Gonococcal infection in the newborn

INTRODUCTION — 

Perinatal acquisition of sexually transmitted infections can have serious consequences for the newborn. Ophthalmia neonatorum (newborn conjunctivitis) was caused principally by Neisseria gonorrhoeae at one time in the United States and was the most common cause of blindness. Although this newborn infection has decreased considerably throughout the world with the advent of routine newborn ophthalmologic prophylaxis, the consequences of untreated disease remain grave.

Gonococcal infection in the newborn is reviewed here. The epidemiology and pathogenesis of N. gonorrhoeae infection are discussed separately. (See "Epidemiology and pathogenesis of Neisseria gonorrhoeae infection".)

Neonatal infection with other sexually transmitted organisms is discussed separately:

●(See "Chlamydia trachomatis infections in newborns and young infants".)

●(See "Congenital syphilis: Management and outcome".)

●(See "Neonatal herpes simplex virus (HSV) infection: Clinical features and diagnosis" and "Neonatal herpes simplex virus (HSV) infection: Management and prevention".)

●(See "Hepatitis viruses and the newborn: Clinical manifestations and treatment".)

●(See "Pediatric HIV infection: Diagnostic testing in children younger than 18 months".)

EPIDEMIOLOGY

Incidence — The incidence of neonatal gonococcal infection relates to the prevalence of infection among individuals of childbearing age, which varies somewhat worldwide. In high-income countries, the prevalence of gonococcal infection among pregnant individuals is <1 percent; the prevalence in low- and middle-income countries is considerably higher. (See "Epidemiology and pathogenesis of Neisseria gonorrhoeae infection", section on 'Global incidence'.)

In pregnant individuals, coinfection with Chlamydia trachomatis is common and HIV transmission is heightened in the presence of gonorrhea [1,2]. (See "Epidemiology of Chlamydia trachomatis infections" and "Epidemiology and pathogenesis of Neisseria gonorrhoeae infection", section on 'Association with HIV'.)

In the newborn, the eye is the most frequent site of gonococcal infection [3]. (See 'Ophthalmia neonatorum' below.)

The epidemiology of N. gonorrhoeae infection is discussed in greater detail separately. (See "Epidemiology and pathogenesis of Neisseria gonorrhoeae infection", section on 'Epidemiology'.)

Perinatal transmission — Newborns typically acquire gonococcal infection during vaginal delivery. Perinatal transmission occurs in 30 to 40 percent of cases in which the birth parent has gonococcal cervical infection [4]. Intrauterine infection also can occur after rupture of the membranes.

Association with prematurity — Gonococcal infection during pregnancy is associated with increased risk of preterm delivery [5-13]. In a population-based study from the United States (2016 to 2019), rates of preterm birth among pregnancies with and without maternal gonorrhea were 12 versus 8 percent, respectively (adjusted odds ratio 1.11; 95% CI 1.08-1.15) [12]. (See "Spontaneous preterm birth: Overview of risk factors and prognosis", section on 'Infection'.)

OPHTHALMIA NEONATORUM — 

The eye is the most frequent site of gonococcal infection in the newborn.

Epidemiology — N. gonorrhoeae is a rare cause of neonatal conjunctivitis in areas of the world where pregnant individuals are routinely screened for gonorrhea and newborns routinely receive ocular prophylaxis [14]. In the United States, the reported rate of gonococcal conjunctivitis in infants <12 months of age was estimated to be 0.3 cases per 100,000 live births in 2022 [15].

Viral pathogens, other bacteria, and noninfectious etiologies (eg, chemical irritation, blocked tear duct) are far more common than N. gonorrhoeae as causes of conjunctivitis in newborns in high-resource settings in the contemporary era. In one study of 173 neonates with conjunctivitis, approximately 60 percent had no pathogen detected [16]. The most common bacterial pathogens were S. aureus (16 percent), M. catarrhalis (9 percent), S. pneumoniae (3 percent), and H. influenzae (2 percent). Viral pathogens were detected in 5 percent of patients. No cases of gonococcal or chlamydial infection were identified.

