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.

A sepsis treatment algorithm to improve early antibiotic de-escalation while maintaining adequacy of coverage (Early-IDEAS): A prospective observational study.

BACKGROUND: Empiric antibiotic treatment selection should provide adequate coverage for potential pathogens while minimizing unnecessary broad-spectrum antibiotic use. We sought to pilot a sepsis treatment algorithm to individualize antibiotic recommendations, and thereby improve early antibiotic de-escalation while maintaining adequacy of coverage (Early-IDEAS). METHODS: In this observational study, the Early-IDEAS decision support algorithm was derived from previous Gram- negative and Gram-positive prediction rules and models along with local guidelines, and then applied to prospectively identified consecutive adults within 24 hours of suspected sepsis. The primary outcome was the proportion of patients for whom de-escalation of the primary antibiotic regimen was recommended by the algorithm. Secondary outcomes included: (1) proportion of patients for whom escalation was recommended; (2) number of recommended de-escalation steps along a pre-specified antibiotic cascade; and (3) adequacy of therapy in patients with culture-confirmed infection. RESULTS: We screened 578 patients, of whom 107 eligible patients were included. The Early-IDEAS treatment recommendation was informed by Gram-negative models in 76 (71%) patients, Gram-positive rules in 64 (59.8%), and local guidelines in 27 (25.2%). Antibiotic de-escalation was recommended in almost half of all patients (n = 52, 48.6%), with a median of 2 steps down the a priori antibiotic treatment cascade. No treatment change was recommended in 45 patients (42.1%), and escalation was recommended in 10 (9.3%). Among the 17 patients with positive blood cultures, both the clinician prescribed regimen and the algorithm recommendation provided adequate coverage for the isolated pathogen in 12 patients (70.6%), (p = 1). Among the 25 patients with positive relevant, non-blood cultures, both the clinician prescribed regimen and the algorithm recommendation provided adequate coverage in 20 (80%), (p = 1). CONCLUSION: An individualized decision support algorithm in early sepsis could lead to substantial antibiotic de-escalation without compromising adequate antibiotic coverage.

Optimizing Cefazolin Prophylaxis in Obstetrical Patients with Reported Beta-Lactam Allergy Undergoing Cesarean Delivery.

OBJECTIVES: Evaluate the impact of an allergy history-guided algorithm for optimizing perioperative cefazolin use in patients with reported beta-lactam allergy undergoing cesarean delivery. METHODS: The Allergy Clarification for Cefazolin Evidence-based Prescribing Tool (ACCEPT) was developed through consensus by allergists, anesthesiologists, and infectious diseases specialists, and implemented over a 2-month period (December 1, 2018, to January 31, 2019). A segmented regression on monthly cefazolin use was conducted during the baseline (January 1 to November 30, 2018) and intervention (February 1 to December 31, 2019) periods to evaluate the impact of ACCEPT on the monthly use of perioperative cefazolin in patients with reported beta-lactam allergy undergoing cesarean delivery. The frequency of perioperative allergic reactions and surgical site infections was collected during both periods. RESULTS: Of the 3128 eligible women who underwent a cesarean delivery, 282 (9%) reported a beta-lactam allergy. The most common beta-lactam allergens were penicillin (64.3%), amoxicillin (16.0%), and cefaclor (6.0%). The most frequently reported allergic reactions were rash (38.1%), hives (21.4%), and unknown (11.6%). Use of cefazolin increased from 52% (baseline) to 87% during the intervention period. Segmented regression analysis confirmed a statistically significant increase following implementation (incidence rate ratio 1.62, 95% CI 1.19-2.21, P = 0.002). There was 1 perioperative allergic reaction in the baseline period and 2 during the intervention period. Cefazolin use remained high (92%) 2 years after algorithm implementation. CONCLUSIONS: Implementation of a simple allergy history-guided algorithm in obstetrical patients with reported beta-lactam allergy resulted in a sustained increase in perioperative cefazolin prophylaxis.

Addition of anaerobic coverage for treatment of biliary tract infections: a propensity score-matched cohort study.

