Antipneumococcal Activity of DK-507k, a New Quinolone,Compared with the Activities of 10 OtherAgents

Browne, Frederick A.; Bozdoğan, Bülent; Clark, Catherine L.; Kelly, Linda M.; Ednie, Lois M.; Kosowska, Klaudia; Dewasse, Bonifacio; Jacobs, Michael; Appelbaum, Peter C.

doi:10.1128/aac.47.12.3815-3824.2003

Cited by 16 publications

(10 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of two clones selected for resistance to moxifloxacin, one (derived from parent 3406) had an S81Y alteration in GyrA, whereas the other (derived from parent 2749) contained no changes in topoisomerase II or topoisomerase IV. The S81Y substitution, which has been described previously (7,38), was also identified in one of the clones with reduced susceptibility to moxifloxacin selected during serial passage (Table 5).…”

Section: ϫ8supporting

confidence: 62%

“…Four of the five clones contained amino acid substitutions in topoisomerase II (7), and four had mutations in topoisomerase IV (Table 5). Most of the topoisomerase mutations detected in these mutants have been associated previously with reduced susceptibility to fluoroquinolones (7,10,11,34,38), though the GyrB G406V and ParE K458N substitutions have not been reported before.…”

mentioning

confidence: 85%

“…Ten pneumococcal strains (1 penicillin susceptible, 2 penicillin intermediate, and 7 penicillin resistant; 2 macrolide susceptible and 8 macrolide resistant; and 7 fluoroquinolone susceptible and 3 fluoroquinolone resistant) were chosen from the panel of 299 clinical isolates for a multipassage study of emergence of endogenous resistance. Methods were based upon previous publications (7,11,34,41) but with a higher initial inoculum (18). Each initial inoculum was prepared by suspending cells from an overnight Trypticase soy-blood agar plate (BBL) in CAMHB.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Antipneumococcal Activity of Ceftobiprole, a Novel Broad-Spectrum Cephalosporin

Kosowska

Hoellman

Lin

et al. 2005

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

Ceftobiprole (previously known as BAL9141), an anti-methicillin-resistant Staphylococcus aureus cephalosporin, was very highly active against a panel of 299 drug-susceptible and -resistant pneumococci, with MIC 50 and MIC 90 values (g/ml) of 0.016 and 0.016 (penicillin susceptible), 0.06 and 0.5 (penicillin intermediate), and 0.5 and 1.0 (penicillin resistant). Ceftobiprole, imipenem, and ertapenem had lower MICs against all pneumococcal strains than amoxicillin, cefepime, ceftriaxone, cefotaxime, cefuroxime, or cefdinir. Macrolide and penicillin G MICs generally varied in parallel, whereas fluoroquinolone MICs did not correlate with penicillin or macrolide susceptibility or resistance. All strains were susceptible to linezolid, quinupristindalfopristin, daptomycin, vancomycin, and teicoplanin. Time-kill analyses showed that at 1؋ and 2؋ the MIC, ceftobiprole was bactericidal against 10/12 and 11/12 strains, respectively. Levofloxacin, moxifloxacin, vancomycin, and teicoplanin were each bactericidal against 10 to 12 strains at 2؋ the MIC. Azithromycin and clarithromycin were slowly bactericidal, and telithromycin was bactericidal against only 5/12 strains at 2؋ the MIC. Linezolid was mainly bacteriostatic, whereas quinupristin-dalfopristin and daptomycin showed marked killing at early time periods. Prolonged serial passage in the presence of subinhibitory concentrations of ceftobiprole failed to yield mutants with high MICs towards this cephalosporin, and single-passage selection showed very low frequencies of spontaneous mutants with breakthrough MICs towards ceftobiprole.The incidence of pneumococci resistant to penicillin G and other ␤-lactam antibiotics, as well as non-␤-lactam antibiotics, has increased worldwide at an alarming rate. Major foci of infection include South Africa, Spain, and central and eastern Europe (1,21,22,35,48). A survey published in the mid-1990s showed an increase in resistance by pneumococci to penicillin from Ͻ5% before 1989 (including Ͻ0.02% of isolates with MICs of Ն2 g/ml) to 6.6% in 1991 to 1992 (with 1.3% of isolates with MICs of Ն2 g/ml) (5). A more recent survey (23) reported that 50.4% of 1,476 clinically significant pneumococcal isolates were not susceptible to penicillin and that high rates of macrolide-resistant pneumococci occurred in strains with elevated penicillin MICs, for an overall pneumococcal macrolide resistance rate of approximately 33%. Rates of macrolide resistance are even higher in Spain, France, central and eastern Europe, Korea, and Japan (1, 23, 24, 35). Although pneumococcal fluoroquinolone resistance is still uncommon, relatively high rates have been reported in Canada, Hong Kong, Spain, and Croatia (19,29,39,45). Moreover, there is a high rate of isolation of penicillin-intermediate and -resistant pneumococci (approximately 30%) in middle ear fluids from patients with refractory otitis media, compared to rates from other isolation sites (3,15,16). The problem of drug-resistant pneumococci is compounded by the ability of resistant clones to spread rapi...

