Treatment and prevention of meningococcal infection

INTRODUCTION — Neisseria meningitidis is an important cause of community-acquired bacterial meningitis and sepsis in children and adults in the United States and in many other countries. (See "Epidemiology of Neisseria meningitidis infection" and "Bacterial meningitis in children older than one month: Clinical features and diagnosis", section on 'Causative organisms' and "Epidemiology of community-acquired bacterial meningitis in adults".)

The clinical manifestations of meningococcal disease can be quite varied, ranging from transient fever and bacteremia to fulminant disease with death ensuing within hours of the onset of clinical symptoms. (See "Clinical manifestations of meningococcal infection".)

The treatment and prevention of meningococcal infection will be reviewed here [1-3]. The microbiology, pathobiology, epidemiology, and diagnosis of N. meningitidis infection are discussed separately. (See "Microbiology and pathobiology of Neisseria meningitidis" and "Epidemiology of Neisseria meningitidis infection" and "Diagnosis of meningococcal infection".)

TREATMENT OF MENINGITIS AND SEPSIS — The treatment of meningococcal sepsis is a complex medical problem, requiring a team approach by physicians skilled in intensive care medicine, infectious diseases, and the management of coagulopathies. Whenever possible, treatment should be given in a facility capable of administering the full range of medical care.

Antibiotic therapy

Importance of early administration — Invasive meningococcal infection is a medical emergency. Early and appropriate antibiotic treatment markedly improves the outcome of invasive meningococcal infections [4-6]. (See 'Prognosis' below.)

For patients with known or suspected invasive meningococcal infection (patients with severe sepsis syndrome, fever with petechiae and/or ecchymoses, or suspected bacterial meningitis), all attempts should be made to initiate parenteral antibiotics as quickly as possible. Concern for meningococcal disease should be particularly high in the setting of an outbreak or in patients with risk factors for meningococcal disease, such as those with complement deficiencies. (See "Clinical manifestations of meningococcal infection" and "Epidemiology of Neisseria meningitidis infection", section on 'Risk factors for acquisition of infection'.)

Advisory groups suggest antibiotics be administered as soon as one hour from the time of presentation given the variability in, and sometimes fulminant, clinical presentation [7,8]. Patients with meningococcal sepsis have extremely high bacterial loads, and increasing bacterial loads have been associated with increased odds of death [9,10]. Given the rapid division time of meningococcus in vitro, a delay of 70 minutes would result in such an increase and a higher risk of a poor outcome. Appropriate parenteral therapy can clear the cerebrospinal fluid (CSF) of meningococci in less than six hours [11].

Blood cultures should be drawn prior to initiation of antibiotic therapy if possible, but antibiotic therapy should not be delayed while waiting for lumbar puncture to be performed. Although administration of antibiotic therapy prior to lumbar puncture can substantially diminish the probability of a positive CSF culture, the diagnosis can often be established from the pretreatment blood cultures and/or polymerase chain reaction (PCR) or other molecular tools. (See "Diagnosis of meningococcal infection".)

If meningococcal infection is suspected in a physician's office or outpatient clinic, the patient should be stabilized and transported promptly to an appropriate hospital facility. Many experts also suggest giving antibiotics (eg, intramuscular ceftriaxone) in the outpatient setting if a patient cannot be transferred within an hour to a hospital but do not delay transfer for antibiotic administration [12,13]. Studies performed during epidemics in the 1990s suggested that administration of antibiotics prior to transfer was associated with improved outcome [4,6]. In addition, a statistical analysis of 125 patients with meningococcal disease who received antibiotic therapy prior to admission (oral or parenteral) suggested that treatment was not harmful and benefitted some less severely ill populations of patients [14].

Additional care should be taken with infants, for whom an adequate history may not be obtainable. In such situations, direct observation in a controlled setting (eg, emergency room or hospital admission) with empiric treatment until the diagnosis can be excluded is appropriate. (See "Bacterial meningitis in the neonate: Clinical features and diagnosis" and "Bacterial meningitis in children older than one month: Clinical features and diagnosis".)

Regimen selection — In cases of suspected bacterial meningitis, patients should be treated empirically to cover the most likely pathogens while awaiting culture results or molecular diagnostic tests. The following discussion will focus on the treatment of presumed meningococcal infection. Topic reviews that provide a more general overview of initial therapy for bacterial meningitis are presented separately. (See "Initial therapy and prognosis of community-acquired bacterial meningitis in adults" and "Bacterial meningitis in children older than one month: Treatment and prognosis" and "Bacterial meningitis in the neonate: Treatment and outcome".)

Therapy pending results of susceptibility testing — Intravenous (IV) ceftriaxone should be used for treatment of meningococcal meningitis or sepsis pending the results of susceptibility testing. For adults, ceftriaxone is administered as 2 g IV every 12 hours. For children, the dose is 50 mg/kg (maximum 2 g) IV every 12 hours. Cefotaxime can be used instead of ceftriaxone, but this agent is not available in many settings and must be administered more frequently than ceftriaxone.

