Search

Background: Antimicrobial resistance (AMR) is a multifaceted global challenge, partly driven by inappropriate antibiotic prescribing. The objectives of this study were to evaluate the impact of the COVID-19 pandemic on treatment of common infections, develop risk prediction models and examine the effects of antibiotics on infection-related hospital admissions. Methods: With the approval of NHS England, we accessed electronic health records from The Phoenix Partnership (TPP) through OpenSAFELY platform. We included adult patients with primary care diagnosis of common infections, including lower respiratory tract infection (LRTI), upper respiratory tract infections (URTI), and lower urinary tract infection (UTI), from 1 January 2019 to 31 August 2022. We excluded patients with a COVID-19 record in the 90 days before to 30 days after the infection diagnosis. Risk prediction models using Cox proportional-hazard regression were developed for infection-related hospital admission in the 30 days after the common infection diagnosis. Results: We found 12,745,165 infection diagnoses from 1 January 2019 to 31 August 2022. Of them, 80,395 (2.05%) cases were admitted to the hospital during follow-up. Counts of hospital admission for infections dropped during COVID-19, for example LRTI from 3,950 in December 2019 to 520 in April 2020. Comparing those prescribed an antibiotic to those without, reduction in risk of hospital admission were largest with LRTI (adjusted hazard ratio (aHR) of 0.35; 95% confidence interval (CI), 0.35–0.36) and UTI (aHR 0.45; 95% CI, 0.44–0.46), compared to URTI (aHR 1.04; 95% CI, 1.03–1.06). Conclusions: A substantial variation in hospital admission risks between infections and patient groups was found. Antibiotics appeared more effective in preventing infection-related complications with LRTI and UTI, but not URTI. While this study has several limitations, the results indicate that a focus on risk-based antibiotic prescribing could help tackle AMR in primary care. [ABSTRACT FROM AUTHOR]

Background: Adverse drug reactions (ADRs) are common and a leading cause of injury. However, information on ADR risks of individual medicines is often limited. The aim of this hypothesis‐generating study was to assess the relative importance of ADR‐related and emergency hospital admission for large group of medication classes. Methods: This study was a propensity‐matched case‐control study in English primary care. Data sources were Clinical Practice Research Databank and Aurum with longitudinal, anonymized, patient level electronic health records (EHRs) from English general practices linked to hospital records. Cases aged 65–100 with ADR‐related or emergency hospital admission were matched to up to six controls by age, sex, morbidity and propensity scores for hospital admission risk. Medication groups with systemic administration as listed in the British National Formulary (used by prescribers for medication advice). Prescribing in the 84 days before the index date was assessed. Only medication groups with 50+ cases exposed were analysed. The outcomes of interest were ADR‐related and emergency hospital admissions. Conditional logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CI). Results: The overall population included 121 546 cases with an ADR‐related and 849 769 cases with emergency hospital admission. The percentage of hospitalizations with an ADR‐related code for admission diagnosis was 1.83% and 6.58% with an ADR‐related code at any time during hospitalization. A total of 137 medication groups was included in the main ADR analyses. Of these, 13 (9.5%) had statistically non‐significant adjusted ORs, 58 (42.3%) statistically significant ORs between 1.0 and 1.5, 37 (27.0%) between 1.5–2.0, 18 (13.1%) between 2.0–3.0 and 11 (8.0%) 3.0 or higher. Several classes of antibiotics (including penicillins) were among medicines with largest ORs. Evaluating the 14 medications most often associated with ADRs, a strong association was found between the number of these medicines and the risk of ADR‐related hospital admission (adjusted OR of 7.53 (95% CI 7.15–7.93) for those exposed to 6+ of these medicines). Conclusions and Relevance: There is a need for a regular systematic assessment of the harm‐benefit ratio of medicines, harvesting the information in large healthcare databases and combining it with causality assessment of individual case histories. [ABSTRACT FROM AUTHOR]

This study evaluated drug–drug interactions (DDIs) between antibiotic and nonantibiotic drugs listed with warnings of severe outcomes in the British National Formulary based on adverse drug reaction (ADR) detectable with routine International Classification of Diseases, Tenth Revision coding. Data sources were Clinical Practice Research Databank GOLD and Aurum anonymized electronic health records from English general practices linked to hospital admission records. In propensity‐matched case‐control study, outcomes were ADR or emergency admissions. Analyzed were 121,546 ADR‐related admission cases matched to 638,238 controls. For most antibiotics, adjusted odds ratios (aORs) for ADR‐related hospital admission were large (aOR for trimethoprim 4.13; 95% confidence interval (CI), 3.97–4.30). Of the 51 DDIs evaluated for ADR‐related admissions, 38 DDIs (74.5%) had statistically increased aORs of concomitant exposure compared with nonexposure (mean aOR 3.96; range 1.59–11.42); for the 89 DDIs for emergency hospital admission, the results were 75 (84.3%) and mean aOR 2.40; range 1.43–4.17. Changing reference group to single antibiotic exposure reduced aORs for concomitant exposure by 76.5% and 83.0%, respectively. Medicines listed to cause nephrotoxicity substantially increased risks that were related to number of medicines (aOR was 2.55 (95% CI, 2.46–2.64) for current use of 1 and 10.44 (95% CI, 7.36–14.81) for 3 or more medicines). In conclusion, no evidence of substantial risk was found for multiple DDIs with antibiotics despite warnings of severe outcomes in a national formulary and flagging in electronic health record software. It is proposed that the evidence base for inclusion of DDIs in national formularies be strengthened and made publicly accessible and indiscriminate flagging, which compounds alert fatigue, be reduced. [ABSTRACT FROM AUTHOR]