Clinical features — Infection typically causes a purulent conjunctivitis, with profuse exudate and swelling of the eyelids (picture 1). Without treatment, the infection can extend from the superficial epithelial layers into the subconjunctival connective tissue and the cornea, leading to ulceration, scarring, and visual impairment.

The infection usually becomes manifest two to five days after birth. However, factors including ophthalmic prophylaxis, inoculum size, or variations in virulence may result in a more indolent course and delay in onset.

Diagnosis — Ophthalmia neonatorum is confirmed by microbiologic testing of the exudate. Neonates who develop conjunctivitis after the first day of age or appear to have severe or persistent chemical conjunctivitis should be evaluated.

In general, nucleic acid amplification testing (NAAT) is the test of choice for the initial microbiologic diagnosis of N. gonorrhoeae infection, although culture remains an important diagnostic tool. A positive Gram stain of the conjunctival exudate showing typical gram-negative intracellular kidney bean-shaped diplococci is supportive but not diagnostic. Caution should be used in interpreting the Gram stain results since other nonpathogenic Neisseria species can be mistaken for N. gonorrhoeae [1]. Culture of the exudate should be performed using selective media (eg, modified Thayer-Martin medium) that inhibit normal flora and nonpathogenic Neisseria organisms. Testing other sites (eg, oropharyngeal and rectal swabs) can also be helpful in confirming the diagnosis.

Additional evaluation

●Evaluation for coinfection and/or other causes – Newborns with conjunctivitis should be evaluated for C. trachomatis using NAAT. Coinfection with this organism is common with gonococcal disease. (See "Chlamydia trachomatis infections in newborns and young infants".)

In addition to testing for N. gonorrhoeae and C. trachomatis, newborns with purulent conjunctivitis should have a bacterial culture performed on the exudate to evaluate for other bacterial causes. In some cases, viral testing (eg, for herpes simplex virus) may also be warranted. (See 'Differential diagnosis' below.)

●Evaluation of the birth parent – The birth parent and sexual partner(s) should be evaluated and treated for gonococcal infection. (See "Treatment of uncomplicated gonorrhea (Neisseria gonorrhoeae infection) in adults and adolescents".)

The birth parent also should be evaluated for other sexually transmitted infections, including HIV infection. (See "Screening for sexually transmitted infections".)

Differential diagnosis — Other causes of purulent conjunctivitis in newborns include other bacteria (eg, Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae, C. trachomatis) and viral infections (eg, adenovirus, herpes simplex virus). As previously discussed, S. aureus, H. influenzae, and S. pneumoniae are considerably more common causes of purulent conjunctivitis in newborns in areas of the world where ophthalmologic prophylaxis is routine. (See 'Epidemiology' above.)

Noninfectious causes of neonatal conjunctivitis include chemical conjunctivitis (caused by prophylactic eye drops or ointment) and dacryostenosis. However, these causes typically are not associated with purulent eye discharge. (See "Congenital nasolacrimal duct obstruction (dacryostenosis) and dacryocystocele" and "Toxic conjunctivitis" and "Allergic conjunctivitis: Clinical manifestations and diagnosis".)

The timing of onset and clinical findings can help distinguish N. gonorrhoeae from other causes of neonatal conjunctivitis. N. gonorrhoeae infection typically presents two to five days after birth and is characterized by profuse exudate and swelling of the eyelids (picture 1). However, microbiologic tests (NAAT, Gram stain, and culture) are necessary to confirm the diagnosis.

Treatment — Treatment of neonatal N. gonorrhoeae conjunctivitis consists of a single dose of ceftriaxone (25 to 50 mg/kg [maximum dose 250 mg] given intravenously [IV] or intramuscularly [IM]) [2].

Ceftriaxone should not be used in neonates receiving calcium-containing IV fluids, including parenteral nutrition, since this can cause precipitation leading to severe reactions [17,18]. In addition, we avoid use of ceftriaxone in preterm neonates and newborns with clinically significant hyperbilirubinemia since ceftriaxone displaces bilirubin from albumin and may increase the risk of neurotoxicity. While this usually is not a concern when giving only a single dose, we generally avoid ceftriaxone in neonates requiring treatment of hyperbilirubinemia. (See "Unconjugated hyperbilirubinemia in neonates: Risk factors, clinical manifestations, and neurologic complications", section on 'Risk factors for neurotoxicity'.)

