TREATMENT Meningococcal Infections
Death from meningococcal disease is associated most commonly with hypovolemic shock (meningococcemia) and occasionally with raised intracranial pressure (meningococcal meningitis). Therefore, management should focus on the treatment of these urgent clinical issues in addition to the administration of specific antibiotic therapy. Delayed recognition of meningococcal disease or its associated physiologic derangements, together with inadequate emergency management, is associated with poor outcome. Since the disease is rare, protocols for emergency management have been developed (see www.meningitis.org).
Airway patency may be compromised if the level of consciousness is depressed as a result of shock (impaired cerebral perfusion) or raised intracranial pressure; this situation may require intervention. In meningococcemia, pulmonary edema and pulmonary oligemia (presenting as hypoxia) require oxygen therapy or elective endotracheal intubation. In cases with shock, aggressive fluid resuscitation (with replacement of the circulating volume several times in severe cases) and inotropic support may be necessary to maintain cardiac output. If shock persists after volume resuscitation at 40 mL/kg, the risk of pulmonary edema is high, and elective intubation is recommended to improve oxygenation and decrease the work of breathing. Metabolic derangements, including hypoglycemia, acidosis, hypokalemia, hypocalcemia, hypomagnesemia, hypophosphatemia, anemia, and coagulopathy, should be anticipated and corrected. In the presence of raised intracranial pressure, management includes correction of coexistent shock and neurointensive care to maintain cerebral perfusion.
Empirical antibiotic therapy for suspected meningococcal disease consists of a third-generation cephalosporin such as ceftriaxone (75–100 mg/kg per day [maximum, 4 g/d] in one or two divided IV doses) or cefotaxime (200 mg/kg per day [maximum, 8 g/d] in four divided IV doses) to cover the various other (potentially penicillin-resistant) bacteria that may produce an indistinguishable clinical syndrome. Although unusual in most isolates, reduced meningococcal sensitivity to penicillin (a minimal inhibitory concentration of 0.12–1.0 μg/mL) has been reported widely.
Both meningococcal meningitis and meningococcal septicemia are conventionally treated for 7 days, although courses of 3–5 days may be equally effective. Furthermore, a single dose of ceftriaxone or an oily suspension of chloramphenicol has been used successfully in resource-poor settings. No data are available to guide the duration of treatment for meningococcal infection at other foci (e.g., pneumonia, arthritis); antimicrobial therapy is usually continued until clinical and laboratory evidence of infection has resolved. Cultures usually become sterile within 24 h of initiation of appropriate antibiotic chemotherapy.
The use of glucocorticoids for adjunctive treatment of meningococcal meningitis remains controversial since no relevant studies have had sufficient power to determine true efficacy. One large study in adults did indicate a trend toward benefit, and in clinical practice a decision to use glucocorticoids usually must precede a definite microbiologic diagnosis. Therapeutic doses of glucocorticoids are not recommended in meningococcal septicemia, but many intensivists recommend replacement glucocorticoid doses for patients who have refractory shock in association with impaired adrenal gland responsiveness.
Various other adjunctive therapies for meningococcal disease have been considered, but few have been subjected to clinical trials and none can currently be recommended. An antibody to LPS (HA1A) failed to confer a demonstrable benefit. Recombinant bactericidal/permeability-increasing protein (which is not currently available) was tested in a study that had inadequate power to show an effect on mortality rates; however, there were trends toward lower mortality rates among patients who received a complete infusion, and this group also had fewer amputations, fewer blood-product transfusions, and a significantly improved functional outcome. Given that protein C concentrations are reduced in meningococcal disease, the use of activated protein C has been considered since a survival benefit was demonstrated in adult sepsis trials; however, trials in pediatric sepsis (of particular relevance for meningococcal disease) found no benefit and indicated a potential risk of bleeding complications with use of activated protein C.
The postmeningococcal immune-complex inflammatory syndrome has been treated with nonsteroidal anti-inflammatory agents until spontaneous resolution occurs.