Efficacy of a new fluoroquinolone, JNJ-Q2, in murine models of Staphylococcus aureus and Streptococcus pneumoniae skin, respiratory, and systemic infections.

Abstract

The in vivo efficacy of JNJ-Q2, a new broad-spectrum fluoroquinolone (FQ), was evaluated in a murine septicemia model with methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) and in a Streptococcus pneumoniae lower respiratory tract infection model. JNJ-Q2 and comparators were also evaluated in an acute murine skin infection model using a community-acquired MRSA strain and in an established skin infection (ESI) model using a hospital-acquired strain, for which the selection of resistant mutants was also determined. JNJ-Q2 demonstrated activity in the MSSA septicemia model that was comparable to that moxifloxacin (JNJ-Q2 50% effective dose [ED(50)], 0.2 mg/kg of body weight administered subcutaneously [s.c.] and 2 mg/kg administered orally [p.o.]) and activity in the MRSA septicemia model that was superior to that of vancomycin (JNJ-Q2 ED(50), 1.6 mg/kg administered s.c.). In an S. pneumoniae lower respiratory tract infection model, JNJ-Q2 displayed activity (ED(50), 1.9 mg/kg administered s.c. and 7.4 mg/kg administered p.o.) that was comparable to that of gemifloxacin and superior to that of moxifloxacin. In both MRSA skin infection models, treatment with JNJ-Q2 resulted in dose-dependent reductions in bacterial titers in the skin, with the response to JNJ-Q2 at each dose exceeding the responses of the comparators ciprofloxacin, moxifloxacin, linezolid, and vancomycin. Additionally, in the ESI model, JNJ-Q2 showed a low or nondetectable propensity for ciprofloxacin resistance selection, in contrast to the selection of ciprofloxacin-resistant mutants observed for both ciprofloxacin and moxifloxacin. JNJ-Q2 demonstrated activity that was comparable or superior to the activity of fluoroquinolone or antistaphylococcal comparators in several local and systemic skin infection models performed with both S. aureus and S. pneumoniae and is currently being evaluated in phase II human clinical trials.

• Authors: Jeffrey Fernandez, Jamese J Hilliard, Brian J Morrow, John L Melton, Robert K Flamm, Alfred M Barron, A Simon Lynch
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 55 Issue 12 Pg. 5522-8 (Dec 2011) ISSN: 1098-6596 [Electronic] United States
• PMID: 21911568 (Publication Type: Journal Article)

Chemical References

• 7-(3-(2-amino-1-fluoroethylidene)-1-piperidinyl)-1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid
• Anti-Bacterial Agents
• Fluoroquinolones
• Methicillin

Topics

• Animals
• Anti-Bacterial Agents (pharmacology, therapeutic use)
• Bacteremia (drug therapy, microbiology)
• Community-Acquired Infections (drug therapy, microbiology)
• Disease Models, Animal
• Female
• Fluoroquinolones (pharmacology, therapeutic use)
• Humans
• Methicillin (pharmacology)
• Methicillin-Resistant Staphylococcus aureus (drug effects)
• Mice
• Respiratory Tract Infections (drug therapy, microbiology)
• Staphylococcal Infections (drug therapy, microbiology)
• Staphylococcal Skin Infections (drug therapy, microbiology)
• Staphylococcus aureus (drug effects)
• Streptococcus pneumoniae (drug effects)
• Treatment Outcome