Statewide sentinel surveillance for antibiotic nonsusceptibility among Streptococcus pneumoniae isolates in South Carolina, 2003-2004.

Background: In 2003, the South Carolina Department of Health and Environmental Control established the Carolina Antibiotic Resistance Surveillance System (CARSS), an active sentinel surveillance system for antibiotic-resistant Streptococcus pneumoniae.

Methods: CARSS includes twelve hospitals. Each hospital was assigned a weighted sample size. Minimum inhibitory concentrations were determined using the E-test method.

Results: A total of 452 isolates were collected. The prevalence of penicillin nonsusceptibility in the study was 44.9%. Penicillin intermediate resistance (PCN-I) was 33.2%, and penicillin high-level resistance (PCN-R) was 11.7%. One hundred six (23.5%) isolates were nonsusceptible to one antibiotic. One hundred twenty-four (27.4%) isolates were nonsusceptible to three or more antibiotics.

Conclusions: CARSS confirmed the prevalences of antibiotic nonsusceptibility previously reported for South Carolina. However, CARSS suggests resistance is shifting from PCN-R to PCN-I in South Carolina. There is a high prevalence of multidrug nonsusceptibility in South Carolina. CARSS will continue to monitor these trends.

Key Words: antibiotic resistance, Streptococcus pneumoniae, surveillance.

**********

Streptococcus pneumoniae is the most common cause of community-acquired pneumonia, meningitis, acute otitis media, and sinusitis in the United States. (1-4) The emergence of antibiotic nonsusceptibility threatens the successful treatment of S. pneumoniae infections. (5) A number of surveillance studies have shown that penicillin nonsusceptibility (PCN-N) among S. pneumoniae isolates has spread rapidly and its prevalence continues to increase. (6,7) In addition, a number of studies have demonstrated that the prevalence of PCN-N and nonsusceptibility to other antibiotics varies by geographic regions of the United States and even within those regions. In fact, the prevalence of nonsusceptibility can even vary by region in a single state. (8,9) The PROTEKT US surveillance study, a large prospective study of respiratory tract isolates conducted in the United States from 2000 to 2001, confirmed these findings and found that nonsusceptibility rates were highest in the southeastern United States. (4,10-12)

The South Carolina Department of Health and Environmental Control (DHEC) conducted cross-sectional studies of clinical microbiology laboratories in South Carolina in 1998 and 2001 to estimate the prevalence of penicillin nonsusceptibility, extended-spectrum cephalosporin nonsusceptibility (ESC-N), and levofloxacin nonsusceptibility (LEV-N) among sterile and nonsterile S pneumoniae isolates. The 1998 study collected data from January 1, 1998 through September 30, 1998. The follow-up study in 2001 collected data from January 1, 2000 through December 31, 2000. The 2001 study indicated a high prevalence of PCN-N (38.4%), ESC-N (17.7%) and LEV-N (0.8%). This included an increase in PCN-N prevalence from 1998 (34.5%, chi-square P = 0.01). (8) More recent national studies indicate an increase in high-level (MIC [greater than or equal to] 2 [micro]g/mL) and very high-level (MIC [greater than or equal to] 8 [micro]g/mL) penicillin resistance (3,5,10) and an increase in the number of multidrug resistant S. pneumoniae (MDRSP) isolates. (3,10)

Given the high prevalence of antibiotic resistance among S pneumoniae isolates in South Carolina, in 2003, DHEC established the Carolina Antibiotic Resistance Surveillance System (CARSS), an active sentinel surveillance system for antibiotic resistant S pneumoniae. The Centers for Disease Control and Prevention (CDC) and other national professional organizations recommend active, population-based surveillance based on laboratory-confirmed disease as the most accurate method of estimating rates of antibiotic nonsusceptible S pneumoniae. (13-15) However, these systems can be costly and labor intensive. Sentinel surveillance systems, which collect data on antibiotic non-susceptible S pneumoniae from a sample of hospitals, clinics, and/or laboratories, have been suggested as a feasible alternative. (14-16) This article summarizes the development of the sentinel surveillance system and its results from October 1, 2003 through September 30, 2004. The results will aid in identifying time and geographic trends in antibiotic nonsusceptible rates, as well as suggesting guidelines for empiric therapy for practitioners in South Carolina.

