WHO DRUG INFORMATION - World Health Organization

Untreated, gonococcal ophthalmia progresses withalarming rapidity (2). Corneal involvement commonlyresults in blindness and sometimes perforation ofthe eye. Chlamydial infection is generally lesssevere, but signs of conjunctivitis may persist forseveral weeks during which vision may be impairedas a result of corneal scarring, vascularization andpseudomembrane formation (3, 4).Notwithstanding widespread reports of gonococciresistant to tetracycline (5-7), it is current practiceto treat all cases of neonatal ophthalmia withfrequent applications of 1 % tetracycline eyeointment, initially at hourly intervals decreasingprogressively after several days to 4 times daily (1).It is vital, however, that infants with gonococcalinfection — which is readily diagnosed byexamining a conjunctival smear for Gram-negativeintracellular diplococci (8) — additionally receiveeffective antigonococcal therapy. This is mostconveniently administered as a single intramuscularinjection of spectinomycin, kanamycin, or acefalosporin such as cefotaxime which haspronounced activity against Gram-negativeorganisms (9). The diagnosis of chlamydial diseaseis often established on a presumptive basis whengonococci cannot be detected, since laboratoryconfirmation demands cell culture or testing forspecific antigens. It is less responsive to antibiotics,and a two week course of erythromycin (50 mg/kgdaily in 4 divided doses) is widely used (9).The essential need for protectionEstimates of the prevalence of neonatal ophthalmiain less developed countries range as high as 4% oflive births for gonococcal infection and 8% forchlamydial infection (10). The prevalence of gonorrhoealand chlamydial infections among pregnantwomen in many of these countries is far higher, andin some surveys it has exceeded 20% (1, 2). Thesegrim statistics press home the urgent need to betterprotect the sight of infants throughout the lessdeveloped world by more effective treatment ofsexually transmitted diseases in pregnant women,and more effective chemoprophylaxis of infants atbirth. Meanwhile, considerable effort andexpenditure is directed to an often despairing effortto treat cases of neonatal ophthalmia that couldreadily have been prevented.Opportunity may now be at hand to protect agreater proportion of infants in developingcountries. Case-management of sexuallytransmitted diseases is improving in many countriesas a result of the HIV pandemic. Recentlygenerated evidence suggests that this effort andrelated educational programmes can reduce theprevalence of these infections both in mothers andin babies (11, 12). These improvements, however,can do no more than supplement the need forroutine prophylaxis at the time of delivery. Sincesilver nitrate was first instilled into the eyes ofnewborn infants as a protection against infectionover 100 years ago, this intervention has been themainstay in the management of neonatalophthalmia. Once the practice had become widelyaccepted the incidence of blindness in children innineteenth-century Europe was reduced 20 to 30-fold (13). Precisely the same technique — or somecomparably effective form of prophylaxis —remains a statutory requirement in many highlydeveloped countries. Yet, through lack ofresources, prophylaxis is failing in the leastdeveloped countries, where it is most needed.Erythromycin and tetracycline preparations aresome 20-fold less expensive than silver nitrate andhave been preferred in some centres on the basisof claims that they are more effective againstChlamydia trachomatis and less likely to causesevere toxic conjunctivitis (14,15). However, itseems that the protective efficacy of topicalerythromycin may have been overstated (16-19): inone recent study it did not significantly reduce theoverall incidence of ophthalmia (17); failure rates ashigh as 10 to 20% are quoted for chlamydialconjunctivitis (18); and outbreaks of erythromycinresistantstaphylococcal conjunctivitis have beenreported following its use (19).Tetracycline was found to be significantly superiorto silver nitrate in protecting against bothgonococcal and chlamydial infection in one largecontrolled trial undertaken in Kenya (20). However,concerns about the global prevalence of tetra¬cycline-resistant gonococci (5-7) have accentuatedthe need for a new approach to prophylaxis.Experience with povidone-iodineOne highly-promising candidate prophylacticsubstance is the non-organic broad-spectrumantimicrobial compound, povidone (INN =polyvidone) -iodine. A 2.5% ophthalmic solution canbe prepared at a cost estimated to be 70-fold lessthan that of 1% silver nitrate and 3-fold less thantetracycline ointment (9). In vitro, it is active againsta wide spectrum of microorganisms and noevidence of bacterial resistance has yet beenreported (21). Sensitive organisms include not onlygonococci and chlamydia but also the herpessimplex virus (22), an occasional yet serious causeof an insidious form of keratoconjunctivitis (23).