Increasing pathomorphism of pulmonary tuberculosis: an observational study of slow clinical, microbiological and imaging response of lung tuberculosis to specific treatment. Which role for linezolid?

Abstract

During recent years, a progressive emerging of tuberculosis occurred, related to the overall increased age of general population, primary and secondary (iatrogenic) immunodeficiencies, the availability of invasive procedures, surgical interventions and intensive care supports, bone marrow and solid organ transplantation, and especially the recent immigration flows of people often coming from areas endemic for tuberculosis, and living with evident social-economical disadvantages, and with a reduced access to health care facilities. Since January 2006, at our reference centre we followed 81 consecutive cases of pulmonary tuberculosis, with 65 of them which remained evaluable for the absence of extrapulmonary complications, and a continuative and effective clinical and therapeutic follow-up. The majority of episodes of evaluable pulmonary tuberculosis (49 cases out of 65: 75,4%) occurred in patients who immigrated from developing countries. In two patients multiresistant (MDR) Mycobacterium tuberculosis strains were found, while two more subjects (both immigrated from Eastern Europe) suffered from a disease due to extremely resistant (XDR) M. tuberculosis strains. Although enforcing all possible measures to increase patients' adherence to treatment (empowerment, delivery of oral drugs under direct control, use of i.v. formulation whenever possible), over 72% of evaluable patients had a very slow clinical, microbiological, and imaging ameliorement (1-6 months), with persistance of sputum and/or bronchoalveolar lavage (BAL) fluid positive for M.tuberculosis microscopy and/or culture for over 1-4 months (mean 9.2+/-3.2 weeks), during an apparently adequate treatment. When excluding patients suffering from XDR and MDR tuberculosis, in four subjects we observed that off-label linezolid adjunct together with at least three drugs with residual activity against tuberculosis, led to a significantly more rapid clinical-radiological improvement and negative microbiological search, with consequent possibility to led to a protected discharge, supported by a sequential, oral therapy. Linezolid was also successfully employed in all the four patients with XDR or MDR pulmonary tuberculosis: among these patients, a definitive or temporarily negativization of respiratory secretions, and consequent discharge, was achieved only after linezolid adjunct. Notwithstanding the maintained microbiological susceptibility of M. tuberculosis strains responsible of the great majority of cases of pulmonary tuberculosis to first-line drugs, an unexpected tendency of patients to have a persistingly positive sputum and/or BAL, and to experience prolonged hospitalization for cure and isolation, has been recognized in the last years. No particularly suggestive radiological imaging seems predictive of a so prolonged course, so that we presently lack of clinical and imaging elements which may be predictive of this slow treatment response. The same is for demographic and epidemiological issues, eventual underlying diseases, and clinical presentation, so th...

Multidrug-resistant tuberculosis treatment adherence in migrants: a systematic review and meta-analysis

“…Studies were conducted in 11 countries: Canada (2) [ 43 , 44 ], Australia (2) [ 32 , 45 ], Czech Republic (1) [ 46 ], Finland (1) [ 47 ], France (1) [ 48 ], Germany (1) [ 49 ], Iran (1) [ 50 ], Italy (3) [ 51 – 53 ], New Zealand (1) [ 54 ], Switzerland (1) [ 55 ] and USA (1) [ 56 ] (Table 1 ). A number of studies indicated that treatment was provided at specialist TB centres or centres that otherwise specialised in infectious and pulmonary diseases [ 43 , 46 , 50 , 52 , 55 ], whilst the remaining studies either did not indicate the institutions providing treatment or were based on national-level data. Data were not consistently reported on migrant characteristics, including the reason for migration, time since migration or country of origin.…”

WHO Group 5 Drugs and Difficult Multidrug-Resistant Tuberculosis: a Systematic Review with Cohort Analysis and Meta-Analysis

“…These included prospective and retrospective observational studies. Figure 1 shows how a cohort of fluoroquinoloneresistant MDR-TB patients treated with WHO group 5 drugs was assembled from 20 articles (6,(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39). The cohort consisted of 194 patients from 12 countries: 117 from four Asian regions (South Korea, China, Hong Kong, and India), 40 from five European countries (Portugal, Italy, Germany, Belgium, and Spain), 36 from two North and South American countries (the United States and Argentina), and 1 from South Africa.…”

Multidrug and extensively drug-resistant tuberculosis from a general practice perspective

“…There are various other factors favoring the spread of tuberculosis, which include increasing high-risk groups (eg, the elderly, prisoners, immigrants, drug addicts6), recurrent defaulters, multidrug-resistant and extensively drug-resistant treatment failures,3 increasing age of the general population, increasing number of patients with immunosuppression due to bone marrow and solid organ transplantation,16 and lack of optimal recommended duration of treatment for multidrug-resistant and extensively drug-resistant tuberculosis in controlled clinical trials 4. In addition, certain host genetic factors and coexistent HIV infection may also predispose to the development of multidrug-resistant tuberculosis 11,17…”

“…Some of the new drugs and vaccines having the potential to cure multidrug-resistant and extensively drug-resistant tuberculosis are linezolid,16,22,23 thioridazine (a neuroleptic phenothiazine),24–26 myrtle leaf extracts (used as an antiseptic in Sardinian traditional medicine),27 medicinal plants having antituberculous activity (Acalypha indica, Adhatoda vasica, Allium cepa, Allium sativum, Aloe vera28), and HSP65+IL-12/HVJ vaccine 29. HSP65+IL-12/HVJ is a combination of DNA vaccines expressing mycobacterial heat-shock protein 65 and interleukin-12, delivered by the hemagglutinating virus of Japan envelope and liposome) 29.…”