Materials and Methods

CARSS includes 12 hospitals in South Carolina. Each hospital was assigned a weighted sample size based on their total number of S pneumoniae isolates in 2002. A total of 1,192 isolates were reported from the twelve hospitals in 2002. Sample sizes varied by hospital.

Hospitals submitted isolates on a quarterly basis to a single reference laboratory for susceptibility testing. Isolates were from consecutive patients, and duplicate isolates were excluded. Isolates were collected from both sterile (ie, blood, cerebrospinal fluid) and nonsterile (ie, sputum, nasopharyngeal swab) sites. In addition, patient demographic data, including age, gender, race or ethnicity, and hospitalization status were collected. CARSS started collecting isolates on October 1, 2003.

Antibiotic Susceptibility Testing

Minimum inhibitory concentrations (MICs) were determined using the E-test method as described by the Clinical and Laboratory Standards Institute (CLSI, formerly NCCLS). MIC testing was conducted for the following antibiotics: amoxicillin, penicillin, cefdinir, cefotaxime, azithromycin, levofloxacin, clindamycin, and vancomycin. CLSI breakpoints were used to define susceptibility. (17) MIC testing for azithromycin and clindamycin started on March 1, 2004. All MIC testing was performed at the reference laboratory.

Data Analysis

Hospital sample sizes were determined using EpiInfo Version 6.04b (CDC, Atlanta, GA). A sample size of 291 isolates was needed to achieve a statistical power of 95% and detect a 5% difference from the true prevalence. Data was analyzed using SAS Version 8.2 (SAS Institute Inc., Cary, NC). A [chi square] test was used to detect a significant difference (P < 0.05) between prevalence rates. Fisher's exact test was used to detect a significant difference when at least one cell size was less than five. A pearson correlation coefficient was used to indicate the strength of linear relationships among MICs.

Results

A total of 452 isolates were collected from October 1, 2003 through September 30, 2004. Patient demographic data is summarized in Table 1. Overall, a majority of the patients were male (54.2%), white (64.4%), had inpatient hospital status (64.1%), and 48% of the isolates came from nonsterile sites. Patient demographic data is also reported by age group. Age groups were defined by quartiles and reported as 0 to 17, 18 to 49, 50 to 64, and [greater than or equal to]65.

Statewide Prevalence

Table 2 summarizes the statewide and age-group specific prevalences of nonsusceptibility for the 8 antibiotics. The prevalence of PCN-N in South Carolina in the study was 44.9%. Penicillin intermediate resistance (PCN-I) was 33.2%, and penicillin high-level resistance (PCN-R) was 11.7%. The prevalence of azithromycin nonsusceptibility (AZN-N) was 30.1%, with 3.2% of the isolates having azithromycin intermediate resistance and 26.9% having azithromycin high-level resistance. The prevalence of LEV-N was 1.6%, with 0.4% of the isolates having levofloxacin intermediate resistance and 1.1% having levofloxacin high-level resistance. All isolates were susceptible to vancomycin.

The prevalence of antibiotic nonsusceptibility varied across age groups. PCN-N (58.8%) was highest in the 0 to 17 age group. Cefdinir nonsusceptibility (42.1%) and cefotaxime nonsusceptibility (13.2%) were also highest in the 0 to 17 age group. LEV-N increased with age. LEV-N (0.0%) was lowest in the 0 to 17 age group and highest in the 50 to 64 age group (3.7%). All other antibiotic prevalences were similar across age groups (Table 2).

Statewide prevalences of nonsusceptibility were also determined by site of isolate (sterile versus nonsterile) and hospitalization status (inpatient versus outpatient). The prevalence of PCN-N was significantly higher in nonsterile isolates (47.9%) than in sterile isolates (36.0%, [chi square] test, P = 0.02). No other prevalences of nonsusceptibility differed by site of isolate. The prevalence of PCN-N was significantly higher in outpatient isolates (54.3%) than in inpatient isolates (39.7%, [chi square] test, P < 0.01), and the prevalence of PCN-I was significantly higher in outpatient isolates (42.5%) than in inpatient isolates (28.3%, [chi square] test, P < 0.01). No other prevalences of nonsusceptibility differed by hospitalization status.

