Patient predictors of pathogenic versus commensal Gram-positive bacilli organisms isolated from blood cultures.

Objective: Gram-positive bacilli represent a diverse species of bacteria that range from commensal flora to pathogens implicated in severe and life-threatening infection. Following the isolation of Gram-positive bacilli from blood cultures, the time to species identification may take upward of 24 hours, leaving clinicians to conjecture whether they may represent a contaminant (inadvertent inoculation of commensal flora) or pathogenic organism. In this study, we sought to identify patient variables that could help predict the isolation of contaminant versus pathogenic Gram-positive bacilli from blood cultures. Design: Retrospective cohort study. Settings: One quaternary academic medical center affiliated with the University of Toronto. Patients: Adult inpatients were admitted to hospital over a 5-year period (May 2014 to December 2019). Methods: A total of 260 unique Gram-positive bacilli blood culture results from adult inpatients were reviewed and analyzed in both a univariable and multivariable model. Results: Malignancy (aOR 2.78, 95% CI 1.33-5.91, p = 0.007), point increments in the Quick Sepsis Related Organ Failure Assessment score for sepsis (aOR 2.25, 95% CI 1.50-3.47, p < 0.001), peptic ulcer disease (aOR 5.63, 95% CI 1.43-21.0, p = 0.01), and the receipt of immunosuppression prior to a blood culture draw (aOR 3.80, 95% CI 1.86-8.01, p < 0.001) were associated with an increased likelihood of speciating pathogenic Gram-positive bacilli from blood cultures such as Clostridium species and Listeria monocytogenes. Conclusion: Such predictors can help supplement a clinician's assessment on determining when empirical therapy is indicated when faced with Gram-positive bacilli from blood cultures and may direct future stewardship interventions for responsible antimicrobial prescribing.

Identifying clusters of coexisting conditions and outcomes among adults admitted to hospital with community-acquired pneumonia: a multicentre cohort study.

BACKGROUND: Little is known about patterns of coexisting conditions and their influence on clinical care or outcomes in adults admitted to hospital for community-acquired pneumonia (CAP). We sought to evaluate how coexisting conditions cluster in this population to advance understanding of how multimorbidity affects CAP. METHODS: We studied 11 085 adults admitted to hospital with CAP at 7 hospitals in Ontario, Canada. Using cluster analysis, we identified patient subgroups based on clustering of comorbidities in the Charlson Comorbidity Index. We derived and replicated cluster analyses in independent cohorts (derivation sample 2010-2015, replication sample 2015-2017), then combined these into a total cohort for final cluster analyses. We described differences in medications, imaging and outcomes. RESULTS: Patients clustered into 7 subgroups. The low comorbidity subgroup (n = 3052, 27.5%) had no comorbidities. The DM-HF-Pulm subgroup had prevalent diabetes, heart failure and chronic lung disease (n = 1710, 15.4%). One disease category defined each remaining subgroup, as follows: pulmonary (n = 1621, 14.6%), diabetes (n = 1281, 11.6%), heart failure (n = 1370, 12.4%), dementia (n = 1038, 9.4%) and cancer (n = 1013, 9.1%). Corticosteroid use ranged from 11.5% to 64.9% in the dementia and pulmonary subgroups, respectively. Piperacillin-tazobactam use ranged from 9.1% to 28.0% in the pulmonary and cancer subgroups, respectively. The use of thoracic computed tomography ranged from 5.7% to 36.3% in the dementia and cancer subgroups, respectively. Adjusting for patient factors, the risk of in-hospital death was greater in the cancer (adjusted odds ratio [OR] 3.12, 95% confidence interval [CI] 2.44-3.99), dementia (adjusted OR 1.57, 95% CI 1.05-2.35), heart failure (adjusted OR 1.66, 95% CI 1.35-2.03) and DM-HF-Pulm subgroups (adjusted OR 1.35, 95% CI 1.12-1.61), and lower in the diabetes subgroup (adjusted OR 0.67, 95% CI 0.50-0.89), compared with the low comorbidity group. INTERPRETATION: Patients admitted to hospital with CAP cluster into clinically recognizable subgroups based on coexisting conditions. Clinical care and outcomes vary among these subgroups with little evidence to guide decision-making, highlighting opportunities for research to personalize care.

