Pharmacokinetics and other risk factors for kanamycin-induced hearing loss in patients with multi-drug resistant tuberculosis.

Objective: The toxicity associated with the use of kanamycin includes irreversible hearing loss. There are limited data describing the relationship between hearing loss and kanamycin pharmacokinetics (PK). We explored the association of kanamycin PK with hearing loss in patients on MDR-TB treatment.Design: We prospectively recruited patients on kanamycin-based MDR-TB treatment in Cape Town. Hearing thresholds from 0.25 to 16 kHz were tested at baseline and at 4, 8 and 12 weeks. We determined kanamycin concentrations at steady-state in serial plasma samples over 10 h, and explored factors associated with hearing loss.Study sample: One hundred and two participants including 58 (56.9%) men had analysable audiometric data; median age was 34.9 years, 65 (63.7%) were HIV-positive, and 24 (23.5%) had been treated for MDR-TB previously.Results: Eighty-four participants (82.4%) developed hearing loss. We found a 3% (95% CI: 1-6%, p = 0.028) increased risk of cochleotoxicity for each 10 µg h/L increase in 0-10 h AUC.Conclusion: We describe a high incidence of hearing loss in MDR-TB patients treated with kanamycin, with higher AUC0-10 significantly associated with hearing loss.

Elective reconstruction of the ascending aorta for aneurysmal disease restores normal life expectancy. An analysis of risk factors for early and late mortality.

OBJECTIVE: We investigated the survival of patients who had undergone elective reconstruction of the ascending aorta for degenerative aneurysms. The long-term survival was compared to an age- and sex-matched case-control population. An analysis of risk factors, influencing survival was made. METHODS AND RESULTS: From May 1998 to January 2012, 72 patients underwent elective reconstruction of the ascending aorta for degenerative disease at the department of Cardiothoracic Surgery of the Jessa Hospital, Hasselt, Belgium. Sixty patients were treated with Bentall procedures, whereas 12 received valve-sparing procedures. The average age of the patient group was 65.5 years (range 24-80), with 64% males. Thirty-day mortality was 9.7% (consistent with calculated Euroscore II: 9.2%). The long-term survival was 80.9% at 3, 5 and 10 years. No deaths occurred between 3 and 10 years postoperatively. In an age- and sex case-matched Belgian population, 3-, 5- and 10-year survival were 95.7%, 94.7% and 85.2%, respectively. Long-term survival was not significantly different between both groups. Poor NYHA class at the time of surgery (P = 0.041) and COPD (P = 0.028) had a significant impact on global survival. Valve-sparing operations provide similar long-term survival, avoiding thrombo-embolic complications. CONCLUSIONS: Reconstruction of the ascending aorta for degenerative aneurysmal disease restores normal life expectancy, compared with an age- and sex-matched case-control population. Early mortality is consistent with the Euroscore II risk calculation. Whereas late survival progressively declines in the average population, it remains constant in the treated group after 3 years. COPD and poor functional class significantly impair survival. Valve-sparing procedures confer a similar long-term survival as valve replacement.