In-vitro activities of 11 antibiotics against 75 strains of Streptococcus pneumoniae with reduced susceptibilities to penicillin isolated from patients in Washington State

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; 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. 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 (1995–1996). 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 5 0.06 mg/L), 52 exhibited intermediate susceptibility (MICs 5 0.1–1 mg/L) and nine were resistant (MICs > 2 mg/L). 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. The medium used was Mueller– Hinton agar (Difco, Detroit, MI, USA) supplemented with 5% sheep blood, and inocula of 10 cfu were delivered to the surfaces of the plates with a Steers replicator. S. pneu moniae 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 penicillinsusceptible 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 (51.9–86.5%), 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 (44.4–100% 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. We also determined the MICs of the two macrolides and clindamycin for the study isolates following induction, i.e. after incubation of the strains in the presence of erythromycin at a concentration of 0.5 mg/L, and compared them with those determined without induction. The MICs of all three antibiotics for six of the strains (one penicillinsusceptible and five exhibiting intermediate susceptibility) increased by at least two two-fold dilutions following exposure to erythromycin. These six isolates harboured the ermB gene, which encodes methylation of 23S rRNA, were resistant to both the macrolides and clindamycin, and exhibited inducible resistance. The remaining 22 erythromycinresistant isolates were not phenotypically inducible, exhib-