Antibiotic Resistance

Antibiotic Resistance Of Streptococcus pneumoniae In Hawaii
by Renee A. Watase, M.T. (A.S.C.P.), MBA; Thomas S. Reppun, M.D.;
Kirk Y. Hirata, M.D.; and Xiaotian Zheng, Ph.D., February 11, 1998

Introduction

Streptococcus pneumoniae is an important pathogen causing bacteremia, meningitis, pneumonia, and otitis media. During the past two decades, the incidence of resistance to penicillin has been steadily increasing (3,7,8). This organism is also becoming resistant to non-beta lactam antibiotics, including chloramphenicol, tetracycline, trimethoprim-sulfamethoxazole, erythromycin, and broad-spectrum cephalosporins (1,2). Recently the Centers for Disease Control and Prevention (CDC) reported data from the National Pneumococcal Sentinel Surveillance System during 1993-1994 (4). The penicillin non-susceptible Strep. pneumoniae (MIC =0.1 mcg/ml: intermediate and resistant) was shown to be 14.1%, with 3.2% penicillin-resistant (MIC =2 mcg/ml). Of the penicillin non-susceptible Strep. pneumoniae isolates, 64.4% were also non-susceptible to one other class of antimicrobial drug. Similar data were reported by other multi-center surveillance studies (5,9). Since Strep. Pneumoniae infections are primarily considered to be community-acquired, it is important that population-based surveillance data are collected at the state and local levels. It is recommended that clinicians conduct their empirical antibiotic therapy for presumptive pneumococcal infections based on local prevalence data (4).

Results

In 1995, of the 92 isolates from clinical specimens tested in our laboratory (DLS), we found that 10 (13%) were penicillin non-susceptible (1 resistant and 9 intermediate by MIC). In the present study (1997), we tested 94 consecutively collected Strep. pneumoniae clinical isolates for their antibiotic susceptibilities. These isolates were from various sources including blood, CSF, ear, nose, sputum, urine, throat, and eye specimens, and were from pediatric as well as adult patients. Additionally, susceptibility data obtained from four other local clinical laboratories (Labs A, B, C, D) were analyzed. The oxacillin screening susceptibility test is done to presumptively determine if a Strep. Pneumoniae isolate is non-susceptible to penicillin. MIC testing must be done to see if the organism is truly non-susceptible; and if it is non-susceptible, whether it is of low-level resistance (intermediate, MIC =0.1 mcg/ml to <2 mcg/ml) or high-level resistance (MIC = 2 mcg/ml) organism. Results from labs A and B were limited to the oxacillin screening for penicillin only, with Lab A exhibiting 15% presumptive penicillin resistance; and Lab B with 21%. Because complete susceptibilities were not performed routinely on all isolates from Labs A and B, data comparisons were made only between our laboratory and the other two local laboratories (Labs C and D). Table 1 shows the results of the study in comparison to national surveys. For the Strep. pneumoniae isolates tested in DLS, 25% of these isolates were penicillin non-susceptible (6% were resistant and 19% were intermediate), in increase from 13% in 1995. Note that while all isolates tested in this study were susceptible to vancomycin, some isolates were found to be resistant to chloramphenicol (2%), erythromycin (7%), or tetracycline (9%). Of the penicillin non-susceptible isolates, 15 (62%) were resistant to at least one other antibiotic that was tested by our lab, whereas only 3 (4%) of penicillin susceptible isolates were resistant to other antibiotics (see table 2). Similar results were noted in the data from laboratories C and D for the different antibiotics that they tested.

Due to the limited number of isolates in our study, we were not able to draw conclusive results on age or source distribution of non-susceptible organisms. According to references, penicillin non-susceptible Strep. pneumoniae infections were found most commonly among children younger than age 4-6 years. (18% to 28%). However, more than 10% of isolates obtained from adults were non- susceptible to penicillin (3,5). This demonstrates that drug resistant Strep. pneumoniae infection is no longer just a pediatric problem. Previous studies also document the increasing resistance to broad-spectrum cephalosporins such as cefotaxime or ceftriaxone. Because of this potential for resistance, parenteral cefotaxime or ceftriaxone in combination with vancomycin is suggested as empirical therapy for Strep. pneumoniae meningitis (1,6,10,11).

