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Haemophilus influenzae - the most important causative agent of acute otitis media

One of the most common infectious diseases in children is acute otitis media (ACC). The number of doctor visits in the United States under the CCA for the period from 1975 to 1990. doubled, each year the number of episodes of this disease exceeds 20 million cases. ACC is one of the most common causes of antibiotic use in children.

The etiology of acute otitis media has not changed in the past 50 years; its causative agents are Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pyogenes , and the first two pathogens are the most common. Recent data indicates that in countries where vaccination with pneumococcal vaccine is widespread, the role of H. influenza as a causative agent of CCA is increasing.

Almost all strains of H. influenzae that cause acute otitis media are capsule-free, and this was before vaccination against H. influenzae type b. Boys with H. influenzae CCA stand out twice as often as girls, with the highest incidence occurring in November-December. H. influenzae causes ACC more often in children aged 1.5 years, while S. pneumoniae - in children younger than one year. In the initial episode, CCA H. influenzae is several times less frequent than in repeated cases.

H. influenzae is detected much more often in patients in whom the use of antimicrobial agents in CCA was ineffective. Even after the end of antibiotic treatment, H. influenzae in most cases continues to be detected in the discharge from the middle ear. For example, according to various authors, the degree of eradication with azithromycin is 45%, cefaclor - 56%, amoxicillin - 76%, trimethoprim / sulfamethoxazole - 83%, cefuroxime / axetil - 86%, amoxicillin / clavulanate - 94% and was 100% only when using gatifloxacin or an intramuscular injection of ceftriaxone (within 1 to 3 days).

It is impossible to pinpoint the causative agent of acute otitis media from the clinical picture. However, it can be said that for the bacterial etiology of the disease, unlike that of the viral one, symptoms such as coughing and a runny nose are less characteristic; swelling of the eardrum, on the contrary, is more common. It is generally believed that ACC caused by pneumococcus occurs with more pronounced local and general symptoms, but this is not always the case. A combination of CCA and conjunctivitis is considered to be fairly specific for the infection caused by H. influenzae. Complications of ACC in the form of mastoiditis and H. influenzae eardrum perforation are less common than S. pneumoniae.

Carrying H. influenzae is widespread - it is found in the nasopharynx in 80% of people. The nasopharynx of children is colonized during the first year of life; in children who have had a CCA, porting is more frequent. The immune response consists of the production of antibodies against the proteins of the H. influenzae outer membrane, but they do not protect against new diseases.

The resistance of the hemophilic bacillus to beta-lactam antibiotics is determined by the production of beta-lactamases TEM-1 and less often ROB-1, as well as by a modification of the penicillin-binding protein. There is a problem of resistance to antimicrobials of other classes, in particular to macrolides and trimethoprim / sulfamethoxazole.

The MIC of amoxicillin for strains H. influenzae which do not have resistance mechanisms is 0.25 to 1.0 μg / ml, and for strains producing beta-lactamases, the MPC exceeds 16 μg / ml. The addition of clavulanate brings the amoxicillin MIC to a level of 0.5 μg / ml. The most active cephalosporin is ceftriaxone, its BMD is less than 0.004 μg / ml.

According to the NCCLS criteria, most of the H. influenzae strains are sensitive to macrolides, azithromycin being the most active. However, by focusing on the limit values determined on the basis of pharmacokinetic and pharmacodynamic factors, almost all strains of H. influenzae, on the other hand, are insensitive to macrolides and azalides. Fluoroquinolones exhibit high activity; reports of isolation of H. influenzae strains that are resistant to them are rare.

When evaluating the efficacy of an antimicrobial drug in the treatment of patients with acute otitis media caused by H. influenzae, it should be borne in mind that eradication spontaneous pathogen (with placebo) reaches 48%. In this context, the activity of amoxicillin (38 to 63% of eradication when taken at doses of 40 to 80 mg / kg / day) seems rather modest. If the infection was caused by H. influenzae producing beta-lactamases, amoxicillin was only effective in 62% of cases. Amoxicillin / clavulanate at a dose of 45 / 6.4 mg / kg / day was more effective - up to 77% of eradication, and at a higher dose (90 / 6.4 mg / kg / day) ) - up to 90-94%.

Trimethoprim / sulfamethoxazole is only effective if acute otitis media is caused by a hemophilic bacillus that does not resist this drug, but in some countries the resistance level reaches 25%, which does not allow us to consider the drug as a means of choice.

Even a single injection of ceftriaxone at a dose of 50 mg / kg provided a 100% level of bacteriological healing. Cefuroxime / asetil is also very effective, the activity of cefaclor is weak even against non-beta-lactamase producing strains.

The efficacy of azithromycin does not differ from placebo. The low bacteriological efficacy of the drug (very active against H. influenzae in vitro) with CCA can be explained by low concentrations in the fluid of the middle ear.

Despite the fact that the use of fluoroquinolones in pediatrics is not authorized, a study confirms the high efficacy (100% eradication level of H. influenzae) of gatifloxacin in children with of TOC.

The level of eradication of H. influenzae with ACC is correlated with clinical efficacy. Thus, clinical ineffectiveness is noted only in 8% of cases when the pathogen is eliminated, and in 95% if eradication is not achieved.

The fact that patients with acute otitis media are characterized by spontaneous healing makes it difficult to assess the effectiveness of antibacterial drugs and may inspire unreasonable optimism. At the same time, on the basis of data on the eradication of bacteria, it is possible to distribute the available drugs according to their degree of activity. The most effective are ceftriaxone, cefixime, amoxicillin / clavulanate at a dose of 90 / 6.4 mg / kg / day and gatifloxacin, amoxicillin / clavulanate at a dose of 45 / 6.4 mg / kg / day and cefuroxime / asetil are of moderate efficacy. Amoxicillin is a weak drug, even at high doses, it is ineffective against beta-lactamase producing strains, cefaclor and azithromycin.

These data should be kept in mind when choosing a drug for empirical antimicrobial therapy, given the growing role of the bacillus hemophiliac as a causative agent of acute otitis media in the era of pneumococcal vaccine.