Hospital Medicine

Neisseria

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Neisseria

I. What every physician needs to know.

Neisseria meningitidis is the second most common cause of bacterial meningitis in developed countries. Mortality can be high if this disease is left untreated and longterm sequelae can persist despite adequate treatment because of endotoxin-mediated vascular collapse. In general, meningococcal meningitis is one of the most devastating illnesses that can strike either an individual or a community. Even with appropriate treatment, mortality rates are from 10 to 15%. Patients with a complement deficiency are particularly at risk.

Neisseria gonorrhoeae is another strain of Neisseria seen more commonly than N. meningitidis. N. gonorrhoeae can cause localized urogenital infections and more complicated infections if bacteremia occurs, such as disseminated gonococcal infection (DGI). DGI can require intravenous therapy and a complicated inpatient treatment plan and will, therefore, be the focus of this entry.

II. Diagnostic Confirmation: Are you sure your patient has Neisseria?

A. History Part I: Pattern Recognition:

A typical patient with meningococcal meningitis will present with the sudden onset of fever, nausea and vomiting, headache, trouble focusing, and myalgias. In meningococcemia, there is a rapid progression of symptoms, with the above occurring in the first 4-6 hours; by 8 hours patients can progress with leg pains, cold hands and feet, respiratory distress and rash with death possible within 24 hours.

DGI typically presents as polyarthralgias, polyarthritis, or oligoarthritis in a young person.

B. History Part 2: Prevalence:

There are 2,500 to 3,500 cases of meningococcal meningitis annually, with over half of cases occurring in adolescents and adults. In the US, serogroups B and C are most common.

After Chlamydia, Gonorrhea is the second most common sexually transmitted infection in the United States; approximately one quarter will be co-infected. DGI occurs in 0.5 to 3% of patients infected with gonorrhea. DGI is about three times more common in women than men, and many of the infected men are either homosexual or bisexual. Most disseminated cases are not preceded by a symptomatic genital infection. Risk factors for dissemination include recent menstruation, pregnancy, complement deficiency, and lupus.

C. History Part 3: Competing diagnoses that can mimic Neisseria.

Meningococcal meningitis can be confused with other causes of bacterial meningitis, viral meningitis, encephalitis, Human Immunodeficiency Virus (HIV) seroconversion, pharyngitis, influenza infection, and any other viral prodrome.

Disseminated gonococcal infection can be confused with septic (bacterial) arthritis, connective-tissue diseases, reactive arthritis, rheumatic fever, hepatitis B, HIV infection, syphilis, Lyme disease, Parvovirus B19 and endocarditis.

D. Physical Examination Findings.

In meningococcal meningitis, vital signs will frequently show a low blood pressure and an elevated heart rate. A suspected patient should be carefully examined for petechiae and ecchymoses. Meningeal irritation can be provoked with the Kernig and Brudzinski signs, but these tests have a low sensitivity and specificity. Up to one third of patients will have focal neurologic deficits.

Patients with disseminated gonococcal infection will usually present with either a triad of tenosynovitis, dermatitis, and polyarthralgias without purulent arthritis or purulent arthritis without associated skin lesions. Acute infection is usually preceded by fever, chills, and general malaise. The tenosynovitis usually involves multiple small joints, such as the wrists, fingers, ankles, and toes. The dermatitis usually consists of a few painless, pustular lesions that are due to embolic disease. The purulent-arthritis variety usually involves the knees, wrists, and ankles.

E. What diagnostic tests should be performed?

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

All patients with suspected bacterial meningitis should have a lumbar puncture, and gram stain and culture of the cerebrospinal fluid (CSF) should be obtained. Blood cultures should also be done, although the rate of positive blood cultures is lower than positive CSF cultures.

Disseminated gonococcal infection can be diagnosed with synovial fluid analysis or blood cultures. The former is more useful with purulent arthritis and the latter with the tenosynovitis, dermatitis, polyarthralgia variety. All patients should also have the following specimens sent for testing: cervical or urethral, rectal, and skin. If available, nucleic acid amplification testing (NAAT) is preferred. If not, cultures must be submitted on Thayer-Martin media. If a urethritis is also present, a gram stain should be obtained from a urethral specimen.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

A computed tomography (CT) scan of the head should be obtained before lumbar puncture in patients with suspected bacterial meningitis and any of the following comorbidities: immunosuppression, a history of central nervous system (CNS) disease, new seizure, papilledema, altered consciousness, or a focal neurologic deficit.

