Association between infectious diseases consultation and mortality in hospitalized patients with Gram-negative bloodstream infection: a retrospective population-wide cohort study.

OBJECTIVES: Data supporting routine infectious diseases (ID) consultation in Gram-negative bloodstream infection (GN-BSI) are limited. We evaluated the association between ID consultation and mortality in patients with GN-BSI in a retrospective population-wide cohort study in Ontario using linked health administrative databases. METHODS: Hospitalized adult patients with GN-BSI between April 2017 and December 2021 were included. The primary outcome was time to all-cause mortality censored at 30 days, analyzed using a mixed effects Cox proportional hazards model with hospital as a random effect. ID consultation 1-10 days after the first positive blood culture was treated as a time-varying exposure. RESULTS: Of 30,159 patients with GN-BSI across 53 hospitals, 11,013 (36.5%) received ID consultation. Median prevalence of ID consultation for patients with GN-BSI across hospitals was 35.0% with wide variability (range 2.7-76.1%, interquartile range 19.6-41.1%). 1041 (9.5%) patients who received ID consultation died within 30 days, compared to 1797 (9.4%) patients without ID consultation. In the fully-adjusted multivariable model, ID consultation was associated with mortality benefit (adjusted HR 0.82, 95% CI 0.77-0.88, p < 0.0001; translating to absolute risk reduction of -3.8% or NNT of 27). Exploratory subgroup analyses of the primary outcome showed that ID consultation could have greater benefit in patients with high-risk features (nosocomial infection, polymicrobial or non-Enterobacterales infection, antimicrobial resistance, or non-urinary tract source). CONCLUSIONS: Early ID consultation was associated with reduced mortality in patients with GN-BSI. If resources permit, routine ID consultation for this patient population should be considered to improve patient outcomes.

Follow-up blood cultures do not reduce mortality in hospitalized patients with Gram-negative bloodstream infection: a retrospective population-wide cohort study.

OBJECTIVES: The utility of follow-up blood cultures (FUBCs) in patients with Gram-negative bloodstream infection (GN-BSI) is controversial. Observational studies have suggested significant mortality benefit but may be limited by single-centre designs, immortal time bias, and residual confounding. We examined the impact of FUBCs on mortality in patients with GN-BSI in a retrospective population-wide cohort study in Ontario, Canada. METHODS: Adult patients with GN-BSI hospitalized between April 2017 and December 2021 were included. Primary outcome was all-cause mortality within 30 days. FUBC was treated as a time-varying exposure. Secondary outcomes were 90-day mortality, length of stay, and number of days alive and out of hospital at 30 and 90 days. RESULTS: Thirty-four thousand one hundred patients were included; 8807 (25.8%) patients received FUBC, of which 966 (11.0%) were positive. Median proportion of patients receiving FUBC was 18.8% (interquartile range, 10.0-29.7%; range, 0-66.1%) across 101 hospitals; this correlated with positivity and contamination rate. Eight hundred ninety (10.1%) patients in the FUBC group and 2263 (8.9%) patients in the no FUBC group died within 30 days. In the fully adjusted model, there was no association between FUBC and mortality (hazard ratio, 0.97; 95% CI, 0.90-1.04). Patients with FUBC had significantly longer length of stay (median, 11 vs. 7 days; adjusted risk ratio, 1.18; 95% CI, 1.16-1.21) and fewer number of days alive and out of hospital at 30 and 90 days. DISCUSSION: FUBC collection in patients with GN-BSI varies widely across hospitals and may be associated with prolonged hospitalization without clear survival benefit. Residual confounding may be present given the observational design. Clear benefit should be demonstrated in a randomized trial before widespread adoption of routine FUBC.

An Analysis of Solicitations From Predatory Journals in Ophthalmology.

