Susceptibility of
            <i>Streptococcus pneumoniae</i>
            to Fluoroquinolones in Canada

Patel, Samir N.; McGeer, Allison; Melano, Roberto G.; Tyrrell, Gregory J.; Green, Karen; Pillai, Dylan R.; Low, Donald E.

doi:10.1128/aac.00237-11

Cited by 57 publications

(45 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Likewise, CC156 was maintained in 2012 and was associated with serotype 11A (5 out of 7 isolates). In line with a previous study from Canada (36), this increase in FQ consumption has not led to increased FQ resistance rates. One explanation for this could be the greater efficacy of the new FQs, which may reduce selective pressure in relation to the pneumococcal QRDR mutations involved in FQ resistance (37).…”

Section: Dynamics Of Pneumococcal Serotypes and Genotypessupporting

confidence: 75%

Fluoroquinolone-Resistant Pneumococci: Dynamics of Serotypes and Clones in Spain in 2012 Compared with Those from 2002 and 2006

Domenech

Tirado-Vélez

Fenoll

et al. 2014

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Section: Dynamics Of Pneumococcal Serotypes and Genotypessupporting

confidence: 75%

Fluoroquinolone-Resistant Pneumococci: Dynamics of Serotypes and Clones in Spain in 2012 Compared with Those from 2002 and 2006

Domenech

Tirado-Vélez

Fenoll

et al. 2014

Antimicrob Agents Chemother

View full text Add to dashboard Cite

“…Penicillin, a ␤-lactam antibiotic, has long been the mainstay against pneumococcal infections (2,3), but the worldwide spread of antibiotic-resistant clones over the past decades has impaired its usefulness for dealing with S. pneumoniae infections (4)(5)(6). The rates of resistance against ␤-lactams and macrolides among S. pneumoniae isolates have translated into an increased usage of fluoroquinolone antibiotics in the treatment of respiratory diseases (7)(8)(9)(10).…”

mentioning

confidence: 99%

Genomic Characterization of Ciprofloxacin Resistance in a Laboratory-Derived Mutant and a Clinical Isolate of Streptococcus pneumoniae

Lupien

Billal

Fani

et al. 2013

Antimicrob Agents Chemother

View full text Add to dashboard Cite

The broad-spectrum fluoroquinolone ciprofloxacin is a bactericidal antibiotic targeting DNA topoisomerase IV and DNA gyrase encoded by the parC and gyrA genes. Resistance to ciprofloxacin in Streptococcus pneumoniae mainly occurs through the acquisition of mutations in the quinolone resistance-determining region (QRDR) of the ParC and GyrA targets. A role in low-level ciprofloxacin resistance has also been attributed to efflux systems. To look into ciprofloxacin resistance at a genome-wide scale and to discover additional mutations implicated in resistance, we performed whole-genome sequencing of an S. pneumoniae isolate selected for resistance to ciprofloxacin in vitro (128 g/ml) and of a clinical isolate displaying low-level ciprofloxacin resistance (2 g/ml). Gene disruption and DNA transformation experiments with PCR fragments harboring the mutations identified in the in vitro S. pneumoniae mutant revealed that resistance is mainly due to QRDR mutations in parC and gyrA and to the overexpression of the ABC transporters PatA and PatB. In contrast, no QRDR mutations were identified in the genome of the S. pneumoniae clinical isolate with low-level resistance to ciprofloxacin. Assays performed in the presence of the efflux pump inhibitor reserpine suggested that resistance is likely mediated by efflux. Interestingly, the genome sequence of this clinical isolate also revealed mutations in the coding region of patA and patB that we implicated in resistance. Finally, a mutation in the NAD(P)H-dependent glycerol-3-phosphate dehydrogenase identified in the S. pneumoniae clinical strain was shown to protect against ciprofloxacin-mediated reactive oxygen species. Streptococcus pneumoniae is a major Gram-positive pathogen responsible for pneumonia, bacteremia, otitis media, and meningitis leading to considerable morbidity and mortality among children and elderly individuals (1). Penicillin, a ␤-lactam antibiotic, has long been the mainstay against pneumococcal infections (2, 3), but the worldwide spread of antibiotic-resistant clones over the past decades has impaired its usefulness for dealing with S. pneumoniae infections (4-6). The rates of resistance against ␤-lactams and macrolides among S. pneumoniae isolates have translated into an increased usage of fluoroquinolone antibiotics in the treatment of respiratory diseases (7-10).Fluoroquinolones are part of a class of synthetic broad-spectrum antibiotics that inhibit DNA synthesis in bacteria by targeting DNA gyrase (GyrA and -B subunits) and topoisomerase IV (ParC and -E subunits), two enzymes that are vital for DNA supercoiling and chromosome segregation, respectively (11,12). Although the worldwide prevalence of fluoroquinolone-resistant S. pneumoniae remains low in relation to ␤-lactam resistance (Յ1%) (13-15), the dissemination of successful resistant clones has nonetheless increased the prevalence in some countries (16,17). Resistance to fluoroquinolones in S. pneumoniae arises in a stepwise fashion and results from alterations in the target binding site due to...

