Is Ophthalmia Neonatorum Associated With Invasive Bacterial Infection? A Single-Center Retrospective Study.

OBJECTIVE: Ophthalmia neonatorum (ON) is a conjunctivitis occurring in neonates and can be caused by multiple bacterial pathogens. The risk of invasive bacterial infection (IBI) in neonates with ON is poorly known. Our objectives were to document the association of ON with IBI in term neonates and to investigate practice variation. METHODS: This was a retrospective observational study of all neonates who presented to a single emergency department (ED) between January 2018 and December 2019. Participants were all children with a final diagnosis of ON according to the treating physician as registered in the ED computerized database. Newborns with craniofacial malformations and premature infants were excluded. The primary outcome was IBI as defined by growth of any bacterial pathogen in the blood or cerebrospinal fluid. Perinatal risk factors, ED visit details (symptoms on presentation, management, and treatment plan) as well as complications (ocular morbidity, death, and unscheduled return visits) were collected. Data were analyzed using descriptive statistics. RESULTS: Fifty-two term neonates were included. There were no cases of IBI associated with ON (0%; 95% confidence interval [CI], 0%-6.9%). Six ocular bacterial infections were identified, one of which was Chlamydia trachomatis . Although there were no IBIs, ocular complications, deaths, or unscheduled return visits to the ED, there was a wide variation in physician's management of ON. Physicians ordered investigations in 49% (95% CI, 34%-62%) of neonates, prescribed antibiotics to 87% (95% CI, 74%-94%), and involved specialists in 39% (95% CI, 27%-52%) of cases. CONCLUSIONS: Emergency department presentations of term neonates with ON are associated with a low risk of IBI. A better understanding of the current practice variation is needed to inform clinical guidelines for the management of neonates with ON presenting to the ED.

Case series and literature review of chlamydial ophthalmia neonatorum in Botswana.

BACKGROUND: We describe 12 cases of chlamydial ophthalmia neonatorum and the current scientific evidence on its prevention and treatment. The data presented were obtained from the "Maduo" study, a prospective observational study of the relationship between curable sexually transmitted infections and adverse neonatal outcomes at four antenatal clinics in Gaborone, Botswana. METHODS: Infants of mothers with perinatal chlamydia infection were evaluated for chlamydial ophthalmia neonatorum based on clinical presentation of conjunctivitis or positive test via GeneXpert CT/NG assay. Data on 29 infants born to mothers with postnatal C. trachomatis infection were analysed. RESULTS: 12 infants were diagnosed with chlamydial ophthalmia neonatorum. Eight of those cases were confirmed with the GeneXpert CT/NG assay while four were identified as probable cases based on clinical history and presentation. Overall, nine infants presented with signs of conjunctivitis, while three who had a positive diagnostic test result had asymptomatic infection. All but one infant had received ocular 1% tetracycline prophylaxis at birth, and four infants had signs suggestive of chlamydial pneumonia at presentation. Two out of five symptomatic cases whose mothers reported completion of their treatment course with erythromycin had lingering symptoms. CONCLUSIONS: Our findings affirm that the current prophylaxis and treatment modalities for chlamydial ophthalmia neonatorum are inadequate. To the extent feasible in low- and middle-income countries, we recommend implementation of routine C. trachomatis screening and treatment in pregnant women.

Neonatal ocular prophylaxis in the United States: is it still necessary?

INTRODUCTION: Much has changed since Credé reported that silver nitrate decreases the incidence of ophthalmia neonatorum. Prenatal screening and treatment of pregnant women for Neisseria gonorrhoeae became standard in the 1950s and for Chlamydia trachomatis in 1993. Neonatal gonococcal and chlamydial conjunctivitis are consequently uncommon today. Currently, only 0.5% erythromycin ophthalmic ointment is available in the United States (U.S.) for neonatal ocular prophylaxis, which is ineffective against C. trachomatis. AREAS COVERED: This article addresses the altered epidemiology of ophthalmia neonatorum in the U.S. since prophylactic practices began, the lack of data supporting ophthalmic erythromycin for prevention of neonatal gonococcal and chlamydial conjunctivitis, and the impact of prenatal screening and treatment of pregnant women for N. gonorrhoeae and C. trachomatis on conjunctivitis incidence. The authors discuss why erythromycin ophthalmic ointment is likely ineffective against gonococcal ophthalmia, including the development of macrolide resistance. Physiologic limitations and pharmacokinetic properties are considered with respect to ophthalmic erythromycin for the prevention of gonococcal and chlamydial conjunctivitis. EXPERT OPINION: Administration of erythromycin ophthalmic ointment for the prevention of neonatal conjunctivitis is not literature-supported. Prenatal screening and treatment of pregnant women is the most effective way to prevent ophthalmia neonatorum. National mandates for prophylaxis should be withdrawn.

