Fluoroquinolone Resistance in <i>Streptococcus pneumoniae</i>

Kuehnert, Matthew J.; Nolte, Frederick S.; Perlino, Carl A.

doi:10.7326/0003-4819-131-4-199908170-00023

Cited by 33 publications

(15 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, reports of failures to LVX treatment of pneumococcal diseases have been occurring (16,23,25,37,39,64,69,71). Some of these failures occurred in patients previously exposed to fluoroquinolones and/or when the pneumococcus exhibited an decreased susceptibility to fluoroquinolones, which was sometimes related to a preexisting parC mutation.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Mutant Selection Window in Levofloxacin and Moxifloxacin Treatments of Experimental Pneumococcal Pneumonia in a Rabbit Model of Human Therapy

Croisier¹,

Etienne²,

Bergoin³

et al. 2004

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

“…Recently, two major observations have emerged: first, failures of LVX treatment for pneumococcal pneumonia have been described in patients, most of whom were previously exposed to fluoroquinolones (16,24,37,39,64,69,71; N. Fishman, B. Suh, L. Weigel, B. Lorber, S. Gelone, A. Truant, T. Gootz, J. Christie, and P. Edelstein, Abstr.…”

mentioning

confidence: 99%

Mutant Selection Window in Levofloxacin and Moxifloxacin Treatments of Experimental Pneumococcal Pneumonia in a Rabbit Model of Human Therapy

Croisier¹,

Etienne²,

Bergoin³

et al. 2004

Antimicrob Agents Chemother

View full text Add to dashboard Cite

“…There are bacteriologically confirmed failures of ciprofloxacin and, more recently, of levofloxacin, in the management of pneumococcal pneumonia, sinusitis, bronchitis, and exacerbation of chronic bronchitis (table 3) [38][39][40][41][42][43]. The pharmacodynamics of ciprofloxacin suggest that strains of pneumococci may not respond to therapy, even in the absence of resistance mutations.…”

Section: Fluoroquinolonesmentioning

confidence: 99%

“…Once this and other fluoroquinolones, ) to levofloxacin in isogenic strains from sputum, associated with treatment failure [40]. Seven further patients treated with ciprofloxacin or levofloxacin for pneumonia or exacerbations of chronic bronchitis failed clinically and had resistant strains isolated on therapy from the sputum [38,39,[41][42][43].…”

Section: Fluoroquinolonesmentioning

confidence: 99%

Bacteriological evidence of antibiotic failure in pneumococcal lower respiratory tract infections

2002

European Respiratory Journal

View full text Add to dashboard Cite

Bacteriological evidence of antibiotic failure in pneumococcal lower respiratory tract infections. K.P. Klugman. #ERS Journals Ltd 2002. ABSTRACT: The global pandemic of antimicrobial resistance, particularly in the pneumococcus, has had a major impact on the management of community-acquired pneumonia.A number of prospective and retrospective studies have analysed the impact of penicillin resistance on clinical outcome in pneumonia. Pharmacodynamic principles predicting success when the antibiotic dose exceeds the minimum inhibitory concentration (MIC) for 40-50% of the dosing interval have proved remarkably accurate. There is no evidence of bacteriological failure of penicillins active against resistant strains. There is a single report of the failure of the less active agent, ticarcillin. High dose oral and intravenous amoxicillin should treat strains with MICs ¡4 mg?mL -1 , as should high doses of intravenous penicillin, ceftriaxone and cefotaxime. Strains of pneumococci resistant to these agents at an MIC o8 mg?mL -1 are rare at the present time. Most other cephalosporins are less active and should not be used empirically for drug-resistant Streptococcus pneumoniae. Bacteriological failures of cefazolin, cefuroxime and ceftazidime have been reported.There is increasing evidence of bacteriologically confirmed macrolide failure of pneumonia therapy at MICs o4 mg?mL -1 . The molecular basis of the resistance is irrelevant if the MIC is in that range or higher. Double mutants in the parC and gyrA genes lead to fluoroquinolone resistance that has been found to cause bacteriological failure of the fluoroquinolones, particularly levofloxacin and ciprofloxacin, in the management of pneumonia and exacerbations of chronic bronchitis. Two mutations in these genes can greatly increase the MICs of all the marketed fluoroquinolones, and raise the prospect of failure of therapy even with the more active ones. However, demonstration of bacteriological failure of gatifloxacin or moxifloxicin has not yet been reported.High dose, active b-lactams or fluoroquinolones with enhanced activity against Gram positive pathogens remain the drugs of choice for the management of communityacquired pneumonia caused by the drug-resistant pneumococcus.

