Gonococcal Conjunctivitis


Article Author:
John Costumbrado


Article Editor:
Sassan Ghassemzadeh


Editors In Chief:
Shane Havens
Jim Wang
Koushik Tripathy


Managing Editors:
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
Kristina Soman-Faulkner
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John Shell
Matthew Varacallo
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Hajira Basit
Phillip Hynes


Updated:
2/15/2019 4:09:18 PM

Introduction

While typically thought of as a disease in neonates, gonococcal conjunctivitis (GC) is an infectious process that has also become an increasing issue in other age groups. When it occurs in neonates, GC is also known as gonococcal ophthalmia neonatorum and is most likely due to maternal transmission during birth. In older age groups, GC is more associated with sexually transmitted infections (STIs) but can also present without evidence of concomitant genital infection. The condition is important to recognize as untreated cases can lead to significant life-threatening like meningitis and/or altering consequences for patients, for example, blindness.[1][2][3][4]

Etiology

GC is due to ophthalmic infection with Neisseria gonorrhoeae, which is a gram-negative diplococcus. In neonates, transmission of N. gonorrhoeae and subsequent development of GC often occurs during delivery and exposure to infectious vaginal secretions. This occurs since the mucosa of the cervix and urethra of infected mothers can act as bacterial reservoirs. Even with delivery via cesarean section, vertical transmission of N. gonorrhoeae is still possible. Approximately 10% of neonates exposed to gonorrheal exudates during delivery may go on to develop GC, even with appropriate prophylaxis. In populations other than neonates, transmission can occur via direct sexual contact with infective secretions or indirectly, for example via manual or fomite transmission, though this is thought to be less likely since N. gonorrhea does not typically survive more than a few minutes outside the human body. There has also been evidence that suggests that GC could potentially be due to different strains of gonococci that are not associated with STIs.[5][6][7]

Epidemiology

Worldwide, the incidence of gonococcal infection in the newborn is less than 1%. Developed countries tend to have lower incidences due to the availability of screening and treatment options. Rates in developing countries are likely to be significantly higher considering the prevalence of gonococcal infection in pregnancy nears 5% in some parts of Africa. In the United States, the incidence of conjunctivitis ranges from 1% to 2% in neonates with the incidence of neonatal GC estimated to be less than 1%. As mentioned previously, in neonates that have appropriate chemoprophylaxis, up to 10% may still develop GC compared to up to 48% of neonates that do not.

In the non-neonatal populations, GC is rare. In the United States, STI surveillance estimates nearly 146 cases of gonorrhea per 100,000 population, but specific estimates of GC have not been well-studied. However, a recent study in Ireland estimated that the prevalence of GC was 0.19 cases per 1000 patients evaluated for eye emergencies with the majority presenting in young adult males.

Pathophysiology

The main concept is that N. gonorrhoeae can attach to and penetrate the epithelial cells of mucosal surfaces such as the conjunctiva. Once inside, the bacteria can proliferate and induce pro-inflammatory mechanisms. However, there is evidence that N. gonorrhoeae have developed methods for evading and even modulating immune responses, which can potentially lead to disseminated infection, for example, bacteremia or meningitis.

History and Physical

Neonatal GC is often acquired during delivery; thus, there usually is a history of suspected or confirmed maternal gonorrheal infection. Bacterial conjunctivitis can occur at any time, but GC is considered in symptomatic neonates after the first day of life, specifically, days 2 to 5, since chemical conjunctivitis (secondary to silver nitrate, antibiotic drops) is often the cause in the first 24 hours. A physical exam may reveal the following:

  • Conjunctival injection, chemosis
  • Edema of the eyelids
  • Mucopurulent discharge
  • Tenderness of the globe
  • Lymphadenopathy, preauricular

In the non-neonatal population, GC may present with similar symptoms and should at least be considered in sexually active individuals that present with conjunctivitis with or without genital symptoms. Regardless, a detailed sexual history of the mother and non-neonatal cases of conjunctivitis should be obtained to refine the differential diagnoses for conjunctivitis.