Universal ophthalmia neonatorum prophylaxis in Ontario: a cost-effectiveness analysis.

BACKGROUND: Although prophylaxis for ophthalmia neonatorum at birth is required by law in Ontario, declining prevalence of disease and efficacy of prophylaxis have called this practice into question. The objective of this modelling study was to assess the cost-effectiveness of universal prophylaxis for ophthalmia neonatorum to inform decision-makers on the potential impact of a change in this policy. METHODS: We compared the cost-effectiveness of prophylaxis for ophthalmia neonatorum with no prophylaxis through cost-utility analysis with a lifetime time horizon, considering a provincial government payer, for a hypothetical population of newborns in Ontario. We assessed both the mean incremental costs of prophylaxis and its mean incremental effectiveness using a hybrid (part decision tree, part Markov) model. We used a scenario analysis to evaluate alternative time horizons and discount rates. We conducted a threshold analysis to evaluate the impact of variations in the cost of prophylaxis and in the prevalence of sexually transmitted infections (gonorrhea and chlamydia). RESULTS: In our model, prophylaxis for ophthalmia neonatorum did not meet a willingness-to-pay threshold of Can$50 000 per quality-adjusted life-year (QALY). Although prophylaxis was effective in reducing morbidity associated with ophthalmia neonatorum, the number needed to treat to prevent 1 case of ophthalmia neonatorum blindness was 500 000, with an associated cost of more than Can$4 000 000. When compared with no prophylaxis, prophylaxis had an incremental cost of Can$355 798 per long-term QALY gained (incremental cost-effectiveness ratio). INTERPRETATION: We found that prophylaxis for ophthalmia neonatorum, although individually inexpensive, leads to very high costs on a population level. These findings contribute to the discussion on mandatory prophylaxis currently underway in several jurisdictions.

A Newborn with a Purulent Ocular Discharge.

An 11-day-old girl, who was diagnosed with Neisseria gonorrhoeae ophthalmia neonatorum, presents with a purulent ocular discharge. Although rare in regions with high implementation rates of ocular prophylaxis, ophthalmia neonatorum remains an important diagnostic consideration, especially in developing countries and areas of low socioeconomic status. In this article, we review the evolving epidemiology, diagnostic considerations, prevention, and treatment of ophthalmia neonatorum. [Pediatr Ann. 2022;51(5):e206-e208.].

Ophthalmia neonatorum in a tertiary referral children's hospital: A retrospective study.

OBJECTIVES: The purpose of this study was to examine the aetiology, investigation and management of ophthalmia neonatorum (ON) presenting to a tertiary referral children's hospital over 5 years. METHODS: The eye swab data of all neonates presenting to Children's Health Ireland at Temple Street (Dublin, Ireland) between 1st January 2013 and 3rd September 2018 was analysed. The medical records of all patients with positive eye swab results were retrospectively reviewed. RESULTS: A total of 157 neonates had positive eye swab results. 54 cases were identified as ON. Chlamydia trachomatis (20.4%) was the most common organism identified, followed by Staphylococcus aureus (18.5%), Haemophilus influenzae (14.8%), Moraxella catarrhalis (7.4%), Streptococcus pneumoniae (5.6%), Escherischia coli (3.7%), Klebsiella pneumoniae (1.9%) and Pseudomonas aeruginosa (1.9%). A bacterial culture swab was tested in all cases (100%), a C. trachomatis/N. gonorrhoeae PCR swab in 70.4% and a viral PCR swab in 35.2%. On subanalysis of the cases that had C. trachomatis/N. gonorrhoeae PCR testing, C. trachomatis was responsible for 28.9% of cases. 50% of cases were hospitalised, intravenous antibiotics were administered in 46.3% and macrolide therapy was prescribed in 38.9%. CONCLUSIONS: C. trachomatis was the most common cause of ON in this study and may be responsible for an even higher proportion of cases due to incomplete testing. In keeping with studies in different populations, S. aureus, H. influenzae and S. pneumoniae were also common. As a result, an improved management algorithm for cases of ON has been introduced in this centre.

Ophthalmia neonatorum as the presenting sign of SARS-CoV-2.

