Availability of drugs and resistance testing for BPaLM regimen for rifampicin-resistant tuberculosis in Europe.

OBJECTIVES: Multidrug-resistant/Rifampicin-resistant tuberculosis (TB) is a major obstacle to successful TB control. The recommendation by the World Health Organization to use bedaquiline, pretomanid, linezolid and moxifloxacin (BPaL(M)) for 6 months, based on results of three trials with high efficacy and low toxicity, has revolutionized treatment options. METHODS: In this study, representatives of the Tuberculosis Network European Trialsgroup (TBnet) in 44/54 countries of the WHO Europe region document the availability of the medicines and drug susceptibility testing (DST) of the BPaL(M) regimen through a structured questionnaire between September to November 2023. RESULTS: 24/44 (54.5%), 42/44 (95.5%), 43/44 (97.7%), and 43/44 (97.7%) had access to pretomanid, bedaquiline, linezolid, and moxifloxacin, respectively. Overall, 23/44 (52.3%) had access to all the drugs composing the BPaL(M) regimen. 7/44 (15.9%), 28/44 (63.6%), 34/44 (77.3%) and 36/44 (81.8%) had access to DST for pretomanid, bedaquiline, linezolid and moxifloxacin, respectively. DST was available for all medicines composing the BPaL(M) regimen in 6/44 (13.6%) countries. CONCLUSION: Only in about half of the countries participating in the survey clinicians have access to all the BPaL(M) regimen drugs. In less than a fifth of countries, a complete DST is possible. Rapid scale up of DST capacity to prevent unnoticed spread of drug resistance and equal access to new regimens are urgently needed in Europe.

Association of Inflammatory Markers with Disease Severity and Outcome in Covid-19 Patients.

Objectives: The coronavirus pandemic was associated with a high mortality rate in the Republic of North Macedonia. Finding early markers of the disease's severity may predict outcomes and guide the treatment of the disease. The aim of our study was to evaluate the role of inflammatory markers in predicting the outcome of COVID-19 in hospitalized patients. Methods: The study included 104 PCR-confirmed COVID-19 patients who underwent hospital treatment at the Institute of Lung Diseases and Tuberculosis in Skopje, North Macedonia, between November 2020 and May 2021. Inflammatory markers were assessed in all patients and correlated with the disease severity and outcome in terms of survival or death. Results: IL-6 and LDH at admission were significantly elevated in patients with a severe or critical form of the disease and among non-survivors. In addition, IL-6 showed 87.9% of sensitivity and 61.8% of specificity for distinguishing non-survivors from survivors with a cut-off value of 21.7 pg/ml in the receiver operator curve (ROC). Procalcitonin was significantly increased in non-survivors. Parallel to the increase of disease severity, the values of CRP and LDH increased significantly during hospitalization. Conclusion: The results of the study indicate that a significant association exists between the highly increased levels of CRP, LDH, IL-6 and procalcitonin and the severity of the disease and mortality in COVID-19 patients. Their measurements and follow-up during the course of the disease could be used as predictors for prognosis and outcome but also as a subject for targeted therapy.

Burden and Characteristics of the Comorbidity Tuberculosis-Diabetes in Europe: TBnet Prevalence Survey and Case-Control Study.

BACKGROUND: The growing burden of diabetes mellitus (DM) is posing a threat to global tuberculosis (TB) control. DM triples the risk of developing TB, modifies the presenting features of pulmonary TB, and worsens TB treatment outcomes. We aimed to analyze the prevalence of DM among TB patients and to describe the characteristics and clinical presentation of TB-DM patients in Europe. METHODS: We performed a cross-sectional survey on the prevalence of DM among consecutively diagnosed adult TB patients in 11 European TB referral centers located in France, Germany, Greece, Italy, Russia, Slovakia, Spain, and the United Kingdom over the period 2007-2015. We also selected DM-TB cases and TB only controls with a 1:3 ratio to perform a case-control analysis, including patients selected from the countries mentioned above plus Norway and Ukraine. RESULTS: Among 3143 TB enrolled patients, DM prevalence overall was 10.7% and ranged from 4.4% in Greece to 28.5% in the United Kingdom. Patients' median ages ranged from 36 to 49 years, and all centers had >60% males; the proportion of foreign-born patients varied widely across sites. In the case-control study, DM was independently associated with older age and, among older patients, with being foreign-born. Among patients with pulmonary involvement, cavities on chest imaging were more frequently observed among those with DM. CONCLUSIONS: Diabetes mellitus represents a challenge for TB control in Europe, especially in foreign-born and in elderly patients. Specific screening strategies should be evaluated.

Key Issues in the Management of Multi-Drug Resistant Tuberculosis: A Case Report.

BACKGROUND: Global tuberculosis (TB) epidemic is being driven to an increasing extent by the emergence and spread of drug-resistant strains of Mycobacterium tuberculosis complex (MTBC). We present a case of primary multidrug-resistant tuberculosis (MDR-TB), highlighting Macedonian MDR-TB management issues. CASE REPORT: A 39-year old previously healthy Caucasian male, with no previous history of TB or close contact to TB, was admitted in referral TB-hospital due to respiratory bleeding. Chest X-ray revealed opacity with cavernous lesions in the right upper lobe. Sputum samples showed no presence of acid-fast bacilli (AFB) on fluorescence microscopy, but molecular tests (real-time PCR-based assay and multiplex PCR-based reverse hybridisation Line Probe Assay) confirmed the presence of MTBC, also revealing rifampicin and isoniazid resistance and absence of resistance to second-line anti-tubercular drugs. The strain was considered multidrug-resistant, lately confirmed by conventional methods in liquid and solid culture. Following the protocol of the World Health Organization, we started the longer treatment of MDR-TB comprised of at least five effective anti-tubercular drugs. Due to patient's extreme non-adherence, we had to delay and modify the regimen (i.e. omitting parenteral aminoglycoside) and to discharge him from the hospital a month after directly observed therapy (DOT) in negative pressure room. As there is no legal remedy in our country regarding involuntary isolation, our patient continued the regimen under ambulatory control of referral TB-hospital. Ignoring the risk of additional acquisition of drug resistance and prolonged exposure of the community to MDR-TB strain - for which he was repeatedly advised - he decided to cease the therapy six months after beginning. CONCLUSION: The benefit of molecular tests in the early diagnosis of TB and drug resistance is unequivocal for adequate treatment of resistant forms of TB. Whole genome sequencing ensures additional knowledge of circulating strains and their resistance patterns. These are essentials of effective TB control programs and can provide evidence to medical and legal authorities for more active policies of screening, involuntary confinement and compliance with therapy, and alternative modalities for successful treatment, as a part of infection control.