Correspondence

Meningitis Due to Ceftriaxone-Resistant Streptococcus pneumoniae

N Engl J Med 1995; 332:893-894March 30, 1995

Article

To the Editor:

Penicillin-resistant strains of Streptococcus pneumoniae are found in many countries and are spreading, especially among children in day-care centers. Many authorities now recommend treating suspected cases of pneumococcal meningitis with ceftriaxone (or cefotaxime) and adding vancomycin, with or without rifampin, in communities where pneumococci highly resistant to penicillin are prevalent,1,2 because many such strains of pneumococci are not susceptible to ceftriaxone.3 In Providence, Rhode Island, only 2.3 percent of blood isolates of S. pneumoniae obtained at two hospitals in 1990 and 1991 had intermediate-level resistance to penicillin, and none were highly resistant.4 Hence, we presumed the prevalence of resistant strains in our area to be low.

In June 1994 a 33-year-old man, previously healthy, who lived 50 km from Providence, contracted meningitis due to a penicillin-resistant strain of S. pneumoniae. He received dexamethasone and 4 g of ceftriaxone daily for the first four days. There was initial improvement in his condition, but hydrocephalus developed, followed by a grand mal seizure on the seventh hospital day. Ventriculostomy yielded fluid that showed many granulocytes and gram-positive diplococci. Culture yielded S. pneumoniae resistant to both penicillin and ceftriaxone (Table 1Table 1Susceptibilities of the RIH94 178-0911 Strain of S. pneumoniae to Penicillin, Cefotaxime, and Ceftriaxone, as Determined by Various Methods.). The patient received vancomycin (2 g intravenously every 12 hours and 10 mg intraventricularly every 48 hours) for 18 days and rifampin (600 mg intravenously every 12 hours) for 9 days. Bilateral ventriculoperitoneal shunts were placed. The patient's condition improved and he was discharged home.

This case demonstrates the danger of basing recommendations for the empirical therapy of meningitis on the local prevalence of S. pneumoniae highly resistant to penicillin. In many communities this prevalence is not known. Our patient's isolate was capsular type 9V (as classified by Dr. Robert Austrian), a type not previously associated with resistance to ceftriaxone. Its occurrence indicates that resistance to ceftriaxone continues to spread among S. pneumoniae. More than half the 28 published reports of meningitis caused by ceftriaxone-resistant S. pneumoniae were made in 1994. Moreover, meningitis due to ceftriaxone-resistant strains may go unrecognized, because most clinical laboratories do not test the susceptibility of S. pneumoniae to this drug routinely. Gellert et al. described a 30-year-old patient with meningitis due to penicillin-resistant S. pneumoniae who responded poorly to ceftriaxone.5 The authors ascribed the persistent fever to a drug reaction. We obtained a sample of their isolate and found that it was highly resistant to penicillin (minimal inhibitory concentration, 2.0 μg per milliliter) and intermediately resistant to ceftriaxone (minimal inhibitory concentration, 1 μg per milliliter).

We suggest that all patients with the presumptive diagnosis of pneumococcal meningitis should receive high-dose ceftriaxone (or cefotaxime) plus vancomycin, with or without rifampin, until the isolate is proved to be susceptible to penicillin or ceftriaxone.

John R. Lonks, M.D.
Margaret R. Durkin, M.D.
Andrea N. Meyerhoff, M.D.
Antone A. Medeiros, M.D.
Brown University, Providence, RI 02906

5 References

1. 1

   Drug-resistant Streptococcus pneumoniae -- Kentucky and Tennessee, 1993MMWR Morb Mortal Wkly Rep 1994;43:23-31
   Medline

2. 2

   The choice of antibacterial drugsMed Lett Drugs Ther 1994;36:53-60
   Medline

3. 3

   Jette LP, Ringuette L, Dascal A, Lapointe J-R, Turgeon P. Pneumococcal resistance to antimicrobial agents in the province of Québec, Canada. J Clin Microbiol 1994;32:2572-2575
   Web of Science | Medline

4. 4

   Lonks JR, Medeiros AA. High rate of erythromycin and clarithromycin resistance among Streptococcus pneumoniae isolates from blood cultures from Providence, R.I. Antimicrob Agents Chemother 1993;37:1742-1745
   Web of Science | Medline

5. 5

   Gellert G, Bock BV, Meyers H, Robertson C, Ehling LR. Penicillin-resistant pneumococcal meningitis in an HIV-infected man. N Engl J Med 1991;325:1047-1048
   Web of Science | Medline

Citing Articles (9)

Citing Articles

1. 1

   M.-H. Tsai, S.-H. Chen, C.-Y. Hsu, D.-C. Yan, M.-H. Yen, C.-H. Chiu, Y.-C. Huang, T.-Y. Lin. (2008) Pneumococcal Meningitis in Taiwanese Children: Emphasis on Clinical Outcomes and Prognostic Factors. Journal of Tropical Pediatrics 54:6, 390-394
   CrossRef

2. 2

   Michael E. Klepser, Donald G. Klepser, Erika J. Ernst, John Brooks, Daniel J. Diekema, Essy Mozaffari, Joseph Hendrickson, Gary V. Doern. (2003) Health Care Resource Utilization Associated with Treatment of Penicillin-Susceptible and -Nonsusceptible Isolates of Streptococcus pneumoniae. Pharmacotherapy 23:3, 349-359
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3. 3

   Tina Q. Tan. (2002) Prevention of pneumococcal meningitis. Current Infectious Disease Reports 4:4, 317-323
   CrossRef

4. 4

   Steven I Aronin. (2002) Current pharmacotherapy of pneumococcal meningitis. Expert Opinion on Pharmacotherapy 3:2, 121-129
   CrossRef

5. 5

   Harriet M. Lamb, Douglas Ormrod, Lesley J. Scott, David P. Figgitt. (2002) Ceftriaxone. Drugs 62:7, 1041-1089
   CrossRef

6. 6

   STEVEN C. BUCKINGHAM, JONATHAN A. MCCULLERS, JORGE LUJÁN-ZILBERMANN, KATHERINE M. KNAPP, KAREN L. ORMAN, B. KEITH ENGLISH. (2001) Pneumococcal meningitis in children: relationship of antibiotic resistance to clinical characteristics and outcomes. The Pediatric Infectious Disease Journal 20:9, 837-843
   CrossRef

7. 7

   A. E. Fiore, J. F. Moroney, M. M. Farley, L. H. Harrison, J. E. Patterson, J. H. Jorgensen, M. Cetron, M. S. Kolczak, R. F. Breiman, A. Schuchat. (2000) Clinical Outcomes of Meningitis Caused by Streptococcus pneumoniae in the Era of Antibiotic Resistance. Clinical Infectious Diseases 30:1, 71-77
   CrossRef

8. 8

   Geoffrey S. Greene, Ronald Demasi. (1996) Penicillin-Resistant Pneumococcal Meningitis: Navigating a Therapeutic Minefield. The American Journal of the Medical Sciences 311:4, 180-185
   CrossRef

9. 9

   Charles W. Stratton, Kenneth E. Aldridge, Michael S. Gelfand. (1995) In vitro killing of penicillin-suseceptible, -intermediate, and -resistant strains of streptococcus pneumoniae by cefotaxime, ceftriaxone, and ceftizoxime: A comparison of bactericidal and inhibitory activity with achievable CSF levels. Diagnostic Microbiology and Infectious Disease 22:1-2, 35-42
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