No association was seen between antibiotic exposure during pregnancy or early infancy and overall incidence of autoimmune diseases.

Urinary tract infections (UTIs) caused by MDR Escherichia coli present a growing challenge in elderly patients, often leading to limited therapeutic options and poor clinical outcomes.1 Laboratory studies of E. coli resistance patterns can guide rational prescribing, but clinical decision-making must also account for patient-specific factors, comorbidities and antimicrobial stewardship (AMS) principles.2,3 This study bridges laboratory findings on E. coli resistance with real-world clinical application in an elderly patient with MDR E. coli UTI.ObjectivesTo evaluate antibiotic susceptibility trends in E. coli using the agar plate method under controlled laboratory conditions and to apply these findings to a real-world clinical case of a 72-year-old female with MDR E. coli UTI, highlighting AMS-guided therapeutic decision-making.MethodsThe laboratory phase involved agar plate diffusion assays testing broad- and narrow-spectrum antibiotics (ampicillin, chloramphenicol, cefoxitin, erythromycin) against E. coli, with inhibition zones measured over four weeks to monitor susceptibility trends. In the clinical phase, we reviewed microbiology results from a 72-year-old female with symptomatic UTI, whose urine culture revealed E. coli (>100 000 cfu/mL) resistant to multiple β-lactams, fluoroquinolones and third generation cephalosporins, but sensitive to sulfonamides, carbapenems, nitrofurantoin and tetracyclines.ResultsLaboratory findings demonstrated variability in E. coli susceptibility, with ampicillin showing reduced efficacy over time, cefoxitin maintaining stable activity and erythromycin demonstrating no activity. Clinical findings showed resistance to ampicillin, ciprofloxacin, levofloxacin, amoxicillin/clavulanate, piperacillin/tazobactam and most cephalosporins, with susceptibility retained to trimethoprim/sulfamethoxazole, imipenem, meropenem, nitrofurantoin, tetracycline, doxycycline and ertapenem. These results suggest a MDR strain likely producing ESBLs (Figure 1).ConclusionsIntegrating laboratory resistance surveillance with clinical case evaluation supports targeted antibiotic therapy in MDR E. coli UTIs, particularly in vulnerable elderly populations. For the presented patient, oral nitrofurantoin or trimethoprim/sulfamethoxazole could be appropriate first-line agents for lower UTI, with carbapenems reserved for complicated or systemic infections. Where a broad-spectrum agent is initiated empirically, timely de-escalation to the narrowest effective oral option based on culture results is essential to reduce selective pressure and minimize collateral damage to the microbiome. This combined approach emphasizes the importance of continuous local susceptibility monitoring, prompt review of microbiology results, prudent antimicrobial selection and adherence to AMS strategies (Figure 2)—including early de-escalation, shortest effective treatment duration and avoidance of unnecessary broad-spectrum use—to optimize patient outcomes, prevent recurrence and slow the progression of antimicrobial resistance.Figure 1.Antimicrobial resistance profile of Escherichia coli isolate from a 72-year-old patient, showing ESBL production and preserved carbapenem susceptibility.  Figure 2.Proposed antimicrobial stewardship workflow for the rapid detection, review and protocol optimization in elderly UTI management.

