Pulmonary Tuberculosis with Polyclonal Infection – Diagnostic Challenges and the Importance of Sequencing to the Improvement of Case Management – Case Report

Monika Kozińska, Dorota Filipczak, Ewa Augustynowicz-Kope&#x0107Department of Microbiology, National Tuberculosis and Lung Diseases Research Institute, Warsaw, PolandCorrespondence: Monika Kozińska, Department of Microbiology, National Tuberculosis and Lung Diseases Research Institute, Plocka 26, Warsaw, 01-138, Poland, Tel/Fax +48224312182, Email m.kozinska@igichp.edu.plAbstract: Many studies on the molecular epidemiology of tuberculosis (TB) have shown that 10– 20% of patients may be infected with more than one strain of Mycobacterium tuberculosis (MTB), during a single episode of the disease. However, data on the frequency of this phenomenon are underestimated, and methodological difficulties mean that most cases are not detected. Below we present the first case of polyclonal/mixed infection documented in Poland. We described the case of a 33-year-old Ukrainian man, imprisoned in a Polish prison, who was diagnosed with pulmonary TB confirmed by culture. During the 6-month therapy, the patient was treated in three Polish hospitals, but no negative sputum test result was obtained. In the course of microbiological and molecular diagnostics, conducted from June 2021 to February 2022, divergent results were obtained from drug susceptibility testing and genotyping of MTB strains isolated from clinical materials from the patient. In the final stage of the tests, it was confirmed that the patient was infected with two strains of MTB - one of them was drug-sensitive and belonged to the T1 267 genotype, the other was pre-extensively drug resistant (pre-XDR) and belonged to the Beijing 265 genotype. The existence of clonally complex TB infections resulting in heteroresistance to basic antituberculosis drugs has important implications for patient care. Established molecular methods complemented by routine microbiological diagnostics allow rapid detection of these infections and appropriate adjustment of therapy.Keywords: Mycobacterium tuberculosis mixed infection, polyclonal infection, heteroresistance, genotyping methods, next-generation sequencing