Population-based evaluation of the effectiveness of nirmatrelvir-ritonavir for reducing hospital admissions and mortality from COVID-19.

BACKGROUND: A randomized controlled trial involving a high-risk, unvaccinated population that was conducted before the Omicron variant emerged found that nirmatrelvir-ritonavir was effective in preventing progression to severe COVID-19. Our objective was to evaluate the effectiveness of nirmatrelvir-ritonavir in preventing severe COVID-19 while Omicron and its subvariants predominate. METHODS: We conducted a population-based cohort study in Ontario that included all residents who were older than 17 years of age and had a positive polymerase chain reaction test for SARS-CoV-2 between Apr. 4 and Aug. 31, 2022. We compared patients treated with nirmatrelvir-ritonavir with patients who were not treated and measured the primary outcome of hospital admission from COVID-19 or all-cause death at 1-30 days, and a secondary outcome of all-cause death. We used weighted logistic regression to calculate weighted odds ratios (ORs) with confidence intervals (CIs) using inverse probability of treatment weighting (IPTW) to control for confounding. RESULTS: The final cohort included 177 545 patients, 8876 (5.0%) who were treated with nirmatrelvir-ritonavir and 168 669 (95.0%) who were not treated. The groups were well balanced with respect to demographic and clinical characteristics after applying stabilized IPTW. We found that the occurrence of hospital admission or death was lower in the group given nirmatrelvir-ritonavir than in those who were not (2.1% v. 3.7%; weighted OR 0.56, 95% CI 0.47-0.67). For death alone, the weighted OR was 0.49 (95% CI 0.39-0.62). Our findings were similar across strata of age, drug-drug interactions, vaccination status and comorbidities. The number needed to treat to prevent 1 case of severe COVID-19 was 62 (95% CI 43-80), which varied across strata. INTERPRETATION: Nirmatrelvir-ritonavir was associated with significantly reduced odds of hospital admission and death from COVID-19, which supports use to treat patients with mild COVID-19 who are at risk for severe disease.

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

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

Streptococcus agalactiae infective endocarditis in Canada: a multicenter retrospective nested case control analysis.

BACKGROUND: Infective endocarditis (IE) caused by Streptococcus agalactiae (GBS) is increasingly reported and associated with an aggressive course and high mortality rate. Existing literature on GBS IE is limited to case series; we compared the characteristics of patients with GBS IE to patients with GBS bacteremia without IE to identify risk factors for development of IE. METHODS: A nested case-control study in a cohort of adult patients with GBS bacteremia over a 18-year period was conducted across seven centres in three Canadian cities. A chart review identified patients with possible or definite IE (per Modified Duke Criteria) and patients with IE were matched to those without endocarditis in a 1:3 fashion. Multivariate analyses were completed using logistic regression. RESULTS: Of 520 patients with GBS bacteremia, 28 cases of possible or definite IE were identified (5.4%). 68% (19/28) met criteria for definite IE, surgery was performed in 29% (8/28), and the overall in-hospital mortality rate was 29% (8/28). Multivariate analysis demonstrated that IE was associated with injection drug use (OR = 19.6, 95% CI = 3.39-111.11, p = 0.001), prosthetic valve (OR = 11.5, 95% CI = 1.73-76.92, p = 0.011) and lack of identified source of bacteremia (OR = 3.81, 95% CI = 1.24-11.65, p = 0.019). CONCLUSIONS: GBS bacteremia, especially amongst people who inject drugs, those with prosthetic valves, and those with no apparent source of infection, should increase clinical suspicion for IE.

Adjunctive vitamin D in tuberculosis treatment: meta-analysis of individual participant data.

BACKGROUND: Randomised controlled trials of adjunctive vitamin D in pulmonary tuberculosis (TB) treatment have yielded conflicting results. Individual participant data meta-analysis could identify factors explaining this variation. METHODS: We meta-analysed individual participant data from randomised controlled trials of vitamin D in patients receiving antimicrobial therapy for pulmonary TB. Primary outcome was time to sputum culture conversion. Secondary outcomes were time to sputum smear conversion, mean 8-week weight and incidence of adverse events. Pre-specified subgroup analyses were done according to baseline vitamin D status, age, sex, drug susceptibility, HIV status, extent of disease and vitamin D receptor genotype. RESULTS: Individual participant data were obtained for 1850 participants in eight studies. Vitamin D did not influence time to sputum culture conversion overall (adjusted HR 1.06, 95% CI 0.91-1.23), but it did accelerate sputum culture conversion in participants with multidrug-resistant pulmonary TB (adjusted HR 13.44, 95% CI 2.96-60.90); no such effect was seen in those whose isolate was sensitive to rifampicin and/or isoniazid (adjusted HR 1.02, 95% CI 0.88-1.19; p-value for interaction=0.02). Vitamin D accelerated sputum smear conversion overall (adjusted HR 1.15, 95% CI 1.01-1.31), but did not influence other secondary outcomes. CONCLUSIONS: Vitamin D did not influence time to sputum culture conversion overall, but it accelerated sputum culture conversion in patients with multidrug-resistant pulmonary TB.