Importance  The US Food and Drug Administration (FDA) has issued a warning and a label change regarding a potential association between trimethoprim-sulfamethoxazole (TMP-SMX) and acute respiratory failure in healthy adolescents and young adults.Objective  To examine the 30-day risk of a hospital visit (ie, hospitalization or emergency department visit) with acute respiratory failure in adolescents and young adults aged 10 to younger than 25 years old newly dispensed oral TMP-SMX compared with new users of amoxicillin or a cephalosporin.Design, Setting, and Participants  This retrospective, population-based, new-user cohort study in Ontario, Canada (2003-2023) used linked administrative health care data. The TMP-SMX vs amoxicillin and TMP-SMX vs cephalosporins cohorts both included adolescents and young adults aged 10 to younger than 25 years who were newly dispensed oral TMP-SMX, amoxicillin, or cephalosporins for 3 or more days from an outpatient pharmacy. Data were analyzed from January 1 to April 30, 2025.Exposure  TMP-SMX for 3 days or more.Main Outcomes and Measures  The primary outcome was a composite outcome of the 30-day risk of a hospital visit with acute respiratory failure (defined as a diagnosis of acute respiratory failure or receipt of mechanical ventilation, tracheotomy, or extracorporeal membrane oxygenation). Secondary outcomes were the individual components of the composite outcome, all-cause hospitalization, and all-cause mortality. Overlap weighting on the propensity score was used to balance comparison groups on 84 indicators of baseline health. Weighted risk ratios were obtained using log-binomial regression and weighted risk differences using binomial regression. Sensitivity analyses using a negative control outcome, and case-crossover analysis were also performed.Results  The TMP-SMX vs amoxicillin cohort included 575 218 individuals (44 801 TMP-SMX users and 530 417 amoxicillin users; median age after weighting, 19 years [IQR, 16-22 years]; 74.3% female). The TMP-SMX vs cephalosporins cohort included 248 236 individuals (51 197 TMP-SMX users and 197 039 cephalosporin users; median age after weighting, 19 years [IQR, 16-22 years]; 72.3% were female). The risk of the composite outcome occurred in 15 of 44 801 patients (0.03%) who started TMP-SMX and in 49 of 530 417 (0.01%) who started amoxicillin (number of weighted events, 7 of 21 579 [0.03%] for TMP-SMX and 2 of 21 579 [0.01%] for amoxicillin; weighted risk ratio, 2.79 [95% CI, 1.01-7.71]; weighted risk difference, 0.02% [95% CI, 0.001%-0.04%]). The risk of the composite outcome occurred in 17 of 51 197 patients (0.03%) who started TMP-SMX and in 21 of 197 039 (0.01%) who started cephalosporins (number of weighted events, 8 of 20 538 [0.04%] for TMP-SMX and 3 of 20 538 [0.01%] for cephalosporins; weighted risk ratio, 2.85 [95% CI, 1.11-7.31]; weighted risk difference, 0.02% [95% CI, 0.005%-0.05%]). Results were consistent in sensitivity analyses.Conclusions and Relevance  These findings suggest that the 30-day risk of a hospital visit with acute respiratory failure was higher among those receiving TMP-SMX compared with those receiving amoxicillin or cephalosporins. These findings supported the FDA warning, and if replicated, the risks should be carefully weighed against the benefits of TMP-SMX use. Regulatory agencies could reinforce the FDA warning, and product monographs and prescribing guidelines should be updated and revised accordingly.

Importance  The US Food and Drug Administration (FDA) has issued a warning and a label change regarding a potential association between trimethoprim-sulfamethoxazole (TMP-SMX) and acute respiratory failure in healthy adolescents and young adults.Objective  To examine the 30-day risk of a hospital visit (ie, hospitalization or emergency department visit) with acute respiratory failure in adolescents and young adults aged 10 to younger than 25 years old newly dispensed oral TMP-SMX compared with new users of amoxicillin or a cephalosporin.Design, Setting, and Participants  This retrospective, population-based, new-user cohort study in Ontario, Canada (2003-2023) used linked administrative health care data. The TMP-SMX vs amoxicillin and TMP-SMX vs cephalosporins cohorts both included adolescents and young adults aged 10 to younger than 25 years who were newly dispensed oral TMP-SMX, amoxicillin, or cephalosporins for 3 or more days from an outpatient pharmacy. Data were analyzed from January 1 to April 30, 2025.Exposure  TMP-SMX for 3 days or more.Main Outcomes and Measures  The primary outcome was a composite outcome of the 30-day risk of a hospital visit with acute respiratory failure (defined as a diagnosis of acute respiratory failure