In children under 2 years of age, Streptococcus pneumoniae is the main causative agent of meningitis and bacteremia with no primary objective. Pneumococcus is also one of the main bacterial pathogens of acute sinusitis, acute otitis media, and pneumonia in children. In the United States, approximately 35% of clinical strains of S. pneumoniae are resistant to penicillin and 26% are resistant to erythromycin. There are 2 phenotypes of pneumococcus resistance to macrolides. The M phenotype (due to the antibiotic efflux mechanism) is characterized by resistance to macrolides with only 14 and 15 members and a low level of resistance (the minimum inhibitory concentration (MIC) does not exceed 32 μg / ml). With the MLSB phenotype (due to the methylation of ribosomes), resistance to all macrolides and lincosamides is observed, and the level of resistance is high (BMD greater than 64 μg / ml).

On the one hand, it is possible to underestimate the impact of the ineffectiveness of macrolides; on the other hand, a small number of failures can be evidence of their high efficiency. At the same time, the clinical importance of resistance is proven by cases of ineffectiveness of macrolides when a patient isolates a pathogenic strain resistant to this class of antibiotics. Regarding β-lactam antibiotics, despite the increasing prevalence of pneumococcal strains with reduced susceptibility to penicillin and wide spectrum cephalosporins, the ineffectiveness of β-lactam antibiotics in patients with infections S. pneumoniae (except for CNS infections) rarely reported.

There is the following hypothesis: if the ineffectiveness of the treatment is more often observed with azithromycin than with β-lactams, then in children with an invasive pneumococcal infection which developed in the following month the use of any of these antibiotics, the ineffectiveness of azithromycin will prevail.

In order to test this hypothesis, a retrospective study was conducted with 54 children who had developed an invasive pneumococcal infection within one month after using azithromycin or a β-lactam antibiotic. 21 patients were included in the azithromycin administration group, 33 in the β-lactam group. The demographic indicators in the two groups were similar.

Drug treatment ineffectiveness has been defined as the development of an invasive pneumococcal infection during antibiotic treatment, within 3 days after treatment with azithromycin ends or 1 day after treatment with antibiotic treatment ends β-lactam.

The most common indication for antibiotic therapy was otitis media. All patients in the azithromycin group received the drug orally. In the β-lactam group, 4 patients received ceftriaxone IM, the rest received oral β-lactams. The average duration of the course was 4 and 5 days respectively. In the azithromycin group, pneumonia was the main indication for hospitalization. In the β-lactam group, the most common cause of hospitalization (33%) was meningitis.

In the azithromycin group of 21 pneumococcal strains, 18 (86%) were resistant to macrolides. In the second group of 32 strains available for research, 13 (41%) were resistant to penicillin and 7 (22%) with intermediate sensitivity (only 20 (63%) of the strains insensitive to penicillin). The risk of developing an invasive infection with a macrolide-resistant strain during treatment with azithromycin was the same as the risk of invading a penicillin-insensitive strain when treated with a β-lactam antibiotic (p = 0.67).

The incidence of treatment failure in the two groups was 11 (52%) and 11 (33%) cases (p = 0.24), respectively. In 10 out of 11 patients (93%) with ineffective azithromycin, a macrolide-resistant pneumococcal strain was isolated; in 1 patient, a sensitive strain. In the second group of 11 patients in therapeutic failure with a β-lactam antibiotic, 10 (93%) isolated a strain of pneumococcus insensitive to penicillin (7 resistant and 3 with intermediate sensitivity) and 1 sensitive. Thus, strains of pneumococci resistant to macrolides with ineffective macrolides and insensitive (resistant and with intermediate sensitivity) to strains of penicillin with ineffective antibiotics β-lactams are isolated with the same frequency (p = 1.0).

Of the patients in whom treatment with azithromycin was ineffective, 7 developed pneumonia. Of the 7 pneumococcal strains, 4 had an MLSB phenotype with an MIC of more than 16 μg / ml, and 3 had an M phenotype with an MIC of 4 μg / ml. Therefore, even a resistance level as low as BMD = 4 μg / ml due to the efflux mechanism can have clinical significance.

Thus, it has been proven that in children with an invasive pneumococcal infection, which developed in the month following antibiotic therapy, therapeutic failure is observed at the same frequency with macrolides and β-lactams. In addition, resistance to macrolides leads to ineffective treatment with this class of antibiotics with the same probability as insensitivity to penicillin - to the clinical ineffectiveness of β-lactam antibiotics.