The Onclarity Human Papillomavirus Trial: Design, methods, and baseline results.

OBJECTIVES: The baseline phase of the Onclarity trial was conducted to determine the screening performance of the Onclarity human papillomavirus (HPV) assay for detecting cervical cancer and precancer (≥CIN2) during triage of women ≥21 years with ASC-US cytology, as an adjunct test in women ≥30 years with normal cytology and for primary screening (HPV alone) in women ≥25 years. METHODS: 33,858 women ≥21 years were enrolled during routine clinic visits. All women with abnormal cytology, women ≥25 years that were high-risk HPV positive, and a random subset of women ≥25 years, negative by cytology and for HPV, were referred for colposcopy and cervical biopsy. Verification bias adjustment with 95% confidence intervals was applied. RESULTS: ASC-US prevalence was 5.8%. The overall HPV prevalence was 14.7%; for HPV 16, 18, and the 12 other HPV types it was 2.7%, 0.8%, and 11.2%, respectively. The prevalence of ASC-US and HPV was inversely proportional with age. The verification bias adjusted prevalence of ≥CIN2 and ≥CIN3 was 1.8% and 0.8%, respectively. Overall, five cases of cervical cancer were identified (all were HPV positive). The odds ratios associated with any HPV positive genotype, or with individual genotypes HPV 16, HPV 18, and HPV 31, for ≥CIN3, were statistically significant when compared to negative histology (p < 0.0001 for all). CONCLUSIONS: This report provides demographic information, cytology findings, HPV genotype information, and histopathology for participants in the baseline phase of this trial and offers further evidence to support genotype-specific screening for cervical cancer and precancer. Clinical Trial Registry URL:https://clinicaltrials.gov/ct2/show/NCT01944722.

Better tests, better care: improved diagnostics for infectious diseases.

In this IDSA policy paper, we review the current diagnostic landscape, including unmet needs and emerging technologies, and assess the challenges to the development and clinical integration of improved tests. To fulfill the promise of emerging diagnostics, IDSA presents recommendations that address a host of identified barriers. Achieving these goals will require the engagement and coordination of a number of stakeholders, including Congress, funding and regulatory bodies, public health agencies, the diagnostics industry, healthcare systems, professional societies, and individual clinicians.

Performance of the BD GeneOhm MRSA achromopeptidase assay for real-time PCR detection of methicillin-resistant Staphylococcus aureus in nasal specimens.

We evaluated the BD GeneOhm MRSA achromopeptidase (ACP) assay, which incorporates a new specimen preparation approach. A total of 1,216 leftover nasal samples were tested; using culture as the gold standard, the sensitivity and specificity were 92% and 94.6%, respectively. The new lysis method provides good sensitivity and simplifies specimen preparation.

Prospective, multicenter evaluation of the BD GeneOhm VanR assay for direct, rapid detection of vancomycin-resistant Enterococcus species in perianal and rectal specimens.

The BD GeneOhm VanR assay (BD Diagnostics, San Diego, CA), a qualitative test for the rapid detection of vancomycin-resistant enterococci (VRE) from rectal and/or perianal swabs, combines integrated nucleic acid extraction and automated polymerase chain reaction for the detection of vanA and/or vanB gene sequences. We studied 1,027 perianal and rectal swab specimens from 3 geographically distinct US sites (prevalence rates, 13.1%-25.8%). Direct swab specimens were tested by the assay and compared with direct culture. The sensitivity, specificity, and positive and negative predictive values of the assay were 93.2%, 81.9%, 54.4%, and 98.1%, respectively. The specificity was limited largely due to false-positives in the vanB portion of the assay. Specificity with perianal swabs was significantly greater than with rectal swabs, 87.1% vs 74.7%, respectively (P < .0001). When used only to detect resistance conferred by vanA, the assay was 88.3% (158/179) sensitive and 95.8% (802/837) specific, with positive and negative predictive values of 81.9% and 97.4%, respectively. The assay is a simple, rapid, and acceptable method for screening for VRE in a variety of populations in which vanA is the predominant genotype. Samples positive for the vanB genotype should be confirmed by culture owing to the apparent high number of false-positive results.

Health care-associated bloodstream infections associated with negative- or positive-pressure or displacement mechanical valve needleless connectors.