Factors associated with lung function response with oral antibiotic treatment of pulmonary exacerbations in cystic fibrosis.

Pulmonary exacerbations treated with oral antibiotics (oPEx) have a significant effect on lung function decline in people with cystic fibrosis (CF). However, factors associated with lung function response with oPExs are not well defined. We performed a retrospective cohort study of pediatric and adult patients with CF followed in the Toronto CF Database. Lung function response was measured both as the change in forced expiratory volume in 1 second (FEV1) from Day 0 of antibiotic therapy to end of treatment as well as from baseline to end of treatment. Drop from baseline to Day 0 FEV1 was strongly associated with lung function response (p<0.001). Greater FEV1 improvements were associated with longer antibiotic treatment durations. Older, female patients had less improvements in FEV1 at end of treatment compared to younger, male patients.

Nursing home crowding and its association with outbreak-associated respiratory infection in Ontario, Canada before the COVID-19 pandemic (2014-19): a retrospective cohort study.

BACKGROUND: Studies conducted during the COVID-19 pandemic have shown that crowding in nursing homes is associated with high incidence of SARS-CoV-2 infections, but this effect has not been shown for other respiratory pathogens. We aimed to measure the association between crowding in nursing homes and outbreak-associated respiratory infection incidence and related mortality before the COVID-19 pandemic. METHODS: We conducted a retrospective cohort study of nursing homes in Ontario, Canada. We identified, characterised, and selected nursing homes through the Ontario Ministry of Long-Term Care datasets. Nursing homes that were not funded by the Ontario Ministry of Long-Term Care and homes that closed before January, 2020 were excluded. Outcomes consisting of respiratory infection outbreaks were obtained from the Integrated Public Health Information System of Ontario. The crowding index equalled the mean number of residents per bedroom and bathroom. The primary outcomes were the incidence of outbreak-associated infections and mortality per 100 nursing home residents per year. We examined the incidence of infections and deaths as a function of the crowding index by use of negative binomial regression with adjustment for three home characteristics (ie, ownership, number of beds, and region) and nine mean resident characteristics (ie, age, female sex, dementia, diabetes, chronic heart failure, renal failure, cancer, chronic obstructive pulmonary disease, and activities of daily living score). FINDINGS: Between Sept 1, 2014, and Aug 31, 2019, 5107 respiratory infection outbreaks in 588 nursing homes were recorded, of which 4921 (96·4%), involving 64 829 cases of respiratory infection and 1969 deaths, were included in this analysis. Nursing homes with a high crowding index had higher incidences of respiratory infection (26·4% vs 13·8%; adjusted rate ratio per one resident per room increase in crowding 1·89 [95% CI 1·64-2·17]) and mortality (0·8% vs 0·4%; 2·34 [1·88-2·92]) than did homes with a low crowding index. INTERPRETATION: Respiratory infection and mortality rates were higher in nursing homes with high crowding index than in homes with low crowding index, and the association was consistent across various respiratory pathogens. Decreasing crowding is an important safety target beyond the COVID-19 pandemic to help to promote resident wellbeing and decrease the transmission of prevalent respiratory pathogens. FUNDING: None.

Remdesivir for the treatment of patients in hospital with COVID-19 in Canada: a randomized controlled trial.

