Perspectives for personalized therapy for patients with multidrug-resistant tuberculosis.

According to the World Health Organization (WHO), tuberculosis is the leading cause of death attributed to a single microbial pathogen worldwide. In addition to the large number of patients affected by tuberculosis, the emergence of Mycobacterium tuberculosis drug-resistance is complicating tuberculosis control in many high-burden countries. During the past 5 years, the global number of patients identified with multidrug-resistant tuberculosis (MDR-TB), defined as bacillary resistance at least against rifampicin and isoniazid, the two most active drugs in a treatment regimen, has increased by more than 20% annually. Today we experience a historical peak in the number of patients affected by MDR-TB. The management of MDR-TB is characterized by delayed diagnosis, uncertainty of the extent of bacillary drug-resistance, imprecise standardized drug regimens and dosages, very long duration of therapy and high frequency of adverse events which all translate into a poor prognosis for many of the affected patients. Major scientific and technological advances in recent years provide new perspectives through treatment regimens tailor-made to individual needs. Where available, such personalized treatment has major implications on the treatment outcomes of patients with MDR-TB. The challenge now is to bring these adances to those patients that need them most.

Impact of lung function on treatment outcome in patients with TB.

BACKGROUND: The potential association between the lung function status at baseline and TB treatment outcome has not been evaluated previously. We aimed to investigate the impact of lung function status at the time of TB diagnosis on treatment outcome in patients with pulmonary TB (PTB).METHODS: A retrospective cohort study on data from all consecutive patients with culture-confirmed PTB and available spirometry test results admitted during the year 2016 to the Regional anti-TB dispensary no.1 in Kharkiv, Ukraine.RESULTS: A total of 278 patients with PTB were included into the study. The rate of negative treatment outcome (failure or death) was higher in patients with restrictive and mixed lung dysfunction than in those with normal spirometry results (25.6% vs. 6.8%, P = 0.0007; 37.5% vs. 6.8%, P = 0.003, respectively). In a logistic regression model, restrictive lung disease and mixed-type lung disease were associated with negative treatment outcome (OR 4.19, 95% CI 1.60-13.28, P = 0.007 and OR 5.46, 95% CI 1.28-24.44, P = 0.02, respectively).CONCLUSIONS: Lung function at the time of diagnosis has an important impact on treatment outcomes in patients with PTB; the more severe the restriction in lung function the higher the likelihood of a negative treatment outcome.

Multidrug-resistant tuberculosis in the Kharkiv Region, Ukraine.

OBJECTIVE: To document the level of drug resistance in MDR-TB patients and to characterize management capacities for their medical care and MDR-TB treatment outcomes in the Kharkiv region of Ukraine. This area has one of the highest frequencies of MDR-TB worldwide.METHODS: A retrospective observational cohort study was performed on registry data from the regional anti-TB dispensary in Kharkiv. All microbiologically confirmed MDR-TB patients registered in 2014 were included. Diagnostic, treatment and post-treatment follow-up data were analysed.RESULTS: Of 169 patients with MDR-TB, 55.0% had pre-extensively drug-resistant (pre-XDR) or XDR resistant patterns. Rapid molecular diagnosis by GeneXpert and liquid M. tuberculosis cultures were only available for 66.9% and 56.8% of patients, respectively. Phenotypic drug-susceptibility testing (DST) for high priority TB drugs (bedaquiline, linezolid, clofazimine) were not available. DST for later generation fluroquinolones was available only in 53.2% of patients. 50.9% of patients had less than 4 drugs in the treatment regimen proven to be effective by DST. More than 23.1% of patients with MDR-TB failed their treatment and only 45.0% achieved a cure.CONCLUSION: The high prevalence of MDR-TB and poor MDR-TB treatment outcomes in the Kharkiv region, is associated with substantial shortages in rapid molecular and phenotypic DST, a lack of high priority MDR-TB drugs, poor treatment monitoring and follow-up capacities.

Cigarette smoking and culture conversion in patients with susceptible and M/XDR-TB.

BACKGROUND: Tuberculosis (TB) is a leading cause of morbidity and mortality worldwide. Active cigarette smoking may have a significant impact on treatment responses to anti-tuberculosis treatment. OBJECTIVE: To ascertain the effect of smoking on Mycobacterium tuberculosis sputum culture conversion rates following treatment initiation in patients with susceptible, multidrug-resistant and extensively drug-resistant TB (M/XDR-TB). METHOD: Sputum cultures of smoking and non-smoking patients with pulmonary TB (PTB) treated at a referral centre in Germany were evaluated. RESULTS: Between January 2012 and March 2017, 247 patients with PTB treated at the Medical Clinic of Research Center Borstel, Borstel, Germany, were included in the study. Of 247 patients, 65 (26.3%) were infected with multidrug-resistant strains of M. tuberculosis (MDR-TB). Sputum culture examinations were performed on a weekly basis. Active smoking (n = 111; time to culture conversion [TCC] 50.7 days, interquartile range [IQR] 26.5-73.0) and former smoking (n = 72; TCC 43.1 days, IQR 19.8-56.0) significantly delayed culture conversion rates (P < 0.001) when compared with never smoking (n = 64; TCC 33.2 days, IQR 8.0-50.3). Delay in TCC among smoking, non-MDR-TB patients (n = 138; TCC 47.3 days, IQR 19.0-89.0) was comparable with non-smoking, MDR-TB patients (n = 20; TCC 53.0 days, IQR 18.0-71.0). The shortest TCC was observed in non-smoking, non-MDR-TB patients (n = 44; TCC 33.0 days, IQR 10.0-48.5), whereas the longest was seen in smoking, MDR-TB patients (n = 45; TCC 60.7 days, IQR 33.3-89.0); P < 0.001). CONCLUSION: Active cigarette smoking and, to a lesser extent, former cigarette smoking, substantially delayed culture conversion in PTB.

