Gonococcal meningitis: An unusual presentation of disseminated gonococcal infection

Abstract

Gonorrhea is a sexually transmitted infection caused by Neisseria gonorrhoeae. The rate of N. gonorrhoeae infections in Canada has increased from 2010 to 2015. Disseminated gonococcal infection typically results from bacteremic spread of N. gonorrhoeae from a preceding mucosal site of disease (e.g., urogenital). Common clinical manifestations of disseminated gonococcal infection include skin lesions, tenosynovitis, and septic arthritis. Bacterial meningitis as a manifestation of disseminated gonococcal infection has been rarely described. A case of bacterial meningitis due to N. gonorrheae, complicated by an ischemic stroke, is reported here. Clinical features that may point to N. gonorrhoeae as the pathogen in a patient with bacterial meningitis include a concomitant active urogenital infection, skin rash, arthritis, and/or tenosynovitis. Parenteral ceftriaxone for 10 to 14 days combined with a single oral dose of azithromycin is currently recommended as the treatment for gonococcal meningitis in recent guidelines. This case is presented to highlight a potential, albeit rare, complication of a preventable disease that has resurged in the last decade in our community.

Case presentation

A 35-year-old male presented to a tertiary care hospital emergency department in Winnipeg (Manitoba, Canada) with a 10-day history of self-reported fever, general malaise, and confusion. He had a history of methamphetamine abuse, alcohol use disorder, and smoking. Approximately 13 months prior to admission, he had a positive urine nucleic acid amplification test (NAAT) for both Neisseria gonorrhoeae and Chlamydia trachomatis. It is not clear what treatment he received, but a follow-up urine molecular test 10 months prior to admission was negative for both pathogens. The patient was currently living in an apartment with four roommates and had previously been involved in the sale of street drugs. A sexual history was not obtained at presentation due to his impaired cognition. Physical examination at the time of presentation revealed a temperature of 36.9°C, a heart rate of 77 beats per minute, and a blood pressure of 160/108 mm Hg. The patient was disorientated to place and time and had nuchal rigidity. The remainder of the physical examination was unremarkable. In particular, no rash or joint swelling was observed.

Laboratory investigations revealed a peripheral leukocytosis of 15.9 × 10⁹/L (normal 4.5–11.0 × 10⁹/L) with a neutrophil predominance (93.4% of the total leukocyte count). The absolute lymphocyte count was depressed at 0.51 × 10⁹/L (normal 1.3–3.2 × 10⁹/L). A lumbar puncture was performed. The cerebrospinal fluid (CSF) had a total cell count of 350 × 10⁶/L (normal 0–5 × 10⁶/L) with 73% polymorphonuclear leukocytes (PMN), a total protein of 6 g/L (normal 0.2–0.4 g/L), and a glucose of 0.6 mmol/L (normal 2.3– 4.7 mmol/L, concomitant serum glucose of 7.1 mmol/L). A urine toxicology drug screen was not done. The patient was initially started on therapy with intravenous ceftriaxone, vancomycin, and acyclovir for a presumed diagnosis of meningitis. The CSF gram stain was subsequently reported as showing 4+ PMNs and 1+ gram-negative diplococci (Figure 1). Vancomycin and acyclovir were discontinued. While the patient was being monitored in the emergency department, he developed acute onset of left-sided weakness and right deviation of the eyes. An emergent uninfused computed tomography (CT) scan of the brain did not reveal any abnormalities; however, CT angiography (CTA) demonstrated severe vasospasm of the entire intracranial circulation, most markedly involving the right middle cerebral artery (MCA) territory with early ischemic changes (Figure 2). The patient underwent an electroencephalogram which showed epileptiform activity consistent with a seizure. Phenytoin was started and the patient was admitted to a high observation unit under the general medicine service.