Multidrug Nonsusceptibility

One hundred fifty-seven (34.7%) isolates were susceptible to all eight antibiotics. One hundred six (23.5%) isolates were nonsusceptible to one antibiotic. One hundred twenty-four (27.4%) isolates were nonsusceptible to three or more antibiotics. Zero isolates were nonsusceptible to all eight antibiotics (Table 3).

Table 4 summarizes the prevalences of antibiotic nonsusceptibility by penicillin susceptibility. Penicillin susceptibility was defined as penicillin susceptible (PCN-S) and PCN-N. The prevalence of antibiotic nonsusceptibility was higher in the PCN-N isolates when compared with PCN-S isolates.

A correlation was observed between penicillin MICs and the MICs of the other seven antibiotics. Five of the seven antibiotics had MICs with a significant positive correlation coefficient with penicillin MICs (P < 0.01). Correlation coefficients ranged from 0.25 to 0.92. Levofloxacin (r = 0.04, P = 0.37) and vancomycin (r = 0.07, P = 0.16) MICs did not have a significant correlation with penicillin MICs.

Discussion

The CARSS study determined high prevalences of antibiotic nonsusceptibility among S pneumoniae isolates in South Carolina. Our prevalences of antibiotic nonsusceptibility were similar to those found in a previous study, which were reported for either South Carolina or the southeastern United States. (10-12,18) The prevalence of LEV-N (1.6%) was low, but was higher than previously reported prevalences for South Carolina (0%) or the southeastern United States (0.3%). The prevalence of AZN-N was 30.1%. This result was lower than previously reported prevalences for azithromycin or erythromycin. The CARSS study did find a difference among prevalences of PCN-I and PCN-R in South Carolina compared with previous studies. Our prevalence of PCN-I (33.2%) was higher than the PROTEKT US study result (8.3%), and our prevalence of PCN-R (11.7%) was lower than the PROTEKT US study (41.7%). (10-12) When looking at just PCN-R isolates, 26 (49.1%) of 53 isolates had an MIC = 2 [micro]g/mL and 13 (24.5%) isolates had an MIC = 3 [micro]g/mL. The CARSS study identified 3 (<0.01%) isolates with very high-level (MIC [greater than or equal to] 8 [micro]g/mL) penicillin resistance. This is an important difference because other studies emphasize that the prevalence of PCN-R is increasing. (5,10)

The results from CARSS emphasize the importance of PCN-N surveillance. The prevalence of nonsusceptibility among PCN-N isolates was greater for five antibiotics (amoxicillin, azithromycin, cefdinir, cefotaxime, and clindamycin) when compared with PCN-S isolates (Table 4). This agrees with the findings of other studies. Penicillin nonsusceptibility correlates with resistance to other antibiotics. (5) The MICs of the five antibiotics above all had significant positive correlation coefficients with penicillin MICs. Despite being significant, the correlation coefficients for azithromycin (r = 0.25) and clindamycin (r = 0.26) were very low. The low correlation coefficients could be explained by differing mechanisms of resistance. Azithromycin resistance is typically mediated through efflux (mef(A) gene) and to a lesser extent by altered target sites through the erm gene. Clindamycin resistance is due to the erm gene. (18) [beta]-lactam resistance is mediated through two different mechanisms: [beta]-lactamase and altered-target sites (penicillin-binding protein).

The prevalence of multidrug nonsusceptibility is high in South Carolina. Doern et al. (19) determined the national prevalence of multidrug nonsusceptibility, defined as nonsusceptibility to two or more antibiotics, to be 16% in 1997 to 1998. In a 2001 study, Mera et al. (3) reported 17.5% of isolates were nonsusceptible to three or more antibiotics. In 2003 to 2004, the CARSS study found that 41.8% of the isolates were nonsusceptible to two or more antibiotics, and 27.4% were nonsusceptible to three or more antibiotics (Table 3).

Conclusions

Results from the first year of the CARSS study confirm the prevalence of antibiotic nonsusceptibility reported for South Carolina and the southeastern United States in previous studies. However, the CARSS study suggests that a shift from PCN-R to PCN-I is occurring in South Carolina. This finding is important because current clinical guidelines for the treatment of acute otitis media and sinusitis advise high dose penicillin, amoxicillin, or amoxicillin-clavulanic acid to overcome penicillin resistance in S pneumoniae. (20,21) High dose regimens are more likely to treat PCN-I isolates than PCN-R isolates. In addition, this data suggests that healthcare providers would have more treatment options when selecting a [beta]-lactam for treatment of S pneumoniae infections. By having options in [beta]-lactam selection, healthcare providers can reserve newer antibiotics (ie, fluoroquinolones) for unresponsive infections.

