure and Autoimmune Peripheral Neuropathy.

INTRODUCTION: Foodborne Campylobacter jejuni infection has been associated with an increased risk of autoimmune peripheral neuropathy, but risks of occupational exposure to C. jejuni have received less attention. This study compared anti-C. jejuni IgA, IgG, and IgM antibody levels, as well as the likelihood of testing positive for any of five anti-ganglioside autoantibodies, between animal farmers and non-farmers. Anti-C. jejuni antibody levels were also compared between farmers with different animal herd or flock sizes. The relationship between anti-C. jejuni antibody levels and detection of anti-ganglioside autoantibodies was also assessed. METHODS: Serum samples from 129 Agricultural Health Study swine farmers (some of whom also worked with other animals) and 46 non-farmers, all from Iowa, were analyzed for anti-C. jejuni antibodies and anti-ganglioside autoantibodies using ELISA. Information on animal exposures was assessed using questionnaire data. Anti-C. jejuni antibody levels were compared using Mann-Whitney tests and linear regression on log-transformed outcomes. Fisher's Exact Tests and logistic regression were used to compare likelihood of positivity for anti-ganglioside autoantibodies. RESULTS: Farmers had significantly higher levels of anti-C. jejuni IgA (p < 0.0001) and IgG (p = 0.02) antibodies compared to non-farmers. There was no consistent pattern of anti-C. jejuni antibody levels based on animal herd or flock size. A higher percentage of farmers (21%) tested positive for anti-ganglioside autoantibodies compared to non-farmers (9%), but this difference was not statistically significant (p = 0.11). There was no significant association between anti-C. jejuni antibody levels and anti-ganglioside autoantibodies. CONCLUSIONS: The findings provide evidence that farmers who work with animals may be at increased risk of exposure to C. jejuni. Future research should include longitudinal studies of exposures and outcomes, as well as studies of interventions to reduce exposure. Policies to reduce occupational exposure to C. jejuni should be considered.

Risk factors for gyrA and parC mutations in Pseudomonas aeruginosa.

OBJECTIVE: The major mechanism of fluoroquinolone (FQ) resistance in Pseudomonas aeruginosa (PSA) is modification of target proteins in DNA gyrase and topoisomerase IV, most commonly the gyrA and parC subunits. The objective of this study was to determine risk factors for PSA with and without gyrA or parC mutations. DESIGN: Case-case-control study SETTING: Two adult academic acute-care hospitals PATIENTS: Case 1 study participants had a PSA isolate on hospital day 3 or later with any gyrA or parC mutation; case 2 study participants had a PSA isolate on hospital day 3 or later without these mutations. Controls were a random sample of all inpatients with a stay of 3 days or more. METHODS: Each case group was compared to the control group in separate multivariate models on the basis of demographics and inpatient antibiotic exposure, and risk factors were qualitatively compared. RESULTS: Of 298 PSA isolates, 172 (57.7%) had at least 1 mutation. Exposure to vancomycin and other agents with extended Gram-positive activity was a risk factor for both cases (case 1 odds ratio [OR], 1.09; 95% confidence interval [CI], 1.04-1.13; OR, 1.14; 95% CI, 1.03-1.26; case 2 OR, 1.09; 95% CI, 1.03-1.14; OR, 1.13; 95% CI, 1.01-1.25, respectively). CONCLUSIONS: Exposure to agents with extended Gram-positive activity is a risk factor for isolation of PSA overall but not for gyrA/parC mutations. FQ exposure is not associated with isolation of PSA with mutations.

The effect of a hospital-wide urine culture screening intervention on the incidence of extended-spectrum ß-lactamase-producing Escherichia coli and Klebsiella species.

OBJECTIVE: Optimal strategies for limiting the transmission of extended-spectrum ß-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. DESIGN: Prospective quasi-experimental study. SETTING: Two intervention hospitals and one control hospital within a university health system from 2005 to 2009. PATIENTS AND INTERVENTION: 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). RESULTS: 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). CONCLUSIONS: 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.

Impact of antibiotic use during hospitalization on the development of gastrointestinal colonization with Escherichia coli with reduced fluoroquinolone susceptibility.

