Antimicrobial activity against obligate intracellular bacteria

Abstract

Antimicrobial susceptibility testing is crucial to guide effective treatment against obligate intracellular bacteria and to understand therapeutic successes and failures. To be efficient against intracellular pathogens, an antibiotic compound must reach the infected tissue, enter the infected cell and be active within the pathogen's specific intracellular niche, that is, not be inactivated by pH or anaerobic conditions. For these reasons, the laboratory testing of antibiotic susceptibility of intracellular bacteria is difficult and lacks standardization. In some studies, antibiotics and bacteria are included in the assay simultaneously, meaning that delayed bacteriostatic and bacteriocidal effects of the antibiotic cannot be properly evaluated. For example, aminoglycosides, currently used to treat many intracellular bacterial infections, do accumulate within cells but this process occurs slowly. If the assay incubation time is short 1xAutoradiographic evidence for the impermeability of mouse peritoneal macrophages to tritiated streptomycin. Bonventre, P.F et al. J. Bacteriol. 1967; 93: 445–450PubMedSee all References1, the penetration of the antibiotic within cells is limited and inaccurate data are obtained 2xUptake of 3H dihydrostreptomycin by macrophages in culture. Bonventre, P.F and Imhoff, J.G. Infect. Immun. 1970; 2: 89–95PubMedSee all References2. A second problem outlined by Steven McOrist in the November issue of Trends in Microbiology 3xObligate intracellular bacteria and antibiotic resistance. McOrist, S. Trends Microbiol. 2000; 8: 483–486Abstract | Full Text | Full Text PDF | PubMed | Scopus (12)See all References3 is defining the minimum inhibitory concentration (MIC) for an antibiotic and correlating the MIC with clinical efficacy. The serum levels of antibiotic compounds do not reflect intracellular accumulation. Additionally, it is difficult to determine breakpoints for susceptibility testing for intracellular bacteria 4xMethodology of antibiotics testing for intracellular pathogens. Drancourt, M and Raoult, D. : 71–85See all References4.A specific problem for resistance gene acquisition by intracellular bacteria is that there appears to be little horizontal gene transfer in intracellular bacteria 5xLateral gene transfer and the nature of bacterial innovation. Ochman, H et al. Nature. 2000; 405: 299–304Crossref | PubMed | Scopus (1749)See all References5 and only the development of resistance by mutation has been described. This has been observed in the laboratory and can occur, in vivo, in the development of macrolide resistance in Rickettsia prowazekii or quinolone resistance in Coxiella burnetii 6xAntimicrobial therapy of rickettsial spotted fever. Drancourt, M and Raoult, D. : 139–153See all References6. The main risk factor for the development of antibiotic resistance appears to lie in massive veterinary use of antibiotic compounds. However, for Chlamydia pneumoniae and Chlamydia trachomatis, the rare use of doxycycline in the human population makes it unlikely that these species will develop resistance in the short term. Resistance is also unlikely to develop in Rickettsia spp. owing to arthropod cell dependency.