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Geographic Variation in Penicillin Resistance in Streptococcus pneumoniae -- Selected Sites, United States, 1997

Streptococcus pneumoniae is the leading cause of bacterial pneumonia, meningitis, and otitis media in the United States. Since 1995, CDC has maintained a population-based surveillance system for S. pneumoniae as part of the Emerging Infections Program's Active Bacterial Core Surveillance to collect information on the susceptibility patterns of all invasive strains of S. pneumoniae within the entire area of surveillance (population-based) instead of from selected hospitals only (sentinel surveillance). This report presents surveillance data for 1997, which indicated that the prevalence of S. pneumoniae that was not susceptible to penicillin varied among geographic regions and among hospitals within a geographic region.

In 1997, surveillance personnel conducted active surveillance for invasive S. pneumoniae infection in seven regions in the United States with a total population of 16 million. The surveillance sites were California (San Francisco County), Connecticut (entire state), Georgia (20-county Atlanta area), Maryland (six-county Baltimore area), Minnesota (seven-county Minneapolis-St. Paul area), Oregon (three-county Portland area), and Tennessee (five urban counties). Invasive infection was defined as isolation of S. pneumoniae from a normally sterile site, such as blood or cerebrospinal fluid, in a resident of one of the surveillance areas. Pneumococcal isolates were sent to reference laboratories, where in vitro antibiotic susceptibility testing was conducted by broth microdilution. Intermediate susceptibility to penicillin was defined as a minimum inhibitory concentration (MIC) of 0.12-1.0 ug/mL; resistance was defined as an MIC greater than or equal to 2.0 ug/mL (1). The term "nonsusceptible" refers to both intermediate and resistant organisms.

To determine whether pneumococcal resistance in individual hospitals would be representative of resistance in a surveillance area, the proportion of penicillin-nonsusceptible isolates from individual hospitals was compared with the proportion of nonsusceptible isolates from the entire surveillance area where each hospital was located. To reduce random variation because of hospitals with small numbers of isolates, only hospitals that had greater than or equal to 10 isolates in 1997 were included in this analysis. The proportion of nonsusceptible isolates for a hospital was considered representative of that surveillance area if the proportion was within 5% of the overall proportion of nonsusceptible isolates for the area. Certain demographic characteristics of the hospital's patient population were assessed to determine predictors of that hospital's representativeness of the proportion of nonsusceptible isolates in the area. In particular, the analysis evaluated hospitals with a high proportion of pediatric cases (greater than 30% of isolates from children aged less than 18 years), hospitals with a large proportion of cases among blacks (greater than 50% of isolates from black patients), and hospitals with many isolates (greater than or equal to 30 isolates). The chi-square test was used for comparison of proportions.

In 1997, 3237 cases of invasive pneumococcal disease were detected in the surveillance areas. Of the isolates from these cases, 3123 (96.5%) were from blood, 65 (2.0%) from cerebrospinal fluid, 20 (0.6%) from pleural fluid, and 29 (0.9%) from other sources. Overall, 25.0% of isolates were not susceptible to penicillin: 11.4% had intermediate susceptibility and 13.6% were resistant. The proportion of penicillin-nonsusceptible isolates varied significantly among the areas (Figure 1). The proportion of nonsusceptible S. pneumoniae was lowest in Maryland (15.3%) and the highest in Tennessee (38.3%).

A substantial number of hospitals in each geographic area had proportions of penicillin-nonsusceptible isolates that were greater than 5% below or above the proportion of nonsusceptible isolates for that area (Table 1). For example, the proportion of nonsusceptible isolates ranged from 0.0% to 39.1% in the 22 hospitals in Connecticut (Figure 2); seven (32%) hospitals had proportions within 5% of the overall proportion of nonsusceptible isolates for Connecticut (18.1%). The number of hospitals with the proportion of nonsusceptible isolates within 5% of the overall proportion for the surveillance area varied by site. In Maryland, significantly more hospitals (65%) had a proportion of nonsusceptible isolates within 5% of the overall proportion than did hospitals in Tennessee (24%, chi-square=5.5, p=0.02) and Minnesota (24%, chi-square=4.8, p=0.03).

