The Effect of COVID-19 Vaccination on Outpatient Antibiotic Prescribing in Older Adults: A Self-Controlled Risk-Interval Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) vaccination has been associated with reduced outpatient antibiotic prescribing among older adults with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We assessed the impact of COVID-19 vaccination on outpatient antibiotic prescribing in the broader population of older adults, regardless of SARS-CoV-2 infection status. METHODS: We included adults aged ≥65 years who received their first, second, and/or third COVID-19 vaccine dose from December 2020 to December 2022. We used a self-controlled risk-interval design and included cases who received an antibiotic prescription 2-6 weeks before vaccination (pre-vaccination or control interval) or after vaccination (post-vaccination or risk interval). We used conditional logistic regression to estimate the odds of being prescribed (1) any antibiotic, (2) a typical "respiratory" infection antibiotic, or (3) a typical "urinary tract" infection antibiotic (negative control) in the post-vaccination interval versus the pre-vaccination interval. We accounted for temporal changes in antibiotic prescribing using background monthly antibiotic prescribing counts. RESULTS: 469 923 vaccine doses met inclusion criteria. The odds of receiving any antibiotic or a respiratory antibiotic prescription were lower in the post-vaccination versus pre-vaccination interval (aOR, .973; 95% CI, .968-.978; aOR, .961; 95% CI, .953-.968, respectively). There was no association between vaccination and urinary antibiotic prescriptions (aOR, .996; 95% CI, .987-1.006). Periods with high (>10%) versus low (<5%) SARS-CoV-2 test positivity demonstrated greater reductions in antibiotic prescribing (aOR, .875; 95% CI, .845-.905; aOR, .996; 95% CI, .989-1.003, respectively). CONCLUSIONS: COVID-19 vaccination was associated with reduced outpatient antibiotic prescribing in older adults, especially during periods of high SARS-CoV-2 circulation.

Association between infectious diseases consultation and mortality in hospitalized patients with Gram-negative bloodstream infection: a retrospective population-wide cohort study.

OBJECTIVES: Data supporting routine infectious diseases (ID) consultation in Gram-negative bloodstream infection (GN-BSI) are limited. We evaluated the association between ID consultation and mortality in patients with GN-BSI in a retrospective population-wide cohort study in Ontario using linked health administrative databases. METHODS: Hospitalized adult patients with GN-BSI between April 2017 and December 2021 were included. The primary outcome was time to all-cause mortality censored at 30 days, analyzed using a mixed effects Cox proportional hazards model with hospital as a random effect. ID consultation 1-10 days after the first positive blood culture was treated as a time-varying exposure. RESULTS: Of 30,159 patients with GN-BSI across 53 hospitals, 11,013 (36.5%) received ID consultation. Median prevalence of ID consultation for patients with GN-BSI across hospitals was 35.0% with wide variability (range 2.7-76.1%, interquartile range 19.6-41.1%). 1041 (9.5%) patients who received ID consultation died within 30 days, compared to 1797 (9.4%) patients without ID consultation. In the fully-adjusted multivariable model, ID consultation was associated with mortality benefit (adjusted HR 0.82, 95% CI 0.77-0.88, p < 0.0001; translating to absolute risk reduction of -3.8% or NNT of 27). Exploratory subgroup analyses of the primary outcome showed that ID consultation could have greater benefit in patients with high-risk features (nosocomial infection, polymicrobial or non-Enterobacterales infection, antimicrobial resistance, or non-urinary tract source). CONCLUSIONS: Early ID consultation was associated with reduced mortality in patients with GN-BSI. If resources permit, routine ID consultation for this patient population should be considered to improve patient outcomes.

Does adjunctive clindamycin have a role in Staphylococcus aureus bacteremia? A protocol for the adjunctive treatment domain of the S. aureus Network Adaptive Platform (SNAP) randomized controlled trial.