A cross sectional study of animal and human colonization with Methicillin-Resistant Staphylococcus aureus (MRSA) in an Aboriginal community.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infections are common among humans in Aboriginal communities in Canada, for unknown reasons. METHODS: Cross sectional study of humans and dogs in an Aboriginal community of approximately 1200 persons. Our objectives were to measure community-based prevalence of nasal MRSA colonization among humans, use multivariable logistic regression to analyze risk factors for MRSA colonization, and perform molecular typing of Staphylococci isolated to investigate interspecies transmission. RESULTS: 461 humans were approached for consent and 442 provided complete data. 109/442 (24.7 %, 95 % C.I. = 20.7-28.7 %) of humans were colonized with MRSA. 169/442 (38.2 %) of humans had received antibiotics in the last 12 months. Only number of rooms in the house (OR 0.86, p = 0.023) and recreational dog use (OR 7.7, p = 0.002) were significant risk factors for MRSA colonization. 95/109 (87.1 %) of MRSA strains from humans were of the same spa type (CMRSA10/USA300). 8/157 (5.1 %, 95 % C.I. = 1.7-8.5 %) of dogs were colonized with methicillin-susceptible S. aureus, and no dogs were colonized with MRSA. CONCLUSIONS: Human MRSA colonization in this community is very common, and a single clone is predominant, suggesting local transmission. Antibiotic use is also very common. Crowding may partially explain high colonization, but most considered risk factors including animal exposure were not predictive. Very few dogs carried human Staphylococcal strains.

The Performance of Direct Disk Diffusion for Community Acquired Bacteremia due to Gram-Negative Bacilli and Its Impact on Physician Treatment Decisions.

Background. Direct disk diffusion susceptibility testing provides faster results than standard microtitre susceptibility. The direct result may impact patient outcome in sepsis if it is accurate and if physicians use the information to promptly and appropriately change antibiotic treatment. Objective. To compare the performance of direct disk diffusion with standard susceptibility and to consider physician decisions in response to these early results, for community acquired bacteremia with Gram-negative Bacilli. Methods. Retrospective observational study of all positive blood cultures with Gram-negative Bacilli, collected over one year. Physician antibiotic treatment decisions were assessed by an infectious diseases physician based on information available to the physician at the time of the decision. Results. 89 bottles growing Gram-negative Bacilli were included in the analysis. Direct disk diffusion agreement with standard susceptibility varied widely. In 47 cases (52.8%), the physician should have changed to a narrower spectrum but did not, in 18 cases (20.2%), the physician correctly narrowed from appropriate broad coverage, and in 8 cases (9.0%), the empiric therapy was correct. Discussion. Because inoculum is not standardized, direct susceptibility results do not agree with standard susceptibility results for all drugs. Physicians do not act on direct susceptibility results. Conclusion. Direct susceptibility should be discontinued in clinical microbiology laboratories.

Operator Influence on Blinded Diagnostic Accuracy of Point-of-Care Antigen Testing for Group A Streptococcal Pharyngitis.

Background. Acute pharyngitis caused by Group A Streptococcus (GAS) is a common presentation to pediatric emergency departments (ED). Diagnosis with conventional throat culture requires 18-24 hours, which prevents point-of-care treatment decisions. Rapid antigen detection tests (RADT) are faster, but previous reports demonstrate significant operator influence on performance. Objective. To measure operator influence on the diagnostic accuracy of a RADT when performed by pediatric ED nurses and clinical microbiology laboratory technologists, using conventional culture as the reference standard. Methods. Children presenting to a pediatric ED with suspected acute pharyngitis were recruited. Three pharyngeal swabs were collected at once. One swab was used to perform the RADT in the ED, and two were sent to the clinical microbiology laboratory for RADT and conventional culture testing. Results. The RADT when performed by technologists compared to nurses had a 5.1% increased sensitivity (81.4% versus 76.3%) (p = 0.791) (95% CI for difference between technologists and nurses = -11% to +21%) but similar specificity (97.7% versus 96.6%). Conclusion. The performance of the RADT was similar between technologists and ED nurses, although adequate power was not achieved. RADT may be employed in the ED without clinically significant loss of sensitivity.

Rat Bite Fever Resembling Rheumatoid Arthritis.

