Treatment of Invasive Pneumococcal Infections
ABSTRACT & COMMENTARY
Synopsis: Two large retrospective studies showed that the outcome of invasive pneumococcal infections outside the central nervous system is similar for children with susceptible and penicillin-resistant pneumococci.
Sources: Silverstein M, et al. Clinical implications of penicillin and ceftriaxone resistance among children with pneumococcal bacteremia. Pediatr Infect Dis J 1999;18:35-41; Deeks SL, et al. Risk factors and course of illness among children with invasive penicillin-resistant Streptococcus pneumoniae. Pediatrics 1999;103:409-413.
The first study is a retrospective review of 922 cases of Streptococcus pneumoniae bacteremia in children in Boston from 1987 to 1997. Susceptibility studies were not done in all cases. Fifty-six of 744 S. pneumoniae isolates (7.5%) had reduced susceptibility to penicillin (most with intermediate resistance), and 14 of 73 isolates (2%) had resistance to cephalosporins. There were no differences in the clinical presentation, including temperature and other vital signs, chest radiographs, or white blood cell counts. Immunodeficient or functionally hyposplenic patients (e.g., HIV infection and sickle cell disease) were more likely to have drug-resistant isolates; 7 of 44 (16%) immunodeficient patients had penicillin-resistant organisms (P = 0.03). Children with ceftriaxone-resistant isolates who were initially treated as outpatients were more likely to be febrile at follow-up (67% vs 24%; P = 0.04), but there were no other differences in sequelae or eventual outcome.
The second study is a retrospective review from Argentina and Uruguay of 274 children 5 years of age with S. pneumoniae isolated from blood or another normally sterile site, between 1993 and 1996. Of 274 isolates, 46 (17%) showed intermediate susceptibility and 53 (19%) showed high-level resistance to penicillin. Risk factors for drug-resistant S. pneumoniae included use of penicillin or ampicillin in the three months before the present illness (odds ratio = 2.9; 95% CI 1.5-5.7) and possession of private medical coverage (odds ratio = 2.4; 95% CI 1.2-5.0). Pneumonia, which was confirmed radiographically, was the most common form of invasive infection, occurring in 189 children (69%). Children with meningitis were less likely to have drug-resistant S. pneumoniae (relative risk = 0.5; 95% CI 0.2-0.9). There was no correlation of response to therapy or clinical outcome to penicillin susceptibility.
Comment by Hal B. Jenson, MD, FAAP
These are the first studies comparing invasive disease and clinical outcome in children with drug-resistant S. pneumoniae infections. The results of both studies are similar, and are also similar to a previous study of adults with severe pneumococcal pneumonia.1 The comparable prognosis and outcome for drug-resistant S. pneumoniae reflects, in part, the greater percentage of relative or low-level resistance (MIC of 0.1-1 mcg/mL) as opposed to absolute or high-level resistance (MIC of 2 mcg/mL).
These results are reassuring in that they emphasize that, although the antimicrobial susceptibilities have changed, the virulence of the organisms has not become enhanced. They also indicate that we do not have to change our general approach to suspected pneumococcal pneumonia or other pneumococcal infections outside of the central nervous system. We should use beta-lactam antibiotics at the higher range of the recommended dosages for presumed or proven invasive pneumococcal infections. If meningitis is suspected, empiric treatment should include vancomycin (at higher doses of 60 mg/kg/d) in addition to a third-generation cephalosporin until susceptibilities are known. Prior administration of lactam antibiotics is associated with an increased frequency of nasopharyngeal carriage, and now also infection, as found in the study from Argentina and Uruguay, with drug-resistant pneumococcus. This is also the reason behind the increased prevalence of drug-resistant isolates among children with health insurance and in more affluent groups of children in the United States, who have better access to health care and greater use of antibiotics. The widespread use of antibiotics in children has been identified as a significant factor for development of pneumococcal resistance. This has led to a re-emphasis of the need for appropriate use of antibiotics and underscores the potential public health consequences of inappropriate antibiotic prescribing. Antibiotics are certainly inappropriate for the common cold and other viral infections; some experts have even recommended that we rethink our routine use of antibiotics for acute otitis media and, instead, follow the model of the Scandinavian countries and reserve the use of antibiotics for children who continue with symptoms (fever and ear pain) for more than 48 hours.
The development of penicillin- and cephalosporin-resistant pneumococci emphasizes the importance of attempting to obtain a culture isolate from blood cultures in all cases of suspected occult bacteremia in children 3 months to 2-3 years of age and from other sites (e.g., pleural fluid) whenever foci are present, and to determine the antimicrobial susceptibilities to guide therapy. The lack of any specific clinical predictors of drug susceptibility emphasizes that whether a blood culture is obtained, or whether the patient is treated empirically, that close clinical follow-up is the key to identifying complications early and facilitating a good clinical outcome.
Reference
1. Pallares R, et al. Resistance to penicillin and cephalosporin and mortality from severe pneumococcal pneumonia in Barcelona, Spain. N Engl J Med 1995;333:474-480.
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