INTRODUCTION: The use of adjunctive antibiotics directed against exotoxin production in Staphylococcus aureus bacteremia (SAB) is widespread, and is recommended in many guidelines, but there is limited evidence underpinning this. Existing guidelines are based on the theoretical premise of toxin suppression, as many strains of S. aureus produce toxins such as leucocidins (e.g., Panton-Valentine Leucocidin (PVL), toxic shock syndrome toxin 1 (TSST-1), exfoliative toxins, and various enterotoxins). Many clinicians therefore believe that limiting exotoxin production release by S. aureus could reduce its virulence and improve clinical outcomes. Clindamycin, a protein synthesis inhibitor antibiotic, is commonly used for this purpose. We report the domain-specific protocol, embedded in a large adaptive, platform trial, seeking to definitively answer this question. METHODS AND ANALYSIS: The Staphylococcus aureus Network Adaptive Platform (SNAP) trial is a pragmatic, randomized, multi-center adaptive platform trial that aims to compare different SAB therapies, simultaneously, for 90-day mortality. The adjunctive treatment domain aims to test the effectiveness of adjunctive antibiotics, initially comparing clindamycin to no adjunctive antibiotic, but future adaptations may include other agents. Individuals will be randomized to receive either five days of adjunctive clindamycin (or lincomycin) or no adjunctive antibiotic therapy alongside standard of care antibiotics. Most participants with SAB (within 72hr of index blood culture and not contraindicated) will be eligible to participate in this domain. Prespecified analyses are defined in the statistical appendix to the core protocol and domain-specific secondary analyses will be adjusted for resistance to clindamycin, disease phenotype (complicated or uncomplicated SAB) and PVL-positive isolate.

Epidemiology and clinical relevance of persistent bacteraemia in patients with Gram-negative bloodstream infection: a retrospective cohort study.

OBJECTIVES: The risk factors and outcomes associated with persistent bacteraemia in Gram-negative bloodstream infection (GN-BSI) are not well described. We conducted a follow-on analysis of a retrospective population-wide cohort to characterize persistent bacteraemia in patients with GN-BSI. METHODS: We included all hospitalized patients >18 years old with GN-BSI between April 2017 and December 2021 in Ontario who received follow-up blood culture (FUBC) 2-5 days after the index positive blood culture. Persistent bacteraemia was defined as having a positive FUBC with the same Gram-negative organism as the index blood culture. We identified variables independently associated with persistent bacteraemia in a multivariable logistic regression model. We evaluated whether persistent bacteraemia was associated with increased odds of 30- and 90-day all-cause mortality using multivariable logistic regression models adjusted for potential confounders. RESULTS: In this study, 8807 patients were included; 600 (6.8%) had persistent bacteraemia. Having a permanent catheter, antimicrobial resistance, nosocomial infection, ICU admission, respiratory or skin and soft tissue source of infection, and infection by a non-fermenter or non-Enterobacterales/anaerobic organism were associated with increased odds of having persistent bacteraemia. The 30-day mortality was 17.2% versus 9.6% in those with and without persistent bacteraemia (aOR 1.65, 95% CI 1.29-2.11), while 90-day mortality was 25.5% versus 16.9%, respectively (aOR 1.53, 95% CI 1.24-1.89). Prevalence and odds of developing persistent bacteraemia varied widely depending on causative organism. CONCLUSIONS: Persistent bacteraemia is uncommon in GN-BSI but is associated with poorer outcomes. A validated risk stratification tool may be useful to identify patients with persistent bacteraemia.

Coronavirus Disease 2019 Vaccination Is Associated With Reduced Outpatient Antibiotic Prescribing in Older Adults With Confirmed Severe Acute Respiratory Syndrome Coronavirus 2: A Population-Wide Cohort Study.