Evaluation

For patients presenting with conjunctivitis concerning for possible GC, further diagnostics are suggested to confirm the diagnosis. A sampling of conjunctival scrapings or exudative fluid can be sent for the following:

  • Gram stain, which may reveal gram-negative intracellular diplococci
  • Culture on Thayer-Martin media and/or chocolate agar for N. gonorrhoeae and blood agar for non-gonococcal species
  • Polymerase chain reaction (PCR) can also be used to test for N. gonorrhoeae as well as Chlamydia trachomatis
  • Screening for other STIs such as the human immunodeficiency virus (HIV) is also recommended in mothers and non-neonatal cases due to co-infections that can occur with STIs
  • Consideration should also be given to taking genital and throat swabs in patients with risk factors.

Treatment / Management

Due to the progression risk of disseminated gonococcal infection, neonates with GC should be approached as emergent cases that warrant admission and observation. The most effective treatment of GC is prevention, and it is recommended that females be screened for gonorrhea and other STIs if considered high-risk (prior history of STI, commercial sex workers) and should be appropriately treated. Nevertheless, cases of neonatal GC can occur even with appropriate prophylactic measures. Below is a summary of the recommended therapies.[8][9][10][11]

Neonatal Prophylaxis

  • Erythromycin (0.5%) ophthalmic ointment, or
  • Tetracycline (1%) ophthalmic ointment

Symptomatic or High-Risk (mother with untreated gonorrhea) neonate

  • Ceftriaxone (25 mg/k to 50 mg/kg, max 125 mg intravenously (IV) or  intramuscularly (IM), single dose, or
  • Cefotaxime (100 mg/kg IV/IM), single dose, which may be preferred if available due to the risk of increasing bilirubin levels associated with ceftriaxone
  • Hourly saline lavage

Non-Neonate with Symptoms (generally, can be managed on an outpatient basis)

  • Ceftriaxone (1 gm IM), single dose, and
  • Azithromycin (1 gm oral), single dose, which is added on due to the frequent co-infection with Chlamydia trachomatis
  • Saline lavage can be considered but is not a necessity

Pearls and Other Issues

GC is a disease process that should not be dismissed. Untreated cases can result in severe complications such as vision loss if the bacteria penetrate further and cause corneal ulceration and scarring. Timely ophthalmology consultation is warranted due to the significant risks to the patient’s vision. Providers should also be aware of the risks of a systemic infection that may present as septic arthritis, meningitis, or septicemia. Furthermore, attention should be given to appropriate treatment since fluoroquinolone resistance has become a growing issue, which is part of the reason why cephalosporins have become the mainstay of gonococcal treatment.

Enhancing Healthcare Team Outcomes

Gonococcal conjunctivitis is a serious illness that is best managed by a multidisciplinary team that consists of a pediatrician, ophthalmologist, infectious disease expert, nurse practitioner and the primary care physician. Untreated cases can result in severe complications such as vision loss if the bacteria penetrate further and cause corneal ulceration and scarring. Timely ophthalmology consultation is warranted due to the significant risks to the patient’s vision. Providers should also be aware of the risks of a systemic infection that may present as septic arthritis, meningitis, or septicemia. Furthermore, attention should be given to appropriate treatment since fluoroquinolone resistance has become a growing issue, which is part of the reason why cephalosporins have become the mainstay of gonococcal treatment.Following treatment, the outcomes in most infants are good.[12] (Level V)


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Gonococcal Conjunctivitis - Questions

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A newborn presents 2 days after birth with purulent eye discharge. What is the most likely etiologic agent?



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A 17-year-old female presents to the emergency department with left-sided eye discharge for the past few days. She reports no sick contacts. She does not wear contact lenses. She denies any medical history. She is sexually active with multiple male partners and reports that her last sexual engagement was oral sex approximately 2 weeks ago. She gets sexually transmitted infection testing regularly, with negative urine screening about 1 week ago. Vitals are stable. On exam, visual acuity is 20/20 bilaterally. Her left upper eyelid is swollen, erythematous, and positive for mucopurulent discharge. She has a conjunctival injection of the left eye. Extraocular movements are intact without significant pain bilaterally. There are no other positive exam findings. Which of the following treatments would be appropriate for this patient?