BACKGROUND: The role of remdesivir in the treatment of patients in hospital with COVID-19 remains ill defined in a global context. The World Health Organization Solidarity randomized controlled trial (RCT) evaluated remdesivir in patients across many countries, with Canada enrolling patients using an expanded data collection format in the Canadian Treatments for COVID-19 (CATCO) trial. We report on the Canadian findings, with additional demographics, characteristics and clinical outcomes, to explore the potential for differential effects across different health care systems. METHODS: We performed an open-label, pragmatic RCT in Canadian hospitals, in conjunction with the Solidarity trial. We randomized patients to 10 days of remdesivir (200 mg intravenously [IV] on day 0, followed by 100 mg IV daily), plus standard care, or standard care alone. The primary outcome was in-hospital mortality. Secondary outcomes included changes in clinical severity, oxygen- and ventilator-free days (at 28 d), incidence of new oxygen or mechanical ventilation use, duration of hospital stay, and adverse event rates. We performed a priori subgroup analyses according to duration of symptoms before enrolment, age, sex and severity of symptoms on presentation. RESULTS: Across 52 Canadian hospitals, we randomized 1282 patients between Aug. 14, 2020, and Apr. 1, 2021, to remdesivir (n = 634) or standard of care (n = 648). Of these, 15 withdrew consent or were still in hospital, for a total sample of 1267 patients. Among patients assigned to receive remdesivir, in-hospital mortality was 18.7%, compared with 22.6% in the standard-of-care arm (relative risk [RR] 0.83 (95% confidence interval [CI] 0.67 to 1.03), and 60-day mortality was 24.8% and 28.2%, respectively (95% CI 0.72 to 1.07). For patients not mechanically ventilated at baseline, the need for mechanical ventilation was 8.0% in those assigned remdesivir, and 15.0% in those receiving standard of care (RR 0.53, 95% CI 0.38 to 0.75). Mean oxygen-free and ventilator-free days at day 28 were 15.9 (± standard deviation [SD] 10.5) and 21.4 (± SD 11.3) in those receiving remdesivir and 14.2 (± SD 11) and 19.5 (± SD 12.3) in those receiving standard of care (p = 0.006 and 0.007, respectively). There was no difference in safety events of new dialysis, change in creatinine, or new hepatic dysfunction between the 2 groups. INTERPRETATION: Remdesivir, when compared with standard of care, has a modest but significant effect on outcomes important to patients and health systems, such as the need for mechanical ventilation. Trial registration: ClinicalTrials.gov, no. NCT04330690.

Testing for non-inferior mortality: a systematic review of non-inferiority margin sizes and trial characteristics.

OBJECTIVE: To describe the size and variability of non-inferiority margins used in non-inferiority trials of medications with primary outcomes involving mortality, and to examine the association between trial characteristics and non-inferiority margin size. DESIGN: Systematic review. DATA SOURCES: Medline, Medline In Process, Medline Epub Ahead of Print and Embase Classic+Embase databases from January 1989 to December 2019. ELIGIBILITY CRITERIA: Prospective non-inferiority randomised controlled trials comparing pharmacological therapies, with primary analyses for non-inferiority and primary outcomes involving mortality alone or as part of a composite outcome. Trials had to prespecify non-inferiority margins as absolute risk differences or relative to risks of outcome and provide a baseline risk of primary outcome in the control intervention. RESULTS: 3992 records were screened, 195 articles were selected for full text review and 111 articles were included for analyses. 82% of trials were conducted in thrombosis, infectious diseases or oncology. Mortality was the sole primary outcome in 23 (21%) trials, and part of a composite primary outcome in 88 (79%) trials. The overall median non-inferiority margin was an absolute risk difference of 9% (IQR 4.2%-10%). When non-inferiority margins were expressed relative to the baseline risk of primary outcome in control groups, the median relative non-inferiority margin was 1.5 (IQR 1.3-1.7). In multivariable regression analyses examining the association between trial characteristics (medical specialty, inclusion of paediatric patients, mortality as a sole or part of a composite primary outcome, presence of industry funding) and non-inferiority margin size, only medical specialty was significantly associated with non-inferiority margin size. CONCLUSION: Absolute and relative non-inferiority margins used in published trials comparing medications are large, allowing conclusions of non-inferiority in the context of large differences in mortality. Accepting the potential for large increases in outcomes involving mortality while declaring non-inferiority is a challenging methodological issue in the conduct of non-inferiority trials.

Long-Term Sustainability and Acceptance of Antimicrobial Stewardship in Intensive Care: A Retrospective Cohort Study.