Alternative agents that can be used in these circumstances include:

●Cefotaxime (if available) – Given as a single dose (100mg/kg) IV or IM

●Ceftazidime – Given as a single dose (50 mg/kg) IV or IM

Topical antibiotic therapy alone is inadequate for treatment of gonococcal conjunctivitis [1].

In addition to systemic antibiotic therapy, the eyes should be irrigated frequently with saline until the discharge clears.

Infants with gonococcal ophthalmic disease should be hospitalized and observed for response to therapy. If the infant develops evidence of disseminated infection or is deemed to be at high risk (eg, birth parent with no prenatal care, history of sexually transmitted infections, or substance use disorder), additional evaluation should be performed (including blood and CSF cultures) and presumptive treatment for disseminated infection should be administered. (See 'Disseminated infection and scalp abscess' below.)

Prevention — The most effective measure to prevent both gonococcal and chlamydial infections is to diagnosis and treat these infections in pregnant individuals. In addition, prophylactic antibiotic eye therapy reduces the risk of gonococcal conjunctivitis; however, it is not effective in preventing C. trachomatis conjunctivitis.

Screening during pregnancy — Screening for gonorrhea during pregnancy is discussed separately. (See "Prenatal care: Initial assessment", section on 'Gonorrhea'.)

Newborn ocular prophylaxis — The risk of contracting gonococcal conjunctivitis is reduced by prophylactic administration of an ophthalmic antibiotic agent shortly after birth [19,20]. In the United States, most states have legislation in place mandating administration of ocular prophylaxis to all newborns. This practice is endorsed by the United States Preventive Services Task Force (USPSTF), and the Centers for Disease Control and Prevention, and the World Health Organization [2,21,22]. However, increasingly, the continued need for legal mandates has been called into question given declining rates of neonatal gonococcal conjunctivitis, rising rates of macrolide resistance among N. gonorrhea strains, and recurrent shortages of erythromycin ophthalmic ointment [23-25]. The American Academy of Pediatrics (AAP) has called for a reevaluation of this practice [24,26]. In some countries, including Canada and Italy, the practice of administering ocular prophylaxis to all newborns was discontinued in the late 2010s to early 2020s [25,27]. In these countries, the emphasis has shifted to enhanced screening for N. gonorrhoeae and C. trachomatis during pregnancy [25,27].

●Choice of agent – Erythromycin (0.5 percent) ophthalmic ointment is the only approved agent available in the United States for prevention of gonococcal ophthalmia neonatorum. Erythromycin ophthalmic ointment causes less chemical conjunctivitis than does silver nitrate solution.

Other agents that are not commercially available the United States for this indication, but may be available elsewhere include [22]:

•Silver nitrate (1 percent solution), which may be more effective as a prophylaxis for penicillinase-producing N. gonorrhoeae compared with erythromycin [28,29].

•Tetracycline (1 percent ointment)

•Chloramphenicol (1 percent ointment)

•Povidone-iodine solution (2.5 percent water-based solution), which has the advantage of being low cost and having little toxicity.

●Technique – The ophthalmic antibiotic should be applied in each eye within two hours of birth, regardless of mode of delivery [1,2,21]. After wiping each eyelid with sterile cotton gauze, the prophylactic agent is placed in each of the lower conjunctival sacs [30]. When administering erythromycin ointment, a 1 cm ribbon is applied to each eye. The agent should be spread by gentle massage of the eyelids, and excess solution or ointment can be wiped away after one minute. The eyes should not be irrigated after the application because doing so may reduce efficacy.

●Side effects – The principal side effect is chemical (noninfectious) conjunctivitis, which is usually mild. This condition typically appears within the first 24 hours after administration and resolves by 48 hours. It is most often seen after application of silver nitrate, which is not used in the United States.