PURPOSE: To evaluate trends associated with email communication from potentially predatory publishers to faculty in ophthalmology. DESIGN: Cross-sectional study METHODS: Ophthalmologists (n = 14) from various subspecialties and institutions were recruited to participate. Participants identified unsolicited emails that they had received originating from publishers in May 2021. Information collected included details on email contents and publisher organizations. Trends in communications from predatory publishers were evaluated. RESULTS: Over a 30-day study period, a total of 1813 emails were received from 383 unique publishers and 696 unique journals, with a mean (SD) of 4.73 (2.46) emails received per day per participant. Of the 1813 emails identified, 242 (13%) emails were invitations to conferences, whereas 1440 (80%) were solicitations for article submissions to open-access, pay-to-publish journals. A total of 522 (29.0%) emails were related to ophthalmology, and reference to a prior publication of the participant occurred in 262 emails (14%). Of the 696 unique journals identified, 174 (25%) journals were indexed on PubMed and 426 (61%) were listed on Beall's list. When comparing journals that were listed on PubMed vs those that were not, PubMed indexed journals had a higher impact factor (2.1 vs 1.5, P = .002), were less likely to use "greetings" (76% vs 91%, P < .001), had fewer spelling/grammar errors (40% vs 51%, P = .01), and were less likely to offer rapid publication (16% vs 25%, P = .02). CONCLUSIONS: Unsolicited requests to publish occur frequently and may diminish the quality of the scientific literature. We encourage individuals in ophthalmology to be aware of these trends in predatory publishing.

Risk of Endophthalmitis Based on Cumulative Number of Anti-VEGF Intravitreal Injections.

PURPOSE: To determine the risk of endophthalmitis in eyes undergoing intravitreal injections (IVIs) of anti-VEGF based on cumulative number of injections per eye. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients from a single center undergoing IVIs of ranibizumab, aflibercept, or bevacizumab. METHODS: Eyes were divided into quartiles based on injection number causative of endophthalmitis between January 1, 2011, and June 1, 2022. MAIN OUTCOME MEASURES: Interquartile clinical outcomes and cumulative risk of endophthalmitis per injection and per eye. RESULTS: A total of 43 393 eyes received 652 421 anti-VEGF injections resulting in 231 endophthalmitis cases (0.035% per injection, 1 in 2857), of which 215 were included. The cumulative endophthalmitis risk increased from 0.0018% (1 in 55 556) after 1 injection to 0.013% (1 in 7692) after 11 injections (0.0012 percentage point change), versus 0.014% (1 in 7143) after 12 injections to 0.025% (1 in 4000) after 35 injections (0.00049 percentage point change), versus 0.025% (1 in 4000) after 36 injections to 0.031% (1 in 3226) after 66 injections (0.00017 percentage point change), versus 0.031% (1 in 3226) after 63 injections to 0.033% (1 in 3030) after 126 injections (0.000042 percentage point change) (P < 0.001). Likewise, the cumulative endophthalmitis risk per eye increased from 0.028% (1 in 3571) to 0.20% (1 in 500) between injections 1 and 11 (0.018 percentage point change), versus 0.21% (1 in 476) to 0.38% (1 in 263) between injections 12 and 35 (0.0075 percentage point change), versus 0.38% (1 in 263) to 0.46% (1 in 217) between injections 36 and 66 (0.0026 percentage point change), versus 0.46% (1 in 217) to 0.50% (1 in 200) between injections 67 and 126 (0.00063 percentage point change) (P < 0.001). CONCLUSIONS: The cumulative endophthalmitis risk per injection and per eye increased with greater number of injections received but appeared to do so at a higher rate during earlier injections and at a lower rate further into the treatment course. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Risk factors for surgical failure after primary scleral buckling for rhegmatogenous retinal detachment.

OBJECTIVE: To identify risk factors for surgical failure after scleral buckling (SB) for primary rhegmatogenous retinal detachment (RRD) repair. DESIGN: Single-centre retrospective consecutive case series. PARTICIPANTS: All patients who underwent SB for repair of primary RRD at Wills Eye Hospital between January 1, 2015, and December 31, 2018, were included. METHODS: Single-surgery anatomic success (SSAS) rate and risk factors associated with surgical failure were evaluated. A multivariable logistic regression model was completed to assess the effect of demographic, clinical, and operative variables on SSAS rate. RESULTS: A total of 499 eyes of 499 patients were included. Overall SSAS rate was 86% (n = 430 of 499). Using multivariate analysis, surgical failure was more likely in males (adjusted odds ratio [adjusted OR] = 2.98; 95% CI, 1.58-5.62; p = 0.0007) with a macula-off status on preoperative examination (adjusted OR = 2.15; 95% CI, 1.10-4.20; p = 0.03) and preoperative proliferative vitreoretinopathy (adjusted OR = 4.26; 95% CI, 1.10-16.5; p = 0.04). Time interval between initial examination and surgery (p = 0.26), distribution of buckle or band material used (p = 0.88), and distribution of tamponade used (p = 0.74) were not significantly different between eyes with and without surgical failure. CONCLUSION: Male sex, macula-off status, and preoperative proliferative vitreoretinopathy were factors with increased odds of surgical failure after SB for primary RRD repair. Operative characteristics, such as type of band or use of tamponade, were not associated with surgical failure.