Objectives: To evaluate whether additional antibiotics that target anaerobes, including Bacteroides spp., are associated with improved clinical outcomes in patients with biliary tract infections (BTIs). Methods: This was a retrospective propensity score-matched cohort of adults aged ≥18 years with BTIs, admitted to hospital between 1 April 2015 and 30 March 2021. Eligible patients treated with antibiotics that provided coverage of anaerobes were compared with those treated with comparable regimens without anaerobic coverage. The primary outcome was a composite of mortality within 30 days or relapse within 90 days of source control or completion of antibiotics. Secondary outcomes included length of stay (LOS), duration of antibiotic therapy and adverse drug reactions. ORs were calculated using a weighted generalized linear regression model with propensity-score matching. Results: Among 398 patients included, 209 were treated without anaerobic coverage and 189 with anaerobic coverage. After propensity-score matching, there was no significant difference in primary outcome between propensity-matched patients who received additional anaerobic coverage and those who did not [adjusted OR (aOR) 1.23; 95% CI 0.69-2.22)]. Those with anti-anaerobic coverage had longer LOS (aOR 4.85; 95% CI 1.68-13.98) and longer duration of antibiotic treatment (aOR 4.14; 95% CI 2.61-6.57) than those who did not receive additional anaerobic therapy, but not more adverse drug reactions (aOR 1.01; 95% CI 0.97-1.05). Conclusions: Omitting anti-anaerobic antibiotics may be a safe antimicrobial stewardship intervention. However, a randomized controlled trial may be warranted to definitively conclude whether additional anaerobic coverage in BTI treatment is necessary.

The utility of routine autologous bone-flap swab cultures in predicting post-cranioplasty infection.

OBJECTIVE: To evaluate the utility of autologous bone-flap swab cultures performed at the time of cranioplasty in predicting postcranioplasty surgical site infection (SSI). DESIGN: Retrospective cohort study. PARTICIPANTS: Patients undergoing craniectomy (with bone-flap storage in tissue bank), followed by delayed autologous bone-flap replacement cranioplasty between January 1, 2010, and November 30, 2020. SETTING: Tertiary-care academic hospital. METHODS: We framed the bone-flap swab culture taken at the time of cranioplasty as a diagnostic test for predicting postcranioplasty SSI. We calculated, sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios. RESULTS: Among 282 unique eligible cases, 16 (5.6%) developed SSI after cranioplasty. A high percentage of bone-flap swab cultures were positive at the time of craniectomy (66.7%) and cranioplasty (59.5%). Most organisms from bone-flap swab cultures were Cutibacterium acnes or coagulase-negative staphylococci (76%-85%), and most SSI pathogens were methicillin-susceptible Staphylococcus aureus (38%). Bone-flap swab culture had poor sensitivity (0.07; 95% CI, 0.01-0.31), specificity (0.4; 95% CI, 0.34-0.45), and positive likelihood ratio (0.12) for predicting postcranioplasty SSI. CONCLUSION: Overall, autologous bone-flap swab cultures performed at the time of cranioplasty have poor utility in predicting postcranioplasty SSI. Eliminating this low-value practice would result in significant workload reductions and associated healthcare costs.

Trends in hospital antibiotic utilization during the coronavirus disease 2019 (COVID-19) pandemic: A multicenter interrupted time-series analysis.

Objective: To describe the evolution of respiratory antibiotic prescribing during the coronavirus disease 2019 (COVID-19) pandemic across 3 large hospitals that maintained antimicrobial stewardship services throughout the pandemic. Design: Retrospective interrupted time-series analysis. Setting: A multicenter study was conducted including medical and intensive care units (ICUs) from 3 hospitals within a Canadian epicenter for COVID-19. Methods: Interrupted time-series analysis was used to analyze rates of respiratory antibiotic utilization measured in days of therapy per 1,000 patient days (DOT/1,000 PD) in medical units and ICUs. Each of the first 3 waves of the pandemic were compared to the baseline. Results: Within the medical units, use of respiratory antibiotics increased during the first wave of the pandemic (rate ratio [RR], 1.76; 95% CI, 1.38-2.25) but returned to the baseline in waves 2 and 3 despite more COVID-19 admissions. In ICU, the use of respiratory antibiotics increased in wave 1 (RR, 1.30; 95% CI, 1.16-1.46) and wave 2 of the pandemic (RR, 1.21; 95% CI, 1.11-1.33) and returned to the baseline in the third wave, which had the most COVID-19 admissions. Conclusions: After an initial surge in respiratory antibiotic prescribing, we observed the normalization of prescribing trends at 3 large hospitals throughout the COVID-19 pandemic. This trend may have been due to the timely generation of new research and guidelines developed with frontline clinicians, allowing for the active application of new research to clinical practice.

Evaluation of different antimicrobial stewardship models at a rehabilitation hospital: An interrupted time series (ITS) study.

