Meningococcal Infections

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Background

Meningococcal (Neisseria meningitidis) bloodstream infections (known as meningococcemia) can range in severity from a transient bacteremia that is relatively benign to an overwhelming infection that is rapidly fatal. Meningitis commonly occurs during the course of meningococcemia. In rare cases, N meningitidis organisms can spread hematogenously to other sites, such as the pericardium, the joints, and the eyes.

Pathophysiology

The human nasopharynx is the only known reservoir for N meningitidis. Meningococci spread from person to person by airborne droplets of infected nasopharyngeal secretions. Meningococcal organisms attach to mucosal surfaces, where they produce few symptoms. Concomitant viral respiratory infections, particularly those involving influenza viruses, appear to enhance the spread of meningococcal infection and the likelihood of nasopharyngeal carriage after exposure to meningococci.

Nasopharyngeal meningococcal infection is usually subclinical. Asymptomatic nasopharyngeal carriage of meningococci is transient and resolves within several weeks. In very rare cases, N meningitidis organisms invade the bloodstream and cause clinical disease. Clinical meningococcal disease can be arbitrarily classified into 3 general forms: (1) an uncomplicated bacteremic process, (2) a metastatic infection that commonly involves the meninges, or (3) an overwhelming systemic infection with circulatory collapse and evidence of disseminated intravascular coagulation (DIC).

The fundamental pathologic change in meningococcemia is widespread vascular injury characterized by endothelial necrosis, intraluminal thrombosis, and perivascular hemorrhage. Skin lesions usually contain numerous meningococci undergoing phagocytosis by neutrophils. Occlusive thrombi composed of platelets, red blood cells, and fibrin are most prominent in deep dermal vessels. Serous surfaces and other organs incur the same vascular injury, although N meningitidis bacteria are difficult to find in tissues other than the skin.

Patients with fulminant meningococcemia develop thrombosis and hemorrhage in the skin, the mucous membranes, the serosal surfaces, the adrenal sinusoids, and the renal glomeruli. Adrenal hemorrhage is rarely extensive. Thrombosis of the glomerular capillaries may cause renal cortical necrosis, the chief characteristic of the generalized Shwartzman reaction. Thrombi containing numerous leukocytes are occasionally found in the lungs, and extensive intra-alveolar hemorrhage can occur. Myocarditis has been observed in adults with fatal meningococcal infections.

Epidemiology

Frequency

United States

During the past 6 decades, the occurrence of meningococcal disease has been mostly sporadic, and no widespread outbreaks have occurred. The prevalence has been approximately 1-2 cases per 100,000 population, although it has shown variation from year to year.

Limited outbreaks of meningococcal disease have occurred in some populations. Public health officials arbitrarily define an outbreak of meningococcal disease as the occurrence of 3 or more cases during a 3-month period, with a primary attack rate of at least 10 cases per 100,000 population, which is approximately 10 times greater than normal. Outbreaks may be restricted to a closed population or may involve a larger community. In a Los Angeles County outbreak of meningococcal disease, nearly one half of community residents with the disease had had contact with persons who had been incarcerated.[1]

Recently, the incidence of meningococcal disease in adolescents and college-aged young adults appears to have increased. College students living in dormitories seemed to be the population at an increased risk (see Deterrence/Prevention).

Meningococcal disease is also a relatively common problem in military recruit populations.[2]

International

Meningococcal disease occurs sporadically or in episodic epidemics worldwide. Massive outbreaks of meningococcal disease have occurred in many parts of the world. Large-scale outbreaks have spread at cyclic intervals through Central African countries, with attack rates as high as 400-500 cases per 100,000 population, as shown in the image below.


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Areas with frequent epidemics of meningococcal disease. This is known as the Meningitis Belt of Africa, and visitors to these locales may benefit from....

Outbreaks of meningococcal disease have also occurred in Mecca, Saudi Arabia, and in visitors returning from that city.

Mortality/Morbidity

The case-fatality rate of meningococcal infections varies depending on the prevalence of disease, the clinical form of disease, and the socioeconomic conditions of the society in which the infections occur. In the United States, the case-fatality rate is approximately 10%.

During endemic situations in industrialized countries, the case-fatality rate can be as low as 3% for meningitis and as high as 50% for fulminant meningococcemia. The mortality rate of meningococcal disease may be lower during epidemic situations because heightened diagnostic awareness may result in detection and treatment of greater numbers of cases before the disease progresses to a more lethal form.

Fulminant meningococcemia carries the highest mortality rate; it can exceed 50% despite the use of appropriate antibiotic therapy. It can be as high as 70% in developing countries. Survivors of fulminant meningococcemia may have ischemic complications.

Meningococcal meningitis without antibiotic therapy is uniformly fatal.

