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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. 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. 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. 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. 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.

Treatment of NTM lung disease (NTM-LD) is based on combinations of antimycobacterial drugs. It lasts 12 months if respiratory samples become culture negative, while in refractory cases it can last up to 18–24 months. Therapeutic pathway is complicated by frequent adverse events (AEs). Sometimes, symptomatic therapy is not sufficient to control AEs, making necessary to suspend the drug involved or the entire treatment. This study aims to describe the frequency and type of AEs in patients with NTM-LD and to evaluate their impact on the outcomes of treatment. This is a retrospective observational study. We analysed clinical data, regimen composition, AEs and outcomes of NTM-LD patients followed between January 2016 and June 2023 at the National Institute for Infectious Diseases “L. Spallanzani” in Rome. Out of 131 patients, fifty-eight (44.3%) were men; median age was 66 years (IQR: 56–73). One hundred (76.3%) developed AEs. Total AEs were 229, of which 81 were serious adverse events (SAEs). Cure was obtained in 113 cases (86.3%), therapeutic failure occurred in 10 (7.6%), 6 patients died (4.6%), and 2 (1.5%) were lost-to-follow-up. Despite of AEs, most patients were able to complete treatment with appropriate management and monitoring. AEs affect patient quality of life and treatment adherence. Therefore, it is important to identify factors that can predict and prevent them. Clear and detailed information about drug side effects, with instructions to follow in case of AEs, active monitoring at every contact, flexibility and accessibility to healthcare professionals are key factors for therapy success.

Aim of this study was to compare the diagnostic yield of induced sputum (IS) and bronchoalveolar lavage (BAL) in patients with suspected pulmonary tuberculosis (PTB) and negative sputum smears. We enrolled 215 patients who underwent both IS and BAL after two negative spontaneous sputum samples. PTB was confirmed by culture or molecular test in 26 patients (12.1%). IS detected 10 cases (38.5%) of all PTB, while BAL detected 22 cases (84.6%) of all PTB. IS had a sensitivity of 38.46% and a specificity of 100%, while BAL had a sensitivity of 84.62% and a specificity of 100%. BAL had a higher diagnostic yield than IS and was useful for ruling out alternative diagnoses. According to our experience FBS execution is mandatory in case of strong TB suspicion and sputum smear negative patients, especially in a low TB prevalence country. Moreover, it consents testing microorganism sensitivity and assessing possible alternative diagnosis with similar clinical presentation. The choice of the best diagnostic method may depend on the clinical context and the availability of resources. Highlights The study compared IS and BAL in suspected PTB patients with negative sputum smears. BAL had a higher diagnostic yield than IS and detected 84.6% of all PTB cases. BAL was also useful for ruling out alternative diagnoses. FBS execution is mandatory in case of strong TB suspicion and sputum smear negative patients, especially in a low TB prevalence country. The choice of the best diagnostic method may depend on the clinical context and the availability of resources.

Background: The WHO advised that the impact of COVID-19 pandemic on TB services was estimated to be dramatic due to the disruption of TB services. Methods: A retrospective data collection and evaluation was conducted to include all the patients hospitalized for TB at INMI from 9 March to 31 August 2020 (lockdown period and three months thereafter). For the purpose of the study, data from patients hospitalized in the same period of 2019 were also collected. Results: In the period of March–August 2019, 201 patients were hospitalized with a diagnosis of TB, while in the same period of 2020, only 115 patients, with a case reduction of 43%. Patients with weight loss, acute respiratory failure, concurrent extrapulmonary TB, and higher Timika radiographic scores were significantly more frequently hospitalized during 2020 vs. 2019. The median patient delay was 75 days (IQR: 40–100) in 2020 compared to 30 days (IQR: 10–60) in 2019 (p < 0.01). Diagnostic delays in 2020 remain significant in the multiple logistic model (AOR = 6.93, 95%CI: 3.9–12.3). Conclusions: Our experience suggests that COVID-19 pandemic had an impact on TB patient care in terms of higher diagnostic delay, reduction in hospitalization, and a greater severity of clinical presentations.

Pembrolizumab is used as a first-line treatment of non-small cell lung cancer. Pneumonitis and interstitial lung disease are among the most common immune-related adverse events. The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections on patients with cancer treated with chemotherapy or immune checkpoint inhibitors (ICIs) is not fully known. Blocking immune checkpoints may conversely augment dysfunctional T-cell responses in severe patients and, in turn, mediate immunopathology. Here, we present a case of SARS-CoV-2 infection complicated by acute respiratory distress syndrome (ARDS) and a fibrotic-like pattern in a patient treated with pembrolizumab for lung cancer. The patient showed a dramatic clinical and radiological response after steroid therapy. Further research is needed to better understand the long-term implications of pembrolizumab therapy in patients recovering from coronavirus disease 2019 (COVID-19) and to develop evidence-based guidelines for managing these complex cases. Patients undergoing oncologic immunotherapy might benefit from early high-dose steroid treatment in cases of viral infections, such as SARS-CoV-2.

Tuberculosis (TB) is top infectious disease killer caused by a single organism responsible for 1.5 million deaths in 2018. Both COVID-19 and the pandemic response are risking to affect control measures for TB and continuity of essential services for people affected by this infection in western countries and even more in developing countries. Knowledge about concomitant pulmonary TB and COVID-19 is extremely limited. The double burden of these two diseases can have devastating effects. Here, we describe from both the clinical and the immunological point of view a case of a patient with in vitro immune cell anergy affected by bilateral cavitary pulmonary TB and subsequent COVID-19-associated pneumonia with a worst outcome. COVID-19 can be a precipitating factor in TB respiratory failure and, during ongoing SARS-COV-2 pandemic, clinicians must be aware of this possible co-infection in differential diagnosis of patients with active TB and new or worsening chest imaging.