BACKGROUND: Antibiotics are frequently prescribed unnecessarily in outpatients with coronavirus disease 2019 (COVID-19). We sought to evaluate factors associated with antibiotic prescribing in outpatients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: We performed a population-wide cohort study of outpatients aged ≥66 years with polymerase chain reaction-confirmed SARS-CoV-2 from 1 January 2020 to 31 December 2021 in Ontario, Canada. We determined rates of antibiotic prescribing within 1 week before (prediagnosis) and 1 week after (postdiagnosis) reporting of the positive SARS-CoV-2 result, compared to a self-controlled period (baseline). We evaluated predictors of prescribing, including a primary-series COVID-19 vaccination, in univariate and multivariable analyses. RESULTS: We identified 13 529 eligible nursing home residents and 50 885 eligible community-dwelling adults with SARS-CoV-2 infection. Of the nursing home and community residents, 3020 (22%) and 6372 (13%), respectively, received at least 1 antibiotic prescription within 1 week of a SARS-CoV-2 positive result. Antibiotic prescribing in nursing home and community residents occurred, respectively, at 15.0 and 10.5 prescriptions per 1000 person-days prediagnosis and 20.9 and 9.8 per 1000 person-days postdiagnosis, higher than the baseline rates of 4.3 and 2.5 prescriptions per 1000 person-days. COVID-19 vaccination was associated with reduced prescribing in nursing home and community residents, with adjusted postdiagnosis incidence rate ratios (95% confidence interval) of 0.7 (0.4-1) and 0.3 (0.3-0.4), respectively. CONCLUSIONS: Antibiotic prescribing was high and with little or no decline following SARS-CoV-2 diagnosis but was reduced in COVID-19-vaccinated individuals, highlighting the importance of vaccination and antibiotic stewardship in older adults with COVID-19.

A Meta-Analysis to Derive Population-Based Quality Benchmarks of the Incidence of Surgical Site Infection after Lower Limb Revascularization Surgery.

BACKGROUND: The reported incidence of surgical site infection (SSI) after lower limb revascularization surgery varies. We conducted a systematic review and meta-analysis of population-based studies reporting the incidence of SSI in adults who underwent these surgeries in high-income countries to derive SSI quality benchmarks. METHODS: We searched MEDLINE, EMBASE, CENTRAL, and Evidence-Based Medicine Reviews (inception-to-April 28th, 2022) for population-based studies estimating the cumulative incidence of SSI among adults who underwent lower limb revascularization surgery for peripheral artery disease (PAD) in high-income countries. Two investigators independently screened abstracts and full-text articles, extracted data, and assessed risks of bias. We used random-effects models to pool data and GRADE to assess certainty. RESULTS: Among 6,258 citations, we included 53 studies (n = 757,726 patients); 8 of which (n = 435,769 patients) reported nonoverlapping data that were meta-analyzed. The pooled cumulative incidence of any SSI was 6.0 in 100 patients [95% confidence interval (CI) = 4.3-8.0 in 100 patients; n = 8 studies; n = 435,769 patients; moderate certainty]. The cumulative incidence of Szilagyi grade I (cellulitis), grade II (subcutaneous tissue), and grade III (prosthetic graft) SSI was 6.5 in 100 patients (95% CI = 4.3-8.6 in 100 patients; n = 2 studies; n = 39,645 patients; low certainty), 2.1 in 100 patients (95% CI = 2.0-2.3 in 100 patients; n = 2 studies; low certainty), and 0.4 in 100 patients (95% CI = 0.4-0.4 in 100 patients; n = 1 study; n = 333,275 patients; low certainty), respectively. The pooled cumulative incidence of any early (in-hospital/≤30-days) and late (>30-days) SSI was 6.2 in 100 patients (95% CI = 4.4-8.0 in 100 patients; n = 7 studies; n = 431,273 patients; moderate certainty) and 3.7 in 100 patients (95% CI = 2.2-5.2 in 100 patients; n = 2 studies; n = 10,565 patients; low certainty), respectively. CONCLUSIONS: This systematic review derived population-based benchmarks of the incidence of any SSI; Szilagyi I, II, and III SSI; and early and late SSI after lower limb revascularization surgery. These may be used by practicing surgeons and healthcare leaders/administrators to guide quality improvement efforts in the United States and perhaps other countries.

Introducing the Escalation Antibiogram: A Simple Tool to Inform Changes in Empiric Antimicrobials in the Nonresponding Patient.

