In Vitro
 Activities of the Benzoquinolizine Fluoroquinolone Levonadifloxacin (WCK 771) and Other Antimicrobial Agents against Mycoplasmas and Ureaplasmas in Humans, Including Isolates with Defined Resistance Mechanisms

Xue, Guanhua; Crabb, Donna M.; Xiao, Li; Liu, Y.; Waites, Ken B.

doi:10.1128/aac.01348-18

Cited by 13 publications

(6 citation statements)

References 10 publications

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“…(including macrolide-, tetracycline-, and levofloxacin-resistant strains), Chlamydophila pneumoniae, and Legionella pneumophila is established. 21,22 Anaerobes WCK 771 was found to be active against Gram-positive anaerobes such as Clostridium perfringens and C. difficile. Similarly, Gram-negative anaerobes Bacteroides fragilis, 'Prevotella and Porphyromonas strains, and β-lactamase-producing Fusobacteria were found to be susceptible to WCK 771.…”

Section: Mechanism Of Action Of Wck 771mentioning

confidence: 99%

“…Minimum bactericidal concentrations (MBCs) of WCK 771 were ≤2 dilutions higher than the MICs, suggesting its potential role in the treatment of infections caused by atypical bacteria with or without macrolide or tetracycline resistance. 21 Kohlhoff et al performed WCK 771 susceptibility testing against Chlamydophila pneumoniae (N=10) using HEp-2 cells grown in 96-well microtiter plates. WCK 771 MICs against these isolates ranged from 0.5 to 4 mg/L, while MIC 50/90 and MBC 90 were 1/2 mg/L and 4 mg/L, respectively.…”

Section: Mic Determination Studiesmentioning

confidence: 99%

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Levonadifloxacin, a Novel Broad-Spectrum Anti-MRSA Benzoquinolizine Quinolone Agent: Review of Current Evidence

Bhagwat

Nandanwar

Kansagara

et al. 2019

DDDT

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Levonadifloxacin and its prodrug alalevonadifloxacin are novel broad-spectrum anti-MRSA agents belonging to the benzoquinolizine subclass of quinolone, formulated for intravenous and oral administration, respectively. Various in vitro and in vivo studies have established their antimicrobial spectrum against clinically significant Gram-positive, Gram-negative, atypical, and anaerobic pathogens. The potent activity of levonadifloxacin against MRSA, quinolone-resistant Staphylococcus aureus, and hetero-vancomycin-intermediate strains is an outcome of its welldifferentiated mechanism of action involving preferential targeting to DNA gyrase. Potent antistaphylococcal activity of levonadifloxacin was also observed in clinically relevant experimental conditions such as acidic pH, the intracellular environment, and biofilms, suggesting that the drug is bestowed with enabling features for the treatment of difficult-to-treat MRSA infections. Levonadifloxacin also retains clinically relevant activity against resistant respiratory pathogens such as macrolide-and penicillin-resistant Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, and Moraxella catarrhalis and, in conjunction with clinically established best-in-class human epithelial lung fluid concentration, has promising potential in the management of recalcitrant respiratory infections. Attractive features, such as resistance to NorA efflux, divergent mechanism of action in S. aureus, cidality against high-inoculum cultures, and low mutant prevention concentration, are likely to confer favorable resistance-suppression features to both agents. In vivo studies have shown promising efficacy in models of acute bacterial skin and skin structure infection, respiratory infections, pyelonephritis, and peritonitis at human-equivalent mouse doses. Both formulations were well tolerated in multiple phase I studies and overall showed a dose-dependent exposure. In particular, oral alalevonadifloxacin showed excellent bioavailability (~90%), almost mirroring the pharmacokinetic profile of intravenous levonadifloxacin, indicating the prodrug's seamless absorption and efficient cleavage to release the active parent drug. Hepatic impairment studies showed that clinical doses of levonadifloxacin/alalevonadifloxacin are not required to be adjusted for various degrees of hepatic impairment. With the successful completion of phase II and phase III studies for both levonadifloxacin and alalevonadifloxacin, they represent clinically attractive therapeutic options for the treatment of infections caused by multi-drugresistant Gram-positive organisms. Herein, we review the current evidence on therapeutically appealing attributes of levonadifloxacin and alalevonadifloxacin, which are based on a range of nonclinical in vitro and in vivo investigations and clinical studies.

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Section: Mechanism Of Action Of Wck 771mentioning

confidence: 99%

Section: Mic Determination Studiesmentioning

confidence: 99%

Levonadifloxacin, a Novel Broad-Spectrum Anti-MRSA Benzoquinolizine Quinolone Agent: Review of Current Evidence

Bhagwat

Nandanwar

Kansagara

et al. 2019

DDDT

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“…When ammonia levels began to rise again, the patient was switched to a different fluoroquinolone because available susceptibility data suggest that moxifloxacin may have a lower rate of resistance. 8,9 Eventually, the patient's ammonia levels declined to normal levels by hospital day 77.…”

Section: Case Reportmentioning

confidence: 99%

Hyperammonemic Encephalopathy due to Ureaplasma parvum Infection in an Immunocompromised Child

Smith¹,

Crews

Cheek³

et al. 2019

Pediatrics

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“…has also been demonstrated. [7071] A recent study has demonstrated that the ratios of ELF concentration and concentration in AMs relative to plasma concentration were 7.66 and 1.58, respectively, suggesting better lung penetration. [72] Achievement of such good levels in lung combined with its broad-spectrum activity covering Gram-positive, Gram negative, and atypical pathogens, makes levonadifloxacin a potent antibiotic for the treatment of CABP.…”

Section: Future Therapiesmentioning

confidence: 99%

Management of community-acquired bacterial pneumonia in adults: Limitations of current antibiotics and future therapies

et al. 2019

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Community-acquired bacterial pneumonia (CABP) is one of the leading causes of morbidity and mortality in India and worldwide. Evidence indicates that Gram-positive, Gram-negative, and atypical bacteria are encountered with near-equal frequency. Despite guideline recommendations and antibiotic options for the management of CABP, burden of morbidity and mortality is high, which is attributable to a variety of factors. Failure of empirical therapy, probably because of insufficient microbial coverage, increasing bacterial resistance, and adverse effects of existing treatments, underlies the unsuccessful treatment of CABP, especially in India. Multiple novel therapies that have entered clinical development phases have potential to address some of these issues. This article discusses the current treatment guidelines in CABP, management limitations, and emerging potential treatment options in the management of CABP.

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In Vitro Activities of the Benzoquinolizine Fluoroquinolone Levonadifloxacin (WCK 771) and Other Antimicrobial Agents against Mycoplasmas and Ureaplasmas in Humans, Including Isolates with Defined Resistance Mechanisms

Cited by 13 publications

References 10 publications

<p>Levonadifloxacin, a Novel Broad-Spectrum Anti-MRSA Benzoquinolizine Quinolone Agent: Review of Current Evidence</p>

<p>Levonadifloxacin, a Novel Broad-Spectrum Anti-MRSA Benzoquinolizine Quinolone Agent: Review of Current Evidence</p>

Hyperammonemic Encephalopathy due to Ureaplasma parvum Infection in an Immunocompromised Child

Management of community-acquired bacterial pneumonia in adults: Limitations of current antibiotics and future therapies

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