Mathematical model of the cost-effectiveness of the BioFire FilmArray Blood Culture Identification (BCID) Panel molecular rapid diagnostic test compared with conventional methods for identification of Escherichia coli bloodstream infections.

BACKGROUND: Gram-negative pathogens, such as Escherichia coli, are common causes of bloodstream infections (BSIs) and increasingly demonstrate antimicrobial resistance. Molecular rapid diagnostic tests (mRDTs) offer faster pathogen identification and susceptibility results, but higher costs compared with conventional methods. We determined the cost-effectiveness of the BioFire FilmArray Blood Culture Identification (BCID) Panel, as a type of mRDT, compared with conventional methods in the identification of E. coli BSIs. METHODS: We constructed a decision analytic model comparing BCID with conventional methods in the identification and susceptibility testing of hospitalized patients with E. coli BSIs from the perspective of the public healthcare payer. Model inputs were obtained from published literature. Cost-effectiveness was calculated by determining the per-patient admission cost, the QALYs garnered and the incremental cost-effectiveness ratios (ICERs) where applicable. Monte Carlo probabilistic sensitivity analyses and one-way sensitivity analyses were conducted to assess the robustness of the model. All costs reflect 2019 Canadian dollars. RESULTS: The Monte Carlo probabilistic analyses resulted in cost savings ($27 070.83 versus $35 649.81) and improved QALYs (8.65 versus 7.10) in favour of BCID. At a willingness to pay up to $100 000, BCID had a 72.6%-83.8% chance of being cost-effective. One-way sensitivity analyses revealed length of stay and cost per day of hospitalization to have the most substantial impact on costs and QALYs. CONCLUSIONS: BCID was found to be cost-saving when used to diagnose E. coli BSI compared with conventional testing. Cost savings were most influenced by length of stay and cost per day of hospitalization.

A Comprehensive Review of the Pathogenesis, Diagnosis, and Management of Diabetic Foot Infections.

GENERAL PURPOSE: To review an approach to diabetic foot infections (DFIs), including acute osteomyelitis, while also discussing current practices and the challenges in diagnosis and management. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will1. Identify the risk factors for developing DFIs.2. Outline diagnostic techniques for assessing DFIs.3. Select the assessment techniques that support a diagnosis of osteomyelitis.4. Choose the appropriate pharmacologic and nonpharmacologic treatment options for patients who have DFIs. ABSTRACT: Diabetic foot ulcers result from a combination of peripheral neuropathy, vascular compromise, and repetitive trauma. Approximately 50% of individuals with diabetic foot ulcers will develop a diabetic foot infection (DFI), and 20% of individuals with a DFI will develop osteomyelitis. Herein, the authors review an approach to DFIs including acute osteomyelitis and discuss current practices and challenges in diagnosis and management.The diagnosis of a skin and soft tissue DFI is based on clinical criteria. A bone biopsy is considered the criterion standard for diagnosis of osteomyelitis; however, biopsy is not always feasible or available. Consequently, diagnosis can be made using a combination of clinical, biochemical, and radiographic findings. X-ray is the recommended imaging modality for initial evaluation; however, because of its lower relative sensitivity, advanced imaging may be used when clinical suspicion remains after negative initial testing.The microbiology of skin and soft tissue DFIs and osteomyelitis is similar. Staphylococcus aureus and other Gram-positive cocci are the most common pathogens identified. Deep cultures are preferred in both DFI and osteomyelitis to identify the etiologic pathogens implicated for targeted antimicrobial therapy. Management also requires a multidisciplinary approach. Surgical debridement in those with deep or severe infections is necessary, and surgical resection of infected bone is curative in cases of osteomyelitis. Finally, appropriate wound care is critical, and management of predisposing factors, such as peripheral neuropathy, peripheral arterial disease, tinea, and edema, aids in recovery and prevention.

Fixed versus individualized treatment for five common bacterial infectious syndromes: a survey of the perspectives and practices of clinicians.