BACKGROUND: Hospital antibiograms guide initial empiric antibiotic treatment selections, but do not directly inform escalation of treatment among nonresponding patients. METHODS: Using gram-negative bacteremia as an exemplar condition, we sought to introduce the concept of an escalation antibiogram. Among episodes of gram-negative bacteremia between 2017 and 2020 from 6 hospitals in the Greater Toronto Area, we generated escalation antibiograms for each of 12 commonly used agents. Among organisms resistant to that antibiotic, we calculated the likelihood of susceptibility to each of the other 11 agents. In subgroup analyses, we examined escalation antibiograms across study years, individual hospitals, community versus hospital onset, and pathogen type. RESULTS: Among 6577 gram-negative bacteremia episodes, the likelihood of coverage was ampicillin 31.8%, cefazolin 62.7%, ceftriaxone 67.1%, piperacillin-tazobactam 72.5%, ceftazidime 74.1%, trimethoprim-sulfamethoxazole 74.4%, ciprofloxacin 77.1%, tobramycin 88.3%, gentamicin 88.8%, ertapenem 91.0%, amikacin 97.5%, and meropenem 98.2%. The escalation antibiograms revealed marked shifts in likelihood of coverage by the remaining 11 agents. For example, among ceftriaxone-resistant isolates, piperacillin-tazobactam susceptibility (21.2%) was significantly lower than trimethoprim-sulfamethoxazole (54.2%, P < .0001), ciprofloxacin (63.0%, P < .0001), ertapenem (73.4%, P < .0001), tobramycin (80.1%, P < .0001), gentamicin (82.8%, P < .0001), meropenem (94.3%, P < .0001), and amikacin (97.1%, P < .0001). Trimethoprim-sulfamethoxazole was the second-ranked agent in the meropenem escalation antibiogram (49.6%) and first in the amikacin escalation antibiogram (86.0%). Escalation antibiograms were consistent across 4 study years and 6 hospitals. CONCLUSIONS: Escalation antibiograms can be generated to inform empiric treatment changes in nonresponding patients. These tools can yield important insights such as avoiding the common maneuver of escalating from ceftriaxone to piperacillin-tazobactam in suspected gram-negative bacteremia.

Prevalence and Mortality Associated with Bloodstream Organisms: a Population-Wide Retrospective Cohort Study.

Bloodstream infections (BSIs) represent a substantial mortality risk, yet most studies are limited to select pathogens or populations. The aim of this study was to describe the population-wide prevalence of BSIs and examine the associated mortality risk for the responsible microorganisms. We conducted a population-wide retrospective cohort study of BSIs in Ontario in 2017. Blood culture data was collected from almost all microbiology laboratories in Ontario and linked to data sets of patient characteristics. For each organism, we determined the prevalence and crude mortality risk, and using logistic regression models, the adjusted odds of 30-day mortality was calculated relative to patients with negative blood cultures and matched patients without blood culture testing. From 531,065 blood cultures, we identified 22,935 positive BSI episodes in 19,326 patients, for an incidence of 150 per 100,000 population. The most frequently isolated organisms were Escherichia coli, Staphylococcus aureus, coagulase-negative staphylococci, Klebsiella species, and Enterococcus species with 40.2, 22.4, 12.1, 11.1, and 7.1 episodes per 100,000 population respectively. BSI episodes were associated with 17.0% mortality at 30 days. Compared to patients with negative cultures, the adjusted 30-day mortality risk for positive BSIs was 1.47 (95% confidence interval (CI), 1.41 to 1.54) and compared to matched patients without blood culture testing was 2.62 (95% CI, 2.52 to 2.73). Clostridium species were associated with the highest adjusted odds of mortality compared to that of negative cultures (adjusted odds ratio, 5.81; 95% CI, 4.00 to 8.44). Among high incidence pathogens, Staphylococcus aureus had the highest odds ratio of mortality (adjusted odds ratio, 2.14; 95% CI, 1.94 to 2.36). BSIs are associated with increased mortality risk, varying across organisms.

Using Prior Culture Results to Improve Initial Empiric Antibiotic Prescribing: An Evaluation of a Simple Clinical Heuristic.