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

Latex-agglutination tests for common meningeal antigens have been used in the past but are no longer recommended because of a high false-positive rate.

III. Default Management.

NA

A. Immediate management.

Prognosis for meningococcal meningitis is heavily dependent on prompt administration of antibiotics. Specifically, no more than 30 minutes should elapse between serious suspicion of meningitis and the first dose of antibiotics. First-line therapy is a third-generation cephalosporin, such as ceftriaxone at a dose of 2 grams (g) IV every 12 hours. While dexamethasone is useful in pneumococcal meningitis it has not proven beneficial with meningococcal meningitis. If steroids are given empirically, they should be stopped once the diagnosis of meningococcal meningitis is made. With vascular collapse, vasopressor agents and intubation may be required. All close contacts of an index patient should be administered either ciprofloxacin, rifampin, or ceftriaxone within 24 hours of identification of the index patient. Droplet precautions should be placed for the initial 24 hours of therapy.

For disseminated gonococcal infections, at least 7 days are generally required. Joints with purulent drainage also need to be tapped. Ceftriaxone 1g IV daily with azithromycin 1g po once (for concomitant Chlamydia) is the treatment of choice for the initial 24 to 48 hours of treatment. With improvement and sensitivity results, patients can be transitioned to oral ciprofloxacin or cefixime to complete at least 7 days of treatment. Increasing resistance to oral agents means sensitivities must be done; if they are not done or if the isolate is resistant to oral options, ceftriaxone 250 milligrams intramuscularly can be done to finish 7 days.

B. Physical Examination Tips to Guide Management.

A patient with meningococcal meningitis should be monitored for changes in mental functioning or signs of disseminated intravascular coagulation.

A patient with DGI should be evaluated for resolution of a purulent arthritis once the joint has been tapped and appropriate antibiotics have been started.

C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.

Patients with meningococcal meningitis should have regular complete blood counts (CBC) to monitor for evolving or worsening disseminated intravascular coagulation. They also should have regular chemistry panels to monitor especially for hyponatremia.

D. Long-term management.

NA

E. Common Pitfalls and Side-Effects of Management.

Important to let lab know you are looking for Neisseria so they will put swabs on Thayer-Martin instead of blood agar.

With DGI, important to send off a rectal swab since this is often higher yield than cervical and throat swabs in DGI.

For patients with recurrent Neisseria, consider outpatient workup for complement deficiency and make sure resistance testing is being done on cultures.

IV. Management with Co-Morbidities.

A. Renal Insufficiency.

All antibiotics must be renally adjusted for both meningococcal meningitis and disseminated gonococcal disease in a patient with renal impairment.

B. Liver Insufficiency.

No change in standard management.

C. Systolic and Diastolic Heart Failure.

No change in standard management.

D. Coronary Artery Disease or Peripheral Vascular Disease.

No change in standard management.

E. Diabetes or other Endocrine issues.

No change in standard management.

F. Malignancy.

No change in standard management.

G. Immunosuppression (HIV, chronic steroids, etc.).

No change in standard management except to stress-dose steroids.

H. Primary Lung Disease (COPD, Asthma, ILD).

No change in standard management.

I. Gastrointestinal or Nutrition Issues.

No change in standard management.

J. Hematologic or Coagulation Issues.

No change in standard management.

K. Dementia or Psychiatric Illness/Treatment.

No change in standard management.

V. Transitions of Care.

A. Sign-out considerations While Hospitalized.

Covering physicians should be instructed to monitor meningococcal patients closely for deteriorating mental status (likely requiring intensive care unit upgrade and intubation or reintubation), along with signs of evolving or worsening disseminated intravascular coagulation. In case of the latter, patients should be monitored with frequent CBC's and coagulation studies and be considered for platelet transfusions and/or fresh frozen plasma infusions.

B. Anticipated Length of Stay.

For meningococcal meningitis, this will usually be at least 7 days. For disseminated gonorrhea, the stay might be slightly shorter but could require several weeks of inpatient care.

C. When is the Patient Ready for Discharge.

For both Neisseria meningitidis and Neisseria gonorrhoeae, there is a required period of intravenous antibiotics. For meningococcal meningitis, this is 7 days. For DGI, the Centers for Disease Control recommends at least 7 days of antibiotics, with a switch to an oral agent after 24 to 48 hours if the patient shows improvement and if cultures show appropriate susceptibilities.

