Correspondence
Povidone-Iodine to Prevent Ophthalmia Neonatorum
N Engl J Med 1995; 333:126-127July 13, 1995
- Article
To the Editor:
Isenberg and colleagues (March 2 issue)1 demonstrated the effectiveness of povidone-iodine prophylaxis against ophthalmia neonatorum but limited their observation of side effects to local toxic reactions. Were the systemic effects of povidone-iodine, such as alterations in thyroid metabolism, evaluated in a pilot study?
Topical application of povidone-iodine has been known to cause transient hypothyroidism in newborns as a result of iodine excess.2 Iodine-induced hyperthyroidism has also been described in a newborn exposed to large doses of iodine.3 Although probably unimportant in most cases, the systemic effects of the conjunctival application of povidone-iodine should be thoroughly evaluated before the use of this form of prophylaxis becomes widespread, with special attention given to its impact on thyroid function in newborns.
3 ReferencesAlexandre T. Rotta, M.D.
Children's Hospital of Michigan, Detroit, MI 482011
Isenberg SJ ,Apt L ,Wood M . A controlled trial of povidone-iodine as prophylaxis against ophthalmia neonatorum. N Engl J Med 1995;332:562-566
Full Text | Web of Science | Medline2
Albengres E ,Riant P ,Meistelman C ,Chevais M ,Canet J ,Tillement JP . Application locale d'un antiseptique iode et hypothyroidie biologique neo-natale. Therapie 1983;38:565-567
Web of Science | Medline3
Bryant WP ,Zimmerman D . Iodine-hyperthyroidism in a newborn. Pediatrics 1995;95:434-436
Web of Science | Medline
To the Editor:
The statement by Isenberg et al. that no bacteria are resistant to a 2.5 percent ophthalmic solution of povidone-iodine is based on a 1976 study by Houang et al.1 However, Krasilnikow et al. subsequently found resistant Pseudomonas aeruginosa in 6.5 percent of clinical isolates and resistant Enterobacteriaceae species in 15 percent of such isolates.2 The prevalence of resistant strains of P. aeruginosa increased between 1978-1979 and 1986-1988. There has already been a published report of an isolate of Staphylococcus aureus that was resistant to povidone-iodine.3 These resistant organisms are responsible for the colonization of commercially available iodophor solutions with pseudomonas species.4 Although the antimicrobial activity of iodine is well known, proteins inactivate iodophors, especially in more dilute solutions.5 In addition, they are cytotoxic to some types of cells, such as fibroblasts, and can deter wound healing.6
All these facts do not diminish the practical importance of the findings of Isenberg et al., especially the concept of using a topical antiseptic for infection prophylaxis. Further studies with povidone-iodine, as well as with other antiseptics to which no microbes are resistant and that have lower rates of protein-induced inactivation and no tissue toxicity, are necessary. Monitoring for the development of microbial resistance is also important in studying antiseptics.
6 ReferencesAndreas R. Petri, M.D.
University of Connecticut Health Center, Farmington, CT 06030Michael Pietsch, M.D.
University of Mainz, 55131 Mainz, Germany1
Houang ET ,Gilmore OJ ,Reid C ,Shaw EJ . Absence of bacterial resistance to povidone iodine. J Clin Pathol 1976;29:752-755
CrossRef | Web of Science | Medline2
Krasilnikow AP, Adartschenko AA, Gudkowa EI. Klinische Bedeutung der Empfindlichkeit nosokomialer bakterieller Krankheitserreger gegen Antiseptika. In: Kramer A, Groschel D, Heeg P, et al., eds. Klinische Antiseptik. Berlin, Germany: Springer-Verlag, 1993:401-4.
3
Mycock G . Methicillin/antiseptic-resistant Staphylococcus aureus. Lancet 1985;2:949-950
CrossRef | Web of Science | Medline4
Anderson RL . Iodophor antiseptics: intrinsic microbial contamination with resistant bacteria. Infect Control Hosp Epidemiol 1989;10:443-446
CrossRef | Web of Science | Medline5
Werner HP . Microbicidal effectiveness of selected antiseptics. Hyg Med 1992;17:51-596
Werner HP . Antibakterielle Wirksamkeit und lokale Nebenwirkungen der Povidon-Jod-Anwendung. Fortschr Antimikr Antineoplast Chemother 1987;6:139-139
To the Editor:
I must quibble with the statement by Drs. Foster and Klauss (March 2 issue)1 that ``a single intramuscular injection of cefotaxime... is highly effective in gonococcal ophthalmia.'' Although cefotaxime is an alternative for nondisseminated as well as disseminated gonococcal infection in neonates, only ceftriaxone is recommended as single-dose therapy.2 Cefotaxime (50 to 100 mg per kilogram of body weight per day) is administered for 7 days for localized infections and for 10 to 14 days for disseminated gonococcal infections.