show abstract

“…Moxifloxacin and solithromycin may thus offer an advantage over the other molecules within their pharmacological class since both molecules are less prone to select resistance than others in their respective class (31,69). Moreover, moxifloxacin MICs have remained stable over the last 10 years, despite extensive usage (70,71), and preclinical studies show that solithromycin is barely affected by mechanisms conferring resistance to other macrolides (31,72).…”

Section: Discussionmentioning

confidence: 99%

Antibiotic Activity against Naive and Induced Streptococcus pneumoniae Biofilms in an In Vitro Pharmacodynamic Model

Vandevelde

Tulkens

2014

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Biofilms play a role in the pathogenicity of pneumococcal infections. A pharmacodynamic in vitro model of biofilm was developed that allows characterization of the activity of antibiotics against viability and biomass by using in parallel capsulated (ATCC 49619) and noncapsulated (R6) reference strains. Naive biofilms were obtained by incubating fresh planktonic cultures for 2 to 11 days in 96-well polystyrene plates. Induced biofilms were obtained using planktonic bacteria collected from the supernatant of 6-day-old naive biofilms. Biomass production was more rapid and intense in the induced model, but the levels were similar for both strains. Full concentration responses fitting sigmoidal regressions allowed calculation of maximal efficacies and relative potencies of drugs. All antibiotics tested (amoxicillin, clarithromycin, solithromycin, levofloxacin, and moxifloxacin) were more effective against young naive biofilms than against old or induced biofilms, except macrolides/ketolides, which were as effective at reducing viability in 2-day-old naive biofilms and in 11-day-old induced biofilms of R6. Macrolides/ketolides, however, were less potent than fluoroquinolones against R6 (approximately 5-to 20-fold-higher concentrations needed to reduction viability of 20%). However, at concentrations obtainable in epithelial lining fluid, the viabilities of mature or induced biofilms were reduced 15 to 45% (amoxicillin), 17 to 44% (macrolides/ketolides), and 12 to 64% (fluoroquinolones), and biomasses were reduced 5 to 45% (amoxicillin), 5 to 60% (macrolides/ketolides), and 10 to 76% (fluoroquinolones), with solithromycin and moxifloxacin being the most effective and the most potent agents (due to lower MICs) in their respective classes. This study allowed the ranking of antibiotics with respect to their potential effectiveness in biofilm-related infections, underlining the need to search for still more effective options.

show abstract

Susceptibility of Streptococcus pneumoniae to Fluoroquinolones in Canada

Cited by 57 publications

References 28 publications

Fluoroquinolone-Resistant Pneumococci: Dynamics of Serotypes and Clones in Spain in 2012 Compared with Those from 2002 and 2006

Fluoroquinolone-Resistant Pneumococci: Dynamics of Serotypes and Clones in Spain in 2012 Compared with Those from 2002 and 2006

Genomic Characterization of Ciprofloxacin Resistance in a Laboratory-Derived Mutant and a Clinical Isolate of Streptococcus pneumoniae

Antibiotic Activity against Naive and Induced Streptococcus pneumoniae Biofilms in an In Vitro Pharmacodynamic Model

Contact Info

Product

Resources

About