BACKGROUND: Health care-associated, central venous catheter-related bloodstream infections (HA-BSIs) are a major cause of morbidity and mortality. Needleless connectors (NCs) are an important component of the intravenous system. NCs initially were introduced to reduce health care worker needlestick injuries, yet some of these NCs may increase HA-BSI risk. METHODS: We compared HA-BSI rates on wards or intensive care units (ICUs) at 5 hospitals that had converted from split septum (SS) connectors or needles to mechanical valve needleless connectors (MV-NCs). The hospitals (16 ICUs, 1 entire hospital, and 1 oncology unit; 3 hospitals were located in the United States, and 2 were located in Australia) had conducted HA-BSI surveillance using Centers for Disease Control and Prevention definitions during use of both NCs. HA-BSI rates and prevention practices were compared during the pre-MV period, MV period, and post-MV period. RESULTS: The HA-BSI rate increased in all ICUs and wards when SS-NCs were replaced by MV-NCs. In the 16 ICUs, the HA-BSI rate increased significantly when SS-NCs or needles were replaced by MV-NCs (6.15 vs 9.49 BSIs per 1000 central venous catheter [CVC]-days; relative risk, 1.54; 95% confidence interval, 1.37-1.74; P < .001). The 14 ICUs that switched back to SS-NCs had significant reductions in their BSI rates (9.49 vs 5.77 BSIs per 1000 CVC-days; relative risk, 1.65; 95% confidence interval, 1.38-1.96; p < .001). BSI infection prevention strategies were similar in the pre-MV and MV periods. CONCLUSIONS: We found strong evidence that MV-NCs were associated with increased HA-BSI rates, despite similar BSI surveillance, definitions, and prevention strategies. Hospital personnel should monitor their HA-BSI rates and, if they are elevated, examine the role of newer technologies, such as MV-NCs.

Surgical site infection as a surrogate marker of physician impairment.

Our report details an implant-associated outbreak of surgical site infections related to the adverse effects of treatment for hepatitis C virus infection administered to surgeon X. During the 12-month period of this outbreak, 14 (9.5%) of 148 of surgeon X's patients developed a surgical site infection, a rate of SSI that was 8-fold higher than the rate during the 14-month baseline period or the 14-month follow-up period (P = .001), and higher than the rate among peer surgeons (P = .02).

The prevalence of resistant bacterial colonization in chronic hemodialysis patients.

BACKGROUND: Hospitalized dialysis patients are at increased risk for colonization and infection with resistant bacterial strains. METHODS: We performed a cross-sectional analysis of the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) colonization in 198 hemodialysis outpatients, 75 of whom had longitudinal screening data from prior hospitalization. Nasal specimens for MRSA, perirectal specimens for VRE, and permanent catheter exit site specimens were collected. RESULTS: MRSA colonization was present in 5.6% and VRE colonization in 3.14%. Univariate analyses revealed that prior exposure (defined as infection/colonization) with MRSA, hospitalization, and low serum albumin were associated with MRSA colonization. VRE colonization was associated with hospitalization, prior VRE or MRSA exposure, low serum albumin, and low ferritin. Multivariate analyses revealed MRSA colonization was predicted by prior MRSA exposure and VRE colonization was predicted by prior VRE exposure and number of hospitalizations. Among the 75 participants with longitudinal screening data, MRSA colonization was associated with prior MRSA history, and VRE colonization was associated with prior MRSA or VRE. CONCLUSIONS: Generally low rates of MRSA and VRE colonization were observed in hemodialysis outpatients. Prior hospital screening was predictive of future outpatient colonization and may be useful in risk assessment.

Legislative mandates for use of active surveillance cultures to screen for methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci: Position statement from the Joint SHEA and APIC Task Force.

Legislation aimed at controlling antimicrobial-resistant pathogens through the use of active surveillance cultures to screen hospitalized patients has been introduced in at least 2 US states. In response to the proposed legislation, the Society for Healthcare Epidemiology of America (SHEA) and the Association for Professionals in Infection Control and Epidemiology, Inc., (APIC) have developed this joint position statement. Both organizations are dedicated to combating health care-associated infections with a wide array of methods, including the use of active surveillance cultures in appropriate circumstances. This position statement reviews the proposed legislation and the rationale for use of active surveillance cultures, examines the scientific evidence supporting the use of this strategy, and discusses a number of unresolved issues surrounding legislation mandating use of active surveillance cultures. The following 5 consensus points are offered. (1) Although reducing the burden of antimicrobial-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), is of preeminent importance, the APIC and the SHEA do not support legislation to mandate use of active surveillance cultures to screen for MRSA, VRE, or other antimicrobial-resistant pathogens. (2) The SHEA and the APIC support the continued development, validation, and application of efficacious and cost-effective strategies for the prevention of infections caused by MRSA, VRE, and other antimicrobial-resistant and antimicrobial-susceptible pathogens. (3) The APIC and the SHEA welcome efforts by health care consumers, together with private, local, state, and federal policy makers, to focus attention on and formulate solutions for the growing problem of antimicrobial resistance and health care-associated infections. (4) The SHEA and the APIC support ongoing additional research to determine and optimize the appropriateness, utility, feasibility, and cost-effectiveness of using active surveillance cultures to screen both lower-risk and high-risk populations. (5) The APIC and the SHEA support stronger collaboration between state and local public health authorities and institutional infection prevention and control experts.