●Efficacy – The efficacy of newborn ocular prophylaxis has been evaluated in clinical trials and meta-analyses [19,20]. A 2020 meta-analysis identified 30 trials (>79,000 newborns) evaluating various interventions for prevention of ophthalmia neonatorum [19]. Approximately one-half of the trials were performed in high-income countries, while the others were performed in low- and middle-income countries. Nearly all trials had one or more important methodologic limitation (eg, nonrandomized study design, lack of blinding, incomplete follow-up, selective reporting, or other bias). In an analysis of trials comparing any type of prophylaxis versus no prophylaxis (eight trials; 9666 neonates), prophylaxis modestly reduced the incidence of conjunctivitis (4 versus 6 percent; RR 0.65, 95% CI 0.54-0.78). In trials directly comparing erythromycin ointment versus silver nitrate (four trials; 13,472 newborns), there were fewer episodes of conjunctivitis in the erythromycin group (1.7 versus 2.1), though the difference was not statistically significant (RR 0.75, 95% CI 0.51-1.09). No studies reported long-term vision outcomes.

●Challenges, uncertainties, and limitations – Increasingly, the practice of routinely administering newborn ocular prophylaxis has come into question based on the following considerations [23-25]:

•The trials that established the efficacy of newborn ocular prophylaxis were performed in an era or setting in which pregnant individuals were not routinely screened for gonorrhea and chlamydia and thus the baseline risk of ophthalmia neonatorum was considerably higher than it is in contemporary practice in high-resource settings.

•In the era of routine screening for gonorrhea during pregnancy, neonatal gonococcal conjunctivitis is rare and thus the incremental benefit of providing universal newborn ocular prophylaxis is uncertain. (See 'Epidemiology' above.)

•In the United States, topical erythromycin ointment is the only agent currently available for newborn prophylaxis; shortages and unavailability are common.

•The development of macrolide resistance among N. gonorrhoeae strains and pharmacokinetic limitations of topical erythromycin therapy suggest that it may be ineffective as a prophylactic agent in contemporary practice. (See "Epidemiology and pathogenesis of Neisseria gonorrhoeae infection", section on 'Epidemiology of antimicrobial resistance'.)

The AAP has taken the position that the need for legal mandates for ocular prophylaxis should be re-examined [24]. Instead, the AAP advocates for states to adopt alternative strategies to prevent ophthalmia neonatorum, including [1,24,26]:

•Improving compliance with recommendations for prenatal screening and treatment of gonococcal and chlamydial infections during pregnancy. (See "Prenatal care: Initial assessment", section on 'Gonorrhea'.)

•Testing of unscreened individuals for N. gonorrhoeae and C. trachomatis infection at the time of labor or delivery, and providing treatment, if warranted.

•If gonorrhea is prevalent in the region, and prenatal screening and treatment cannot be ensured, prophylaxis of the newborn may be warranted.

•Counseling parents/caregivers and educating newborn care providers that purulent conjunctivitis in a newborn infant requires evaluation and prompt treatment.

Despite the calls to re-evaluate the need for legal mandates for ocular prophylaxis, the USPSTF reaffirmed its recommendation in favor of universal ocular prophylaxis in 2019 [21], and most states in the United States continue to mandate ocular prophylaxis for all newborns.

OTHER LOCALIZED INFECTION — 

In addition to conjunctivitis, localized infection of other mucosal surfaces can occur. The pharynx, vagina, urethra, and anus can be affected [31]. Scalp abscesses may result from infection introduced by a fetal monitoring electrode [32]. Neonates with a scalp abscess or in whom sepsis is suspected should be treated for disseminated infection. (See 'Treatment' below.)

Diagnostic evaluation consists of cultures from the affected site, blood, and cerebrospinal fluid (CSF) to assess for disseminated infection.

Most localized infections can be treated with a single dose of an extended-spectrum cephalosporin (eg, ceftriaxone, cefotaxime [if available], or ceftazidime) using the same dosing as for conjunctivitis. (See 'Treatment' above.)

The exception is gonococcal scalp abscess, which is treated in the same manner as disseminated infection. (See 'Treatment' below.)