Background: Traditionally, bacterial infections have been treated with fixed-duration antibiotic courses; however, some have advocated for individualized durations. It is not known which approach currently predominates. Methods: We conducted a multinational clinical practice survey asking prescribers their approach to treating skin and soft tissue infection (SSTI), community-acquired pneumonia (CAP), pyelonephritis, cholangitis and bloodstream infection (BSI) of an unknown source. The primary outcome was self-reported treatment approach as being fully fixed duration, fixed minimum, fixed maximum, fixed minimum and maximum, or fully individualized durations. Secondary questions explored factors influencing duration of therapy. Multivariable logistic regression with generalized estimating equations was used to examine predictors of use of fully fixed durations. Results: Among 221 respondents, 170 (76.9%) completed the full survey; infectious diseases physicians accounted for 60.6%. Use of a fully fixed duration was least common for SSTI (8.5%) and more common for CAP (28.3%), BSI (29.9%), cholangitis (35.7%) and pyelonephritis (36.3%). Fully individualized therapy, with no fixed minimum or maximum, was used by only a minority: CAP (4.9%), pyelonephritis (5.0%), cholangitis (9.9%), BSI (13.6%) and SSTI (19.5%). In multivariable analyses, a fully fixed duration approach was more common among Canadian respondents [adjusted OR (aOR) 1.76 (95% CI 1.12-2.76)] and for CAP (aOR 4.25, 95% CI 2.53-7.13), cholangitis (aOR 6.01, 95% CI 3.49-10.36), pyelonephritis (aOR 6.08, 95% CI 3.56-10.39) and BSI (aOR 4.49, 95% CI 2.50-8.09) compared with SSTI. Conclusions: There is extensive practice heterogeneity in fixed versus individualized treatment; clinical trials would be helpful to compare these approaches.

Co-infection of SARS-CoV-2 with human coronavirus OC43 in a patient with underlying lung disease: A case report.

Co-infections with SARS-CoV-2 remain relatively rare and there is limited published data on the consequences of these events. We present the case of a 26-year-old man with SARS-CoV-2 and human coronavirus OC43 who had a severe infection resulting in prolonged hospitalization. Consideration of co-infections should be considered in high-risk patients.

Les co-infections par le SRAS-CoV-2 restent relativement rares et les données publiées sur les conséquences de ces événements sont limitées. Nous présentent le cas d'un homme de 26 ans atteint du SRAS-CoV-2 et du coronavirus humain OC43 qui a eu une infection grave entraînant une hospitalisation. La prise en compte des co-infections doit être envisagée chez les patients à haut risque.

Antimicrobial resistance in patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: Frequent use of antibiotics in patients with COVID-19 threatens to exacerbate antimicrobial resistance. We aimed to establish the prevalence and predictors of bacterial infections and antimicrobial resistance in patients with COVID-19. METHODS: We did a systematic review and meta-analysis of studies of bacterial co-infections (identified within ≤48 h of presentation) and secondary infections (>48 h after presentation) in outpatients or hospitalised patients with COVID-19. We searched the WHO COVID-19 Research Database to identify cohort studies, case series, case-control trials, and randomised controlled trials with populations of at least 50 patients published in any language between Jan 1, 2019, and Dec 1, 2021. Reviews, editorials, letters, pre-prints, and conference proceedings were excluded, as were studies in which bacterial infection was not microbiologically confirmed (or confirmed via nasopharyngeal swab only). We screened titles and abstracts of papers identified by our search, and then assessed the full text of potentially relevant articles. We reported the pooled prevalence of bacterial infections and antimicrobial resistance by doing a random-effects meta-analysis and meta-regression. Our primary outcomes were the prevalence of bacterial co-infection and secondary infection, and the prevalence of antibiotic-resistant pathogens among patients with laboratory-confirmed COVID-19 and bacterial infections. The study protocol was registered with PROSPERO (CRD42021297344). FINDINGS: We included 148 studies of 362 976 patients, which were done between December, 2019, and May, 2021. The prevalence of bacterial co-infection was 5·3% (95% CI 3·8-7·4), whereas the prevalence of secondary bacterial infection was 18·4% (14·0-23·7). 42 (28%) studies included comprehensive data for the prevalence of antimicrobial resistance among bacterial infections. Among people with bacterial infections, the proportion of infections that were resistant to antimicrobials was 60·8% (95% CI 38·6-79·3), and the proportion of isolates that were resistant was 37·5% (26·9-49·5). Heterogeneity in the reported prevalence of antimicrobial resistance in organisms was substantial (I2=95%). INTERPRETATION: Although infrequently assessed, antimicrobial resistance is highly prevalent in patients with COVID-19 and bacterial infections. Future research and surveillance assessing the effect of COVID-19 on antimicrobial resistance at the patient and population level are urgently needed. FUNDING: WHO.

