Pharmakokinetische und klinische Untersuchungen mit Azlocillin in der Pädiatrie*

Abstract

Azlocillin, an acylureido penicillin with bactericidal activity, is particularly effective against Pseudomonas, enterococci and Haemophilus influenzae. It is also very active against E. coli, various Proteus species and Bacteroides. Pharmacokinetic studies were carried out in 138 children of various ages (prematures, newborns, infants, schoolchildren) after administering 50-75-100 mg/kg/ body weight azlocillin via the i.v. or i.m. routes; The constant of elimination and the distribution volumes were calculated besides the serum levels. In prematures and newborns, therapeutically effective serum levels were obtained on administering 50 or 100 mg/kg body weight twice daily. Infants and older children required 100 or 75 mg/kg body weight t.i.d. Determination of azlocillin in the bronchial secretion after i.v. doses of 75 mg/kg body weight showed good elimination. Azlocillin was always identified up to the 5th hour post injectionem. Inspite of parenteral administration, azlocillin was identified in different concentrations in the meconium as well. 39 children were treated with azlocillin, 35 of whom had Pseudomonas infection. Very good results were obtained in infections of the urinary tract, wound infections, conjunctivitis, dacryocystitis and in one case of meningitis. Bronchopulmonary diseases did not take an equally good course, but in these cases the conditions had not been favourable. No serious side effects were revealed by testing several laboratory parameters.

Pharmacokinetics of Azlocillin in Neonates

“…65 h. Heimann et al [5] gave the serum half-life of azlo cillin in 3-week-old premature infants and 3-week-old infants as 147 and 155 min, respectively. The azlocillin half-life in new born babies is shorter than in premature babies, but significantly longer than in older infants (calculated by us being 0.97 h) [16] and in adults with normal kidney function (reported as 1 h) [2,8,10,11,17].…”

“…The aver age minimal inhibitory concentrations (MIC) for carbenicillin and gentamicin-sen sitive Pseudomonas strains vary between 4 and 8 /¿g/ml. For Pseudomonas strains moderately sensitive or resistant to carbeni cillin and gentamicin the MIC's are between 16 and 32 ,«g/ml [1,[7][8][9]12,13], Since bacterial infections, particularly with P. aeruginosa, remain a significant cause of neonatal mortality, especially in neonatal intensive care units, the potential value of any new antibiotic should be stud ied. Owing to their wide antibacterial spec trum and their very low toxicity penicillins are antibiotics of choice for neonate infants.…”