Clinical Implications

As the prevalence of fluoroquinolone resistance increases, clinical failures during empiric treatment are being reported. Various accounts have begun to emerge of levofloxacin failure during treatment of pneumococcal pneumonia.[6,11] Three of the depicted patients had a history of recent fluoroquinolone treatment.[6,11] The S. pneumoniae responsible for this fluoroquinolone failure was subsequently found to have QRDR substitutions in both ParC (Ser79Phe) and GyrA (Ser81Phe/Tyr, Glu85Lys).[6,11] These reports suggest that recent (within the last 3 months) fluoroquinolone therapy must be considered during treatment decisions.[6,11] Two other patients were described who had no history of fluoroqui-nolone therapy.[11] For one patient, the initial isolate had no detected substitutions in ParC or GyrA; however, following therapy, the resulting isolate had mutations in both ParC (Ser79Phe) and GyrA (Ser81Phe).[11] The other patient's initial isolate was considered susceptible but was found to have a Ser79Phe substitution in ParC.[11] After levofloxacin therapy, the isolate had mutations in both ParC (Ser79Phe) and GyrA (Ser81Phe).

The increasing use of fluoroquinolones as empiric therapy of community-acquired respiratory infections likely caused by S. pneumoniae, the rise in fluoroquino-lone resistance, and these reports of levofloxacin therapy failure indicate that fluoroquinolone susceptibility testing should be routinely conducted. This could reduce treatment failures in cases in which the infecting isolates have high MICs resulting from mutations in ParC and GyrA. Unfortunately, it has been shown that susceptibility testing is not able to identify isolates containing only a ParC mutation.[7] These are the isolates that are most clinically disconcerting as the acquisition of a second mutation, and the resultant rise to high-level resistance MICs, occurs much more readily than a primary mutation.[7] It has recently been reported that 19% and 60% of S. pneumoniae isolates with levofloxacin MICs of 1 and 2 mg/mL, respectively, have ParC mutations.[12] These isolates are considered susceptible and the mutations would not be identified throughout susceptibility testing. Even with routine fluoroquinolone susceptibility testing, these isolates would be considered susceptible, treated with fluoroquinolones, and provide an opportunity for rapid development of highly fluoroquinolone resistant S. pneumoniae isolates. Thus, routine fluoroquinolone susceptibility testing should be conducted to reduce treatment failures resulting from S. pneumoniae isolates with substitutions in ParC and GyrA and additional testing methods should be developed that can rapidly identify isolates with only ParC mutations.

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Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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