Tuberculosis (TB) in the elderly (>65 years old) has increasingly become a global health problem. It has long been recognized that older people are vulnerable to developing tuberculosis. We retrospectively evaluated data from patients older than 65 years diagnosed with pulmonary TB admitted to the National Institute for Infectious Diseases L. Spallanzani, Rome, Italy, from 1 January 2016 to 31 December 2019. One hundred and six consecutive patients were diagnosed with pulmonary TB and 68% reported at least one comorbidity and 44% at least one of the TB risk-factors. Out of the 26 elderly patients who reported an adverse event, having risk factors for TB (O.R. (Odds Ratios) = 1.45; 95% CI 1.12–3.65) and the presence of cavities on Chest X-rays (O.R. = 1.42; 95% CI 1.08–2.73) resulted in being more likely to be associated with adverse events in elderly patients. Having weight loss (O.R. = 1.31; 95% CI 1.08–1.55) and dyspnea (O.R. = 1.23; 95% CI 1.13–1.41) resulted in being significant predictors of unsuccessful treatment outcome in elderly patients. Older people with TB represent a vulnerable group, with high mortality rate, with a challenging diagnosis. Hospitalizations in tertiary referral hospital with clinical expertise in TB management can be useful to improve the outcome of these fragile patients.

Tuberculosis (TB), due to Mycobacterium tuberculosis infection, is still the principal cause of death caused by a single infectious agent. The balance between the bacillus and host defense mechanisms reflects the different manifestations of the pathology. Factors defining this variety are unclear and likely involve both mycobacterial and immunological components. Myeloid derived suppressor cells (MDSC) have been shown to be expanded during TB, but their role in human TB pathogenesis is not clear. We evaluated the frequency of circulating MDSC by flow-cytometry in 19 patients with active TB, 18 with latent TB infection (LTBI), and 12 healthy donors (HD) as control. Moreover, we investigated the capacity of MDSC to modulate the mycobactericidal activity of monocytes. The association between MDSC level and TB chest X-ray severity score was analyzed. We observed that, unlike active TB, polymorphonuclear (PMN)-MDSC are not expanded in LTBI patients, and, by performing a receiver operating characteristic (ROC) curve analysis, we found that PMN-MDSC frequency supported the discrimination between active disease and LTBI. Interestingly, we observed an association between PMN-MDSC levels and the severity of TB disease evaluated by chest X-ray. Specifically, PMN-MDSC frequency was higher in those classified with a low/mild severity score compared to those classified with a high severity score. Moreover, PMN-MDSC can impact mycobacterial growth by inducing ROS production in Bacillus Calmette et Guerin (BCG)-infected monocytes. This effect was lost when tested with M. tuberculosis (MTB), In conclusion, our data indicate that the elevated frequency of PMN-MDSC in IGRA-positive individuals is associated with active TB. Our findings also pointed out a beneficial role of PMN-MDSC during human active TB, most likely associated with the limitation of inflammation-induced tissue damage.

Background Multidrug-resistant tuberculosis (MDR-TB) requires lengthy use of second-line drugs, burdened by many side effects. Hepatitis C virus (HCV) chronic infection increases risk of drug-induced liver injury (DILI) in these patients. Data on MDR-TB patients with concurrent HCV chronic infection treated at the same time with second-line antitubercular drugs and new direct-acting antivirals (DAAs) are lacking. We evaluate if treating at the same time HCV infection and pulmonary MDR-TB is feasible and effective. Cases presentation In this study, we described two cases of patients with pulmonary MDR-TB and concurrent HCV chronic infection cured with DAAs at a Tertiary Infectious Diseases Hospital in Italy. During antitubercular treatment, both patients experienced a DILI before treating HCV infection. After DAAs liver enzymes normalized and HCV RNA was undetectable. Then antitubercular regimen was started according to the institutional protocol, drawn up following WHO MDR-TB guidelines. It was completed without further liver side effects and patients were declared cured from both HCV infection and MDR-TB. Conclusions We suggest to consider treatment of chronic hepatitis C with DAAs as a useful intervention for reintroduction of second-line antitubercular agents in those patients who developed DILI, reducing the risk of treatment interruption when re-exposed to these drugs.

Background: Tuberculosis (TB) can seriously affect the hematopoietic system, with involvement of both myeloid and lymphoid cell lines as well as plasma components. These hematological changes act as a marker for the diagnosis, prognosis and response to therapy. Methods: We searched PubMed, Scopus, Google Scholar, EMBASE, Cochrane Library and WHO websites from 1950 to May 2021 for papers on the interaction between TB and common and rare hematological manifestation. Results: Hematological reactions in patients with TB are possible in both young and old women and men but seem more frequent in the elderly, and they can be predictors of both diagnosis and worse outcome for TB, regardless of whether it is pulmonary, extra pulmonary or miliary. Even anti-TB therapies can cause hematological adverse events, among which some are serious and rare and can compromise the patient’s recovery pathway to completing treatment. Conclusion: Hematological screening and follow-up, including complete blood count and coagulation, are always necessary both at the diagnosis of TB and during antitubercular treatment in order to monitor hematological parameters. Short therapy regimens for multidrug-resistant TB (MDR-TB) may also be useful for reducing hematological toxicity, especially in contexts where this cannot be monitored. Close monitoring of drug interactions and hematological adverse events is always recommended.