First Canadian report of transmission of fluconazole-resistant Candida parapsilosis within two hospital networks confirmed by genomic analysis.

Candida parapsilosis is a common cause of non-albicans candidemia. It can be transmitted in healthcare settings resulting in serious healthcare-associated infections and can develop drug resistance to commonly used antifungal agents. Following a significant increase in the percentage of fluconazole (FLU)-nonsusceptible isolates from sterile site specimens of patients in two Ontario acute care hospital networks, we used whole genome sequence (WGS) analysis to retrospectively investigate the genetic relatedness of isolates and to assess potential in-hospital spread. Phylogenomic analysis was conducted on all 19 FLU-resistant and seven susceptible-dose dependent (SDD) isolates from the two hospital networks, as well as 13 FLU susceptible C. parapsilosis isolates from the same facilities and 20 isolates from patients not related to the investigation. Twenty-five of 26 FLU-nonsusceptible isolates (resistant or SDD) and two susceptible isolates from the two hospital networks formed a phylogenomic cluster that was highly similar genetically and distinct from other isolates. The results suggest the presence of a persistent strain of FLU-nonsusceptible C. parapsilosis causing infections over a 5.5-year period. Results from WGS were largely comparable to microsatellite typing. Twenty-seven of 28 cluster isolates had a K143R substitution in lanosterol 14-α-demethylase (ERG11) associated with azole resistance. As the first report of a healthcare-associated outbreak of FLU-nonsusceptible C. parapsilosis in Canada, this study underscores the importance of monitoring local antimicrobial resistance trends and demonstrates the value of WGS analysis to detect and characterize clusters and outbreaks. Timely access to genomic epidemiological information can inform targeted infection control measures.

Early diagnosis of monomicrobial Clostridioides difficile bacteremia in a patient without colitis.

Bacteremia is a rare finding among Clostridioides difficile infections. We describe a case of a 67-year-old man with resected colorectal cancer with colostomy who presented with small bowel obstruction and was admitted for lysis of adhesions. On day 8 of admission, he developed leukocytosis and raised inflammatory markers with isolation of Gram-positive bacilli in several blood cultures, which was presumptively identified through blood culture pelleting and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) as C. difficile. The diagnosis was confirmed with conventional culture and reference lab identification and the patient demonstrated clinical response with parenteral then oral vancomycin that briefly worsened when therapy was switched to parenteral metronidazole and then improved once oral vancomycin was resumed. Our case was notable in that the combination of pelleting and MALDI-TOF offered early diagnosis in this patient whose positive blood cultures were suspicious for contamination and in whom there was an absence of diarrheal illness or features of colitis on abdominal imaging. Early diagnosis is critical for the timely initiation of therapy, implementation of infection prevention and control measures and in selection of appropriate therapy for antimicrobial stewardship.

La bactériémie est rare lors d'une infection à Clostridioides difficile. Les auteurs décrivent le cas d'un homme de 67 ans ayant une colostomie découlant de la résection d'un cancer colorectal, qui a consulté à cause d'une occlusion du grêle et a été hospitalisé pour traiter des adhésiolyses. Le huitième jour de l'hospitalisation, il a présenté une leucocytose et une augmentation des marqueurs inflammatoires, des bacilles à Gram positif ont été isolés dans plusieurs hémocultures, et un diagnostic provisoire de C. difficile a été posé par culot de sang et désorption/ionisation laser assistée par matrice par temps de vol (MALDI-TOF). Le diagnostic a été confirmé par une culture classique et par le laboratoire de référence, et le patient a affiché une réponse clinique à la vancomycine par voie parentérale, puis par voie orale. Son état s'est brièvement aggravé lors du passage au métronidazole par voie parentérale, puis s'est amélioré à la reprise de la vancomycine par voie orale. Le cas était remarquable parce que la combinaison du culot et de la MALDI-TOF a permis d'obtenir un diagnostic rapide chez ce patient dont les hémocultures positives ont suggéré une contamination dont l'imagerie abdominale ne révélait pas de maladie diarrhéique ni de caractéristiques de colite. Il est essentiel de poser un diagnostic précoce pour entreprendre le traitement rapidement, adopter des mesures de prévention et de contrôle des infections et sélectionner le traitement approprié à la gouvernance antimicrobienne.