The shift from PCN-R to PCN-I could be a result of DHEC's statewide Careful Antibiotic Use program, which educates healthcare providers and the public on appropriate antibiotic use. It could also be due to the CDC's National Campaign for Appropriate Antibiotic Use and clinical practice guidelines provided by professional societies and the CDC. The CARSS study will continue to monitor this trend in its second year. This study emphasizes the importance of local or regional surveillance for antibiotic nonsusceptibility among S pneumoniae isolates.

Multidrug nonsusceptibility is a problem in South Carolina. The results of the CARSS study are sufficient to guide healthcare providers in selecting appropriate empiric therapy for suspected pneumococcal infections. Due to high prevalences of nonsusceptibility, South Carolina healthcare providers should consider the possibility of antibiotic nonsusceptibility when treating suspected S pneumoniae infections.

References

1. Whitney CG, Farley MM, Hadler J, et al. Increasing prevalence of multidrug-resistant Streptococcus pneumoniae in the United States. N Engl J Med 2000;343:1917-1924.

2. Jacobs MR. Streptococcus pneumoniae: epidemiology and patterns of resistance. Am J Med 2004;117:3S-15S.

3. Mera RM, Miller LA, Daniels JJD, et al. Increasing prevalence of multidrug-resistant Streptococcus pneumoniae in the United States over a 10-year period: Alexander Project. Diagn Microbiol Infect Dis 2005;51:195-200.

4. Brown SD, Farrell DJ. Antibacterial susceptibility among Streptococcus pneumoniae isolated from paediatric and adult patients as part of the PROTEKT US study in 2001-2002. J Antimicrob Chemother 2004;54(Suppl 1):i23-i29.

5. Schrag SJ, McGee L, Whitney CG, et al. Emergence of Streptococcus pneumoniae with very-high-level resistance to penicillin. Antimicrob Agents Chemother 2004;48:3016-3023.

6. Felmingham D, Gruneberg RN. The Alexander Project 1996-1997: latest susceptibility data from this international study of bacterial pathogens from community-acquired lower respiratory tract infections. J Antimicrob Chemother 2000;45:191-203.

7. Hoban DJ, Doern GV, Fluit AC, et al. Worldwide prevalence of anti-microbial resistance in Streptococcus pneumoniae, Haemophilus in-fluenzae, and Moraxella catarrhalis in the SENTRY antimicrobial surveillance program, 1997-1999. Clin Infect Dis 2001;32(Suppl 2):S81-S93.

8. Dauner DG, Gibson JJ, Roberts DF, et al. Laboratory survey of antibiotic nonsusceptibility among Streptococcus pneumoniae isolates in South Carolina, 1998 versus 2000. South Med J 2003;96:960-967.

9. Quale J, Landman D, Ravishankar J, et al. Streptococcus pneumoniae, Brooklyn, New York: fluoroquinolone resistance at our doorstep. Emerg Infect Dis 2002;8:594-597.

10. Rybak MJ. Increased bacterial resistance: PROTEKT US: an update. Ann Pharmacother 2004;38:S8-S13.

11. Waites K, Brown S. Antimicrobial resistance among isolates of respiratory tract infection pathogens from the southern United States: data from the PROTEKT US surveillance program 2000/2001. South Med J 2003;96:974-985.

12. Doern GV, Brown SD. Antimicrobial susceptibility among community-acquired respiratory tract pathogens in the USA: data from PROTEKT US 2000-01. J Infect 2004;48:56-65.

13. Van Beneden CA, Lexau C, Baughman W, et al. Aggregated antibio-grams and monitoring of drug-resistant Streptococcus pneumoniae. Emerg Infect Dis 2003;9:1089-1095.

14. Schrag SJ, Zell ER, Schuchat A, et al. Sentinel surveillance: a reliable way to track antibiotic resistance in communities? Emerg Infect Dis 2002;8:496-502.