Demographic characteristics of a hospital's patient population that might influence representativeness of the overall proportion of nonsusceptible isolates were analyzed. Hospitals with a higher proportion of isolates from children (greater than 30%) or black patients (greater than 50%) and more isolates overall (greater than or equal to 30) did not differ significantly from other hospitals in the proportion of nonsusceptible isolates within 5% of the overall proportion in their area.

Reported by: L Gelling, MPH, G Rothrock, MPH, A Reingold, MD, California Emerging Infections Program, Berkeley; D Vugia, MD, S Waterman, MD, State Epidemiologist, California Dept of Health Svcs. NL Barrett, MS, CA Morin, MPH, Q Phan, MPH, PA Mshar, M Cartter, MD, J Hadler, MD, State Epidemiologist, Connecticut Dept of Public Health. W Baughman, MSPH, M Bardsley, MPH, S Whitfield, MPH, M Farley, MD, Veterans Administration Medical Svcs and Emory Univ School of Medicine, Atlanta; P Blake, MD, Acting State Epidemiologist, Div of Public Health, Georgia Dept of Human Resources. L Billmann, MPH, L Harrison, MD, Johns Hopkins Univ, Baltimore; D Dwyer, MD, State Epidemiologist, Maryland State Dept of Health and Mental Hygiene. J Rainbow, MPH, C Lexau, MPH, R Danila, PhD, Acting State Epidemiologist, Minnesota Dept of Health. K Stefonek, MPH, J Donegan, M Cassidy, P Cieslak, MD, D Fleming, MD, State Epidemiologist, Oregon Health Div, Oregon Dept of Human Resources. B Barnes, MS, L Lefkowitz, MD, Dept of Preventive Medicine, Vanderbilt Medical Center, Nashville. J Jorgensen, PhD, Univ of Texas Health Science Center, San Antonio. Respiratory Diseases Br, Div of Bacterial and Mycotic Diseases and Active Bacterial Core Surveillance/Emerging Infections Program Network, National Center for Infectious Diseases, CDC.

Editorial Note:

Drug-resistant S. pneumoniae (DRSP) has become more common in the United States (2), increasing from 14% of tested isolates in 1993-94 (3) to 25% in 1997. The findings in this report indicate that despite the overall increase, the prevalence of resistance varies regionally. Resistance also varies substantially by hospital within a region, even in regions where overall resistance is low.

Sentinel surveillance for DRSP, which collects data from a selected sample of hospitals and clinics, is a focused, efficient, and economical method to gather regional epidemiologic information (3-5). Sentinel surveillance systems detected the emergence of DRSP in the United States in the late 1980s and provided some data to assess trends at the national and regional levels. However, the prevalence of DRSP among the patient populations of sentinel hospitals may not represent the prevalence among patient populations served by other area health-care facilities. Health departments that plan to target areas with high prevalences of DRSP for campaigns to promote judicious antibiotic use should consider that the prevalence of DRSP can vary markedly among hospitals in one geographic area. Although active population-based surveillance systems can provide a more representative picture of the distribution of resistance within a region, they may be too costly and labor-intensive for most health departments to maintain. The utility of alternative surveillance systems for DRSP, such as pooled hospital antibiograms, electronic laboratory surveillance, and sentinel networks that use many hospitals in selected regions of a state, is being evaluated.

The findings in this study have at least two limitations. First, despite previous associations between higher levels of resistance in children and lower levels in blacks (6), the findings described in this report indicate that these demographic characteristics were not consistently correlated with the proportion of nonsusceptible isolates in an individual hospital. The study may not have had sufficient data to define characteristics of hospitals and populations in which the prevalence of resistance is higher or lower than in the general population. Second, the representative range of nonsusceptibility for a surveillance area was defined as plus or minus 5% of the overall proportion of nonsusceptible isolates for the area. Further work is needed to define a clinically and epidemiologically meaningful threshold of antibiotic nonsusceptibility among pneumococci.

As the prevalence of resistance increases, the public health response requires a multidisciplinary approach. Surveillance can increase awareness among clinicians and public health practitioners and assist in targeting areas for intervention. Clinical guidelines can improve management of clinical syndromes commonly attributable to pneumococcal infections (7,8). Adoption of intervention strategies, including use of pneumococcal vaccines and campaigns to promote judicious use of antibiotics, offer potential to prevent infections with DRSP (9). Information and materials regarding judicious use of antimicrobial agents are available on the World-Wide Web at; additional surveillance data are available at Information is also available from ABCs, Respiratory Diseases Branch, Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Mailstop C-23, 1600 Clifton Road, N.E., Atlanta, GA 30333.