Objective: To evaluate different prospective audit-and-feedback models on antimicrobial prescribing at a rehabilitation hospital. Design: Retrospective interrupted time series (ITS) and qualitative methods. Setting: A 178-bed rehabilitation hospital within an academic health sciences center. Methods: ITS analysis was used to analyze monthly days of therapy (DOT) per 1,000 patient days (PD) and monthly urine cultures ordered per 1,000 PD. We compared 2 sequential intervention periods to the baseline: (1) a period when a dedicated antimicrobial stewardship (AMS) pharmacist performed prospective audit and feedback and provided urine culture education followed by (2) a period when ward pharmacists performing audit and feedback. We conducted an electronic survey with physicians and semistructured interviews with pharmacists, respectively. Results: Audit and feedback conducted by an AMS pharmacist resulted in a 24.3% relative reduction in total DOT per 1,000 PD (incidence rate ratio [IRR], 0.76; 95% confidence interval [CI], 0.58-0.99; P = .04), whereas we detected no difference between ward pharmacist audit and feedback and the baseline (IRR, 1.20; 95% CI, 0.53-2.70; P = .65). We detected no statistically significant change in monthly urine-culture orders between the AMS pharmacist period and the baseline (level coefficient, 0.81; 95% CI, 0.65-1.01; P = .07). Compared to baseline, the ward pharmacist period showed a statistically significant increase in urine-culture ordering over time (slope coefficient, 1.04; 95% CI, 1.01-1.08; P = .02). The barrier most identified by pharmacists was insufficient time. Conclusions: Audit and feedback conducted by an AMS pharmacist in a rehabilitation hospital was associated with decreased antimicrobial use.

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.

Improving Intrapartum Group B Streptococcus Prophylaxis in Patients with a Reported Penicillin or Cephalosporin Allergy: A Quality Improvement Project.

OBJECTIVE: To evaluate the impact of a standardized allergy-guided approach to Group B Streptococcus (GBS) prophylaxis in pregnant women with reported penicillin or cephalosporin allergy. METHODS: This interrupted time-series analysis included obstetric patients requiring GBS prophylaxis who reported penicillin or cephalosporin allergies. Patients were divided into baseline (April 1, 2019 to July 21, 2020) and intervention (July 22, 2020 to July 31, 2021) groups. The primary outcome was prophylaxis appropriateness, based on antibiotic type, nature of reaction, and cross-reactivity risk. Secondary outcomes included type of prophylaxis received and antibiotic-related adverse events. RESULTS: The study included 88 patients in the baseline period and 52 patients in the intervention period. Appropriate prophylaxis increased from 47% (41/88) to 85% (44/52), with the segmented regression model confirming a statistically significant increase over time (incidence rate ratio 1.57; 95% CI 1.02-2.43, P = 0.04, slope coefficient 1.06/month; 95% CI 1.01-1.10, P = 0.01). Penicillin and cefazolin use increased from 61% (54/88) to 87% (45/52) in the intervention period (P = 0.002), and no hypersensitivity reactions occurred during this period. CONCLUSIONS: Implementation of standardized allergy-guided prophylaxis safely improved appropriate ß-lactam antibiotic use in obstetric patients requiring GBS prophylaxis who reported penicillin and cephalosporin allergies.

Development and validation of a screening tool for early identification of bloodstream infection in acute burn injury patients.

BACKGROUND: Standard diagnostic criteria are not useful for identifying bloodstream infection in patients with an acute burn injury patients. The study objective was to develop and validate a tool using common laboratory, clinical, and patient parameters for early identification of bloodstream infection after acute burn injury (within 10 days after a burn). METHODS: We retrospectively and prospectively reviewed for tool development the hospital course of patients with an acute burn injury (n = 156) and validated the tool in different cohorts (retrospective [n = 26] and prospective [n = 90]). The Pearson correlation identified independent variables associated with bloodstream infection (P < .1) in the development cohort that were then analyzed using binary logistic regression to identify the simplest model (P < .05; adjusted odds ratio >1). Classification and regression tree analysis was used to identify tool parameter breakpoints. Performance metrics were completed to evaluate and validate the tool. RESULTS: The best model (P < .05) was: Ln [odds of bloodstream infection] = -96.749 + 3.230 (platelet volatility) + 2.235 (max temperature [°C]) + 0.339 (% full burn) + 0.242 (% partial burn) + 0.045 (max heart rate [bpm]), with a threshold probability categorizing bloodstream infection of >48%. The sensitivity, specificity, accuracy, false positive rate, false negative rate, and positive (+) and negative (-) likelihood ratios of the tool in the developmental cohort (n = 156) were 89%, 98%, 96%, 2%, 11%, 53, and 0·11, respectively; and in the prospective validation cohort (n = 90 were 91%, 90%, 90%, 10%, 9%, 9, and 0·1, respectively (n = 90). CONCLUSION: The validated bloodstream infection screening tool in patients with acute burn injury has excellent predictive ability to assist in the identification of patients for whom blood cultures should be requested.