The most common ocular manifestation of SARS-CoV-2 in adults and children is acute conjunctivitis. We report the case of a 4-day-old infant who presented with acute-onset mucopurulent discharge of the left eye as well as subconjunctival hemorrhage and palpebral injection, without corneal findings. A diagnosis of ophthalmia neonatorum was established, for which ocular cultures and Gram staining were performed. No bacterial growth was noted, and polymerase chain reaction (PCR) testing for Chlamydia trachomatis, Neisseria gonorrhea, and herpes simplex were negative. Nasopharyngeal and conjunctival SARS-CoV-2 PCR were positive. Given the identification of SARS-CoV-2 illness, lack of other underlying bacterial or viral etiology on testing, and the well-documented ability for SARS-CoV-2 to cause conjunctivitis, the clinical picture was supportive of ophthalmia neonatorum secondary to SARS-CoV-2. The infant was treated with ceftriaxone and azithromycin prior to culture results. During admission, no systemic findings of Covid-19 illness were observed.

Using Historical Data to Support Approval of Drug Products for Ophthalmia Neonatorum: Innovative Approach Toward Evidence-Based Medicine.

Importance: Off-label treatment was common for ophthalmia neonatorum because only erythromycin ointment had been approved by the US Food and Drug Administration (FDA) for this indication. Ophthalmia neonatorum was previously considered a different indication from bacterial conjunctivitis in older children and adults because of uncertain similarities in the cause of disease and the treatment course between the 2 populations. Prospective therapeutic clinical studies were required to demonstrate the effectiveness of treatment for ophthalmia neonatorum. Objective: To review the therapeutic clinical trials for patients with bacterial conjunctivitis to evaluate the similarity in the cause of disease and the treatment response between neonates and older children and adults. Design, Setting, and Participants: In this comparative effectiveness research review of pooled data from the most recent 30 bacterial conjunctivitis trials (N = 2018) submitted to the FDA to support the approval of topical ophthalmic solutions for older children and adults, 95% CIs were constructed from clinical cure rates. Cure rates in 3 neonatal randomized clinical trials (N = 392) of patients treated with ophthalmic anti-infective solutions of ciprofloxacin, gatifloxacin, and moxifloxacin were constructed and compared. The baseline ocular swab cultures were analyzed. Main Outcomes and Measures: Cure rates of neonatal trials were compared with the 95% CIs among older children and adults. The bacterial organisms isolated from these 2 populations were compared. Results: The 3 neonatal trials enrolled a total of 392 patients, and the 30 trials of older children and adults enrolled a total of 2018 patients. Neonatal clinical cure rates for moxifloxacin (day 4, 48%), ciprofloxacin (day 4, 49%; day 5, 61%), and gatifloxacin (day 7, 79%) were within the 95% CI for products approved to treat older children and adults with bacterial conjunctivitis. Bacterial organisms were consistent between these 2 populations. Conclusions and Relevance: Comparison of the pooled analysis of these historical trial data suggests similarity in the cause of disease and the treatment response between neonates and older children and adults with bacterial conjunctivitis. Therefore, it was appropriate to extrapolate the effectiveness from older children and adults to neonates to support the approval of therapies for ophthalmia neonatorum. Based on this analysis, ophthalmic solutions of ciprofloxacin, gatifloxacin, and moxifloxacin are now approved for all age groups. This analysis presents an approach of using pooled data from previously underpowered individual trials to establish the similarities in the cause of disease and in treatment response between children and adults, which are the fundamental elements used to evaluate whether extrapolation of effectiveness can be used to support drug approval.

Prophylaxis for ophthalmia neonatorum in Brazil: A snapshot using a multi-professional national survey.

BACKGROUND: Brazil is a large country with an elevated incidence of Chlamydiatrachomatis (CT) and Neisseriagonorrhoeae (NG) during pregnancy and variable access to health care. The objective of the study was to identify ophthalmia neonatorum prophylaxis practices in the country. METHODS: A prospective multidisciplinary survey was conducted using a closed social media group. Fifteen questions were developed after literature review. Specific content included categorization of respondents and practices such as type of medication, age at administration, occurrence of clinical and/or chemical conjunctivitis and microbiology identification. Questions were multiple choice, but some allowed written response. RESULTS: A total of 1.015 professionals responded, representing 24 states (92%) and 181 cities; mainly neonatologists (64%) and general pediatricians (21%). 96% of respondents reported performing prophylaxis at their institutions, mostly at birth or <1 h of life (99%), and regardless the mode of delivery (73%). Frequently used medications are: 1% silver nitrate (64%), 2.5% povidone iodine (18%) or 10% silver vitelinate (12%), with some regional variations. Occurrence of chemical conjunctivitis was stated by 58% of the respondents and microbiology identification was unusual. CONCLUSIONS: Ophthalmia neonatorum prophylaxis Brazil is almost universal and mainly performed by the use of anti-septic medications, with some regional variability. However, identification and treatment of CT and NG in both parents and newborns is not accomplished.