DISSEMINATED INFECTION AND SCALP ABSCESS — 

Disseminated infection may present as sepsis, arthritis, or meningitis. Septic arthritis is the most common manifestation of disseminated infection [33-35]. Gonococcal bacteremia and/or meningitis are rare in the newborn but can be a complication of ophthalmia neonatorum and other localized infections, particularly scalp abscess [4,36].

Clinical features — The clinical features vary depending on the type of infection:

●Sepsis – The signs and symptoms of neonatal sepsis are nonspecific. They are summarized in the table and are discussed in greater detail separately (table 1). (See "Neonatal bacterial sepsis: Clinical features and diagnosis in neonates born at or after 35 weeks gestation", section on 'Clinical manifestations'.)

●Meningitis – Common presenting signs and symptoms include fever, irritability, lethargy, apnea, seizures, vomiting, and poor feeding. The clinical features of neonatal meningitis are discussed in greater detail separately. (See "Bacterial meningitis in the neonate: Clinical features and diagnosis", section on 'Clinical features'.)

●Arthritis – Gonococcal arthritis typically presents at 2 to 21 days of age. The infant may appear only mildly to moderately ill, and the temperature may be normal or slightly elevated [35]. Multiple joints usually are affected. The infant typically refuses to move the painful, affected limb. (See "Bacterial arthritis: Clinical features and diagnosis in infants and children".)

●Scalp abscess – Infection can occur in infants who underwent fetal scalp electrode placement prior to delivery if the birth parent had an unknown or untreated infection [32,37]. Necrosis and scalp abscess can occur, which is associated with a high risk of disseminated infection.

Diagnosis — Diagnosis of disseminated infection is confirmed by a positive culture for N. gonorrhoeae from blood, cerebrospinal fluid (CSF), or synovial fluid. Nucleic acid amplification testing (NAAT) can be used to confirm the diagnosis in specimens other than blood.

Cultures should be obtained of blood and CSF in all infants with suspected disseminated infection. For neonates with signs and symptoms of arthritis, synovial fluid should be aspirated from an affected joint for testing with NAAT, Gram stain and culture. For neonates with scalp abscess, a specimen should be collected from the site and tested with NAAT and culture (in addition to performing blood and CSF cultures). Additional specimens obtained from the conjunctiva, vagina, oropharynx, and rectum are useful for identifying the primary site(s) of infection. A positive NAAT or Gram stain of exudate, CSF, or joint aspirate provides a presumptive basis for initiating treatment [2].

Treatment — Disseminated infection is treated with ceftriaxone or an alternative extended-spectrum cephalosporin (eg, cefotaxime [if available] or ceftazidime) [1,2]. The duration of treatment is seven days for septicemia, arthritis, or scalp abscess and 10 to 14 days for meningitis [1,2].

As previously discussed, ceftriaxone should not be used in the following settings [17,18]:

●Infants with clinically significant hyperbilirubinemia (since it displaces bilirubin from albumin and may increase the risk of neurotoxicity)

●Preterm neonates (due to increased risk of hyperbilirubinemia neurotoxicity)

●Infants receiving calcium-containing intravenous fluids including parenteral nutrition (due to risk of precipitation)

Alternative agents that can be used in these circumstances include cefotaxime (if available) or ceftazidime.

Other classes of antibiotics (eg, macrolides, fluoroquinolones) should not be used to treat N. gonorrhoeae infections, because of high resistance rates. N. gonorrhoeae drug resistance is discussed in detail separately. (See "Treatment of uncomplicated gonorrhea (Neisseria gonorrhoeae infection) in adults and adolescents", section on 'Antibiotic resistance'.)

ASYMPTOMATIC NEWBORN BORN TO UNTREATED BIRTHING PARENT — 

An asymptomatic newborn who is born to a birthing parent with untreated gonococcal infection is at high risk for acquiring infection. These newborns also should receive systemic treatment with a single dose of ceftriaxone or an alternative extended-spectrum cephalosporin (eg, cefotaxime [if available], or ceftazidime) using the same dose as for conjunctivitis [1,2]. (See 'Treatment' above.)

In addition, the newborn should be evaluated for chlamydial infection [2]. (See "Chlamydia trachomatis infections in newborns and young infants", section on 'Diagnosis'.)