BACKGROUND: A patient's prior cultures can inform the subsequent risk of infection from resistant organisms, yet prescribers often fail to incorporate these results into their empiric antibiotic selection. Given that timely initiation of adequate antibiotics has been associated with improved outcomes, there is an urgent need to address this gap. METHODS: In order to better incorporate prior culture results in the selection of empiric antibiotics, we performed a pragmatic, prospective, hospital-wide intervention: (1) empiric antibiotic prescriptions were assessed for clinically significant discordance with the most recent methicillin-resistant Staphylococcus aureus (MRSA) surveillance swab, previous cultures for extended-spectrum beta-lactamases (ESBLs), and the most recent culture for a Gram-negative (GN) organism; and (2) if discordant, an antimicrobial stewardship pharmacist provided recommendations for alternative therapy. The impact was analyzed using a quasi-experimental design comparing two 9-month periods (pre- and postintervention) at a large academic, tertiary care institution. RESULTS: Clinically significant discordance was identified 99 times in the preintervention period and 86 times in the intervention period. The proportion of patients that received concordant therapy increased from 73% (72/99) in the control group to 88% (76/86) in the intervention group (P = .01). The median time to concordant therapy was shorter in the intervention group than the control group (25 vs 55 hrs, respectively; P < .001; adjusted hazard ratio = 1.95 [95% confidence interval {CI}, 1.37-2.77; P < .001]). The median duration of unnecessary vancomycin therapy was reduced by 1.1 days (95% CI, .5-1.6 days; P < .001). CONCLUSIONS: This intervention improved prescribing, with a shorter time to concordant therapy and an increased proportion of patients receiving empiric therapy concordant with prior culture results. The use of unnecessary vancomycin was also reduced.

Improving Decision Making in Empiric Antibiotic Selection (IDEAS) for Gram-negative Bacteremia: A Prospective Clinical Implementation Study.

BACKGROUND: Timely selection of adequate empiric antibiotics has become increasingly difficult due to rising resistance rates and the competing desire to apply antimicrobial stewardship (AMS) principles. Individualized clinical prediction models offer the promise of reducing broad-spectrum antibiotic use and preserving/improving adequacy of treatment, but few have been validated in the clinical setting. METHODS: Multivariable models were used to predict the probability of susceptibility for gram-negative (GN) bacteria in bloodstream infections (bacteremia) to ceftriaxone, ciprofloxacin, ceftazidime, piperacillin-tazobactam, and meropenem. The models were combined with existing resistance-prediction methods to generate optimized and individualized suggestions for empiric therapy that were provided to prescribers by an AMS pharmacist. De-escalation of empiric antibiotics and adequacy of therapy were analyzed using a quasi-experimental design comparing two 9-month periods (pre- and postintervention) at a large academic tertiary care institution. RESULTS: Episodes of bacteremia (n = 182) were identified in the preintervention and postintervention (n = 201) periods. Patients who received the intervention were more likely to have their therapy de-escalated (29 vs 21%; aOR = 1.77; 95% CI, 1.09-2.87; P = .02). The intervention also increased the proportion of patients who were on the narrowest adequate therapy at the time of culture finalization (44% in the control and 55% in the intervention group; aOR = 2.04; 95% CI, 1.27-3.27; P = .003). Time to adequate therapy was similar in the intervention and control groups (5 vs 4 hours; P = .95). CONCLUSIONS: An AMS intervention, based on individualized predictive models for resistance, can influence empiric antibiotic selections for GN bacteremia to facilitate early de-escalation of therapy without compromising adequacy of antibiotic coverage.

The Benefits and Harms of Antibiotic Prophylaxis for Urinary Tract Infection in Older Adults.

BACKGROUND: The role of antibiotics in preventing urinary tract infection (UTI) in older adults is unknown. We sought to quantify the benefits and risks of antibiotic prophylaxis among older adults. METHODS: We conducted a matched cohort study comparing older adults (≥66 years) receiving antibiotic prophylaxis, defined as antibiotic treatment for ≥30 days starting within 30 days of a positive culture, with patients with positive urine cultures who received antibiotic treatment but did not receive prophylaxis. We matched each prophylaxis recipient to 10 nonrecipients based on organism, number of positive cultures, and propensity score. Outcomes included (1) emergency department (ED) visit or hospitalization for UTI, sepsis, or bloodstream infection within 1 year; (2) acquisition of antibiotic resistance in urinary tract pathogens; and (3) antibiotic-related complications. RESULTS: Overall, 4.7% (151/3190) of UTI prophylaxis patients and 3.6% (n = 1092/30 542) of controls required an ED visit or hospitalization for UTI, sepsis, or bloodstream infection (hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.12-1.57). Acquisition of antibiotic resistance to any urinary antibiotic (HR, 1.31; 95% CI, 1.18-1.44) and to the specific prophylaxis agent (HR, 2.01; 95% CI, 1.80-2.24) was higher in patients receiving prophylaxis. While the overall risk of antibiotic-related complications was similar between groups (HR, 1.08; 95% CI, .94-1.22), the risk of Clostridioidesdifficile and general medication adverse events was higher in prophylaxis recipients (HR [95% CI], 1.56 [1.05-2.23] and 1.62 [1.11-2.29], respectively). CONCLUSIONS: Among older adults with UTI, the harms of long-term antibiotic prophylaxis may outweigh their benefits.

