Drugs for treating infections caused by non-tubercular mycobacteria: a narrative review from the study group on mycobacteria of the Italian Society of Infectious Diseases and Tropical Medicine.

BACKGROUND: Non-tuberculous mycobacteria (NTM) are generally free-living organism, widely distributed in the environment, with sporadic potential to infect. In recent years, there has been a significant increase in the global incidence of NTM-related disease, spanning across all continents and an increased mortality after the diagnosis has been reported. The decisions on whether to treat or not and which drugs to use are complex and require a multidisciplinary approach as well as patients' involvement in the decision process. METHODS AND RESULTS: This review aims at describing the drugs used for treating NTM-associated diseases emphasizing the efficacy, tolerability, optimization strategies as well as possible drugs that might be used in case of intolerance or resistance. We also reviewed data on newer compounds highlighting the lack of randomised clinical trials for many drugs but also encouraging preliminary data for others. We also focused on non-pharmacological interventions that need to be adopted during care of individuals with NTM-associated diseases CONCLUSIONS: Despite insufficient efficacy and poor tolerability this review emphasizes the improvement in patients' care and the needs for future studies in the field of anti-NTM treatments.

Therapeutic strategies and outcomes of MDR and pre-XDR-TB in Italy: a nationwide study.

BACKGROUND: Treatment outcomes in multidrug-resistant TB (MDR-TB) patients are suboptimal in several low-incidence countries.METHODS: The primary outcome measure was the proportion of successfully treated patients in Italy during an 18-year period. Secondary outcomes were treatment outcomes in certain drug-containing regimens and the possibility for the WHO shorter MDR-TB regimen.RESULTS: In the 191 patients included (median age at admission: 33 years; 67.5% male, following drug-resistance patterns were found: MDR-TB in 68.6%, pre-extensively drug-resistant TB (pre-XDR-TB) in 30.4% and XDR-TB in 1.1% patients. The most frequently prescribed drugs were fluoroquinolones in 84.6% cases, amikacin in 48.7%, linezolid in 34.6% and meropenem/clavulanic acid in 29.5%. The median duration of treatment was 18 months. Treatment success was achieved in 71.2% patients, of whom, 44% were cured and 27.2% completed treatment. Treatment success rates did not statistically differ between the MDR- (68.8%) and pre-XDR-TB (77.6%) groups (P = 0.26). Treatment success rates had large variability between North and South of Italy (81.3% vs. 53.3%). Only 22.5% of the cases would have been eligible for shorter MDR-TB regimensCONCLUSION: Our study highlights variability in treatment outcomes in MDR- and pre-XDR-TB patients. Study findings confirmed the potential utility of linezolid and, for patients with limited oral options, meropenem/clavulanic acid and amikacin.

TB management in the European Union/European Economic Area: a multi-centre survey.

BACKGROUND: Essential TB care in the European Union/European Economic Area (EU/EEA) comprises 21 standards for the diagnosis, treatment and prevention of TB that constitute the European Union Standards for Tuberculosis Care (ESTC).METHODS: In 2017, we conducted an audit on TB management and infection control measures against the ESTC standards. TB reference centres in five EU/EEA countries were purposely selected to represent the heterogeneous European TB burden and examine geographic variability.RESULTS: Data from 122 patients, diagnosed between 2012 and 2015 with multidrug-resistant TB (n = 49), extensively drug-resistant TB (XDR-TB) (n = 11), pre-XDR-TB (n = 29) and drug-susceptible TB (n = 33), showed that TB diagnosis and treatment practices were in general in agreement with the ESTC.CONCLUSION: Overall, TB management and infection control practices were in agreement with the ESTC in the selected EU/EEA reference centres. Areas for improvement include strengthening of integrated care services and further implementation of patient-centred approaches.

Outcome of treatment of MDR-TB or drug-resistant patients treated with bedaquiline and delamanid: Results from a large global cohort.