SUMMARY AND RECOMMENDATIONS

●Transmission – Newborns acquire gonococcal infection during delivery. Perinatal transmission occurs in 30 to 40 percent of cases in which the birth parent has gonococcal cervical infection. (See 'Perinatal transmission' above.)

●Ophthalmia neonatorum – In the newborn, the eye is the most frequent site of gonococcal infection (see 'Ophthalmia neonatorum' above):

•Clinical features and diagnosis – Gonococcal ophthalmia neonatorum is characterized by a purulent conjunctivitis with profuse exudate and swelling of the eyelids. Without treatment, the infection can extend from the superficial epithelial layers into the subconjunctival connective tissue and the cornea, leading to ulceration, scarring, and visual impairment. The diagnosis is confirmed by nucleic acid amplification testing (NAAT) and/or culture of the exudate. (See 'Clinical features' above and 'Diagnosis' above.)

•Prevention – The most effective measure to prevent both gonococcal and chlamydial infections is to diagnosis and treat these infections in pregnant individuals. The practice of routinely providing ocular prophylaxis (eg, administering erythromycin 0.5% ophthalmic ointment shortly after birth) varies by region. In the United States, most states have legislation in place mandating this practice. However, the continued need for legal mandates has been called into question given declining rates of neonatal gonococcal conjunctivitis, rising rates of macrolide resistance among N. gonorrhea strains, and recurrent shortages of erythromycin ophthalmic ointment. In some countries, including Canada and Italy, the practice of routine newborn ocular prophylaxis has been discontinued and the emphasis has shifted to enhanced screening for N. gonorrhoeae and C. trachomatis during pregnancy. (See 'Prevention' above.)

•Treatment – For neonates with gonococcal conjunctivitis, we suggest treatment with a single dose of ceftriaxone rather than topical therapy (Grade 2C). Ceftriaxone can be administered intravenously (IV) or intramuscularly (IM) at a dose of 25 to 50 mg/kg (maximum dose 250 mg). Ceftriaxone should not be used in preterm neonates, infants with clinically significant hyperbilirubinemia, and neonates receiving calcium-containing IV fluids. Alternative agents that can be used in these circumstances include cefotaxime (where available) or ceftazidime. Infants receiving treatment for gonococcal conjunctivitis should be hospitalized and observed for response to therapy and for disseminated disease. Infants with confirmed gonococcal disease should also be evaluated for coinfection with Chlamydia trachomatis. (See 'Treatment' above and 'Additional evaluation' above.)

●Other localized infections – Localized infection of other mucosal surfaces can occur, including the pharynx, vagina, urethra, and anus. For treatment of these infections in the absence of signs of disseminated disease, we suggest a single dose of ceftriaxone or an alternative extended-spectrum cephalosporin (eg, cefotaxime [if available] or ceftazidime) (Grade 2C). The exception is newborns with gonococcal scalp abscess, who should undergo additional evaluation and receive treatment for disseminated infection. (See 'Other localized infection' above.)

●Disseminated infection – Disseminated infection may present as sepsis, arthritis, or meningitis (see 'Disseminated infection and scalp abscess' above):

•Septic arthritis is the most common manifestation of disseminated infection. Gonococcal bacteremia and/or meningitis are rare in the newborn but can be a complication of ophthalmia neonatorum and other localized infections, particularly scalp abscesses. (See 'Clinical features' above.)

•For neonates with disseminated infection, we suggest treatment with ceftriaxone or an alternative extended-spectrum cephalosporin (eg, cefotaxime [if available] or ceftazidime) rather than other agents (Grade 2C). The duration of treatment is seven days for septicemia, arthritis, or scalp abscess and 10 to 14 days for meningitis. (See 'Other localized infection' above and 'Disseminated infection and scalp abscess' above.)

●Asymptomatic infants – For an asymptomatic infant whose birthing parent has untreated gonococcal infection, we suggest treatment with a single dose of an extended-spectrum cephalosporin (eg, ceftriaxone, cefotaxime [if available], or ceftazidime) (Grade 2C). (See 'Asymptomatic newborn born to untreated birthing parent' above.)