Multidrug-resistant tuberculosis (MDR-TB) treatment in the UK: a study of injectable use and toxicity in practice.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is an increasing challenge to health services globally. Although new drugs are in development, current guidelines still recommend prolonged use of injectable antimicrobials (usually amikacin, kanamycin or capreomycin). The evidence base to inform treatment and monitoring strategies is very limited. METHODS: We conducted a retrospective study of patients initiating injectable antimicrobials for MDR-TB treatment in five UK centres between January 2004 and December 2009. (i) Current treatment and monitoring strategies were reviewed. (ii) The incidence of ototoxicity (defined both clinically and on audiological testing) and factors associated with ototoxicity were investigated using logistic regression. RESULTS: (i) The choice of injectable antimicrobial varied. Of 50 MDR-TB patients, 29/50 (58%) received amikacin, 11/50 (22%) received capreomycin and 10/50 (20%) received streptomycin or a combination; reflecting a difference in policy between centres. Only 21/50 (42%) patients received baseline screening by audiogram within 2 weeks of starting treatment and 16/50 (32%) then had monthly audiograms, with the majority screened more infrequently and 12/50 (24%) receiving no screening. (ii) Of the 50 patients, 14 (28%) experienced ototoxicity, with 9/50 (18%) left with long-term hearing loss. Increased age (P = 0.02), use of amikacin (P = 0.02) and decreased renal function (P = 0.01) were significantly associated with ototoxicity. CONCLUSIONS: There is local variation in both the choice of injectable agent and in ototoxicity screening practices. Long-term morbidity from injectable treatment is significant even in this well-resourced setting, and the data suggest capreomycin might be associated with less ototoxicity when compared with amikacin. There is a need for more high-quality clinical data to inform future guidelines for treatment and monitoring.

Frontal assault on tuberculosis. Interview by Eileen Fursland.

Nurses working with people who have TB in London battle to reduce the stigma attached to the disease. For many patients, TB is just one of many problems they have to contend with. People living in shared accommodation can face homelessness as a result of their infection. In some countries TB is associated with HIV, increasing the stigma patients face. Some patients are given incentives to encourage concordance with treatment.

Viral hepatitis prevalence in patients with active and latent tuberculosis.

AIM: To assess the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection and association with drug induced liver injury (DILI) in patients undergoing anti-tuberculosis (TB) therapy. METHODS: Four hundred and twenty nine patients with newly diagnosed TB - either active disease or latent infection - who were due to commence anti-TB therapy between September 2008 and May 2011 were included. These patients were prospectively tested for serological markers of HBV, HCV and human immunodeficiency virus (HIV) infections - hepatitis B core antigen (HBcAg), hepatitis B surface antigen (HBsAg), hepatitis B e antigen, IgG and IgM antibody to HBcAg (anti-HBc), HCV IgG antibody and HIV antibody using a combination of enzyme-linked immunosorbent assay, Western blot assay and polymerase chain reaction techniques. Patients were reviewed at least monthly during the TB treatment initiation phase. Liver function tests were measured prior to commencement of anti-TB therapy and 2-4 wk later. Liver function tests were also performed at any time the patient had significant nausea, vomiting, rash, or felt non-specifically unwell. Fisher's exact test was used to measure significance in comparisons of proportions between groups. A P value of less than 0.05 was considered statistically significant. RESULTS: Of the 429 patients, 270 (62.9%) had active TB disease and 159 (37.1%) had latent TB infection. 61 (14.2%) patients had isolated anti-HBc positivity, 11 (2.6%) were also HBsAg positive and 7 (1.6%) were HCV-antibody positive. 16/270 patients with active TB disease compared to 2/159 patients with latent TB infection had markers of chronic viral hepatitis (HBsAg or HCV antibody positive; P = 0.023). Similarly the proportion of HBsAg positive patients were significantly greater in the active vs latent TB infection group (10/43 vs 1/29, P = 0.04). The prevalence of chronic HBV or HCV was significantly higher than the estimated United Kingdom prevalence of 0.3% for each. We found no association between DILI and presence of serological markers of HBV or HCV. Three (5.3%) patients with serological markers of HBV or HCV infection had DILI compared to 25 (9.5%) patients without; P = 0.04. CONCLUSION: Viral hepatitis screening should be considered in TB patients. DILI risk was not increased in patients with HBV/HCV.

Concomitant use of nonnucleoside analogue reverse transcriptase inhibitors and rifampicin in TB/HIV type 1-coinfected patients.

Pharmacokinetic interactions between rifampicin and nonnucleoside analogue reverse transcriptase inhibitors (NNRTIs) pose challenges in the treatment of TB/HIV coinfection. We describe NNRTI plasma concentrations (PC) and treatment outcomes in TB/HIV coinfected patients receiving rifampicin and NNRTIs concomitantly. Single center prospective data were collected on all TB/HIV-coinfected patients who received concomitant NNRTI and rifampicin between 2001 and 2005. Of 103 TB/HIV coinfected patients, 26 received concomitant rifampicin with efavirenz (EFV) and 17 with nevirapine (NVP). NNRTIs were commenced after rifampicin in 18/26 (69%) and 7/17 (41%) subjects treated with EFV and NVP, respectively. Of these 88% completed antituberculosis therapy. There were two (5%) deaths, both due to lymphoproliferative malignancy. Three (7%) patients transferred care or discontinued therapy. Of subjects 83% had normal liver function tests (LFTs) and 11% had Grade 1-2 and 6% Grade 3-4 LFT abnormalities during concomitant therapy. PCs were measured in 31 patients. The first PCs were within the therapeutic range in 5/7 on NVP 200 mg bd, 2/4 on NVP 300 mg bd, 3/7 EFV 600 mg od, and 7/13 on EFV 800 mg od. PCs were subtherapeutic in 4/11 (36%) and 3/20 (20%) subjects on NVP and EFV, respectively. No virological rebounds were observed. Of subjects receiving concomitant NVP or EFV with rifampicin, 64% and 80%, respectively, had therapeutic NNRTI PCs. Subtherapeutic PCs were not associated with virological failure. Good clinical outcomes and a low incidence of hepatotoxicity were observed.