OBJECTIVES: To evaluate long-term uptake of an antimicrobial stewardship audit-and-feedback program along with potential predictors of stewardship suggestions and acceptance across a diverse ICU population. DESIGN: A retrospective cohort study. SETTING: An urban, academic medical institution. PATIENTS: Patients admitted to an ICU who received an antimicrobial stewardship program suggestion between June 2010 and September 2019. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The antimicrobial stewardship program provided 7,749 antibiotic assessments over the study period and made a suggestion to alter therapy in 2,826 (36%). Factors associated with a higher likelihood of receiving a suggestion to alter therapy included shorter hospital length of stay prior to antimicrobial stewardship program review (odds ratio 1.15 for ≤ 5 d; 95% CI 1.00-1.32), admission to cardiovascular (1.37; 1.06-1.76) or burn surgery (1.88; 1.50-2.36) versus general medicine, and preceding duration of antibiotic use greater than 5 days (1.33; 1.10-1.60). Assessment of aminoglycosides (2.91; 1.85-4.89), carbapenems (1.93; 1.54-2.41), and vancomycin (2.71; 2.19-3.36) versus ceftriaxone was more likely to result in suggestions to alter therapy. The suggestion acceptance rate was 67% (1,895/2,826), which was stable throughout the study period. Admission to a level 3 ICU was associated with higher likelihood of acceptance of suggestions (1.50; 1.14-1.97). Factors associated with lower acceptance rates were admission to burn surgery (0.64; 0.45-0.91), treatment of pneumonia (0.64; 0.42-0.97 for community-acquired and 0.65; 0.44-0.94 for ventilator-acquired), unknown source of infection (0.66; 0.48-0.92), and suggestion types of "narrow spectrum" (0.65; 0.45-0.94), "change formulation of antibiotic" (0.42; 0.27-0.64), or "change agent of therapy" (0.63; 0.40-0.97) versus "change of dose". CONCLUSIONS: An antimicrobial stewardship program implemented over a decade resulted in sustained suggestion and acceptance rates. These findings support the need for a persistent presence of audit-and-feedback over time with more frequent suggestions to alter potentially nephrotoxic agents, increased efforts toward specialized care units, and further work approaching infectious sources that are typically treated without pathogen confirmation and identification.

Incidence of Hospitalizations and Emergency Department Visits for Herpes Zoster in Immunocompromised and Immunocompetent Adults in Ontario, Canada, 2002-2016.

BACKGROUND: Immunocompromised adults are at .increased risk of herpes zoster (HZ) infection and related complications. We aimed to assess the incidence of hospital-attended HZ (ie, seen in hospital or emergency department) in immunocompromised populations and compare it to immunocompetent populations. METHODS: We calculated incidence rates (IRs) of hospital-attended HZ in Ontario, Canada, between 1 April 2002 and 31 August 2016 in adults ≥18 years of age categorized as immunocompromised or immunocompetent. We repeated these analyses by type of immunocompromising condition and provided incidence rate ratios (IRRs) comparing to immunocompetent adults. We also calculated IRs and IRRs of HZ complications by immunocompromised status. RESULTS: There were 135 206 incident cases of hospital-attended HZ during the study period. Immunocompromised adults accounted for 13% of these cases despite representing 3% of the population. The risk of hospital-attended HZ was higher for immunocompromised adults compared with immunocompetent adults (IRR, 2.9 [95% confidence interval {CI}, 2.9-3.0]) and ranged across type of immunocompromising conditions, from 2.6 (95% CI, 2.6-2.7) in those with a solid tumor malignancy to 12.3 (95% CI, 11.3-13.2) in those who had undergone hematopoietic stem cell transplant. The risk of any HZ complication was higher in immunocompromised adults (IRR, 3.6 [95% CI, 3.5-3.7]) and highest for disseminated zoster (IRR, 32.8 [95% CI, 27.8-38.6]). CONCLUSIONS: The risk of hospital-attended HZ and related complications was higher in immunocompromised populations compared with immunocompetent populations. Our findings underscore the high-risk nature of this population and the potential benefits that may be realized through HZ vaccination.

Case conferences for infective endocarditis: A quality improvement initiative.

