Relative Fitness of Fluoroquinolone-resistant<i>Streptococcus pneumoniae</i>

Johnson, Crystal N.; Briles, David E.; Benjamin, William H.; Hollingshead, Susan K.; Waites, Ken B.

doi:10.3201/eid1106.040840

Cited by 36 publications

(24 citation statements)

References 41 publications

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“…Our model suggests the risk that this benefit would come at the cost of promoting high-level fluoroquinolone resistance; however, the properties of these agents to date seem to minimize such risk. Although resistance to newer fluoroquinolones has been reported (27), high-level resistance remains largely associated with previous treatment, and there has been only limited evidence of clonal spread of fluoroquinolone-resistant pneumococci (10)(11)(12)(13)28). These observations may imply a considerable fitness cost from acquiring incremental mutations associated with high-level fluoroquinolone resistance, a finding recently confirmed in animal models (28).…”

Section: Discussionmentioning

confidence: 57%

“…If the use were kept below a level that limits the population-wide selection of the highly resistant strain (22), then it might be possible to combine a low failure rate for high-risk or the most severe cases (because the new drug is used) with continued suppression of resistance (because the drug is used sparingly). Such a strategy is especially reasonable for a pathogen like S. pneumoniae, for which most antibiotic use is for non-life-threatening conditions (e.g., otitis media), and evidence suggests considerable fitness cost to high-level fluoroquinolone resistance (28). The herd immunity exerted from the pneumococcal conjugate vaccine has provided evidence that young children play a key role in the transmission of pneumococci (46).…”

Section: Discussionmentioning

confidence: 99%

“…Although resistance to newer fluoroquinolones has been reported (27), high-level resistance remains largely associated with previous treatment, and there has been only limited evidence of clonal spread of fluoroquinolone-resistant pneumococci (10)(11)(12)(13)28). These observations may imply a considerable fitness cost from acquiring incremental mutations associated with high-level fluoroquinolone resistance, a finding recently confirmed in animal models (28). If such a fitness cost is present and persists despite possible compensatory evolution, then it might be possible to use the new fluoroquinolones for an extended period of time before high-level resistance becomes a problem.…”

Section: Discussionmentioning

confidence: 99%

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Upgrading antibiotic use within a class: Tradeoff between resistance and treatment success

Wang¹,

Lipsitch

2006

Proc. Natl. Acad. Sci. U.S.A.

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Increasing resistance to antibiotics creates the need for prudent antibiotic use. When resistance to various antibiotics within a class is driven by stepwise accumulation of mutations, a dilemma may exist in regard to replacing an antibiotic that is losing effectiveness due to resistance with a new drug within the same class. Such replacement may enhance treatment success in the short term but promote the spread of highly resistant strains. We used mathematical models to quantify the tradeoff between minimizing treatment failures (by switching early) and minimizing the proliferation of the highly resistant strain (by delaying the switch). Numerical simulations were applied to investigate the cumulative prevalence of the highly resistant strain (Resistance) and the cumulative number of treatment failures (Failure) that resulted from following different antibiotic use policies. Whereas never switching to the new drug always minimizes Resistance and maximizes Failure, immediate switching usually maximizes Resistance and minimizes Failure. Thus, in most circumstances, there is a strict tradeoff in which early use of the new drug enhances treatment effectiveness while hastening the rise of high-level resistance. This tradeoff is most acute when acquired resistance is rare and the highly resistant strain is readily transmissible. However, exceptions occur when use of the new drug frequently leads to acquired resistance and when the highly resistant strain has substantial ''fitness cost''; these circumstances tend to favor an immediate switch. We discuss the implications of these considerations in regard to antibiotic choices for Streptococcus pneumoniae.antibiotic resistance ͉ fluoroquinolones ͉ mathematical models ͉ optimization

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Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Upgrading antibiotic use within a class: Tradeoff between resistance and treatment success

Wang¹,

Lipsitch

2006

Proc. Natl. Acad. Sci. U.S.A.

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“…Moreover, isogenic quinolone resistance may have reduced ability to initiate infections in the absence of fluoroquinolone selection. This suggests that the correct use of antimicrobial drugs may maintain the prevalence of IQR clones at low levels because of the relatively low fitness of these clones (132).…”

Section: Resistance To Fluoroquinolones and Effect On Virulencementioning

confidence: 99%

Antimicrobial Resistance and Virulence: a Successful or Deleterious Association in the Bacterial World?

