Ophthalmia Neonatorum Research Articles

Studies of Extracellular and Intracellular Antimicrobial Activity of Povidone-iodine: An Alternative Prophylactic Regimen of Ophthalmia Neonatorum? 1490

Results of recent studies support the clinical efficacy of providone-iodine as a new prophylactic regimen for ophthalmia neonatorum (Isenberg et al, N Engl J Med 1995; 332:562). The present study was performed to better define the antimicrobial action(s) of povidone-iodine, i.e., dosage, time, plasma membrane penetration and toxicity. A series of experiments were performed with an in vitro tissue culture cell system employing human conjuctival and rabbit corneal cells using S. aureus (SA), P. aeruginosa (PA) and N. gonorrhoeae (GC) as test organisms. Assays of extracellular bacterial adherence and intracellular penetration were performed using 1 to 6×106 organisms/ 8×104 tissue culture cells. Effects of 0.5%, 1%, 5%, 7.5% and 10% povidone-iodine on killing of both extracellular and intracellular organisms were measured at 5, 10, and 20 minutes using ciprofloxacin (0.3%) as a methodologic control. The antimicrobial% concentration of povidone-iodine needed for complete killing of extracellular organisms varied with each organism, i.e., GC 1%, SA 5%, PA 10%. Killing of intracellular organisms required greater concentrations of povidone-iodine and was related to the number of intracellular organisms, i.e., SA 4×104 @ 1% vs 1×105 @ 10%; PA 1×103 @ 1% vs 1×104 ± killing @ 10%. Maximal killing of each test organism occurred by 10 minutes and no toxicity was observed in tissue culture cells up to 60 minutes of povidone-iodine treatment. Ciprofloxacin showed less antimicrobial activity than povidone-iodine. Collectively, these results suggest that there is not only a concentration-dependent antimicrobial activity of povidone-iodine, with greatest killing at higher concentrations, but also an organism-specific sensitivity, i.e., GC > SA > PA. Moreover, the results of these studies support the distinct advantages of povidone-iodine prophylaxis for ophthalmia neonatorum over most antibiotics based upon its ability to kill intracellular organisms in addition to its stability, low cost, and its refractoriness to the development of resistance.

Polymerase chain reaction for detection of Chlamydia trachomatis in conjunctival swabs

AIMS/BACKGROUNDOcular Chlamydia trachomatis infection in the west occurs as ophthalmia neonatorum, acquired from the mother, or adult paratrachoma which is also associated with current genital tract infection. Accurate rapid laboratory...

Ophthalmia neonatorum caused by Chlamydia trachomatis. Rapid diagnosis and therapy

In up to 73% of ophthalmia neonatorum, Chlamydia trachomatis is the causative agents. Untreated sequelae to the eyes and organs may be the result. The aim of this study was to determine the bacterial spectrum of ophthalmia neonatorum with special regard to chlamydia and their diagnostic tests. We compared the results of 15 newborn with ophthalmia neonatorum. For the diagnosis we used a rapid diagnostic test, Immunofluorescent Antibody Staining and Culture on McCoy cells. Bacteria that were cultured on culture media were also identified. In 66% the newborn showed a positive rapid diagnostic test result that was confirmed by Immunofluorescent Antibody Staining. In 5 patients all tests were negative. In this study C. trachomatis was the most frequent pathogen. In the culture media we isolated mostly gram-positive cocci but not Neisseria gonorrhoeae. We point out the value of an exact rapid diagnosis and specific treatment to avoid sequelae to the eye and organs.

Neonatal Chlamydial Infections in Massachusetts, 1992-1993

An increase in the numbers of babies reported with Chlamydia trachomatis infections in Massachusetts prompted a review of the medical records of both infants and mothers to evaluate the clinical presentation, the maternal epidemiologic profile, risks of transmission, and the screening practices of health care providers. Medical records of 44/47 infants reported with a chlamydial infection in 1992-1993 were analyzed, as were 40 of the maternal records. Almost all of the infants (39, or 89%) had conjunctivitis, despite the fact that ocular prophylaxis with erythromycin was documented at birth for 34 infants. Five other infants presented with respiratory tract infections without conjunctivitis, and they had all received prophylaxis at birth either with erythromycin (3) or silver nitrate instillation (2). More than one fifth (10, or 22.7%) had a respiratory tract infection. Seventy percent of the mothers were younger than 25. More than 85% were receiving prenatal care by the end of the second trimester. Twenty-five (62.5%) were screened for chlamydia. Nine women tested positive, seven of whom were tested beyond the first trimester. Seventy-five percent of the women who tested negative were tested in the first trimester. This case series supports previous data documenting that ocular prophylaxis can fail to prevent neonatal chlamydial conjunctivitis, and does not prevent colonization or infection at other sites. This study reinforces the importance of primary prevention of neonatal infections through prenatal screening in the third trimester, treatment of infected mothers and their sexual partner(s), and active follow-up.