Management of patients with multidrug-resistant tuberculosis.

The emergence of multidrug-resistant tuberculosis (MDR-TB; defined as resistance to at least rifampicin and isoniazid) represents a growing threat to public health and economic growth. Never before in the history of mankind have more patients been affected by MDR-TB than is the case today. The World Health Organization reports that MDR-TB outcomes are poor despite staggeringly high management costs. Moreover, treatment is prolonged, adverse events are common, and the majority of affected patients do not receive adequate treatment. As MDR-TB strains are often resistant to one or more second-line anti-TB drugs, in-depth genotypic and phenotypic drug susceptibility testing is needed to construct personalised treatment regimens to improve treatment outcomes. For the first time in decades, the availability of novel drugs such as bedaquiline allow us to design potent and well-tolerated personalised MDR-TB treatment regimens based solely on oral drugs. In this article, we present management guidance to optimise the diagnosis, algorithm-based treatment, drug dosing and therapeutic drug monitoring, and the management of adverse events and comorbidities, associated with MDR-TB. We also discuss the role of surgery, physiotherapy, rehabilitation, palliative care and smoking cessation in patients with MDR-TB. We hope that incorporating these recommendations into patient care will be helpful in optimising treatment outcomes, and lead to more MDR-TB patients achieving a relapse-free cure.

Treatment responses in multidrug-resistant tuberculosis in Germany.

BACKGROUND: Excellent treatment outcomes have recently been reported for patients with multi/extensively drug-resistant tuberculosis (M/XDR-TB) in settings where optimal resources for individualised therapy are available. OBJECTIVE: To ascertain whether differences remain in treatment responses between patients with M/XDR-TB and those with non-M/XDR-TB. METHOD: Patients with TB were prospectively enrolled between March 2013 and March 2016 at five hospitals in Germany. Treatment was conducted following current guidelines and individualised on the basis of drug susceptibility testing. Two-month and 6-month sputum smear and sputum culture conversion rates were assessed. A clinical and radiological score were used to assess response to anti-tuberculosis treatment. RESULTS: Non-M/XDR-TB (n = 29) and M/XDR-TB (n = 46) patients showed similar rates of microbiological conversion: 2-month smear conversion rate, 90% vs. 78%; culture conversion rate, 67% vs. 61%; time to smear conversion, 19 days (IQR 10-32) vs. 31 days (IQR 14-56) (P = 0.066); time to culture conversion, 39 days (IQR 17-67) vs. 39 days (IQR 6-85) (P = 0.191). Both clinical and radiological scores decreased after the introduction of anti-tuberculosis treatment. CONCLUSION: There were no significant differences in scores between the two groups until 6 months of treatment. Under optimal clinical conditions, with the availability of novel diagnostics and a wide range of therapeutic options for individualised treatment, patients with M/XDR-TB achieved 6-month culture conversion rates that were compatible with those in patients with non-M/XDR-TB.

[Mother and son between omnipotence and coma]. / Mutter und Sohn zwischen Allmacht und Koma.

An academic and his mother, both with Chinese roots, present to the emergency department due to acute confusion. After short latency nausea, complex-focal seizures and finally coma with preserved protective reflexes occur. The cardiorespiratory stable patients are observed in an intensive care unit. The extended emergency diagnostic work-up revealed no cause for the underlying symptoms. Following medical request, the apartment of the patient is inspected by the police, where a meal with self-picked mushrooms is found. Special laboratory exams lead to the diagnosis of pantherina syndrome.

[Tuberculosis]. / Tuberkulose.

Tuberculosis is still one of the most important infectious disease worldwide. In Germany the tuberculosis incidence has been declining for decades to currently about 4500 new cases per year. A new challenge poses the rising number tuberculosis cases with drug resistant strains of Mycobacterium tuberculosis. Substantiell progress has been achieved in the diagnosis of tuberculosis with new molecular techniques that can lead to a much faster and more reliable identification of cases with acid-fast bacilli smear-negative tuberculosis and in the identification of drug-resistant strains of M. tuberculosis. Tuberculosis caused by drug resistant strains of M. tuberculosis is difficult to treat with the currently available medications and is related to very high costs of care. New therapeutic approaches and drugs are urgently needed. Interferon-γ tests have made the diagnosis of latent infection with M. tuberculosis more specific, but hardly contribute to the diagnosis of active tuberculosis.This article presents a brief summary of current knowledge concerning the epidemiology, risk factors, diagnosis and treatment of active tuberculosis and latent infection with M. tuberculosis. Moreover, current treatment approaches and economic aspects of care are discussed.