Antibiotic Selection and Duration for Catheter-Associated Urinary Tract Infection in Non-Hospitalized Older Adults: A Population-Based Cohort Study.

Background: We sought to evaluate the impact of antibiotic selection and duration of therapy on treatment failure in older adults with catheter-associated urinary tract infection (CA-UTI). Methods: We conducted a population-based cohort study comparing antibiotic treatment options and duration of therapy for non-hospitalized adults aged 66 and older with presumed CA-UTI (defined as an antibiotic prescription and an organism identified in urine culture in a patient with urinary catheterization documented within the prior 90 d). The primary outcome was treatment failure, a composite of repeat urinary antibiotic prescribing, positive blood culture with the same organism, all-cause hospitalization or mortality, within 60 days. We determined the risk of treatment failure accounting for age, sex, comorbidities, and healthcare exposure using log-binomial regression. Results: Of 4,436 CA-UTI patients, 2,709 (61.1%) experienced treatment failure. Compared to a reference of TMP-SMX (61.9% failure), of those treated with fluoroquinolones, 56.3% experienced failure (RR 0.91, 95% CI: 0.85-0.98) and 60.9% of patients treated with nitrofurantoin experienced failure (RR 1.02, 95% CI: 0.94-1.10). Compared to 5-7 days of therapy (treatment failure: 59.4%), 1-4 days was associated with 69.5% failure (RR 1.15, 95% CI: 1.05-1.27), and 8-14 days was associated with a 62.0% failure (RR 1.05, 95% CI: 0.99-1.11). Conclusions: Although most treatment options for CA-UTI have a similar risk of treatment failure, fluoroquinolones, and treatment durations ≥ 5 days in duration appear to be associated with modestly improved clinical outcomes. From a duration of therapy perspective, this study provides reassurance that relatively short courses of 5-7 days may be reasonable for CA-UTI.

Antimicrobial resistance and mortality following E. coli bacteremia.

Background: Global estimates suggest millions of deaths annually are associated with antimicrobial resistance (AMR) but these are generated from scarce data on the relative risk of death attributable to drug-resistant versus drug-sensitive infections. Methods: We examined all episodes of E. coli bloodstream infection in Ontario, Canada between 2017 and 2020, and measured 90 day mortality among those with resistant versus sensitive isolates for each of 8 commonly used antibiotic classes and a category of difficult to treat resistance (DTTR). We used multivariable logistic regression to calculate an adjusted odds of mortality associated with AMR, after accounting for patient demographics, comorbidities, and prior healthcare exposure. Findings: Among 14,548 eligible episodes of E. coli bloodstream infection, resistance was most common to aminopenicillins (46.8%), followed by first generation cephalosporins (38.8%), fluoroquinolones (26.5%), sulfonamides (24.1%), third generation cephalosporins (13.8%), aminoglycosides (11.7%), beta-lactam-beta-lactamase-inhibitors (9.1%) and carbapenems (0.2%). Only 18 (0.1%) episodes exhibited DTTR. For each antibiotic class, the unadjusted odds of mortality (OR) were higher among resistant isolates, but after accounting for patient characteristics the adjusted odds (aOR) of mortality were attenuated: aminopenicillins (OR 1.22, 95% CI 1.12-1.33; aOR 1.09, 95% CI 0.99-1.20), first generation cephalosporins (OR 1.24, 95% CI 1.14-1.35; aOR 1.07, 95% CI 0.97-1.18), third generation cephalosporins (OR 1.64, 95% CI 1.47-1.82; aOR 1.29, 95% CI 1.15-1.46), beta-lactam-beta-lactamase-inhibitors (OR 1.69, 95% CI 1.52-1.89, aOR 1.28, 95% CI 1.13-1.45), carbapenems (OR 3.11, 95% CI 1.52-6.34; aOR 2.06, 95% CI 0.91-4.66), sulfonamides (OR 1.19, 95% CI 1.07-1.31, aOR 1.06, 95% CI 0.95-1.18), fluoroquinolones (OR 1.49, 95% CI 1.36-1.64, aOR 1.16, 95% CI 1.05-1.29), aminoglycosides (OR 1.43, 95% CI 1.27-1.62; aOR 1.27, 95% CI 1.11-1.46), and DTTR (OR 3.71, 95% CI 1.46-9.41; aOR 2.58, 95% CI 0.87-7.66). Interpretation: AMR is associated with substantial increased mortality among patients with E. coli bloodstream infection, particularly for resistance to classes commonly used as empiric treatment. Surveillance for AMR-associated mortality should incorporate adjustment for patient characteristics and prior healthcare utilization. Funding: This work was supported by a project grant from CIHR (grant number 159503). This study was also supported by ICES, which is funded by an annual grant from Ontario Ministry of Health and Long-Term Care (MOHLTC).

