Association Between Periprosthetic Joint Infection and Mortality Following Primary Total Hip Arthroplasty.

BACKGROUND: Periprosthetic joint infection (PJI) remains a dreaded and unpredictable complication after total hip arthroplasty (THA). In addition to causing substantial morbidity, PJI may contribute to long-term mortality risk. Our objective was to determine the long-term mortality risk associated with PJI following THA. METHODS: This population-based, retrospective cohort study included adult patients (≥18 years old) in Ontario, Canada, who underwent their first primary elective THA for arthritis between April 1, 2002, and March 31, 2021. The primary outcome was death within 10 years after the index THA. Mortality was compared between propensity-score-matched groups (PJI within 1 year after surgery versus no PJI within 1 year after surgery) with use of survival analyses. Patients who died within 1 year after surgery were excluded to avoid immortal time bias. RESULTS: A total of 175,432 patients (95,883 [54.7%] women) with a mean age (and standard deviation) of 67 ± 11.4 years underwent primary THA during the study period. Of these, 868 patients (0.49%) underwent surgery for a PJI of the replaced joint within 1 year after the index procedure. After matching, patients with a PJI within the first year had a significantly higher 10-year mortality rate than their counterparts (11.4% [94 of 827 patients] versus 2.2% [18 of 827 patients]; absolute risk difference, 9.19% [95% confidence interval (CI), 6.81% to 11.6%]; hazard ratio, 5.49 [95% CI, 3.32 to 9.09]). CONCLUSIONS: PJI within 1 year after surgery is associated with over a fivefold increased risk of mortality within 10 years. The findings of this study underscore the importance of prioritizing efforts related to the prevention, diagnosis, and treatment of PJIs. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Implementation of point-of-care molecular testing for respiratory viruses in congregate living settings.

OBJECTIVE: To implement and evaluate a point-of-care (POC) molecular testing platform for respiratory viruses in congregate living settings (CLS). DESIGN: Prospective quality improvement study. SETTING: Seven CLS, including three nursing homes and four independent-living facilities. PARTICIPANTS: Residents of CLS. METHODS: A POC platform for COVID-19, influenza A and B, and respiratory syncytial virus was implemented at participating CLS from December 1, 2022 to April 15, 2023. Residents with respiratory symptoms underwent paired testing, with respiratory specimens tested first with the POC platform and then delivered to an off-site laboratory for multiplex respiratory virus panel (MRVP) polymerase chain reaction (PCR) as per standard protocol. Turn-around time and diagnostic accuracy of the POC platform were compared against MRVP PCR. In an exploratory analysis, time to outbreak declaration among participating CLS was compared against a convenience sample of 19 CLS that did not use the POC platform. RESULTS: A total of 290 specimens that underwent paired testing were included. Turn-around time to result was significantly shorter with the POC platform compared to MRVP PCR, with median difference of 36.2 hours (interquartile range 21.8-46.4 hours). The POC platform had excellent diagnostic accuracy compared to MRVP PCR, with area under the curve statistic of .96. Time to outbreak declaration was shorter in CLS that used the POC platform compared to CLS that did not. CONCLUSION: Rapid POC testing platforms for respiratory viruses can be implemented in CLS, with high diagnostic accuracy, expedited turn-around times, and shorter time to outbreak declaration.

Predictors of SARS-CoV-2 transmission in congregate living settings: a multicenter prospective study.