D. Arranging for Clinic Follow-up.

1. When should clinic follow up be arranged and with whom.

If patients are being discharged home, for both Neisseria meningitidis and Neisseria gonorrhoeae, they will likely require follow-up in an outpatient clinic within the next 1 to 2 weeks to verify resolution of symptoms.

2. What tests should be conducted prior to discharge to enable best clinic first visit.

None

3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit.

None

E. Placement Considerations.

Since the prognosis for meningococcal meningitis is so variable, the placement options are also varied. Patients with a successful course can likely be discharged to home with outpatient follow-up, but complications could result in either skilled-nursing placement or even a nursing home.

Barring unusual circumstances, a patient with DGI can likely be discharged to home directly from the hospital.

F. Prognosis and Patient Counseling.

The prognosis for meningococcal meningitis is largely dependent on appropriate administration of antibiotics and the presence or absence of several potential sequelae, such as disseminated intravascular coagulation, pericarditis, coma, and nosocomial pneumonia. For meningococcal meningitis, outbreak-associated infections are linked to a significantly higher mortality rate.

All patients with DGI should be counselled on safe-sex practices and routine STI screening.

VI. Patient Safety and Quality Measures.

A. Core Indicator Standards and Documentation.

NA

B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

For patients hospitalized with N. meningitidis or disseminated N. gonorrhoeae requiring intravenous antibiotic therapy, heparin prophylaxis to prevent deep vein thromboses should be considered. However, the benefits of this measure will need to weighed against, for example, the risk of spontaneous bleeding from thrombocytopenia in the setting of meningococcal infection.

For intubated patients, the hospitalist should also consider stress-ulcer prophylaxis.

All patients with DGI should also be tested for HIV coinfection and treated empirically for chlamydia.

VII. What's the evidence?

Talan, DA, Hoffman, JR, Yoshikawa, TT, Overturf, GD. "Role of empiric parenteral antibiotics prior to lumbar puncture in suspected bacterial meningitis: state of the art". Rev Infect Dis. vol. 10. 1988. pp. 365.

Thigpen, MC, Whitney, CG, Messonnier, NE. "Bacterial meningitis in the United States, 1998-2007". N Engl J Med. vol. 364. 2011. pp. 2016.

Durand, ML, Calderwood, SB, Weber, DJ. "Acute bacterial meningitis in adults. A review of 493 episodes". N Engl J Med. vol. 328. 1993. pp. 21.

Tunkel, AR, Hartman, BJ, Kaplan, SL. "Practice guidelines for the management of bacterial meningitis". Clin Infect Dis. vol. 39. 2004. pp. 1267.

Fijen, CA, Kuiiper, EJ, te Bulte, MT. "Assessment of complement deficiency in patients with meningococcal disease in The Netherlands". Clin Infectious Disease. vol. 28. 1999. pp. 98.

Ross, SC, Densen, P. "Complement deficiency states and infection: epidemiology, pathogenesis and consequences of neisserial and other infections in an immune deficiency". Medicine (Baltimore). vol. 63. 1984. pp. 243.

Rompalo, AM, Hook, EW, Roberts, PL. "The acute arthritis-dermatitis syndrome. The changing importance of Neisseria gonorrhoeae and Neisseria meningitidis". Arch Intern Med. vol. 147. 1987. pp. 281.

O'Brien, JP, Goldenberg, DL, Rice, PA. "Disseminated gonococcal infection: a prospective analysis of 49 patients and a review of pathophysiology and immune mechanisms". Medicine (Baltimore). vol. 62. 1983. pp. 395.

Rice, PA. "Gonococcal arthritis (disseminated gonococcal infection)". Infect Dis Clin North Am. vol. 19. 2005. pp. 853.

"Centers for Disease Control and Prevention". MMWR Recomm Rep. vol. 63. 2014. pp. 1.

Ghosn, SH, Kibbi, AG. "Cutaneous gonococcal infections". Clin Dermatol. vol. 22. 2004. pp. 476.

"Centers for Disease Control and Prevention (CDC). Sexually Transmitted Diseases Treatment Guidelines, 2015". MMWR. 2015. pp. 63.

Stephens, DS, Apicella, MA. "Principles and Practices of Infectious Diseases". Elsevier. c2015. pp. 2425-2445.

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