Rat bite fever is rare in Western countries. It can be very difficult to diagnose as blood cultures are typically negative and a history of rodent exposure is often missed. Unless a high index of suspicion is maintained, the associated polyarthritis can be mistaken for rheumatoid arthritis. We report a case of culture-positive rat bite fever in a 46-year-old female presenting with fever and polyarthritis. The clinical presentation mimicked rheumatoid arthritis. Infection was complicated by discitis, a rare manifestation. We discuss the diagnosis and management of this rare zoonotic infection. We also review nine reported cases of rat bite fever, all of which had an initial presumptive diagnosis of a rheumatological disorder. Rat bite fever is a potentially curable infection but can have a lethal course if left untreated.

Urinary tract infection diagnosis and response to therapy in long-term care: A prospective observational study.

BACKGROUND: The prevalence of asymptomatic bacteriuria among residents of long-term care (LTC) facilities is high, and is a source of inappropriate antibiotic prescription. OBJECTIVE: To establish symptoms and signs associated with a positive urine culture, and to determine whether antibiotic therapy is associated with functional improvement. METHODS: A total of 101 LTC patients were prospectively observed after submission of urine for culture. RESULTS: The culture positivity rate was consistent with the expected asymptomatic bacteriuria rate. Change in mental status and male sex were associated with culture positivity. Treatment decisions were not consistent with culture results. Treatment did not lead to improvement in activities of daily living scores at two days or seven days. DISCUSSION: Significant growth cannot be well predicted based on clinical variables; thus, the decision to submit urine is somewhat arbitrary. Because urine culture testing and treatment does not lead to functional improvement, restricting access to the test may be reasonable. CONCLUSION: Urine culture testing in LTC facilities does not lead to functional improvement.

HISTORIQUE: La prévalence de bactériuries asymptomatiques est élevée chez les résidents d'établissements de soins de longue durée (SLD). Elle suscite la prescription inappropriée d'antibiotiques. OBJECTIF: Déterminer les signes et symptômes associés à une culture d'urine positive et établir si l'antibiothérapie favorise une amélioration fonctionnelle. MÉTHODOLOGIE: Au total, 101 patients en SLD ont fait l'objet d'une observation prospective après l'envoi d'un prélèvement d'urine pour culture. RÉSULTATS: Le taux de cultures positives était conforme au taux prévu de bactériuries asymptomatiques. La détérioration de l'état mental et le sexe masculin s'associaient à des cultures positives. Les décisions thérapeutiques n'étaient pas en accord avec les résultats des cultures. Le traitement ne suscitait pas d'amélioration à l'indice d'activités de la vie quotidienne au bout de deux ou sept jours. EXPOSÉ: Les variables cliniques ne permettent pas de prévoir une croissance importante. Ainsi, la décision de faire une culture d'urine est quelque peu arbitraire. Puisque les cultures d'urine et le traitement n'assurent pas d'amélioration fonctionnelle, il est peut-être raisonnable de restreindre l'accès aux analyses. CONCLUSION: Dans les établissements de SLD, les analyses d'urine ne favorisent pas d'amélioration fonctionnelle.

Partial oral versus full intravenous antibiotic treatment of endocarditis in people who inject drugs: A systematic review.

Background: Prolonged intravenous (IV) antibiotic therapy may not be optimal for people who inject drugs (PWID) with infective endocarditis (IE) due to unique social and medical needs. The role of partial IV antibiotic therapy with continued oral (PO) antibiotic therapy is unclear. Methods: A systematic review was performed using EMBASE and MEDLINE databases. Included studies compared PO to IV antibiotic treatment for IE in PWID. Results: Four studies met eligibility. Observational studies included full IV treatment groups and partial IV, partial PO treatment groups for severe injection-related infections. PWID with IE comprised 41.0%-64.7% of the study populations but outcomes specific to IE were not separately reported. All-cause 90-day readmission rates were comparable between the IV treatment group (27.9%-31.5%) and partial IV, partial PO treatment group (24.8%-32.5%). Ninety-day mortality was non-significantly different between IV treatment (4.9%-10.7%) and partial IV, partial PO treatment groups (2.4%-13.0%). One small randomized clinical trial compared IV oxacillin or vancomycin with gentamicin to PO ciprofloxacin plus rifampin. The cure rates were 91% and 90%, respectively. Conclusion: There is limited evidence comparing IV treatment to partial IV, partial PO antibiotic treatment in PWID with IE. Observational studies suggest that PO antibiotic therapy after initial IV treatment may be equivalent to full IV treatment alone within specific parameters, but randomized trials are needed to inform recommendations. Substantial clinical and social benefits for PWID and advantages for the health care system will result if PO treatment strategies with equal efficacy can be implemented.