The mobility gap: estimating mobility thresholds required to control SARS-CoV-2 in Canada.

BACKGROUND: Nonpharmaceutical interventions remain the primary means of controlling severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) until vaccination coverage is sufficient to achieve herd immunity. We used anonymized smartphone mobility measures to quantify the mobility level needed to control SARS-CoV-2 (i.e., mobility threshold), and the difference relative to the observed mobility level (i.e., mobility gap). METHODS: We conducted a time-series study of the weekly incidence of SARS-CoV-2 in Canada from Mar. 15, 2020, to Mar. 6, 2021. The outcome was weekly growth rate, defined as the ratio of cases in a given week versus the previous week. We evaluated the effects of average time spent outside the home in the previous 3 weeks using a log-normal regression model, accounting for province, week and mean temperature. We calculated the SARS-CoV-2 mobility threshold and gap. RESULTS: Across the 51-week study period, a total of 888 751 people were infected with SARS-CoV-2. Each 10% increase in the mobility gap was associated with a 25% increase in the SARS-CoV-2 weekly case growth rate (ratio 1.25, 95% confidence interval 1.20-1.29). Compared to the prepandemic baseline mobility of 100%, the mobility threshold was highest in the summer (69%; interquartile range [IQR] 67%-70%), and dropped to 54% in winter 2021 (IQR 52%-55%); a mobility gap was present in Canada from July 2020 until the last week of December 2020. INTERPRETATION: Mobility strongly and consistently predicts weekly case growth, and low levels of mobility are needed to control SARS-CoV-2 through spring 2021. Mobility measures from anonymized smartphone data can be used to guide provincial and regional loosening and tightening of physical distancing measures.

Using Genetic Distance from Archived Samples for the Prediction of Antibiotic Resistance in Escherichia coli.

The rising rates of antibiotic resistance increasingly compromise empirical treatment. Knowing the antibiotic susceptibility of a pathogen's close genetic relative(s) may improve empirical antibiotic selection. Using genomic and phenotypic data for Escherichia coli isolates from three separate clinically derived databases, we evaluated multiple genomic methods and statistical models for predicting antibiotic susceptibility, focusing on potentially rapidly available information, such as lineage or genetic distance from archived isolates. We applied these methods to derive and validate the prediction of antibiotic susceptibility to common antibiotics. We evaluated 968 separate episodes of suspected and confirmed infection with Escherichia coli from three geographically and temporally separated databases in Ontario, Canada, from 2010 to 2018. Across all approaches, model performance (area under the curve [AUC]) ranges for predicting antibiotic susceptibility were the greatest for ciprofloxacin (AUC, 0.76 to 0.97) and the lowest for trimethoprim-sulfamethoxazole (AUC, 0.51 to 0.80). When a model predicted that an isolate was susceptible, the resulting (posttest) probabilities of susceptibility were sufficient to warrant empirical therapy for most antibiotics (mean, 92%). An approach combining multiple models could permit the use of narrower-spectrum oral agents in 2 out of every 3 patients while maintaining high treatment adequacy (∼90%). Methods based on genetic relatedness to archived samples of E. coli could be used to predict antibiotic resistance and improve antibiotic selection.

Rates of increase of antibiotic resistance and ambient temperature in Europe: a cross-national analysis of 28 countries between 2000 and 2016.