BACKGROUND: A multidisciplinary approach has been recommended for the management of patients with infective endocarditis. We evaluated the impact of multidisciplinary case conferences on morbidity, mortality, and quality of care for these patients. METHODS: We conducted a quasi-experimental study of consecutive patients admitted for infective endocarditis before (2013/10/1-2015/10/12, n = 97) and after (2015/10/13-2017/11/30, n = 80) implementation of case conferences to discuss medical and surgical management. These occurred as face-to-face discussions or electronically (for non-complex patients), and included physicians from cardiac surgery, cardiology, critical care, infectious diseases and neurology. We assessed process-of-care and clinical outcomes, with the primary outcome being complications up to 90 days after hospital discharge. RESULTS: A case conference was held for 80/80 (100%) of patients in the post-intervention group. After the intervention, more patients received inpatient cardiology assessment (81.3% [post-intervention] vs. 63.9% [pre-intervention], p = 0.01), and more patients with definite infective endocarditis underwent cardiac surgery treatment (44.6% vs. 21.7%, p = 0.007). All pre-intervention and post-intervention patients received guideline-concordant antimicrobial therapy. There was no difference in rates of complications (40.0% vs. 51.5%, p = 0.13) or mortality up to 90 days after hospital discharge (26.3% vs. 17.5%, p = 0.20). In multivariable analyses, the intervention was not associated with differences in mortality (odds ratio 1.87, 95% confidence interval 0.88-3.99) or a composite measure of complications and mortality (odds ratio 0.86, 95% confidence interval 0.46-1.58). CONCLUSION: We successfully implemented a standardized multidisciplinary case conference protocol for patients with infective endocarditis. This intervention had no detectable effect on complications or mortality.

Factors Associated with Choice and Success of One- Versus Two-Stage Revision Arthroplasty for Infected Hip and Knee Prostheses.

BACKGROUND: Prosthetic joint infections (PJI) of hip and knee arthroplasties are becoming increasingly common with an aging population and an increasing demand for these procedures. Despite attempts at standardization, medical and surgical approaches vary widely among practitioners. QUESTIONS/PURPOSES: We first sought to determine if there were specific factors associated with choice of one- versus two-stage revision. Then we investigated whether the type of revision approach influenced clinical treatment success. Finally, among two-stage revisions, we assessed if an antibiotic holiday prior to the second procedure affected clinical treatment success. METHODS: We retrospectively reviewed patients who had revision surgery for infection of a hip or knee arthroplasty between January 1, 2000, and December 31, 2013, at the Sunnybrook Health Sciences Centre and the Holland Orthopedic and Arthritic Centre. PJI cases were identified using the Ontario Joint Replacement Registry. Infection was defined by gross intraoperative evidence of infection, positive intraoperative culture(s), and/or sinus tract prior to operation. The primary outcome was treatment failure at 1 year after revision surgery based on requirement for further surgery, ongoing infection, and/or continuous suppressive antibiotics. RESULTS: Of 110 eligible patients identified, 35 patients had a one-stage and 75 patients had a two-stage revision. Choice of a one-stage approach was most influenced by particular surgeon preference and was more likely for hip revision versus knee revision (OR 3.39 (95%CI 1.85-6.23). There was no statistical difference in clinical treatment success rate between one-stage (33/35; 94.2% success) and two-stage revision (63/75; 84%; p = 0.13). Enterococcus spp. (21 versus 3%; p = 0.027) and Peptostreptococcus spp. (14 versus 1%; p = 0.042) were more common among clinical treatment failures than successes, with a trend towards the same for Staphylococcus aureus (29 versus 9%; p = 0.06). Additionally, treatment success was not influenced by whether the patient had an antibiotic holiday with a two-stage revision. CONCLUSION: Our findings confirm the uncertainty of surgical strategy for treatment of PJI in hip and knee arthroplasty. Superiority of one- versus two-stage revision and the value of antibiotic-free periods prior to definitive revision remain unclear. Large prospective studies or randomized controlled trials are needed to inform best practice for treatment of these complex clinical problems.

Frailty and Potentially Inappropriate Medication Use at Nursing Home Transition.

