Efficacy and safety profile of linezolid in the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis: a systematic review and meta-analysis

Background

Treatment options for drug-resistant tuberculosis are still limited. Linezolid has been recommended for treatment of patients with multidrug-resistant (MDR) or extensively-drug-resistant (XDR) tuberculosis, although uncertainties remain regarding its safety and tolerability in these circumstances.

Objective

To systematically evaluate the existing evidence regarding the efficacy and tolerability of linezolid in the treatment of MDR or XDR tuberculosis.

Methods

We conducted a systematic review and meta-analysis in accordance with the PRISMA guidelines. Searches were conducted in PubMed, Web of Science and EMBASE followed by direct search of abstracts in the International Journal of Tuberculosis and Lung Disease to retrieve primary studies published between January 2000 and January 2016 assessing linezolid efficacy and safety in the treatment of drug-resistant TB. We evaluated the occurrence of outcomes including culture conversion, treatment success and incidence of adverse events such as myelosuppression and neuropathy.

Results

Twenty-three (23) studies conducted in fourteen (14) countries and involving 507 patients were retrieved. Only 1 randomized controlled trial was identified and none of the identified studies involved participants from Africa. The pooled proportion for treatment success was 77.36 % (95 % CI = 71.38–82.83 %, I² = 37.6 %) with culture conversion rate determined as 88.45 % (95 % CI = 83.82–92.38 %, I² = 45.4 %). There was no strong evidence for both culture conversion (p = 0.0948) and treatment success (p = 0.0695) between linezolid daily doses ≤ 600 and > 600 mg. Only myelosuppression showed a strong statistical significance (p < 0.0001) between dose comparisons. The incidence of neuropathy and other adverse events leading to permanent discontinuation of linezolid also showed no significance upon dose comparisons (p = 0.3213, p = 0.9050 respectively).

Conclusion

Available evidence presents Linezolid as a viable option in the treatment of MDR/XDR TB although patients ought to be monitored closely for the incidence of major adverse events such as myelosuppression and neuropathy. Additionally, highly powered randomized controlled trials including participants from endemic regions are urgently needed to better inform the magnitude and significance of Linezolid treatment effect in MDR and XDR TB patients.

     

When ‘blood speaks’: naming the father and the mystics of kinship in Dominica,Eastern Caribbean

This article explores the mystical implication of fathers in reproduction in Dominica, Eastern Caribbean. It traces naming acts that assign paternity at various points in the filial life course, each attempting to disambiguate paternity. Confronting a recurring anthropological problematic – the problem of paternity (paternity's inherent putativity) – the article argues that Dominicans contest uncertain physical fatherhood through the proverb ‘blood speaks’. The article elaborates how relatedness reveals itself in the subtle bodies of kin at three moments: through a local version of the couvade (‘sympathetic pregnancy’); in elders’ post-partum ritual scrutiny of children's bodies for familial resemblances; and during serendipitous encounters in later life. The article highlights how physical fatherhood is disclosed in fathers’ and children's symptoms, appearances, and sensations, revealing their kinship in transpersonal terms. Therefore, blood ‘speaks’ to counter broad-brushed narratives of Caribbean fatherly absence by revealing the physical and spiritual significance of fatherhood. Herein, the article revives classic anthropological debates on legitimacy, the couvade, and Caribbean kinship, whilst contributing to contemporary theorizations of blood and naming.