Legislative mandates for use of active surveillance cultures to screen for methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci: position statement from the Joint SHEA and APIC Task Force.

Legislation aimed at controlling antimicrobial-resistant pathogens through the use of active surveillance cultures to screen hospitalized patients has been introduced in at least 2 US states. In response to the proposed legislation, the Society for Healthcare Epidemiology of America (SHEA) and the Association of Professionals in Infection Control and Epidemiology (APIC) have developed this joint position statement. Both organizations are dedicated to combating healthcare-associated infections with a wide array of methods, including the use of active surveillance cultures in appropriate circumstances. This position statement reviews the proposed legislation and the rationale for use of active surveillance cultures, examines the scientific evidence supporting the use of this strategy, and discusses a number of unresolved issues surrounding legislation mandating use of active surveillance cultures. The following 5 consensus points are offered. (1) Although reducing the burden of antimicrobial-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), is of preeminent importance, APIC and SHEA do not support legislation to mandate use of active surveillance cultures to screen for MRSA, VRE, or other antimicrobial-resistant pathogens. (2) SHEA and APIC support the continued development, validation, and application of efficacious and cost-effective strategies for the prevention of infections caused by MRSA, VRE, and other antimicrobial-resistant and antimicrobial-susceptible pathogens. (3) APIC and SHEA welcome efforts by healthcare consumers, together with private, local, state, and federal policy makers, to focus attention on and formulate solutions for the growing problem of antimicrobial resistance and healthcare-associated infections. (4) SHEA and APIC support ongoing additional research to determine and optimize the appropriateness, utility, feasibility, and cost-effectiveness of using active surveillance cultures to screen both lower-risk and high-risk populations. (5) APIC and SHEA support stronger collaboration between state and local public health authorities and institutional infection prevention and control experts.

Using local microbiologic data to develop institution-specific guidelines for the treatment of hospital-acquired pneumonia.

BACKGROUND: While current guidelines recommend consideration of local microbiologic data when selecting empiric treatment for hospital-acquired pneumonia (HAP), few specifics of how to do this have been offered. METHODS: We conducted a retrospective analysis of HAP pathogens in 111 consecutive patients who acquired HAP during July to December 2004 and had a corresponding positive culture finding for a bacterial pathogen. These data were used to develop institution-specific guidelines. RESULTS: The most common bacteria identified were Staphylococcus aureus, Acinetobacter baumannii, and Pseudomonas aeruginosa, which were associated with 38%, 25%, and 19% of pneumonias, respectively. Susceptibility of Gram-negative bacteria to piperacillin-tazobactam and cefepime was 80% and 81%, respectively. The isolation of organisms resistant to piperacillin-tazobactam or cefepime was significantly more frequent in patients who had been hospitalized > or = 10 days. Of Gram-negative isolates resistant to piperacillin-tazobactam or cefepime, ciprofloxacin was active against < 10%, while amikacin was active against > 80%. New treatment guidelines were developed that divided the American Thoracic Society/Infectious Diseases Society of America "late onset/risk of multidrug-resistant pathogens" group of patients into two subcategories: "early-late" pneumonias (< 10 days of hospitalization) and "late-late" pneumonias (> or = 10 days of hospitalization). Guideline-directed treatment regimens would be predicted to provide adequate initial therapy for > 90% of late-onset pneumonias at our institution. CONCLUSIONS: Current guidelines suggest adding either an aminoglycoside or a fluoroquinolone to beta-lactam therapy for empiric Gram-negative coverage. However, in our institution, adding ciprofloxacin would not appreciably enhance the likelihood of providing initial appropriate antibiotic coverage. This underscores the importance of employing a systematic analysis of local data when developing treatment guidelines.