Figure 1:

Gram stain of CSF showing gram-negative diplococci

Figure 2:

Coronal reformatted image from the CTA at time of presentation shows irregular narrowing of the intracranial internal carotid arteries (ICA) above the level of the clinoid process involving the ICA terminus, A1, and M1 segments (←). Note the severe narrowing of the proximal right middle cerebral artery (↓). Comparison to the more normal caliber proximal ICAs (*) is shown

CTA = computed tomography angiography

On day 1 post admission, a magnetic resonance imaging (MRI) study of the brain was performed and this confirmed the presence of a right MCA ischemic stroke (Figure 3). Within 24 hours of collection, the cerebrospinal fluid culture was growing gram-negative diplococci. The organism was identified by day 2 post admission as N. gonorrhoeae. Initial identification was performed by matrix assisted laser desorption ionization (MALDI)-time of flight mass spectrometry (Bruker MALDI Biotyper System, RUO MBT Compass 4.1.70, Bruker Daltonics Ltd., East Milton, ON). The organism identity was confirmed with biochemical testing using an API-NH strip (BioMerieux, St. Laurent, QC). The isolate was forwarded on to a provincial reference laboratory for susceptibility testing. Blood cultures obtained 3 days post admission (following initiation of antimicrobial therapy) were negative. Serology for human immunodeficiency virus (HIV), syphilis, hepatitis B, and hepatitis C was also negative. Complement testing demonstrated normal C3 and C4 levels, and normal total complement activity. A urine NAAT was positive for C. trachomatis but negative for N. gonorrhoeae. Of note, this testing was performed 3 days after the initiation of antimicrobial therapy. Pharyngeal and rectal cultures for N. gonorrhoeae were not obtained. A transthoracic echocardiogram (TTE) with a bubble study performed 4 days post admission did not reveal any evidence of cardiac vegetations or intracardiac shunt.

Figure 3:

Axial diffusion weighted image (DWI) from a brain MRI shows diffusion restriction within the cortex of the right cerebral hemisphere conforming to the right middle cerebral artery vascular territory in keeping with acute infarction

Susceptibility testing results for the N. gonorrhoeae isolate were available on day 6 post admission. The isolate was susceptible to ciprofloxacin, azithromycin, cefixime, and ceftriaxone. The patient was treated with ceftriaxone 2 g intravenously every 12 hours for a total of 14 days. He received a single 1 g oral dose of azithromycin to treat the associated C. trachomatis urogenital infection. After 2 weeks of hospital admission, he regained near-normal motor function but had persistently impaired cognitive function. The patient left the hospital against medical advice on day 18 post admission. The police were contacted to bring him back due to safety concerns related to his persisting cognitive deficits, but they were not successfully able to locate him. Public health was notified of the patient, such that follow-up and contract tracing could be attempted.

Discussion

Gonorrhea is a sexually transmitted bacterial infection caused by N. gonorrhoeae (1). In Canada, infections with N. gonorrhoeae are on the rise (2). The Public Health Agency of Canada reported that the rate of N. gonorrhoeae infection per 100,000 population increased by 65.4% between 2010 and 2015 (2). Persons at risk for infection with N. gonorrhoeae include individuals with a previous history of gonococcal infection or another sexually transmitted infection, sexual contacts of individuals with a suspected or confirmed gonococcal infection, sex workers and their sexual partners, sexually active youth less than 25 years of age, street-involved youth and other homeless populations, men who have unprotected sex with men, and individuals that have sex with multiple partners (1).

Patients with gonorrhea may present with symptoms of urethritis, cervicitis, proctitis, and/or pharyngitis. Infection can also be asymptomatic, particularly among females (1,3). If left untreated, complications including disseminated disease may occur (4,5). Disseminated gonococcal infection can present with cutaneous manifestations (petechial or pustular skin lesions), tenosynovitis, asymmetric polyarthralgia, septic arthritis, endocarditis, and meningitis (1,3,4). Two publications from 1971 estimated that disseminated gonococcal infection (arthritis-dermatitis syndrome) occurred in 0.5% to 3% of patients with gonorrhea (5–7). However, it is unclear if this estimate is still valid (5,8).