Chlamydia trachomatis Genital Infections— United States, 1995

GENITAL TRACT infections with<i>Chlamydia trachomatis</i>are a major cause of pelvic inflammatory disease (PID), ectopic pregnancy, and infertility among women, and perinatal transmission of<i>C. trachomatis</i>to infants can cause neonatal conjunctivitis and pneumonia. In 1994, the estimated cost of untreated chlamydial infections and their complications was $2 billion in the United States.¹To determine the number of reported cases of infection and to assess the impact of screening and treatment programs on chlamydial infection in 1995, CDC analyzed notifiable disease surveillance data on chlamydia and data on chlamydia test positivity among women screened in family-planning clinics funded through CDC and the Office of Population Affairs as a result of the Preventive Health Amendments of 1992.^*2This report summarizes the findings of the analysis, which indicate that, although the number of reported cases of chlamydial infection among women continued to increase concomitantly with the expansion of screening

Povidone-Iodine Liposomes – An Overview

In recent years, liposomes have been increasingly explored as novel drug delivery systems, and several liposome-based drug products have been approved in Europe, the USA and Japan. Depending on size, composition and surface characteristics, liposomes interact specifically with biological structures. Liposomal drug products provide a topical activity at the desired locus of action and are deemed more effective and less toxic than conventional drug formulations. The combination of povidone-iodine (PVP-I) and liposomes unites the exceptional microbicidal activity of the antiseptic substance with the excellent tolerability and lack of immunogenicity of liposomes; in addition, liposomes provide a moist molecular film for the wound environment. The multilamellar vesicles act as microreservoirs hence prolonging the release of the active ingredient. Although no commercial product for repeated application on the eye is currently available, PVP-I has been used in ophthalmology not only for pre- and postoperative antisepsis, but also for the treatment of bacterial and viral conjunctivitis and for prophylaxis against ophthalmia neonatorum. For these indications, liposomal formulations with 2.5 and 5.0% PVP-I were developed. These eye drops are isotonic with tear fluid at pH 6. First in vitro tests demonstrated an excellent antimicrobial efficacy, and a placebo-controlled clinical study on volunteers showed a very good local tolerability. A study on rabbits demonstrated positive results of the PVP-I liposome eye drops compared to placebo and the broadspectrum antibiotic Polyspectran in a standardized model of Staphylococcus aureus deep eye infection. The other aim is a well-tolerated liposomal PVP-I hydrogel for improved antiseptic wound treatment with moisturizer. It has been reported that liposomes are enriched at the wound bottom for direct action against infection and support of wound healing. An animal study on the efficacy and tolerability of different formulations of a hydrogel with PVP-I liposomes in deep dermal burn wounds has indicated an outstanding quality of wound healing with smooth granulation tissue, less inflammation, less wound contraction and no hyperkeratotic reactivity, especially with the 3% PVP-I liposome formulation.

Prophylactic use of topical anti-infectives in ophthalmology.

The prophylactic use of topical anti-infectives is indicated on the eye (1) prior to any surgery on the eye, by periorbital and conjunctival administration and, if required, intraoperatively as well; (2) in the form of the Credé prophylaxis against ophthalmia neonatorum; (3) with accidental pathogenic contamination of the eye; (4) to prevent conjunctivitis by intensive care surgical patients; (5) for the antiseptic irrigation of donor bulbi prior to keratoplasty, and (6) if required, to prevent ocular infection in a given epidemiological situation. The drug of first choice is polyvinylpyrrolidone-iodine at a concentration ranging from 1.5 to 5%. Another topical anti-infective is a 0.02 or 0.01% solution of polyhexanide, a promising medication, currently in the process of being approved.

Treatment of chlamydial conjunctivitis.

