Westyn Branch-Elliman

Mutation Master: profiles of substitutions in hepatitis C virus RNA of the core, alternate reading frame, and NS2 coding regions.

The RNA genome of the hepatitis C virus (HCV) undergoes rapid evolutionary change. Efforts to control this virus would benefit from the advent of facile methods to identify characteristic features of HCV RNA and proteins, and to condense the vast amount of mutational data into a readily interpretable form. Many HCV sequences are available in GenBank. To facilitate analysis, consensus sequences were constructed to eliminate the overrepresentation of certain genotypes, such as genotype 1, and a novel package of sequence analysis tools was developed. Mutation Master generates profiles of point mutations in a population of sequences and produces a set of visual displays and tables indicating the number, frequency, and character of substitutions. It can be used to analyze hundreds of sequences at a time. When applied to 255 HCV core protein sequences, Mutation Master identified variable domains and a series of mutations meriting further investigation. It flagged position 4, for example, where 90% or more of all sequences in genotypes 1, 2, 4, and 5, have N4, whereas those in genotypes 3, 6, 7, 8, 9, and 10 have L4. This pattern is noteworthy: L (hydrophobic) to N (polar) substitutions are generally rare, and genotypes 1, 2, 4, and 5 do not form a recognized super family of sequences. Thus, the L4N substitution probably arose independently several times. Moreover, not one member of genotypes 1, 2, 4, or 5 has L4 and not one member of genotypes 3, 6, 7, 8, 9, or 10 has N4. This nonoverlapping pattern suggests that coordinated changes at position 4 and a second site are required to yield a viable virus. The package generated a table of genotype-specific substitutions whose future analysis may help to identify interacting amino acids. Three substitutions were present in 100% of genotype 2 members and absent from all others: A68D, R74K, and R114H. Finally, this study revealed thatARFP, a novel protein encoded in an overlapping reading frame, is as conserved as conventional HCV proteins, a result supporting a role for ARFP in the viral life cycle. Whereas most conventional programs for phylogenetic analysis of sequences provide information about overall relatedness of genes or genomes, this program highlights and profiles point mutations. This is important because determinants of pathogenicity and drug susceptibility are likely to result from changes at only one or two key nucleotides or amino acid sites, and would not be detected by the type of pairwise comparisons that have usually been performed on HCV to date. This study is the first application of Mutation Master, which is now available upon request (http://tandem.biomath.mssm.edu/mutationmaster.html).

Determining the Ideal Strategy for Ventilator-associated Pneumonia Prevention. Cost–Benefit Analysis

RATIONALE Ventilator-associated pneumonia (VAP) is a common healthcare-associated infection with high associated cost and poor patient outcomes. Many strategies for VAP reduction have been evaluated. However, the combination of strategies with the optimal cost-benefit ratio remains unknown. OBJECTIVES To determine the preferred VAP prevention strategy, both from the hospital and societal perspectives. METHODS A cost-benefit decision model with a Markov model was constructed. Baseline probability of VAP, death, reintubation, and discharge from the intensive care unit (ICU) alive were ascertained from clinical trial data. Model inputs were obtained from the medical literature and the U.S. Department of Labor; a device cost was obtained from the manufacturer. Sensitivity analyses were completed to test the robustness of model results. MEASUREMENTS AND MAIN RESULTS Overall least expensive strategy and the strategy with the best cost-benefit ratio, up to a willingness to pay threshold of

Direct feedback with the ATP luminometer as a process improvement tool for terminal cleaning of patient rooms.

50,000-100,000 per case of VAP averted was sought. We examined a total of 120 unique combinations of VAP prevention strategies. The preferred strategy from the hospital perspective included subglottic suction endotracheal tubes, probiotics, and the Institute for Healthcare Improvement VAP Prevention Bundle. The preferred strategy from the point of view of society also included additional prevention measures (oral care with chlorhexidine and selective oral decontamination). No preferred strategies included silver endotracheal tubes or selective gut decontamination. CONCLUSIONS Despite their infrequent use, current data suggest that the use of prophylactic probiotics and subglottic endotracheal tubes are cost-effective for preventing VAP from the societal and hospital perspectives.

Risk Factors for Staphylococcus aureus Postpartum Breast Abscess

We assessed the adenosine triphosphate luminometer as a tool for point-of-cleaning education. Following a terminal cleaning, infection preventionists met with cleaning staff and used the luminometer to evaluate multiple surfaces; 820 surfaces in 210 rooms were sampled. The mean proportion of clean surfaces improved significantly over the study period, P = .012. These findings suggest that direct measurement and education at the point of cleaning with an objective tool is useful for improving terminal cleaning.