BACKGROUND: Older adults residing in congregate living settings (CLS) such as nursing homes and independent living facilities remain at increased risk of morbidity and mortality from coronavirus disease 2019. We performed a prospective multicenter study of consecutive severe acute respiratory coronavirus virus 2 (SARS-CoV-2) exposures to identify predictors of transmission in this setting. METHODS: Consecutive resident SARS-CoV-2 exposures across 17 CLS were prospectively characterized from 1 September 2022 to 1 March 2023, including factors related to environment, source, and exposed resident. Room size, humidity, and ventilation were measured in locations where exposures occurred. Predictors were incorporated in a generalized estimating equation model adjusting for the correlation within CLS. RESULTS: Among 670 consecutive exposures to SARS-CoV-2 across 17 CLS, transmission occurred among 328 (49.0%). Increased risk was associated with nursing homes (odds ratio (OR) = 90.8; 95% CI, 7.8-1047.4), Jack and Jill rooms (OR = 2.2; 95% CI, 1.3-3.6), from source who was pre-symptomatic (OR = 11.2; 95% CI, 4.1-30.9), symptomatic (OR = 6.5; 95% CI, 1.4-29.9), or rapid antigen test positive (OR = 35.6; 95% CI, 5.6-225.6), and in the presence of secondary exposure (OR = 6.3; 95% CI, 1.6-24.0). Exposure in dining room was associated with reduced risk (OR = 0.02; 95% CI, 0.005-0.08) as was medium room size (OR = 0.3; 95% CI, 0.2-0.6). Recent vaccination of exposed resident (OR = 0.5; 95% CI, 0.3-1.0) and increased ventilation of room (OR = 0.9; 95% CI, 0.8-1.0) were marginally associated with reduced risk. CONCLUSION: Prospective assessment of SARS-CoV-2 exposures in CLS suggests that source characteristics and location of exposure are most predictive of resident transmission. These findings can inform risk assessment and further opportunities to prevent transmission in CLS.

Utility of routine post-admission testing for SARS-CoV-2 in a rehabilitation facility.

Asymptomatic screening for SARS-CoV-2 is recommended in healthcare settings during periods of increased incidence, yet studies in rehabilitation settings are lacking. Routine weekly post-admission asymptomatic testing in a rehabilitation facility offered marginal gain beyond syndromic and targeted unit testing and was not associated with a reduced risk of healthcare-associated COVID-19.

"4 E's" Ways That Clinicians Can Reduce Low-Value Care on Medical Wards.

This JAMA Network Insight demonstrates examples of how clinicians can implement stepwise changes to reduce unnecessary patient harms, using the 4 E's.

Influenza outbreak management tabletop exercise for congregate living settings.

We conducted a tabletop exercise on influenza outbreak preparedness that engaged a large group of congregate living settings (CLS), with improvements in self-reported knowledge and readiness. This proactive approach to responding to communicable disease threats has potential to build infection prevention and control capacity beyond COVID-19 in the CLS sector.

Humoral Response Following 3 Doses of mRNA COVID-19 Vaccines in Patients With Non-Dialysis-Dependent CKD: An Observational Study.

Background: Chronic kidney disease (CKD) is associated with a lower serologic response to vaccination compared to the general population. There is limited information regarding the serologic response to coronavirus disease 2019 (COVID-19) vaccination in the non-dialysis-dependent CKD (NDD-CKD) population, particularly after the third dose and whether this response varies by estimated glomerular filtration rate (eGFR). Methods: The NDD-CKD (G1-G5) patients who received 3 doses of mRNA COVID-19 vaccines were recruited from renal clinics within British Columbia and Ontario, Canada. Between August 27, 2021, and November 30, 2022, blood samples were collected serially for serological testing every 3 months within a 9-month follow-up period. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-spike, anti-receptor binding domain (RBD), and anti-nucleocapsid protein (NP) levels were determined by enzyme-linked immunosorbent assay (ELISA). Results: Among 285 NDD-CKD patients, the median age was 67 (interquartile range [IQR], 52-77) years, 58% were men, 48% received BNT162b2 as their third dose, 22% were on immunosuppressive treatment, and COVID-19 infection by anti-NP seropositivity was observed in 37 of 285 (13%) patients. Following the third dose, anti-spike and anti-RBD levels peaked at 2 months, with geometric mean levels at 1131 and 1672 binding antibody units per milliliter (BAU/mL), respectively, and seropositivity rates above 93% and 85%, respectively, over the 9-month follow-up period. There was no association between eGFR or urine albumin-creatinine ratio (ACR) with mounting a robust antibody response or in antibody levels over time. The NDD-CKD patients on immunosuppressive treatment were less likely to mount a robust anti-spike response in univariable (odds ratio [OR] 0.43, 95% confidence interval [CI]: 0.20, 0.93) and multivariable (OR 0.52, 95% CI: 0.25, 1.10) analyses. An interaction between age, immunoglobulin G (IgG) antibody levels, and time was observed in both unadjusted (anti-spike: P = .005; anti-RBD: P = .03) and adjusted (anti-spike: P = .004; anti-RBD: P = .03) models, with older individuals having a more pronounced decline in antibody levels over time. Conclusion: Most NDD-CKD patients were seropositive for anti-spike and anti-RBD after 3 doses of mRNA COVID-19 vaccines and we did not observe any differences in the antibody response by eGFR.

