Treatment of Neonatal Chlamydial Conjunctivitis With Azithromycin

Chlamydia trachomatis is the most frequent identifiable infectious cause of neonatal conjunctivitis in the United States.1, 2 Because infants are often infected at other anatomic sites besides the conjunctiva, systemic treatment with a 14-day course of oral erythromycin suspension is the current recommendation.1 However, treatment with erythromycin has been associated with a 20 to 30% failure rate, often requiring second and third courses of therapy.3, 4, 5, 6 The advent of new macrolide and azalide antibiotics offers the potential for shorter courses of treatment. Single dose azithromycin has been demonstrated to be effective for treatment of genital C. trachomatis infection in adults.1, 7 Currently azithromycin suspension is approved for infants as young as 6 months of age. There are no data on the efficacy and safety of azithromycin in younger infants. Therefore we evaluated short courses of azithromycin suspension for the treatment of neonatal chlamydial conjunctivitis. Patients. Infants ≤4 weeks of age presenting with conjunctivitis to the Pediatric Emergency Room and Neonatal Services at Kings County Hospital, Brooklyn, were screened for C. trachomatis infection by direct fluorescent antibody (DFA) testing. If the DFA was positive the patient was invited to enroll. This study was approved by the institutional review board at SUNY Health Science Center at Brooklyn. Written informed consent was obtained from the parent or legal guardian. DFA testing. Conjunctival specimens for DFA testing were obtained by firmly stroking the lower conjunctiva with an aluminum-shafted, Dacron-tipped swab. The swab was then rolled on a glass slide, fixed and stained according to the instructions of the manufacturer (Syva MicroTrak, Chlamydia Direct Test®). A smear was considered positive if ≥5 elementary bodies were seen.8 Culture ofC. trachomatis. Cultures for C. trachomatis were obtained from the eye and nasopharynx (NP) of infants who were DFA-positive. Specimens were obtained with wire-shafted Dacron swabs as described above. Culture of C. trachomatis was performed in cycloheximide-treated HEp-2 cells grown in 96-well microtiter plates. Treatment with azithromycin suspension. Infants were treated with 20 mg/kg azithromycin suspension either as a single dose, or once daily for 3 days. Infants were cultured at baseline and 7 to 14 days after treatment. Results. From October, 1994, through May, 1998, we screened a total of 105 infants presenting with conjunctivitis; 25 (23.7%) were positive by DFA and culture for C. trachomatis. We enrolled 13 positive infants. Most of the infants who were not enrolled were excluded because of prior antibiotic treatment. The infants presented at 6 through 18 days of age (mean, 8 days). Five infants were given the single dose by a nurse in our office. As shown in Table 1 one infant also had a positive nasopharyngeal culture. Three infants improved clinically and were culture-negative after treatment, but the remaining 2 were mildly symptomatic and DFA- and culture-positive, including the infant with positive NP cultures, 2 weeks later. Both infants became culture-negative after treatment with erythromycin suspension. Patient 1 required two 14-day courses of erythromycin before becoming DFA- and culture-negative.TABLE 1: Treatment of neonatal Chlamydia conjunctivitis with single dose azithromycin We then treated eight infants with 20 mg/kg azithromycin once daily for 3 days. The first dose of azithromycin was given in our office. One infant did not return for follow-up. As shown in Table 2 six of the remaining seven culture-positive infants were asymptomatic and culture-negative when seen 2 to 6 weeks after treatment, including one infant who had a positive nasopharyngeal culture. One infant remained culture- and DFA-positive in the eye and NP, although she was improved clinically when seen 6 days after treatment. This infant became culture-negative after a 14-day course of erythromycin.TABLE 2: Treatment of neonatal chlamydial conjunctivitis with three doses of azithromycin The azithromycin suspension was well-tolerated and there were no observed adverse effects, including gastrointestinal side effects. However, it was observed that the entire dose was not successfully administered to three of the infants. These were also the infants who remained culture-positive after treatment with azithromycin. Discussion. These preliminary results suggest that a short course of azithromycin treatment may effective for neonatal chlamydial conjunctivitis, although the optimum dosage and duration of therapy need to be determined. The results of this study also demonstrate that we may not be able to extrapolate from the experience of treatment of C. trachomatis infections in adults to infants. Data on the use of azithromycin in small infants are limited. Use in infants ≥6 months of age, primarily for respiratory infections such as otitis media or pneumonia at doses of either 10 mg/kg/day on Day 1 followed by 5 mg/kg/day for 4 days or 10 mg/kg/day for 3 days, appears to be well-tolerated and has not been associated with significant adverse effects.9, 10 The 20-mg/kg dose was selected as being equivalent to the single 1-g dose used for treatment of chlamydial cervicitis and urethritis in adults which equates with a dose of 17 mg/kg in a 60-kg adult. There are also limited data on the use of azithromycin for the treatment of chlamydia conjunctivitis in adults. There is only one study from Croatia that has evaluated azithromycin for this indication.11 In a retrospective analysis 44 patients, 12 through 68 years of age, were treated with either a single 1-g dose or 500 mg/day for 3 days. Both regimens were equally effective with a 100% eradication of C. trachomatis from the conjunctivae after treatment. We think that the three treatment failures were probably caused by these infants not having received the full dose. The numbers of infants treated were too small to conclude that three doses were more effective than one, but the efficacy of the three dose azithromycin regimen was similar to that seen with 14 days of erythromycin suspension. Modification of the concentration of the azithromycin suspension might improve efficacy. Neonatal chlamydial conjunctivitis is becoming less frequent as more women are screened and treated during pregnancy. Inevitably some women will not be screened, be missed on screening or be reinfected because their sexual partner was not treated; thus we still need an effective, well-tolerated treatment for chlamydial infection in infants. Acknowledgments. This study was supported in part by a grant from Pfizer Pharmaceuticals. Margaret R. Hammerschlag, M.D. Maureen Gelling, R.N. Patricia M. Roblin, M.S. Andrei Kutlin, Ph.D. Jose E. Jule, M.D.