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Activity of Newer Fluoroquinolones (FQ) Against Isolates of Streptococcus pneumoniae (SPN) with Increasing Resistance to Ciprofloxacin

D. Bast, J. C. S. de Azavedo, C. DUNCAN, S. Pong-Porter, L. Trpeski, R. Davidson, L. Mandell, and D. E. Low Mount Sinai and Princess Margaret Hospitals, University of Toronto, Toronto, ON., McMaster University, Hamilton ON. and Queen Elizabeth II Health Sciences Centre, Dalhousie University, Halifax, N.S.

Background: Several FQ’s have been designed for greater activity against gram-positive bacteria. We evaluated the activity of these against SPN with reduced susceptibility to ciprofloxacin(CIP).

Methods: Twenty isolates with CIP MIC’s of ³ 16mg/L, collected from across Canada between 1994-1997 were evaluated. Susceptibilities to levofloxacin (LEV), trovafloxacin (TRO), moxifloxacin (MOX), grepafloxacin (GRE), gatifloxacin (GAT), sparfloxacin (SPA), and gemifloxacin (GEM) were determined by broth microdilution according to NCCLS guidelines. Mutations in Topoisomerase IV (parC/E) and DNA gyrase (gyrA/B) were confirmed by amplification and sequencing of the QRDR region of each gene. All isolates were serotyped and analyzed by PFGE. Inhibition of CIP MIC in the presence of reserpine was performed by agar dilution for evidence of efflux.

Results: Strains were of different serotypes and various PFGE patterns demonstrating lack of clonality. With the exception of GEM, strains with high MIC’s to CIP also showed varying degrees of decreased susceptibility to the other FQ’s :

CIP MIC

No.of isolates

MIC Range (mg/L) of :

SPA

LEV

TRO

GRE

GAT

MOX

GEM

64

6

16-64

16-32

8-16

8-16

4-8

4-8

0.25-1

32

4

8

16

4-8

4-8

4

2-4

0.12-0.25

16

10

1*-8

4*-16

0.05*-4

1*-8

1*-4

0.25*-4

0.12-0.25

*Low MIC value only shown by a single strain.

The strain showing susceptibility to low MIC’s of the newer FQ’s was the only one with no AA substitutions in the QRDR region of GyrA. The CIP MIC in this strain decreased in the presence of reserpine. All other strains had substitutions in both ParC and GyrA and all but 4 had a substitution in GyrB.

Conclusion: Topoisomerase mutations resulting in reduced susceptibility to CIP are likely to contribute to decreased susceptibility to several of the newer generation FQ’s.

Presented at:

39th INTERSCIENCE CONFERENCE ON ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (ICAAC), San Francisco, CA., Sept. 26-29, 1999.



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