Race

One population-based study in the United States found that the incidence of meningococcal disease was significantly higher among African Americans (1.5 cases per 100,000 population) than among Anglo Americans (1.1 cases per 100,000 population). The relative risk (RR) was 1.4 (95% confidence interval [CI], 1.1-1.8).

Sex

Males accounted for 55% of all cases, with an incidence of 1.2 cases per 100,000 population, compared to 1 case per 100,000 population among females (RR, 1.3; 95% CI, 1.0-1.6).

Age

Age is a major determinant of susceptibility to meningococcal disease; however, most infected individuals experience a period of asymptomatic carriage rather than symptomatic disease.[3]

The age-specific incidence of meningococcal disease is highest in young children, although maternal antibodies usually protect infants in the first few months of life. A multicenter study evaluating the serogroups in children with N meningitis infection found that meningococcal disease continues to result in substantial morbidity and mortality in children. The study found that, overall, 55 (44%) of isolates were serogroup B, 32 (26%) were serogroup C, and 27 (22%) were serogroup Y. All but one isolate (intermediate) were susceptible to penicillin. The overall mortality rate in this pediatric population was 8%.[4]

A 1995 study in the United States found that the incidence of meningococcal disease among infants aged 1-23 months was 11.1 cases per 100,000 population. The age-specific rate was 1.5 per 100,000 population among individuals aged 2-29 year, 0.6 among individuals aged 30-50 years, and 1.3 among individuals aged 60 years and older. See the image below.


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A 9-month-old baby in septic shock with purpuric Neisseria meningitis skin lesions. Photo by D. Scott Smith, MD, taken at Stanford University Hospital....

About one third of meningococcal disease cases occur in adults.

History

The clinical pattern of meningococcemia varies. After a few days of upper respiratory symptoms, the temperature rises abruptly, often after a chill. Malaise, weakness, myalgias, headache, nausea, vomiting, and arthralgias are common presenting symptoms. A skin rash, which is essential for recognizing meningococcemia, is the characteristic manifestation. The skin rash may advance from a few ill-defined lesions to a widespread petechial eruption within a few hours.

Fulminant meningococcemia is the most serious form of meningococcal disease. This form occurs in approximately 5-15% of cases of meningococcal disease. It begins abruptly with a high fever, chills, myalgias, weakness, nausea, vomiting, and headache. Apprehension, restlessness, and, frequently, delirium occur within the next few hours. The rash appears suddenly and is widespread, purpuric, and ecchymotic.

In adults, bacterial meningitis has a characteristic clinical pattern, although the progression of symptoms varies somewhat. Symptoms of meningitis may accompany the petechial rash of meningococcemia and may produce the predominant features on presentation.

Bacterial meningitis is a febrile illness of short duration; the major symptoms include headache and a stiff neck. Lethargy or drowsiness is common. Confusion, agitated delirium, and stupor are rarer; however, coma is an ominous prognostic sign.

The clinical pattern of bacterial meningitis is often atypical in young children because headache and nuchal rigidity are frequently absent. Irritability, especially upon movement, is a common presenting manifestation of meningitis in a young child. Convulsions may signal the onset of meningitis at this age. Progression of the illness results in the development of lassitude and a more constant fever, often accompanied by abdominal discomfort. Projectile vomiting may occur.

Chronic meningococcemia is a rare form of meningococcal disease. This is an intermittent bacteremic illness that lasts from at least one week to as long as several months. The fever tends to be intermittent, with afebrile periods ranging from 2-10 days, during which the patient seems completely healthy. As the disease progresses, the febrile periods become more common, and the fever may become continuous.

Eventually, a skin eruption or some other manifestation of meningococcal disease appears during a febrile episode.

Physical

Petechiae are the most common skin lesions of meningococcemia, and they may be distributed sparsely over the body, as depicted in the image below.


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Scattered petechial lesions in a patient with acute meningococcemia.

Critically ill patients with sepsis may develop rapidly progressing petechiae, ecchymoses, and extensive palpable purpura or retiform purpura, accompanied by DIC and vascular collapse.

Ill-defined pink macules are noted in some cases. Maculopapular lesions also occur and are sometimes large and plaquelike with a central petechia. Rash may be missed early in an individual with dark skin.

The skin lesions tend to occur in crops on any part of the body, occasionally presenting on the conjunctivae and the mucous membranes. The face is usually spared, and involvement of the palms and the soles is less common.

Patients with acute meningococcemia usually present with moderate fever (average, 39.5°C) and no signs of shock.

Fulminant meningococcemia is associated with a purpuric eruption, as shown in the images below. Lesions are generally characterized by maplike purpuric or necrotic areas. Amputation may be required in severe cases.


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The legs of a 22-year-old woman in septic shock with a rapidly evolving purpuric rash. Photo by D. Scott Smith, MD, taken at Stanford University Hospi....


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Purpuric lesions in a young adult with fulminant meningococcemia.

