Drug-Resistant Streptococcus pneumoniae -- Kentucky and Tennessee, 1993

Streptococcus pneumoniae is the most common bacterial cause of pneumonia worldwide in children and adults and a leading cause of sepsis and meningitis (1). In addition, it is the etiology of 30%- 50% of episodes of acute otitis media (2), the most frequent reason for pediatric office visits in the United States (approximately 24.5 million per year) (3). Because sensitive and rapid diagnostic tests are not available, most pneumococcal infections are treated empirically; until recently, penicillin (PCN) and related drugs have been the treatment of choice. However, because of the emergence of infections with drug-resistant S. pneumoniae (DRSP), decisions regarding the management of infections caused by this pathogen have become increasingly complicated (4). This report summarizes results of recent investigations by CDC and state public health officials of DRSP in communities in Kentucky and Tennessee. Kentucky

In January 1993, pediatricians in a community in central Kentucky reported to the Kentucky Department for Health Services the detection of PCN resistance (minimum inhibitory concentration {MIC} greater than or equal to 0.1 ug/mL) in 24 (28%) of 85 S. pneumoniae isolates cultured from middle-ear fluid of children with acute otitis media during 1992-1993; of the PCN-resistant isolates, 11 (13%) were characterized by high-level (MIC greater than or equal to 2 ug/mL) PCN resistance. A subsequent investigation determined that child day care center attendance and antibiotic use were risk factors for infection with DRSP. To assess the prevalence of DRSP among children in the community, during February 11-19, nasopharyngeal swab cultures were obtained from 158 children (aged 3-96 months) attending the largest child day care center in the community and 82 nonacutely ill children (aged 2-66 months) visiting the county public health department. PCN resistance was detected in 49 (61%) of the 80 pneumococcal isolates obtained from children attending the child day care center and in 14 (33%) of the 43 isolates from children visiting the county health department.

Of the 63 PCN-resistant isolates, 41 (65%) were highly resistant to PCN, and 17 (27%) were highly resistant to cefotaxime (MIC greater than or equal to 2 ug/mL) (5), an extended spectrum cephalosporin. In addition, 53 (43%) of all 123 isolates were resistant to three commonly used oral antimicrobial drugs (PCN, erythromycin {ERY} {MIC greater than or equal to 1 ug/mL}, and trimethoprim/sulfamethoxazole {TMP/SMZ} {MIC greater than or equal to 1/19 ug/mL}), and 30 (24%) isolates were resistant to chloramphenicol (MIC greater than or equal to 8 ug/mL). Eight serotypes of DRSP were identified; serotypes 6A, 6B, 19F, and 23F accounted for 87% of all drug-resistant isolates. Tennessee

During October 1989-September 1993, a pediatric hospital in Memphis identified 10 children (nine of whom were aged less than 2 years) with community-acquired invasive pneumococcal infections resistant to both PCN and extended spectrum cephalosporins; six had meningitis, and four had other invasive pneumococcal infections. Onset in six cases occurred since January 1992.

As a result of the detection of DRSP, from May 1993 through September 1993, nasopharyngeal swab cultures were obtained from 361 children (aged less than or equal to 6 years) with otitis media enrolled at 17 sites in Memphis, including public health clinics, emergency departments, and private practice settings. PCN resistance was detected in 32 (29%) of 110 pneumococcal isolates; of the 32 PCN-resistant isolates, six (19%) were highly resistant to PCN, eight (25%) were highly resistant to cefotaxime, and eight (25%) were resistant to ERY and TMP/SMZ. Six serotypes of PCN-resistant S. pneumoniae were identified; serotypes 6B, 19A, 19F, and 23F accounted for 79% of all PCN-resistant isolates. Reported by: S Block, MD, J Hedrick, MD, Kentucky Pediatric Research; P Wright, R Finger, MD, State Epidemiologist, Kentucky Dept for Health Svcs. R Leggiadro, MD, LeBonheur Children's Medical Center, Dept of Pediatrics, M Appleton, MD, Dept of Internal Medicine, Univ of Tennessee, Memphis; S Kahn, MD, Memphis-Shelby County Health Dept; R Hutcheson, MD, State Epidemiologist, Tennessee Dept of Health. Child and Adult Immunization Br, National Immunization Program; Nosocomial Pathogens Laboratory Br and Special Studies Activity, Hospital Infections Program; Childhood and Respiratory Diseases Br, Div of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: The emergence of community-acquired DRSP underscores that anti-microbial resistance is a potentially widespread problem affecting persons of different age groups within the community. While DRSP was reported with increasing frequency in Europe during the 1980s (4), it was uncommon in the United States through 1987 (6). From 1987 to 1992, however, the proportion of S. pneumoniae strains highly resistant to PCN increased from 0.02% to 1.3% (7).