Resistance to penicillin is an increasing concern due to the widespread appearance in 2019 of beta-lactamase-containing meningococci that are resistant to penicillin but sensitive to third-generation cephalosporins [15-18]. In one report that evaluated 372 N. meningitidis serogroup isolates in the United States from 2013 to 2020, approximately 9 percent were resistant to penicillin but sensitive to third generation cephalosporins [15]. In another study of 695 meningococcal isolates collected in the United States from 2012 to 2016, all were susceptible to cefotaxime, ceftriaxone, meropenem, rifampin, minocycline, and azithromycin, but approximately 25 percent were penicillin or ampicillin intermediate [18]. Although isolates with reduced susceptibility to third generation cephalosporins have been reported, they are less common. In one study from France, invasive meningococcal isolates with reduced susceptibility to third generation cephalosporins represented 2 percent of cases between 2012 and 2015 [19].

Therapy based on results of susceptibility testing — If susceptibility testing is not reflexively performed, it should be requested. Treatment decisions can be impacted by the appearance of bla_ROB-1 beta-lactamase gene containing invasive N. meningitidis, which has been found in the United States and elsewhere [15]. These isolates are penicillin resistant but susceptible to third-generation cephalosporins.

●Isolates susceptible to penicillin – If susceptibility testing indicates that the isolate is penicillin susceptible (minimum inhibitory concentration [MIC] <0.1 mcg/mL), either ceftriaxone or penicillin can be used [20-22]. Ceftriaxone has the advantage of more convenient dosing, but aqueous penicillin IV may be less costly in some cases. If penicillin is selected, patients should undergo subsequent eradication therapy for presumed nasopharyngeal carriage. (See 'Eradication of nasal carriage for select patients' below.)

If penicillin is used, the typical regimen for adults is penicillin G 4 million units IV every four hours. For children, the dose is 300,000 units/kg per day in a divided dose every six hours; the usual maximum dose is 12 million units/day [23]. Penicillin should never be administered intrathecally because of the danger of severe neurotoxicity; in addition, intrathecal therapy is not necessary since both penicillins and cephalosporins readily cross the blood-brain barrier to attain adequate CSF concentrations.

The dose of ceftriaxone is described above. (See 'Therapy pending results of susceptibility testing' above.)

Ceftriaxone and penicillin are bactericidal and have been shown to clear the CSF of viable organisms quickly. They reach levels in the CSF in excess of those needed to treat meningococcus, and the duration of antibiotic activity is prolonged, resulting in stable levels [24,25].

However, there are limited clinical data comparing outcomes with penicillin or ceftriaxone [20-22]. In an observational study in which most patients received penicillin for four or seven days or ceftriaxone for four days, the overall case-fatality rate was approximately 6 to 7 percent, and the rate of chronic neurologic sequelae was also 6 to 7 percent [26]. These are greatly improved over historical mortality rates prior to the availability of antibiotics. (See 'Prognosis' below.)

●Isolates with reduced susceptibility to penicillin – If the isolate has reduced susceptibility to penicillin, the approach to treatment depends upon sensitivity to ceftriaxone.

•Most isolates that have reduced susceptibility to penicillin (MIC ≥0.1 mcg/mL) are susceptible to ceftriaxone. The dose of ceftriaxone is the same as those used for penicillin-susceptible isolates (2 g IV every 12 hours for adults, or 50 mg/kg (maximum 2 g) IV every 12 hours for children). Although high-dose penicillin may be effective if the penicillin MIC is between 0.1 and 1.0 mcg/mL, ceftriaxone is preferred.

•In the rare event that the isolate is resistant to both penicillin and ceftriaxone, chloramphenicol can be used if locally available; other possible choices are meropenem, a fluoroquinolone such as levofloxacin or moxifloxacin, or aztreonam [27], similar to patients who cannot receive a beta-lactam. (See 'Patients intolerant of beta-lactams' below.)

Relative resistance to penicillin is caused by a reduced binding affinity to specific penicillin-binding proteins [28]. The first reports of N. meningitidis resistant to penicillin appeared in 1988 [29,30].

Patients intolerant of beta-lactams — Systemic meningococcal infection has a high mortality unless treated appropriately. The use of the most effective antibiotics is paramount. Patients who are intolerant to beta-lactams should be managed in consultation with an infectious diseases specialist.

For such patients, it is important to evaluate the nature of the beta-lactam allergy, since the approach to treatment in these critically ill patients depends upon the type of reaction (algorithm 1).

●Patients with mild reaction without features of an immunoglobulin (Ig)E-mediated reaction – In general, most patients who are labeled as allergic to penicillin who do not report a history of severe immediate allergy (eg anaphylaxis) are able to receive a third-generation cephalosporin such as ceftriaxone. (See "Choice of antibiotics in penicillin-allergic hospitalized patients".)

