Medical Treatment of Bacterial Meningitis in Children

Initial Treatment

Initial antimicrobial therapy is most commonly antibacterial, as most cases of acute meningitis have a bacterial cause. Because the etiology of meningitis varies with patient age, initial empiric therapy should be directed against the expected pathogens but should remain with broad coverage until cultures are definitive.

Drugs for empiric therapy of meningitis

Age	First choice	Alternative choice
Younger than 6 weeks	Cefotaxime and ampicillin                    or Ceftriaxone* and ampicillin                    or  Gentamicin and ampicillin	Ceftazidime and ampicillin
Older than 6 weeks	Ceftriaxone and vancomycin                    or Cefotaxime and vancomycin	Chloramphenicol and ampicillin

 

*Ceftriaxone is relatively contraindicated in neonates younger than 1 week of age with hyperbilirubinemia due to possibility of displacement of bilirubin from albumin by drug.

Drugs for neonates

• Ampicillin or third-generation cephalosporin and gentamycin or amikacin: These combinations will cover most bacteria responsible for neonatal meningitis.
• Tailor treatment to culture results: The combination of ampicillin and gentamicin or amikacin is considered the treatment of choice for neonates with group B streptococcal meningitis. There is bactericidal synergy with this combination in vitro in killing group B streptococcus, and also, presumably in vivo as well. Cefotaxime is also effective. The drug of choice for neonates with meningitis caused by L. monocytogenes is ampicillin. None of the third-generation cephalosporins are active against this organism and thus should never be used as monoagent therapy for L. monocytogenes or for empiric therapy of neonatal meningitis. Cefotaxime is the drug of choice for meningitis caused by E. coli, the most common gram-negative organism causing neonatal meningitis in the United States. Ceftriaxone has the advantage of once-daily dosing. Aminoglycosides may be associated with lower cure rates and should not be used once a gram-negative causative organism has been identified. Gram-negative organisms are more difficult to clear from the CSF, and repeat lumbar puncture may be needed to assess treatment effectiveness.
• Intrathecal gentamicin has been historic treatment: Intraventricular administration of antibiotics for neonates with meningitis has the theoretical advantage of achieving higher CSF levels than intravenous administration alone. Some studies have suggested that intravenous and intraventricular administration of antibiotics, particularly gentamicin, may be accomplished safely, with increased CSF drug levels compared to intravenous administration alone (42). Several more recent studies have shown, however, that there is no difference in duration of culture positivity of the CSF with intraventricular administration of antibiotics in gram-negative neonatal meningitis and that there is potential for damage from the ventricular taps, as well as toxicity from the antibiotic itself, resulting in a significant increase in mortality rate with intraventricular antibiotic administration (45, 61, 62).

Drugs for infants and older children

• Third-generation cephalosporin with or without vancomycin: Based on the most common pathogens for this age group, including S.pneumoniae, N. meningitidis, and H. influenzae, third-generation cephalosporins are the drugs of choice for initial therapy of bacterial meningitis. Although penicillin-resistant strains of S. pneumoniae are increasing, cefotaxime and ceftriaxone are still effective for most of these patients. In patients with unknown sensitivities, vancomycin should be used in addition to cefotaxime or ceftriaxone.
• Tailor treatment to culture results: Once a specific organism is isolated from the CSF cultures, antibiotic therapy should be tailored as shown in the table below. Ceftriaxone has the advantages of once-a-day dosing and the potential for intramuscular injection if the intravenous route is inaccessible, with no loss in efficacy (76). Failures of treatment with vancomycin alone for S.pneumoniae meningitis have been reported, perhaps due to variations in CSF penetration of vancomycin. The addition of meropenem or rifampin improves therapeutic response. Both intravenous penicillin G and ampicillin are effective in the treatment of N. meningitidis meningitis. Ceftriaxone and cefotaxime are also effective. Chloramphenicol is another effective choice and has the advantage of possible oral administration.

Ventriculitis

• Treatment is similar to that for meningitis: Ventriculitis occurring in the setting of meningitis will usually respond to intravenous antibiotic therapy. There is no clear role for intrathecal antibiotics, even in shunt infection, which is discussed in another chapter. Patients should be monitored with imaging studies including ultrasound and CT or MRI scans for development of hydrocephalus or loculated infection or CSF collections.

Duration of therapy

• Minimum 10 days of treatment: Acute bacterial meningitis is a very serious infection, and antibiotic therapy generally should be continued for at least 10 days, except for N. meningitidis meningitis, where 7 days may suffice (45). In very severe infections, 14 days of intravenous antibiotic therapy is probably indicated. For gram-negative meningitis, therapy should be even longer, up to 21 days. In general, antibiotic therapy for meningitis is intravenous and should be completed in hospital. In more debilitated or younger patients, therapy should also be of longer duration.
• Afebrile for at least 48 hours: Patients should be afebrile for at least 48–72 hours before antibiotic therapy is discontinued.

Supportive Care in the Therapy of Meningitis

Patients with meningitis may be quite ill, with multisystem abnormalities, including cardiovascular, pulmonary, gastrointestinal, and neurological findings.

• ABCs: Initial treatment should focus as always on the ABCs: airway, breathe, circulate. If there is significant respiratory compromise or alteration of consciousness, the patient should be intubated and ventilated. Patients may be dehydrated from insensible losses due to fever and sweating or from vomiting.
• Fluid volume: Adequate fluid resuscitation is critical, but careful monitoring of intravascular volume, cardiac filling pressures, urine output, and serum and urine osmolality and electrolytes is vital. The syndrome of inappropriate antidiuretic hormone (SIADH) has been a matter of debate in patients with meningitis. Some reports indicate that SIADH may be present in up to 75% of patients with bacterial meningitis, and less commonly in other meningitides (78). Mild fluid restriction, particularly in the setting of a serum sodium level less than 135 mEq/dl, is recommended to avoid increasing cerebral edema with development of SIADH. Other reports conclude that there is elevated secretion of ADH in response to hypovolemia, and fluid resuscitation should not be withheld (78).
• Shock and hemodynamic stability: Particularly in acute bacterial meningitis, systemic circulatory collapse may occur early in the course of the disease, with profound shock. Inadequately treated, this may be fatal. In fulminant N. meningiditis meningitis, a petechial hemorrhagic rash may be seen, with disseminated intravascular coagulation triggered by release of bacterial toxins, potentially causing gangrene of the distal extremities. In addition to maintenance of adequate fluid volume, systemic pressors such as dopamine may be needed to maintain cardiovascular tone.
• Seizures: Patients with meningitis and seizures should be treated with anticonvulsants. Early seizures before or at the start of antibiotic therapy are fairly common and usually resolve rapidly. Later onset seizures are more ominous. Focal seizures suggest a focal process, such as brain abscess or subdural empyema, and require either CT or MRI scanning. In patients with prolonged alterations in consciousness, imaging may also be useful.