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In Italy, rifampicin-resistant and MDR-TB were high in foreign-born persons, but decreased from 2009 to 2016

The emergence of drug resistant strains of Mycobacterium tuberculosis is a challenge to global tuberculosis (TB) control. Although culture based methods have been regarded as the gold standard for drug susceptibility testing (DST) molecular methods provide rapid information on mutations in the M. tuberculosis genome associated with resistance to anti tuberculosis drugs. We ascertained consensus on the use of the results of molecular DST for clinical treatment decisions in TB patients. This document has been developed by TBNET and RESIST TB groups to reach a consensus about reporting standards in the clinical use of molecular DST results. Review of the available literature and the search for evidence included hand searching journals and searching electronic databases. The panel identified single nucleotide mutations in genomic regions of M. tuberculosis coding for katG inhA rpoB embB rrs rpsL and gyrA that are likely related to drug resistance in vivo. Identification of any of these mutations in clinical isolates of M. tuberculosis has implications for the management of TB patients pending the results of in vitro DST. However false positive and false negative results in detecting resistance associated mutations in drugs for which there is poor or unproven correlation between phenotypic and clinical drug resistance complicate the interpretation. Reports of molecular DST results should therefore include specific information on the mutations identified and provide guidance for clinicians on interpretation and on the choice of the appropriate initial drug regimen.

Background: The World Health Organization recommends drug-susceptibility testing of Mycobacterium tuberculosis complex for all patients with tuberculosis to guide treatment decisions and improve outcomes. Whether DNA sequencing can be used to accurately predict profiles of susceptibility to first-line antituberculosis drugs has not been clear.\ud \ud \ud \ud Methods: We obtained whole-genome sequences and associated phenotypes of resistance or susceptibility to the first-line antituberculosis drugs isoniazid, rifampin, ethambutol, and pyrazinamide for isolates from 16 countries across six continents. For each isolate, mutations associated with drug resistance and drug susceptibility were identified across nine genes, and individual phenotypes were predicted unless mutations of unknown association were also present. To identify how whole-genome sequencing might direct first-line drug therapy, complete susceptibility profiles were predicted. These profiles were predicted to be susceptible to all four drugs (i.e., pansusceptible) if they were predicted to be susceptible to isoniazid and to the other drugs or if they contained mutations of unknown association in genes that affect susceptibility to the other drugs. We simulated the way in which the negative predictive value changed with the prevalence of drug resistance.\ud \ud \ud \ud Results: A total of 10,209 isolates were analyzed. The largest proportion of phenotypes was predicted for rifampin (9660 [95.4%] of 10,130) and the smallest was predicted for ethambutol (8794 [89.8%] of 9794). Resistance to isoniazid, rifampin, ethambutol, and pyrazinamide was correctly predicted with 97.1%, 97.5%, 94.6%, and 91.3% sensitivity, respectively, and susceptibility to these drugs was correctly predicted with 99.0%, 98.8%, 93.6%, and 96.8% specificity. Of the 7516 isolates with complete phenotypic drug-susceptibility profiles, 5865 (78.0%) had complete genotypic predictions, among which 5250 profiles (89.5%) were correctly predicted. Among the 4037 phenotypic profiles that were predicted to be pansusceptible, 3952 (97.9%) were correctly predicted.\ud \ud \ud \ud Conclusions: Genotypic predictions of the susceptibility of M. tuberculosis to first-line drugs were found to be correlated with phenotypic susceptibility to these drugs. (Funded by the Bill and Melinda Gates Foundation and others.)

Background A substantial increase in pulmonary and extra-pulmonary diseases due to non-tuberculous mycobacteria (NTM) has been documented worldwide, especially among subjects suffering from chronic respiratory diseases and immunocompromised patients. Many questions remain regarding the epidemiology of pulmonary disease due to NTM (NTM-PD) mainly because reporting of NTM-PD to health authorities is not mandated in several countries, including Italy. This manuscript describes the protocol of the first Italian registry of adult patients with respiratory infections caused by NTM (IRENE). Methods IRENE is an observational, multicenter, prospective, cohort study enrolling consecutive adult patients with either a NTM respiratory isolate or those with NTM-PD. A total of 41 centers, including mainly pulmonary and infectious disease departments, joined the registry so far. Adult patients with all of the following are included in the registry: 1) at least one positive culture for any NTM species from any respiratory sample; 2) at least one positive culture for NTM isolated in the year prior the enrolment and/or prescribed NTM treatment in the year prior the enrolment; 3) given consent to inclusion in the study. No exclusion criteria are applied to the study. Patients are managed according to standard operating procedures implemented in each IRENE clinical center. An online case report form has been developed to collect patients’ demographics, comorbidities, microbiological, laboratory, functional, radiological, clinical, treatment and outcome data at baseline and on an annual basis. An IRENE biobank has also been developed within the network and linked to the clinical data of the registry. Conclusions IRENE has been developed to inform the clinical and scientific community on the current management of adult patients with NTM respiratory infections in Italy and acts as a national network to increase the disease’s awareness. Trial registration Clinicaltrial.gov: NCT03339063.