●Patients with IgE-mediated reactions – Patients with a severe immediate allergy (eg, anaphylaxis) to a penicillin can usually be treated with a third-generation cephalosporin, such as ceftriaxone, given with a test-dose procedure. (See "Choice of antibiotics in penicillin-allergic hospitalized patients", section on 'Test dose procedure (graded challenge)'.)

If there is also a history of a severe immediate allergy to ceftriaxone, most patients can tolerate carbapenems because cross-reactivity rates between penicillins or cephalosporins and carbapenems for patients with proven immediate allergy are <1 percent, although several reactions have been reported [31]. In such patients, meropenem should be administered using a test-dose procedure. Carbapenems have been used for bacterial meningitis with meningococcus and other gram-negative organisms, although the experience with meningococcal meningitis is limited [32]. The dose of meropenem recommended for treatment of meningitis is 2 g IV every eight hours for adults or 40 mg/kg every eight hours for children (up to a maximum of 6 g/day) [32]. Imipenem should not be administered, as seizures have been reported with this combination in children [33].

●Patients with serious delayed reactions – When there is concern for a severe delayed allergy to a penicillin or a cephalosporin (Stevens Johnson syndrome/toxic epidermal necrolysis [SJS/TEN], drug reaction with eosinophilia and systemic symptoms [DRESS], acute generalized exanthematous pustulosis [AGEP]), all beta-lactams and carbapenems should generally be avoided. In this case, chloramphenicol (100 mg/kg per day IV in divided doses every six hours, up to a maximum dose of 4 g/day) is an acceptable alternative antibiotic choice, although its availability is limited, particularly in resource-rich settings. Resistance of meningococcal strains to chloramphenicol has rarely been described [34].

Fluoroquinolones are also a potential alternative in patients with meningococcal infection who cannot use beta-lactams or carbapenems. Clinical experience is extremely limited for systemic infection, and the optimal dosing is unclear. As an example, one pharmacokinetic study suggested that in adults, levofloxacin 500 mg IV every 12 hours would be sufficient to treat N. meningitidis if the MICs are <0.1 to 0.2 mcg/mL [35]; however, other experts would consider a higher dose of levofloxacin (eg, 750 mg every 12 hours). In either case, the dose may need to be adjusted in patients with known renal insufficiency because of an increased risk of toxicity [36]. Information on renal dosing can be found in the drug information topic within UpToDate.

Although fluoroquinolones may be suitable for some patients, resistance to fluoroquinolones is becoming widespread and use of this class of antibiotics should be avoided in areas with known resistance to these agents. Additional information on fluoroquinolone resistance is found below. (See 'Regimens' below.)

If an agent other than a third-generation cephalosporin is used, patients should undergo subsequent eradication therapy for presumed nasopharyngeal carriage. (See 'Eradication of nasal carriage for select patients' below.)

Duration of therapy — An adequate response to therapy includes clearing of fever, stability of blood pressure, improving mental status, and stabilizing of hematologic parameters. A repeat lumbar puncture is not typically required, since the expected clinical improvement is rapid.

The precise duration of antibiotic therapy will vary based upon the patient's age, the severity of initial illness, and the response to therapy:

●Adults – For adults, we suggest a minimum of four days of total therapy for meningococcal meningitis. For patients with a severe presentation and/or delayed response to therapy, extending treatment to seven days is appropriate.

●Children – For children, we generally treat for five to seven days; this recommendation is consistent with guidelines from the American Academy of Pediatrics [23].

Treatment for longer than seven days has not proven necessary unless a secondary infection complicates meningococcal disease.

Data informing the optimal duration of therapy are limited. In an observational study of 527 cases of invasive meningococcal infection that occurred over a time period when the recommended duration changed from seven to four days, mortality rates and rates of complications were comparable with both durations [26]. Short courses have also been studied in epidemic settings and appear comparably effective to longer courses. (See 'Considerations during epidemics in resource-limited settings' below.)

Previous studies had suggested that seven days was comparable with longer durations, and seven days had been the previously preferred duration [20,37].

Eradication of nasal carriage for select patients — Patients with invasive meningococcal disease who were treated with an agent other than a third-generation cephalosporin should receive chemoprophylaxis for eradication of presumed nasopharyngeal carriage prior to discharge from the hospital to prevent subsequent transmission to close contacts [38-40]. Treatment with antimicrobial agents other than third-generation cephalosporins does not reliably eradicate nasopharyngeal carriage of N. meningitidis.

Chemoprophylaxis regimens for such patients are the same as for post-exposure prophylaxis (table 1). (See 'Regimens' below.)

Considerations during epidemics in resource-limited settings — Since 1995, the World Health Organization (WHO) has recommended empiric treatment of suspected cases of meningococcal infection with one or two intramuscular injections of long-acting chloramphenicol (oily suspension); however, the continued production of this drug is uncertain. Although alternative drugs with proven efficacy against N. meningitidis are available (eg, benzylpenicillin, ampicillin, and IV or intramuscular chloramphenicol or ceftriaxone), protocols requiring multiple injections are impractical during an epidemic.