Integration of hospital with congregate care homes in response to the COVID-19 pandemic.

Background: The coronavirus disease 2019 (COVID-19) pandemic has highlighted the need to improve the safety of the environments where we care for older adults in Canada. After providing assistance during the first wave, many Ontario hospitals formally partnered with local congregate care homes in a "hub and spoke" model during second pandemic wave onward. The objective of this article is to describe the implementation and longitudinal outcomes of residents in one hub and spoke model composed of a hospital partnered with 18 congregate care homes including four long-term care and 14 retirement or other congregate care homes. Intervention: Homes were provided continuous seven-day per week access to hospital support, including infection prevention and control (IPAC), testing, vaccine delivery and clinical support as needed. Any COVID-19 exposure or transmission triggered a same-day meeting to implement initial control measures. A minimum of weekly on-site visits occurred for long-term care homes and biweekly for other congregate care homes, with up to daily on-site presence during outbreaks. Outcomes: Case detection among residents increased following implementation in context of increased testing, then decreased post-immunization until the Omicron wave when it peaked. After adjusting for the correlation within homes, COVID-related mortality decreased following implementation (OR=0.51, 95% CI, 0.30-0.88; p=0.01). In secondary analysis, homes without pre-existing IPAC programs had higher baseline COVID-related mortality rate (OR=19.19, 95% CI, 4.66-79.02; p<0.001) and saw a larger overall decrease during implementation (3.76% to 0.37%-0.98%) as compared to homes with pre-existing IPAC programs (0.21% to 0.57%-0.90%). Conclusion: The outcomes for older adults residing in congregate care homes improved steadily throughout the COVID-19 pandemic. While this finding is multifactorial, integration with a local hospital partner supported key interventions known to protect residents.

Plasmid genomic epidemiology of blaKPC carbapenemase-producing Enterobacterales in Canada, 2010-2021.

Carbapenems are considered last-resort antibiotics for the treatment of infections caused by multidrug-resistant Enterobacterales, but carbapenem resistance due to acquisition of carbapenemase genes is a growing threat that has been reported worldwide. Klebsiella pneumoniae carbapenemase (blaKPC) is the most common type of carbapenemase in Canada and elsewhere; it can hydrolyze penicillins, cephalosporins, aztreonam, and carbapenems and is frequently found on mobile plasmids in the Tn4401 transposon. This means that alongside clonal expansion, blaKPC can disseminate through plasmid- and transposon-mediated horizontal gene transfer. We applied whole genome sequencing to characterize the molecular epidemiology of 829 blaKPC carbapenemase-producing isolates collected by the Canadian Nosocomial Infection Surveillance Program from 2010 to 2021. Using a combination of short-read and long-read sequencing, we obtained 202 complete and circular blaKPC-encoding plasmids. Using MOB-suite, 10 major plasmid clusters were identified from this data set which represented 87% (175/202) of the Canadian blaKPC-encoding plasmids. We further estimated the genomic location of incomplete blaKPC-encoding contigs and predicted a plasmid cluster for 95% (603/635) of these. We identified different patterns of carbapenemase mobilization across Canada related to different plasmid clusters, including clonal transmission of IncF-type plasmids (108/829, 13%) in K. pneumoniae clonal complex 258 and novel repE(pEh60-7) plasmids (44/829, 5%) in Enterobacter hormaechei ST316, and horizontal transmission of IncL/M (142/829, 17%) and IncN-type plasmids (149/829, 18%) across multiple genera. Our findings highlight the diversity of blaKPC genomic loci and indicate that multiple, distinct plasmid clusters have contributed to blaKPC spread and persistence in Canada.