Historique: L'antibiothérapie intraveineuse (IV) prolongée n'est peut-être pas optimale chez les utilisateurs de drogues par injection (UDI) atteints d'une endocardite infectieuse (EI) découlant de besoins médicaux et sociaux particuliers. On ne connaît pas clairement le rôle de l'antibiothérapie IV partielle conjuguée à l'antibiothérapie par voie orale (PO). Méthodologie: Les chercheurs ont procédé à une analyse systématique au moyen des bases de données EMBASE et MEDLINE. Les études incluses comparaient l'antibiothérapie PO à l'antibiothérapie IV en cas d'EI chez les UDI. Résultats: Quatre études respectaient les critères d'admissibilité. Les études observationnelles incluaient des groupes de traitement IV complets et des groupes de traitements IV et PO partiels en raison de de graves infections liées aux injections. Les UDI atteints d'une IE formaient de 41,0 % à 64,7 % de la population à l'étude, mais les résultats cliniques propres à l'IE n'étaient pas déclarés séparément. Les taux de réadmission toutes causes confondues au bout de 90 jours étaient comparables entre le groupe de traitement IV (27,9 % à 31,5 %) et le groupe de traitement IV et PO partiel (24,8 % à 32,5 %). La mortalité au bout de 90 jours n'était pas sensiblement différente entre le groupe de traitement IV (4,9 % à 10,7 %) et le groupe de traitement IV et PO partiel (2,4 % à 13,0 %). Une petite étude clinique randomisée a comparé l'oxacilline ou la gentamicine IV à la ciprofloxacine conjuguée à la rifampine PO. Les taux de guérison actuels s'élevaient à 91 % et à 90 %, respectivement. Conclusion: Les données probantes sur la comparaison entre l'antibiothérapie IV et l'antibiothérapie IV et PO partielle sont limitées chez les UDI ayant une IE. Selon les études observationnelles, l'antibiothérapie PO après un traitement IV initial pourrait équivaloir à un traitement IV complet unique selon des paramètres précis, mais des études randomisées s'imposent pour étayer les recommandations. Les UDI tireront des avantages cliniques et sociaux importants s'il est possible d'adopter des stratégies de traitement PO de même efficacité, et le système de santé en profitera également. Summary: Injection drug use significantly increases the risk of infective endocarditis, a bacterial infection of one or more heart valves. When diagnosed, infective endocarditis typically requires weeks of antibiotic therapy, often intravenous. This can amount to long hospital stays, particularly for people who inject drugs, as outpatient antibiotic therapies are often not feasible. As a result, there can be significant consequences in this population such as loss of housing, childcare, and employment, which may have already been unstable at the time of their hospital admission. As such, some people who inject drugs leave the hospital before their antibiotic course is completed. This can predispose them to redeveloping the infection and can lead to other complications including death. In the general population with infective endocarditis, the outcomes with oral antibiotics after a short course of intravenous antibiotics has been shown to be similar to a full course of intravenous treatment in some patients or in patients with specific clinical characteristics. Most of the current studies, however, do not include, or include very few people who inject drugs, so limited conclusions can be made for this population. This systematic review examines the current literature for oral compared to intravenous antibiotic treatment of infective endocarditis in people who inject drugs, in order to provide a baseline of our current understanding and advocate for more research.

Population-based outpatient antimicrobial use in Newfoundland and Labrador: a retrospective descriptive study.

BACKGROUND: Data that have been reported on antimicrobial use in Newfoundland and Labrador (NL) do not appear to be representative of use at the population level. We sought to use pharmacy network data on prescriptions to describe outpatient antimicrobial use in NL. METHODS: We analyzed all outpatient antimicrobial prescriptions dispensed between June 1, 2017, and June 8, 2021, from the provincial pharmacy network database and translated deidentified data into SPSS. We excluded prescriptions for parenteral and topical antimicrobials, antivirals and antifungals. We described antimicrobial use using the prescription rate and defined daily dose (DDD) rate. RESULTS: Overall, we analyzed 1 586 534 prescriptions dispensed to 394 708 people by 3431 prescribers. The rate of antimicrobial use was 741 prescriptions per 1000 population per year (7161 DDD/1000 population/yr). The median duration of prescriptions was 7 (interquartile range 7-10) days. The prescription rate decreased from 867 to 546 per 1000 population per year (-37%) over the study period, and the mean DDD rate decreased from 8387 to 5356 DDD per 1000 population per year (-36.1%). Antimicrobials with the highest DDD rate were amoxicillin (1568 DDD/1000/yr), doxycycline (864 DDD/1000/yr) and ciprofloxacin (633 DDD/1000/yr). Prescribers wrote a mean of 102 (standard deviation 248) prescriptions per year; 3 prescribers wrote more than 2500 prescriptions per year. Overall, 9203 (2.3%) of the 394 708 people in the study population received 4 or more prescriptions per year. INTERPRETATION: The rate of antimicrobial use in NL is lower than previously described in national surveillance data. Potential targets for stewardship intervention include prolonged duration of prescriptions, high-rate prescribers and high-rate patients, but further research is needed to assess the appropriateness of prescriptions according to diagnosis.

Characteristics and clinical outcomes of nirmatrelvir/ritonavir (PaxlovidTM) recipients in Canada, 2022: a descriptive cohort study.

