Fluoroquinolones and isoniazid-resistant tuberculosis: implications for the 2018 WHO guidance.

INTRODUCTION: 2018 World Health Organization (WHO) guidelines for the treatment of isoniazid (H)-resistant (Hr) tuberculosis recommend a four-drug regimen: rifampicin (R), ethambutol (E), pyrazinamide (Z) and levofloxacin (Lfx), with or without H ([H]RZE-Lfx). This is used once Hr is known, such that patients complete 6 months of Lfx (≥6[H]RZE-6Lfx). This cohort study assessed the impact of fluoroquinolones (Fq) on treatment effectiveness, accounting for Hr mutations and degree of phenotypic resistance. METHODS: This was a retrospective cohort study of 626 Hr tuberculosis patients notified in London, 2009-2013. Regimens were described and logistic regression undertaken of the association between regimen and negative regimen-specific outcomes (broadly, death due to tuberculosis, treatment failure or disease recurrence). RESULTS: Of 594 individuals with regimen information, 330 (55.6%) were treated with (H)RfZE (Rf=rifamycins) and 211 (35.5%) with (H)RfZE-Fq. The median overall treatment period was 11.9 months and median Z duration 2.1 months. In a univariable logistic regression model comparing (H)RfZE with and without Fqs, there was no difference in the odds of a negative regimen-specific outcome (baseline (H)RfZE, cluster-specific odds ratio 1.05 (95% CI 0.60-1.82), p=0.87; cluster NHS trust). Results varied minimally in a multivariable model. This odds ratio dropped (0.57, 95% CI 0.14-2.28) when Hr genotype was included, but this analysis lacked power (p=0.42). CONCLUSIONS: In a high-income setting, we found a 12-month (H)RfZE regimen with a short Z duration to be similarly effective for Hr tuberculosis with or without a Fq. This regimen may result in fewer adverse events than the WHO recommendations.

Incidence of tuberculosis is high in chronic kidney disease patients in South East England and drug resistance common.

The risk of tuberculosis (TB) is significantly increased in chronic kidney disease (CKD). Data on TB in CKD in the UK are sparse; most information stems from countries with high background prevalence. The aim of this study was to estimate the incidence of TB in CKD patients in South East London and to describe the epidemiology, treatment, and outcome. CKD patients with TB between 1994 and 2010 were identified retrospectively. Data were collected on type of renal replacement therapy, the method of TB diagnosis, disease site, treatment regimens, and risk factors. Forty patients were identified of whom 67.5% had CKD stages IV-V. Sixty-five percent were from non-UK born ethnic minorities. Median time from diagnosis of CKD to TB development was 12 months (range 0-192 months). Cumulative incidence of TB was 1267/100,000 [95% confidence interval (CI): 630-1904; 85 × background UK rate] in hemodialysis patients; 398/100,000 (95% CI: 80-1160; 26 × background UK rate) in peritoneal dialysis; and 522/100,000 (CI: 137-909; 35 × background UK rate) in transplant recipients. Sixty-three percent of patients had pulmonary TB and 25% of patients with culture-positive TB had resistant isolates. Fifty percent of patients were immunosuppressed due to drugs, diabetes, and/or retroviral disease. Treatment regimens were according to recent national guidance in 73% of cases. Seventy-six percent of patients experienced side effects. Greater awareness of risk factors, drug resistance, treatment regimens, and potential side effects is needed.