BNT162b2 versus mRNA-1273 Third Dose COVID-19 Vaccine in Patients with CKD and Maintenance Dialysis Patients.

BACKGROUND: There is a lack of randomized controlled trial data regarding differences in immunogenicity of varying coronavirus disease 2019 (COVID-19) mRNA vaccine regimens in CKD populations. METHODS: We conducted a randomized controlled trial at three kidney centers in Toronto, Ontario, Canada, evaluating the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody response after third dose vaccination. Participants ( n =273) with CKD not on dialysis or receiving dialysis were randomized 1:1 to third dose 30- µ g BNT162b2 (Pfizer-BioNTech) or 100- µ g mRNA-1273 (Moderna). The primary outcome of this study was SARS-CoV-2 IgG-binding antibodies to the receptor-binding domain (anti-RBD). Spike protein (antispike), nucleocapsid protein, and vaccine reactogenicity were also evaluated. Serology was measured before third dose and 1, 3, and 6 months after third dose. A subset of participants ( n =100) were randomly selected to assess viral pseudovirus neutralization against wild-type D614G, B.1.617.2 (Delta), and B.1.1.529 (Omicron BA.1). RESULTS: Among 273 participants randomized, 94% were receiving maintenance dialysis and 59% received BNT162b2 for initial two dose COVID-19 vaccination. Third dose of mRNA-1273 was associated with higher mean anti-RBD levels (1871 binding antibody units [BAU]/ml; 95% confidence interval [CI], 829 to 2988) over a 6-month period in comparison with third dose BNT162b2 (1332 BAU/ml; 95% CI, 367 to 2402) with a difference of 539 BAU/ml (95% CI, 139 to 910; P = 0.009). Neither antispike levels nor neutralizing antibodies to wild-type, Delta, and Omicron BA.1 pseudoviruses were statistically different. COVID-19 infection occurred in 10% of participants: 15 (11%) receiving mRNA-1273 and 11 (8%) receiving BNT162b2. Third dose BNT162b2 was not associated with a significant different risk for COVID-19 in comparison with mRNA-1273 (hazard ratio, 0.78; 95% CI, 0.27 to 2.2; P = 0.63). CONCLUSIONS: In patients with CKD, third dose COVID-19 mRNA vaccination with mRNA-1273 elicited higher SARS-CoV-2 anti-RBD levels in comparison with BNT162b2 over a 6-month period. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: COVID-19 Vaccine Boosters in Patients With CKD (BOOST KIDNEY), NCT05022329 .

Omicron variant neutralizing antibodies following BNT162b2 BA.4/5 versus mRNA-1273 BA.1 bivalent vaccination in patients with end-stage kidney disease.

Neutralization of Omicron subvariants by different bivalent vaccines has not been well evaluated. This study characterizes neutralization against Omicron subvariants in 98 individuals on dialysis or with a kidney transplant receiving the BNT162b2 (BA.4/BA.5) or mRNA-1273 (BA.1) bivalent COVID-19 vaccine. Neutralization against Omicron BA.1, BA.5, BQ.1.1, and XBB.1.5 increased by 8-fold one month following bivalent vaccination. In comparison to wild-type (D614G), neutralizing antibodies against Omicron-specific variants were 7.3-fold lower against BA.1, 8.3-fold lower against BA.5, 45.8-fold lower against BQ.1.1, and 48.2-fold lower against XBB.1.5. Viral neutralization was not significantly different by bivalent vaccine type for wild-type (D614G) (P = 0.48), BA.1 (P = 0.21), BA.5 (P = 0.07), BQ.1.1 (P = 0.10), nor XBB.1.5 (P = 0.10). Hybrid immunity conferred higher neutralizing antibodies against all Omicron subvariants. This study provides evidence that BNT162b2 (BA.4/BA.5) and mRNA-1273 (BA.1) induce similar neutralization against Omicron subvariants, even when antigenically divergent from the circulating variant.

An ethical framework adapted for infection prevention and control.