BackgroundThe rapid increase of bacterial antibiotic resistance could soon render our most effective method to address infections obsolete. Factors influencing pathogen resistance prevalence in human populations remain poorly described, though temperature is known to contribute to mechanisms of spread.AimTo quantify the role of temperature, spatially and temporally, as a mechanistic modulator of transmission of antibiotic resistant microbes.MethodsAn ecologic analysis was performed on country-level antibiotic resistance prevalence in three common bacterial pathogens across 28 European countries, collectively representing over 4 million tested isolates. Associations of minimum temperature and other predictors with change in antibiotic resistance rates over 17 years (2000-2016) were evaluated with multivariable models. The effects of predictors on the antibiotic resistance rate change across geographies were quantified.ResultsDuring 2000-2016, for Escherichia coli and Klebsiella pneumoniae, European countries with 10°C warmer ambient minimum temperatures compared to others, experienced more rapid resistance increases across all antibiotic classes. Increases ranged between 0.33%/year (95% CI: 0.2 to 0.5) and 1.2%/year (95% CI: 0.4 to 1.9), even after accounting for recognised resistance drivers including antibiotic consumption and population density. For Staphylococcus aureus a decreasing relationship of -0.4%/year (95% CI: -0.7 to 0.0) was found for meticillin resistance, reflecting widespread declines in meticillin-resistant S. aureus across Europe over the study period.ConclusionWe found evidence of a long-term effect of ambient minimum temperature on antibiotic resistance rate increases in Europe. Ambient temperature might considerably influence antibiotic resistance growth rates, and explain geographic differences observed in cross-sectional studies. Rising temperatures globally may hasten resistance spread, complicating mitigation efforts.

The Relative Impact of Community and Hospital Antibiotic Use on the Selection of Extended-spectrum Beta-lactamase-producing Escherichia coli.

Antibiotic stewardship programs have traditionally focused on reducing hospital antibiotic use. However, reducing community antibiotic prescribing could have substantial impacts in both hospital and community settings. We developed a deterministic model of transmission of extended-spectrum beta-lactamase-producing Escherichia coli in both the community and hospitals. We fit the model to existing, national-level antibiotic use and resistance prevalence data from Sweden. Across a range of conditions, a given relative change in antibiotic use in the community had a greater impact on resistance prevalence in both the community and hospitals than an equivalent relative change in hospital use. However, on a per prescription basis, changes in antibiotic use in hospitals had the greatest impact. The magnitude of changes in prevalence were modest, even with large changes in antimicrobial use. These data support the expansion of stewardship programs/interventions beyond the walls of hospitals, but also suggest that such efforts would benefit hospitals themselves.

Empiric Antibiotic Treatment Thresholds for Serious Bacterial Infections: A Scenario-based Survey Study.

BACKGROUND: Physicians face competing demands of maximizing pathogen coverage while minimizing unnecessary use of broad-spectrum antibiotics when managing sepsis. We sought to identify physicians' perceived likelihood of coverage achieved by their usual empiric antibiotic regimen, along with minimum thresholds of coverage they would be willing to accept when managing these patients. METHODS: We conducted a scenario-based survey of internal medicine physicians from across Canada using a 2 × 2 factorial design, varied by infection source (undifferentiated vs genitourinary) and severity (mild vs severe) denoted by the Quick Sequential Organ Failure Assessment (qSOFA) score. For each scenario, participants selected their preferred empiric antibiotic regimen, estimated the likelihood of coverage achieved by that regimen, and considered their minimum threshold of coverage. RESULTS: We had 238 respondents: 87 (36.6%) residents and 151 attending physicians (63.4%). The perceived likelihood of antibiotic coverage and minimum thresholds of coverage (with interquartile range) for each scenario were as follows: (1) severe undifferentiated, 90% (89.5%-95.0%) and 90% (80%-95%), respectively; (2) mild undifferentiated, 89% (80%-95%) and 80% (70%-89.5%); (3) severe genitourinary, 91% (87.3%-95.0%) and 90% (80.0%-90.0%); and (4) mild genitourinary, 90% (81.8%-91.3%) and 80% (71.8%-90%). Illness severity and infectious disease specialty predicted higher thresholds of coverage whereas less clinical experience and lower self-reported prescribing intensity predicted lower thresholds of coverage. CONCLUSIONS: Pathogen coverage of 80% and 90% are physician-acceptable thresholds for managing patients with mild and severe sepsis from bacterial infections. These data may inform clinical guidelines and decision-support tools to improve empiric antibiotic prescribing.

