Linezolid to treat extensively drug-resistant TB: retrospective data are confirmed by experimental evidence

Extensively drug-resistant tuberculosis (XDR-TB) on top of being a growing public health concern, represents a nightmare for the clinician. The crucial therapeutic issue is the difficulty of identifying at least four available ‘‘active’’ anti-TB drugs, to ensure treatment success as well as to prevent the emergence of additional drug resistance.
After more than 40 years without new anti-TB drugs appearing on the horizon, new chemical compounds (i.e. bedaquiline, PA-824 and delamanid) seem promising for these difficult-to-treat cases of TB. While the necessary experimental studies will prove how to use them, more and more interest is currently focused on existing antibacterial drugs with new indications for drug-resistant TB, particularly linezolid, meropenem, clofazimine and cotrimoxazole.
Based on in vitro and pharmacological data, suggesting that linezolid (an oxazolidinone antibiotic) could be efficacious in treating mycobacterial infections, and on anedoctal evidence of its effectiveness in the smallest groups of patients, it was used off-label, despite its high price, to treat multidrug-resistant (MDR) TB cases in several countries. A growing amount of data from linezolid-exposed cohorts more and more clearly supports the rationale of prescribing the drug daily at a low dose, tailored to the pharmacokinetic profile obtained through therapeutic drug monitoring. The identification of the adequate daily exposure to linezolid will prevent occurrence of adverse events, both life-threatening (e.g. determining the physician’s decision to stop the drug) and non-serious (e.g. lowering the patient’s motivation to continue the prescribed treatment). The obvious consequence will be improved patient adherence and an increased chance of achieving treatment success.