15. Billeter M. American Society of Health-System Pharmacists. ASHP therapeutic position statement on strategies for identifying and preventing pneumococcal resistance. Am J Health Syst Pharm 2004;61:2430-2435.

16. Jernigan DB, Kargacin L, Poole A, et al. Sentinel surveillance as an alternative approach for monitoring antibiotic-resistant invasive pneumococcal disease in Washington State. Am J Public Health 2001;91:142-145.

17. National Committee for Clinical Laboratory Standards (NCCLS). Performance Standards for Antimicrobial Susceptibility Testing; Fifteenth Informational Supplement. M100-S15. Wayne, PA, National Committee for Clinical Laboratory Standards, 2004.

18. Farrell DJ, Jenkins SG. Distribution across the USA of macrolide resistance and macrolide resistance mechanisms among Streptococcus pneumoniae isolates collected from patients with respiratory tract infections: PROTEKT US 2001-2002. J Antimicrob Chemother 2004;54 (Suppl 1):i17-i22.

19. Doern GV, Brueggemann AB, Huynh H, et al. Antimicrobial resistance with Streptococcus pneumoniae in the United States, 1997-1998. Emerg Infect Dis 1999;5:757-765.

20. American Academy of Pediatrics Subcommittee on Management of Acute Otitis Media. Diagnosis and management of acute otitis media. Pediatrics 2004;113:1451-1465.

21. American Academy of Pediatrics Subcommittee on Management of Sinusitis and Committee on Quality Improvement. Clinical practice guidelines: management of sinusitis. Pediatrics 2001;108:798-808.

It is what you do from now on that will either move our civilization
forward a few tiny steps, or else ... begin to march us steadily
backward.
--Patrick Stewart

Daniel G. Dauner, PharmD, MSPH, Dixie F. Roberts, RN, MPH, and George S. Kotchmar, MD

From the College of Pharmacy, University of South Carolina; the Division of Acute Epidemiology, Department of Health and Environmental Control; and the Division of Infectious Diseases, Department of Pediatrics, School of Medicine, University of South Carolina, Columbia, SC.

Reprint requests to Daniel G. Dauner, Medical College of Georgia, 1120 15th Street, B1-2101, Augusta, GA 30912. Email: [e-mail]

Accepted April 20, 2006.

RELATED ARTICLE: Key Points

* The prevalence of penicillin nonsusceptibility was 44.9%, with 33.2% of isolates being intermediate resistant and 11.7% being high-level resistant.

* The prevalence of azithromycin nonsusceptibility was 30.1%, with 3.2% of isolates being intermediate resistant and 26.9% being high-level resistant.

* The prevalence of levofloxacin nonsusceptibility was 1.6%, with 0.4% isolates being intermediate resistant and 1.1% being high-level resistant.

* The prevalence of isolates which were nonsusceptible to two or more antibiotics was 41.8%, and 27.4% were nonsusceptible to three or more antibiotics.

Table 1. Demographic characteristics of patients with Streptococcus
pneumoniae in South Carolina, 2003-2004 (a)

                                 Age groups in years
                               0-17       18-49      50-64
Characteristic     All ages    (N = 114)  (N = 116)  (N = 108)

Gender
  Male             245 (54.2)  64 (56.1)  66 (56.9)  56 (51.9)
  Female           203 (44.9)  48 (42.1)  50 (43.1)  51 (47.2)
  Unknown            4 (0.9)    2 (1.8)    0 (0.0)    1 (0.9)
Race/ethnicity
  White            291 (64.4)  72 (63.2)  55 (47.4)  71 (65.7)
  Black            114 (25.2)  26 (22.8)  46 (39.7)  29 (26.9)
  Hispanic           8 (1.8)    4 (3.5)    4 (3.5)    0 (0.0)
  Native American    1 (0.2)    1 (0.9)    0 (0.0)    0 (0.0)
  Unknown           38 (8.4)   11 (9.7)   11 (9.5)    8 (7.4)
Isolate site
  Nonsterile       217 (48.0)  48 (42.1)  50 (43.1)  57 (52.8)
  Sterile          164 (36.3)  47 (41.2)  45 (38.8)  32 (29.6)
  Unknown           71 (15.7)  19 (16.7)  21 (18.1)  19 (17.6)
Hospitalization
  Inpatient        213 (47.1)  34 (29.8)  56 (48.3)  51 (47.2)
  Outpatient       153 (33.9)  70 (61.4)  33 (28.5)  28 (25.9)
  Inpatient ICU     77 (17.0)   8 (7.0)   26 (22.4)  26 (24.1)
  Unknown            9 (2.0)    2 (1.8)    1 (0.9)    3 (2.8)

