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Background: Australian guidelines recommend trimethoprim or nitrofurantoin as first-line agents for uncomplicated urinary tract infections (UTIs). Laboratory surveillance indicates high rates of trimethoprim resistance among urinary bacterial isolates, but there are scant local clinical data about risk factors and impact of trimethoprim resistance., Objectives: To determine the prevalence, risk factors, mechanism and impact of resistance to first-line antibiotic therapy for uncomplicated UTIs in the community setting., Methods: A prospective observational study from October 2019 to November 2021 in four general practices in Melbourne, Australia. Female adult patients prescribed an antibiotic for suspected or confirmed uncomplicated acute cystitis were eligible. Primary outcome was urine isolates with resistance to trimethoprim and/or nitrofurantoin., Results: We recruited 87 participants across 102 UTI episodes with median (IQR) age of 63 (47-76) years. Escherichia coli was the most common uropathogen cultured (48/62; 77%); 27% (13/48) were resistant to trimethoprim (mediated by a dfrA gene) and none were resistant to nitrofurantoin. Isolates with resistance to a first-line therapy were more common among patients reporting a history of recurrent UTIs [risk ratio (RR): 2.08 (95% CI: 1.24-3.51)] and antibiotic use in the previous 6 months [RR: 1.89 (95% CI: 1.36-2.62)]. Uropathogen resistance to empirical therapy was not associated with worse clinical outcomes., Conclusions: Resistance to trimethoprim is common in uncomplicated UTIs in Australia but may not impact clinical outcomes. Further research is warranted on the appropriateness of trimethoprim as empirical therapy, particularly for patients with antimicrobial resistance risk factors., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Background: There is limited understanding of the epidemiology of generalized pustular psoriasis (GPP) internationally, with no population-based estimates of GPP in South East Asia., Objectives: To determine the incidence and prevalence of GPP in the Malaysian population and characterize its flares and trigger factors., Methods: We conducted a population-based cohort study using the Teleprimary Care database between January 2010 and December 2020. We identified 230 dermatologist-confirmed GPP cases using International Classification of Diseases, 10th revision, diagnostic codes. Annual prevalence and incidence rates were stratified by age, sex and ethnicity. We compared data regarding flares and trigger factors for patients with GPP who had associated psoriasis vulgaris (PV) with those who did not have associated PV., Results: The prevalence of GPP was 198 per million (267 women, 127 men) and incidence was 27.2 per million person-years [95% confidence interval (CI) 22.8-31.6]; 35.3 (28.4-42.2) per million person-years for women and 18.3 (13.1-23.5) per million person-years for men. Rates were higher in Chinese individuals [prevalence 271 per million; incidence 41.6 per million person-years (28.9-54.3)] than in the Malay population [prevalence 186; incidence 24.6 (19.4-29.7)] or the Indian ethnic group [prevalence 179; incidence 25.0 (13.8-36.3)]. Annual prevalence was consistently higher in women than in men and highest among the Chinese population, followed by the Indian and Malay populations. Overall, 67% of patients with GPP had associated PV. The prevalence and incidence of GPP without PV were lower than GPP with PV at 66 vs. 132 per million and 19.3 (95% CI 15.6-23.0) vs. 8.0 (95% CI 5.6-10.3) per million person-years, respectively. The mean age at GPP onset was 42.7 years (SD 18.4). A bimodal trend in the age of GPP onset was observed, with first and second peaks at age 20-29 years and age 50-59 years, respectively. Disease onset was significantly earlier in patients with GPP without PV than in those with PV [mean age 37.5 years (SD 20.7) vs. 44.9 years (SD 17.0), P = 0.026]. Flares occurred more frequently in patients without PV than in those with PV [mean number of flares per patient per year was 1.35 (SD 0.77) vs. 1.25 (SD 0.58), P = 0.039]. Common triggers of flares in patients with GPP who did not have PV were infections, pregnancy, menstruation and stress, whereas withdrawal of therapy, particularly systemic corticosteroids, was a more frequent trigger in patients with GPP who also had PV., Conclusions: Our findings contribute to the global mapping of GPP, which will help inform the management of this rare condition., Competing Interests: Conflicts of interest: S.E.C. declares paid activities as advisor, speaker or consultant for AbbVie, Boehringer Ingelheim, Eli Lilly, Janssen, LEO Pharma, MSD, Novartis, Pfizer, Sanofi and UCB. C.E.M.G. has received honoraria and/or research grants from