OBJECTIVE: The ethical implications of infection prevention and control (IPAC) are recognized, yet a framework to guide the application of ethical principles is lacking. We adapted an ethical framework to provide a systematic approach for fair and transparent IPAC decision making. METHODS: We conducted a literature search for existing ethical frameworks in IPAC. Working with practicing healthcare ethicists, an existing ethical framework was adapted for use in IPAC. Indications were developed for application to practice, with integration of ethical principles and process conditions specifically relevant to IPAC. Practical refinements were made to the framework based on end-user feedback and application to 2 real-world situations. RESULTS: In total, 7 articles were identified that discussed ethical principles within IPAC, but none proposed a systematic framework to guide ethical decision making. The adapted framework, named the Ethical Infection Prevention and Control (EIPAC) framework, takes the user through 4 intuitive and actionable steps, centering key ethical principles that facilitate reasoned and just decision making. In applying the EIPAC framework to practice, weighing the predefined ethical principles in different scenarios was a challenge. Although no hierarchy of principles can apply to all contexts in IPAC, our experience highlighted that the equitable distribution of benefits and burdens, and the proportional impacts of options under review, are particularly important considerations for IPAC. CONCLUSIONS: The EIPAC framework can serve as an actionable ethical principles-based decision-making tool for use by IPAC professionals encountering complex situations in any healthcare context.

Value in Primary Care: Evidence from the Canadian Primary Care Sentinel Surveillance Network.

Primary care antimicrobial stewardship programs are virtually non-existent. Using electronic medical record (EMR) data for an interrupted time series study, the authors examined the relationship between antibiotic prescriptions for acute respiratory tract infections (RTIs) and the COVID-19 pandemic. The main outcome of the study was to gauge the proportion of RTI encounters with an antibiotic prescription. The pre-pandemic RTI antibiotic prescribing rate was 27.8%. During the COVID-19 pandemic, prescribing dropped significantly by 9.4% (p < 0.001). Almost 750,000 fewer patients could potentially avoid receiving an antibiotic prescription for RTI. The authors also discuss the value of EMR data; their use can help develop insights for health system improvement.

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.

Antimicrobial use among paediatric inpatients at hospital sites within the Canadian Nosocomial Infection Surveillance Program, 2017/2018.

BACKGROUND: Antimicrobial resistance threatens the ability to successfully prevent and treat infections. While hospital benchmarks regarding antimicrobial use (AMU) have been well documented among adult populations, there is less information from among paediatric inpatients. This study presents benchmark rates of antimicrobial use (AMU) for paediatric inpatients in nine Canadian acute-care hospitals. METHODS: Acute-care hospitals participating in the Canadian Nosocomial Infection Surveillance Program submitted annual AMU data from paediatric inpatients from 2017 and 2018. All systemic antimicrobials were included. Data were available for neonatal intensive care units (NICUs), pediatric ICUs (PICUs), and non-ICU wards. Data were analyzed using days of therapy (DOT) per 1000 patient days (DOT/1000pd). RESULTS: Nine hospitals provided paediatric AMU data. Data from seven NICU and PICU wards were included. Overall AMU was 481 (95% CI 409-554) DOT/1000pd. There was high variability in AMU between hospitals. AMU was higher on PICU wards (784 DOT/1000pd) than on non-ICU (494 DOT/1000pd) or NICU wards (333 DOT/1000pd). On non-ICU wards, the antimicrobials with the highest use were cefazolin (66 DOT/1000pd), ceftriaxone (59 DOT/1000pd) and piperacillin-tazobactam (48 DOT/1000pd). On PICU wards, the antimicrobials with the highest use were ceftriaxone (115 DOT/1000pd), piperacillin-tazobactam (115 DOT/1000pd), and cefazolin (111 DOT/1000pd). On NICU wards, the antimicrobials with the highest use were ampicillin (102 DOT/1000pd), gentamicin/tobramycin (78 DOT/1000pd), and cefotaxime (38 DOT/1000pd). CONCLUSIONS: This study represents the largest collection of antimicrobial use data among hospitalized paediatric inpatients in Canada to date. In 2017/2018, overall AMU was 481 DOT/1000pd. National surveillance of AMU among paediatric inpatients is necessary for establishing benchmarks and informing antimicrobial stewardship efforts.