Risk of surgical site infection, acute kidney injury, and Clostridium difficile infection following antibiotic prophylaxis with vancomycin plus a beta-lactam versus either drug alone: A national propensity-score-adjusted retrospective cohort study

BACKGROUND Staphylococcus aureus (SA) breast abscesses are a complication of the postpartum period. Risk factors for postpartum SA breast abscesses are poorly defined, and literature is conflicting. Whether risk factors for methicillin-resistant SA (MRSA) and methicillin-susceptible SA (MSSA) infections differ is unknown. We describe novel risk factors associated with postpartum breast abscesses and the changing epidemiology of this infection. METHODS We conducted a cohort study with a nested case-control study (n = 216) involving all patients with culture-confirmed SA breast abscess among >30 000 deliveries at our academic tertiary care center from 2003 through 2010. Data were collected from hospital databases and through abstraction from medical records. All SA cases were compared with both nested controls and full cohort controls. A subanalysis was completed to determine whether risk factors for MSSA and MRSA breast abscess differ. Univariate analysis was completed using Students t test, Wilcoxon rank-sum test, and analysis of variance, as appropriate. A multivariable stepwise logistic regression was used to determine final adjusted results for both the case-control and the cohort analyses. RESULTS Fifty-four cases of culture-confirmed abscess were identified: 30 MRSA and 24 MSSA. Risk factors for postpartum SA breast abscess in multivariable analysis include in-hospital identification of a mother having difficulty breastfeeding (odds ratio, 5.00) and being a mother employed outside the home (odds ratio, 2.74). Risk factors did not differ between patients who developed MRSA and MSSA infections. CONCLUSIONS MRSA is an increasingly important pathogen in postpartum women; risk factors for postpartum SA breast abscess have not changed with the advent of community-associated MRSA.

Development and Validation of a Simple and Easy-to-Employ Electronic Algorithm for Identifying Clinical Methicillin- Resistant Staphylococcus aureus Infection

Background The optimal regimen for perioperative antimicrobial prophylaxis is controversial. Use of combination prophylaxis with a beta-lactam plus vancomycin is increasing; however, the relative risks and benefits associated with this strategy are unknown. Thus, we sought to compare postoperative outcomes following administration of 2 antimicrobials versus a single agent for the prevention of surgical site infections (SSIs). Potential harms associated with combination regimens, including acute kidney injury (AKI) and Clostridium difficile infection (CDI), were also considered. Methods and findings Using a multicenter, national Veterans Affairs (VA) cohort, all patients who underwent cardiac, orthopedic joint replacement, vascular, colorectal, and hysterectomy procedures during the period from 1 October 2008 to 30 September 2013 and who received planned manual review of perioperative antimicrobial prophylaxis regimen and manual review for the 30-day incidence of SSI were included. Using a propensity-adjusted log-binomial regression model stratified by type of surgical procedure, the association between receipt of 2 antimicrobials (vancomycin plus a beta-lactam) versus either single agent alone (vancomycin or a beta-lactam) and SSI was evaluated. Measures of association were adjusted for age, diabetes, smoking, American Society of Anesthesiologists score, preoperative methicillin-resistant Staphylococcus aureus (MRSA) status, and receipt of mupirocin. The 7-day incidence of postoperative AKI and 90-day incidence of CDI were also measured. In all, 70,101 procedures (52,504 beta-lactam only, 5,089 vancomycin only, and 12,508 combination) with 2,466 (3.5%) SSIs from 109 medical centers were included. Among cardiac surgery patients, combination prophylaxis was associated with a lower incidence of SSI (66/6,953, 0.95%) than single-agent prophylaxis (190/12,834, 1.48%; crude risk ratio [RR] 0.64, 95% CI 0.49, 0.85; adjusted RR 0.61, 95% CI 0.46, 0.83). After adjusting for SSI risk, no association between receipt of combination prophylaxis and SSI was found for the other types of surgeries evaluated, including orthopedic joint replacement procedures. In MRSA-colonized patients undergoing cardiac surgery, SSI occurred in 8/346 (2.3%) patients who received combination prophylaxis versus 4/100 (4.0%) patients who received vancomycin alone (crude RR 0.58, 95% CI 0.18, 1.88). Among MRSA-negative and -unknown cardiac surgery patients, SSIs occurred in 58/6,607 (0.9%) patients receiving combination prophylaxis versus 146/10,215 (1.4%) patients who received a beta-lactam alone (crude RR 0.61, 95% CI 0.45, 0.83). Based on these associations, the number needed to treat to prevent 1 SSI in MRSA-colonized patients is estimated to be 53, compared to 176 in non-MRSA patients. CDI incidence was similar in both exposure groups. Across all types of surgical procedures, risk of AKI was increased in the combination antimicrobial prophylaxis group (2,971/12,508 [23.8%] receiving combination versus 1,058/5,089 [20.8%] receiving vancomycin alone versus 7,314/52,504 [13.9%] receiving beta-lactam alone). We found a significant association between absolute risk of AKI and receipt of combination regimens across all types of procedures. If the observed association is causal, the number needed to harm for severe AKI following cardiac surgery would be 167. The major limitation of our investigation is that it is an observational study in a predominantly male population, which may limit generalizability and lead to unmeasured confounding. Conclusions There are benefits but also unintended consequences of antimicrobial and infection prevention strategies aimed at “getting to zero” healthcare-associated infections. In our study, combination prophylaxis was associated with both benefits (reduction in SSIs following cardiac surgical procedures) and harms (increase in postoperative AKI). In cardiac surgery patients, the difference in risk–benefit profile by MRSA status suggests that MRSA-screening-directed prophylaxis may optimize benefits while minimizing harms in this selected population. More information about long-term outcomes and patient and societal preferences regarding risk of SSI versus risk of AKI is needed to improve clinical decision-making.