OBJECTIVE: Infections due to fluoroquinolone-resistant Escherichia coli (FQREC) are associated with significant morbidity and mortality. Fluoroquinolone resistance likely arises at the level of gastrointestinal colonization. The objective of this study was to identify risk factors for the development of FQREC gastrointestinal tract colonization in hospitalized patients, including the impact of antibiotics prescribed during hospitalization. DESIGN: A prospective cohort study was conducted from 2002 to 2004 within a university health system. METHODS: Hospitalized patients initially colonized with fluoroquinolone-susceptible E. coli were followed up with serial fecal sampling for new FQREC colonization or until hospital discharge or death. A Cox proportional hazards regression model was developed to identify risk factors for new FQREC colonization, with antibiotic exposure modeled as time-varying covariates. RESULTS: Of 395 subjects, 73 (18.5%) became newly colonized with FQREC. Length of stay before sampling (hazard ratio [HR], 1.02 [95% confidence interval (CI), 1.1-1.03]; P = .003) and malignancy (HR, 0.37 [95% CI, 0.21-0.67]; P = .001) were significantly associated with the development of FQREC colonization. In addition, receipt of a first-generation cephalosporin (HR, 1.19 [95% CI, 1.10-1.29]; P < .001) or cefepime (HR, 1.05 [95% CI, 1.00-1.10]; P = .048) during hospitalization increased the risk of new FQREC colonization. CONCLUSIONS: The acquisition of FQREC in the hospital setting is complex, and antimicrobial stewardship programs should take into account patterns of antibiotic use in implementing strategies to reduce the development of new FQREC colonization. Future studies are needed to identify risk factors for infection in hospitalized patients newly colonized with FQREC.

Fungal rhinosinusitis: a retrospective microbiologic and pathologic review of 400 patients at a single university medical center.

Fungal Rhinosinusitis (FRS) is a well known entity, but only in more recent times have the types of FRS been more fully defined. In this study, we evaluate the diagnosis of FRS in a single medical center. Cases were divided into 2 main categories, non-invasive and invasive. Non-invasive FRS included fungus ball (FB) and allergic fungal rhinosinusitis (AFRS). Invasive FRS included acute invasive fungal rhinosinusitis (AIFRS), chronic invasive fungal rhinosinusitis (CIFRS), and chronic invasive granulomatous fungal rhinosinusitis (CGFRS). Fungal culture data, if available was reviewed. 400 patients with FRS were identified. 87.25% were non-invasive (45% AFRS, 40% FB, and 2% combined AFRS and FB and 12.5% were invasive 11% AIFRS 1.2% CIFRS 0.5% CGFRS. One patient (0.25%) had combined FB/CGFRS. Aspergillus sp. or dematiaceous species were the most common fungi isolated in AFS while Aspergillus sp. was most common in FB and AIFRS. In our experience, most FRS is non-invasive. In our patient population, invasive FRS is rare with AIFRS representing >90% of cases. Culture data supports that a variety of fungal agents are responsible for FRS, but Aspergillus sp. appears to be one of the most common organisms in patients with FRS.

Characteristics and pregnancy outcomes of pregnant women asymptomatic for bacterial vaginosis.

STUDY DESIGN: To determine the clinical, behavioral or demographic factors associated with asymptomatic bacterial vaginosis (BV) and to examine if women with asymptomatic BV had a higher risk of a variety of pregnancy outcomes compared to symptomatic BV positive women. For this study, 1916 pregnant women who were 12 weeks' gestation or less were enrolled. Interviewers facilitated vaginal swab collection for BV assessment, and completed the baseline questionnaire. BV was identified by Gram stain. RESULTS: Forty percent of pregnant women screened positive for BV and a substantial proportion of BV positive pregnant women were asymptomatic (67%). Asymptomatic BV positive women reported lower stress scores (RR = 0.78, 95% CI: 0.67-0.89), slightly more prior STD's (RR = 1.03, 95% CI: 1.01-1.07), and a higher quantity of Mobiluncus (RR = 1.04 95% CI: 1.01-1.07) compared to symptomatic BV positive women. We did not find an increase in adverse pregnancy outcomes related to BV symptomatology. CONCLUSION: Among first trimester pregnant women, only stress, STD history, and quantity of Mobiluncus were associated with symptom reports among BV positive pregnant women. We also found that women with asymptomatic BV did not have an increased risk of a variety of adverse pregnancy outcomes compared to symptomatic BV positive women.

Central nervous system infections due to Abiotrophia and Granulicatella species: an emerging challenge?

Although Abiotrophia and Granulicatella species, previously referred to as nutritionally variant streptococci, were initially identified over 40 years ago, isolation of these pathogens from the central nervous system (CNS) was first noted only recently. Recognition of CNS involvement with these organisms is of great concern given the association of Abiotrophia/Granulicatella infections with increased morbidity and mortality as well as greater bacteriologic failure and relapse rates. We describe A. defectiva and G. adiacens CNS infections in two patients and review the existing literature of CNS involvement with these bacteria. The clinical presentation and initial cerebrospinal fluid analysis has varied substantially across reported patients. While most infections have been characterized primarily by a localized infection (e.g., abscess), evidence of meningitis has usually also been present. Furthermore, nearly all cases have followed neurosurgical procedures suggesting possible introduction of the organism into the CNS at the time of surgery. Given the significant negative clinical impact of Abiotrophia/Granulicatella infections, elucidation of the emerging epidemiology of CNS infections with these bacteria is warranted.