The first well documented case of gonococcal meningitis was described by Smith in 1922 (9). Over the last century, less than 50 cases of gonococcal meningitis have been published in the literature, with the most recent case reported by Spanish investigators in 2008 (10). Seeding of the meninges is thought to occur secondary to bacteremia, presumably from infection at a genital, anorectal, or pharyngeal source (4,5). Cachay et al reviewed 32 cases of CSF culture-positive gonococcal meningitis (11). Clinical symptoms of a concomitant active urogenital infection were present in 56% of patients. A co-existent skin rash was observed in 38% of cases, and 34% had associated arthritis/tenosynovitis. Fever was reported in 94% of patients. Among the 29 adult patients included in the review, headache was documented in 79% and meningeal signs were present in 72% (11). CSF analysis typically demonstrated an elevated cell count (neutrophil predominance), elevated protein, and low glucose, as is observed with other bacterial causes of meningitis (11).

Treatment recommendations for patients with infection due to N. gonorrhoeae are described in the Canadian Guidelines on Sexually Transmitted Infections from the Public Health Agency of Canada (1). The optimal therapy for patients with gonococcal meningitis has not been systemically evaluated due to the rarity of this presentation. Current sexually transmitted diseases treatment guidelines from the Centers for Disease Control and Prevention in the United States recommend ceftriaxone 1–2 g intravenously every 12 to 24 hours for a total duration of 10 to 14 days, combined with a single 1 g oral dose of azithromycin (3). An increase in the number of N. gonorrhoeae isolates with reduced susceptibility to cefixime and ceftriaxone was observed in Canada between 2001 and 2010 (12). However, among isolates tested at Canada’s National Microbiology Laboratory (Winnipeg, Manitoba) more recently between 2010 and 2015, the proportion with reduced susceptibility to cefixime declined from 3.3% to 1.9%, while the proportion with reduced susceptibility to ceftriaxone declined from 7.3% to 3.5% (13). In contrast, over the same time period, azithromycin resistance was observed to increase from 1.3% to 4.7% (13). The isolate in the present case was susceptible to third-generation cephalosporins, azithromycin, and ciprofloxacin.

The present case of gonococcal meningitis is unusual in that it was complicated by an ischemic stroke and associated seizure. Seizures have been described in pediatric patients with gonococcal meningitis (11). There is a single report of an adult patient (34-year-old male) with gonococcal meningitis who had a generalized convulsion as part of his presentation (14). Focal neurological findings in patients with gonococcal meningitis are typically absent, and ischemic stroke in association with this infection has not been previously described (11). Ischemic stroke has been reported as a complication of community-acquired bacterial meningitis due to other more common pathogens such as Streptococcus pneumoniae (15,16). Stroke in the setting of bacterial meningitis is thought to be secondary to localized cerebral vasculitis, although other mechanisms such as vasospasm and septic emboli from a concomitant endocarditis could also play a role (15,16). While we cannot prove that the stroke in the patient described here was precipitated by N. gonorrhoeae infection of the central nervous system, the temporal association makes this likely. Gonococcal endocarditis as a cause of stroke was thought to be unlikely given the absence of vegetations on a transthoracic echocardiogram and the presence of vasospasm on a CT angiogram, although this was not completely excluded as a transesophageal echocardiogram was not performed. Vasospasm secondary to illicit drug use causing stroke was also not excluded as a toxicology screen was not performed for the patient.

In summary, a case of gonococcal meningitis in an immunocompetent adult is described. Despite the negative urine NAAT for N. gonorrhoeae, we believe that dissemination most likely occurred from a preceding urogenital infection. The negative NAAT is thought to be related to prior antimicrobial treatment. However, rectal and/or pharyngeal infection was not excluded. This case is reported to highlight a potential, albeit rare, complication of a preventable disease that has resurged in the last decade in our community.

Competing Interests:

The authors have no conflict of interest to declare related to this work.

Ethics Approval:

The authors consulted with the ethics board at University of Manitoba and were granted an ethical approval letter to proceed with submission of the case.

Informed Consent:

An attempt was made to obtain written consent from the patient for publication of the case report. Publication of the case was discussed with the patient and he provided verbal consent, but he left the hospital against medical advice before signing a written consent form.

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No funding was received for this article.

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This article has been peer reviewed.