Adult inclusion conjunctivitis and neonatal inclusion conjunctivitis are important infectious diseases commonly encountered by ophthalmologists in industrialized countries. Patients with inclusion conjunctivitis are frequently complicated by genitourinary and epipharyngeal chlamydial infections. Thus, treatment of chlamydial conjunctivitis must include systemic antibiotics and not be limited to topical application of antibiotics to the eye. Effective anti-chlamydial agents include tetracyclines, macrolides, and some of the fluoroquinolones. Prolonged and frequent application of ophthalmic agents is vital for successful treatment of conjunctivitis.

In vitro activity of human milk against the causative organisms of ophthalmia neonatorum in Benin City, Nigeria.

The aim of the study was to evaluate the in vitro activity of term human milk on the organisms of Ophthalmia neonatorum and was a prospective study of consecutive neonates with the organism. The study was undertaken in a special care baby unit/lying-in ward in Benin City, Nigeria, and consisted of 22 neonates with ophthalmia neonatorum. Bacterial organisms grown on blood agar, were obtained from eye swabs of neonates with ophthalmia neonatorum. Inoculated isolates were incubated with known antibiotic discs, term colostrum, and mature milk. Bacteria were isolated in 77 per cent (17/22) of the neonatal eye swabs, 59 per cent of which were Staphylococcus aureus and 41 per cent coliform organisms. Sensitivity of Staphylococcus aureus to gentamicin was 100 per cent and for coliform organisms 42 per cent. The sensitivity of Staphylococcus aureus to term colostrum was 50 per cent and to mature milk 0. Coliform organisms had a sensitivity of 57 per cent to colostrum and 28 per cent to mature milk. The zone of inhibition of colostrum against Staphylococcus aureus and coliform organisms was between 3 and 5 mm, while for mature milk, there was partial or no inhibition, respectively, to coliform organisms and Staphylococcus aureus. The mean duration of inhibition was 6 hours for colostrum and 3 hours for mature milk. Colostrum has about half the in vitro inhibitory activity of gentamicin (recommended as a first line topical agent, based on the bacteriological sensitivity of this study) against Staphylococcus aureus and coliform organisms. The inhibitory activity of colostrum is > or = 50 per cent against Staphylococcus aureus and coliform organisms for a mean duration of 6 hours. Mature milk had no inhibitory activity against Staphylococcus aureus and only 28 per cent inhibition, for a mean duration of 3 hours to coliform organisms.

Ophthalmia neonatorum in the United Arab Emirates.

Ophthalmia neonatorum in small babies is a common problem in neonatal units in Al Ain, but is infrequently associated with sexually transmitted disease agents. A study of 81 babies with ophthalmia neonatorum showed that 81.5% had bacterial or fungal infections. Staphylococcus aureus was the commonest causative organism followed by Escherichia coli and Pseudomonas aeruginosa while Chlamydia trachomatis and Neisseria gonorrhoeae were responsible for less than 5% of all cases. The disease was predominantly mild to moderately severe and easily treated with topical broad-spectrum antibiotic agents which are effective against Gram-positive and Gram-negative bacteria, including hospital-associated strains. The most effective antimicrobial agents were gentamicin topically or ceftriaxone systemically.

A controlled trial of povidone-iodine as prophylaxis against ophthalmia neonatorum: Isenberg S.J.; Apt L.; Wood M. USA New Engl J Med 1995 332/9 (562–5660)

A controlled trial of povidone-iodine as prophylaxis against ophthalmia neonatorum: Isenberg S.J.; Apt L.; Wood M. USA New Engl J Med 1995 332/9 (562–5660)

A controlled trial of povidone-iodine as prophylaxis against ophthalmia neonatorum

A controlled trial of povidone-iodine as prophylaxis against ophthalmia neonatorum

A Controlled Trial of Povidone-Iodine as Prophylaxis Against Opthalmia Neonatorum

Department of Opthamology, Jules Stein Eye Institute, Harbor-UCLA School of Medicine, Los Angeles and Torrance, California and the Eye Department, Presbyterian Church Hospital, Kikuyu, Kenya. N Engl J Med 1995;332:562-566

