Correspondence

Treatment of Bacterial Infections

N Engl J Med 1997; 337:793-794September 11, 1997

Article

To the Editor:

The Committee on Infectious Diseases of the American Academy of Pediatrics (AAP) has recently issued guidelines for the care of children with meningitis and other infections possibly caused by Streptococcus pneumoniae. 1 Several recommendations by Quagliarello and Scheld (March 6 issue)2 are inconsistent with these guidelines. In particular, they recommend a “broad-spectrum cephalosporin” for the empirical treatment of children 3 months to less than 18 years of age with suspected bacterial meningitis who have a nondiagnostic smear of cerebrospinal fluid on Gram's staining. The AAP recommends initial therapy with vancomycin plus ceftriaxone or cefotaxime for children with bacterial meningitis. Although a high proportion of young children with pneumococcal meningitis have positive Gram's staining of cerebrospinal fluid smears, only 50 to 68 percent of such smears are positive in older children and adults.3,4 Therefore, we would not withhold optimal therapy for S. pneumoniae from children with a high probability of bacterial meningitis even if no organisms are seen on Gram's staining.

Among the broad-spectrum cephalosporins, only cefotaxime and ceftriaxone have sufficient activity against S. pneumoniae to be recommended for the treatment of meningitis.5 In some centers, however, 20 percent of pneumococcal isolates are not susceptible to ceftriaxone or cefotaxime. Therefore, combination therapy with vancomycin and ceftriaxone or cefotaxime is indicated. Vancomycin should be discontinued as soon as quantitative tests demonstrate the susceptibility of the infecting strain to an appropriate alternative drug.

The AAP guidelines agree with Quagliarello and Scheld's recommendation that dexamethasone be used in children who are more than two months of age and who have meningitis caused by Haemophilus influenzae type b. However, the limited and inconsistent data regarding the beneficial effect of dexamethasone on the outcome of meningitis due to S. pneumoniae support the consideration of this drug rather than its recommendation.1

P. Joan Chesney, M.D.
University of Tennessee, Memphis, College of Medicine, Memphis, TN 38111

Neal A. Halsey, M.D.
Johns Hopkins University, Baltimore, MD 21205

S. Michael Marcy, M.D.
California Kaiser Permanente Health Care Program, Panorama City, CA 91402

5 References

1. 1

   American Academy of Pediatrics Committee on Infectious Diseases. Therapy for children with invasive pneumococcal infections. Pediatrics 1997;99:289-299
   CrossRef | Web of Science | Medline

2. 2

   Quagliarello VJ, Scheld WM. Treatment of bacterial meningitis. N Engl J Med 1997;336:708-716
   Full Text | Web of Science | Medline

3. 3

   Bonadio WA. The cerebrospinal fluid: physiologic aspects and alterations associated with bacterial meningitis. Pediatr Infect Dis J 1992;11:423-431
   CrossRef | Web of Science | Medline

4. 4

   Bonadio WA, Mannenbach M, Krippendorf R. Bacterial meningitis in older children. Am J Dis Child 1990;144:463-465
   Web of Science | Medline

5. 5

   Cabellos C, Viladrich PF, Verdaguer R, Pallares R, Linares J, Gudiol F. A single daily dose of ceftriaxone for bacterial meningitis in adults: experience with 84 patients and review of the literature. Clin Infect Dis 1995;20:1164-1168
   CrossRef | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: Recommendations for the empirical treatment of S. pneumoniae meningitis remain inherently controversial because antibiotic resistance continues to evolve and there are no studies documenting the superiority of any antimicrobial regimen. As stated in our review, our recommendations were based on results in animal models and small case series. For patients with meningitis and evidence of gram-positive cocci in cerebrospinal fluid, we agree that the combination of vancomycin and ceftriaxone (or cefotaxime) would be the preferred regimen. In such patients, the diagnosis of bacterial meningitis is secure and the likelihood of S. pneumoniae overwhelming, so that empirical treatment with the combination is warranted pending the results of susceptibility studies.

However, when the Gram's stain of cerebrospinal fluid reveals no organisms, the likelihood of bacterial meningitis is reduced and that of S. pneumoniae is very low. This fact, as well as a case series1 documenting the therapeutic efficacy of cefotaxime or ceftriaxone in antibiotic-resistant S. pneumoniae meningitis, led us to recommend those drugs as empirical therapy for children and adults up to the age of 50 years. We acknowledge that the patients in this case series received higher doses of cefotaxime (300 mg per kilogram of body weight per day) than we recommended (200 mg per kilogram per day). However, unless the prevalence of S. pneumoniae with high-level resistance to ceftriaxone or cefotaxime in a community is known to be high (e.g., >3 percent), the routine use of vancomycin for meningitis in a patient with a nondiagnostic Gram's stain is unwarranted and will only further increase the prevalence of vancomycin-resistant organisms.

We agree that the beneficial effects of adjunctive dexamethasone therapy in S. pneumoniae meningitis in children are less certain than in H. influenzae meningitis, and for that reason we particularly recommended dexamethasone for children who were not vaccinated against H. influenzae and those with gram-negative coccobacilli on Gram's staining of cerebrospinal fluid.

Vincent Quagliarello, M.D.
Yale University, New Haven, CT 06520-8022

W. Michael Scheld, M.D.
University of Virginia, Charlottesville, VA 22908

1 References

1. 1

   Viladrich PF, Cabellos C, Pallares R, et al. High doses of cefotaxime in treatment of adult meningitis due to Streptococcus pneumoniae with decreased susceptibilities to broad-spectrum cephalosporins. Antimicrob Agents Chemother 1996;40:218-220
   Web of Science | Medline

Citing Articles (2)

Citing Articles

1. 1

   Kameshwar Prasad, Neha Karlupia, Amit Kumar. (2009) Treatment of bacterial meningitis: An overview of Cochrane systematic reviews. Respiratory Medicine 103:7, 945-950
   CrossRef

2. 2

   B. Kevin Park, Paul M. O'Neill, James L. Maggs, Munir Pirmohamed. (1998) Safety assessment of peroxide antimalarials: clinical and chemical perspectives. British Journal of Clinical Pharmacology 46:6, 521
   CrossRef