National nosocomial infection surveillance system: from benchmark to bedside in trauma patients.

INTRODUCTION: Ventilator-associated pneumonia (VAP) is an important cause of morbidity and mortality in the injured patient. Identification of those with VAP is important both in immediate clinical decision making as well as for the epidemiologic evaluation of the disease and benchmarking of rates across institutions with variable practice patterns. Despite this, controversy exists over the optimal method of VAP diagnosis. Many centers currently use invasive culture methods such as bronchoalveolar lavage (BAL) for diagnosis. Another diagnostic method, and the most common epidemiologic tool used to track VAP, is the definition employed by the National Nosocomial Infections Surveillance (NNIS) system. This relies on a combination of clinical and culture data. Our goal was to evaluate the accuracy of the NNIS definition as compared with BAL diagnosis in trauma patients. METHODS: Records of all ventilated patients admitted to the trauma intensive care unit at a Level I center who were evaluated for the presence of pneumonia over a 2.5-year period were reviewed. VAP diagnosis was established if > or =10 cfu/mL were cultured on BAL. VAP rates and time of onset were compared with the hospital infection control database, which defines VAP by NNIS criteria. Assuming BAL to be correct, sensitivity, specificity, and positive and negative predictive values were calculated for NNIS VAP. RESULTS: From September 1, 2001, through December 31, 2003, 292 patients underwent BAL for suspected pneumonia. The pneumonia rate in this group was 34 per 1,000 ventilator days. The NNIS definition showed excellent overall agreement, with a rate of 36 per 1,000 ventilator days. The use of the NNIS definition for bedside decision making, however, is less accurate. Sensitivity and positive predictive value were reasonably good (84% and 83%, respectively), whereas specificity and negative predictive value suffer (69% and 69%, respectively). Most importantly, the use of NNIS would have led to no treatment in 16% of patients diagnosed with VAP by BAL. CONCLUSIONS: Compared with strict bacteriologic criteria for VAP, the NNIS definition has good overall agreement and seems to have utility as an epidemiologic benchmarking tool in trauma patients. However, the NNIS definition has less utility as a bedside decision-making tool in this population, leading to under-treatment in a significant number of patients.

A prospective trial of a novel, silicone-based, silver-coated foley catheter for the prevention of nosocomial urinary tract infections.

OBJECTIVE: To evaluate the efficacy of silicone-based, silver ion-impregnated urinary catheters in the prevention of nosocomial urinary tract infections (NUTIs). DESIGN: Prospective, crossover study to compare the efficacy of a silicone-based, hydrogel-coated, silver-impregnated Foley catheter with that of a silicone-based, hydrogel-coated catheter in the prevention of NUTIs. SETTING: Adult medical and surgical wards of a university teaching hospital. RESULTS: A total of 3,036 patients with catheters were evaluated; 1,165 (38%) of the catheters were silver impregnated, and 1,871 (62%) were not silver impregnated. Study groups were not identical; there were more men, a shorter duration of catheterization, and fewer urine cultures per 1,000 catheter-days in the silver catheter group. The rate of NUTIs per 1,000 Foley-days was 14.29 in the silver catheter group, compared with 16.15 in the nonsilver catheter group (incidence rate ratio, 0.88; 95% confidence interval, 0.70-1.11; P = .29). The median length of catheterization prior to the onset of a urinary tract infection (ie, exposure time) was 4 days for each group. There were no differences in the recovery of gram-positive, gram-negative, or fungal organisms in NUTIs. In a multivariate survival analysis, no factors, including silver catheters, were protective against NUTI. CONCLUSIONS: Unlike previous trials of latex-based, silver ion-impregnated Foley catheters, we found that silicone-based, silver-impregnated Foley catheters were not effective in preventing NUTIs; however, this study was affected by differences in the study groups. Prospective trials remain important in assessing the efficacy and cost-effectiveness of new silver-coated products.

Isoniazid-resistant cavitary tuberculosis in a physician following isoniazid prophylaxis.

Single-drug prophylaxis is recommended after tuberculin skin test conversion, but not when there is active disease on chest radiograph because resistance develops frequently. Isoniazid-resistant tuberculosis developed in a physician receiving prophylaxis despite "faint left upper lobe soft tissue density" on chest radiograph. Ignoring active disease on chest x-ray renders this strategy counterproductive and cost ineffective.