Longitudinal Analysis of Mpox Virus DNA Detectability From Multiple Specimen Types During Acute Illness: A Cohort Study.

Background: Longitudinal data on the detectability of monkeypox virus (MPXV) genetic material in different specimen types are scarce. Methods: We describe MPXV-specific polymerase chain reaction (PCR) results from adults with confirmed mpox infection from Toronto, Canada, including a cohort undergoing weekly collection of specimens from multiple anatomic sites until 1 week after skin lesions had fully healed. We quantified the time from symptom onset to resolution of detectable viral DNA (computed tomography [Ct] ≥ 35) by modeling exponential decay in Ct value as a function of illness day for each site, censoring at the time of tecovirimat initiation. Results: Among 64 men who have sex with men, the median (interquartile range [IQR]) age was 39 (32.75-45.25) years, and 49% had HIV. Twenty received tecovirimat. Viral DNA was detectable (Ct < 35) at baseline in 74% of genital/buttock/perianal skin swabs, 56% of other skin swabs, 44% of rectal swabs, 37% of throat swabs, 27% of urine, 26% of nasopharyngeal swabs, and 8% of semen samples. The median time to resolution of detectable DNA (IQR) was longest for genital/buttock/perianal skin and other skin swabs at 30.0 (23.0-47.9) and 22.4 (16.6-29.4) days, respectively, and shortest for nasopharyngeal swabs and semen at 0 (0-12.1) and 0 (0-0) days, respectively. We did not observe an effect of tecovirimat on the rate of decay in viral DNA detectability in any specimen type (all P > .05). Conclusions: MPXV DNA detectability varies by specimen type and persists for over 3-4 weeks in skin specimens. The rate of decay did not differ by tecovirimat use in this nonrandomized study.

Impact of extended-infusion piperacillin-tazobactam in a Canadian community hospital.

Background: Studies have demonstrated improved clinical outcomes with extended infusion (EI) piperacillin/tazobactam (TZP) compared to standard infusion (SI). However, there is less evidence on its benefits in noncritically-ill patients. Hospital-wide EI TZP was implemented at our site on February 21, 2012. Our objectives were to compare clinical, safety and economic outcomes between EI and SI TZP. Methods: A retrospective cohort study of all adult patients who received EI TZP (3.375 g IV q8h infused over 4 hours and SI TZP for ≥ 48 hours during 3 years pre-and postimplementation was conducted. The primary study outcome was 14-day mortality while secondary outcomes included length of hospital stay (LOS), nursing plus pharmacy cost, occurrence of Clostridioides difficile infection, readmission within 30 days and change in Pseudomonas aeruginosa minimum inhibitory concentration (MIC) distribution for TZP. The primary outcome and binary secondary outcomes were analyzed using a logistic regression model. LOS was examined using time to event analysis. Cost was examined using linear regression modelling. Results: Overall, 2034 patients received EI TZP and 1364 patients received SI TZP. EI TZP was associated with lower odds of mortality (OR 0.76, 95% CI 0.63-0.91), lower odds of C. difficile infection (OR 0.59, 95% CI 0.41-0.84) and 8% lower cost (estimate 0.92, 95% CI 0.87-0.98) compared to SI TZP. Conclusions: Hospital-wide implementation of EI TZP was associated with lower odds of 14-day mortality and incidence of C. difficile infection with cost savings at our institution.

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.

Prevalence of Clostridioides difficile Infection in Critically Ill Patients with Extreme Leukocytosis and Diarrhea.

While early empiric antibiotic therapy is beneficial for patients presenting with sepsis, the presentation of sepsis from Clostridioides difficile (formerly Clostridium difficile) infection (CDI) has not been well studied in large cohorts. We sought to determine whether the combination of extreme leukocytosis and diarrhea was strongly predictive of CDI in a cohort of 8659 patients admitted to the intensive care unit. We found that CDI was present in 15.0% (95% CI, 12.1-18.3%) of patients with extreme leukocytosis and diarrhea and that mortality for those with CDI, diarrhea, and extreme leukocytosis was 33.8% (95% CI, 23.2-44.3%). These data support consideration of empiric treatment for CDI in unstable critically ill patients with extreme leukocytosis and diarrhea, along with treatment of other possible sources of sepsis as appropriate. Empiric treatment for CDI can usually be discontinued promptly, along with narrowing of other broad-spectrum antimicrobial coverage, if a sensitive C. difficile test is negative.

Nudging In MicroBiology Laboratory Evaluation (NIMBLE): A scoping review.