Background: Nirmatrelvir/ritonavir (N/R) (PaxlovidTM) was introduced in Canada in January 2022. This was the first oral coronavirus disease 2019 (COVID-19) antiviral therapy that was deployed on a large scale in Canada. Since N/R was a new therapeutic option to reduce severe outcomes in high-risk populations, clinical and implementation questions were raised about its real-world utilization and impact. The objective of this retrospective observational study was to describe the characteristics and clinical outcomes of recipients of N/R in the first several months of its availability in Canada, during the Omicron wave. Methods: Provincial summary data were pooled together for the analysis. Descriptive statistics were used to explore the characteristics and clinical outcomes of the recipients. Pearson's Chi-square test and unadjusted odds ratio along with 95% confidence intervals were used to identify the potential risk factors for severe outcomes. Data were generally collected between January and September 2022. Results: Seventy-six percent of N/R recipients were 60 years of age and older and 56% were female. Eighty-four percent of recipients had received three or more COVID-19 vaccinations and 67% had comorbidities. All-cause severe 30-day outcomes were uncommon, with 0.4% reported as deceased, 0.1% admitted to the intensive care unit and 2.0% hospitalized after N/R administration. Risk factors statistically associated with severe outcomes were immunosuppression, comorbidities, age of 60 years and older, and being unvaccinated. Conclusion: In the first months of its availability in Canada, N/R was mostly used in vaccinated patients 60 years and older with one or more comorbidities. Severe outcomes in N/R recipients were uncommon and mostly reported in patients with risk factors.

Retrospective review of rates of sexually transmitted and blood-borne infection (STBBI) testing in provincial corrections facilities in Newfoundland and Labrador.

Background: Sexually transmitted and blood borne infection (STBBI) testing is recommended for people who are incarcerated (PWAI). We sought to determine the rate of STBBI testing during admissions to provincial correctional institutions in Newfoundland and Labrador (NL). Methods: This retrospective cohort study collected the identification of all admissions records in provincial correctional facilities in NL between July 1, 2020 and June 31, 2021 using the Provincial Corrections Offender Maintenance System database. Admissions to provincial detention centers were excluded. Records were linked with STBBI results, when available, within the electronic medical record (Meditech) using demographics. Testing rates, STBBI positivity rates, and univariate analysis of predictors for STBBI testing were completed. Results: Of the 1,824 admissions identified, 1,716 were available for linkage to laboratory results. Admissions to detention centers (n = 105) were excluded. Any STBBI test result was available for 72 (4.5%) of admissions. No admission had complete testing for all STBBI. Facility testing rates ranged from 1.9 to 11.2% and 37.5% of STBBI tests had any positive results. Sixteen out of the 21 (76.2%) hepatitis C virus (HCV) antibody positives received HCV RNA testing, and 11/16 (88.8%) were HCV RNA positive. Institution (p = 0.001) and sex (p = 0.004) were found to be significant predictors of STBBI testing, while age was not significant (p = 0.496). Conclusions: STBBI testing rates were low in provincial correctional facilities in NL, and STBBI prevalence, especially for HCV, was high among those tested. Strategies to increase the rate of testing could contribute to STBBI control in corrections facilities.

Culture-negative endocarditis diagnosed using 16S DNA polymerase chain reaction.

16S DNA polymerase chain reaction (PCR) is a molecular amplification technique that can be used to identify bacterial pathogens in culture-negative endocarditis. Bacterial DNA can be isolated from surgically excised valve tissue or from blood collected in EDTA vials. Use of this technique is particularly helpful in identifying the bacterial pathogen in cases of culture-negative endocarditis. A case involving a 48-year-old man who presented with severe aortic regurgitation and a four-month prodrome of low-grade fever is reported. Blood and valve tissue cultures following valve replacement were negative. A valve tissue sample was sent for investigation with 16S DNA PCR, which successfully identified Streptococcus salivarius and was interpreted as the true diagnosis. A review of the literature suggests that 16S DNA PCR from valve tissue is a more sensitive diagnostic test than culture. It is also extremely specific, based on a sequence match of at least 500 base pairs.

La réaction en chaîne de la polymérase (PRN) ADN 16S est une technique d'amplification moléculaire qui peut être utilisée pour déterminer les pathogènes bactériens en cas d'endocardite à culture négative. L'ADN bactérien peut être isolé des tissus valvulaires excisés par voie chirurgicale ou du sang recueilli dans des fioles d'EDTA. Cette technique est particulièrement utile pour déterminer le pathogène bactérien dans les cas d'endocardite à culture négative. Les auteurs présentent le cas d'un homme de 48 ans qui a consulté à cause d'une régurgitation aortique importante et d'un prodrome de faible fièvre depuis quatre mois. Les cultures du sang et des tissus valvulaires effectuées après le remplacement valvulaire se sont révélées négatives. Un échantillon de tissu valvulaire a été soumis à une PCR ADN 16S, laquelle a déterminé la présence de Streptococcus salivarius, interprété comme le véritable diagnostic. D'après une analyse bibliographique, la PCR ADN 16S prélevée dans le tissu valvulaire serait un test diagnostique plus sensible que la culture. Elle est également d'une extrême spécificité, grâce à un appariement séquentiel d'au moins 500 paires de base.