Hemorrhages may appear on the buccal mucosa and the conjunctivae.

Less frequently, fulminant meningococcemia presents as purpura fulminans. In rare cases, no skin lesions develop.

Symmetric peripheral gangrene has been described in this form.

Signs of meningitis are typically absent. However, cyanosis, hypotension, and profound shock eventually appear.

Patients with fulminant meningococcemia usually present with a high fever (average temperature, 40.6°C). The blood pressure is lowered, and pulmonary insufficiency develops within a few hours.

Many patients with fulminant meningococcemia die despite appropriate antibiotic therapy and intensive care. Patients with fatal forms of fulminant meningococcemia are likely to die within 24-48 hours of presentation.

The characteristic physical examination findings of meningitis include pain and resistance to neck flexion. Other signs of meningeal irritation can also be elicited. Children with meningitis may have none of these findings.

The Kernig sign is positive when the leg cannot be extended more than 135° on the thigh when flexed 90° at the hip.

The Brudzinski sign is positive when neck flexion causes involuntary flexion of the thighs and the legs.

Focal neurologic signs are uncommon presenting findings of bacterial meningitis. However, nuchal rigidity may not be elicited in patients who are comatose and who may have signs of focal or diffuse neurologic deficits.

Papilledema is not a presenting feature of bacterial meningitis and suggests the presence of an accompanying process.

A common presenting sign of meningococcal meningitis is a petechial rash.

Most patients with meningitis are febrile, although the height of fever varies.

Causes

N meningitidis is a gram-negative diplococcus that grows well on solid media supplemented with blood and incubated in a moist atmosphere enriched with carbon dioxide.

Oxidase and catalase are biochemical markers for preliminary identification of N meningitidis. Sugar fermentations are required for final identification of the species. N meningitidis ferments glucose and maltose, not sucrose or lactose.

Agglutination reactions with immune serum subdivide N meningitidis into serogroups A, B, C, W135, X, Y, and Z, depending on a group-specific capsular polysaccharide antigen. Most strains that cause meningococcal disease have the polysaccharide antigen of groups A, B, or C. Group Y and group W135 meningococci cause disease more commonly than groups X and Z. Meningococcal strains that lack these group-specific antigens are believed to be nonpathogenic. The cell wall of pathogenic meningococci contains a toxic lipopolysaccharide or endotoxin. Meningococcal endotoxin appears to be chemically identical to enteric bacilli endotoxin.

Susceptibility to meningococcal disease has been linked with the absence of bactericidal antibody against pathogenic meningococci. Immunoglobulin G (IgG) antibodies that have specificity for the meningococcal polysaccharides mediate bactericidal activity. Complement is needed for expression of this activity. Asymptomatic nasopharyngeal carriage of meningococci induces a humoral antibody response, and most individuals acquire immunity to meningococcal disease by age 20 years. Passively transferred maternal antibody provides temporary protection to infants for the first 3-6 months of life. Colonization with nonpathogenic meningococci seems to induce cross-reacting protective antibodies. An episode of meningococcal disease confers group-specific immunity, but a second episode may be caused by another meningococcal serogroup.

Recurrent meningococcal disease has been linked to congenital complement deficiencies, which usually affect the terminal components of the complement cascade.

Hereditary properdin deficiency may also predispose to meningococcal disease.

Laboratory Studies

Collect blood cultures (2 sets, with at least 10 mL per bottle) in any febrile patient with a petechial rash.

CBC count, platelet count, BUN study, creatinine clearance evaluation, and a series of coagulation studies can be used to evaluate a consumptive coagulopathy. DIC is a laboratory diagnosis, but no single laboratory test is diagnostic. Instead, DIC is recognized clinically by a pattern of changes in numerous coagulation tests. Typically, these changes include lowered platelet count, prolonged prothrombin time, prolonged partial thromboplastin time, lowered fibrinogen levels, and the presence of fibrin-split products in the circulation. Not all of these changes are found in all patients. Fibrinogen, an acute-phase reactant, may be elevated in patients with DIC.

Gram stain of the peripheral blood buffy coat may reveal gram-negative diplococci in fulminant meningococcemia.

Needle aspirates or skin biopsy specimens from patients with meningococcal sepsis tested using Gram stain yield a 72% sensitivity based on one study and was reportedly 80% using scraped material from petechial lesions in another retrospective study.[5] A prospective controlled study combining Gram stain and culture of skin biopsy specimens reported a sensitivity of 56%.[6]

A study of adults with fulminant meningococcemia found that 4 variables at the time of admission portend a fatal outcome (odds ratio, 2; CI, 1.5-2.7).

Imaging Studies

Brain imaging studies before a lumbar puncture (LP) are unnecessary unless the patient is obtunded, has focal neurologic signs, has experienced a seizure within the previous week, or presents with papilledema.