BACKGROUND: Nudging in microbiology is an antimicrobial stewardship strategy to influence decision making through the strategic reporting of microbiology results while preserving prescriber autonomy. The purpose of this scoping review was to identify the evidence that demonstrates the effectiveness of nudging strategies in susceptibility result reporting to improve antimicrobial use. METHODS: A search for studies in Ovid MEDLINE, Embase, PsycINFO, and All EBM Reviews was conducted. All simulated and vignette studies were excluded. Two independent reviewers were used throughout screening and data extraction. RESULTS: Of a total of 1,346 citations screened, 15 relevant studies were identified. Study types included pre- and postintervention (n = 10), retrospective cohort (n = 4), and a randomized controlled trial (n = 1). Most studies were performed in acute-care settings (n = 13), and the remainder were in primary care (n = 2). Most studies used a strategy to alter the default antibiotic choices on the antibiotic report. All studies reported at least 1 outcome of antimicrobial use: utilization (n = 9), appropriateness (n = 7), de-escalation (n = 2), and cost (n = 1). Moreover, 12 studies reported an overall benefit in antimicrobial use outcomes associated with nudging, and 4 studies evaluated the association of nudging strategy with subsequent antimicrobial resistance, with 2 studies noting overall improvement. CONCLUSIONS: The number of heterogeneous studies evaluating the impact of applying nudging strategies to susceptibility result reports is small; however, most strategies do show promise in altering prescriber's antibiotic selection. Selective and cascade reporting of targeted agents in a hospital setting represent the majority of current research. Gaps and opportunities for future research identified from our scoping review include performing prospective randomized controlled trials and evaluating other approaches aside from selective reporting.

Antimicrobial Stewardship and Intensive Care Unit Mortality: A Systematic Review.

BACKGROUND: Antimicrobial stewardship programs (ASPs) using audit and feedback in the intensive care unit (ICU) setting can reduce harms related to inappropriate antibiotic use. However, inappropriate discontinuation or narrowing of antibiotic treatment could increase infection-related mortality in this population. Individual ASP studies are underpowered to detect differences in mortality. METHODS: We conducted a systematic review and meta-analysis of audit and feedback in the ICU setting, using mortality as our outcome. RESULTS: Of 2447 citations, 11 studies met our inclusion criteria. Although a variety of study designs were used to assess reductions in antibiotic use, mortality was analyzed using an uncontrolled before-after study design in all studies. Five studies directed audit and feedback to all or most ICU patients receiving antibiotics and measured overall ICU mortality. In the meta-analysis of these studies, the pooled relative risk of ICU mortality was 1.03 (95% confidence interval, .93-1.14). A second meta-analysis of 3 smaller studies that evaluated mortality only in patients directly assessed by the ASP found a pooled relative risk of ICU mortality of 1.06 (95% confidence interval, .80 to 1.4). Three studies were not appropriate for meta-analysis, but their results were consistent with our overall findings. CONCLUSIONS: Our systematic review did not identify a change in mortality associated with antimicrobial stewardship using audit and feedback in the ICU setting. These results increase our confidence that audit and feedback can be safely implemented in this setting. Future studies should report standardized estimates of mortality and use more robust study designs to assess mortality, when feasible.

Cumulative Antimicrobial Susceptibility Data from Intensive Care Units at One Institution: Should Data Be Combined?

Cumulative susceptibility test data (CSTD) are used to guide empirical antimicrobial therapy and to track trends in antibiotic resistance. The Clinical and Laboratory Standards Institute recommends reporting CSTD at least annually and sets the minimum number of isolates per reported organism at 30. To comply, many hospitals combine data from multiple intensive care units (ICUs); however, this may not be appropriate to guide empirical therapy because of variations in patient populations. In this study, susceptibility data for two different ICUs at a tertiary care hospital in Toronto, Canada, were used to create a traditional CSTD report, which combined data from different ICUs, and a rolling-average CSTD report, which pooled 2 years of data for each ICU separately. For simplicity, data for only the most common Gram-negative organisms (Escherichia coli,Pseudomonas aeruginosa) and the most relevant antibiotics (ciprofloxacin, piperacillin-tazobactam) were examined. With the rolling-average method, significant differences in susceptibility were seen between the ICUs in 50% of the organism-antimicrobial combinations. Furthermore, the 3% median year-over-year difference in susceptibilities seen for the 16 organism-antibiotic combinations by using the traditional method was lower than the 14% median difference seen for the 20 between-ICU within-year comparisons obtained using the rolling-average method. Changes in our selection of empirical antibiotics resulted from this revised approach, and our results suggest that pooling data from ICUs with different patient populations may not be appropriate. A rolling-average method may be an appropriate strategy for the creation of individual-unit CSTD reports.

Differential outcome of an antimicrobial stewardship audit and feedback program in two intensive care units: a controlled interrupted time series study.

