Actividad in vitro de delafloxacina frente a microorganismos aislados de infecciones osteoarticulares y de piel y partes blandas en Buenos Aires, Argentina

Resumen Se estudió la actividad in vitro de delafloxacina, ciprofloxacina y levofloxacina por los métodos epsilométrico y de difusión por discos frente a 181 aislamientos clínicos de infecciones de piel y osteoarticulares. Se incluyeron 40 Staphylococcus aureus resistentes a meticilina (SARM), 44 S. aureus sensibles a meticilina (SASM), 46 estafilococos coagulasa negativos (ECN), 23 Klebsiella pneumoniae y 28 Pseudomonas aeruginosa. Las CIM50/CIM90 (mg/l) de delafloxacina, ciprofloxacina y levofloxacina respectivamente fueron 0,004/0,064, 0,25/16 y 0,125/4 frente a SARM; 0,002/0,004, 0,125/0,25 y 0,125/0,25 frente a SASM; 0,008/0,25, 0,125/>32 y 0,25/>32 frente a ECN; 4/>32,>32/>32 y 16/>32 frente a K. pneumoniae y 1/>32, 0,5/>32 y 4/>32 frente a P. aeruginosa. La proporción de aislamientos sensibles a delafloxacina, ciprofloxacina y levofloxacina fue la siguiente: SARM, 97,5%; 82,5% y 82,5%; SASM, 97,7%; 95,5% y 95,5%; ECN, 93,5%; 63,0% y 60,9%; K. pneumoniae, 21,7%; 26,1% y 43,5%; P. aeruginosa, 35,7%; 53,6% y 42,8%. La concordancia categórica del método de difusión por discos y el método epsilométrico para evaluar la actividad in vitro de la delafloxacina fue del 98,8% en S. aureus y del 91,3% en ECN.

Abstract In vitro activities of delafloxacin, ciprofloxacin and levofloxacin were evaluated by epsilometric and disk diffusion methods against 181 bacterial isolates recovered from bone and skin infections. Isolates included were 84 Staphylococcus aureus (40 MRSA and 44 MSSA), 46 coagulase-negative staphylococci (CNS), 23 Klebsiella pneumoniae and 28 Pseudomonas aeruginosa. The MIC50/MIC90 (mg/l) for delafloxacin, ciprofloxacin and levofloxacin, respectively, were: MRSA, 0.004/0.064, 0.25/16 and 0.125/4; MSSA, 0.002/0.004, 0.125/0.25 and 0.125/0.25; CNS, 0.008/0.25, 0.125/>32 and 0.25/>32; K. pneumoniae, 4/>32,>32/>32 and 16/>32; P. aeruginosa, 1/>32, 0,5/>32 and 4/>32. Susceptibilities for delafloxacin, ciprofloxacin and levofloxacin, respectively, were: MRSA, 97.5%, 82.5% and 82.5%; MSSA, 97.7%, 95.5% and 95.5%; CNS, 93.5%, 63.0% and 60.9%; K. pneumoniae, 21.7%, 26.1% and 43.5%; P aeruginosa, 35.7%, 53.6% and 42.8%. The disk diffusion and epsilometric methods were concordant for evaluating in vitro susceptibility in staphylococci (categorical concordance of 98.8% for S. aureus and 91.3% for CNS).

[In vitro activity of delafloxacin against bacterial isolates from osteoarticular and skin infections in Buenos Aires, Argentina]. / Actividad in vitro de delafloxacina frente a microorganismos aislados de infecciones osteoarticulares y de piel y partes blandas en Buenos Aires, Argentina.

In vitro activities of delafloxacin, ciprofloxacin and levofloxacin were evaluated by epsilometric and disk diffusion methods against 181 bacterial isolates recovered from bone and skin infections. Isolates included were 84 Staphylococcus aureus (40 MRSA and 44 MSSA), 46 coagulase-negative staphylococci (CNS), 23 Klebsiella pneumoniae and 28 Pseudomonas aeruginosa. The MIC50/MIC90 (mg/l) for delafloxacin, ciprofloxacin and levofloxacin, respectively, were: MRSA, 0.004/0.064, 0.25/16 and 0.125/4; MSSA, 0.002/0.004, 0.125/0.25 and 0.125/0.25; CNS, 0.008/0.25, 0.125/>32 and 0.25/>32; K. pneumoniae, 4/>32,>32/>32 and 16/>32; P. aeruginosa, 1/>32, 0,5/>32 and 4/>32. Susceptibilities for delafloxacin, ciprofloxacin and levofloxacin, respectively, were: MRSA, 97.5%, 82.5% and 82.5%; MSSA, 97.7%, 95.5% and 95.5%; CNS, 93.5%, 63.0% and 60.9%; K. pneumoniae, 21.7%, 26.1% and 43.5%; P aeruginosa, 35.7%, 53.6% and 42.8%. The disk diffusion and epsilometric methods were concordant for evaluating in vitro susceptibility in staphylococci (categorical concordance of 98.8% for S. aureus and 91.3% for CNS).