Other Tests

A polymerase chain reaction (PCR) test has been developed for detection of N meningitidis DNA in clinical specimens.[7, 8, 9, 10, 11] PCR can be used to detect small amounts of meningococcal DNA in CSF. It is thought to be a more sensitive test for meningococcal meningitis than culture methods. Because of the cost and expertise necessary to operate a PCR assay, this diagnostic test is used only in large-scale outbreaks when numerous specimens can be analyzed. Several studies have confirmed the usefulness of this method in an epidemic setting. A recent small case series reported the utility of PCR assay using skin biopsy specimens to assist in diagnosis when routine microbiologic tests fail to isolate the bacteria.[11]

Procedures

Perform LP for CSF evaluation. Immediately stain and culture spinal fluid. Gram stain of the CSF should be immediately performed and examined microscopically. Organisms can be observed in the CSF in approximately half of patients who present with meningococcal meningitis. Send the CSF for WBC count, WBC differential, total protein content, and glucose studies. Send additional tests as indicated for ruling out other diagnoses.

Bacterial meningitis produces various inflammatory changes in the CSF. The CSF becomes turbid with more than 1000 WBC/µL, and the cells are predominantly polymorphonuclear. The intracranial pressure (ICP) may be elevated. The total protein content is increased, and the glucose level, which is normally 60% of the simultaneous blood glucose level, becomes lowered (hypoglycorrhachia).

Histologic Findings

Leukocytoclastic vasculitis, thrombosis, and organisms are often demonstrated in biopsy specimens collected from patients with acute meningococcemia.

Perivascular lymphocytic infiltrate with few neutrophils characterize chronic meningococcemia, although leukocytoclastic vasculitis may be seen in biopsies of petechial lesions.

Medical Care

If the presentation is consistent with bacterial meningitis and/or the CSF findings are compatible with pyogenic meningitis, promptly start appropriate antimicrobial therapy. Some authors recommend initiation of appropriate antimicrobial therapy even before LP is performed in highly suspected cases.

Gram-negative diplococci identified in the CSF with microscopy further suggest meningococcal meningitis.

Fulminant meningococcemia is the most life-threatening form of meningococcal disease and may be the most difficult to recognize early. Patients with fulminant meningococcemia are likely to be hypotensive and have a severe coagulation abnormality consistent with disseminated intravascular clotting. Perform LP upon presentation, although most study findings other than the culture may be unremarkable.

Patients with fulminant meningococcemia should be treated in an intensive care setting where frequent monitoring is readily available. Initiate appropriate antimicrobial therapy as soon as possible. Therapy is also directed at correcting circulatory collapse and maintaining renal function. Fulminant meningococcemia infrequently leads to adrenal insufficiency. If adrenal insufficiency occurs, corticosteroid replacement may be considered.

Meningococci are susceptible to several antimicrobial agents. Penicillin G is more active against N meningitidis than other penicillins. The minimal inhibitory concentration (MIC) of penicillin usually ranges from 0.01-0.05 µg/mL against meningococcal isolates.

Relative resistance to penicillin (MIC = 0.1-1 µg/mL) was not recognized in the United States until 1991, although it had previously been reported in Europe. The mechanism of resistance is decreased affinity of its penicillin-binding protein 2 for penicillin. Meningococci with relative resistance to penicillin made up only 3% of isolates in the United States in 1991. No isolates that are highly resistant to penicillin (MIC >1 µg/mL) have been found in the United States, although isolates producing beta-lactamase have been reported in South Africa.[12]

Ceftriaxone, cefotaxime, and cefuroxime are cephalosporins that penetrate sufficiently into CSF from blood and are useful in the treatment of bacterial meningitis. These cephalosporins are known to have a potent action against meningococci, as do chloramphenicol, rifampin, erythromycin, and tetracyclines. Meningococci were found to be susceptible to ciprofloxacin at low concentrations.

Meningococci resistant to sulfadiazine (MIC >0.128 µg/mL) have appeared. Surveillance studies in the last 10 years indicate that approximately one third of clinical isolates in the United States are resistant to sulfonamides.

Meningococci are not inherently susceptible to vancomycin, polymyxin, or achievable serum levels of aminoglycoside antibiotics.

Surgical Care

Ischemic complications of fulminant meningococcemia may require surgical care for management.

Diet

Patients with meningitis or fulminant meningococcemia are at risk of vomiting and should be prevented from taking anything by mouth prior to substantial clinical improvement with antimicrobial therapy.

Activity

Bed rest is recommended for patients suspected of having meningococcal disease. Place patients with meningococcal disease on respiratory precautions for the first 24 hours of effective chemotherapy. Respiratory precautions generally include placement in a private room with proper air handling and the use of a respiratory mask by any person entering the patient's room.