Impact of Rejection of Low-Quality Wound Swabs on Antimicrobial Prescribing: A Controlled Before-After Study.

In this controlled before-after study, wound swabs were only processed for culture, identification, and susceptibility testing if a quality metric, determined by the Q score, was met. Rejection of low-quality wound swabs resulted in a modest decrease in reflexive antibiotic initiation while reducing laboratory workload and generating few clinician requests.

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.

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.

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.

Impact of the Allergy Clarification for Cefazolin Evidence-based Prescribing Tool on Receipt of Preferred Perioperative Prophylaxis: An Interrupted Time Series Study.

Implementation of a perioperative allergy and antibiotic assessment tool in patients with reported beta-lactam allergy resulted in a pronounced and sustained increase in perioperative cefazolin use. This intervention could result in improved efficiencies surrounding perioperative antibiotic administration and possible reductions in surgical site infection rates.

Self-reported beta-lactam allergy and the risk of surgical site infection: A retrospective cohort study.

OBJECTIVE: To assess whether a self-reported ß-lactam allergy is associated with an increased risk of surgical site infection (SSI) across a broad range of procedures and to determine whether this association is mediated by the receipt of an alternate antibiotic to cefazolin. DESIGN: Retrospective cohort study. PARTICIPANTS: Surgical procedures sampled by an institutional National Surgical Quality Improvement Program database over an 18-month period (January 2017 to June 2018) from 7 surgical specialties. SETTING: Tertiary-care academic hospital. RESULTS: Of the 3,589 surgical procedures included in the study, 369 (10.3%) were performed in patients with a reported ß-lactam allergy. Those with a reported ß-lactam allergy were significantly less likely to receive cefazolin (38.8% vs 95.5%) or metronidazole (20.3% vs 26.1%) and were more likely to receive clindamycin (52.0% vs 0.2%), gentamicin (3.5% vs 0%), or vancomycin (2.2% vs 0.1%) than those without allergy. An SSI occurred in 154 of 3,220 procedures (4.8%) in patients without reported allergy and 27 of 369 (7.3%) with reported allergy. In the multivariable regression model, a reported ß-lactam allergy was associated with a statistically significant increase in SSI risk (adjusted odds ratio [aOR], 1.61; 95% confidence interval [CI], 1.04-2.51; P = .03). This effect was completely mediated by receipt of an alternate antibiotic to cefazolin (indirect effect aOR, 1.68; 95% CI, 1.17-2.34; P = .005). CONCLUSIONS: Self-reported ß-lactam allergy was associated with an increased SSI risk mediated through receipt of alternate antibiotic prophylaxis. Safely increasing use of cefazolin prophylaxis in patients with reported ß-lactam allergy can potentially lower the risk of SSIs.

Retrospective multicentre matched cohort study comparing safety and efficacy outcomes of intermittent-infusion versus continuous-infusion vancomycin.

BACKGROUND: Patients with good renal function receiving intermittent-infusion vancomycin (IIV) may require total daily doses ≥4 g to achieve trough concentrations of 15-20 mg/L, increasing the risk of vancomycin-associated nephrotoxicity. Continuous-infusion vancomycin (CIV) may be associated with a lower risk of vancomycin-associated nephrotoxicity compared with IIV, but studies comparing safety of both dosing strategies are lacking. OBJECTIVES: To compare the risk of nephrotoxicity with CIV versus IIV when target concentration ranges were the same with both dosing modalities. METHODS: A retrospective multicentre matched cohort study of admitted patients between 1 January 2010 and 31 December 2016 was completed. Adult patients who received ≥48 h of vancomycin with at least one steady-state vancomycin concentration were eligible. The primary outcome was to compare the rates of nephrotoxic risk and renal injury, defined by the RIFLE criteria, between CIV and IIV. RESULTS: Of 2136 patients who received vancomycin during the study period, 146 CIV patients were eligible and matched to 146 IIV patients. After adjustment of potential confounders, CIV was found to have a lower odds of developing nephrotoxic risk (OR 0.42, 95% CI 0.21-0.98, P = 0.025) and renal injury (OR 0.19, 95% CI 0.05-0.59, P = 0.004). CONCLUSIONS: CIV is associated with a lower odds of nephrotoxicity compared with IIV when targeting the same concentration range and should be an alternative dosing strategy for patients who will receive prolonged therapy or require >4 g/day to achieve therapeutic levels.