The World Health Organization (WHO) recommends countries introduce new anti-TB drugs in the treatment of multidrug-resistant tuberculosis. The aim of the study is to prospectively evaluate the effectiveness of bedaquiline (and/or delamanid)- containing regimens in a large cohort of consecutive TB patients treated globally. This observational, prospective study is based on data collected and provided by Global Tuberculosis Network (GTN) centres and analysed twice a year. All consecutive patients (including children/adolescents) treated with bedaquiline and/or delamanid were enrolled, and managed according to WHO and national guidelines. Overall, 52 centres from 29 countries/regions in all continents reported 883 patients as of January 31st 2021, 24/29 countries/regions providing data on 100% of their consecutive patients (10-80% in the remaining 5 countries). The drug-resistance pattern of the patients was severe (>30% with extensively drug-resistant -TB; median number of resistant drugs 5 (3-7) in the overall cohort and 6 (4-8) among patients with a final outcome). For the patients with a final outcome (477/883, 54.0%) the median (IQR) number of months of anti-TB treatment was 18 (13-23) (in days 553 (385-678)). The proportion of patients achieving sputum smear and culture conversion ranged from 93.4% and 92.8% respectively (whole cohort) to 89.3% and 88.8% respectively (patients with a final outcome), a median (IQR) time to sputum smear and culture conversion of 58 (30-90) days for the whole cohort and 60 (30-100) for patients with a final outcome and, respectively, of 55 (30-90) and 60 (30-90) days for culture conversion. Of 383 patients treated with bedaquiline but not delamanid, 284 (74.2%) achieved treatment success, while 25 (6.5%) died, 11 (2.9%) failed and 63 (16.5%) were lost to follow-up.

Tuberculosis, COVID-19 and migrants: Preliminary analysis of deaths occurring in 69 patients from two cohorts.

Little is known about the relationship between the COVID-19 and tuberculosis (TB). The aim of this study is to describe a group of patients who died with TB (active disease or sequelae) and COVID-19 in two cohorts. Data from 49 consecutive cases in 8 countries (cohort A) and 20 hospitalised patients with TB and COVID-19 (cohort B) were analysed and patients who died were described. Demographic and clinical variables were retrospectively collected, including co-morbidities and risk factors for TB and COVID-19 mortality. Overall, 8 out of 69 (11.6%) patients died, 7 from cohort A (14.3%) and one from cohort B (5%). Out of 69 patients 43 were migrants, 26/49 (53.1%) in cohort A and 17/20 (85.0%) in cohort B. Migrants: (1) were younger than natives; in cohort A the median (IQR) age was 40 (27-49) VS. 66 (46-70) years, whereas in cohort B 37 (27-46) VS. 48 (47-60) years; (2) had a lower mortality rate than natives (1/43, 2.3% versus 7/26, 26.9%; p-value: 0.002); (3) had fewer co-morbidities than natives (23/43, 53.5% versus 5/26-19.2%) natives; p-value: 0.005). The study findings show that: (1) mortality is likely to occur in elderly patients with co-morbidities; (2) TB might not be a major determinant of mortality and (3) migrants had lower mortality, probably because of their younger age and lower number of co-morbidities. However, in settings where advanced forms of TB frequently occur and are caused by drug-resistant strains of M. tuberculosis, higher mortality rates can be expected in young individuals.

Multidrug-Resistant Tuberculosis In A Referral Center In Rome: 2011- 2016.