Acute Conjunctivitis

Conjunctivitis, or inflammation of the conjunctiva, usually occurs as a result of infection or allergy. It is an exceedingly common occurrence, certainly the most common acute disease of the eye seen by primary care physicians of children. When it occurs in the neonatal period, it has been given the appellation ophthalmia neonatorum; in older infants and children, it sometimes is called "pink eye." This review covers the etiology, epidemiology, pathogenesis, diagnosis, and therapy of conjunctivitis in infants and children. Etiology Neonatal conjunctivitis occurs in 1.6% to 12% of newborns during the first month of life. The chemical irritation from antimicrobial prophylaxis against bacterial infection is the most frequent cause, followed by Chlamydia trachomatis infection. Other important pathogens in this setting are Haemophilus influenzae and Streptococcus pneumoniae. It is unusual to isolate any of these organisms from healthy eyes. Various streptococci and Staphylococcus aureus have been isolated not only from significant numbers of infected eyes, but also from a substantial number of healthy eyes, leaving their exact role less clear. Rarely, gram-negative organisms such as Escherichia coli, Klebsiella, or Pseudomonas sp have been implicated as causes of neonatal conjunctivitis, especially in infants in intensive care units. Neisseria gonorrhoeae no longer is a major cause of neonatal conjunctivitis in this country because of the mandated use of neonatal ocular prophylaxis.

Povidone-iodine for Ophthalmia Neonatorum Prophylaxis

The agents currently used to prevent ophthalmia neonatorum are less than optimal, with reports indicating evidence of bacterial resistance, ineffectiveness, and toxicity. Povidone-iodine ophthalmic solution, which has been shown to be effective in the preoperative preparation of the eye, generates no resistance, is an effective antimicrobial agent, and has low toxicity. We evaluated the effectiveness and safety of povidone-iodine for ophthalmia neonatorum prophylaxis. A bacterial culture was taken from the conjunctiva of each eye of 100 infants within 30 minutes of birth. A drop of 2.5% povidone-iodine solution was then placed on one eye, while the other eye received either one drop of silver nitrate 1% ophthalmic solution or 0.5% erythromycin ointment. Conjunctival bacterial cultures were again taken two to four hours after birth. At each culture and at 24 hours after birth, the eyes were examined for toxic changes. To measure the effectiveness of the medications, the number of bacterial colony-forming units and species from each culture was compared. All three agents significantly reduced the number of colony-forming units, but povidone-iodine caused the most significant decrease. The number of species was reduced significantly by povidone-iodine (P = .00051) and silver nitrate (P = .007), with povidone-iodine yielding the most significant decrease. Erythromycin did not significantly reduce the number of species. Silver nitrate demonstrated more ocular toxicity at the 24-hour determination point than did either of the other two medications (P < .001). Povidone-iodine 2.5% ophthalmic solution is an effective antibacterial agent on the conjunctiva of newborns and causes less toxicity than silver nitrate.

Child health in Malaysia.

In Malaysia the Ministry of Healths (MOH) general hospitals in each state and some larger district hospitals provide pediatric specialty services. The countrys only childrens hospital provides pediatric subspecialty services and is the ultimate referral center for Malaysia. MOH operates maternal and child health clinics. Common child health problems are communicable diseases and malnutrition. Emerging problems are HIV infection chloroquine resistant malaria severe dengue (encephalopathy renal failure fulminant hepatopathy) gonococcal ophthalmia neonatorum and asthma. Child morbidity and other problems related to social changes include child physical and sexual abuse accidents runaways and drug abuse. MOH child-centered prevention activities are primary immunization vitamin K prophylaxis against hemorrhagic disease of the newborn and glucose-6-phosphate dehydrogenase screening in newborns to prevent favism. Malaysia will soon expand the child health card system nationwide. This system allows the parents to record and monitor their childs growth development and immunization status. Malaysia promotes the baby-friendly hospital concept to encourage breast feeding. New technologies are bone transplant and kidney transplant capabilities availability of new drugs (e.g. interferon) magnetic resonance imaging at a MOH hospital and neonatal intensive care units. MOH operates a quality assurance program. The Malaysian Paediatric Association oversees and advises on the quality of pediatric care in the country. The larger cities have the best health facilities. Families only take children to the hospital after treatment by traditional healers has failed. Pediatric research is commonplace. In 1992 MOH hospitals only had 48 pediatricians compared to around 100 in private practice and teaching hospitals. There is also a shortage of nurses. Some private hospitals have begun training their own nurses. In the past only MOH and university hospitals trained them.