Development and validation of a screening tool for early identification of bloodstream infection in older patients - a retrospective case-control study.

BACKGROUND: Delayed diagnosis of bloodstream infection (BSI) occurs in > 20% of older patients, with misdiagnosis in 35%. Our objective was to develop and validate a clinically useful screening tool to identify older patients with a high probability of having a BSI. METHODS: Hospitalized patients > 80 years old with BSI (n = 105/group) were evaluated for the tool development in this retrospective matched case-controlled study (learn cohort). The tool was validated in different retrospectively matched case and control patients > 80 years old (n = 120/group) and 65 to 79 years old (n = 250/group) (test cohort). Binary logistic regression was used to develop a screening tool using laboratory and clinical parameters that were significantly associated with BSI (P < 0.05; adjusted odds ratio (OR) > 1); and Classification and Regression Tree (CART) analysis was used to identify parameter breakpoints. Performance metrics were used to evaluate and validate the tool. RESULTS: The significant parameters associated with BSI were maximum temperature (Tmax)(> 37.55C)(OR = 42.575), neutrophils (> 7.95)(OR = 1.923), a change in level of consciousness (LOC) (Yes = 1, No = 0)(OR = 1.571), blood urea nitrogen (BUN)(> 10.05)(OR = 1.359), glucose (> 7.35)(OR = 1.167), albumin (< 33.5)(OR = 1.038) and alanine aminotransferase (ALT) (> 19.5)(OR = 1.005). The optimal screening tool [Ln (odds of BSI) = - 150.299 + 3.751(Tmax) + 0.654(neutrophils) + 0.452(change in LOC) + 0.307(BUN) + 0.154(glucose) + 0.038(albumin) + 0.005(ALT)] had favorable performance metrics in the learn and test cohorts (sensitivity, specificity and accuracy of 95% in the learn cohort and 77, 89, and 81% in the total test cohort); and performed better than using only temperature and neutrophil count. CONCLUSIONS: The validated tool had high predictive value which may improve early identification and management of BSI in older patients.

Voriconazole prophylaxis in leukemic patients: A retrospective single-center study.

BACKGROUND: Invasive fungal infections commonly occur in acute myeloid and lymphoblastic leukemia patients receiving chemotherapy. In these patients with acute leukemia, posaconazole prophylaxis is recommended; however, voriconazole may be a less costly alternative. OBJECTIVES: The objective of this study was to evaluate the efficacy and safety of voriconazole prophylaxis in acute leukemia patients. METHODS: A retrospective chart review of inpatients at Sunnybrook Health Sciences Centre between 2005 and 2017 was completed. Hospitalized adult acute leukemia patients who received voriconazole prophylaxis (cases) were compared to patients who received fluconazole or no prophylaxis during chemotherapy (controls). Statistical analyses comparing baseline characteristics, safety, and efficacy outcomes between the study cohorts were completed. A posaconazole literature-based weighted mean risk was compared to the voriconazole risk of invasive fungal infection identified in this study. RESULTS: Of 490 acute myeloid leukemia or acute lymphoblastic leukemia patients, 83 controls and 92 cases were eligible. Case patients received an average of 24.4 ± 10.8 days of voriconazole prophylaxis. The incidence of proven or probable invasive fungal infections with voriconazole was 3.3% (3/92) versus 7.2% (6/83) in the control cohort (p > 0.05) and was comparable to the literature reported weighted incidence of invasive fungal infection with posaconazole (2.4 ± 2.1%; 95% CI 1.3%-3.4%; p > 0.05). Voriconazole was well tolerated by patients (91%; 84/91; seven discontinued due to asymptomatic elevated liver function tests). CONCLUSIONS: Voriconazole prophylaxis was found to be safe, effective, and comparable to literature-based efficacy data for risk of invasive fungal infection with posaconazole antifungal prophylaxis in patients with acute leukemia undergoing chemotherapy and could represent a significant cost advantage.