ARCHIVED - The rise of penicillin-susceptible Streptococcus pneumoniae - Providence Health Care, Vancouver, British Columbia, 1998-2003

Introduction

Since its emergence nearly 40 years ago, Streptococcus pneumoniae resistant to penicillin has emerged as a worldwide phenomenon; indeed, it is likely that no other mode of resistance has been so well documented from an epidemiologic and microbiologic point of view(1,2,3). In Canada, there has been an alarming increase in the reported prevalence of penicillin non-susceptible isolates (intermediate plus high-level resistance) over the past decade(4,5). This report summarizes 6 years of S. pneumoniae, penicillin susceptibility surveillance at a large secondary, tertiary, and quaternary-care health care centre in Western Canada.

Methods

Laboratory-based surveillance for S. pneumoniae susceptibility to penicillin was performed for the period 1 January 1998 to 31 December 2003. All S. pneumoniae isolates recovered from clinical specimens that were formally reported by the microbiology laboratory to the ordering physician were included in the database. The specimens originated from one large, academic referral centre (St. Paul's Hospital), two community-based hospitals (Mount St. Joseph's Hospital and St. Vincent's Hospital), as well as a number of community care outpatient clinics and residential care facilities. All isolates with finalized reports were included in the analysis, regardless of specimen site.

Alpha-haemolytic colonies suspicious for S. pneumoniae were subcultured on 5% sheep agar plates and incubated for 18-24 h at 35° C in 5-10% CO₂. Organisms were identified using a number of techniques, including Gram's stain, colonial morphology and growth characteristics, susceptibility to optochin, and Phadebact® Pneumococcus coagglutination test. Supplementary testing for bile solubility was performed when necessary.

Resistance to penicillin was screened using a 1 µg oxacillin disk and all isolates with inhibition zones of >= 20 mm were considered susceptible according to the recommendations of the NCCLS (previously known as the National Committee for Clinical Laboratory Standards)⁽⁶⁾. The minimum inhibitory concentration (MIC) for penicillin-susceptible S. pneumoniae was defined as 0.06 mg/L⁽⁶⁾.

Annual cumulative susceptibility data for S. pneumoniae and penicillin were extracted from the microbiology laboratory's computerized information system. A chi-squared test for trend was calculated for statistical significance using Epi-Info 6 (edition 6.04d, CDC, Atlanta and WHO, Geneva).

Results

A total of 1218 S. pneumoniae isolates were recovered over the 6-year surveillance period. Of these, 793 (65%) originated from St. Paul's Hospital. Table 1 shows the cumulative susceptibility data for S. pneumoniae and the number of annual isolates identified and tested according to year. From 1998 to 2003, the proportion of S. pneumoniae isolates susceptible to penicillin rose steadily from 77% in 1998 to 88% in 2003 (p = 0.001).

Table 1. Cumulative penicillin susceptibility data for Streptococcus pneumoniae isolates, Providence Health Care, 1998-2003 (n = 1218)

Figure 1 shows the breakdown of isolates according to specimen type. Of the total number of isolates, the majority were recovered from sputum, 664 (54.5%). Invasive isolates originating from sterile sites (blood, cerebrospinal fluid, and joint fluid) accounted for 252 (20.7%) of the total. Miscellaneous specimens from which S. pneumoniae was recovered included eye, ear, wound, and urine specimens.

Figure 1. Streptococcus pneumoniae isolates according to specimen type, Providence Health Care, 1998-2003 (n = 1218)

Discussion

S. pneumoniae with reduced susceptibility to penicillin is a major concern to clinicians and public health officials across Canada and around the world. Although the prevalence of S. pneumoniae with reduced susceptibility to penicillin varies greatly depending on geography, reports of disturbingly high rates of penicillin resistance have been widely publicized and, in turn, have influenced national treatment guidelines on community-acquired pneumonia, as well as other manifestations of pneumococcal disease^(7,8). Physicians treating patients with infections presumed to be due to S. pneumoniae are under increasing pressure to prescribe broad-spectrum antibiotics such as newer-generation fluoroquinolones and vancomycin.

