Department of Pathobiology, Box 357238, School of Public Health and Community Medicine, University of Washington, Seattle, WA 98195-7238, USA
Sir,
The incidence of multidrug resistance (i.e. resistance to two or more antibiotic classes) amongst clinical isolates of Streptococcus pneumoniae has increased markedly over the last 10 years;1 most of these strains belong to one of five serogroups (6, 9, 14, 19 and 23). This situation has prompted a search for alternative antibiotics, especially for the treatment of patients with invasive pneumococcal diseases.2 The present study was undertaken to evaluate the in-vitro activities of some of the newer agents against isolates of S. pneumoniae recovered from patients in Washington State.
The organisms studied included 62 non-replicate pneumococci isolated from patients with
sterile site infections during a Washington State Surveillance Study (19951996). Of
these strains, 12 belonged to serogroup 6, 13 to serogroup 9, nine to serogroup 14, 17 to
serogroup 19 and eight to serogroup 23; three were non-typeable. Additional non-replicate strains
(three of which belonged to serogroup 19 and nine of which were non-typeable) were recovered
in the course of a Paediatric Carriage Study (1996), and one further strain (serogroup 19F) was
isolated from a patient in 1997. The 75 isolates were selected because the MICs of penicillin for
them were 0.06 mg/L; 14 were categorized as susceptible (MICs = 0.06 mg/L), 52
exhibited intermediate susceptibility (MICs = 0.11 mg/L) and nine were resistant
(MICs
2 mg/L).3 The antibiotics tested were as
follows: clindamycin, erythromycin and penicillin (Sigma Chemical Co., St Louis, MO, USA),
ciprofloxacin and sparfloxacin (Bayer, Lansing, IL, USA), cefprozil (Bristol-Myers Squibb,
Princeton, NJ, USA), grepafloxacin (GlaxoWellcome Co., Triangle Park, NC, USA),
levofloxacin and the novel ketolide, HMR 3647 (Hoechst Marion Roussel, France), the
oxazolidinone, linezolid (Pharmacia and Upjohn, Kalamazoo, MI, USA), and trovafloxacin and
azithromycin (Pfizer, Groton, CT, USA). MICs were determined by an agar dilution method
recommended by the National Committee for Clinical Laboratory Standards.3 The medium used was MuellerHinton agar (Difco, Detroit, MI,
USA) supplemented with 5% sheep blood, and inocula of 104 cfu were delivered to
the surfaces of the plates with a Steers replicator. S. pneumoniae ATCC 6305 and
ATCC 40619 were included as controls.
The in-vitro activities of the 11 antibiotics against the 75 isolates are shown in the Table. Most of the penicillin-susceptible isolates were susceptible to all
of the antibiotics tested, the exception being ciprofloxacin to which all but one strain were
resistant. Of the 52 isolates exhibiting intermediate susceptibility to penicillin, at least 51 were
susceptible to each of the newer fluoroquinolones and linezolid. The susceptibilities of these
strains to azithromycin, erythromycin and clindamycin were variable (51.986.5%), and
only 7.7% and 3.8% were susceptible to cefprozil and ciprofloxacin, respectively. The
susceptibility patterns of the penicillin-resistant isolates were broadly similar to those of the
strains with intermediate susceptibilities, with the novel fluoroquinolones and linezolid being
highly active, the macrolides and clindamycin having variable activities (44.4100% of
isolates being susceptible) and all of the isolates being resistant to cefprozil and ciprofloxacin. As
neither validated nor tentative MIC breakpoints for HMR 3647 were available at the time the
study was undertaken, susceptibility categories could not be assigned. However, the MICs of this
drug are very low (0.03 mg/L) and it is likely that all of the isolates tested, irrespective of
their penicillin susceptibilities, would be regarded as susceptible.
|
This is the first study to compare the in-vitro activities of grepafloxacin, levofloxacin, trovafloxacin, linezolid and HMR 3647 against clinical isolates of S. pneumoniae with reduced susceptibilities to penicillin which were recovered in the USA, although the MICs of the quinolones are similar to those reported previously.4,5 Other investigators have shown clindamycin to be highly active against pneumococci, but they did not characterize the erythromycin resistance genes carried by the strains.6 Our results suggest that the newer fluoroquinolones, linezolid and HMR 3647 would provide appropriate empirical therapy of patients with invasive pneumococcal infections, irrespective of their susceptibilities to penicillin.
Notes
* Corresponding author. Fax: +1-206-543-3873; E-mail: marilynr{at}u.washington.edu
References
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3 . National Committe for Clinical Laboratory Standards. (1998). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow AerobicallyThird Edition: Approved Standard M8-A4. NCCLS, Villanova, PA.
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