Medication Summary

Institute specific antimicrobial therapy promptly when clinical features suggest meningococcemia or meningococcal meningitis. The recommended drug for the treatment of meningococcal disease is intravenous penicillin G. Infections caused by organisms that are relatively resistant to penicillin seem to respond to this drug as well as fully susceptible organisms do.

Most authorities believe that ceftriaxone and cefotaxime are equally as efficacious as penicillin in the treatment of meningococcal meningitis. Ceftriaxone has the added advantage of having been proven able to eradicate the nasopharyngeal carriage of meningococci. Chloramphenicol is recommended for patients who are severely allergic to penicillin.

Most patients with uncomplicated meningococcemia defervesce within the first 24 hours of antibiotic therapy. Antibiotic therapy for uncomplicated meningococcemia needs to be administered for only 4-5 days after defervescence occurs, and, in adults, the dosage needed to complete the course of therapy can be reduced.

Corticosteroids are recommended for some types of meningitis, but they are not advocated for the treatment of meningococcal meningitis.

Other drugs used in the treatment of fulminant meningococcemia are those used to support the circulation, such as dopamine, and those used to treat DIC. The treatment of DIC with heparin is controversial.

Other drugs used to treat meningococcal meningitis are those that reduce ICP. Treatment of complications with steroids and mannitol is not very effective and is controversial.

Penicillin G (Pfizerpen)

Clinical Context:  Patients suspected of having meningococcal disease should receive a high dosage of penicillin G for the initial 48 h of therapy because meningitis is a likely complication. Infections caused by organisms classified as relatively resistant to penicillin, based on a MIC = 0.1-1 µg/mL of penicillin, seem to respond to this drug as well as fully susceptible organisms do.

Ceftriaxone (Rocephin)

Clinical Context:  Third-generation cephalosporin with broad-spectrum, gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. Arrests bacterial growth by binding to 1 or more penicillin-binding proteins. Equally efficacious as penicillin in treatment of meningococcal disease; however, it is more expensive.

Cefotaxime (Claforan)

Clinical Context:  Third-generation cephalosporin with gram-negative spectrum. Lower efficacy against gram-positive organisms. More expensive than penicillin, but most authorities believe that it is equally efficacious as penicillin in the treatment of meningococcal disease

Chloramphenicol (Chloromycetin)

Clinical Context:  Binds to 50S bacterial ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis. Effective against gram-negative and gram-positive bacteria. Alternate therapy of meningococcal meningitis in patients who are allergic to penicillin.

Cefuroxime (Kefurox, Zinacef)

Clinical Context:  Only second-generation cephalosporin approved for use in the treatment of meningitis. Has significant penetration into CSF and enhanced stability against beta-lactamases of Haemophilus influenzae, Neisseria gonorrhoeae, and some Enterobacteriaceae, compared to other first- and second-generation cephalosporins. Its pharmacologic properties most closely resemble those of cefotaxime. Condition of the patient, severity of the infection, and susceptibility of microorganism determines proper dose and route of administration.

Rifampin (Rifadin, Rimactane)

Clinical Context:  Commonly used for meningococcal prophylaxis of household contacts in United States, where one third of prevalent strains are sulfadiazine resistant.

Sulfadiazine (Microsulfon)

Clinical Context:  Through a competitive antagonism of PABA, this agent interferes with microbial growth. Commonly used for meningococcal prophylaxis.

Ciprofloxacin (Cipro)

Clinical Context:  A single dose of 500 mg ciprofloxacin has been found to provide an effective alternative to rifampin for the eradication of meningococcal carriage in adults. Not recommended for persons younger than 18 y because it has caused cartilage damage in immature experimental animals.

Commonly used for meningococcal prophylaxis.

Ceftriaxone (Rocephin)

Clinical Context:  Third-generation cephalosporin with broad-spectrum, gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. Arrests bacterial growth by binding to 1 or more penicillin-binding proteins. A single IM injection has been found to eradicate meningococcal carriage.

Commonly used for meningococcal prophylaxis.

Minocycline (Minocin)

Clinical Context:  A member of the tetracycline class of antimicrobial agents. It is a broad-spectrum agent that inhibits susceptible organisms by blocking their protein synthesis. Although an oral form of the drug has been approved for chemoprophylactic use to eradicate the meningococcal carrier state, its use for these purposes was associated with a high incidence of general and gastrointestinal symptoms. Thus, it is now only of historic interest.

Commonly used for meningococcal prophylaxis.

Erythromycin base

Clinical Context:  Antibiotic that interferes with protein synthesis of susceptible organisms. Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes causing RNA-dependent protein synthesis to arrest. Mostly used orally; however, a parenteral form is available. Although meningococci are susceptible to erythromycin, this drug is not recommended for use either as treatment for meningococcal infection or as a prophylactic agent.