The epidemiology of delayed HIV diagnosis in Ibadan, Nigeria.

BACKGROUND: Human immunodeficiency virus infection (HIV) is one of the major health burdens in Nigeria. Delayed HIV diagnosis remains a significant driver of HIV transmission. The risk factors of delayed HIV diagnosis have not been widely studied in Nigeria. This observational study examined demographic risk factors for delayed HIV diagnosis and the trends in the annual total cases of delayed HIV diagnosis in Ibadan, Nigeria. METHODS: We examined the data on HIV patients enrolled in care at the University College Hospital's Antiretroviral Therapy (ART) clinic in Ibadan, Nigeria. Delayed HIV diagnosis was defined as a Cluster of Differentiation 4 (CD4) count of less than 350 cells/mm³ at the time of diagnosis. The association between delayed HIV diagnosis and risk factors was analyzed using logistic regression. The trends in the annual total cases of delayed HIV diagnosis over time were examined. RESULTS: This study included 3458 HIV patients. There were 1993/3458 prevalent cases of delayed HIV diagnosis (57.6%). The risk factors for delayed HIV diagnosis were older age, retirement, marriage separation, never married, and widowed female. The factors that were significantly associated with a low risk of delayed HIV diagnosis were student and tertiary education. There was a progressive decline in the annual cases of delayed HIV diagnosis. CONCLUSIONS: Although the cases of delayed HIV diagnosis are still high, they are declining. Human immunodeficiency virus testing should be targeted at populations at risk of delayed diagnosis. Considerable public awareness and education programs about HIV testing may significantly reduce delayed HIV diagnosis in Nigeria.

Two cases of tularemia in hunters from rural Newfoundland.

BACKGROUND: Tularemia is a rare zoonosis caused by Francisella tularensis, a small gram-negative intracellular coccobacillus. Transmission occurs through direct contact with small mammals such as hares and rabbits, exposure to ticks, or ingestion or inhalation of aerosolized particles. It is a highly variable disease with six subtypes based on clinical features. Tularemia is a very rare disease in Canada, with only 0.01 cases per 100,000 people reported in 2017. METHODS: In this case report, we describe two cases of tularemia affecting hunters from rural Newfoundland and Labrador. RESULTS: The first case describes a patient with glandular tularemia diagnosed with serology; the second describes a patient with typhoidal tularemia diagnosed on blood culture. Both patients recovered after treatment with gentamicin. DISCUSSION: These cases highlight the importance of eliciting a careful social history from patients presenting with an unexplained febrile illness. Tularemia should be considered in the differential diagnosis of fever after hunting in rural areas.

HISTORIQUE: La tularémie est une zoonose rare causée par le Francisella tularensis, un petit coccobacille intracellulaire à Gram négatif. La transmission se produit par contact direct avec des petits mammifères comme des lièvres et des lapins, l'exposition aux tiques, l'ingestion ou l'inhalation de particules aérosolisées. C'est une maladie extrêmement variable possédant six sous-types en fonction des caractéristiques cliniques. La tularémie est une maladie très rare au Canada; seulement 0,01 cas sur 100 000 habitants a été signalé en 2017. MÉTHODOLOGIE: Dans le présent rapport de cas, les auteurs décrivent deux cas de tularémie chez des chasseurs de régions rurales de Terre-Neuve-et-Labrador. RÉSULTATS: Le premier cas décrit un patient atteint de tularémie glandulaire diagnostiquée par sérologie et le deuxième, un patient atteint d'une tularémie typhoïde diagnostiquée par culture sanguine. Les deux patients se sont rétablis après avoir été traités à la gentamicine. DISCUSSION: Ces cas font ressortir l'importance d'une histoire sociale attentive des patients qui ont consulté à cause d'une maladie fébrile inexpliquée. Il faut envisager une tularémie lors du diagnostic différentiel de fièvre chez des personnes qui ont chassé dans des régions rurales.

Modified reporting of positive urine cultures to reduce treatment of asymptomatic bacteriuria in long-term care facilities: a randomized controlled trial.