BACKGROUND/OBJECTIVES: To estimate the prevalence of potentially inappropriate medication (PIM) use among older adults with cognitive impairment or dementia prior to and following admission to nursing homes and in relation to frailty. DESIGN: Retrospective cohort study using health administrative databases. SETTING: Ontario, Canada. PARTICIPANTS: 41,351 individuals with cognitive impairment or dementia, aged 66+ years newly admitted to nursing home between 2011 and 2014. MEASUREMENTS: PIMs were defined with 2015 Beers Criteria and included antipsychotics, H2 -receptor antagonists, benzodiazepines, and drugs with strong anticholinergic properties. Medication information was obtained at nursing home admission and in the subsequent 180 days. Multivariable Cox proportional-hazards models were used to assess the impact of frailty status (determined by a 72-item frailty index) on the hazard of starting and discontinuing PIMs. RESULTS: At admission, 44% of residents with cognitive impairment or dementia were on a PIM and prevalence varied by frailty (38.7% non-frail, 42.8% pre-frail, and 48.1% frail, P < .001). Following admission, many residents discontinued PIMs (23.5% for antipsychotics, 49.3% benzodiazepines, 32.2% anticholinergics, and 30.9% H2 -receptor antagonists). However, PIMs were also introduced with 10.9% newly started on antipsychotics, benzodiazepines (10.1%), anticholinergics (6.6%), and H2 -receptor antagonists (1.2%). After adjustment for other characteristics, frail residents had a similar risk of PIM discontinuation as non-frail residents except for anticholinergics (HR = 1.21, 95% CI 1.06-1.39) but were more likely to be newly prescribed benzodiazepines (HR = 1.32, 95% CI 1.20-1.44), antipsychotics (HR = 1.36, 1.23-1.49), and anticholinergics (HR = 1.34, 95% CI 1.20-1.50). CONCLUSION: Many residents with cognitive impairment or dementia enter nursing homes on PIMs. PIMs are more likely to be started in frail individuals following admission. Interventions to support deprescribing of PIMs should be implemented targeting frail individuals during the transition to nursing home.

Adult-onset opsoclonus-myoclonus syndrome due to West Nile Virus treated with intravenous immunoglobulin.

A 63-year-old female with no significant past medical history was presented with a 5-day history of progressive opsoclonus-myoclonus, headaches, and fevers. Her workup was significant only for positive West-Nile Virus serum serologies. She received a 2-day course of intravenous immunoglobulin (IvIG). At an 8-week follow up, she had a complete neurological remission. Adult-onset opsoclonus-myoclonus syndrome is a rare condition for which paraneoplastic and infectious causes have been attributed. To our knowledge, this is the first case reported of opsoclonus-myoclonus secondary to West-Nile Virus treated with intravenous immunoglobulin monotherapy.

Accuracy of administrative data for identification of patients with infective endocarditis.

BACKGROUND: Infective endocarditis is associated with high morbidity and mortality rates that have plateaued over recent decades. Research to improve outcomes for these patients is limited by the rarity of this condition. Therefore, we sought to validate administrative database codes for the diagnosis of infective endocarditis. METHODS: We conducted a retrospective validation study of International Classification of Diseases (ICD-10-CM) codes for infective endocarditis against clinical Duke criteria (definite and probable) at a large acute care hospital between October 1, 2013 and June 30, 2015. To identify potential cases missed by ICD-10-CM codes, we also screened the hospital's valvular heart surgery database and the microbiology laboratory database (the latter for patients with bacteremia due to organisms commonly causing endocarditis). RESULTS: Using definite Duke criteria or probable criteria with clinical suspicion as the reference standard, the ICD-10-CM codes had a sensitivity (SN) of 0.90 (95% confidence interval (CI), 0.81-0.95), specificity (SP) of 1 (95% CI, 1-1), positive predictive value (PPV) of 0.78 (95% CI, 0.68-0.85) and negative predictive value (NPV) of 1 (95% CI, 1-1). Restricting the case definition to definite Duke criteria resulted in an increase in SN to 0.95 (95% CI, 0.86-0.99) and a decrease in PPV to 0.6 (95% CI, 0.49-0.69), with no change in specificity. CONCLUSION: ICD-10-CM codes can accurately identify patients with infective endocarditis, and so administrative databases offer a potential means to study this infection over large jurisdictions, and thereby improve the prediction, diagnosis, treatment and prevention of this rare but serious infection.

Administrative data measured surgical site infection probability within 30 days of surgery in elderly patients.

