Noviello Silvana, Ianniello Filomena, Leone Sebastiano, Esposito Silvano
Dottorato di Ricerca in Scienze Farmacologiche e Fisiopatologia Respiratoria XVII degrees ciclo, Seconda Università degli Studi di Napoli, Napoli.
J Antimicrob Chemother. 2003 Nov;52(5):869-72. doi: 10.1093/jac/dkg429. Epub 2003 Sep 30.
Garenoxacin is a novel des-F(6)quinolone that has shown excellent antimicrobial activity against a wide range of clinically important microorganisms. In this study, its activity was examined, in comparison with that of other antimicrobial agents, by susceptibility and time-kill testing against Staphylococcus aureus, Streptococcus pyogenes and respiratory pathogens.
Overall, 200 bacterial strains were tested. The antimicrobial activity of garenoxacin was compared with that of ciprofloxacin, levofloxacin, moxifloxacin, amoxicillin, co-amoxiclav, cefuroxime, cefotaxime, ceftriaxone, imipenem, erythromycin and clarithromycin. In addition, the bactericidal activity of garenoxacin, moxifloxacin, levofloxacin and ciprofloxacin was evaluated by time-kill analysis against four strains each of staphylococci [two methicillin-susceptible (MSSA) and two methicillin-resistant (MRSA)], pneumococci (two penicillin-susceptible and two penicillin-resistant) and Streptococcus pyogenes (two erythromycin-susceptible and two erythromycin-resistant). Antibiotics were tested at concentrations 1-8 x MIC.
MIC90 values of garenoxacin for the MSSA and MRSA strains were 0.03 and 2 mg/L, respectively. Among all the quinolones tested, garenoxacin yielded the lowest MIC values against all pneumococci (MIC90 0.12 mg/L) irrespective of macrolide resistance; the rank order of activity was garenoxacin> moxifloxacin>levofloxacin>ciprofloxacin. Excellent activity was shown also against Haemophilus influenzae (MIC90 <or= 0.03 mg/L) and Moraxella catarrhalis (MIC90 <or= 0.03 mg/L). Ninety percent of S. pyogenes were inhibited at garenoxacin concentrations equal to 0.25 mg/L, its activity not being influenced by macrolide susceptibility. Garenoxacin was rapidly bactericidal against staphylococci, producing a >or= 3 log10 decrease in viable counts (cfu/mL) within 3 h at 4 x MIC, whereas a moderate, slower killing rate was observed versus streptococci.
This investigational des-F(6)quinolone represents a promising alternative for the treatment of respiratory tract infections.
加替沙星是一种新型的去氟（6）喹诺酮类药物，已显示出对多种临床上重要的微生物具有优异的抗菌活性。在本研究中，通过对金黄色葡萄球菌、化脓性链球菌和呼吸道病原体进行药敏试验和时间杀菌试验，将其活性与其他抗菌药物进行了比较。
总共测试了200株细菌菌株。将加替沙星的抗菌活性与环丙沙星、左氧氟沙星、莫西沙星、阿莫西林、阿莫西林克拉维酸钾、头孢呋辛、头孢噻肟、头孢曲松、亚胺培南、红霉素和克拉霉素进行了比较。此外，通过对葡萄球菌（两株甲氧西林敏感菌和两株甲氧西林耐药菌）、肺炎球菌（两株青霉素敏感菌和两株青霉素耐药菌）和化脓性链球菌（两株红霉素敏感菌和两株红霉素耐药菌）各四株菌株进行时间杀菌分析，评估了加替沙星、莫西沙星、左氧氟沙星和环丙沙星的杀菌活性。抗生素在1 - 8倍MIC浓度下进行测试。
加替沙星对甲氧西林敏感金黄色葡萄球菌和甲氧西林耐药金黄色葡萄球菌菌株的MIC90值分别为0.03和2mg/L。在所有测试的喹诺酮类药物中，无论大环内酯类耐药情况如何，加替沙星对所有肺炎球菌的MIC值最低（MIC90为0.12mg/L）；活性顺序为加替沙星>莫西沙星>左氧氟沙星>环丙沙星。对流感嗜血杆菌（MIC90≤0.03mg/L）和卡他莫拉菌（MIC90≤0.03mg/L）也显示出优异的活性。90%的化脓性链球菌在加替沙星浓度等于0.25mg/L时受到抑制，其活性不受大环内酯类敏感性的影响。加替沙星对葡萄球菌具有快速杀菌作用，在4倍MIC浓度下3小时内活菌数（cfu/mL）减少≥3个对数级，但对链球菌的杀菌速度适中且较慢。
这种研究性的去氟（6）喹诺酮类药物是治疗呼吸道感染的一种有前景的替代药物。