Objectives: We conducted a prospective, randomized, unblinded superiority trial of the safety and efficacy of modified reporting of positive urine cultures to improve the appropriateness of treatment for asymptomatic bacteriuria (ASB) and urinary tract infection (UTI) in long-term care facilities (LTCFs). Methods: Consecutive positive urine cultures collected from LTCF patients were randomized between standard (identification and susceptibility) or modified (without identification and susceptibility) laboratory reports. Exclusion criteria were current antibiotic treatment, neutropenia, or transfer to acute care. The diagnosis of UTI or ASB was made prospectively. Results: One hundred and sixty-nine urine cultures were considered, 100 were randomized and included in ITT analysis, and 96 were included in PP analysis. Sixty-two out of 100 (62%) patients had ASB [41/62 (66%) treated] and 38/100 (38%) had UTI [35/38 (92%) treated]. The lab was called to report the identification and susceptibility in 31/51 (61%) modified reports. The rate of appropriate treatment was higher in the modified report arm: 31/51 (61%) versus 25/49 (51%) (+10%, P = 0.33). Untreated ASB was higher in the modified report arm: 13/32 (41%) versus 8/30 (27%) (+14%, P = 0.25). There were two deaths (one treated ASB, one untreated ASB) and 15 adverse events in the modified arm. There were no deaths (P = 0.16) and 11 adverse events (P = 0.43) in the standard arm. Three patients with untreated UTI survived. Conclusions: Modified reporting of urine culture improved the appropriateness of treatment by reducing treatment of ASB, but not significantly. Many LTCF prescribers requested standard urine culture reports. Modified reporting may not be suitable for LTCF implementation.

Cost-effectiveness of remdesivir plus usual care versus usual care alone for hospitalized patients with COVID-19: an economic evaluation as part of the Canadian Treatments for COVID-19 (CATCO) randomized clinical trial.

BACKGROUND: The role of remdesivir in the treatment of hospitalized patients with COVID-19 remains ill-defined. We conducted a cost-effectiveness analysis alongside the Canadian Treatments for COVID-19 (CATCO) open-label, randomized clinical trial evaluating remdesivir. METHODS: Patients with COVID-19 in Canadian hospitals from Aug. 14, 2020, to Apr. 1, 2021, were randomly assigned to receive remdesivir plus usual care versus usual care alone. Taking a public health care payer's perspective, we collected in-hospital outcomes and health care resource utilization alongside estimated unit costs in 2020 Canadian dollars over a time horizon from randomization to hospital discharge or death. Data from 1281 adults admitted to 52 hospitals in 6 Canadian provinces were analyzed. RESULTS: The total mean cost per patient was $37 918 (standard deviation [SD] $42 413; 95% confidence interval [CI] $34 617 to $41 220) for patients randomly assigned to the remdesivir group and $38 026 (SD $46 021; 95% CI $34 480 to $41 573) for patients receiving usual care (incremental cost -$108 [95% CI -$4953 to $4737], p > 0.9). The difference in proportions of in-hospital deaths between remdesivir and usual care groups was -3.9% (18.7% v. 22.6%, 95% CI -8.3% to 1.0%, p = 0.09). The difference in proportions of incident invasive mechanical ventilation events between groups was -7.0% (8.0% v. 15.0%, 95% CI -10.6% to -3.4%, p = 0.006), whereas the difference in proportions of total mechanical ventilation events between groups was -5.7% (16.4% v. 22.1%, 95% CI -10.0% to -1.4%, p = 0.01). Remdesivir was the dominant intervention (but only marginally less costly, with mildly lower mortality) with an incalculable incremental cost effectiveness ratio; we report results of incremental costs and incremental effects separately. For willingness-to-pay thresholds of $0, $20 000, $50 000 and $100 000 per death averted, a strategy using remdesivir was cost-effective in 60%, 67%, 74% and 79% of simulations, respectively. The remdesivir costs were the fifth highest cost driver, offset by shorter lengths of stay and less mechanical ventilation. INTERPRETATION: From a health care payer perspective, treating patients hospitalized with COVID-19 with remdesivir and usual care appears to be preferrable to treating with usual care alone, albeit with marginal incremental cost and small clinical effects. The added cost of remdesivir was offset by shorter lengths of stay in the intensive care unit and less need for ventilation. STUDY REGISTRATION: ClinicalTrials. gov, no. NCT04330690.

Appropriateness of antibiotic use in community hospitals in rural Newfoundland and Labrador.