Estimated nursing workload for the implementation of ventilator bundles

BACKGROUND With growing demands to track and publicly report and compare infection rates, efforts to utilize automated surveillance systems are increasing. We developed and validated a simple algorithm for identifying patients with clinical methicillin-resistant Staphylococcus aureus (MRSA) infection using microbiologic and antimicrobial variables. We also estimated resource savings. METHODS Patients who had a culture positive for MRSA at any of 5 acute care Veterans Affairs hospitals were eligible. Clinical infection was defined on the basis of manual chart review. The electronic algorithm defined clinical MRSA infection as a positive non-sterile-site culture with receipt of MRSA-active antibiotics during the 5 days prior to or after the culture. RESULTS In total, 246 unique non-sterile-site cultures were included, of which 168 represented infection. The sensitivity (43.4%-95.8%) and specificity (34.6%-84.6%) of the electronic algorithm varied depending on the combination of antimicrobials included. On multivariable analysis, predictors of algorithm failure were outpatient status (odds ratio, 0.23 [95% confidence interval, 0.10-0.56]) and respiratory culture (odds ratio, 0.29 [95% confidence interval, 0.13-0.65]). The median cost was

Hepatitis C transmission due to contamination of multidose medication vials: summary of an outbreak and a call to action.

2.43 per chart given 4.6 minutes of review time per chart. CONCLUSIONS Our simple electronic algorithm for detecting clinical MRSA infections has excellent sensitivity and good specificity. Implementation of this electronic system may streamline and standardize surveillance and reporting efforts.

Natural Language Processing for Real-Time Catheter-Associated Urinary Tract Infection Surveillance: Results of a Pilot Implementation Trial

Background Ventilator-associated pneumonia is a common healthcare-associated infection with high attributable morbidity and mortality. Prevention strategies, including prevention bundles, have been widely adopted across the USA. However, the nursing resources required to implement these bundles, and their effect on other aspects of intensive care unit patient care, are unknown. Methods We conducted a survey of all critical care nurses at our institution to determine the time required, and impact of, a prevention bundle at our hospital. Results Nurses estimated that the standard ventilator bundle requires a median of 115 min (IQR: 74–182) per patient per day. Although the majority of nurses did not perceive that other patient care tasks were delayed by these prevention activities, this was not universal; 29% (95% CI 21% to 39%) of respondents reported that other patient care tasks were sometimes delayed because time was allocated to ventilator bundle activities. Conclusions Our estimates may serve as potentially important inputs for cost-effectiveness and decision analyses related to intensive care unit prevention activities. Further research should include direct observations about nursing time allocation related to prevention activities.

Health and Economic Burden of Post-Partum Staphylococcus aureus Breast Abscess

In May 2001, The New York City Department of Health and Mental Hygiene was informed of a cluster of 4 patients treated at an outpatient gastroenterology center who developed acute hepatitis C virus infection. An investigation identified a total of 12 clinic-associated hepatitis C virus transmissions and the outbreak and was traced to unsafe handling of multidose anesthetic vials and possible re-use of contaminated needles. This report typifies the types of outbreaks that continue to occur despite safe injection guidelines.