Whole genome sequencing of increased number of azithromycin-resistant Shigella flexneri 1b isolates in Ontario.

Azithromycin (AZM) resistance among Shigella is a major public health concern. Here, we investigated the epidemiology of Shigella flexneri serotype 1b recovered during 2016-2018 in Ontario, to describe the prevalence and spread of AZM resistance. We found that 72.3% (47/65) of cases were AZM-resistant (AZMR), of which 95.7% (45/47) were among males (P < 0.001). Whole-genome based phylogenetic analysis showed three major clusters, and 56.9% of isolates grouped within a single closely-related cluster (0-10 ∆SNP). A single AZMR clonal population was persistent over 3 years and involved 67.9% (36/53) of all male cases, and none reported international travel. In 2018, a different AZMR cluster appeared among adult males not reporting travel. A proportion of isolates (10.7%) with reduced susceptibility to ciprofloxacin (CIP) due to S83L mutation in gyrA were AZM susceptible, and 71.4% reported international travel. Resistance to AZM was due to the acquisition of mph gene-bearing incFII plasmids having > 95% nucleotide similarity to pKSR100. Plasmid-borne resistance limiting treatment options to AZM, ceftriaxone (CRO) and CIP was noted in a single isolate. We characterized AZMR isolates circulating locally among males and found that genomic analysis can support targeted prevention and mitigation strategies against antimicrobial-resistance.

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.

Healthcare costs and outcomes associated with laboratory-confirmed Lyme disease in Ontario, Canada: A population-based cohort study.

BACKGROUND: The objective of this study was to estimate the economic burden attributable to laboratory-confirmed Lyme disease (LD) in Ontario, Canada and assess health outcomes associated with LD. METHOD: We conducted a cohort study using laboratory-confirmed LD cases accrued between 2006 and 2018. The exposed cohort was matched 1:3 to the unexposed cohort using a combination of hard and propensity score matching. We used phase-of-care costing methods to calculate attributable costs for four phases of illness: pre-diagnosis, acute care, post-acute care, and continuing care in 2018 Canadian dollars. We used ICD-10-CA and OHIP billing codes to identify emergency department visits, physician billings and hospitalizations related to LD sequelae to assess health outcomes. RESULTS: A total of 2,808 cases were identified with a mean age of 46.5 (20.7) years and 44% female. Within 30-days, 404 (14.3%) cases required an ED visit and 63 (2.4%) cases required hospitalization. The mean (95% CI) total costs for LD cases in pre-diagnosis, acute, and post-acute care phases were $209 ($181, 238), $1,084 ($956, $1,212), and $1,714 ($1,499, $1,927), respectively. The highest mean attributable 10-day cost was $275 ($231, $319) during acute care. At 1-year post-infection, LD increased the relative risk of nerve palsies by 62 (20, 197), and polyneuropathy by 24 (3.0, 190). LD resulted in 16 Lyme meningitis events vs. 0 events in the unexposed. CONCLUSION: Individuals with laboratory-confirmed LD have increased healthcare resource use pre-diagnosis and up to six months post-diagnosis, and were more likely to seek healthcare services related to LD sequelae.

Quantifying Head Position Following Vitrectomy Using a 3-Dimensional Position Sensor Embedded in a Novel Ophthalmic Shield: A Pilot Study.

PURPOSE: To assess head position following pars plana vitrectomy (PPV) using a novel low-energy, non-intrusive 3-D position sensor platform. METHODS: In this prospective non-randomized interventional case series, a low-energy Bluetooth smart sensor housed within a novel eye shield recorded 3-D positional data every five minutes. The device was placed on the patient immediately after PPV and data was retrieved at the postoperative day 1 visit. Readings were processed by vector analysis into 4 groups, stratified by the angle of deviation away from a completely prone head position. The primary outcome was the angle between vectors. RESULTS: Ten patients were enrolled in this pilot study. The mean (SD) age was 57.5 (17.4). A total of 2318 readings with a mean (SD) of 231.8 (26.8) readings per patient were obtained. The mean (SD) number of readings were 132.9 (34.7) while awake and 98.9 (27.9) during sleep. Of total readings, only 11.7% fell into group 1 while a majority of readings fell in group 2 (52.4%), and group 3 (32.4%), and only 3.5% fell into group 4. Positional deviation increased during sleep hours, with about 46.8% of readings at a reclined angle (group 3) and 4.9% supine, which was 21.6% and 2.5% respectively during the wake time (p<0.001, p=0.002, respectively). CONCLUSION: In this pilot study, a non-intrusive wireless 3-D position sensor-shield platform was tolerated well and capable of capturing positional data. Adherence to face-down positioning was low and positional deviation increased significantly while sleeping.