Antimicrobial Prophylaxis

The issue of antimicrobial prophylaxis in preventing infections in infants and children is important in the practice of pediatrics. Children are especially prone to certain infections, and pathogens are amenable to prophylaxis. Chemoprophylaxis may be used to prevent primary disease (eg, ophthalmia neonatorum) or recurrent infections (eg, otitis media). Individuals exposed to certain micro-organisms (eg, Neisseria meningitidis) or immunosuppressed patients (eg, those who are asplenic) may benefit from prophylaxis in certain situations. The duration of chemoprophylaxis may be as short as two doses (eg, endocarditis prophylaxis) or may last a lifetime (eg, rheumatic fever prophylaxis). Questions concerning the potential benefits of antimicrobial prophylaxis are quite common, and many of the answers are controversial. Because the list of specific pathogens and conditions for prophylaxis is quite long, this review will encompass only the more common conditions encountered in a busy general pediatric practice (Table 1). Otitis Media Acute otitis media is the most common diagnosis made in children when visits to the physician are prompted by illness. For every three children who have acute otitis media with effusion, one will suffer from recurrent acute otitis media: antimicrobial prophylaxis, tympanostomy tube placement, and adenoidectomy. Of these options, only chemoprophylaxis can be managed by the primary physician.

CHLAMYDIAL INFECTIONS

SUMMARY Chlamydiae are among the most successful bacterial pathogens, and there are few branches of medicine on which chlamydial infection and its sequelae do not impinge. Chlamydia trachomatis is responsible for many million cases of blindness, pelvic inflammatory disease, urethritis, epididymitis, infertility and ectopic pregnancy annually; it also causes lymphogranuloma venereum, reactive arthritis, ophthalmia neonatorum and infantile pneumonia. C. pneumoniae is among the most common causes of community‐acquired pneumonia, and recent evidence suggests that it may play a part in the pathogenesis of coronary heart disease. C. psittaci is a highly prevalent zoonotic infection with a wide host range. It is of great economic importance, and causes sporadic but sometimes devastating disease in humans. Most chlamydial infections are subclinical, but even if the initial illness is mild there may be serious long‐term sequelae. It is therefore important to identify and treat chlamydial infections in their early stages, but diagnosis usually depends on laboratory tests. Recent trials have shown that single doses of the long‐acting macrolide azithromycin are effective in the treatment of genital and ocular C. trachomatis infection, but longer courses of antimicrobials remain the mainstay of treatment for C. pneumoniae and C. psittaci infections.

Ophthalmia neonatorum in a trachoma endemic area.

Chlamydia trachomatis can be directly transmitted by sexual or perinatal contact and indirectly transmitted by flies or fomites. Whether distinct epidemiologic forces among human populations or biologic characteristics of the organism are responsible for the different routes of transmission is uncertain. To determine if ophthalmia neonatorum and trachoma are linked epidemiologically, 38 infants with ophthalmia and 277 children with trachoma were studied for evidence of C. trachomatis infection using culture, antigen and DNA detection tests. The study was performed in a trachoma endemic area of central Kenya. Of infants with ophthalmia neonatorum, 8% to 9% had microbiologic evidence of ocular C. trachomatis infection. Of the children with trachoma, 31% had evidence of chlamydial infection. Ninety-two percent of the 59 identified strains causing trachoma belonged to the classic trachoma serovars (A, B, Ba and C). Neither of the two chlamydial strains recovered from infants with ophthalmia was a trachoma serovar. Mothers rarely (3%) had cervical C. trachomatis infection. This study does not support a major role for perinatally transmitted C. trachomatis infection in trachoma epidemiology.

Comparative Diagnosis of Neonatal Chlamydial Conjunctivitis by Polymerase Chain Reaction and McCoy Cell Culture

Cervical and ocular swabs from 100 mother/newborn pairs delivering on the clinic service were assayed for Chlamydia trachomatis with standard McCoy cell culture and with standard and biotinylated polymerase chain reaction techniques, using primers directed against the major outer membrane protein gene and C. trachomatis-specific cryptic plasmid, respectively. Using the polymerase chain reaction, 20 (20%) mothers and seven (7%) neonates were positive for Chlamydia. All neonates positive by polymerase chain reaction were from mothers positive by polymerase chain reaction, yielding a 35% transmission rate. Only five of 20 (25%) mothers and two of seven (28%) neonates positive by polymerase chain reaction were positive by cell culture. All cell culture samples were positive by polymerase chain reaction testing. Culture and polymerase chain reaction analysis two weeks after treatment with oral erythromycin were negative. The polymerase chain reaction assay appears to be equally specific and more sensitive than McCoy cell culture for the detection of C. trachomatis from ocular specimens.