In children, age, weight, and severity of infection determine proper dosage. When bid dosing is desired, half-total daily dose may be taken q12h. For more severe infections, double the dose.

Tetracycline (Achromycin)

Clinical Context:  A drug in a class of broad-spectrum agents that inhibits susceptible organisms by blocking protein synthesis. Inhibits bacterial protein synthesis by binding with 30S and, possibly, 50S ribosomal subunits. This drug class is not recommended for use as a treatment of meningococcal infection. One of the drugs in this class is minocycline; it has been used as a prophylactic agent.

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. People who come into household contact with patients who have meningococcal disease are at risk of acquiring this illness. Person-to-person transmission can be interrupted by chemoprophylaxis, which eradicates the asymptomatic nasopharyngeal carrier state. Rifampin, quinolones, and sulfonamides are the antimicrobials used to eradicate meningococci from the nasopharynx.

Dopamine (Intropin)

Clinical Context:  Stimulates both adrenergic and dopaminergic receptors. Hemodynamic effect is dependent on the dose. Lower doses predominantly stimulate dopaminergic receptors that, in turn, produce renal and mesenteric vasodilation. Cardiac stimulation and renal vasodilation produced by higher doses. After initiating therapy, increase dose by 1-4 mcg/kg/min q10-30min until optimal response is obtained. More than 50% of patients are satisfactorily maintained on doses less than 20 mcg/kg/min.

Class Summary

These agents are used to support circulation in patients with shock.

Further Inpatient Care

Patients with meningococcal disease must complete a course of antimicrobial therapy.

Any complications of meningococcal disease must also be treated. One of the most common complications that occur during the course of treatment is arthritis, which has been found in about 10% of patients with meningococcal disease. This complication usually occurs within the first few days of treatment and manifests as effusion of a large joint, often the knee. Joint effusions usually resolve without a change in therapy; occasionally, repeated arthrocentesis is needed to control symptoms.

Other possible complications include ischemic conditions caused by the coagulation abnormality and neurologic complications of meningitis. The patient must be observed for any neurologic sequelae. The frequency of neurologic abnormalities seems to be related to the severity of the acute disease. Some neurologic sequelae can develop in the absence of meningitis.

Respiratory precautions may be discontinued once the patient has received 24 hours of effective antimicrobial therapy.

Further Outpatient Care

Household contacts and close respiratory contacts of a patient should undergo chemoprophylaxis to eliminate the carrier state and to prevent the spread of infection or reinfection.

Observe patients for any late neurologic sequelae. Abnormal findings on electroencephalography, epileptogenic activity, sensorineural hearing loss, impaired vestibular function, abnormal findings on cerebral CT scan, and neuropsychological impairment have been found in up to 30% of survivors 1 year after an episode of meningococcal disease. The frequency of serious neurologic sequelae in individuals who survive an episode is 3%.

Inpatient & Outpatient Medications

Rifampin is used for chemoprophylaxis (see Medications). Single-dose ciprofloxacin has also been recommended for contact prophylaxis in adults.

Sulfadiazine can be used for chemoprophylaxis when the causative meningococcal isolate is known to be susceptible to this antimicrobial (see Medications).

Transfer

Promptly transfer any patient who is acutely ill with fever, headache, and petechial rash to a hospital for medical evaluation. This evaluation should include an LP for examination of the CSF.

Deterrence/Prevention

[13] Antimicrobial chemoprophylaxis of close contacts is the primary means of preventing secondary cases of sporadic meningococcal disease. Person-to-person transmission can be interrupted by administration of an antimicrobial that eradicates the asymptomatic nasopharyngeal carrier state. Sulfonamides, rifampin, minocycline, ciprofloxacin, and ceftriaxone are the drugs that have been shown to eradicate meningococci from the nasopharynx.

Meningococcal infection is probably introduced into families by asymptomatic adults and then spread through one or more household contacts to infect younger family members. Household contacts are defined as individuals who live in the same house with a person who has a meningococcal disease. An operational definition commonly used by public health authorities includes persons eating and sleeping under the same roof with the index case. The attack rate of meningococcal disease among household contacts has been estimated to be several hundred times greater than that in the general population. The secondary attack rate is inversely proportional to age and is estimated to be approximately 10% in household contacts aged 1-4 years.

The risk of acquiring meningococcal disease may also be increased in other closed populations, such as those of daycare facilities and nursery schools. The American Academy of Pediatrics recommends antimicrobial chemoprophylaxis for contacts of persons with invasive meningococcal disease, including household members, individuals at daycare centers and nursery schools, and persons directly exposed to the patient's oral secretions (eg, kissing, sharing food or beverages) within 7 days preceding the onset of the illness in the index case. The decision to administer chemoprophylaxis to other populations should be reached only after consultation with public health authorities who have a better understanding of the patterns of disease that currently exist in the community.

