The treatment of multidrug-resistant (MDR) or extensively drug-resistant (XDR) tuberculosis (TB) remains a challenge for clinicians for several reasons, including the large number of drugs required, ...the cost, the tolerability of single drugs and their combinations, and the effectiveness and long treatment duration 1–6. Therefore, fresh attention has recently been paid to new and repurposed anti-TB drugs 4, 5, 7–18.
Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) continue to be challenging at both the patient and programme level. The World Health Organization (WHO) estimated 480 ...000 new cases of MDR-TB in 2015 and an additional 100 000 cases diagnosed with rifampicin-resistant TB (RR-TB). India, China and the Russian Federation accounted for almost half (45%) of the total burden 1. Out of 580 000 patients eligible for MDR-TB treatment, only 125 000 (20%) were enrolled in treatment programmes 1.
The World Health Organization (WHO) estimated that 490 000 cases of multidrug-resistant (MDR) tuberculosis (TB) (defined as TB caused by Mycobacterium tuberculosis strains resistant to at least ...isoniazid and rifampicin) occurred in 2016. Among them, ∼6.2% had extensively drug-resistant (XDR) TB (i.e. TB caused by MDR strains with additional resistance to fluoroquinolones and at least one second-line injectable drug) 1.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has hit more than 200 countries with more than 750 million confirmed cases and more than 6 million deaths worldwide ....
Over the past few decades, treatment of multidrug-resistant (MDR)/extensively drug-resistant (XDR) tuberculosis (TB) has been challenging because of its prolonged duration (up to 20-24 months), ...toxicity, costs and sub-optimal outcomes.After over 40 years of neglect, two new drugs (bedaquiline and delamanid) have been made available to manage difficult-to-treat MDR-/XDR-TB cases. World Health Organization (WHO) guidelines published in March 2019 endorsed the possibility of treating MDR-TB patients with a full oral regimen, following previous guidelines published in 2016 which launched a shorter regimen lasting 9-10 months.The objectives of this article are to review the main achievements in MDR-TB treatment through the description of the existing WHO strategies, to discuss the main ongoing trials and to shed light on potential future scenarios and revised definitions necessary to manage drug-resistant TB.
•Consilia promote and monitor TB guideline and best practice adherence.•TB Consilia are recommended by the WHO.•TB Consilia are gatekeepers to the new drugs.•There are different types of TB Consilia, ...all have their advantages and disadvantages.•The Global TB Network provides a supranational TB Consilium service.
MDR-TB is a growing challenge worldwide, and an obstacle to TB elimination. It is apparent that TB is being replaced by small but growing number of resistant cases with an anticipated 2 million cases of MDR-TB within the next two decades. One of the potential causes of MDR-TB is iatrogenic and we risk losing our new drugs through inexperience and repetition of basic errors of adding single active drugs to failing regimens. Discussion of MDR-TB cases with senior colleagues is not only best practice; it is now embedded in the WHO and many national and local guidelines.
TB Consilia act as gatekeepers to the new drugs, monitor guideline adherence and mandate active drug safety monitoring. TB Consilia are also excellent educational tools.
TB Consilia are now recommended by funding bodies, the WHO and manufacturers of drugs available for compassionate use in the hope that these drugs will be protected and will continue to be useful in the future. This article briefly discusses Consilia, their origin and evolution and gives some examples of how they operate.
We report the experiences of 5 patients taking bedaquiline with delamanid in combination: 1 patient was cured; 3 culture converted, with 2 continuing and 1 changing therapy; and 1 died from ...respiratory insufficiency. For 2 patients, QT-interval prolongation but no arrhythmias occurred. Use of this therapy is justified for patients with limited options.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The new drugs delamanid and bedaquiline are increasingly being used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB). The World Health Organization, based on ...lack of evidence, recommends their use under specific conditions and not in combination. No systematic review has yet evaluated the efficacy, safety, and tolerability of delamanid and bedaquiline used in combination. A search of peer-reviewed, scientific evidence was carried out, aimed at evaluating the efficacy/effectiveness, safety, and tolerability of delamanid and bedaquiline-containing regimens in individuals with pulmonary/extrapulmonary disease, which were bacteriologically confirmed as M/XDR-TB. We used PubMed to identify any relevant manuscripts in English up to the 23 December 2016, excluding editorials and reviews. Three out of 75 manuscripts retrieved satisfied the inclusion criteria, whilst 72 were excluded for dealing with only one drug (three studies), being recommendations (one study) or identifying need for their use (one study), focusing on drug resistance aspects (six studies) or being generic reviews/other studies (61 papers). The studies retrieved reported two XDR-TB cases observed for six months and achieving consistent sputum smear and culture conversion. Case 2 experienced a short break of bedaquiline, which was re-started after introducing verapamil. After a transient and symptom-free increase of the QT interval from week 5 to 17, it then decreased below the 500 ms threshold.
Background
Computed tomography (CT) enables quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, helping in outcome prediction.
Methods
From 1 to 22 March 2020, ...patients with pneumonia symptoms, positive lung CT scan, and confirmed SARS-CoV-2 on reverse transcription-polymerase chain reaction (RT-PCR) were consecutively enrolled. Clinical data was collected. Outcome was defined as favourable or adverse (
i.e.
, need for mechanical ventilation or death) and registered over a period of 10 days following CT. Volume of disease (VoD) on CT was calculated semi-automatically. Multiple linear regression was used to predict VoD by clinical/laboratory data. To predict outcome, important features were selected using a priori analysis and subsequently used to train 4 different models.
Results
A total of 106 consecutive patients were enrolled (median age 63.5 years, range 26–95 years; 41/106 women, 38.7%). Median duration of symptoms and C-reactive protein (CRP) was 5 days (range 1–30) and 4.94 mg/L (range 0.1–28.3), respectively. Median VoD was 249.5 cm
3
(range 9.9–1505) and was predicted by lymphocyte percentage (
p
= 0.008) and CRP (
p
< 0.001). Important variables for outcome prediction included CRP (area under the curve AUC 0.77), VoD (AUC 0.75), age (AUC 0.72), lymphocyte percentage (AUC 0.70), coronary calcification (AUC 0.68), and presence of comorbidities (AUC 0.66). Support vector machine had the best performance in outcome prediction, yielding an AUC of 0.92.
Conclusions
Measuring the VoD using a simple CT post-processing tool estimates SARS-CoV-2 burden. CT and clinical data together enable accurate prediction of short-term clinical outcome.
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