  1. National Committee for Clinical Laboratory Standards. Performance standards for antimicrobial susceptibility tests (M 100-S8). Vol 18. Villanova, Pennsylvania: National Committee for Clinical Laboratory Standards, 1998.
  2. CDC. Defining the public health impact of drug-resistant Streptococcus pneumoniae: report of a working group. MMWR 1996;45(no. RR-1).
  3. Butler JC, Hofmann J, Cetron MS, Elliott JA, Facklam RR, Breiman RF. The continued emergence of drug-resistant Streptococcus pneumoniae in the United States: an update from the Centers for Disease Control and Prevention's Pneumococcal Sentinel Surveillance System. J Infect Dis 1996;174:986-93.
  4. Thornsberry C, Ogilvie P, Kahn J, Mauriz Y. Surveillance of antimicrobial resistance in Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in the United States in 1996-1997 respiratory season. Diagn Microbiol Infect Dis 1997;29:249-57.
  5. Pfaller MA, Jones RN, Doern GV, Kugler K. Bacterial pathogens isolated from patients with bloodstream infection: frequencies of occurrence and antimicrobial susceptibility patterns from the SENTRY antimicrobial surveillance program (United States and Canada, 1997). Antimicrob Agents Chemother 1998;42:1762-70.
  6. Hofmann J, Cetron MS, Farley MM, et al. The prevalence of drug-resistant Streptococcus pneumoniae in Atlanta. N Engl J Med 1995;333:481-6.
  7. Bartlett JG, Breiman RF, Mandell LA, File TM Jr. Community-acquired pneumonia in adults: guidelines for management. Clin Infect Dis 1998;26:811-38.
  8. Dowell SF, Butler JC, Giebink GS, et al. Acute otitis media: management and surveillance in an era of pneumococcal resistance--a report from the Drug-resistant Streptococcus pneumoniae Therapeutic Working Group. Pediatr Infect Dis J 1999;18:1-9.
  9. Gonzales R, Steiner JF, Lum A, Barrett PH Jr. Decreasing antibiotic use in ambulatory practice: impact of a multidimensional intervention on the treatment of uncomplicated acute bronchitis in adults. JAMA 1999;281:1512-9.

Table 1

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TABLE 1. Proportion of Streptococcus pneumoniae isolates that were nonsusceptible to penicillin (PNSP) in surveillance
areas or in individual hospitals with >=10 isolates, by site -- selected sites, United States, 1997
                Surveillance area*                     Hospital                              Comparison of hospital and area proportions
              ----------------------    ------------------------------------------      -----------------------------------------------------
                                                                                           Hospitals            Hospitals         Hospitals
                          Proportion       No.                         Range of            within 5%             below 5%        above 5% of
                No.      of isolates    hospitals     Median no.    proportions of          of area              of area             area
              isolates    that were     with >=10    isolates per       PNSP by         -----------------------------------------------------
Site          in area       PNSP+       isolates       hospital        hospital          No.       (%)        No.       (%)      No.       (%)
California      182         15.4%           4             26          10.0%-20.0%         1       (25)         3       (75)       0       ( 0)
Connecticut     603         18.1%          22             23           0.0%-39.1%         7       (32)         8       (36)       7       (32)
Georgia         843         34.6%          22             24          18.2%-66.7%        10       (46)         6       (27)       6       (27)
Maryland        557         15.3%          20             26           3.4%-40.0%        13       (65)&        3       (15)       4       (20)
Minnesota       435         21.8%          17             20           0.0%-50.0%         4       (24)         7       (41)       6       (35)
Oregon          178         18.0%           7             19           7.7%-29.4%         4       (57)         1       (14)       2       (29)
Tennessee       439         38.3%          21             15           7.1%-73.5%         5       (24)         8       (38)       8       (38)
* The surveillance areas were San Francisco County, California; the entire state of Connecticut; the 20-county Atlanta area of Georgia; the
  six-county Baltimore area of Maryland; the seven-county Minneapolis-St. Paul area of Minnesota; the three-county Portland area of
  Oregon; and five urban counties in Tennessee.
+ Includes data from all hospitals in the area.
& p<0.05 when the proportion of hospitals within 5% of the overall proportion of PNSP in Maryland is compared with Tennessee and

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