Generation of Antibiotic Tolerant Bacterial Persisters in Immunocompromized Patients with Hematologic and Malignant Diseases: A New Problem of Health-Care Associated Infections

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Abstract

Background: Antibiotic tolerance (AT) represents one of the causes of the phenomenon of antibiotic resistance that allows escape of non-replicating metabolically inert microorganisms (persisters) from any antibiotics attack because molecular targets of antibiotics are lacking thereby creating the potential for chronic infections. 

Aims:Determine the heterogeneity of the strains of opportunistic pathogens E. coli and P. aeruginosa isolates from children with hematologic malignancies containing bacterial persisters that cause the AT phenomenon. 

Methods: Children with hematological malignancies were divided into 2 groups according to the intensity of antibiotic treatment of infectious complications. Ciprofloxacin-induced persisters were quantitatively determined in the biological materials obtained from sick children. 

Results: Within the clinical isolates of E. coli and P. aeruginosa, about a third of the strains belong to high-persisting. The numbers of persistent forms of bacteria did not correlate with a minimal inhibitory concentration values ciprofloxacin (r=0.148, n=25, p>0.05). Interestingly, higher level of formation of persistent E. coli and P. aeruginosa, is associated with higher frequencies of infection attacks, massive antibiotic use and unfavorable course of the disease in children. 

Conclusions: Therefore, detecting the persistent forms of bacterial pathogens including those associated with the health-care associated infection, specifically, in immunocompromised patients, should be included into the contemporary algorithms of microbiological observation and monitoring of patients and intrahospital environment.

About the authors

A. V. Tutelyan

Central Institute of Epidemiology, Moscow;
Dmitry Rogachev’s Federal Scientific and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Moscow;
I.M. Sechenov First Moscow State Medical University

Author for correspondence.
Email: bio-tav@yandex.ru
Доктор медицинских наук, заведующий лабораторией инфекций, связанных с оказанием медицинской помощи, Центрального НИИ эпидемиологии Роспотребнадзора; профессор кафедры эпидемиологии ИПО Первого МГМУ им. И.М. Сеченова Russian Federation

V. M. Pisarev

Central Institute of Epidemiology, Moscow;
Dmitry Rogachev’s Federal Scientific and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Moscow;
V.A. Negovsky Research Institute of General Reanimatology, Moscow

Email: vpisarev@gmail.com
Доктор медицинских наук, профессор, заведующий лабораторией молекулярных механизмов критических состояний НИИ общей реаниматологии им. В.А. Неговского Russian Federation

N. Z. Minaeva

Central Institute of Epidemiology, Moscow

Email: natm9797@ya.ru
Russian Federation

A. M. Gaponov

Central Institute of Epidemiology, Moscow;
Dmitry Rogachev’s Federal Scientific and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Moscow;
V.A. Negovsky Research Institute of General Reanimatology, Moscow

Email: zorba@yandex.ru
Кандидат медицинских наук, заведующий лабораторией инфекционной иммунологии ФНКЦ ДГОИ им. Дмитрия Рогачёва Russian Federation

A. N. Gracheva

Dmitry Rogachev’s Federal Scientific and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Moscow

Email: alnickgrach@mail.ru
Бактериолог отдела инфекционного контроля  Russian Federation

G. G. Solopova

Dmitry Rogachev’s Federal Scientific and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Moscow

Email: galigen@yahoo.co.uk
Кандидат медицинских наук, заведующая отделом инфекционного контроля Russian Federation

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