Characterization of
 grlA
 ,
 grlB
 ,
 gyrA
 , and
 gyrB
 Mutations in 116 Unrelated Isolates of
 Staphylococcus aureus
 and Effects of Mutations on Ciprofloxacin MIC

Schmitz, Franz‐Josef; Jones, Mark; Hofmann, B.; Hansen, Birgit Sehested; Scheuring, Sibylle; Lückefahr, Marc; Fluit, Ad C.; Verhoef, J.; Hadding, U.; Heinz, Hans‐Peter; Köhrer, Karl

doi:10.1128/aac.42.5.1249

Cited by 124 publications

(64 citation statements)

References 20 publications

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“…Most striking has been the rapid emergence of a high prevalence of quinolone resistance (190%) among methicillinresistant but not methicillin-susceptible strains of S. aureus in many parts of the world [88,89]. This same difference in prevalence of quinolone resistance also exists between methicillinresistant and -susceptible strains of coagulase-negative staphylococci [90].…”

Section: Bacterial Resistance Associated With Use Of Quinolonesmentioning

confidence: 89%

New Uses for New and Old Quinolones and the Challenge of Resistance

Hooper¹

2000

Clinical Infectious Diseases

151

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More than a decade ago ciprofloxacin, the first quinolone with broad indications, was released for clinical use in the United States. The release of ofloxacin, which also had broad applications, followed not long thereafter. Since that time there has been extensive use of these 2 agents and more limited use of other quinolones, such as norfloxacin, enoxacin, and lomefloxacin, which were limited to treatment of infections of the genitourinary tract. Applications of these quinolones largely employed their potent activities against gram-negative bacteria [1,2].This article focuses on information developed in the past 4 years on the 4 most recently released quinolones-levofloxacin, sparfloxacin, grepafloxacin, and trovafloxacin [3-8]-and their spectrum of activity, pharmacokinetics, tolerability, and clinical applications. It also focuses on new applications of the older quinolones. Issues of quinolone resistance related to expanding uses of quinolones will also be discussed. Spectrum of ActivityThe newer fluoroquinolones have retained much of the activity of ciprofloxacin and ofloxacin against enteric gramnegative bacteria, but none is more potent than ciprofloxacin against these pathogens or against Pseudomonas aeruginosa. Levofloxacin is the active stereoisomer of the racemic mixture of the 2 stereoisomers that make up ofloxacin and thus is generally 2-fold more potent than ofloxacin [3]. Trovafloxacin [9] and, to a lesser extent, levofloxacin generally have gram-negative coverage similar to that of ciprofloxacin, but both may be less active against some strains of P. aeruginosa.There may also be gaps in trovafloxacin's coverage of some strains of Providencia species, Proteus species, and Serratia marcescens. There are also gaps in the gram-negative coverage of sparfloxacin and grepafloxacin. Sparfloxacin [10,11] has only limited potency against P. aeruginosa, S. marcescens, Citrobacter freundii, and Proteus vulgaris; and grepafloxacin [12] lacks sufficient activity against P. aeruginosa, S. marcescens, Providencia stuartii, and Acinetobacter baumanii among gram-negative bacteria.Like ciprofloxacin and ofloxacin, the newer agents have excellent potency against genital pathogens, including Neisseria gonorrhoeae, Chlamydia trachomatis, and Mycoplasma hominis. Their clinical efficacy in the treatment of genital chlamydial infections may differ, however, as discussed below.Against respiratory pathogens, all of the newer quinolones, such as ciprofloxacin and ofloxacin, are highly potent against Haemophilus influenzae and Moraxella catarrhalis. However, these agents exhibit greater potency than ciprofloxacin and ofloxacin against Streptococcus pneumoniae, with MIC 90 values of 1-2 mg/mL for levofloxacin [13], 0.25-0.5 mg/mL for sparfloxacin [14] and grepafloxacin [15], and 0.12-0.25 mg/mL for trovafloxacin [16]. For this reason, all have been developed for treatment of respiratory tract infections, as discussed below. Other respiratory pathogens, such as Legionella pneumophila, Mycoplasma pneumoniae, and Chlamydia pneum...

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Section: Bacterial Resistance Associated With Use Of Quinolonesmentioning

confidence: 89%

New Uses for New and Old Quinolones and the Challenge of Resistance

Hooper¹

2000

Clinical Infectious Diseases

151

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“…For example, amino acid in parE changes from Pro25 → His, Glu422 → Asp, Lys441 → Ile, Lys428 → Gln, Asp494 → Asn, Lys428→ Gln, Gly442 → Ser, Asp432 → Asn or Gly, Pro451 → Ser or Gln and Asn470 → Asp among fluoroquinolone-resistant S. aureus, (Schmitz et al, 1998;Ince & Hooper, 2001;Fournier & Hooper, 1998). However, these mutations may not be directly responsible for high-level resistance but rather increase the resistance levels in isolates already harboring two gyrA mutations and one parC mutation.…”

Section: Discussionmentioning

confidence: 99%

Mutations in gyrase and topoisomerase genes associated with fluoroquinolone resistance in Salmonella serovars from retail meats

Yang

Cui

et al. 2012

Food Research International

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“…14 The occurrence of low-level resistance against fluoroquinolones after a single mutation in parC has been described earlier for Enterococcus faecalis, S. aureus, and S. pneumoniae, whereas high-level resistant isolates had mutations in both parC and gyrA. 8,20,30,34 In M. bovirhinis, however, a single mutation in parC (position 80) resulted in different MIC profiles, including low-and high-level resistant isolates. 16 The authors suggested that the differences in MIC might have been caused by the level of expression of the quinolone efflux transporter.…”

Section: Mic (G/ml)mentioning

confidence: 90%

Resistance Mechanism Against Fluoroquinolones inMycoplasma hyopneumoniaeField Isolates

Vicca

Maes²,

Stakenborg³

et al. 2007

Microbial Drug Resistance

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The quinolone resistance-determining regions (QRDR) of gyrA, gyrB, parC, and parE of ten Mycoplasma hyopneumoniae field isolates that were either sensitive (5) or resistant (5) to the fluoroquinolones flumequine and enrofloxacin were characterized. In all five resistant isolates, one point mutation (C --> A) in parC was found, resulting in an amino acid change from serine to tyrosine at position 80 (Escherichia coli numbering). For four of these isolates, this was the only mutation found. These isolates had a minimum inhibitory concentration (MIC) of enrofloxacin of 0.5 microg/ml, whereas for sensitive isolates the MIC of enrofloxacin was < or =0.06 microg/ml. One resistant isolate (Mh 20) had an extra mutation (C --> T) in gyrA resulting in an amino acid change from alanine to valine at position 83 (E. coli numbering), leading to a further increase in the MIC of enrofloxacin (>1 microg/ml). No mutations resulting in an amino acid change were detected in the QRDR of the gyrB and parE genes of the selected isolates. This is the first description of the mechanism of stepwise resistance against fluoroquinolones in M. hyopneumoniae.

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Characterization of grlA , grlB , gyrA , and gyrB Mutations in 116 Unrelated Isolates of Staphylococcus aureus and Effects of Mutations on Ciprofloxacin MIC

Cited by 124 publications

References 20 publications

New Uses for New and Old Quinolones and the Challenge of Resistance

New Uses for New and Old Quinolones and the Challenge of Resistance

Mutations in gyrase and topoisomerase genes associated with fluoroquinolone resistance in Salmonella serovars from retail meats

Resistance Mechanism Against Fluoroquinolones inMycoplasma hyopneumoniaeField Isolates

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