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Which of the following is true regarding gonococcal conjunctivitis?



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A 3-day-old female is brought in for "yellowish" skin. On exam, the patient has mildly jaundiced skin and, when assessing for scleral icterus, the provider notes bilateral chemosis and eyelid edema with copious mucopurulent discharge. The mother has a had a history of genital gonorrheal infection, but is unsure of her current status due to inconsistent prenatal follow-up. Relevant labs and cultures are ordered. Regarding the patient's ophthalmic symptoms, which of the following is most appropriate?



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Which of the following can occur in neonates diagnosed with gonococcal conjunctivitis within days if not treated appropriately?



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Gonococcal Conjunctivitis - References

References

Lessing JN,Slingsby TJ,Betz M, Hyperacute Gonococcal Keratoconjunctivitis. Journal of general internal medicine. 2019 Jan 16;     [PubMed]
Tan AK, Ophthalmia Neonatorum. The New England journal of medicine. 2019 Jan 10;     [PubMed]
Fiorito TM,Noor A,Silletti R,Krilov LR, Neonatal Conjunctivitis Caused by Neisseria cinerea: A Case of Mistaken Identity. Journal of the Pediatric Infectious Diseases Society. 2018 Nov 21;     [PubMed]
Kaštelan S,Anić Jurica S,Orešković S,Župić T,Herman M,Gverović Antunica A,Marković I,Bakija I, A Survey of Current Prophylactic Treatment for Ophthalmia Neonatorum in Croatia and a Review of International Preventive Practices. Medical science monitor : international medical journal of experimental and clinical research. 2018 Nov 10;     [PubMed]
Belga S,Gratrix J,Smyczek P,Bertholet L,Read R,Roelofs K,Singh AE, Gonococcal Conjunctivitis in Adults: Case Report and Retrospective Review of Cases in Alberta, Canada, 2000-2016. Sexually transmitted diseases. 2019 Jan;     [PubMed]
Churchward CP,Calder A,Snyder LAS, Mutations in Neisseria gonorrhoeae grown in sub-lethal concentrations of monocaprin do not confer resistance. PloS one. 2018;     [PubMed]
Gallenga PE,Del Boccio M,Gallenga CE,Neri G,Pennelli A,Toniato E,Lobefalo L,Maritati M,Perri P,Contini C,Del Boccio G, Diagnosis of a neonatal ophthalmic discharge, Ophthalmia neonatorum, in the “molecular age”: investigation for a correct therapy. Journal of biological regulators and homeostatic agents. 2018 Jan-Feb;     [PubMed]
Gonçalves Dos Santos Martins T,Fontes de Azevedo Costa AL, A rare ocular complication of neisseria gonorrhoeae. Irish journal of medical science. 2018 Aug;     [PubMed]
Hammerschlag MR,Smith-Norowitz T,Kohlhoff SA, Keeping an Eye on Chlamydia and Gonorrhea Conjunctivitis in Infants in the United States, 2010-2015. Sexually transmitted diseases. 2017 Sep;     [PubMed]
Pak KY,Kim SI,Lee JS, Neonatal Bacterial Conjunctivitis in Korea in the 21st Century. Cornea. 2017 Apr;     [PubMed]
Bodurtha Smith AJ,Holzman SB,Manesh RS,Perl TM, Gonococcal Conjunctivitis: A Case Report of an Unusual Mode of Transmission. Journal of pediatric and adolescent gynecology. 2017 Aug;     [PubMed]
Zuppa AA,D'Andrea V,Catenazzi P,Scorrano A,Romagnoli C, Ophthalmia neonatorum: what kind of prophylaxis? The journal of maternal-fetal     [PubMed]

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