18p Deletion Syndrome With Concurrent Frizzled-4 Mutation: Surgical Management of Bilateral Stage 5 Traction Retinal Detachment.

We report a case of a patient with 18p deletion syndrome and concurrent FZD4 (frizzled-4) mutation. A 6-month-old boy with known 18p deletion syndrome presented with abnormal eye movements in both eyes and an inability to track objects. The patient had a history of laryngomalacia, hypotonia, and developmental delay. Examination showed bilateral total exudative and traction retinal detachment with anomalous retinal vascular development noted on widefield fluorescein angiography. Genetic analysis identified a concurrent FZD4 mutation (c.205C>T [p.H69Y]). Both eyes underwent 25-gauge limbal vitrectomy, lensectomy, and membrane peeling, and the posterior pole successfully reattached with improvement in visual function. The 18p region contains the LAMA1, TGIF1, and APCDD1 genes, which are involved in the vascular basement membrane and Wnt/ß-catenin signaling, which may have potentiated the particularly severe familial exudative vitreoretinopathy phenotype. We present the clinical findings, imaging analyses, and surgical management of concurrent 18p deletion syndrome and FDZ4 mutation. The overlap in molecular mechanisms of the multiple gene products may potentiate the severe phenotype. [Ophthalmic Surg Lasers Imaging Retina 2023;54:284-290.].

Endophthalmitis following cataract surgery: visual outcomes, microbial spectrum and complications.

PURPOSE OF REVIEW: The aim of this study was to update visual outcomes, microbial spectrum and complications in eyes with endophthalmitis following cataract surgery. RECENT FINDINGS: A single-institution, retrospective review of eyes treated for endophthalmitis following cataract surgery between 2 January 2014 and 10 January 2017. This study included 112 cases of endophthalmitis following cataract surgery, 58 of which were culture-positive (51.8%). The most isolated organisms were coagulase-negative Staphylococci (56.9%). Oral flora were present in 17.2% of cases. At 6 months, 71.7% of patients achieved visual acuity of at least 20/200 and 51.7% achieved at least 20/40 or better. Visual acuity was better in culture-negative vs. culture-positive cases (∼20/290 vs. ∼20/80, P   =  0.03), and in nonoral flora-associated vs. oral flora-associated culture-positive cases (∼CF vs. ∼20/150, P   <  0.01). SUMMARY: Following postcataract surgery endophthalmitis, approximately 70% of eyes achieved vision of 20/200 or better and half achieved vision of 20/40 or better 6 months after treatment. Poor visual outcomes were seen in eyes with positive bacterial cultures and with oral flora.

Comparing the transmission potential from sequence and surveillance data of 2009 North American influenza pandemic waves.

Technological advancements in phylodynamic modeling coupled with the accessibility of real-time pathogen genetic data are increasingly important for understanding the infectious disease transmission dynamics. In this study, we compare the transmission potentials of North American influenza A(H1N1)pdm09 derived from sequence data to that derived from surveillance data. The impact of the choice of tree-priors, informative epidemiological priors, and evolutionary parameters on the transmission potential estimation is evaluated. North American Influenza A(H1N1)pdm09 hemagglutinin (HA) gene sequences are analyzed using the coalescent and birth-death tree prior models to estimate the basic reproduction number (R 0 ). Epidemiological priors gathered from published literature are used to simulate the birth-death skyline models. Path-sampling marginal likelihood estimation is conducted to assess model fit. A bibliographic search to gather surveillance-based R 0 values were consistently lower (mean ≤ 1.2) when estimated by coalescent models than by the birth-death models with informative priors on the duration of infectiousness (mean ≥ 1.3 to ≤2.88 days). The user-defined informative priors for use in the birth-death model shift the directionality of epidemiological and evolutionary parameters compared to non-informative estimates. While there was no certain impact of clock rate and tree height on the R 0 estimation, an opposite relationship was observed between coalescent and birth-death tree priors. There was no significant difference (p = 0.46) between the birth-death model and surveillance R 0 estimates. This study concludes that tree-prior methodological differences may have a substantial impact on the transmission potential estimation as well as the evolutionary parameters. The study also reports a consensus between the sequence-based R 0 estimation and surveillance-based R 0 estimates. Altogether, these outcomes shed light on the potential role of phylodynamic modeling to augment existing surveillance and epidemiological activities to better assess and respond to emerging infectious diseases.

