Antimicrobial stewardship in solid organ transplant-Opportunities in the National Health Service.

BACKGROUND: Antimicrobial stewardship (AMS) is an intervention, which ensures the appropriateness of antimicrobial use to avoid in part the rising problem of antimicrobial resistance and negative effects of inappropriate antimicrobial use. In the solid organ transplant (SOT) population, which is prone to a particularly high risk of infection resulting from immunosuppression and anatomical issues with each type of SOT, the need for good stewardship has never been more important. This article looks at current AMS practice in SOT units in the United Kingdom and how things could be improved in the future. METHODS: The current practice of AMS alongside national antimicrobial resistance rates were reviewed using national mandatory reporting data. The background to the current practice and policies in place in the National Health Service (NHS) were also reviewed and possibilities for future approaches explored. RESULTS: AMS is a requirement within all NHS hospitals in the United Kingdom as per government policy. Mandatory reporting of specific bloodstream infections (BSIs) and antimicrobial consumption alongside financial incentives has been the approach nationwide. Gram-negative resistance rates in BSIs have been increasing prior to the COVID-19 pandemic. Little SOT-specific data on antimicrobial resistance exists, and the general approach to AMS in SOT units has generally modeled the national approach. CONCLUSION: Although there is a good, standardized approach to AMS in the NHS, there is a need for SOT-specific AMS approaches to be developed in the United Kingdom. More data is required on antimicrobial resistance rates, and studies are needed to investigate optimal antimicrobial prophylaxis regimens for each solid organ group. Tools to aid AMS efforts and novel treatment options for complex multiresistant infection must also be explored amongst transplant centers.

Toxicity associated with tuberculosis chemotherapy in the REMoxTB study.

BACKGROUND: The incidence and severity of tuberculosis chemotherapy toxicity is poorly characterised. We used data available from patients in the REMoxTB trial to provide an assessment of the risks associated with the standard regimen and two experimental regimens containing moxifloxacin. METHODS: All grade 3 & 4 adverse events (AEs) and their relationship to treatment for patients who had taken at least one dose of therapy in the REMoxTB clinical trial were recorded. Univariable logistic regression was used to test the relationship of baseline characteristics to the incidence of grade 3 & 4 AEs and significant characteristics (p < 0.10) were incorporated into a multivariable model. The timing of AEs during therapy was analysed in standard therapy and the experimental arms. Logistic regression was used to investigate the relationship between AEs (total and related-only) and microbiological cure on treatment. RESULTS: In the standard therapy arm 57 (8.9%) of 639 patients experienced ≥1 related AEs with 80 of the total 113 related events (70.8%) occurring in the intensive phase of treatment. Both four-month experimental arms ("isoniazid arm" with moxifloxacin substituted for ethambutol & "ethambutol arm" with moxifloxacin substituted for isoniazid) had a lower total of related grade 3 & 4 AEs than standard therapy (63 & 65 vs 113 AEs). Female gender (adjOR 1.97, 95% CI 0.91-1.83) and HIV-positive status (adjOR 3.33, 95% CI 1.55-7.14) were significantly associated with experiencing ≥1 related AE (p < 0.05) on standard therapy. The most common adverse events on standard therapy related to hepatobiliary, musculoskeletal and metabolic disorders. Patients who experienced ≥1 related AE were more likely to fail treatment or relapse (adjOR 3.11, 95% CI 1.59-6.10, p < 0.001). CONCLUSIONS: Most AEs considered related to standard therapy occurred in the intensive phase of treatment with female patients and HIV-positive patients demonstrating a significantly higher risk of AEs during treatment. Almost a tenth of standard therapy patients had a significant side effect, whereas both experimental arms recorded a lower incidence of toxicity. That patients with one or more AE are more likely to fail treatment suggests that treatment outcomes could be improved by identifying such patients through targeted monitoring.