PMID- 30817779 OWN - NLM STAT- MEDLINE DCOM- 20191122 LR - 20200309 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 14 IP - 2 DP - 2019 TI - Putting in harm to cure: Drug related adverse events do not affect outcome of patients receiving treatment for multidrug-resistant Tuberculosis. Experience from a tertiary hospital in Italy. PG - e0212948 LID - 10.1371/journal.pone.0212948 [doi] LID - e0212948 AB - RATIONALE: Treatment of multi-drug resistant Tuberculosis (MDR-TB) is challenging because it mostly relies on drugs with lower efficacy and greater toxicity than those used for drug-susceptible TB. OBJECTIVES: Aim of the study was to describe the frequency and type of adverse drug reactions in a cohort of MDR-TB patients and their potential impact on treatment outcome. METHODS: We conducted a retrospective study in a cohort of MDR-TB patients enrolled at a tertiary referral hospital in Italy from January 2008 to December 2016. The records of patients were reviewed for epidemiological, clinical, microbiological and adverse drug reactions data. RESULTS: Seventy-four MDR-TB patients (mean age 32 years, 58.1% males, 2 XDR, 12 pre-XDR TB) were extracted from the Institute data base and included in the retrospective study cohort in the evaluation period (January 2008-December 2016). Median length of treatment duration was 20 months (IQR 14-24). Treatment outcome was successful in 57 patients (77%; 51 cured, 6 treatment completed); one patient died and one failed (2.7% overall); 15 patients were lost to follow-up (20.3%). Sixty-six (89.2%) presented adverse drug reactions during the whole treatment period. Total number of adverse drug reactions registered was 409. Three hundred forty-six (84.6%) were classified as adverse events (AEs) and 63 (15.4%) were serious AEs (SAEs). One third of the total adverse drug reactions (134/409; 32.8%) was of gastrointestinal origin, followed by 47/409 (11.5%) ototoxic drug reactions, thirty-five (8.6%) regarded central nervous system and 33 (8.1%) affected the liver. All 63 SAEs required treatment suspension with 61 SAEs out of 63 (96.8%) occurring during the first six months of treatment. Factors associated with unsuccessful treatment outcome were smoking (p = 0.039), alcohol abuse (p = 0.005) and homeless condition (p = 0.044). Neither the number of antitubercular drugs used in different combinations nor the number of AEs showed significant impact on outcome. Patients who completed the treatment experienced a greater number of AEs and SAEs (p < 0.001) if compared to lost to follow-up patients. CONCLUSIONS: Our data demonstrate that, despite the high frequency of adverse drug reactions and long term therapy, the clinical management of MDR-TB patients in a referral center could reach successful treatment according to WHO target, by implementing active and systematic clinical and laboratory assessment to detect, report and manage suspected and confirmed adverse drug reactions. FAU - Gualano, Gina AU - Gualano G AUID- ORCID: 0000-0001-6149-0005 AD - Respiratory Infectious Diseases Unit, National Institute for Infectious Diseases "L. Spallanzani" IRCCS, Rome, Italy. FAU - Mencarini, Paola AU - Mencarini P AUID- ORCID: 0000-0001-8928-8183 AD - Respiratory Infectious Diseases Unit, National Institute for Infectious Diseases "L. Spallanzani" IRCCS, Rome, Italy. FAU - Musso, Maria AU - Musso M AD - Respiratory Infectious Diseases Unit, National Institute for Infectious Diseases "L. Spallanzani" IRCCS, Rome, Italy. FAU - Mosti, Silvia AU - Mosti S AD - Respiratory Infectious Diseases Unit, National Institute for Infectious Diseases "L. Spallanzani" IRCCS, Rome, Italy. FAU - Santangelo, Laura AU - Santangelo L AD - Pharmacy Unit, National Institute for Infectious Diseases "L. Spallanzani" IRCCS, Rome, Italy. FAU - Murachelli, Silvia AU - Murachelli S AD - Pharmacy Unit, National Institute for Infectious Diseases "L. Spallanzani" IRCCS, Rome, Italy. FAU - Cannas, Angela AU - Cannas A AD - Microbiology Unit, National Institute for Infectious Diseases "L. Spallanzani", IRCCS, Rome, Italy. FAU - Di Caro, Antonino AU - Di Caro A AD - Microbiology Unit, National Institute for Infectious Diseases "L. Spallanzani", IRCCS, Rome, Italy. FAU - Navarra, Assunta AU - Navarra A AD - Clinical Epidemiology Unit, National Institute for Infectious Diseases "L. Spallanzani", IRCCS, Rome, Italy. FAU - Goletti, Delia AU - Goletti D AD - Translational Research Unit, National Institute for Infectious Diseases "L. Spallanzani", IRCCS, Rome, Italy. FAU - Girardi, Enrico AU - Girardi E AD - Clinical Epidemiology Unit, National Institute for Infectious Diseases "L. Spallanzani", IRCCS, Rome, Italy. FAU - Palmieri, Fabrizio AU - Palmieri F AD - Respiratory Infectious Diseases Unit, National Institute for Infectious Diseases "L. Spallanzani" IRCCS, Rome, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190228 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Antitubercular Agents) SB - IM MH - Adult MH - Antitubercular Agents/*adverse effects/therapeutic use MH - Cohort Studies MH - Drug-Related Side Effects and Adverse Reactions/*epidemiology MH - Female MH - Humans MH - Italy/epidemiology MH - Male MH - Retrospective Studies MH - Tertiary Care Centers MH - Treatment Failure MH - Treatment Outcome MH - Tuberculosis, Multidrug-Resistant/*drug therapy PMC - PMC6394924 COIS- The authors have declared that no competing interests exist. EDAT- 2019/03/01 06:00 MHDA- 2019/11/23 06:00 PMCR- 2019/02/28 CRDT- 2019/03/01 06:00 PHST- 2018/10/15 00:00 [received] PHST- 2019/02/12 00:00 [accepted] PHST- 2019/03/01 06:00 [entrez] PHST- 2019/03/01 06:00 [pubmed] PHST- 2019/11/23 06:00 [medline] PHST- 2019/02/28 00:00 [pmc-release] AID - PONE-D-18-29878 [pii] AID - 10.1371/journal.pone.0212948 [doi] PST - epublish SO - PLoS One. 2019 Feb 28;14(2):e0212948. doi: 10.1371/journal.pone.0212948. eCollection 2019.