Highly versus less bioavailable oral antibiotics in the treatment of gram-negative bloodstream infections: a propensity-matched cohort analysis.

OBJECTIVES: In this study, we evaluated the clinical outcomes associated with the use of highly bioavailable oral antibiotics (fluoroquinolones and trimethoprim-sulfamethoxazole) compared with the less-bioavailable oral antibiotics (ß-lactams) in gram-negative bloodstream infections (BSIs). METHODS: Among hospitalized older adult patients in Ontario, Canada, discharged home on oral treatment for gram-negative BSI between 1 January 2017 and 31 December 2019, we used a matched cohort design to compare outcomes among those receiving highly versus less-bioavailable agents; hard-matching 1:1 on sex, BSI pathogen (Escherichia coli vs. non-E. coli), and infection source (urinary vs. non-urinary/unknown source) along with a propensity score, incorporating specific pathogen, patient, and infection characteristics. The primary outcome was the composite of 90-day all-cause mortality, recurrent BSI with the same pathogen (genus and species), and re-admission to any Ontario hospital. RESULTS: A total of 2012 patients were included in the study (1006 in each bioavailability category). Those who received highly (compared with less) bioavailable antibiotics at discharge had lower rates of the composite outcome (171/1006 [17.0%] vs. 216/1006 [21.5%]), adjusted odds ratio being 0.74 (95% CI, 0.60-0.92). Recurrent BSI at 90 days was the main driver for the composite outcome occurring in 64 (5.4%) and 107 (9.4%) patients of the highly and less-bioavailable groups, respectively (p < 0.001) (adjusted odds ratio, 0.56; 95% CI, 0.40-0.78). DISCUSSION: Use of highly (compared with less) bioavailable antibiotics at discharge was associated with significantly better clinical outcomes among patients with gram-negative BSIs.

Economic burden of surgical management of surgical site infections following hip and knee replacements in Calgary, Alberta, Canada.

OBJECTIVE: To evaluate the cost of 1-stage and 2-stage revisions, debridement, antibiotic and implant retention (DAIR) and DAIR with liner exchange for complex surgical site infections (SSIs) following hip and knee replacements. DESIGN: Retrospective population-based economic analysis of patients undergoing intervention for SSIs between April 1, 2012 and March 31, 2019. SETTING: The study was conducted in the Calgary zone of Alberta Health Services (AHS) in Canada. PARTICIPANTS: Individuals >18 years with complex SSI following hip or knee replacement. METHODS: Patients with complex SSIs were identified using the AHS infection prevention and control database. A combination of microcosting and gross costing methods were used to estimate 12- and 24-month costs following the initial hospital admission for arthroplasty. Subgroup, inverse Gaussian and γ regression analyses were used to evaluate the impact of age and comorbidities on cost. RESULTS: In total, 142 patients with complex SSIs were identified, with a mean age of 66.8 years. Total direct medical costs in United States dollars of 2-stage revisions were ($100,992 (95% CI, 34,587-167,396) at 12 months. The 1-stage revision ($41,176; 95% CI, 23,361-58,991), DAIR with liner exchange ($41,267; 95% CI, 29,923-52,612) and DAIR ($46,605; 95% CI, 15,277-76,844) were associated with fewer costs at 12 months. Age >65 years and chronic complications of diabetes and hypertension were associated with increased costs in subgroup and regression analysis. CONCLUSIONS: Medical costs are highest at 12 months and for 2-stage revisions in hip and knee complex SSI cases. Further work should explore surgical outcomes correlated with costs to enhance patient care.

Economic Burden of Surgical Management of Prosthetic Joint Infections Following Hip and Knee Replacements in Alberta, Canada: An analysis and comparison of two major urban centers.