In contrast to findings from multi-centre and national surveillance programs in Canada and abroad(4,9), this report describes increasing susceptibility of S. pneumoniae to penicillin at a large health care centre in Vancouver for the period 1998 to 2003. This a apparent reversal in the trend of increasing pneumococcal resistance has important clinical implications. First, clinicians caring for patients with S. pneumoniae infections need to pay close attention to local antimicrobial resistance patterns when making decisions for empirical treatment. National treatment guidelines play an important role in steering physicians towards appropriate treatment options; however, these guidelines tend to be based on national surveillance data and may be of less use when resistance rates vary greatly from region to region. Following guidelines from other countries is even less desirable as these recommendations are inevitably based on surveillance data which have been collected even further afield.

Second, use of very broad-spectrum "respiratory" fluoroquinolones as first-line antibiotics for community-acquired pneumonia in areas where penicillin resistance is uncommon may be unnecessary and even excessive⁽⁷⁾. It may be more prudent to reserve these agents for patients who are infected with an organism known to exhibit frank resistance to penicillin.

Third, with the introduction and increasing use of heptavalent pneumococcal conjugate vaccination, a potential reduction in the carriage and circulation of penicillin-non-susceptible S. pneumoniae in immunized children and their contacts is expected⁽¹⁰⁾. The data from this report, however, precede the widespread implementation of conjugate vaccine in British Columbia implying that other factors may be responsible for the phenomenon of increasing susceptibility.

Conclusions

Although the rise of penicillin-resistant S. pneumoniae has been well documented in the medical literature, laboratory-based surveillance from Providence Health Care reveals a trend of increasing susceptibility to penicillin for the period 1998 to 2003. MIC testing was not performed routinely on all S. pneumoniae isolates and therefore, exact rates of intermediate and high-level resistance could not be included in the analysis. Nevertheless, this report underscores the importance of reviewing local susceptibility data when making empiric treatment decisions. Physicians should reconsider routinely prescribing "respiratory" fluoroquinolones to patients with uncomplicated pneumococcal infections as first-line drugs when standard penicillins may suffice.

Acknowledgements

The author would like to thank Catherine Haynes for her help in extracting the data. Kate Cummings assisted with the statistical calculations. I would also like to acknowledge the work of laboratory staff in the Division of Medical Microbiology, Providence Health Care.

References

1. Low DE. The era of antimicrobial resistance - implications for the clinical laboratory. Clin Microbiol Infect 2002;8:9-20.

2. Goldstein FW, Garau J. 30 years of penicillin-resistant S. pneumoniae: myth or reality? Lancet 1997;350:233-4.

3. Forward KR. The epidemiology of penicillin resistance in Streptococcus pneumoniae. Semin Respir Infect 1999;14:243-54.

4. Zhanel GG, Palatnick L, Nichol K et al. Antimicrobial resistance in respiratory tract Streptococcus pneumoniae isolates: results of the Canadian Respiratory Organism Susceptibility Study, 1997 to 2002. Antimicrob Agents Chemother 2003;47:1867-74.

5. Greenberg D, Speert DP, Mahenthiralingam E et al. Emergence of penicillin-nonsusceptible Streptococcus pneumoniae invasive clones in Canada. J Clin Microbiol 2002;40:68-74.

6. NCCLS. Performance standards for antimicrobial susceptibility testing; fourteenth informational supplement, NCCLS document M100-S14. 2004, Wayne, Pennsylvania.

7. Mandell LA, Marrie TJ, Grossman RF et al. Canadian guidelines for the initial management of community-acquired pneumonia: an evidence-based update by the Canadian Infectious Diseases Society and the Canadian Thoracic Society. Clin Infect Dis 2000;31:383-421.

8. Mandell LA, Bartlett JG, Dowell SF et al. Update of practice guidelines for the management of community-acquired pneumonia in immunocompetent adults. Clin Infect Dis 2003;37:1405-33.

9. Feldman C. Clinical relevance of antimicrobial resistance in the management of pneumococcal community-acquired pneumonia. J Lab Clin Med 2004;143:269-83.

10. Klugman KP. Efficacy of pneumococcal conjugate vaccines and their effect on carriage and antimicrobial resistance. Lancet Infect Dis 2001;1:85-91.

Source: M Romney, MD, FRCPC, DTM&H, Providence Health Care, Vancouver, BC.