Although infection with DRSP most commonly occurs in young children, sporadic cases of disease and clusters of DRSP infection have been reported in adults (4,8). In addition, transmission of DRSP may be facilitated in institutional settings (e.g., child day care centers and hospitals) in which antimicrobial drug usage and persons in close and prolonged contact frequently coexist (4). The impact of DRSP with intermediate-level PCN resistance on clinical course and outcome is unclear. High-dose PCN therapy may be adequate to treat bacteremia and pneumonia caused by DRSP with intermediate-level PCN resistance (4,9) but not for meningitis.

The findings of the investigations described in this report indicated that a high proportion of pneumococci isolated from children in a rural community and an urban area were resistant to PCN and to other drugs usually reserved for intravenous treatment of meningitis and other serious invasive diseases. Although carriage of DRSP does not result in disease in most persons, increasing carriage rates of DRSP in a community most likely correlates with an increasing proportion of pneumococcal disease resulting from resistant strains. The detection of multiple serotypes of DRSP in both communities in this report suggests that the problem is endemic in these areas.

At least four strategies may play a role in preventing morbidity and mortality associated with infection with DRSP. First, CDC is working with the Association of State and Territorial Public Health Laboratory Directors and the Council of State and Territorial Epidemiologists to develop strategies for more comprehensive surveillance for DRSP. This includes the screening of invasive pneumococcal isolates for resistance to PCN and other drugs that are likely to be used in treating cases (5). * Second, the optimal management strategies must be determined for infections with DRSP. In areas with high rates of pneumococcal resistance to extended spectrum cephalosporins, empiric therapy with vancomycin in addition to an extended spectrum cephalosporin should be considered for cases of meningitis potentially caused by S. pneumoniae until the results of culture and susceptibility testing are available. Third, because infection with DRSP is probably facilitated by increasing exposure to antimicrobial agents (4), strategies for rational antimicrobial use should be promoted. The emergence of DRSP indicates the need to reassess the efficacy of prophylactic antimicrobial drug regimens for otitis media and to develop new antimicrobial drugs for treatment of drug-resistant infection. Fourth, the Advisory Committee on Immunization Practices recommends that persons aged greater than or equal to 2 years who are at increased risk for serious pneumococcal infection and all persons aged greater than or equal to 65 years should receive 23-valent pneumococcal capsular polysaccharide vaccine (1). Although children aged less than 2 years are at increased risk for serious drug-resistant pneumococcal disease, pneumococcal vaccines are not immunogenic in this population; pneumococcal protein-conjugate vaccines are being evaluated for use in this age group.

References

1. ACIP. Update on adult immunization: recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR 1991;40(no. RR-12):42-4.

2. Bluestone CD, ed. Pediatric otolaryngology. 2nd ed. Philadelphia: WB Saunders, 1990.

3. Schappert SM. Office visits for otitis media: United States, 1975-90. Hyattsville, Maryland: US Department of Health and Human Services, Public Health Service, CDC, 1992. (Advance data no. 214).

4. Klugman KP. Pneumococcal resistance to antibiotics. Clin Micro Rev 1990;3:171-96.

5. National Committee for Clinical Laboratory Standards. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically -- third edition; approved standard. Villanova, Pennsylvania: National Committee for Clinical Laboratory Standards, 1993. (NCCLS document M7-A3; vol 12, no. 25).

6. Spika JS, Facklam RR, Plikaytis BD, Oxtoby MJ. Antimicrobial resistance of Streptococcus pneumoniae in the United States, 1979- 1987. J Infect Dis 1991;163:1273-8.

7. Butler JC, Breiman RF, Facklam RR, Pneumococcal Working Group. Emergence of drug-resistant pneumococci in the United States {Abstract no. 1182}. In: Program and abstracts of the 33rd Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington, DC: American Society for Microbiology, 1993:336.

8. Applebaum PC. Antimicrobial resistance in Streptococcus pneumoniae: an overview. Clin Infect Dis 1992;15:77-83.

9. Chesney PJ. The escalating problem of antimicrobial resistance in Streptococcus pneumoniae. Am J Dis Child 1992;146:912-6.

10. National Committee for Clinical Laboratory Standards. Performance standards for antimicrobial disk susceptibility tests -- fifth edition; approved standard. Villanova, Pennsylvania: National Committee for Clinical Laboratory Standards, 1993. (NCCLS document M2-A5; vol 13, no. 24).

Invasive pneumococcal isolates should be screened for PCN resistance using a 1 ug oxacillin disk (10) and MICs determined by dilution methods for isolates with oxacillin zone sizes less than or equal to 19 mm (5).

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