The Effect of Azithromycin on Biofilms Formation by Pathogens of Implant-Associated Infection in Large Joints

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Bulletin of Experimental Biology and Medicine, Vol. 169, No. 6, October, 2020 IMMUNOLOGY AND MICROBIOLOGY

The Effect of Azithromycin on Biofilms Formation by Pathogens of Implant-Associated Infection in Large Joints I. V. Babushkina, V. Yu. Ulyanov, I. A. Mamonova, and S. P. Shpinyak

Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 169, No. 6, pp. 744-747, June, 2020 Original article submitted March 4, 2020 We studied the effect of subbacteriostatic azithromycin concentrations on the formation of microbial biofilms by Pseudomonas aeruginosa strains that caused implant-associated infection of large joints. Azithromycin in subinhibitory for planktonic cells concentrations 0.01-0.02 µg/ml stimulated biofilm formation by both clinical and reference P. aeruginosa strains, while in concentrations of 1 µg/ml and higher completely inhibited the growth of both reference and clinical plankton P. aeruginosa strains, but stimulated biofilm formation. Increasing azithromycin concentration to 10 µg/ml led to inhibition of P. aeruginosa biofilm growth. Key Words: azithromycin; microbic biofilms; Pseudomonas aeruginosa; replacement arthroplasty Biofilm formation is the mechanism responsible for the resistance of pathogens of implant-associated infection to antimicrobial treatments and immune factors as well as the mechanism underlying pathogenicity and persistence of gram-negative bacteria [1,5]. Inefficiency of etiotropic antibiotic treatment in the presence of biofilm infection is due to barrier function of biopolymer matrix providing selective diffusion of antibiotic macromolecules and due to enzyme destruction or modification of antibiotic molecules [1]. It was shown that some antibiotics in low concentrations stimulate the growth of bacterial biofilms, which can be related to expression of genes responsible for biofilm phenotype [6,10]. Some authors hypothesized that adhesion of bacteria to biotic and antibiotic surfaces can by stimulated by carbapenems [2,9]. The principles of rational etiotropic antibacterial chemotherapy do not consider peculiarities of antibiotic resistance of implant-associated infectious agents in the biofilm form. Here we studied the effect of subbacteriostatic azithromycin concentrations on the formation of miResearch Institute of Traumatology, Orthopedics, and Neurosurgery, V. I. Razumovsky Saratov State Medical University, Ministry of Health of the Russian Federation, Saratov, Russia. Address for corre­ spondence: [email protected]. I. V. Babushkina

crobial biofilm by Pseudomonas aeruginosa strains that caused implant-associated infection of large joints.

MATERIALS AND METHODS The study objects were 20 P. aeruginosa strains isolated from various biomaterials of patients with inflammatory complications following large joint replacements in 2016-2019 and a reference P. aeruginosa АТСС 27853 strain. The identification was performed using Crystal Autoreader (Becton Dickinson) identification system. For preparing azithromycin stock solution with a concentration of 1 mg/ml,