PURPOSE: Multidrug-resistant tuberculosis (MDR-TB) is a major burden to public health in low incidence countries in Europe. The aim of this study was to attempt to have a better insight into the trends of MDR-TB in the metropolitan area of Rome, within the Italian and the foreign-born population, based on microbiological and demographic data. PATIENTS AND METHODS: We performed a prospective study, collecting microbiological data based on phenotypic drug-resistant testing (DST) of TB strains consecutively isolated in a referral hospital in Rome, the capital city of a low TB incidence country, over a 6-year period, and correlated them to the geographical origin of patients. This study was carried out in a referral hospital for patients with drug-resistant TB from the whole region. RESULTS: Drug-resistance data from 926 patients with a microbiological diagnosis of TB from 2011 to 2016 show a 5.5% rate of MDR-TB, mostly occurring in patients born in a single East European country, that has a high incidence of MDR-TB. The strains isolated from these patients frequently carry additional resistances, leading to an increased risk of developing extensively drug-resistant (XDR) TB. CONCLUSION: In the great metropolitan area of Rome, MDR-TB more frequently occurs in patients who were born in a single country from Eastern Europe known to have high rates of MDR-TB and long-time residents in Italy. Recent immigrants from non-European countries do not appear to contribute to the rates of MDR-TB reported in this article. This knowledge of local TB trends could help improve the measures of surveillance and prevention of disease.

Phylogenetic analysis of human coronavirus NL63 circulating in Italy.

BACKGROUND: Five known human coronaviruses infect the human respiratory tract: HCoV-OC43, HCoV-229E, SARS-CoV, HCoV-NL63 and HCoV-HKU1. OBJECTIVES: To evaluate the prevalence of HCoV-NL63 in hospitalized adult patients and to perform molecular characterization of Italian strains. STUDY DESIGN: HCoV-NL63 was sought by RT-PCR in 510 consecutive lower respiratory tract (LRT) samples, collected from 433 Central-Southern Italy patients over a 1-year period. Phylogenetic analysis was performed by partial sequencing of S and ORF1a. Additional S sequences from Northern Italy were included in the phylogenetic trees. RESULTS: HCoV-NL63 was detected in 10 patients (2.0%) with symptomatic respiratory diseases, mainly during winter. Phylogenetic analysis indicated a certain degree of heterogeneity in Italian isolates. The ORF1a gene clustering in phylogenetic trees did not match with that of the S gene. CONCLUSIONS: As observed by others, HCoV-NL63 is often associated with another virus. Phylogenetic characterization of HCoV-NL63 circulating in Italy indicates that this virus circulates as a mixture of variant strains, as observed in other countries.

The diabetes-tuberculosis co-epidemic: the role of international migration.

SETTING: A tuberculosis (TB) referral centre in Rome, Italy. OBJECTIVE: To identify demographic and epidemiological characteristics associated with diabetes mellitus (DM) among patients with TB and to compare the clinical presentation of TB and TB-DM in the light of the growing worldwide burden of DM. DESIGN: We performed a retrospective study of TB cases diagnosed from 2007 to 2012. RESULTS: Among 971 TB patients, 723 were foreign-born and 63 (6.5%) had DM. DM prevalence was 12.7% (8/63) among those born in countries with DM prevalence ⩾8%, 4.7% (31/660) among patients from countries with DM prevalence <8% and 9.7% among Italian patients (24/248). In multivariable analysis, DM was independently associated with older age, and with being born in countries other than Italy, compared to Italians; this latter association was stronger in older patients. DM patients were also significantly more likely to be male and less likely to test positive for the human immunodeficiency virus. The presence of cavities was significantly associated with DM. CONCLUSIONS: As individuals born in high TB incidence and high DM prevalence countries emerge as a vulnerable population, greater attention to bidirectional low-cost screening in people from these countries is needed.

Beyond multidrug-resistant tuberculosis in Europe: a TBNET study.

The emergence of drug-resistant tuberculosis (TB) is a challenge to TB control in Europe. We evaluated second-line drug susceptibility testing in Mycobacterium tuberculosis isolates from patients with multidrug-resistant, pre-extensively drug-resistant (pre-XDR-TB) and XDR-TB at 23 TBNET sites in 16 European countries. Over 30% of bacilli from patients with pre-XDR-TB showed resistance to any fluoroquinolone and almost 70% to any second-line injectable drug. Respectively >90% and >80% of the XDR-TB strains tested showed phenotypic resistance to pyrazinamide and ethambutol. Resistance to prothionamide/ethionamide was high in bacilli from pre-XDR-TB patients (43%) and XDR-TB patients (49%).