Shorter regimens of beta-lactams (eg, ceftriaxone) are reasonable, cost-effective alternatives [41-43]. As an example, a single intramuscular dose of ceftriaxone is an alternative first-line treatment to chloramphenicol for epidemic meningococcal meningitis. In a randomized trial of 510 patients (441 under the age of 15 years) with suspected disease during a meningococcal meningitis epidemic in Niger, a single dose of intramuscular ceftriaxone was as effective as a single dose of long-acting chloramphenicol in oil [41]. The treatment failure rate was 9 percent at three days in both groups and the mortality rate was 5 to 6 percent. Results were similar among patients with confirmed meningitis caused by N. meningitidis.

Discontinuing glucocorticoids — Empiric dexamethasone is often administered to adults and children with bacterial meningitis while awaiting microbiologic data. However, the decision to continue dexamethasone treatment for patients who are diagnosed with meningococcal meningitis and sepsis is controversial, since most data supporting the use of dexamethasone has been in persons with confirmed pneumococcal meningitis [44-46]. (See "Dexamethasone to prevent neurologic complications of bacterial meningitis in adults" and "Bacterial meningitis in children: Dexamethasone and other measures to prevent neurologic complications".)

Many experts discontinue dexamethasone in patients with meningococcal meningitis given the limited data supporting its use. However, others would continue dexamethasone [47], and small case reports have found a reduction in length of hospitalization without an increase in adverse events [48].

The possible role of pharmacologic doses of glucocorticoids in septic shock and of dexamethasone in bacterial meningitis is discussed separately. (See "Evaluation and management of suspected sepsis and septic shock in adults" and "Dexamethasone to prevent neurologic complications of bacterial meningitis in adults" and "Bacterial meningitis in children: Dexamethasone and other measures to prevent neurologic complications", section on 'Dexamethasone'.)

Treatment of shock — Vascular collapse and shock are frequent early manifestations of meningococcal disease caused largely by the bacterial product lipooligosaccharide, which is a potent toxin. Details of resuscitative efforts for septic shock are discussed in detail elsewhere. (See "Evaluation and management of suspected sepsis and septic shock in adults".)

Protein C concentrate — In severe meningococcal sepsis, protein C activation is impaired [49]. In severe meningococcal sepsis, we suggest use of protein C concentrate, although it has not been approved by the US Food and Drug Administration for this indication. The suggested dose of protein C is 100 to 120 international units/kg initially followed every six hours for three subsequent doses of 60 to 80 international units/kg. (See "Clinical manifestations of meningococcal infection".)

Limited data suggest that protein C concentrate might be beneficial in patients with meningococcal sepsis and purpura fulminans [50]:

●In a randomized trial including 40 children with purpura fulminans and meningococcal sepsis, treatment with protein C concentrate was associated with resolution of coagulopathy with no adverse effects; there was no significant difference in amputation rate or mortality [51].

●In an open-label study of protein C replacement in 36 patients (mean age 12 years) with purpura fulminans, survival was improved and there were fewer amputations than predicted from historical controls [52]. However, because of the limited data supporting the use of protein C concentrate, it has not been used commonly in the therapy of meningococcal infections.

Supportive care — Since the occurrence of shock is frequent in patients with meningococcal infection, therapy should be provided in a tertiary care medical facility whenever possible. If patients with meningococcal sepsis arrive at hospitals without such capabilities, they should be treated with appropriate antimicrobial therapy and promptly transferred to a facility with a fully staffed intensive care unit. Vasopressor and aggressive fluid replacement are integral components in the management of septic shock. (See "Shock in children in resource-abundant settings: Initial management" and "Evaluation and management of suspected sepsis and septic shock in adults".)

Treatment of complications

Disseminated intravascular coagulation and purpura fulminans — Purpura fulminans is a thrombotic disorder characterized by extravasation of blood into the tissues producing ecchymoses and petechiae and is often accompanied by disseminated intravascular coagulation (DIC). While petechiae are common in meningococcal infection, increasing numbers of petechiae, confluent ecchymoses, persistently bleeding venipuncture sites, and bleeding gums despite adequate antimicrobial therapy and supportive care are suggestive of DIC. (See "Clinical manifestations of meningococcal infection".)

Early and aggressive interventions with antimicrobials and support of vascular perfusion are keys to prevention of DIC and purpura fulminans. Once purpura fulminans has developed, surgical debridement of lesions and skin grafting may be necessary in some cases. Deep necrosis of limbs or digits may necessitate amputation [53]. Other possible therapies of DIC and purpura fulminans are discussed separately. (See "Evaluation and management of disseminated intravascular coagulation (DIC) in adults".)