Gonococcal infection: An unresolved problem. / Infección gonocócica: un problema aún sin resolver.

Gonococcal infection is a current public health problem worldwide, being the second most prevalent bacterial sexually transmitted infection. The etiologic agent is Neisseria gonorrhoeae, a gram-negative diplococcus, and mainly causes urethritis in men. In women up to 50% of infections can be asymptomatic. N. gonorrhoeae has a great ability to develop antibiotic resistance, so the last remaining therapeutic option are extended spectrum cephalosporins. Many guides recommend dual therapy with ceftriaxone and azithromycin, but in recent years the resistance to azithromycin is also increasing, so that dual treatment is being questioned by scientific societies.

Gonococcal Conjunctivitis in Adults: Case Report and Retrospective Review of Cases in Alberta, Canada, 2000-2016.

BACKGROUND: A case of gonococcal conjunctivitis (GC) prompted us to review the reported cases and treatment regimens of GC in Alberta, Canada. METHODS: Gonococcal cases reported from 2000 to 2016 were extracted from the provincial sexually transmitted infection reporting database. The diagnosis of GC was based on a positive culture and/or nucleic acid amplification test from the eye. RESULTS: A total of 45 cases of GC were reported in adults. Three quarters (75.6%; n = 34) of the cases were diagnosed using culture, 57.8% (n = 26) of cases were among men, and 55.5% (n = 25) were diagnosed since 2014. Very few (13.3%; n = 6) of the cases were treated according to current Canadian Guidelines on Sexually Transmitted Infections, using 2 g of ceftriaxone in combination with azithromycin or doxycycline. Results of test of cures were available for 15.6% (n = 7) of the cases and occurred within 10 to 79 days (median = 26 days) after treatment; all were negative. CONCLUSIONS: Gonococcal conjunctivitis was relatively uncommon in our region, but given its potential for severe manifestations and sequelae coupled with the rising rates of gonorrhea; it remains important to consider this diagnosis in sexually active individuals presenting with purulent conjunctivitis. Additional studies are needed to inform treatment recommendations and to evaluate outcomes of infection.

A Survey of Current Prophylactic Treatment for Ophthalmia Neonatorum in Croatia and a Review of International Preventive Practices.

BACKGROUND Ophthalmia neonatorum, or neonatal conjunctivitis, is an acute infection that occurs within the first 28 days of life. This aim of this survey was to evaluate the current methods of preventive treatment for ophthalmia neonatorum in maternity hospitals in Croatia. MATERIAL AND METHODS The annual hospital birth rate in Croatia is approximately 40,000. A clinical survey was undertaken with data collected using questionnaires sent to all 32 maternity hospitals in Croatia. There was a 100% response rate to the questionnaires. RESULTS Preventive treatment for ophthalmia neonatorum was administrated to all newborns in 75% (24/32) of Croatian maternity hospitals. In 45.8% of maternity hospitals, (11/32) these procedures were performed within the first hour after birth. In 54.2% of maternity hospitals (13/32), preventive treatment for ophthalmia neonatorum was administrated to all newborns from one to three hours after birth. The main treatment agent was tobramycin (83.3%). Other topical prophylactic treatments included povidone-iodine (8.3%), erythromycin (4.2%), and silver nitrate (4.2%). In 25% of obstetric units, prophylaxis for ophthalmia neonatorum was not used routinely, but in cases of diagnosed neonatal conjunctivitis, antibiotic treatment with tobramycin was mainly used. CONCLUSIONS A survey of all 32 maternity hospitals in Croatia showed variation in the prevalence of preventive treatment for ophthalmia neonatorum and the methods used. These findings support the need to implement standardized preventive measures that both conform to international clinical guidelines and recognize treatment availability in Croatia, where topical povidone-iodine is currently preferred for the prevention of ophthalmia neonatorum.

Mutations in Neisseria gonorrhoeae grown in sub-lethal concentrations of monocaprin do not confer resistance.

