Pharmacokinetics, microbial response, and pulmonary outcomes of multidose intravenous azithromycin in preterm infants at risk for Ureaplasma respiratory colonization

L. Marcela Merchan, Hazem E. Hassan, Michael L. Terrin, Ken B. Waites, David A. Kaufman, Namasivayam Ambalavanan, Pamela Kimzey Donohue, Susan J. Dulkerian, Robert Schelonka, Laurence S. Magder, Sagar Shukla, Natalie D. Eddington, Rose M. Viscardi

Research output: Contribution to journalArticle

Abstract

The study objectives were to refine the population pharmacokinetics (PK) model, determine microbial clearance, and assess short-term pulmonary outcomes of multiple-dose azithromycin treatment in preterm infants at risk for Ureaplasma respiratory colonization. Fifteen subjects (7 of whom were Ureaplasma positive) received intravenous azithromycin at 20 mg/kg of body weight every 24 h for 3 doses. Azithromycin concentrations were determined in plasma samples obtained up to 168 h post-first dose by using a validated liquid chromatography-tandem mass spectrometry method. Respiratory samples were obtained predose and at three time points post-last dose for Ureaplasma culture, PCR, antibiotic susceptibility testing, and cytokine concentration determinations. Pharmacokinetic data from these 15 subjects as well as 25 additional subjects (who received either a single 10-mg/kg dose [n = 12] or a single 20-mg/kg dose [n = 13]) were analyzed by using a nonlinear mixed-effect population modeling (NONMEM) approach. Pulmonary outcomes were assessed at 36 weeks post-menstrual age and 6 months adjusted age. A 2-compartment model with all PK parameters allometrically scaled on body weight best described the azithromycin pharmacokinetics in preterm neonates. The population pharmacokinetics parameter estimates for clearance, central volume of distribution, intercompartmental clearance, and peripheral volume of distribution were 0.15 liters/h • kg0.75, 1.88 liters • kg, 1.79 liters/h • kg0.75, and 13 liters • kg, respectively. The estimated area under the concentration-time curve over 24 h (AUC24)/MIC90 value was 4 h. All posttreatment cultures were negative, and there were no drug-related adverse events. One Ureaplasma-positive infant died at 4 months of age, but no survivors were hospitalized for respiratory etiologies during the first 6 months (adjusted age). Thus, a 3-day course of 20 mg/kg/day intravenous azithromycin shows preliminary efficacy in eradicating Ureaplasma spp. from the preterm respiratory tract.

Original languageEnglish (US)
Pages (from-to)570-578
Number of pages9
JournalAntimicrobial Agents and Chemotherapy
Volume59
Issue number1
DOIs
StatePublished - Jan 1 2015

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Ureaplasma
Azithromycin
Premature Infants
Pharmacokinetics
Lung
Body Weight
Population
Tandem Mass Spectrometry
Drug-Related Side Effects and Adverse Reactions
Liquid Chromatography
Respiratory System
Newborn Infant
Cytokines
Anti-Bacterial Agents
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Infectious Diseases

Cite this

Pharmacokinetics, microbial response, and pulmonary outcomes of multidose intravenous azithromycin in preterm infants at risk for Ureaplasma respiratory colonization. / Merchan, L. Marcela; Hassan, Hazem E.; Terrin, Michael L.; Waites, Ken B.; Kaufman, David A.; Ambalavanan, Namasivayam; Donohue, Pamela Kimzey; Dulkerian, Susan J.; Schelonka, Robert; Magder, Laurence S.; Shukla, Sagar; Eddington, Natalie D.; Viscardi, Rose M.

In: Antimicrobial Agents and Chemotherapy, Vol. 59, No. 1, 01.01.2015, p. 570-578.

Research output: Contribution to journalArticle

Merchan, LM, Hassan, HE, Terrin, ML, Waites, KB, Kaufman, DA, Ambalavanan, N, Donohue, PK, Dulkerian, SJ, Schelonka, R, Magder, LS, Shukla, S, Eddington, ND & Viscardi, RM 2015, 'Pharmacokinetics, microbial response, and pulmonary outcomes of multidose intravenous azithromycin in preterm infants at risk for Ureaplasma respiratory colonization', Antimicrobial Agents and Chemotherapy, vol. 59, no. 1, pp. 570-578. https://doi.org/10.1128/AAC.03951-14
Merchan, L. Marcela ; Hassan, Hazem E. ; Terrin, Michael L. ; Waites, Ken B. ; Kaufman, David A. ; Ambalavanan, Namasivayam ; Donohue, Pamela Kimzey ; Dulkerian, Susan J. ; Schelonka, Robert ; Magder, Laurence S. ; Shukla, Sagar ; Eddington, Natalie D. ; Viscardi, Rose M. / Pharmacokinetics, microbial response, and pulmonary outcomes of multidose intravenous azithromycin in preterm infants at risk for Ureaplasma respiratory colonization. In: Antimicrobial Agents and Chemotherapy. 2015 ; Vol. 59, No. 1. pp. 570-578.
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