Other life-threatening complications — Other major life-threatening complications necessitating therapy include acute respiratory distress syndrome (ARDS), neurologic sequelae ranging from coma to diabetes insipidus, nosocomial pneumonia due to superinfection or aspiration during the obtunded state, and pericarditis. (See "Acute respiratory distress syndrome: Fluid management, pharmacotherapy, and supportive care in adults".)

Primary purulent meningococcal pericarditis can be particularly insidious, presenting as a massive pericardial effusion and tamponade. Pericardiocentesis is often indicated for improved hemodynamic function. (See "Clinical manifestations of meningococcal infection", section on 'Pericarditis' and "Purulent pericarditis".)

By contrast, sterile pericarditis, a post-infectious immune complex complication, can appear as a manifestation during convalescence and responds to anti-inflammatory drugs.

Prognosis — Before antibiotics and immune serum were available, the mortality of meningococcal infection was 70 to 90 percent [54]. The prognosis of meningococcal disease was dramatically improved by the introduction of sulfonamides in the late 1930s, followed by penicillin a decade later. The mortality rates in the United States, as reported by the Centers for Disease Control and Prevention (CDC), are 10 to 15 percent [55]. This mortality rate is similar to that in the late 1960s despite major advancements in supportive care [56-58].

Several studies have attempted to establish prognostic criteria for the outcome of meningococcal sepsis [4,59]. In a Spanish study, the major significant independent predictors of death were a hemorrhagic diathesis, focal neurologic signs, and age ≥60 years (odds ratio [OR] 101, 25, and 10, respectively) [4]. Early antibiotic therapy was associated with good outcomes. (See 'Importance of early administration' above.)

An increased case-fatality rate is associated with outbreaks compared with sporadic meningococcal disease. The magnitude of this difference was illustrated in a retrospective analysis of cases in the United States from 1994 to 2002 [60]. Active surveillance identified 668 cases, of which 229 patients (69 clusters) met the criteria of either a community-based or organizational outbreak. After controlling for age, serogroup, and clinical presentation, outbreak-associated cases were associated with a significantly higher case-fatality rate than were sporadic cases (21 versus 11 percent; OR 3.3; 95% CI 2.0-5.5).

The presence of hypervirulent meningococcal strains (clonal complex 11) has also been associated with an increased incidence of sepsis and poor outcomes. This clonal complex is found among most serotypes but occurs most frequently among serogroup C strains [61,62].

Sex may influence prognosis. In one study from New York including 151 cases of invasive meningococcal disease between 2008 and 2016, a higher case-fatality rate was observed among women (adjusted relative risk [RR] 2.1, 95% CI 1.2-3.8); among patients with meningitis, the RR was 13.7 (95% CI 3.2-58.1) [63]. The basis for these differences is not understood.

PREVENTION — N. meningitidis is spread by large respiratory droplets or direct contact with respiratory secretions. The methods for the prevention of meningococcal infection include antimicrobial chemoprophylaxis following identification of an index case, use of droplet precautions, vaccination prior to exposure, and avoidance of exposure [2]. (See "Epidemiology of Neisseria meningitidis infection", section on 'Risk factors for acquisition of infection'.)

Droplet precautions — Droplet precautions should be continued for 24 hours after institution of effective antibiotics in patients with suspected or confirmed N. meningitidis infection [2]. After 24 hours, viable organisms can no longer be isolated from treated patients. (See "Infection prevention: Precautions for preventing transmission of infection", section on 'Droplet precautions'.)

Antimicrobial chemoprophylaxis

Following exposure — Antimicrobial chemoprophylaxis was first used successfully to abort the spread of meningococcal infection in the 1930s [64]. The reported attack rate for close contacts of patients with sporadic meningococcal disease is approximately 4 in 1000 persons exposed (0.4 percent), which is 500 to 800 times higher than that of the general population [65,66].

Indications — Chemoprophylaxis is indicated in close contacts of patients with meningococcal infection and should be given as early as possible following the exposure [66,67]. Although "close contact" has not been clearly defined, it generally refers to individuals who have had prolonged (>8 hours) contact while in close proximity (<3 feet) to the patient or who have been directly exposed to the patient's oral secretions during the seven days before the onset of the patient's symptoms and until 24 hours after initiation of appropriate antibiotic therapy [2].

Close contacts may include individuals exposed in the following ways [2,66]:

●Household members, roommates, intimate contacts, contacts at a childcare center, young adults exposed in dormitories, military recruits exposed in training centers

●Travelers who had direct contact with respiratory secretions from an index patient or who were seated directly next to an index patient on a prolonged flight (ie, one lasting ≥8 hours)

●Individuals who have been exposed to oral secretions (eg, intimate kissing, mouth-to-mouth resuscitation, endotracheal intubation, or endotracheal tube management)

Prophylaxis is not indicated if exposure to the index case is brief. This includes the majority of health care workers unless there is direct exposure to respiratory secretions (as with suctioning or intubation). The attack rate in health care workers at risk is increased compared with that of the general population, but the absolute increase in risk is very small, and antimicrobial prophylaxis is therefore not recommended for health care workers who have not had direct exposure to respiratory secretions [66,68].