BACKGROUND: Complex surgical site infections (SSIs) and revisions for these infectious complications following total knee and hip arthroplasties are associated with significant economic costs. AIM: To evaluate the cost of one-stage and two-stage revisions; debridement, antibiotic, and implant retention (DAIR) and DAIR with liner exchange for complex hip or knee SSIs in Alberta, Canada. METHODS: We used the Alberta Health Services Infection Prevention and Control database to identify individuals >18 years old from the two major urban centers in Alberta, Calgary, and Edmonton zone, with complex hip or knee SSIs who underwent surgical intervention between April 1, 2012, and March 31, 2019. Micro-costing and gross-costing methods were used to estimate 12 and 24-month costs following the initial hospital admission for arthroplasty. Subgroup, inverse gaussian and gamma regression analysis were used to evaluate the associations of the revision procedure, age, sex, and comorbidities on cost. FINDINGS: A total of 382 patients with complex SSIs were identified with a mean age of 66.1 years. DAIR and DAIR with liner exchange resulted in the lowest 12- and 24-month costs at $53,197 (95% CI, $38,006 - $68,388) and $57,340 (95% CI, $48,576 - $66,105), respectively; two-stage revision was the costliest procedure. Most of the incurred costs (>98%) were accrued within the first 12 months following the initial procedure. CONCLUSIONS: Medical costs are highest 12 months following initial arthroplasty and for two-stage revisions in hip and knee complex SSI.

Age and sex-specific incidence rates of group A streptococcal pharyngitis between 2010 and 2018: a population-based study.

Aim: Group A streptococcus (GAS) pharyngitis is a common clinical infection with significant morbidity but remains understudied. Materials & methods: We sought to assess the rates of testing and incidence of GAS pharyngitis in Calgary, Alberta based on age and sex. Results: A total of 1,074,154 tests were analyzed (58.8% female, mean age 24.8 years) of which 16.6% were positive. Age-standardized testing and positivity was greatest in the 5-14 years age group and lowest in persons over 75 years. Females had greater rates of testing and positivity throughout. Testing rates (incidence rate ratios: 1.40, 95% CI: 1.39-1.41) and case rates (incidence rate ratios: 1.36, 95% CI: 1.33-1.39) increased over time. Conclusion: Future studies should focus on evaluating disparities in testing and treatment outcomes to optimize the approach to this infection.

Assessing the efficacy and safety of hydroxychloroquine as outpatient treatment of COVID-19: a randomized controlled trial.

BACKGROUND: Identification of therapies to prevent severe COVID-19 remains a priority. We sought to determine whether hydroxychloroquine treatment for outpatients with SARS-CoV-2 infection could prevent hospitalization, mechanical ventilation or death. METHODS: This randomized controlled trial was conducted in Alberta during the first wave of the COVID-19 pandemic without direct contact with participants. Community-dwelling individuals with confirmed SARS-CoV-2 infection (by reverse transcription polymerase chain reaction [RT-PCR] viral ribonucleic acid test) within the previous 4 days, and symptom onset within the previous 12 days, were randomly assigned to oral hydroxychloroquine or matching placebo for 5 days. Enrolment began Apr. 15, 2020. The primary outcome was the composite of hospitalization, invasive mechanical ventilation or death within 30 days. Secondary outcomes included symptom duration and disposition at 30 days. Safety outcomes, such as serious adverse events and mortality, were also ascertained. Outcomes were determined by telephone follow-up and administrative data. RESULTS: Among 4919 individuals with a positive RT-PCR test, 148 (10.2% of a planned 1446 patients) were randomly assigned, 111 to hydroxychloroquine and 37 to placebo. Of the 148 participants, 24 (16.2%) did not start the study drug. Four participants in the hydroxychloroquine group met the primary outcome (4 hospitalizations, 0 mechanical ventilation, 4 survived to 30 days) and none in the placebo group. Hydroxychloroquine did not reduce symptom duration (hazard ratio 0.77, 95% confidence interval 0.49-1.21). Recruitment was paused on May 22, 2020, when a since-retracted publication raised concerns about the safety of hydroxychloroquine for hospitalized patients with COVID-19. Although we had not identified concerns in a safety review, enrolment was slower than expected among those eligible for the study, and cases within the community were decreasing. Recruitment goals were deemed to be unattainable and the trial was not resumed, resulting in a study underpowered to assess the effect of treatment with hydroxychloroquine and safety. INTERPRETATION: There was no evidence that hydroxychloroquine reduced symptom duration or prevented severe outcomes among outpatients with proven COVID-19, but the early termination of our study meant that it was underpowered. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT04329611.