Consider antimicrobial chemoprophylaxis in hospital personnel who have direct exposure to the oral secretions of a patient with meningococcal disease from such activities as mouth-to-mouth resuscitation, endotracheal intubation, or endotracheal tube management. Patients with meningococcal disease who are hospitalized should be placed on respiratory precautions for the first 24 hours of effective antimicrobial therapy. When this is done, the risk for hospital personnel with casual or indirect contact is believed to be negligible. Antimicrobial chemoprophylaxis is not recommended in hospital personnel who have only casual or indirect contact with a patient with meningococcal disease.

For travelers, antimicrobial chemoprophylaxis should be considered for any passenger who had direct contact with respiratory secretions from an index patient or for anyone seated directly next to an index patient on a prolonged flight (ie, one that lasts ≥8 h).

Rifampin is commonly used for meningococcal prophylaxis of household contacts in the United States, where one third of the prevalent strains are sulfadiazine resistant. A 2-day course of rifampin is recommended. The rapid emergence of rifampin-resistant meningococci precludes the use of this drug in large populations. Chemoprophylaxis of sulfadiazine-resistant meningococci by rifampin should be accompanied by close observation of household contacts for signs of disease. A single dose of ciprofloxacin has been found to provide an effective alternative to rifampin for the eradication of meningococcal carriage in adults.

Ciprofloxacin is not recommended in persons younger than 18 years because it has caused cartilage damage in immature experimental animals. A single intramuscular injection of ceftriaxone has been found to eradicate meningococcal carriage. The chemoprophylactic dose of ceftriaxone is 250 mg IM in adults and 125 mg IM in children.

Meningococcal isolates that are susceptible to sulfadiazine can be eradicated by a 2-day course of sulfadiazine. The high incidence of adverse effects has limited acceptance of minocycline as a means of eradicating the carrier state.

Meningococcal disease can be prevented by vaccination with group-specific meningococcal capsular polysaccharides. The CDC has issued an updated 2010 guideline for meningococcal conjugate vaccines (ie, Menactra, Menveo).[13]

Purified polysaccharides of groups A, C, Y, and W135 meningococci have been used to stimulate group-specific humoral bactericidal antibodies.

A meningococcal polysaccharide vaccine (MPSV4), which is quadrivalent, has been a highly effective means of preventing disease caused by these serogroups of meningococci. A single dose of vaccine does not protect younger children, especially those younger than 2 years. Menactra has been approved for high-risk children aged 9-23 months.[14] Use of the vaccine is indicated for the at-risk population whenever an outbreak caused by one of these serogroups of meningococci occurs and for terminal complement deficiency and anatomic asplenia patients. In 2005, a tetravalent meningococcal polysaccharide-protein conjugate (MCV4) was licensed for use among persons aged 2-55 years. This vaccine has the advantage of producing a longer duration of protective antibodies.

The ACIP recommends vaccination with MCV4 before high-school entry as an effective strategy to reduce meningococcal disease incidence among adolescents and young adults. MCV4 is also recommended for at-risk populations, including college freshmen living in dormitories, military recruits, travelers to areas where meningococcal disease is hyperendemic or epidemic, microbiologists who are routinely exposed to meningococci, patients with anatomic or functional asplenia, and patients with terminal complement deficiency. Other adolescents, college students, and persons infected with HIV who wish to decrease their risk for meningococcal disease may elect to receive this vaccine.

The risk of Guillain-Barré Syndrome (GBS) seems to be slightly increased among recipients of the MCV4 (Menactra) vaccine.[15] The CDC estimates the rate to be 0.2 per 100,000 person-months in individuals aged 11-19 years who received the vaccine. The background rate was estimated at 0.11 per 100,000 person-months in this population group. The CDC recommends that persons with a history of GBS not receive MCV4, although persons with a history of GBS at especially high risk for meningococcal disease (eg, microbiologists routinely exposed to isolates of N meningitidis) might consider vaccination. The ACIP is in the process of reviewing the current recommendations for MCV4.

Although the capsular polysaccharide of group B meningococci is not immunogenic, progress has been made in obtaining a satisfactory vaccine for group B meningococcal disease. A vaccine for group B organisms was developed in Cuba and consists of outer-membrane proteins that are capable of inducing group-specific bactericidal antibody. Clinical trials with this vaccine in the United States have not been completed.

Vaccination with the meningococcal polysaccharides has also been used effectively in military recruit populations to control disease caused by group A and group C N meningitidis.

The increased incidence of meningococcal disease in adolescents and college-aged young adults has prompted consideration of a policy of routine vaccination in this population. The ACIP recommends college freshmen and their parents be provided information about the risk of meningococcal disease and the availability of MCV4 so they can make an informed decision regarding vaccination. Routine vaccination with MCV4 of all children is recommended by ACIP beginning at age 11 years.