Oropharyngeal or nasopharyngeal cultures are not helpful in determining the need for chemoprophylaxis and might unnecessarily delay institution of this preventive measure [66].

Evidence supporting chemoprophylaxis is limited, but we favor it because of the potential severity of meningococcal infection in individuals with high-risk exposure. Evidence informing chemoprophylaxis is discussed elsewhere. (See 'Regimens' below.)

Timing of prophylaxis — Antimicrobial chemoprophylaxis should be administered as early as possible (ideally <24 hours after identification of the index patient). Chemoprophylaxis administered >14 days after exposure to the index case is probably of limited or no value and is therefore not recommended by the United States Centers for Disease Control and Prevention (CDC) [66].

The rate of secondary disease in contacts is highest immediately after the onset of disease in the index patient. Secondary cases usually occur within 10 days of the primary case, but longer intervals have been described in rare case reports [69].

In the setting of a suspected meningococcal disease outbreak in which confirmed cases have occurred, it is not necessary to wait for confirmation of N. meningitidis in subsequent cases to initiate chemoprophylaxis of close contacts when meningococcal disease is strongly suspected (eg, identification of gram-negative diplococci, detection of N. meningitidis antigen from cerebrospinal fluid [CSF] by latex or from formalin-fixed tissue by immunohistochemistry, or when there are clinical signs such as purpura) [67].

Regimens — To help inform regimen selection for chemoprophylaxis, clinicians should consult with local public health authorities. In the United States, information can also be found on the CDC website.

●Preferred regimens – Preferred regimens for antimicrobial prophylaxis include rifampin, ciprofloxacin, and ceftriaxone (table 1) [66,70]. The choice of agent depends in part upon antimicrobial susceptibility within a community. As an example, ciprofloxacin should not be used for chemoprophylaxis of close contacts of individuals with meningococcal disease when ciprofloxacin-resistant N. meningitidis has been identified in the local community [66].

Quinolone resistance has been increasingly reported and has been detected worldwide. Ciprofloxacin-resistant N. meningitidis isolates were detected in three patients in North Dakota and Minnesota in 2007 [71,72]. In 2008, a case of pneumonia caused by ciprofloxacin-resistant N. meningitidis was detected in California as part of the United States Active Bacterial Core surveillance system [72]. From 2019 to 2020, 11 ciprofloxacin-resistant, beta-lactamase-producing isolates of N. meningitidis were detected in eight states [15]. Isolated ciprofloxacin-resistant isolates have also been reported from a variety of other countries around the world [71,73,74]. In Spain, 10 of 5300 isolates of N. meningitidis that were collected between 1999 and 2006 had reduced susceptibility to ciprofloxacin [73].

●Alternative regimens – Azithromycin is an alternative agent for prophylaxis if one of the preferred agents cannot be used (eg, if rifampin or ceftriaxone are contraindicated in the setting of a ciprofloxacin-resistant N. meningitidis exposure). In adults, the dose of azithromycin is 500 mg orally as a single dose; in children, the dose is 10 mg/kg orally as a single dose (max dose 500 mg). Although azithromycin has significant activity against meningococcus, it is not recommended as a first-line agent for chemoprophylaxis since it has not been well studied for this indication.

Evidence informing the clinical effectiveness of antimicrobial prophylaxis in preventing disease is limited. The potential clinical benefit of prophylaxis is inferred from studies that demonstrate eradication of nasopharyngeal carriage with antimicrobials.

Specifically, a 2013 meta-analysis of 24 randomized or quasi-randomized clinical trials evaluated the effectiveness of antibiotic treatments for eradication of nasopharyngeal carriage at one to two weeks after treatment [75]. The following findings were noted:

●Rifampin (RR 0.20, 95% CI 0.14-0.29) and ciprofloxacin (RR 0.03, 95% CI 0.00-0.42) were significantly effective at eradicating N. meningitidis carriage compared with placebo at one to two weeks. Rifampin continued to be effective for up to four weeks after therapy, but resistant isolates were seen.

●Based on the results of a single study, ceftriaxone was more effective than rifampin (RR 5.93, 95% CI 1.22-28.68) at eradicating N. meningitidis carriage after one to two weeks of follow-up. No trials have evaluated ceftriaxone against placebo, and the drug must be administered parenterally.

●Clinical efficacy of eradication could not be assessed since there were no cases of disease following antibiotics or placebo.

Follow-up of close contacts — Surveillance of close contacts receiving prophylaxis for at least 10 days following exposure as well as counseling about the signs and symptoms of meningococcal infection ensure prompt treatment of any secondary cases that might arise.

Patients receiving C5 inhibitors — We suggest patients treated with C5 inhibitors (eg, eculizumab and ravulizumab) receive antimicrobial prophylaxis for the duration of C5 inhibitor administration, in addition to meningococcal vaccination. It is also important to keep their vaccines up to date. (See "Meningococcal vaccination in children and adults", section on 'Immunization of persons at increased risk'.)