Delafloxacin as a treatment option for community-acquired pneumonia infection.

Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality in adults. Bacterial pathogens are recognized to be frequent causative agents, which makes antibacterial treatment crucial for the evolution of these patients. There are several antimicrobial options available in daily practice. However, bacterial resistance is a problem. The chemical, pharmacokinetic, pharmacodynamics, and safety characteristics of delafloxacin, a fluoroquinolone, are discussed. The data from one phase 3 clinical trial evaluating the use of delafloxacin in adults with community-acquired pneumonia is also discussed, along with findings from other meaningful studies. In vitro data have shown that delafloxacin has broad spectrum activity. Results from phase 2 and phase 3 studies have demonstrated that delafloxacin use is safe. International guidelines have recommended respiratory fluoroquinolones as second option for non-severe cases and must be considered in very severe patients not improving to a betalactam/macrolide combination. Delafloxacin was compared to moxifloxacin in the phase 3 community-acquired pneumonia trial. Serious and life-long adverse events due to fluoroquinolones use have been recently reported. Delafloxacin may possibly replace currently available fluoroquinolones, particularly in the treatment of resistant pathogens, such as ciprofloxacin-resistant P. aeruginosa isolates when other drugs are inefficient.

In Vitro Activity of Delafloxacin and Microbiological Response against Fluoroquinolone-Susceptible and Nonsusceptible Staphylococcus aureus Isolates from Two Phase 3 Studies of Acute Bacterial Skin and Skin Structure Infections.

Delafloxacin is an investigational anionic fluoroquinolone antibiotic with broad-spectrum in vitro activity, including activity against Gram-positive organisms, Gram-negative organisms, atypical organisms, and anaerobes. The in vitro activity of delafloxacin and the percent microbiological response in subjects infected with fluoroquinolone-susceptible and nonsusceptible Staphylococcus aureus isolates were determined from two global phase 3 studies of delafloxacin versus vancomycin plus aztreonam in patients with acute bacterial skin and skin structure infections (ABSSSI). Patients from 23 countries, predominately the United States but also Europe, South America, and Asia, were enrolled. The microbiological intent-to-treat (MITT) population included 1,042 patients from which 685 S. aureus isolates were submitted for identification and susceptibility testing per CLSI guidelines at the central laboratory (JMI Laboratories, North Liberty, IA). The comparator fluoroquinolone antibiotics included levofloxacin and ciprofloxacin. Nonsusceptibility to these antibiotics was determined using CLSI breakpoints. S. aureus isolates were 33.7% levofloxacin nonsusceptible (LVX-NS). The delafloxacin MIC90 values against levofloxacin-nonsusceptible S. aureus, methicillin-resistant S. aureus (MRSA), and methicillin-susceptible S. aureus isolates were all 0.25 µg/ml. Delafloxacin demonstrated high rates of microbiological response against LVX-NS isolates as well as isolates with documented mutations in the quinolone resistance-determining region (QRDR). S. aureus was eradicated or presumed eradicated in 98.4% (245/249) of delafloxacin-treated patients. Similar eradication rates were observed for delafloxacin-treated subjects with levofloxacin-nonsusceptible S. aureus isolates (80/81; 98.8%) and MRSA isolates (70/71; 98.6%). Microbiological response rates of 98.6% were observed with delafloxacin-treated subjects with S. aureus isolates with the S84L mutation in gyrA and the S80Y mutation in parC, the most commonly observed mutations in global phase 3 studies. The data suggest that delafloxacin could be a good option for the treatment of infections caused by S. aureus isolates causing ABSSSI, including MRSA isolates, where high rates of ciprofloxacin and levofloxacin nonsusceptibility are observed. (The phase 3 studies described in this paper have been registered at ClinicalTrials.gov under identifiers NCT01984684 and NCT01811732.).