or receipt of mechanical ventilation, tracheotomy, or extracorporeal membrane oxygenation). Secondary outcomes were the individual components of the composite outcome, all-cause hospitalization, and all-cause mortality. Overlap weighting on the propensity score was used to balance comparison groups on 84 indicators of baseline health. Weighted risk ratios were obtained using log-binomial regression and weighted risk differences using binomial regression. Sensitivity analyses using a negative control outcome, and case-crossover analysis were also performed.Results  The TMP-SMX vs amoxicillin cohort included 575 218 individuals (44 801 TMP-SMX users and 530 417 amoxicillin users; median age after weighting, 19 years [IQR, 16-22 years]; 74.3% female). The TMP-SMX vs cephalosporins cohort included 248 236 individuals (51 197 TMP-SMX users and 197 039 cephalosporin users; median age after weighting, 19 years [IQR, 16-22 years]; 72.3% were female). The risk of the composite outcome occurred in 15 of 44 801 patients (0.03%) who started TMP-SMX and in 49 of 530 417 (0.01%) who started amoxicillin (number of weighted events, 7 of 21 579 [0.03%] for TMP-SMX and 2 of 21 579 [0.01%] for amoxicillin; weighted risk ratio, 2.79 [95% CI, 1.01-7.71]; weighted risk difference, 0.02% [95% CI, 0.001%-0.04%]). The risk of the composite outcome occurred in 17 of 51 197 patients (0.03%) who started TMP-SMX and in 21 of 197 039 (0.01%) who started cephalosporins (number of weighted events, 8 of 20 538 [0.04%] for TMP-SMX and 3 of 20 538 [0.01%] for cephalosporins; weighted risk ratio, 2.85 [95% CI, 1.11-7.31]; weighted risk difference, 0.02% [95% CI, 0.005%-0.05%]). Results were consistent in sensitivity analyses.Conclusions and Relevance  These findings suggest that the 30-day risk of a hospital visit with acute respiratory failure was higher among those receiving TMP-SMX compared with those receiving amoxicillin or cephalosporins. These findings supported the FDA warning, and if replicated, the risks should be carefully weighed against the benefits of TMP-SMX use. Regulatory agencies could reinforce the FDA warning, and product monographs and prescribing guidelines should be updated and revised accordingly.

Dear Editor,We congratulate Fuller et al.1 who highlight that Shigella in men who have sex with men (MSM) is seen in returning travellers. We would suggest that all MSM presenting with shigellosis, including returning travellers should be managed as having sexually transmitted shigellosis, particularly in those (i) living with human immunodeficiency virus (HIV), (ii) with recent non-regular sexual partners and (iii) with a sexually transmitted co-infection (e.g., Neisseria gonorrhoeae).2,3 Genomic data demonstrate the global and regional transmission of different Shigella species and lineages among large sexual networks of MSM in Europe, North America and Australia including the emergence and transmission of extensively antimicrobial resistant Shigella.4–6 Most sexually transmitted Shigella in high-income settings is likely to be resistant to quinolones, macrolides; and more recently cephalosporins.5,7,8 There are limited guidelines for the clinical management of sexually transmissible shigellosis globally, and those in publication provide conflicting advice.9 We would suggest that the current (2015) Canadian Committee to Advise on Tropical Medicine and Travel guidelines are inadequate for managing shigellosis in MSM as they do not consider the magnitude of antimicrobial resistance (AMR).5,10 Recent data from the United Kingdom (UK) suggest that following expert microbiological advice, fosfomycin, pivmecillinam or carbapenems could be considered where antimicrobials are indicated.2,10In regard to the management of the case, we note that the patient’s travel partners were asymptomatic, and the timing of his sexual contact and onset of symptoms are consistent with an incubation period of up to seven days, so suggest that his infection was acquired through sexual transmission.2 Shigella circulating in sexual networks of MSM in Canada and Europe are likely to be ciprofloxacin resistant; tetracycline resistance among sexually transmissible Shigella is also high, so doxycycline pre-exposure prophylaxis was unlikely to have been effective.10 We note that your patient’s symptoms were resolving by the time he was treated with ciprofloxacin, and no antimicrobial sensitivities were reported.The distinction between managing such cases as sexually transmitted shigellosis rather than travel associated (contaminated food/water) is important, specifically MSM with sexually transmitted Shigella should be offered comprehensive sexually transmitted infection testing (including