2 ReferencesLeslie L. Barton, M.D.
University of Arizona Health Sciences Center, Tucson, AZ 857241
Foster A ,Klauss V . Ophthalmia neonatorum in developing countries. N Engl J Med 1995;332:600-601
Full Text | Web of Science | Medline2
Gonococcal infections. In: Red book: report of the Committee on Infectious Diseases. 23rd ed. Elk Grove Village, Ill.: American Academy of Pediatrics, 1994:197.
Author/Editor Response
The authors reply:
To the Editor: We appreciate the comments of Drs. Petri and Pietsch. Although some rare strains of Staphylococcus aureus may have in vitro resistance to povidone-iodine, clinical experience derived from decades of use indicates that the vast majority of strains, including methicillin-resistant strains, are sensitive to povidone-iodine. Drs. Petri and Pietsch state that Mycock1 reported a hospital isolate of S. aureus resistant to povidone-iodine (Betadine). Actually, she indicated that the isolate had low sensitivity to the drug, not bacterial resistance. The few reports of strains of P. aeruginosa that were supposedly resistant to povidone-iodine do not greatly affect its use in preventing ophthalmia neonatorum. In two investigations of the normal conjunctival bacterial flora at birth, we did not culture P. aeruginosa in samples from any of the more than 200 neonates studied.2,3 In addition, Drs. Petri and Pietsch's statements regarding the inactivation of povidone-iodine by proteins and effects on wound healing do not seem relevant to the prophylactic use of povidone-iodine in the eyes of newborn infants.
Before beginning our studies, we shared Dr. Rotta's concern about inducing a thyroid disorder in neonates. In fact, the human subjects committee of the Harbor-UCLA Medical Center requested information about this possibility before approving the protocol. In our small pilot study, the administration of one drop of a 2.5 percent ophthalmic solution of povidone-iodine in each eye had no effect on thyroid function. This is understandable when one considers the small amount of free iodine (about 0.25 mg) delivered to the eyes, only a portion of which will ever reach the bloodstream. By contrast, the infant in the report of Bryant and Zimmerman cited by Rotta received 28.8 g of iodine by mediastinal lavage over a period of five days.4 Furthermore, in our study clinical thyroid disorders did not develop in any of the more than 3000 newborns who received a 2.5 percent ophthalmic solution of povidone-iodine.
4 ReferencesSherwin J. Isenberg, M.D.
Leonard Apt, M.D.
UCLA School of Medicine, Los Angeles, CA 90095-70011
Mycock G . Methicillin/antiseptic resistant Staphylococcus aureus. Lancet 1985;2:949-950
CrossRef | Web of Science | Medline2
Isenberg SJ ,Apt L ,Yoshimori R ,Alvarez SR . Bacterial flora of the conjunctiva at birth. J Pediatr Ophthalmol Strabismus 1986;23:284-286
Medline3
Isenberg SJ ,Apt L ,Yoshimori R ,McCarty JW ,Alvarez SR . Source of the conjunctival bacterial flora at birth and implications for ophthalmia neonatorum prophylaxis. Am J Ophthalmol 1988;106:458-462
Web of Science | Medline4
Bryant WP ,Zimmerman D . Iodine-induced hyperthyroidism in a newborn. Pediatrics 1995;95:434-436
Web of Science | Medline
Author/Editor Response
In response to Dr. Barton's question regarding the use of cefotaxime in the treatment of ophthalmia neonatorum, I would like to confirm that a single intramuscular dose of 100 mg of cefotaxime per kilogram of body weight is recommended by the World Health Organization for the treatment of ophthalmia neonatorum.1 The British National Formulary has also approved the use of a single dose of cefotaxime for gonococcal infections.2
2 ReferencesAllen Foster, M.D.
International Centre for Eye Health, London EC1V 9EL, United Kingdom