OBJECTIVES: Elderly patients are inordinately affected by surgical site infections (SSIs). This study derived and internally validated a model that used routinely collected health administrative data to measure the probability of SSI in elderly patients within 30 days of surgery. STUDY DESIGN AND SETTING: All people exceeding 65 years undergoing surgery from two hospitals with known SSI status were linked to population-based administrative data sets in Ontario, Canada. We used bootstrap methods to create a multivariate model that used health administrative data to predict the probability of SSI. RESULTS: Of 3,436 patients, 177 (5.1%) had an SSI. The Elderly SSI Risk Model included six covariates: number of distinct physician fee codes within 30 days of surgery; presence or absence of a postdischarge prescription for an antibiotic; presence or absence of three diagnostic codes; and a previously derived score that gauged SSI risk based on procedure codes. The model was highly explanatory (Nagelkerke's R2, 0.458), strongly discriminative (C statistic, 0.918), and well calibrated (calibration slope, 1). CONCLUSION: Health administrative data can effectively determine 30-day risk of SSI risk in elderly patients undergoing a broad assortment of surgeries. External validation is necessary before this can be routinely used to monitor SSIs in the elderly.

Derivation and Validation of the Surgical Site Infections Risk Model Using Health Administrative Data.

OBJECTIVE Surgical site infections (SSIs) are common hospital-acquired infections. Tracking SSIs is important to monitor their incidence, and this process requires primary data collection. In this study, we derived and validated a method using health administrative data to predict the probability that a person who had surgery would develop an SSI within 30 days. METHODS All patients enrolled in the National Surgical Quality Improvement Program (NSQIP) from 2 sites were linked to population-based administrative datasets in Ontario, Canada. We derived a multivariate model, stratified by surgical specialty, to determine the independent association of SSI status with patient and hospitalization covariates as well as physician claim codes. This SSI risk model was validated in 2 cohorts. RESULTS The derivation cohort included 5,359 patients with a 30-day SSI incidence of 6.0% (n=118). The SSI risk model predicted the probability that a person had an SSI based on 7 covariates: index hospitalization diagnostic score; physician claims score; emergency visit diagnostic score; operation duration; surgical service; and potential SSI codes. More than 90% of patients had predicted SSI risks lower than 10%. In the derivation group, model discrimination and calibration was excellent (C statistic, 0.912; Hosmer-Lemeshow [H-L] statistic, P=.47). In the 2 validation groups, performance decreased slightly (C statistics, 0.853 and 0.812; H-L statistics, 26.4 [P=.0009] and 8.0 [P=.42]), but low-risk patients were accurately identified. CONCLUSION Health administrative data can effectively identify postoperative patients with a very low risk of surgical site infection within 30 days of their procedure. Records of higher-risk patients can be reviewed to confirm SSI status.

Red Flags for Necrotizing Fasciitis: A Case Control Study.

OBJECTIVE: to examine the diagnostic accuracy of traditional 'red flags' for necrotizing fasciitis (NF) on history and physical examination. METHODS: retrospective study of all cases of NF admitted to a large tertiary care hospital between January 1 2004 and December 31 2013, each matched to two control patients with cellulitis. We determined the diagnostic test characteristics of clinical features for distinguishing NF from cellulitis, with emphasis on positive (LR+) and negative (LR-) likelihood ratios. RESULTS: There were no individual findings with sufficient sensitivity to rule out NF (sensitivity ≤ 85% and LR- ≥ 0.5 for all findings). The clinical features that most significantly increased the odds of NF were recent surgery (LR+ 7.0) pain-out-of-proportion (LR+ 4.5), diarrhea (LR+ 6.0), hypotension (LR+ 8.0), altered mental status (LR+ 3.3), erythema progressing beyond margins (LR+3.1), fluctuance (LR+ 5.0), hemorrhagic bullae (LR+ 8.0) and skin necrosis (LR+ 30.0). Each individual finding conferred low sensitivity, but absence of all nine ruled out NF (LR- 0.04). The presence of >=3 findings ruled in NF (LR+ undefined). CONCLUSIONS: When considered together, the traditional 'red flags' for NF may be sufficient to rule in or rule out the diagnosis. If future prospective studies validate these findings, there will be a potential opportunity to expedite NF diagnosis and improve patient outcomes.

Reducing antimicrobial therapy for asymptomatic bacteriuria among noncatheterized inpatients: a proof-of-concept study.

