ABSTRACT
The efficacy and safety of azithromycin prophylaxis of community-acquired pneumonia (CAP) in young adults in a military training centre of the Ministry of Defence of the Russian Federation located in the Central European Region of Russia were studied. Two prophylactic regimens with azithromycin vs. the control were evaluated: azithromycin, 500 mg/w for 8 weeks (R1), azithromycin, 1500 mg once upon the enrolment (R2) and no drugs (R3). Nasopharyngeal carriage of Streptococcuspneumoniae and its susceptibility to antibacterials were estimated thrice: before the exposure, after the exposure within the 9th week and after the exposure within the 20th week. The MLS(B) phenotype was suspected when the isolates were resistant to erythromycin and clindamycin. During the observation period of 22 weeks CAP was diagnosed in 20.2% of 678 subjects in group R3, 8.6% of 508 subjects in group R1 (Risk Ratio =0.4, 95% Cl = 0.3-0.6) and 10.3% of 507 subjects in group R2 (Risk Ratio = 0.5, 95% Cl = 0.4-0.7). The S.pneumoniae carriage rate at visit 0 was 34-35%, within the 9th week it was 75, 66 and 50% (p<0.05) in groups R1, R2 and R3 respectively, and within the 20th week it was 69, 57 and 36% in the same groups (p<0.05). At visit 0 no macrolide resistance was detected in any of the 40 isolates tested. The background level of intermediate penicillin resistance was revealed in 0-14% of the isolates. Dramatic growth of macrolide resistance was observed within the 9th week in group R1 (95.7%, 44 resistant strains, Azithro+Clinda resistance in 37% of them) and in group R2 (89.5%, 34 resistant strains, Azithro+Clinda resistance in 11.9% of them). By the 20th week the resistance rate decreased up to 40 % (16 resistant strains, Azithro+Clinda resistance in 10% of them) in group R1 and up to 22.6% (7 resistant strains, Azithro+Clinda resistance in 5.4% of them) in group R2. As for penicillin resistance, no unfavourable shifts were detected. The study demonstrated the effectiveness of the azithromycin prophylaxis of CAP in healthy young men at high transient risk of the disease, as well as the possible risk for selection of resistant endemic pathogens.