Neisseria gonorrhoeae, due to its short lipooligosaccharide structure, is generally more sensitive to the antimicrobial effects of some fatty acids than most other Gram negative bacteria. This supports recent development of a fatty acid-based potential treatment for gonococcal infections, particularly ophthalmia neonatorum. The N. gonorrhoeae genome contains genes for fatty acid resistance. In this study, the potential for genomic mutations that could lead to resistance to this potential new treatment were investigated. N. gonorrhoeae strain NCCP11945 was repeatedly passaged on growth media containing a sub-lethal concentration of fatty acid myristic acid and monoglyceride monocaprin. Cultures were re-sequenced and assessed for changes in minimum inhibitory concentration. Of note, monocaprin grown cultures developed a mutation in transcription factor gene dksA, which suppresses molecular chaperone DnaK and may be involved in the stress response. The minimum inhibitory concentration after exposure to monocaprin showed a modest two-fold change. The results of this study suggest that N. gonorrhoeae cannot readily evolve resistance that will impact treatment of ophthalmia neonatorum with monocaprin.

Gonococcal ophthalmia neonatorum: a case report.

A baby born at home 14 hours earlier was brought to the neonatology department with bilateral upper palpebral chemosis with purulent secretions and pseudomembranes, with no general signs of infection. The gram staining of a secretion sample shows the presence of Neisseria gonorrhoeae. Intramuscular ceftriaxone treatment was initiated, combined with topical application of rifamycin, dexamethasone, and oxytetracycline. Complete healing without sequelae was obtained after two weeks. This case presents an opportunity to review this preventable pathology and its treatment. The only effective way to prevent it is to raise the awareness of disadvantaged population about the value of antenatal care.

[Gonococcal ophthalmia neonatorum: Clinical illustration, prevention, and future prospects]. / Conjonctivite néonatale à Neisseria Gonorrhoeae : illustration clinique, prophylaxie et perspectives d'avenir.

A 6-day-old infant presented with a bilateral suppurative ocular discharge with a conjunctival erythema. Polymerase chain reaction was performed on the pus and showed the presence of Neisseria gonorrhoeae DNA. Therapy with intravenous cefotaxime was initiated and completed with local application of tobramycin. This infection was associated with a small unilateral corneal lesion, with rapid resolution. This case provides the opportunity to focus on newborn suppurative conjunctivitis and its treatment. The different prophylaxes available (silver nitrate, povidone-iodine, local antibiotics, etc.) and their respective advantages and disadvantages are reviewed. There is no clear consensus on the most effective solution. Additionally, universal prophylaxis is challenged in several countries, where it is no longer recommended.

Ophthalmia neonatorum treatment and prophylaxis: IPOSC global study.

INTRODUCTION: Characteristics of ophthalmia neonatorum (ON) amongst paediatric ophthalmologists remain unclear. The purpose of this current study is to examine the incidence, diagnosis, treatment, and prophylaxis of ON cases presenting to members of the American Association of Paediatric Ophthalmology and Strabismus (AAPOS). METHODS: An email containing a web link to a survey was sent to all members of AAPOS. The questionnaire examined the incidence of ON, etiology, diagnostic methods, treatment, and prophylaxis of the disease in different countries around the world. RESULTS: Two hundred and ninety-one ophthalmologists answered the questionnaire. Most were from North America (52.94 %). One hundred and seventy-six (60.69 %) ophthalmologists encountered 0-5 cases of ON per year. The most common pathogens causing ON was Chlamydia trachomatis (35.37 %). Two hundred and forty-two (85.21 %) treat empirically when encountering ON during the first 10 days of life and 205 (75.09 %) after the first 10 days of life. In both cases, erythromycin was the most common first line of treatment. Two hundred and twenty-two (78.72 %) ophthalmologists replied that prophylactic treatment is required in their country. The most common agent for prophylaxis was erythromycin ointment (71.50 %). CONCLUSIONS: We found that the incidence of ON per year per practitioner is 0-5 cases, the most common etiology is C. trachomatis, and most infants receive prophylaxis and treatment.

Klebsiella pneumonia: An unusual cause of ophthalmia neonatorum in a healthy newborn.

Ophthalmia neonatorum is one of the most common infections during the neonatal period. Chlamydia trachomatis and Neisseria gonorrhoea must be ruled out, given their high virulence and systemic complications. We describe a case of ophthalmia neonatroum from Klebsiella pneumonia. Gram-negative organisms have been reported in hospital-acquired conjunctivitis (HAC), but we are unaware of any published reports of K. pneumonia conjunctivitis in an otherwise healthy full-term infant born in the United States who has received prophylaxis. It is important to promptly identify and treat Klebsiella conjunctivitis because it can lead to severe complications.