Utility of Urine Cultures in Predicting Blood Culture Susceptibilities in Patients with Bacteremic Urinary Tract Infection.

In a review of 428 patients with bacteremic urinary tract infections, urine culture susceptibility results accurately predicted blood culture results when the same organism was isolated from both cultures. Early targeted therapy using urine culture results can potentially reduce broad-spectrum antibiotic exposure and its associated adverse effects and the length of hospitalization.

Comparing Patient Risk Factor-, Sequence Type-, and Resistance Locus Identification-Based Approaches for Predicting Antibiotic Resistance in Escherichia coli Bloodstream Infections.

Rapid diagnostic tests for antibiotic resistance that identify the presence or absence of antibiotic resistance genes/loci are increasingly being developed. However, these approaches usually neglect other sources of predictive information which could be identified over shorter time periods, including patient epidemiologic risk factors for antibiotic resistance and markers of lineage. Using a data set of 414 Escherichia coli isolates recovered from separate episodes of bacteremia at a single academic institution in Toronto, Ontario, Canada, between 2010 and 2015, we compared the potential predictive ability of three approaches (epidemiologic risk factor-, pathogen sequence type [ST]-, and resistance gene identification-based approaches) for classifying phenotypic resistance to three antibiotics representing classes of broad-spectrum antimicrobial therapy (ceftriaxone [a 3rd-generation cephalosporin], ciprofloxacin [a fluoroquinolone], and gentamicin [an aminoglycoside]). We used logistic regression models to generate model receiver operating characteristic (ROC) curves. Predictive discrimination was measured using apparent and corrected (bootstrapped) areas under the curves (AUCs). Epidemiologic risk factor-based models based on two simple risk factors (prior antibiotic exposure and recent prior susceptibility of Gram-negative bacteria) provided a modest predictive discrimination, with AUCs ranging from 0.65 to 0.74. Sequence type-based models demonstrated strong discrimination (AUCs, 0.83 to 0.94) across all three antibiotic classes. The addition of epidemiologic risk factors to sequence type significantly improved the ability to predict resistance for all antibiotics (P < 0.05). Resistance gene identification-based approaches provided the highest degree of discrimination (AUCs, 0.88 to 0.99), with no statistically significant benefit being achieved by adding the patient epidemiologic predictors. In summary, sequence type or other lineage-based approaches could produce an excellent discrimination of antibiotic resistance and may be improved by incorporating readily available patient epidemiologic predictors but are less discriminatory than identification of the presence of known resistance loci.

Impact of Defaulting to Single-Lumen Peripherally Inserted Central Catheters on Patient Outcomes: An Interrupted Time Series Study.

Defaulting to single-lumen peripherally inserted central catheters (PICCs) ordered from non-critical care units resulted in a sustained reduction in PICC-related complications. This system of care is transferrable to other institutions, with potential for improved patient safety and efficiency in outpatient parenteral antimicrobial therapy clinics.

Use of Genome Sequencing to Define Institutional Influenza Outbreaks, Toronto, Ontario, Canada, 2014-15.

Adequacy of the current clinical definition of institutional influenza outbreaks is unclear. We performed a retrospective genome sequencing and epidemiologic analysis of institutional influenza outbreaks that occurred during the 2014-15 influenza season in Toronto, Canada. We sequenced the 2 earliest submitted samples positive for influenza A(H3N2) from each of 38 reported institutional outbreaks in long-term care facilities. Genome sequencing showed most outbreak pairs identified by using the current clinical definition were highly related. Inclusion of surveillance samples demonstrated that outbreak sources were likely introductions from broader circulating lineages. Pairwise distance analysis using majority genome and hemagglutinin-specific genes enabled identification of thresholds for discrimination of within and between outbreak pairs; the area under the curve ranged 0.93-0.95. Routine genome sequencing for defining influenza outbreaks in long-term care facilities is unlikely to add significantly to the current clinical definition. Sequencing may prove most useful for investigating sources of outbreak introductions.