Conclusion

In conclusion, the incidence of resistant Strep. Pneumoniae in Hawaii has been increasing rapidly. The actual reason for the steady increase of the incidence of drug-resistant Strep. Pneumoniae is not clear. It is believed that selective pressure resulting from frequent use of antimicrobial drugs is contributing to this development. Since organisms that are resistant to penicillin are more likely to be resistant to other antibiotics, susceptibility test results are important for determining appropriate antibiotic therapy. For organisms isolated from blood or CSF, it is important to perform complete antibiotic susceptibility tests, including MICs for penicillin and broad-spectrum cephalosporins. For organisms isolated from other sources, an oxacillin screen with reflex MIC testing of oxacillin-resistant isolates is the minimal recommendation. Finally, in patients among 2 – 65 years of age, with predisposing conditions, as well as the elderly ( 65 years), consideration should be given towards using the 23-valent pneumococcal capsular polysaccharide vaccine which covers 89% of penicillin non-susceptible Strep. pneumoniae as demonstrated by the CDC survey.

Acknowledgment

We would like to thank the following laboratories for providing their Streptococcus pneumoniae susceptibility data:

  • Clinical Laboratories of Hawaii (Microbiology Dept., Oahu location)
  • Kaiser Medical Center of Hawaii (Microbiology Dept.)
  • Straub Medical Center (Microbiology Dept.)
  • Castle Medical Center (Microbiology Dept.)

Table 1. Comparison of penicillin susceptibility results obtained in Hawaii labs with that of national surveys.

Place isolates collected Time isolates collected Total number of isolates tested Penicillin resistant (%) Penicillin intermediate
Canada (39 labs)* 1994-1995 1089 3.3% 8.4%
U.S. (11 states)** 1993-1994 740 3.2% 10.9%
U.S. (30 medical centers)*** 1994-1995 1527 9.5% 14.1%
DLS 1995 92 1% 12%
DLS 1997 94 6% 19%
Hawaii Lab C 1997 68 9% 16%
Hawaii Lab D 1997 62 3% 13%

* Reference (9).
** Reference (3).
*** Reference (5).

Table 2. Multiple drug resistance of S. pneumoniae isolates tested in lab X in 1997 (tested drugs: penicillin, erythromycin, tetracycline, and chloramphenicol).

Number of isolates tested Resistant to 3 other drugs tested Resistant to 2 other drugs tested Resistant to 1 other drug tested
Penicillin susceptible 70 0 1 (1%) 2 (3%)
Penicillin non-susceptible 24 6 (25%) 7 (29%) 2 (8%)

References

  1. Appelbaum, P.C. 1996. Epidemiology and in vitro susceptibility of drug-resistant Streptococcus pneumoniae. Pediatr. Infect. Dis. J. 15:932-939.
  2. Barry, A.L., P.C. Fuchs, and S.D.Brown. 1997. Macrolide resistance among Streptococcus pneumoniae and Streptococcus pyogenes isolates from out-patients in the USA. J. Antimicrob. Chemother. 40:139-140.
  3. Butler, J.C., J. Hofmann, M.S. Cetron, J.A. Elliot, R.R. Facklam, R.F. Breiman, and the Pneumococcal Sentinel Surveillance Working Group. 1996. 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. 174:986-993.
  4. CDC. 1997. Surveillance for penicillin-non-susceptible Streptococcus pneumoniae – New York City. 1995. JAMA. 277:1585-1586.
  5. Doern, G.V., A. Brueggemann, H.P. Holley, Jr., and A.M. Rauch. 1996. Antimicrobial resistance of Streptococcus pneumoniae recovered from outpatients in the United States during the winter months of 1994 to 1995: results of a 30-center national surveillance study. Anti. Microb. Agents Chemother. 40:1208-1213.
  6. Friedland, I.R. and K.P. Klugman. 1997. Cerebrospinal fluid bactericidal activity against cephalosporin-resistant Streptococcus pneumoniae in children with meningitis treated with high-dosage cefotaxime. Antimicrob. Agents Chemother. 41:1888-1891.
  7. Goldstein, F.W. and J. Garau. 1997. 30 years of penicillin- resistant S. pneumoniae: myth or reality? Lancet. 350:223-224.
  8. Hughes, J.M. and F.C. Tenover. 1997. Approaches to limiting emergence of antimicrobial resistance in bacteria in human populations. Clin. Infect. Dis. 24(Suppl 1): S131-135.
  9. Simor, A.E., M. Louie, The Canadian Bacterial Surveillance Network, and D.E. Low. 1996. Canadian national survey of prevalence of antimicrobial resistance among clinical isolates of Streptococcus pneumoniae. Antimicrob. Agents Chemother. 40:2190-2193.
  10. Viladrich, P.F., C. Cabellos, R. Pallares, F. Tubau, J. Martinez- Lacasa, J. Linares, and F. Gudiol. 1996. High doses of cefotaxime in treatment of adult meningitis due to Streptococcus pneumoniae with decreased susceptibilities to broad-spectrum cephalosporins. Antimicrob. Agents Chemother. 40:218-220.
  11. Tomasz, A. 1997. Antibiotic resistance in Streptococcus pneumoniae. Clin. Infect. Dis. 24(Suppl 1):S85-88.