American Academy of Pediatrics: What's Up, Doc?

This statement provides guidelines for therapy of children with serious infections possibly caused by Streptococcus pneumoniae. Resistance of invasive pneumococcal strains to penicillin, cefotaxime, and ceftriaxone has increased over the past few years. Reports of failures of cefotaxime or ceftriaxone in the treatment of children with meningitis caused by resistant S pneumoniae necessitates a revision of Academy recommendations. For nonmeningeal infections, modifications of the initial therapy need to be considered only for patients who are critically ill and those who have a severe underlying or potentially immunocompromising condition or patients from whom a highly resistant strain is isolated. Because vancomycin is the only antibiotic to which all S pneumoniae strains are susceptible, its use should be restricted to minimize the emergence of vancomycinresistant organisms. Patients with probable aseptic (viral) meningitis should not be treated with vancomycin. These recommendations are subject to change as new information becomes available. ABBREVIATIONS. CDC, Centers for Disease Control and Prevention; MIC, minimum inhibitory concentration; CSF, cerebrospinal fluid; IV, intravenously; MBC, minimal bactericidal concentration; NCCLS, National Committee for Clinical Laboratory Standards. ANTIMICROBIAL RESISTANCE IN STREPTOCOCCUS PNEUMONIAE Epidemiology of Antimicrobial Resistance The Centers for Disease Control and Prevention (CDC) suggest that the same nomenclature used to define resistance for other bacteria, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci, be used for S pneumoniae. All organisms with a minimum inhibitory concentration (MIC) equal to or greater than that defined for the intermediate category of resistance will be classified as nonsusceptible (Table 1). Resistant organisms will have an MIC equal to or greater than that defined for the resistant category. These latter organisms were formerly known as highly resistant. Strains in the resistant category for the penicillins, cephalosporins, and other b-lactam antibiotics are of particular concern, because they are generally also resistant to most other antibiotics, including the cephalosporins, trimethoprim-sulfamethoxazole, erythromycin, chloramphenicol, and tetracycline.1 In children older than 2 months, Streptococcus pneumoniae is the most common cause of invasive bacterial infections. The prevalence of infections caused by penicillin-nonsusceptible S pneumoniae for all ages has increased in the United States during the last 5 years (Figure). 2–6 In recent years, in children, the proportion of penicillin-nonsusceptible invasive isolates has varied from 0% to 41%. Of these nonsusceptible isolates, 5% to 21% were resistant (Table 1). The incidence of cefotaximeand ceftriaxone-nonsusceptible isolates has increased to 20% in some areas (Table 2). 7–25 Mechanism of Antimicrobial Resistance Penicillins, cephalosporins, and other b-lactam antibiotics kill S pneumoniae by binding irreversibly to high molecular weight enzymes located in the bacterial cell wall. These enzymes, also known as penicillin-binding proteins, are responsible for synthesizing peptidoglycan for new cell wall formation. Chromosomal gene changes can alter the structure of these enzymes, thereby decreasing the binding affinity for penicillin and the cephalosporins and resulting in resistance.26 Resistance of S pneumoniae to penicillin and cephalosporins is not mediated by b-lactamase enzymes. Consequently, treatment of pneumococcal infections resistant to these antibiotics with b-lactamase-resistant drugs, such as extended spectrum cephalosporins or combinations of broad spectrum penicillins plus clavulanate or sulbactam, offers no advantage. The highest levels of resistance reported have been MICs of 8 to 16 mg/mL for penicillin27 and 16 to 32 mg/mL for cefotaxime and ceftriaxone.28–30 Although uncommon, resistance also has been described for clindamycin, rifampin, and imipenem.