HIV, Treponema pallidum, hepatitis A and B), partner notification, and be used as an opportunity to ensure other sexual health interventions have been offered such as hepatitis A, B, Human Papilloma Virus and Mpox vaccination, access to HIV pre-exposure prophylaxis in HIV negative MSM, doxycycline post-exposure prophylaxis discussion, condom use and sexual health education.2 Furthermore, we would not advocate for empirical macrolides, quinolones or cephalosporins based on current AMR data in MSM, and treatment decisions, particularly in resolving cases should be informed by antimicrobial susceptibility testing.4–7,10 More work is needed to inform clinical guidelines, clinicians and communities about sexually transmitted Shigella in MSM, recognising emerging extensively drug-resistant shigella in these networks and the importance of antimicrobial susceptibility testing and future design of infection control strategies.AcknowledgmentsNone.ORCID iDsLewis C. E. Mason https://orcid.org/0000-0001-5049-1352Daniel Richardson https://orcid.org/0000-0003-0955-6307

Dear Editor,We congratulate Fuller et al.1 who highlight that Shigella in men who have sex with men (MSM) is seen in returning travellers. We would suggest that all MSM presenting with shigellosis, including returning travellers should be managed as having sexually transmitted shigellosis, particularly in those (i) living with human immunodeficiency virus (HIV), (ii) with recent non-regular sexual partners and (iii) with a sexually transmitted co-infection (e.g., Neisseria gonorrhoeae).2,3 Genomic data demonstrate the global and regional transmission of different Shigella species and lineages among large sexual networks of MSM in Europe, North America and Australia including the emergence and transmission of extensively antimicrobial resistant Shigella.4–6 Most sexually transmitted Shigella in high-income settings is likely to be resistant to quinolones, macrolides; and more recently cephalosporins.5,7,8 There are limited guidelines for the clinical management of sexually transmissible shigellosis globally, and those in publication provide conflicting advice.9 We would suggest that the current (2015) Canadian Committee to Advise on Tropical Medicine and Travel guidelines are inadequate for managing shigellosis in MSM as they do not consider the magnitude of antimicrobial resistance (AMR).5,10 Recent data from the United Kingdom (UK) suggest that following expert microbiological advice, fosfomycin, pivmecillinam or carbapenems could be considered where antimicrobials are indicated.2,10In regard to the management of the case, we note that the patient’s travel partners were asymptomatic, and the timing of his sexual contact and onset of symptoms are consistent with an incubation period of up to seven days, so suggest that his infection was acquired through sexual transmission.2 Shigella circulating in sexual networks of MSM in Canada and Europe are likely to be ciprofloxacin resistant; tetracycline resistance among sexually transmissible Shigella is also high, so doxycycline pre-exposure prophylaxis was unlikely to have been effective.10 We note that your patient’s symptoms were resolving by the time he was treated with ciprofloxacin, and no antimicrobial sensitivities were reported.The distinction between managing such cases as sexually transmitted shigellosis rather than travel associated (contaminated food/water) is important, specifically MSM with sexually transmitted Shigella should be offered comprehensive sexually transmitted infection testing (including HIV, Treponema pallidum, hepatitis A and B), partner notification, and be used as an opportunity to ensure other sexual health interventions have been offered such as hepatitis A, B, Human Papilloma Virus and Mpox vaccination, access to HIV pre-exposure prophylaxis in HIV negative MSM, doxycycline post-exposure prophylaxis discussion, condom use and sexual health education.2 Furthermore, we would not advocate for empirical macrolides, quinolones or cephalosporins based on current AMR data in MSM, and treatment decisions, particularly in resolving cases should be informed by antimicrobial susceptibility testing.4–7,10 More work is needed to inform clinical guidelines, clinicians and communities about sexually transmitted Shigella in MSM, recognising emerging extensively drug-resistant shigella in these networks and the importance of antimicrobial susceptibility testing and future design of infection control strategies.AcknowledgmentsNone.ORCID iDsLewis C. E. Mason https://orcid.org/0000-0001-5049-1352Daniel Richardson https://orcid.org/0000-0003-0955-6307

Study supports FDA's decision to add warnings to drug labeling for trimethoprim-sulfamethoxazole