                   Age groups in years
                   [greater than or equal to]65
Characteristic     (N = 114)

Gender
  Male             59 (51.8)
  Female           54 (47.4)
  Unknown           1 (0.9)
Race/ethnicity
  White            93 (81.6)
  Black            13 (11.4)
  Hispanic          0 (0.0)
  Native American   0 (0.0)
  Unknown           8 (7.0)
Isolate site
  Nonsterile       62 (54.4)
  Sterile          40 (35.1)
  Unknown          12 (10.5)
Hospitalization
  Inpatient        72 (63.2)
  Outpatient       22 (19.3)
  Inpatient ICU    17 (14.9)
  Unknown           3 (2.6)

(a) Isolates are reported from October 1, 2003 through September 30,
2004.

Table 2. Overall and age group specific prevalences of antibiotic
nonsusceptibility among Streptococcus pneumoniae isolates in South
Carolina, 2003-2004 (a)

Age groups                    Amoxicillin  Azithromycin   Cefdinir

All ages (N = 452)
  NS, n (%)                   28 (6.2)     47 (30.1) (b)  129 (28.5)
  I, n (%)                    24 (5.3)      5 (3.2)        30 (6.6)
  R, n (%)                     4 (0.9)     42 (26.9)       99 (21.9)
0-17 (N = 114)
  NS, n (%)                   11 (9.6)     11 (32.3) (b)   48 (42.1)
  I, n (%)                     7 (6.1)      1 (2.9)        10 (8.8)
  R, n (%)                     4 (3.5)     10 (29.4)       38 (33.3)
18-49 (N = 116)
  NS, n (%)                    6 (5.2)     12 (30.8) (b)   24 (20.7)
  I, n (%)                     6 (5.2)      1 (2.6)         5 (4.3)
  R, n (%)                     0 (0.0)     11 (28.2)       19(16.4)
50-64 (N = 108)
  NS, n (%)                    4 (3.7)     11 (31.4) (b)   25 (23.2)
  I, n (%)                     4 (3.7)      2 (5.7)         7 (6.5)
  R, n (%)                     0 (0.0)      9 (25.7)       18 (16.7)
[greater than or equal to]65
  (N = 114)
  NS, n (%)                    7 (6.1)     13 (27.1) (b)   32 (28.1)
  I, n (%)                     7 (6.1)      1 (2.1)         8 (7.0)
  R, n (%)                     0 (0.0)     12 (25.0)       24 (21.1)

Age groups                    Cefotaxime  Clindamycin    Levofloxacin

All ages (N = 452)
  NS, n (%)                   40 (8.9)    33 (18.0) (c)  7 (1.6)
  I, n (%)                    29 (6.4)    17 (9.3)       2 (0.4)
  R, n (%)                    11 (2.4)    16 (8.7)       5 (1.1)
0-17 (N = 114)
  NS, n (%)                   15 (13.2)    7 (18.9) (c)  0 (0.0)
  I, n (%)                    10 (8.8)     4 (10.8)      0 (0.0)
  R, n (%)                     5 (4.4)     3 (8.1)       0 (0.0)
18-49 (N = 116)
  NS, n (%)                    8 (6.9)     7 (14.9) (c)  1 (0.9)
  I, n (%)                     6 (5.2)     2 (4.3)       0 (0.0)
  R, n (%)                     2 (1.7)     5 (10.6)      1 (0.9)
50-64 (N = 108)
  NS, n (%)                    6 (5.6)     9 (18.7) (c)  4 (3.7)
  I, n (%)                     6 (5.6)     5 (10.4)      1 (0.9)
  R, n (%)                     0 (0.0)     4 (8.3)       3 (2.8)
[greater than or equal to]65
  (N = 114)
  NS, n (%)                   11 (9.6)    10 (19.6) (c)  2 (1.8)
  I, n (%)                     7 (6.1)     6 (11.8)      1 (0.9)
  R, n (%)                     4 (3.5)     4 (7.8)       1 (0.9)