Beceiro

Tomás²,

Bou³

2013

Clin Microbiol Rev

833

630

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SUMMARY Hosts and bacteria have coevolved over millions of years, during which pathogenic bacteria have modified their virulence mechanisms to adapt to host defense systems. Although the spread of pathogens has been hindered by the discovery and widespread use of antimicrobial agents, antimicrobial resistance has increased globally. The emergence of resistant bacteria has accelerated in recent years, mainly as a result of increased selective pressure. However, although antimicrobial resistance and bacterial virulence have developed on different timescales, they share some common characteristics. This review considers how bacterial virulence and fitness are affected by antibiotic resistance and also how the relationship between virulence and resistance is affected by different genetic mechanisms (e.g., coselection and compensatory mutations) and by the most prevalent global responses. The interplay between these factors and the associated biological costs depend on four main factors: the bacterial species involved, virulence and resistance mechanisms, the ecological niche, and the host. The development of new strategies involving new antimicrobials or nonantimicrobial compounds and of novel diagnostic methods that focus on high-risk clones and rapid tests to detect virulence markers may help to resolve the increasing problem of the association between virulence and resistance, which is becoming more beneficial for pathogenic bacteria.

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“…Although a few reports have related the fitness cost of fluoroquinolone resistance mutations in S. pneumoniae (18,24,39), there are no reports on the fitness cost for recombinant strains. The Cp r pneumococcal recombinant isolates studied by our group have acquired portions of either parE (unpublished results), parC (11), or parE plus parC (3,11,16) from the SMG.…”

mentioning

confidence: 99%

Fitness of Streptococcus pneumoniae Fluoroquinolone-Resistant Strains with Topoisomerase IV Recombinant Genes

Balsalobre

Campa

2008

Antimicrob Agents Chemother

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The low prevalence of ciprofloxacin-resistant (Cp r ) Streptococcus pneumoniae isolates carrying recombinant topoisomerase IV genes could be attributed to a fitness cost imposed by the horizontal transfer, which often implies the acquisition of larger-than-normal parE-parC intergenic regions. A study of the transcription of these genes and of the fitness cost for 24 isogenic Cp r strains was performed. Six first-level transformants were obtained either with PCR products containing the parC quinolone resistance-determining regions (QRDRs) of S. pneumoniae Cp r mutants with point mutations or with a PCR product that includes parE-QRDR-ant-parC-QRDR from a Cp r Streptococcus mitis isolate. The latter yielded two strains, T6 and T11, carrying parC-QRDR and parE-QRDR-ant-parC-QRDR, respectively. These first-level transformants were used as recipients in further transformations with the gyrA-QRDR PCR products to obtain 18 second-level transformants. In addition, strain Tr7 (which contains the GyrA E85K change) was used. Reverse transcription-PCR experiments showed that parE and parC were cotranscribed in R6, T6, and T11; and a single promoter located upstream of parE was identified in R6 by primer extension. The fitness of the transformants was estimated by pairwise competition with R6 in both one-cycle and two-cycle experiments. In the one-cycle experiments, most strains carrying the GyrA E85K change showed a fitness cost; the exception was recombinant T14. In the two-cycle experiments, a fitness cost was observed in most first-level transformants carrying the ParC changes S79F, S79Y, and D83Y and the GyrA E85K change; the exceptions were recombinants T6 and T11. The results suggest that there is no impediment due to a fitness cost for the spread of recombinant Cp r S. pneumoniae isolates, since some recombinants (T6, T11, and T14) exhibited an ability to compensate for the cost.

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Relative Fitness of Fluoroquinolone-resistantStreptococcus pneumoniae

Cited by 36 publications

References 41 publications

Upgrading antibiotic use within a class: Tradeoff between resistance and treatment success

Upgrading antibiotic use within a class: Tradeoff between resistance and treatment success

Antimicrobial Resistance and Virulence: a Successful or Deleterious Association in the Bacterial World?

Fitness of Streptococcus pneumoniae Fluoroquinolone-Resistant Strains with Topoisomerase IV Recombinant Genes

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