Antimicrobial prophylaxis for prevention of meningococcal infection in the setting of C5 inhibitor use consists of penicillin V (for adults 500 mg orally twice daily; for children ≥3 years of age 250 mg orally twice daily; for children <3 years of age 125 mg orally twice daily). In the presence of penicillin allergy, a macrolide such as azithromycin (in adults 500 mg orally once daily; in children 5 mg/kg orally once daily [maximum dose 500 mg]) can be substituted, based on the relatively narrow spectrum and efficacy against the meningococcus.

Since neither vaccination nor antimicrobial prophylaxis can be expected to prevent all cases of meningococcal disease, patients on C5 inhibitors should be educated about the risk of infection and encouraged to seek medical care immediately if any symptoms (fever, headache, altered mentation, rash) of meningococcal disease occur. (See "Clinical manifestations of meningococcal infection".)

C5 inhibitors are monoclonal antibody terminal complement inhibitors used for treatment of complement-mediated hemolytic uremic syndrome, paroxysmal nocturnal hemoglobinuria, myasthenia gravis, and other autoimmune diseases. Administration of C5 inhibitors has been associated with a 1000- to 2000-fold increased risk of meningococcal infection [76], and life-threatening and fatal meningococcal infections have been reported [77].

Invasive meningococcal disease has occurred in patients receiving C5 inhibitors despite receipt of meningococcal vaccines (both MenA/C/W/Y protein-polysaccharide vaccines and MenB-directed vaccines), including infections caused by nontypeable strains not included as the targets of these vaccines [76,78]. This is due to inhibition of both complement-mediated bactericidal activity and also complement-mediated opsonic functions by C5 inhibitors.

Although there is a lack of clear evidence supporting the use of prophylactic antibiotics, there is a trend toward prolonged time to onset among prophylaxis users [79,80]. However, there is also a trend towards increased penicillin nonsusceptibility if infection occurs, which may impact regimen selection. (See 'Therapy based on results of susceptibility testing' above.)

Vaccination — Meningococcal vaccines and the indications for immunization are discussed separately. (See "Meningococcal vaccination in children and adults" and "Patient education: Vaccines for adults (Beyond the Basics)" and "Patient education: Vaccines for infants and children age 0 to 6 years (Beyond the Basics)" and "Patient education: Vaccines for children age 7 to 18 years (Beyond the Basics)".)

MANAGEMENT OF N. MENINGITIDIS FROM OTHER SITES

Urethritis — Meningococcal urethritis is indistinguishable from acute gonococcal urethritis (a more common cause of genitourinary infection) based on clinical features and Gram stain [81,82]. However, the gonorrhea nucleic acid amplification testing (NAAT) is negative in meningococcal urethritis. Both pathogens are susceptible to similar antibacterial agents (eg, ceftriaxone), so the treatment of presumed gonorrhea infections will typically be effective for patients with meningococcal infections of the genitourinary tract (including urethritis, epididymitis, and pelvic inflammatory disease). (See "Treatment of uncomplicated gonorrhea (Neisseria gonorrhoeae infection) in adults and adolescents" and "Pelvic inflammatory disease: Treatment in adults and adolescents".)

Other rare sites of infection — Antimicrobial regimens used for treatment of other rare sites of infection (eg, arthritis, pericarditis, pneumonia) include ceftriaxone (2 g every 24 hours for adults or 50 mg/kg [maximum 2 g] every 12 to 24 hours for children) or high-dose penicillin G (for adults 4 million units intravenous [IV] every four hours; for children 300,000 units/kg per day in a divided dose every six hours [usual maximum dose 12 million units/day]). There are limited data to guide the duration of treatment; regimens are typically administered for five to seven days but may be extended up to two weeks in patients with pericarditis.

In addition to antimicrobial therapy, some infections (such as arthritis and pericarditis) warrant drainage of fluid from the site of infection.

Incidental nasopharyngeal isolation — Occasionally, N. meningitidis is detected on throat or nasopharyngeal culture obtained for some other reason. The most common indication is pharyngitis, which is not caused by N. meningitidis. Although nasopharyngeal carriage with N. meningitidis plays an important role in the transmission and the development of invasive disease, there is no role for treatment of patients with detection of N. meningitidis on throat or nasopharyngeal culture in the absence of invasive disease or exposure to a case or in an ongoing outbreak. (See "Microbiology and pathobiology of Neisseria meningitidis", section on 'Nasopharyngeal carriage'.)

There are several problems with attempting to eliminate nasopharyngeal carriage in the community:

●Spontaneous loss and acquisition of N. meningitidis carriage is common. This was illustrated in a study in military recruits in which 34 percent experienced one or more changes in carrier status over time [83].