Age groups                    Penicillin  Vancomycin

All ages (N = 452)
  NS, n (%)                   203 (44.9)  0 (0.0)
  I, n (%)                    150 (33.2)  0 (0.0)
  R, n (%)                     53 (11.7)  0 (0.0)
0-17 (N = 114)
  NS, n (%)                    67 (58.8)  0 (0.0)
  I, n (%)                     45 (39.5)  0 (0.0)
  R, n (%)                     22 (19.3)  0 (0.0)
18-49 (N = 116)
  NS, n (%)                    44 (38.0)  0 (0.0)
  I, n (%)                     33 (28.5)  0 (0.0)
  R, n (%)                     11 (9.5)   0 (0.0)
50-64 (N = 108)
  NS, n (%)                    44 (40.8)  0 (0.0)
  I, n (%)                     37 (34.3)  0 (0.0)
  R, n (%)                      7 (6.5)   0 (0.0)
[greater than or equal to]65
  (N = 114)
  NS, n (%)                    48 (42.1)  0 (0.0)
  I, n (%)                     35 (30.7)  0 (0.0)
  R, n (%)                     13 (11.4)  0 (0.0)

(a) Isolates are reported from October 1, 2003 through September 30,
2004.
(b) Azithromycin was tested from March 1, 2004 through September 30,
2004: all ages (N = 156), 0-17 (N = 34), 18-49 (N = 39), 50-64 (N = 35),
[greater than or equal to]65 (N = 48).
(c) Clindamycin was tested from March 1, 2004 through September 30,
2004: all ages (N = 183), 0-17 (N = 37), 18-49 (N = 47), 50-64 (N = 48),
[greater than or equal to]65 (N = 51).
NS, nonsusceptibility; I, intermediate resistance; R, high-level
resistance.

Table 3. Multidrug nonsusceptibility Streptococcus pneumoniae isolates
in South Carolina, 2003-2004

Number of nonsusceptible
antibiotics               Isolates, n (%)

0                         157 (34.7)
1                         106 (23.5)
2                          65 (14.4)
3                          71 (15.7)
4                          24 (5.3)
5                          17 (3.8)
6                          11 (2.4)
7                           1 (0.2)

Table 4. Antibiotic nonsusceptibility among Streptococcus pneumoniae
isolates in South Carolina by penicillin susceptibility, 2003-2004 (a)

                         PCN-S (N = 249)
Antibiotic        NS, n (%)  I, n (%)  R, n (%)

Amoxicillin       0 (0.0)    0 (0.0)   0 (0.0)
Azithromycin (b)  3 (3.9)    0 (0.0)   3 (3.9)
Cefdinir          1 (0.4)    0 (0.0)   1 (0.4)
Cefotaxime        0 (0.0)    0 (0.0)   0 (0.0)
Clindamycin (c)   9 (9.0)    9 (9.0)   0 (0.0)
Levofloxacin      4 (1.6)    1 (0.4)   3 (1.2)
Vancomycin        0 (0.0)    0 (0.0)   0 (0.0)

                          PCN-N (N = 203)
Antibiotic        NS, n (%)   I, n (%)   R, n (%)

Amoxicillin        28 (13.8)  24 (11.8)   4 (2.0)
Azithromycin (b)   44 (55.7)   5 (6.3)   39 (49.4)
Cefdinir          128 (63.1)  30 (14.8)  98 (48.3)
Cefotaxime         40 (19.7)  29 (14.3)  11 (5.4)
Clindamycin (c)    24 (28.9)   8 (9.6)   16 (19.3)
Levofloxacin        3 (1.5)    1 (0.5)    2 (1.0)
Vancomycin          0 (0.0)    0 (0.0)    0 (0.0)

(a) Isolates are from October 1, 2003 through September 30, 2004.
(b) Azithromycin was tested from March 1, 2004 through September 30,
2004: susceptible (N = 77), nonsusceptible (N = 79).
(c) Clindamycin was tested from March 1, 2004 through September 30,
2004: susceptible (N = 100), nonsusceptible (N = 83).
NS, nonsusceptibility; I, intermediate resistance; R, high-level
resistance.