Induction of Resistance of &lt;i&gt;Streptococcus pneumoniae &lt;/i&gt;to Quinolones in vitro

Lafredo, S C; Foleno, Barbara D.; Fu, Kwung P.

doi:10.1159/000238971

Cited by 19 publications

(14 citation statements)

References 4 publications

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“…In this study we showed, on July 10, 2020 by guest http://aac.asm.org/ evaluation period in this study, the condition does not simulate actual human pharmacokinetics when dosing q12h is utilized in patients with normal renal function. In this study, the development of resistance to ciprofloxacin for all study isolates was apparent, especially after 24 h. The induction of resistance of S. pneumoniae to FQ in vitro has been previously reported (19). After repeated transfer in ciprofloxacin, temafloxacin, and norfloxacin there was an 8-to 16-fold decrease in susceptibility, while after transfer in levofloxacin only minimal decreases in susceptibility were observed.…”

Section: Discussionsupporting

confidence: 77%

Pharmacodynamic Comparisons of Levofloxacin, Ciprofloxacin, and Ampicillin against Streptococcus pneumoniae in an In Vitro Model of Infection

Lacy

Lu²,

Xu³

et al. 1999

Antimicrob Agents Chemother

207

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The increasing frequency of penicillin-resistant pneumococcus continues to be of concern throughout the world. Newer fluoroquinolone antibiotics, such as levofloxacin, have shown enhanced in vitro activity against Streptococcus pneumoniae. In this study, the bactericidal characteristics and pharmacodynamic profiles of levofloxacin, ciprofloxacin, and ampicillin against four isolates of S. pneumoniae were compared by using an in vitro model of infection. Standard antibiotic dosing regimens which simulated the pharmacokinetic profile observed in humans were used. Control and treatment models were sampled for bacterial CFU per milliliter over the duration of each 24-or 48-h experiment. In addition, treatment models were sampled for MIC determinations and drug concentration. Regrowth of all isolates as well as an increase in MICs throughout the study period was observed in the ciprofloxacin experiments. A limited amount of regrowth was noted during levofloxacin therapy for one isolate; however, no change in MIC was detected for any isolate. Ampicillin showed rapid and sustained bactericidal activity against all isolates. In this study, ratios of effective fluoroquinolone area under the concentration-time curve (AUC):MIC values ranged from 30 to 55. Levofloxacin, owing to its larger AUC 0-24 values, has excellent and sustained activity against different pneumococcal strains superior to that of ciprofloxacin.

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Section: Discussionsupporting

confidence: 77%

Pharmacodynamic Comparisons of Levofloxacin, Ciprofloxacin, and Ampicillin against Streptococcus pneumoniae in an In Vitro Model of Infection

Lacy

Lu²,

Xu³

et al. 1999

Antimicrob Agents Chemother

207

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“…Ciprofloxacin-resistant strains of S. pneumoniae have been reported, and most troubling is the possibility of cross-resistance to the newer fluoroquinolones (11,21,26,27,32). These compounds have improved activity against topoisomerase IV, which is thought to be the primary target for most fluoroquinolones in gram-positive organisms such as S. pneumoniae and Staphylococcus aureus.…”

mentioning

confidence: 99%

Activities of Newer Fluoroquinolones against Ciprofloxacin-Resistant Streptococcus pneumoniae

Coyle

Kaatz

Rybak

2001

Antimicrob Agents Chemother

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The incidence of ciprofloxacin resistance in Streptococcus pneumoniae is low but steadily increasing, which raises concerns regarding the clinical impact of potential cross-resistance with newer fluoroquinolones. To investigate this problem, we utilized an in vitro pharmacodynamic model and compared the activities of gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin, and trovafloxacin to that of ciprofloxacin against two laboratory-derived, ciprofloxacin-resistant derivatives of S. pneumoniae (strains R919 and R921). Ciprofloxacin resistance in these strains involved the activity of a multidrug efflux pump and possibly, for R919, a mutation resulting in an amino acid substitution in GyrA. Gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin, and trovafloxacin achieved 99.9% killing of both R919 and R921 in <28 h. With respect to levofloxacin, significant regrowth of both mutants was observed at 48 h (P < 0.05). For gatifloxacin, grepafloxacin, moxifloxacin, and trovafloxacin, regrowth was minimal at 48 h, with each maintaining 99.9% killing against both mutants. No killing of either R919 or R921 was observed with exposure to ciprofloxacin. During model experiments, resistance to gatifloxacin, grepafloxacin, moxifloxacin, and trovafloxacin did not develop but the MICs of ciprofloxacin and levofloxacin increased 1 to 2 dilutions for both R919 and R921. Although specific area under the concentration-time curve from 0 to 24 h (AUC 0-24 )/MIC and maximum concentration of drug in serum (C max )/MIC ratios have not been defined for the fluoroquinolones with respect to gram-positive organisms, our study revealed that significant regrowth and/or resistance was associated with AUC 0-24 /MIC ratios of <31.7 and C max /MIC ratios of <3.1. It is evident that the newer fluoroquinolones tested possess improved activity against S. pneumoniae, including strains for which ciprofloxacin MICs were elevated.Streptococcus pneumoniae is a significant cause of morbidity and mortality and is one of the primary pathogens implicated in community-acquired pneumonia (2,3,5,17,36). Newer fluoroquinolones, such as levofloxacin, trovafloxacin, and clinafloxacin, have been shown to possess greater activity than older agents of this class against gram-positive organisms, including S. pneumoniae (3,6,8,13,19,23,34). The newer fluoroquinolones thus are potential alternatives for therapy of infections caused by multidrug-resistant pneumococci. With the increasing use of these drugs, however, there is growing concern regarding the development of quinolone resistance among gram-positive bacteria (10, 21).Animal models, in vitro pharmacodynamic models, and limited human data have demonstrated that the primary pharmacodynamic parameters which most closely correlate with therapeutic efficacy of fluoroquinolones are area under the concentration-time curve from 0 to 24 h (AUC 0-24 )/MIC and maximum concentration of drug in serum (C max )/MIC ratios (1,16,28,37). However, there are limited data correlating pharmacodynamic parameters with the devel...

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“…However, 0.5% of S. pneumoniae in France are resistant to sparfloxacin (MIC>4 μg/ml) and other fluoroquinolones (3, 4. The selection of S. pneumoniae resistant to quinolones has also been demonstrated in vitro (5). We report herein the in vivo selection of a strain of S. pneumoniae resistant to fluoroquinolones, including sparfloxacin.…”

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confidence: 99%

In Vivo Selection of Streptococcus pneumoniae, Resistant to Quinolones, Including Sparfloxin

Bernard

Van

Mainardi

1995

Clinical Microbiology and Infection

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Induction of Resistance of <i>Streptococcus pneumoniae </i>to Quinolones in vitro

Cited by 19 publications

References 4 publications

Pharmacodynamic Comparisons of Levofloxacin, Ciprofloxacin, and Ampicillin against Streptococcus pneumoniae in an In Vitro Model of Infection

Pharmacodynamic Comparisons of Levofloxacin, Ciprofloxacin, and Ampicillin against Streptococcus pneumoniae in an In Vitro Model of Infection

Activities of Newer Fluoroquinolones against Ciprofloxacin-Resistant Streptococcus pneumoniae

In Vivo Selection of Streptococcus pneumoniae, Resistant to Quinolones, Including Sparfloxin

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