This proof-of-concept study demonstrates that no longer routinely reporting urine culture results from noncatheterized medical and surgical inpatients can greatly reduce unnecessary antimicrobial therapy for asymptomatic bacteriuria without significant additional laboratory workload. Larger studies are needed to confirm the generalizability, safety, and sustainability of this model of care.

Antibiotic resistance of ocular surface flora with repeated use of a topical antibiotic after intravitreal injection.

IMPORTANCE: Treatment with intravitreal (IVT) injections has increased during the last several years as evidence has accumulated demonstrating the efficacy of anti-vascular endothelial growth factor agents in the treatment of neovascular age-related macular degeneration (AMD) and various retinal vascular diseases. Although IVT injections are generally safe, infectious endophthalmitis is a rare but devastating complication, and the risk of morbidity and vision loss from endophthalmitis is high. OBJECTIVE: To examine the change in antibiotic resistance of ocular surface flora with repeated prophylactic use of antibiotics after IVT injection for AMD. DESIGN AND SETTING: Prospective, nonrandomized cohort study in 2 tertiary academic hospitals. PARTICIPANTS: Patients 65 years and older with newly diagnosed AMD were recruited by 7 retinal specialists from July 1, 2010, through December 31, 2011. INTERVENTION: The study group received topical moxifloxacin hydrochloride for 3 days after each monthly IVT injection. MAIN OUTCOME MEASURE: Resistance to moxifloxacin and ceftazidime in cultured isolates at baseline and monthly for 3 months by change in minimal inhibitory concentration (MIC) of culture isolates was studied. RESULTS: The study group consisted of 84 patients, and the control group had 94 patients. In the study group, the baseline adjusted MIC increased (from 1.04 to 1.25 µg/mL; P = .01) as did the MIC for 50% of isolates (MIC50) (from 0.64 to 1.00 µg/mL) and the MIC for 90% of isolates (MIC90) (from 0.94 to 4.00 µg/mL). In both groups, the culture-positive rate did not change significantly when adjusted for baseline. No significant change was found in the MIC level, culture-positive rate, MIC50 level, and MIC90 level in the control group. Subgroup analysis found diabetes mellitus to be noncontributory to both the MIC and culture-positive rate. No endophthalmitis or adverse events were reported. CONCLUSIONS AND RELEVANCE: Repeated use of topical moxifloxacin after IVT injection significantly increases antibiotic resistance of ocular surface flora. We recommend that routine use of prophylactic antibiotics after IVT injection be discouraged. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01181713.

The impact of infection on population health: results of the Ontario burden of infectious diseases study.

BACKGROUND: Evidence-based priority setting is increasingly important for rationally distributing scarce health resources and for guiding future health research. We sought to quantify the contribution of a wide range of infectious diseases to the overall infectious disease burden in a high-income setting. METHODOLOGY/PRINCIPAL FINDINGS: We used health-adjusted life years (HALYs), a composite measure comprising premature mortality and reduced functioning due to disease, to estimate the burden of 51 infectious diseases and associated syndromes in Ontario using 2005-2007 data. Deaths were estimated from vital statistics data and disease incidence was estimated from reportable disease, healthcare utilization, and cancer registry data, supplemented by local modeling studies and national and international epidemiologic studies. The 51 infectious agents and associated syndromes accounted for 729 lost HALYs, 44.2 deaths, and 58,987 incident cases per 100,000 population annually. The most burdensome infectious agents were: hepatitis C virus, Streptococcus pneumoniae, Escherichia coli, human papillomavirus, hepatitis B virus, human immunodeficiency virus, Staphylococcus aureus, influenza virus, Clostridium difficile, and rhinovirus. The top five, ten, and 20 pathogens accounted for 46%, 67%, and 75% of the total infectious disease burden, respectively. Marked sex-specific differences in disease burden were observed for some pathogens. The main limitations of this study were the exclusion of certain infectious diseases due to data availability issues, not considering the impact of co-infections and co-morbidity, and the inability to assess the burden of milder infections that do not result in healthcare utilization. CONCLUSIONS/SIGNIFICANCE: Infectious diseases continue to cause a substantial health burden in high-income settings such as Ontario. Most of this burden is attributable to a relatively small number of infectious agents, for which many effective interventions have been previously identified. Therefore, these findings should be used to guide public health policy, planning, and research.