show abstract

“…Of perhaps greater concern are the recent clinical failures of levofloxacin treatment of S. pneumoniae infections and growing evidence of frequent mutations in the isolate population. Since 1999, there have been 21 case reports of levofloxacin treatment failures in the United States and Canada (6,8,12,13,26,27,29 L-902, 2001). Furthermore, a recent report (7) of a study with a subset of the levofloxacin-susceptible pneumococcal isolates from the 1999-2000 respiratory season evaluated as part of the TRUST surveillance program suggests that 6.6 and 71% of the S. pneumoniae isolates for which the levofloxacin MICs are 1.0 and 2.0 g/ml, respectively, contain a first-step parC mutation.…”

mentioning

confidence: 99%

Pharmacodynamics of Moxifloxacin and Levofloxacin at Simulated Epithelial Lining Fluid Drug Concentrations against Streptococcus pneumoniae

Florea

Tessier²,

Zhang³

et al. 2004

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Recent clinical failures associated with levofloxacin treatment for Streptococcus pneumoniae infections and growing evidence of frequent mutations in the isolate population have led to increased concerns regarding fluoroquinolone resistance. Our objective was to characterize the efficacies of levofloxacin and moxifloxacin against various genotypes of S. pneumoniae after simulated bronchopulmonary exposures. An in vitro model was used to simulate a levofloxacin concentration of 500 mg and a moxifloxacin concentration of 400 mg, which were previously determined to be the concentrations in the epithelial lining fluid of older adults receiving once-daily dosing. The effects of the drugs were tested against six S. pneumoniae containing various mutations. Bacterial density and resistance were quantitatively assessed over 48 h. The S. pneumoniae isolate with no mutation displayed a 4-log reduction in CFU after treatment with both agents and did not develop resistance. Isolates containing the parC or parE mutation or both mutations regrew and developed resistance when they were exposed to levofloxacin, despite an unbound area under the concentration-time curve (AUC):MIC ratio of ϳ100. When the isolate containing the parC and gyrA mutations was exposed to levofloxacin, there was a half-log reduction in the number of CFU compared to that for the control, but the isolate subsequently regrew. Likewise, levofloxacin did not kill the isolate containing the parC, gyrA, and parE mutations. Moxifloxacin sustained the killing of all bacterial isolates tested without the development of resistance. Levofloxacin did not sustain bacterial killing and did not prevent the emergence of further resistance in mutants with the parC or parE mutation or both mutations, even though an unbound AUC:MIC ratio for exposure well above the breakpoint of 30 to 40 established in the literature for S. pneumoniae was maintained. Moxifloxacin was effective against all isolates tested, despite the presence of isolates with two-and three-step mutations, for which the MICs were increased.Streptococcus pneumoniae is the most common organism associated with lower respiratory tract infections and accounts for approximately 50% of all cases of community-acquired pneumonia, 35% of cases of acute sinusitis and acute otitis media, and 20% of chronic bronchitis infections (15,28). Of growing concern with S. pneumoniae is the increasing levels of resistance to commonly used antimicrobials, namely, the penicillins and other ␤-lactams, as well as the macrolides. The frequencies of resistance to penicillin and the macrolides among S. pneumoniae strains are estimated to be 40 and 30%, respectively (10). As such, use of one of the antipneumococcal fluoroquinolones (levofloxacin, moxifloxacin, gatifloxacin) as monotherapy for lower respiratory tract infections is fast becoming common practice in both the inpatient and the outpatient settings.With the increasing use of the antipneumococcal fluoroquinolones, issues surrounding the development of resistance to these agents ...

show abstract

Fluoroquinolone Resistance in Streptococcus pneumoniae

Cited by 33 publications

References 5 publications

Mutant Selection Window in Levofloxacin and Moxifloxacin Treatments of Experimental Pneumococcal Pneumonia in a Rabbit Model of Human Therapy

Mutant Selection Window in Levofloxacin and Moxifloxacin Treatments of Experimental Pneumococcal Pneumonia in a Rabbit Model of Human Therapy

Bacteriological evidence of antibiotic failure in pneumococcal lower respiratory tract infections

Pharmacodynamics of Moxifloxacin and Levofloxacin at Simulated Epithelial Lining Fluid Drug Concentrations against Streptococcus pneumoniae

Contact Info

Product

Resources

About