Current concepts in clinical therapeutics: bacterial meningitis in infants and children

The epidemiology and incidence, etiology, pathogenesis and pathophysiology, clinical presentation, diagnosis, principles of therapy, and treatment of bacterial meningitis in infants and children are reviewed. Bacterial meningitis is a major cause of morbidity and mortality, and most cases occur in children less than five years old. Haemophilus influenzae type b, Neisseria meningitidis, and Streptococcus pneumoniae are the major pathogens involved. Bacteremia or colonization of the upper-respiratory-tract epithelium often precedes meningitis. Defense mechanisms are poor in the cerebrospinal fluid; once an organism penetrates the blood-brain barrier, infection may follow quickly. Clinical signs and symptoms are somewhat nonspecific, with lethargy, restlessness, and poor feeding prominent; diagnosis often relies on the patient history along with preliminary results of lumbar punctures. Therapy is based on pharmacologic and pharmacodynamic principles concerning the available antimicrobial agents, the blood-brain barrier, and supportive therapy. Effective antimicrobial therapy requires attainment of adequate bactericidal activity in the cerebrospinal fluid; penetration of agents into the brain depends on their physico-chemical characteristics. Antibiotic therapy must generally be started before culture results are available, making empiric therapy based on the child's age, history, and underlying conditions important. Established therapeutic agents include penicillins, aminoglycosides, and chloramphenicol, though newer expanded-spectrum cephalosporins such as cefuroxime, ceftriaxone, and cefotaxime are being used with increasing frequency. However, the use of these newer, more potent antimicrobial agents have not appreciably altered associated morbidity and mortality. Aggressive supportive care and evaluation of newer nonantibiotic treatments should be addressed in future studies of bacterial meningitis in infants and children.