show abstract

Section: ϫ8supporting

confidence: 62%

mentioning

confidence: 85%

mentioning

confidence: 99%

See 1 more Smart Citation

Antipneumococcal Activity of Ceftobiprole, a Novel Broad-Spectrum Cephalosporin

Kosowska

Hoellman

Lin

et al. 2005

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

show abstract

“…No mutations in L4, L22, or 23S rRNA genes in strain 3548 (Table 4) have been observed in previous studies, which may suggest alteration within the Ϫ10, Ϫ35 putative promoter region of erm(B) (39). Resistance development to moxifloxacin in S. pneumoniae and H. influenzae is likely to be brought about by gene alterations in the quinolone resistance-determining regions encoded by the parC, parE, gyrA, and gyrB, as has been described previously by our group (9,18,35).…”

Section: Discussionsupporting

confidence: 76%

Multistep Resistance Development Studies of Ceftaroline in Gram-Positive and -Negative Bacteria

Clark

McGhee

Appelbaum

et al. 2011

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

Ceftaroline, the active component of the prodrug ceftaroline fosamil, is a novel broad-spectrum cephalosporin with bactericidal activity against Gram-positive and -negative isolates. This study evaluated the potential for ceftaroline and comparator antibiotics to select for clones of Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae, Staphylococcus aureus, and Enterococcus faecalis with elevated MICs. S. pneumoniae and S. pyogenes isolates in the present study were highly susceptible to ceftaroline (MIC range, 0.004 to 0.25 g/ml). No streptococcal strains yielded ceftaroline clones with increased MICs (defined as an increase in MIC of >4-fold) after 50 daily passages. Ceftaroline MICs for H. influenzae and M. catarrhalis were 0.06 to 2 g/ml for four strains and 8 g/ml for a ␤-lactamase-positive, efflux-positive H. influenzae with a mutation in L22. One H. influenzae clone with an increased ceftaroline MIC (quinolone-resistant, ␤-lactamase-positive) was recovered after 20 days. The ceftaroline MIC for this isolate increased 16-fold, from 0.06 to 1 g/ml. MICs for S. aureus ranged from 0.25 to 1 g/ml. No S. aureus isolates tested with ceftaroline had clones with increased MIC (>4-fold) after 50 passages. Two E. faecalis isolates tested had ceftaroline MICs increased from 1 to 8 g/ml after 38 days and from 4 to 32 g/ml after 41 days, respectively. The parental ceftaroline MIC for the one K. pneumoniae extended-spectrum ␤-lactamase-negative isolate tested was 0.5 g/ml and did not change after 50 daily passages.

show abstract

“…18 In the present study, STFX had significantly lower MICs against S. pneumoniae with resistance to LVFX, compared with other quinolones tested, and these findings support previous reports that show the potency of this drug against LVFX-resistant S. pneumoniae with defined multiple mutations within both the gyrase A and topoisomerase IV genes. 19,20 Interestingly, three (#13, #29 and #30) of five strains (#13, #18, #29, #30 and #35) that showed a higher MIC (0.5 mg l À1 ) against LVFX-resistant strains possessed Glu85Lys substitutions in gyrA. This suggests that the primary target of STFX may be gyrA, and Glu85Lys substitution in gyrA reflected the higher MIC for STFX.…”

Section: Discussionmentioning

confidence: 99%

Comparison of drug sensitivity and genotypes of clinically isolated strains of levofloxacin-resistant Streptococcus pneumoniae obtained from Okinawa Island, the Japanese main island and Hong Kong

et al. 2011

View full text Add to dashboard Cite

The prevalence of fluoroquinolone-resistant Streptococcus pneumoniae is increasing worldwide. In the present study, a comparison of drug sensitivity and genotypes of clinically isolated strains of levofloxacin (LVFX)-resistant S. pneumoniae obtained from Hong Kong, Okinawa Island and the Japanese main island (Honshu) was performed. MICs of quinolones (LVFX, tosufloxacin, ciprofloxacin, gatifloxacin and sitafloxacin (STFX)) and other antibiotics (penicillin G, cefcapene, cefditoren, clarithromycin and azithromycin) were determined by a microdilution broth method according to the Clinical and Laboratory Standards Institute Standards. The quinolone-resistance determining regions (QRDRs) of gyrA, gyrB, parC and parE of these strains were analyzed by PCR-based sequencing. All 40 strains tested had more than one amino-acid substitution in the QRDRs of gyrA, gyrB, parC or parE. Although there seemed to be some clonality in strains obtained from Hong Kong, there was no clonality in strains obtained from Okinawa and Japan. Strains obtained from Hong Kong, Okinawa Island and the Japanese main island were genetically different by pulsed-field gel electrophoresis analysis. The range of MIC values of STFX against isolates resistant to LVFX (MIC 4-32 mg l À1 ) was 0.12-0.5 mg l À1 , and MIC 80 values of STFX against LVFX-resistant isolates were 0.25 mg l À1 . This study suggests that LVFX-resistant S. pneumoniae is similar in all three locations and STFX is potent against LVFX-resistant S. pneumoniae with multiple mutations in QRDRs of gyrase A and topoisomerase IV.

show abstract

Antipneumococcal Activity of DK-507k, a New Quinolone,Compared with the Activities of 10 OtherAgents

Cited by 16 publications

References 31 publications

Antipneumococcal Activity of Ceftobiprole, a Novel Broad-Spectrum Cephalosporin

Antipneumococcal Activity of Ceftobiprole, a Novel Broad-Spectrum Cephalosporin

Multistep Resistance Development Studies of Ceftaroline in Gram-Positive and -Negative Bacteria

Comparison of drug sensitivity and genotypes of clinically isolated strains of levofloxacin-resistant Streptococcus pneumoniae obtained from Okinawa Island, the Japanese main island and Hong Kong

Contact Info

Product

Resources

About