BACKGROUND: Antimicrobial decision making in intensive care units (ICUs) is challenging. Unnecessary antimicrobials contribute to the development of resistant pathogens, Clostridium difficile infection and drug related adverse events. However, inadequate antimicrobial therapy is associated with mortality in critically ill patients. Antimicrobial stewardship programs are increasingly being implemented to improve antimicrobial prescribing, but the optimal approach in the ICU setting is unknown. We assessed the impact of an audit and feedback antimicrobial stewardship intervention on antimicrobial use, antimicrobial costs, clinical outcomes and microbiologic outcomes in two ICUs with different patient populations. METHODS: The audit and feedback intervention was implemented in a trauma and neurosurgery ICU (TNICU) and a medical surgical ICU (MSICU) at a 465-bed teaching hospital in Toronto, Canada. ICU patients were reviewed Monday to Friday by a physician and pharmacist with infectious diseases training. Recommendations related to appropriate antimicrobial use were presented to ICU teams during a dedicated daily meeting. A controlled interrupted time series analysis was used to compare outcomes in the 12 months before and after the intervention. Cardiovascular and coronary care ICUs served as control units. RESULTS: Mean total monthly antimicrobial use in defined daily doses (DDD) per 1000 patient days was reduced 28% in the TNICU (1433 vs. 1037) but increased 14% in the MSICU (1705 vs. 1936). In the time series analysis, total monthly antimicrobial use in the TNICU decreased by 375 DDD per 1000 patient days (p < 0.0009) immediately following the intervention, followed by a non-significant downward trend in use of -9 DDD per 1000 patient days (p = 0.56). No significant changes in antimicrobial use were identified in the MSICU. Antimicrobial use temporarily increased in one control unit and remained unchanged in the other. There were no changes in mortality, length of stay, readmission rate, incidence of C. difficile infection or resistance patterns of E. coli and P. aeruginosa in either intervention unit. CONCLUSIONS: Audit and feedback antimicrobial stewardship programs can lead to significant reductions in total antimicrobial use in the ICU setting. However, this effect may be context-dependent and further work is needed to determine the ingredients necessary for success.

Predictors of pandemic influenza infection in adults presenting to two urban emergency departments, Toronto, 2009.

OBJECTIVE: Identifying features that differentiate patients with H1N1 influenza infection from those with other conditions may assist clinical decision making during waves of pandemic influenza activity. METHODS: From April 27 to June 15, 2009, nasopharyngeal swabs were obtained from all adults presenting to two urban emergency departments (EDs) with illness including fever or respiratory symptoms. H1N1 infection was detected by reverse transcriptase-polymerase chain reaction. Chart review was performed to compare cases of H1N1 influenza (n  =  117) to matched controls. RESULTS: The median age of cases was 35 years versus 50 years for controls (p < .001). In those with pre-existing conditions, asthma was present in 31% of cases versus 14% of controls (OR 2.6, 95% CI 1.3-5.4). Cough (OR 7.8, 95% CI 3.2-19), fever (OR 3.0, 95% CI 1.7-5.4), headache (OR 2.0, 95% CI 1.2-3.2), and myalgias (OR 1.9, 95% CI 1.2-3.1) were significantly more common in H1N1 cases. The median white blood cell count was 5.7 × 109/mL versus 10.9 × 109/mL (p < .001). The combination of fever and cough had an OR of 5.3. Fever, cough, low white blood cell (WBC) count, and tachycardia had the highest OR at 11. The absence of both fever and cough had a negative predictive value of 99%, but this occurred in only 8% of controls. CONCLUSION: In patients presenting to the ED, the combination of fever, cough, tachycardia, and WBC count < 10 × 109/mL was suggestive of H1N1 influenza infection. However, clinical features could not reliably distinguish influenza from other acute respiratory illnesses in adult ED patients.

Look good feel better workshops: a "big lift" for women with cancer.

BACKGROUND: Look Good Feel Better (LGFB) aims to help women manage appearance-related side effects of cancer and its treatment. In this pilot study, we assessed the impact of LGFB workshops on self-image, social interactions, perceived social support, and anxiety. METHODS: We administered scales preworkshop and postworkshop participation. We conducted semistructured telephone interviews following attendance. RESULTS: Statistically and qualitatively, subjects experienced significant improvement in self-image, social interaction, and anxiety. Participant anxiety decreased, but greater social support was anticipated than actually obtained. CONCLUSIONS: LGFB workshops increase self-image, improve social interactions, and reduce anxiety.

Ultrasonic characterization of whole cells and isolated nuclei.

High frequency ultrasound imaging (20 to 60 MHz) is increasingly being used in small animal imaging, molecular imaging and for the detection of structural changes during cell and tissue death. Ultrasonic tissue characterization techniques were used to measure the speed of sound, attenuation coefficient and integrated backscatter coefficient for (a) acute myeloid leukemia cells and corresponding isolated nuclei, (b) human epithelial kidney cells and corresponding isolated nuclei, (c) multinucleated human epithelial kidney cells and d) human breast cancer cells. The speed of sound for cells varied from 1522 to 1535 m/s, while values for nuclei were lower, ranging from 1493 to 1514 m/s. The attenuation coefficient slopes ranged from 0.0798 to 0.1073 dB mm(-1) MHz(-1) for cells and 0.0408 to 0.0530 dB mm(-1) MHz(-1) for nuclei. Integrated backscatter coefficient values for cells and isolated nuclei showed much greater variation and increased from 1.71 x 10(-4) Sr(-1) mm(-1) for the smallest nuclei to 26.47 x 10(-4) Sr(-1) mm(-1) for the cells with the largest nuclei. The findings suggest that integrated backscatter coefficient values, but not attenuation or speed of sound, are correlated with the size of the nuclei.