●Recurrent colonization may occur after prophylaxis. In a community-wide prophylaxis program in a semi-closed kibbutz population in Israel, the colonization rate of serogroup B meningococcus dropped from 4.6 percent at baseline to 0 percent at three weeks; it then rose to 0.5 percent at six months and 3.9 percent (similar to the baseline level) at one year [84].

●Antimicrobial prophylaxis has no proven clinical efficacy outside an outbreak setting. The meta-analysis cited above included trials in healthy carriers [75]. Clinical efficacy of eradication could not be assessed since there were no cases of disease following antibiotics or placebo.

●Antibiotic resistance. Rifampin treatment can result in the rapid emergence of rifampin-resistant meningococci in the patients treated [85].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Bacterial meningitis in adults" and "Society guideline links: Meningococcal infection" and "Society guideline links: Bacterial meningitis in infants and children".)

SUMMARY AND RECOMMENDATIONS

●Antimicrobial therapy

•Initial therapy – Empiric coverage for meningococcal infection is warranted in patients with suspected invasive meningococcal infection (severe sepsis syndrome, fever with petechiae and/or ecchymoses, or suspected bacterial meningitis). (See "Initial therapy and prognosis of community-acquired bacterial meningitis in adults".)

Prompt administration of effective antibiotics early in the disease is key to a successful outcome of life-threatening meningococcal infection. (See 'Importance of early administration' above.)

For initial therapy of patients with suspected meningococcal meningitis or sepsis, we recommend ceftriaxone rather than intravenous (IV) penicillin G (Grade 1B). The dose of ceftriaxone is 2 g IV every 12 hours for adults or 50 mg/kg (maximum 2 g) IV every 12 hours for children. Third-generation cephalosporins, such as ceftriaxone, have very low rates of resistance, are easy to dose, and are also effective for eradication of nasopharyngeal carriage of meningococcus. (See 'Therapy pending results of susceptibility testing' above.)

•Therapy based on susceptibility testing – If susceptibility testing indicates that the isolate is penicillin susceptible (minimum inhibitory concentration [MIC] <0.1 mcg/mL), either ceftriaxone or high-dose penicillin G (for adults 4 million units IV every four hours; for children 300,000 units/kg per day in a divided dose every six hours [usual maximum dose 12 million units/day]) can be used. (See 'Therapy based on results of susceptibility testing' above.)

Most isolates that have reduced susceptibility to penicillin (MIC ≥0.1 mcg/mL) are susceptible to ceftriaxone.

•Patients intolerant to beta-lactams – For patients who are intolerant to beta-lactams, the approach to treatment depends upon the nature of the allergy. For those who cannot use beta-lactams, chloramphenicol (100 mg/kg per day IV in divided doses every six hours, up to a maximum dose of 4 g/day) is an effective substitute in areas where it is available. Meropenem, levofloxacin, moxifloxacin, and possibly aztreonam are also alternatives, although clinical experience and data on their use remain limited and increasing resistance to fluoroquinolones a concern. (See 'Patients intolerant of beta-lactams' above.)

•Eradication of nasal carriage – If an antibiotic other than ceftriaxone is used for treatment, we suggest adding a second agent for eradication of presumed nasopharyngeal carriage to prevent subsequent transmission to close contacts (Grade 2C). Options for a second agent are the same as those used for chemoprophylaxis (table 1). (See 'Eradication of nasal carriage for select patients' above.)

●Treatment of shock

•Role of protein C concentrate – For patients with severe meningococcal sepsis, including those with purpura fulminans, we suggest protein C concentrate in addition to supportive care (Grade 2C). Patients with severe meningococcal sepsis have impaired activation of protein C, which contributes to coagulopathic complications. (See 'Protein C concentrate' above.)

●Prevention

•Infection control precautions – Droplet precautions should be used for patients with suspected or confirmed Neisseria meningitidis infection. These should be continued for 24 hours after institution of effective antibiotics. (See 'Droplet precautions' above.)

•Management of close contact – For close contacts of patients with meningococcal meningitis or sepsis, we suggest antimicrobial chemoprophylaxis (Grade 2C). Antimicrobial chemoprophylaxis should be administered as early as possible (ideally <24 hours after identification of the index patient and not >14 days after exposure). (See 'Indications' above and 'Timing of prophylaxis' above.)

Regimens for antimicrobial prophylaxis include rifampin, ciprofloxacin, and ceftriaxone (table 1). (See 'Regimens' above.)

•Persons receiving C5 inhibitors – In patients receiving C5 inhibitors, we suggest administration of daily antimicrobial prophylaxis with oral penicillin V for the duration of C5 inhibitor administration (Grade 2C). Administration of C5 inhibitors has been associated with increased incidence of meningococcal disease. Antimicrobial prophylaxis should be used in addition to meningococcal vaccination. (See 'Patients receiving C5 inhibitors' above.)

•Vaccination – Meningococcal vaccines are discussed separately. (See "Meningococcal vaccination in children and adults".)