La tubercolosi costituisce una emergenza sanitaria per la salute pubblica, oltre che una problematica confinata agli ambienti lavorativi. Per tale ragione le autorità sanitarie redigono ed aggiornano costantemente linee guida di notevole valore scientifico e pratico. Recenti episodi di cronaca hanno riportato alla ribalta la tubercolosi come patologia nosocomiale, la cui trasmissione può avvenire da operatore sanitario a paziente. Per quanto concerne gli operatori sanitari, una recente revisione della letteratura ha confermato che il rischio di infezione tubercolare latente e di tubercolosi sono maggiori in questa categoria rispetto alla popolazione generale. Gli strumenti di riduzione del rischio di tubercolosi in ambito nosocomiale si basano innanzitutto sull’adozione di misure di isolamento respiratorio; tuttavia tali procedure richiedono il rapido riconoscimento del sospetto clinico. La diagnosi microbiologica di tubercolosi si basa sul reperto di bacilli tubercolari nel campione clinico. La ricerca di tali microrganismi può essere eseguita con l’esame microscopico, colturale e con tecniche rapide di biologia molecolare. Tuberculosis is an emergency for public health, as well as an issue confined to working environments. For this reason, the health authorities draw up and regularly update guidelines of considerable scientific and practical value. Recent reports have shown tuberculosis as a nosocomial disease whose transmission can occur from healthcare environment to patient. With regard to healthcare workers, a recent literature review confirmed that the risk of latent TB infection and tuberculosis is greater in this category of workers than in the general population. The tools for risk reduction in nosocomial TB are based primarily on respiratory isolation measures. However such procedures require the rapid recognition of clinical suspicion. The microbiological diagnosis of tuberculosis is based on the detection of tubercular bacilli in clinical specimens. The research of these microorganisms can be done using microscopic and coltural examination as well as rapid molecular biology techniques.

In migrants coming to Italy from 106 countries, MDR-TB was high from the former Soviet Union and low from Africa http://ow.ly/WZDbo

In 1998 a network of 20 regional tuberculosis (TB) laboratories (the Italian Multicentre Study on Resistance to Antituberculosis drugs (SMIRA) network) was established in Italy to implement proficiency testing and to monitor the prevalence of drug resistance nationwide. The network managed 30% of all TB cases reported in Italy each year. The aim of the present report is to describe: 1) the accuracy of drug-susceptibility testing in the network; 2) the prevalence of drug resistance for the period 1998-2000. Data were collected from the network laboratories. Sensitivity to streptomycin and ethambutol increased from the first survey (1998-1999) to the second survey (2000) from 87.7 to 91.9%. Specificity, predictive values for resistance and susceptibility, efficiency and reproducibility were consistent in both surveys. In previously untreated cases, the prevalence of multidrug-resistance was the same in both surveys (1.2%), while a slight decrease from the first to the second survey was observed for monoresistance to rifampicin (from 0.8 to 0.4%) and isoniazid (from 2.9 to 2%). The significant association found between isoniazid resistance and immigration is a useful indicator for both clinicians managing individual tuberculosis cases and public health services planning control strategies.

During the school years 2009-2010 and 2010-2011 a total of 25 cases of Non Tuberculous Cutaneous Mycobacteriosis (NTCM) were notified in children attending the same school with a swimming pool in Rome. Environmental microbiological and epidemiological investigations (only for suspected outbreaks in 2009-2010) were conducted. We screened students with skin lesions, and environmental samples were collected from the school area and the swimming pool. During the school year 2009-10 18 cases were clinically identified among 514 primary school children (3.50%) and all cases attended the swimming pool. Only 2 out of 18 cultures were positive for Mycobacterium chelonae complex (Group III, M. abscessus). Attack Rate for swimming pool use was 13,10% (17/130), with a Relative Risk 54,70 (95% CI: 9,4 - ∞). In February 2011 additional 7 cases of cutaneous NTM among children - who attended the same primary school and swimming pool were notified to the local public health authority followed by environmental microbiological investigation. Environmental samples were positive for NTM but not for M. abscessus. Mycobacteria are not included in water-quality criteria in Italy for this reason it is important to collect evidences of NTM cases caused by these infrequent pathogens, to be able to perform rapid risk assessment and to identify the best practices in prevention and management of such a risk.