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].

References:

  • Ruuskanen, O, Lahti E, Jennings LC, et al. (2011) Viral pneumonia. Lancet. 377(9773): 1264–75.
  • GBD 2016 Causes of Death Collaborators. (2017) Global, regional, and national age-sex specific mortality for 264 causes of death, 1980–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 390(10100): 1151–1210.
  • Mizgerd, JP. (2008) Acute lower respiratory tract infection. N Engl J Med. 358(7): 716–27.
  • Brown, JS. (2012) What’s new in respiratory infections and tuberculosis 2008–2010. Thorax. 67(4): 350–4.
  • O’Brien, KL, Wolfson LJ, Watt JP, et al. (2009) Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates. Lancet. 374(9693): 893–902.
  • Watt JP, Wolfson LJ, O’Brien KL, et al. (2009) Burden of disease caused by Haemophilus influenzae type b in children younger than 5 years: global estimates. Lancet. 374(9693): 903–11.
  • Mandell, LA, Wunderink RG, Anzueto A, et al. (2007) Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community- acquired pneumonia in adults. Clin Infect Dis. 44 Suppl 2: S27–72.
  • Zumla, A. (2014) New developments in the epidemiology, diagnosis, treatment, and prevention of respiratory tract infections. Current Opin Pulm Med. 20(3): 213–4.
  • Ball P, Baquero F, Cars O. (2002) Antibiotic therapy of community respiratory tract infections: strategies for optimal outcomes and minimized resistance emergence. J Antimicrob Chemother. 49(1): 31–40.