In Vitro Activity of Menelofloxacin, a New Fluoroquinolone Antibiotic, Against Respiratory Pathogens

The global morbidity and mortality burden of respiratory tract infections (RTIs) is substantial. In 2016, lower RTIs—the majority of which are of bacterial etiology [1]—were one of the top 10 causes of death worldwide, and one of the 3 leading global causes of death among children under 5 years [2]. They account for a greater burden of disease than cancer, malaria, HIV infection, or myocardial infarctions, and their incidence is highest in children and older persons [3,4]. In particular, in children younger than 5 years, Streptococcus pneumoniae and Haemophilus influenzae cause approximately 13 800 800 and 7 910 000 RTIs every year, resulting in about 741 000 and 292 000 deaths, respectively [5,6]. The economic impact of RTIs is likewise significant, with an estimated annual cost of US $17 billion in the United States alone [1].

RTIs are caused by a wide range of Gram-positive, Gram-negative, and atypical bacteria, and the majority respond adequately to standard first-line empirical antibiotic therapy [7]. However, increasing levels of antibiotic resistance, particularly among Gram-negative pathogens, is compromising their treatment outcomes [8]. In this context, novel antimicrobial agents that offer broad-spectrum activity against all likely pathogens, and that maximize bacteriological efficacy—especially against Gram-negative organisms—would be of significant clinical utility [9].

In this study, we provide a complete microbiological characterization of a new extended- spectrum fluoroquinolone antibiotic, menelofloxacin. Specifically, we describe menelofloxacin’s in vitro antibacterial activity against a panel of respiratory isolates from known cases of RTI, as compared with that of amoxicillin, an aminopenicillin, and ciprofloxacin, a second-generation fluoroquinolone. We demonstrate that menelofloxacin exhibits superior activity relative to ciprofloxacin against all of the Gram-negative isolates, and comparable activity relative to amoxicillin, and superior activity relative to ciprofloxacin, against Gram-positive isolates. For certain isolates, we show that menelofloxacin’s combined pharmacokinetic and pharmacodynamic parameters fall into the optimal range for fluoroquinolones [9].


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