Complications

Many complications occur in fulminant meningococcemia. Patients with fulminant meningococcemia may develop respiratory insufficiency and need mechanical ventilation. Patients with severe DIC may develop a hemorrhagic diathesis with bleeding into the lungs, urinary tract, and gastrointestinal tract. Ischemic complications of DIC have been reported in up to 50% of survivors of fulminant meningococcemia.

Meningococcal meningitis may progress to mental obtundation, stupor, or coma, which may be related to increased ICP, and such patients are prone to herniation. Other rare complications of meningitis include acute and delayed venous thrombosis, which usually manifests as a focal neurologic deficit.

Meningococcal infection may spread through the bloodstream and localize in other parts of the body, where it can cause suppurative complications. Septic arthritis, purulent pericarditis[16] , and endophthalmitis[17] can occur but are uncommon. Meningococcal pneumonia has been described and probably results from aspiration of N meningitidis. The W135 serogroup of meningococci was found to be more likely to cause this form of meningococcal disease, as well as pericarditis or septic arthritis.

Approximately 10% of patients with meningococcal disease develop nonsuppurative arthritis, usually of the knee joints. This usually becomes evident within the first 48 hours of treatment. Nonsuppurative arthritis is believed to occur on an immunologic basis.

Meningococcal disease may progress very quickly and can result in loss of life, neurologic impairment, or peripheral gangrene.

Recurrent meningococcal disease has been associated with hereditary deficiencies of various terminal components of the complement system.

Prognosis

The prognosis of fulminant meningococcemia is guarded. Approximately one half of patients who present with this form of meningococcal disease do not survive, even with prompt administration of appropriate antimicrobial therapy.

The prognosis of meningococcal meningitis is relatively good if the patient is neither comatose nor has focal neurologic findings. Most patients with this form recover completely when appropriate antimicrobial therapy is administered promptly upon presentation.

Author

Darvin Scott Smith, MD, MSc, DTM&H, Adjunct Assistant Professor, Department of Microbiology and Immunology, Stanford University School of Medicine; Chief of Infectious Diseases and Geographic Medicine, Department of Internal Medicine, Kaiser Redwood City Hospital

Disclosure: Nothing to disclose.

Coauthor(s)

Joanna L Chan, MD, Mohs Fellow, California Skin Institute

Disclosure: Nothing to disclose.

Thomas A Hoffman, MD, Professor, Department of Internal Medicine, Division of Infectious Diseases, Jackson Memorial Hospital, University of Miami

Disclosure: Nothing to disclose.

Specialty Editors

Joseph Richard Masci, MD, Professor of Medicine, Professor of Preventive Medicine, Mount Sinai School of Medicine; Director of Medicine, Elmhurst Hospital Center

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Aaron Glatt, MD, Professor of Clinical Medicine, New York Medical College; President and CEO, Former Chief Medical Officer, Departments of Medicine and Infectious Diseases, St Joseph Hospital (formerly New Island Hospital)

Disclosure: Nothing to disclose.

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital

Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital

Disclosure: Nothing to disclose.

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Areas with frequent epidemics of meningococcal disease. This is known as the Meningitis Belt of Africa, and visitors to these locales may benefit from meningitis vaccine. Image courtesy of CDC.

A 9-month-old baby in septic shock with purpuric Neisseria meningitis skin lesions. Photo by D. Scott Smith, MD, taken at Stanford University Hospital.

Scattered petechial lesions in a patient with acute meningococcemia.

The legs of a 22-year-old woman in septic shock with a rapidly evolving purpuric rash. Photo by D. Scott Smith, MD, taken at Stanford University Hospital.

Purpuric lesions in a young adult with fulminant meningococcemia.

Scattered petechial lesions in a patient with acute meningococcemia.

Purpuric lesions in a young adult with fulminant meningococcemia.

The legs of a 22-year-old woman in septic shock with a rapidly evolving purpuric rash. Photo by D. Scott Smith, MD, taken at Stanford University Hospital.

A 9-month-old baby in septic shock with purpuric Neisseria meningitis skin lesions. Photo by D. Scott Smith, MD, taken at Stanford University Hospital.

The leg of a 9-month-old infant in septic shock with a rapidly evolving purpuric rash. Photo by D. Scott Smith, MD, taken at Stanford University Hospital.

Neisseria meningitis purpuric lesions on the ear and cheek of a 9-month-old infant who is in septic shock. Photo by D. Scott Smith, MD, taken at Stanford University Hospital.

Lesions caused by Neisseria meningitis bacteremia on the palm of the hand of a 9-month-old infant. Photo by D. Scott Smith, MD, taken at Stanford University Hospital.

Areas with frequent epidemics of meningococcal disease. This is known as the Meningitis Belt of Africa, and visitors to these locales may benefit from meningitis vaccine. Image courtesy of CDC.