Serum concentration of penicillin and ampicillin in the empirical treatment of community-acquired pneumonia in children

The treatment of children with community-acquired bacterial pneumonia (CAP) is often revised due to changes in the sensitivity of the main pathogens responsible for antibiotics. In Uruguay, the most common causative agent of PFS is S. pneumoniae. In this regard, empirical therapy targets this pathogen. Empirical therapy for hospitalized children with CAP includes the use of high doses of ampicillin (300-400 mg / kg / day) or penicillin (200,000 units / kg / day). This therapy is effective in the treatment of children with CAP caused by S. pneumoniae with reduced sensitivity to penicillin (the minimum inhibitory concentration of BMD is less than 4 μg / ml). Animal studies have shown that when administered intravenously in high doses, beta-lactam antibiotics create a concentration in serum and pleural fluid greater than 4 μg / ml.

Although penicillin and ampicillin in high doses are successfully used in the treatment of children with CAP, there is no consensus on the dose and frequency of administration of these drugs. To answer this question, data on the changes in the concentration of the drug in serum and pleural fluid as a function of time are needed.

At the same time, it is impossible to predict the efficacy of an antibiotic by pharmacokinetic parameters alone. The concentration of the drug in serum and tissues is not always correlated with the frequency of eradication of the pathogen and does not take into account the post-antibiotic effect. For beta-lactam antibiotics, the pharmacokinetic / pharmacodynamic parameter that best corresponds to the bacteriological and clinical efficacy of the drug is the time during which the serum concentration of the drug exceeds the CPI of the pathogen (T is greater than the CPI). The optimal frequency of eradication of S. pneumoniae is observed when T is greater than BMD, which represents 40 to 50% of the interval between doses. The study of this indicator in children will allow the most rational use of beta-lactams in PFS.

Researchers from Uruguay investigated whether the concentration of the antibiotic in serum and pleural fluid is maintained at more than 4 μg / l, at least 40% of the interdose interval with intravenous administration of 400 mg / kg / day of ampicillin and 200,000 units / kg / day of penicillin in 6 doses.

The study involved 30 children aged 9 months to 14 years, hospitalized for bacterial pneumonia of community origin, without concomitant pathology. Of these, 17 received ampicillin and 13 received penicillin. Ampicillin was administered intravenously by bolus, penicillin during a 20-minute intravenous infusion. Blood samples were taken after 30 minutes (C1) and 3 hours (C2), and pleural fluid 1 hour and 4 hours after administration of the drug. Two blood samples were obtained from all patients. Two samples of pleural fluid were obtained from 13 patients and 1 sample from 3 patients. Most patients (n = 22) received 6 or more doses of the antibiotic before taking the material. For the rest, the number of injections before taking material was 5 (n = 1), 4 (n = 4), 3 (n = 1) or 1 (n = 2). S. pneumoniae was isolated from the blood and / or pleural fluid in 8 children. All strains were sensitive to penicillin (BMD less than 0.01 μg / ml). The average length of hospital stay was 14 days. There were no fatal outcomes.

For ampicillin, the mean serum C1 concentration was 37.3 ± 19 μg / ml, C2 11 ± 10.2 μg / ml, the mean concentration in pleural fluid C1 was 25.8 ± 9.9 μg / ml, C2 16.2 ± 7 9 mcg / ml. For penicillin, the mean serum C1 concentration was 21.8 ± 16.4 μg / ml, C2 23.9 ± 3.4 μg / ml, the mean concentration in pleural fluid C1 was 10.9 ± 2 , 2 μg / ml, C2 7 7 ± 3.4 μg / ml. In 6 patients receiving penicillin and in 1 patient receiving ampicillin, the serum concentration of the drug 3 hours after administration (C2) was below the sensitivity threshold of the determination procedure (0.4 μg / ml for penicillin and 1 μg / ml for ampicillin). In 4 patients with C2 penicillin and in 4 patients with C2, serum ampicillin was less than 4 μg / ml. But in these 8 patients, T more MPC (4 μg / ml) exceeded 40% of the interdose interval.

The T plus IPC time calculation was performed for 22 patients. All had a time T greater than the IPC; more than 40% of the interdose interval.

In all but one pleural fluid sample, the antibiotic concentration was greater than 4 μg / ml.

The data obtained for the 4 hour interval were extrapolated to the 6 hour interval. With the introduction of ampicillin at a dose of 400 mg / kg / day in four administrations (after 6 hours) in most T patients, more BMD would be greater than 40% of the interval between doses. For penicillin at a dose of 200,000 IU / kg / day in doses of 4 T, more MPC in most patients would not exceed 40% of the interval between doses.

Thus, the data obtained justify the recommendations for empirical treatment of PFS with ampicillin at a dose of 400 mg / kg / day or penicillin at a dose of 200,000 IU / kg / day in 6 injections.