Background: Surveillance of the appropriateness of antimicrobial prescribing can identify targets for quality improvement in antimicrobial stewardship. Our objective was to measure antibiotic prescription prevalence, indication, and appropriateness at three rural community hospitals in a 1-day point prevalence study. Methods: Inpatient antibiotic prescriptions given at three community hospitals on April 24, 2019 were provided by the hospital pharmacies. These prescriptions were analyzed using the Australian National Antimicrobial Prescribing Survey (NAPS) tool. Prescriptions were assessed by an infectious diseases physician and analyzed per prescription. Results: Eighty prescriptions given to 58 inpatients were included. Antibiotic treatment prevalence was 58/120 beds (48.3%), and overall appropriateness was 37/80 prescriptions (46.3%). The most prescribed antibiotics were ceftriaxone (17 [21.3%]; 47.1% appropriate), piperacillin-tazobactam (10 [12.5%]; 10.0% appropriate), and moxifloxacin (9 [11.3%]; 0% appropriate). The most common indications were respiratory tract infections (36 [45.0%]; 36.1% appropriate), skin and soft tissue infections (14 [17.5%]; 78.6% appropriate), and urinary tract infections (9 [11.3%]; 11.1% appropriate). Of the 80 prescriptions, 50 (62.5%) documented an indication, and 71 (88.8%) documented a stop or review date. Conclusions: We observed a high treatment prevalence and low appropriateness. Overall appropriateness was lower than in urban hospitals.

Historique: La surveillance de la pertinence des prescriptions d'antimicrobiens peut permettre de cibler des mesures d'amélioration de la qualité de la gestion antimicrobienne. Les chercheurs se sont donné l'objectif de mesurer la prévalence des prescriptions d'antibiotiques, leur indication et leur pertinence dans trois hôpitaux généraux ruraux au moyen d'une étude de prévalence ponctuelle d'un jour. Méthodologie: Tous les antibiotiques prescrits aux patients hospitalisés ont été remis aux chercheurs par la pharmacie de trois hôpitaux généraux le 24 avril 2019. Les chercheurs ont analysé ces prescriptions au moyen de l'outil du sondage australien de prescriptions nationales d'antimicrobiens (NAPS, selon l'acronyme anglais). Un infectiologue les a évaluées, et chacune a été analysée. Résultats: Les chercheurs ont inclus 80 prescriptions remises à 58 patients hospitalisés. La prévalence de traitement antibiotique s'élevait à 58 lits sur 120 (48,3 %), et la pertinence globale, à 37 prescriptions sur 80 (46,3 %). Les antibiotiques les plus prescrits étaient la ceftriaxone (17; 21,3 %), dont 47,1 % étaient appropriés; la pipéracilline-tazobactam (dix; 12,5 %), dont 10,0 % étaient appropriés; et la moxifloxacine (neuf; 11,3 %), dont 0 % était appropriés. Les indications les plus courantes étaient les infections respiratoires : 36 (45,0 %), dont 36,1 % étaient appropriées; les infections de la peau et des tissus mous : 14 (17,5 %), dont 78,6 % étaient appropriées; et les infections urinaires : neuf (11,3 %), dont 11,1 % étaient appropriées. Des 80 prescriptions, 50 (62,5 %) comportaient une indication, et 71 (88,8 %) comportaient une date d'arrêt ou de révision. Conclusion: Les chercheurs ont observé une forte prévalence de traitements et une pertinence basse. La pertinence globale était plus basse que dans les hôpitaux urbains.

Modified reporting of positive urine cultures to reduce inappropriate antibiotic treatment of catheter-associated asymptomatic bacteriuria (CA-ASB) among inpatients, a randomized controlled trial.

OBJECTIVE: To determine whether modified reporting of positive urine cultures collected from indwelling catheters improved treatment decisions without causing harm. DESIGN: Prospective, unblinded, randomized control trial. SETTING: Two tertiary-care hospitals. PARTICIPANTS: Overall, 100 consecutive positive urine cultures collected from catheterized inpatients were randomized between standard and modified laboratory reporting between November 2018 and June 2019. Exclusion criteria were pregnancy, current antibiotic treatment, ICU or urology admission, or neutropenia. INTERVENTION: The modified report included significant growth without providing identification, quantification, or susceptibility. The standard report included identification, quantitation and susceptibility. Diagnosis of catheter-associated asymptomatic bacteriuria (CA-ASB) and catheter-associated urinary tract infection (CA-UTI) followed published criteria, using prospective chart review. The appropriate antibiotic treatment was defined as treatment of CA-UTI, and no treatment of CA-ASB. Patients were followed for 7 days. RESULTS: Of 543 urine cultures, 443 (82%) were excluded. Of 100 patients, 75 (75%) had CA-ASB and 25 (25%) had CA-UTI. Treatment was given to 45 of 75 CA-ASB patients (60%) and all 25 CA-UTI patients (100%). Appropriate treatment rate was higher in the modified reporting arm than in the standard reporting arm: 57% vs 50% (+7.4%; relative risk [RR], 1.15; P = .45). Untreated CA-ASB was higher in the modified reporting arm: 45% vs 33% (+12%; RR, 1.36; P = .30). The standard report was requested for 33% of modified reports. Furthermore, 4 deaths and 26.9% adverse events occurred in the modified reporting arm, and 3 deaths and 41.3% adverse events occurred in the standard reporting arm. CONCLUSIONS: Modified reporting increased the appropriateness of treatment, and may be safe.Clinical trials identifier: ClinicalTrials.gov#NCT03488355.