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).

A Ten-Year Retrospective Survey of Antimicrobial Susceptibility Patterns among Salmonella enterica subsp. enterica Serovar Typhi Isolates in Ontario, Canada.

The epidemiology and treatment of typhoid fever are complicated by the emergence and spread of Salmonella enterica subsp. enterica serovar Typhi lineages with resistance to many antimicrobial agents critical for therapy. Current information on the susceptibility patterns of S. Typhi isolates identified in regions where typhoid fever is not endemic is important as these are often acquired after traveling to countries of endemicity where resistant strains circulate. Here, we report a 10-year retrospective survey of S. Typhi antimicrobial susceptibility patterns among 858 unique patient isolates that underwent reference laboratory testing in Ontario, Canada, between 2010 and 2019. Antimicrobial susceptibility patterns remained stable for ampicillin (average, 78.7% susceptible), azithromycin (average, 99.4% susceptible) ertapenem (average, 100.0% susceptible), meropenem (average, 100.0% susceptible), and trimethoprim-sulfamethoxazole (average, 78.2% susceptible) during the study period; however, nonsusceptibility to ciprofloxacin and ceftriaxone increased. While ceftriaxone-resistant isolates comprised 1.6% of the total isolates overall, they represented 10.1% of the total isolates tested in 2019, indicating a significant increase over time. Our findings suggest that when selecting empirical therapy, health care providers should strongly consider current trends in antimicrobial susceptibility and investigate the patient's exposure risk to gauge whether a suspected typhoid infection may be caused by a potentially resistant S. Typhi strain. IMPORTANCE This work provides an updated summary of the antimicrobial susceptibility patterns among Salmonella Typhi strains isolated from patients in Ontario, Canada.

Patient Accessibility to Eye Care in the United States.

PURPOSE: The United States (US) federal government uses health provider shortage areas (HPSAs) to define patient accessibility to primary care physicians. It is unclear whether HPSAs can be applied to eye care providers (ECPs). Our study determined the applicability of federal HPSA designations to ECP availability in the US. DESIGN: Cross-sectional study. PARTICIPANTS: US general population and ophthalmologists/optometrists in the Medicare database. METHODS: The primary care HPSA score, visual impairment prevalence, and ECP location were determined for each census tract or county using data from the US Department of Health and Human Services, the Centers for Disease Control and Prevention, and Centers for Medicare and Medicaid Services. MAIN OUTCOME MEASURES: Association of HPSA with vision loss and ECP density was examined. The 2-step floating catchment area approach was used to newly define eye care shortage areas (patient accessibility score [PAS], higher being worse accessibility) for every county in the US, by weighting the 2-step FCA scores by prevalence of vision loss and ECP density. Multivariable logistic regression was used to identify sociodemographic variables associated with areas of ECP shortage. RESULTS: Among 72 735 census tracts included, statistically significant but weak correlations of HPSA score with visual impairment (VI) (r = 0.38; P < 0.0001) and ECP density per county population (r = -0.18; P < 0.0001) were found. Only 54.0% of census tracts with < 25th percentile ECP density per county were HPSAs (P < 0.0001). Of census tracts > than 75th percentile for VI only 58.0% were HPSAs (P < 0.0001). Multivariable regression found a higher odds of ECP PAS ≥ 75th percentile (worse accessibility) in rural counties (adjusted odds ratio [aOR], 2.47; 95% confidence interval [CI], 1.93-3.67; P < 0.001) and counties with a greater prevalence of residents with less than a high school education (aOR, 1.21; 95% CI, 1.19-1.25; P < 0.001), residents ≥ 65 years of age (aOR, 1.10; 95% CI, 1.07-1.13; P < 0.001), and uninsured residents (aOR, 1.04; 95% CI, 1.01-1.06; P < 0.001). Counties with a greater proportion of men (aOR, 0.93; 95% CI, 0.89-0.967; P < 0.001) or White residents (aOR, 0.99; 95% CI, 0.98-0.99) had a lower odds of ECP PAS ≥ 75th percentile. CONCLUSIONS: Current HPSAs only weakly correlate with ECP supply. We propose a new approach to identify counties with high need but limited access to eye care. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

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.