Abstract
BackgroundDrug-resistant tuberculosis (TB), especially multidrug-resistant TB (MDR-TB), poses a threat to public health. While standard surveillance focuses on Rifampicin and/or Isoniazid resistance, little is known about other resistance patterns. This study aims to identify predominant drug resistance (DR) patterns in Germany and risk factors associated with them in order to inform diagnostic and treatment strategies.MethodsCase-based TB surveillance data notified in Germany from 2008–2017 were utilized to investigate DR and MDR-TB patterns for Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), Ethambutol (E), and Streptomycin (S). Predominant patterns were further analyzed stratified by sex, age, country of birth, prior TB, and disease site. Multivariable logistic regression was conducted to determine risk factors associated with any resistance, MDR-TB, and complete HRZES resistance.Results26,228 cases with complete DST results were included in the study, among which 3,324 cases had any DR (12.7%). Four patterns were predominant, representing about ¾ of all cases with any resistance (S: 814 [3.1%]; H: 768 [2.9%]; HS: 552 [2.1%]; Z: 412 [1.6%]). High proportions of S and H resistances were found among both German and foreign-born populations, especially those born in Eastern Europe, and were unexpectedly high among children (H: 4.3%; S: 4.6%). Foreign-born cases had significantly higher proportion of any resistance (16.0%) and MDR-TB (3.3%) compared to German-born cases (8.3% and 0.6%). Of 556 MDR-TB cases, 39.2% showed complete HRZES resistance. Logistic regression revealed having prior TB and being foreign-born as consistently strong risk factors for any DR, MDR-TB, and complete HRZES resistance.ConclusionsDR patterns observed in Germany, particularly for MDR-TB were more complex than expected, highlighting the fact that detailed drug-testing results are crucial before incorporating HRZES drugs in MDR-TB treatment. Furthermore, the relatively high rate of H-resistance in Germany provides strong rationale against the use of only H-based preventive therapy for LTBI.
Highlights
Tuberculosis (TB) is the ninth leading cause of death worldwide and the leading cause of death from a single infectious agent, exceeding even HIV/AIDS [1]
drug resistance (DR) patterns observed in Germany, for multidrug-resistant TB (MDR-TB) were more complex than expected, highlighting the fact that detailed drug-testing results are crucial before incorporating HRZES drugs in MDR-TB treatment
In 2017, 558,000 cases were estimated to be resistant to Rifampicin (R), the most effective first-line anti-tuberculosis drug [1], with 82% suffering from multidrug-resistant TB (MDR-TB) [1], which is defined as the resistance to at least Rifampicin and Isoniazid, another potent anti-TB drug [1]
Summary
Drug-resistant tuberculosis (TB), especially multidrug-resistant TB (MDR-TB), poses a threat to public health. While standard surveillance focuses on Rifampicin and/or Isoniazid resistance, little is known about other resistance patterns. This study aims to identify predominant drug resistance (DR) patterns in Germany and risk factors associated with them in order to inform diagnostic and treatment strategies. Editor: Alejandro Escobar-Gutierrez, Instituto de Diagnostico y Referencia Epidemiologicos, MEXICO. Data Availability Statement: All data utilized in the study were collected in accordance with the German ‘Protection against Infection Act’ (‘Infektionsschutzgesetz’), which has very stringent data protection guidelines. The Data Protection Office of the Robert Koch Institute restricts sharing of any case-based surveillance data externally as the data are only pseudo-anonymized and contain potentially identifying patient information. Aggregated data can be requested from the authors or the Research Data Management Unit of the
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
