The emergence of resistance to levofloxacin before clinical use in a university hospital in Singapore

G. Kumarasinghea,*, C. Chowa and P. A. Tambyahb

a Department of Laboratory Medicine and b Department of Medicine, National University Hospital, 5 Lower Kent Ridge Road, Singapore 119074

Sir,

Penicillin resistance in Streptococcus pneumoniae is a serious problem among hospitalized patients in the Asia– Pacific region.1 Levofloxacin, a broad-spectrum fluoroquinolone with both intravenous and oral preparations,2 was recently approved by the US Food and Drug Administration with the specific indication for community-acquired pneumonia caused by penicillin-resistant pneumococci. Levofloxacin has not been introduced to the National University Hospital formulary so far. However, ciprofloxacin and other fluoroquinolones have been in use for the past decade.

We studied 33 consecutive clinical isolates of S. pneumoniae from January to March 2000. MICs of levofloxacin were determined using the Etest method, a technique that has been validated to be accurate for susceptibility testing of S. pneumoniae.3 NCCLS criteria were used for interpretation of antibiotic susceptibility tests. ATCC strain 29213 was used as a quality control.

MIC50 and MIC90 for penicillin were 0.23 and 3.8 mg/L respectively, compared with 0.75 and 1.00 mg/L for levofloxacin. The list of MIC values, percentage susceptible and resistant are shown in Table IGo for penicillin and in Table IIGo for levofloxacin.


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Table I. Penicillin susceptibility pattern

 

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Table II. Levofloxacin susceptibility pattern

 
Although levofloxacin had activity against all the penicillin-resistant strains of S. pneumoniae, the presence of a high level of resistance in one penicillin-susceptible strain is a cause for concern. The emergence of resistance to levofloxacin before its clinical use in the community could be the result of cross-resistance to other quinolones,4 or due to acquisition of resistance due to agricultural use of quinolones.5 In another study conducted in this part of the world an increase in levofloxacin resistance to 5.5% in 3 years has been described.6 In contrast to our observation, resistance to levofloxacin has been found only in penicillin-resistant isolates.6

This study suggests that while levofloxacin might be a useful agent in the initial therapy of suspected community-acquired penicillin-resistant pneumonia, there has to be a high level of vigilance to the emergence of levofloxacin resistance even in communities where this drug is not clinically available.

Notes

J Antimicrob Chemother 2000; 46: 862–863

* Corresponding author. Back

References

1 . Song, J. H., Lee, N. Y., Ichiyama, S., Yoshida, R., Hirakata, Y., Fu, W. et al. (1999). Spread of drug-resistant Streptococcus pneumoniae in Asian countries: Asian network for surveillance of resistant pathogens (ANSORP) study. Clinical Infectious Diseases 28, 1206–11.[ISI][Medline]

2 . Wimer, S. M., Schoonover, L. & Garrison, M. W. (1998). Levofloxacin: a therapeutic review. Clinical Therapy 20, 1049–70.

3 . Rowe, A. K., Schwartz, B., Wasas, A. & Klugman, K. P. (2000). Evaluation of the Etest as a means of determining the antibiotic susceptibilities of isolates of Streptococcus pneumoniae and Haemophilus influenzae from children in the Central African Republic. Journal of Antimicrobial Chemotherapy 45, 132–3.[Free Full Text]

4 . Barry, A. L. & Fuchs, P. C. (1991). Cross-resistance and cross-susceptibility between fluoroquinolone agents. European Journal of Clinical Microbiology and Infectious Diseases 10, 1013–8.[ISI][Medline]

5 . Smith, K. E., Besser, J. M., Hedberg, C. W., Leano, F. T., Bender, J. B., Wicklund, J. H. et al. (1999). Quinolone-resistant Campylobacter jejuni infections in Minnesota, 1992–1998. New England Journal of Medicine 340, 1525–32.[Abstract/Free Full Text]

6 . Ho, P. L., Que, T. L., Tsang, D. N., Ng, T. K., Chow, K. H. & Seto, W. H. (1999). Emergence of fluoroquinolone resistance among multiply resistant strains of Streptococcus pneumoniae in Hong Kong. Antimicrobial Agents and Chemotherapy 43, 1310–13.[Abstract/Free Full Text]