Resistance to Levofloxacin and Failure of Treatment of Pneumococcal Pneumonia

Davidson, Ross; Cavalcanti, Rodrigo B.; Brunton, James; Bast, Darrin J.; Azavedo, Joyce C. S. de; Kibsey, Pamela; Fleming, Christine; Low, Donald E.

doi:10.1056/nejmoa012122

Cited by 482 publications

(268 citation statements)

References 21 publications

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“…53 Failures in the treatment of pneumococcal pneumonia have been reported with levofloxacin at 500 mg daily as a result of the emergence of resistance while receiving therapy or resistance from previous exposures to fluoroquinolones. 54 An increased dose of levofloxacin (750 mg daily, given for 5 days) is currently approved by the FDA for adults with pneumonia. The increase in drug exposure at the higher dose is recognized to overcome the most common mechanism for the development of fluoroquinolone resistance.…”

Section: Acute Bacterial Otitis Mediamentioning

confidence: 99%

The Use of Systemic and Topical Fluoroquinolones

Jackson¹,

Schutze²

2016

Pediatrics

142

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Appropriate prescribing practices for fluoroquinolones, as well as all antimicrobial agents, are essential as evolving resistance patterns are considered, additional treatment indications are identified, and the toxicity profile of fluoroquinolones in children has become better defined. Earlier recommendations for systemic therapy remain; expanded uses of fluoroquinolones for the treatment of certain infections are outlined in this report. Prescribing clinicians should be aware of specific adverse reactions associated with fluoroquinolones, and their use in children should continue to be limited to the treatment of infections for which no safe and effective alternative exists or in situations in which oral fluoroquinolone treatment represents a reasonable alternative to parenteral antimicrobial therapy.

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Section: Acute Bacterial Otitis Mediamentioning

confidence: 99%

The Use of Systemic and Topical Fluoroquinolones

Jackson¹,

Schutze²

2016

Pediatrics

142

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“…From the perspective of most patients, using the selection window to guide dosing constitutes a form of altruism: an individual accepts an increased risk of adverse toxic effects in exchange for slower acquisition of drug resistance within the community. However, as drug-resistant mutant subpopulations grow, the selection window will become increasingly important for all patients, because drug-resistance can be acquired during therapy [7][8][9]. Herein, we review recent tests and refinements of the window hypothesis.…”

mentioning

confidence: 99%

Mutant Selection Window Hypothesis Updated

Drlica¹,

Zhao²

2007

Clinical Infectious Diseases

349

338

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The mutant selection window hypothesis postulates that, for each antimicrobial-pathogen combination, an antimicrobial concentration range exists in which selective amplification of single-step, drug-resistant mutants occurs. This hypothesis suggests an antimutant dosing strategy that is keyed to the upper boundary of the selection window: the mutant prevention concentration. Correlations are described between the mutant prevention concentration-a static parameter that is measured with agar plates-and fluctuating drug concentrations that restrict mutant amplification in vitro and in animals. When drug resistance is acquired stepwise, the mutant selection window increases, making the suppression of each successive mutant increasingly more difficult. For agents that kill drug-resistant mutants in a drug concentration-dependent manner, the use of the area under the 24-h time-drug concentration curve value divided by the value of the mutant prevention concentration is suggested as an index for designing antimutant dosing regimens. The need for such regimens is emphasized by a clinical example in which acquisition of drug resistance occurs concurrently with eradication of susceptible bacterial cells. These data support using the mutant selection window to optimize antimicrobial dosing regimens.Antimicrobial resistance is a complex problem that is likely to require attention at many levels [1]. Issues concerning dosing are addressed by the mutant selection window hypothesis [2,3]. This hypothesis maintains that drug-resistant mutant subpopulations present prior to initiation of antimicrobial treatment are enriched and amplified during therapy when antimicrobial concentrations fall within a specific range (the mutant selection window). The upper boundary of the mutant selection window is the MIC of the least drugsusceptible mutant subpopulation, a value called the mutant prevention concentration (MPC) [4]. The lower boundary of the mutant selection window is the lowest concentration that exerts selective pressure, often approximated by the minimal concentration that inhibits colony formation by 99% (MIC 99 ). Two principles emerge from the hypothesis. First, traditional dos-

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“…In quinolones, resistant organisms emerge only due to one or more point mutations in the quinolone binding region of the target enzyme or to a change in the permeability of the organism, (28), this limited the resistance only in streptococcus pneumonia, which is not related to oral conditions (30) .…”

Section: Resistancementioning

confidence: 99%

Amoxicillin vs Levofloxacin in Treatment of Chronic Periodontitis: Review

Ali¹,

Zeiny²

2016

Iraqi dent. j.

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Background: Antibiotics Resistance can be the main problem faced by the specialists in the medical fields. The main reason of such resistance is the improper prescribing of antibiotics. In dentistry this problem must be in concern for 2 reasons, first, limited and outdated knowledge of many dentist in Iraq with recent modalities in the field of therapeutics, so they keep prescribing penicillins, for every odontogenic infection (rationale prescribing), second, the patient who keeps prescribing the same drug for himself every time (i.e. dealing with antibiotic as over-the-counter drug). Aim of the study: This review will clarifies the use of amoxicillin (most prescribed drug in Iraqi dental clinics) vs the use of third generation quinolones (levofloxacin) in an important field of dental practice which is periodontology, with focusing on levofloxacin as it took a privileged position in medical researches. Conclusion: levofloxacin was superior to amoxicillin since it is applied once daily, few nonhazardous side effects, nearly 100 % bioavailability in spite of different rout of administration, and can be applied topically as gels and intra-pocket films. Perhaps this can change a lot among practitioners' and non-practitioners' prescribing (habits).

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Resistance to Levofloxacin and Failure of Treatment of Pneumococcal Pneumonia

Cited by 482 publications

References 21 publications

The Use of Systemic and Topical Fluoroquinolones

The Use of Systemic and Topical Fluoroquinolones

Mutant Selection Window Hypothesis Updated

Amoxicillin vs Levofloxacin in Treatment of Chronic Periodontitis: Review

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