AbbVie, Almirall, Amgen, AnaptysBio, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Evelo Bioscience, Galderma, GSK, Inmagene, LEO Pharma, Janssen, ONO Pharmaceuticals, Novartis, Pfizer, Sandoz and UCB Pharma. D.M.A. reports research grants from AbbVie, Almirall, Eli Lilly, Janssen, Novartis, UCB, and the LEO Foundation., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Objectives: To define the long-term impacts of antibiotic allergy testing (AAT) on patient allergy perception and antibiotic utilization., Methods: Patients were identified from a prospective AAT database as having completed testing during a 15 month period beginning January 2017. Patients were contacted for a follow-up survey at least 12 months post-AAT. For those contacted, baseline demographics, antibiotic allergy label (AAL) history, age-adjusted Charlson comorbidity index, infection history, antibiotic de-labelling (≥1 AAL removed following AAT) and antibiotic usage for 12 months prior to testing (pre-AAT) and 12 months following testing (post-AAT) were recorded for each patient., Results: From the follow-up survey of 112 patients post-AAT, 95.2% (59/62) of patients with complete AAL removal expressed willingness to use 'de-labelled' antibiotics and 91.9% (57/62) were adherent to allergy label modification. Comparing antibiotic utilization 12 months pre-AAT versus 12 months post-AAT, AAT was associated with a significant increase in preferred antibiotic therapy [adjusted odds ratio (aOR) 3.29, 95% CI 1.56-6.92] and reduction in restricted antibiotic utilization (aOR 0.42, 95% CI 0.19-0.93)., Conclusions: An antimicrobial stewardship (AMS)-led AAT programme was safe and effective in the long term in the promotion of preferred and narrow-spectrum antibiotic usage, and favourable patient perception towards the AAT testing results was identified. This study further supports the routine incorporation of AAT into AMS programmes, confirming safety and durability of testing impacts on patients as well as increasing preferred antibiotic utilization., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

The role of panfungal polymerase chain reaction (PCR) assays for diagnosis of invasive fungal disease (IFD) is inadequately defined. We describe the use of an internal transcribed spacer 1 (ITS-1) region-directed panfungal PCR in this context at a tertiary referral transplant center. A retrospective review of patients at Alfred Health, Melbourne, Australia (2009-2014) who had clinical samples referred for panfungal PCR testing was conducted. Baseline patient characteristics, antifungal drug history, fungal culture/histopathology, and radiology results were recorded. For bronchoalveolar lavage (BAL) fluid samples, identification of a fungus other than a Candida spp. was defined as a potential pathogen.Of 138 panfungal PCR tests (108 patients), 41 (30%) were positive for a fungal product. Ninety-seven percent (134/138) of specimens were from immunocompromised hosts. Thirteen percent (19/138) of panfungal PCR positive results were for potential pathogens and potential pathogens were detected more frequently in tissue as compared with BAL (12/13 vs. 6/26; P = .0001). No positive panfungal PCR results were obtained from CSF specimens. If histopathology examination was negative, panfungal PCR identified a potential pathogen in only 12% (11/94) of specimens. For the 20 culture negative/histopathology positive specimens, diagnosis of IFD to causative species level by panfungal PCR occurred in 35% (6/20).Sterile site specimens, in particular tissue, were more frequently panfungal PCR positive for potential pathogens than BAL. The utility of panfungal PCR appears greatest in tissue specimens, as an adjunct to histopathology to improve diagnostic sensitivity and specificity. Based on the results of this study we are now only testing tissue specimens by panfungal PCR., (© The Author 2015. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Staphylococcus aureus remains a major opportunistic human pathogen, and while in many individuals it is associated with asymptomatic colonization, it is also capable of causing a range of clinical syndromes from minor skin infections to life-threatening septicemia. Staphylococcus aureus has also demonstrated a remarkable capacity to acquire antimicrobial resistance. Recent technological advances in genomics have led to an avalanche of studies providing deep insights into how S. aureus is evolving globally and within the human host. However, there are still significant experimental barriers in using these insights to try and better understand the biology of S. aureus. Here, we summarize recent advances in the understanding of S. aureus through the use of genomic approaches, and contemplate what the near future holds for truly functional genomics that will allow us to better understand the biology of this pathogen.