Phenotypic and genotypic analysis of levofloxacin-resistant clinical isolates of Streptococcus pneumoniae collected in 13 countries during 1999–2000

Critchley, Ian A.; Blosser-Middleton, Renée S.; Jones, Mark; Karlowsky, James A.; Karginova, Elena; Thornsberry, Clyde; Sahm, Daniel F.

doi:10.1016/s0924-8579(02)00125-5

Cited by 22 publications

(22 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Therefore, the rate of LVFX Recently, Hong Kong investigators demonstrated high rates of resistance of S. pneumoniae isolates to various fluoroquinolones and the presence of the Spanish 23F clone that had acquired fluoroquinolone resistance while circulating in Hong Kong. [14][15][16] Our data confirmed a prevalence of similar strains of LVFX-resistant S. pneumoniae in Hong Kong. Although the overall rate of strains resistant to fluoroquinolones remains low in most Asian countries, the emergence of highly resistant strains to fluoroquinolones will likely be a concern in the future with regard to the treatment of pneumococcal pneumonia.…”

Section: Discussionsupporting

confidence: 81%

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

Section: Discussionsupporting

confidence: 81%

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

show abstract

“…However, in the absence of competition with EF3030, Phe/Phe was only inferior in nasopharyngeal colonization but was as able as EF3030 to produce lung infection. Conversely, the Phe/Tyr mutant, which contains the GyrA: Ser81Phe and ParC: Ser79Tyr mutation combination found more often in laboratory-selected mutants than in clinical QRSP (18,24,(28)(29)(30), was inferior in vitro and in nasopharyngeal colonization but was as able as EF3030 to produce lung infection, regardless of competition from EF3030. Though counterintuitive, this probably occurred because of the nature of the lung infection model, in which bacteria are intranasally instilled into anesthetized mice without the prerequisite for nasopharyngeal colonization.…”

Section: Discussionmentioning

confidence: 97%

“…We postulated that QRSP may have reduced fitness because fluoroquinolone resistance rates remain very low, and naturally occurring QRSP isolates are generally clonally unrelated. When in competition with EF3030, the Phe/Phe mutant, which contains the GyrA: Ser81Phe and ParC: Ser79Phe mutation combination often found in clinical QRSP (11,18,24,(28)(29)(30), was inferior in all 3 models tested. However, in the absence of competition with EF3030, Phe/Phe was only inferior in nasopharyngeal colonization but was as able as EF3030 to produce lung infection.…”

Section: Discussionmentioning

confidence: 97%

Relative Fitness of Fluoroquinolone-resistantStreptococcus pneumoniae

Johnson

Briles

Benjamin

et al. 2005

Emerg. Infect. Dis.

View full text Add to dashboard Cite

Fluoroquinolone resistance in Streptococcus pneumoniae is primarily mediated by point mutations in the quinolone resistance–determining regions of gyrA and parC . Antimicrobial resistance mutations in housekeeping genes often decrease fitness of microorganisms. To investigate the fitness of quinolone-resistant S. pneumoniae (QRSP), the relative growth efficiencies of 2 isogenic QRSP double mutants were compared with that of their fluoroquinolone-susceptible parent, EF3030, by using murine nasopharyngeal colonization and pneumonia models. Strains containing the GyrA: Ser81Phe, ParC: Ser79Phe double mutations, which are frequently seen in clinical QRSP, competed poorly with EF3030 in competitive colonization or competitive lung infections. However, they efficiently produced lung infection even in the absence of EF3030. The strain containing the GyrA: Ser81Phe, ParC: Ser79Tyr double mutations, which is seen more frequently in laboratory-derived QRSP than in clinical QRSP, demonstrated reduced nasal colonization in competitive or noncompetitive lung infections. However, the strain was equally able to cause competitive or noncompetitive lung infections as well as EF3030.

show abstract

“…Fluoroquinolone resistance among S pneumoniae is appearing in some areas of the world, notably Hong Kong 16 and Spain 17 and, to a lesser extent, North America. 18 Some evidence shows that bacterial resistance may lead to treatment failure.…”

Section: Microbiologic Considerationsmentioning

confidence: 99%

Efficacy and safety of levofloxacin in the context of other contemporary fluoroquinolones: a review

Ball

2003

Current Therapeutic Research

View full text Add to dashboard Cite

Background: In recent years, fluoroquinolone research has focused on achieving several goals, including (1) enhanced potency against gram-positive cocci, notably Streptococcus pneumoniae, and anaerobes, while (2) maintaining potency against gram-negative pathogens, (3) optimizing pharmacokinetics and pharmacodynamics (PK/PD), and (4) minimizing potential adverse drug reactions through recognition and avoidance of structural configurations that have characterized earlier, reactive compounds.Objective: This review examines the efficacy and safety of fluoroquinolones and the specific clinical evidence regarding levofloxacin.Methods: Using published literature collected over time by the author, a review was conducted, focusing on the efficacy and safety profile of levofloxacin and other fluoroquinolones.Results: The newer fluoroquinolones have fulfilled many of the research goals described above. Levofloxacin has improved anti-gram-positive potency, PK/PD properties, a proven clinical trial record (particularly for communityacquired pneumonia [CAP]), and an excellent safety profile-in the context of the treatment of Ͼ250 million patients worldwide in the past decade. It is licensed for management of drug-resistant S pneumoniae infections in the United States and has gained widespread formulary acceptance and guideline inclusion. Studies assessing levofloxacin for CAP therapy show significant advantages over standard therapy, such as trends toward reduced IV therapy and length of hospitalization, reduced mortality, and significant associated cost reduction. In addition, levofloxacin has proved highly effective in acute exacerbations of

show abstract

Phenotypic and genotypic analysis of levofloxacin-resistant clinical isolates of Streptococcus pneumoniae collected in 13 countries during 1999–2000

Cited by 22 publications

References 32 publications

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

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

Relative Fitness of Fluoroquinolone-resistantStreptococcus pneumoniae

Efficacy and safety of levofloxacin in the context of other contemporary fluoroquinolones: a review

Contact Info

Product

Resources

About