Ribeiro Ághata Cardoso da Silva, Santos Fernanda Fernandes, Valiatti Tiago Barcelos, Lenzi Michael Henrique, Santos Ingrid Nayara Marcelino, Neves Raíssa Fidelis Baêta, Moses Ikechukwu Benjamin, Meneses Jaqueline Pilon de, Di Sessa Renata Gebara de Grande, Salles Mauro José, Gales Ana Cristina
Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicinan (EPM), Departamento de Medicina Interna, Divisão de Doenças Infecciosas, Laboratório Alerta, São Paulo, SP, Brazil.
Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicinan (EPM), Departamento de Medicina Interna, Divisão de Doenças Infecciosas, Laboratório Alerta, São Paulo, SP, Brazil.
Braz J Infect Dis. 2024 Nov-Dec;28(6):103867. doi: 10.1016/j.bjid.2024.103867. Epub 2024 Sep 18.
The aim of this study was to compare the in vitro activity of delafloxacin with other fluoroquinolones against bacterial pathogens recovered from inpatients with osteomyelitis, Acute Bacterial Skin and Skin-Structure Infections (ABSSSI). In total, 100 bacterial isolates (58 % Gram-negative and 42 % Gram-positive) recovered from inpatients between January and April 2021, were reidentified at species level by MALDI-TOF MS. Antimicrobial susceptibility testing was conducted using the broth microdilution method and the detection of biofilm formation was assessed through the microtiter plate assay. The screening for mecA was carried out by PCR, while mutations in the Quinolone Resistance Determining Regions (QRDR), specifically gyrA and parC, were analyzed using PCR followed by Sanger sequencing. Results showed that delafloxacin exhibited greater in vitro potency (at least 64-times) than the other tested fluoroquinolones (levofloxacin and ciprofloxacin) when evaluating Staphylococcus aureus (MIC ≤0.008 mg/L) and coagulase-negative Staphylococcus (MIC 0.06 mg/L). Furthermore, delafloxacin (MIC 0.25 mg/L) was at least 4 times more potent than other tested fluoroquinolones (MIC 1 mg/L) against P. aeruginosa. No difference in delafloxacin activity (MIC 0.03 mg/L) was observed against Enterobacter cloacae when compared with ciprofloxacin (MIC 0.03 mg/L). Despite presenting low activity against K. pneumoniae isolates (22.2 %), delafloxacin exhibited twice the activity compared to both levofloxacin and ciprofloxacin. Delafloxacin also exhibited a strong activity (71.4 %‒85.7 %.) against biofilm producing bacterial pathogens tested in this study. Interestingly, 82.14 % of the staphylococci tested in this study harbored mecA gene. In addition, the gyrA and parC genes in fluoroquinolone-resistant Gram-negative isolates displayed different mutations (substitutions and deletions). Herein, we showed that delafloxacin was the most active fluoroquinolone against staphylococci (including MRSA) and P. aeruginosa when compared to other fluoroquinolones such as ciprofloxacin and levofloxacin.
本研究的目的是比较德拉氟沙星与其他氟喹诺酮类药物对从骨髓炎、急性细菌性皮肤及皮肤结构感染（ABSSSI）住院患者中分离出的细菌病原体的体外活性。2021年1月至4月期间从住院患者中分离出的100株细菌（58%为革兰氏阴性菌，42%为革兰氏阳性菌），通过基质辅助激光解吸电离飞行时间质谱（MALDI-TOF MS）在种水平上进行重新鉴定。采用肉汤微量稀释法进行药敏试验，并通过微量滴定板法评估生物膜形成的检测。通过聚合酶链反应（PCR）进行mecA筛查，而喹诺酮耐药决定区（QRDR），特别是gyrA和parC中的突变，采用PCR后进行桑格测序分析。结果表明，在评估金黄色葡萄球菌（MIC≤0.008 mg/L）和凝固酶阴性葡萄球菌（MIC 0.06 mg/L）时，德拉氟沙星的体外效力比其他受试氟喹诺酮类药物（左氧氟沙星和环丙沙星）高（至少64倍）。此外，德拉氟沙星（MIC 0.25 mg/L）对铜绿假单胞菌的效力比其他受试氟喹诺酮类药物（MIC 1 mg/L）至少高4倍。与环丙沙星（MIC 0.03 mg/L）相比，未观察到德拉氟沙星对阴沟肠杆菌的活性（MIC 0.03 mg/L）有差异。尽管对肺炎克雷伯菌分离株的活性较低（22.2%），但德拉氟沙星的活性是左氧氟沙星和环丙沙星的两倍。德拉氟沙星对本研究中测试的产生生物膜的细菌病原体也表现出较强的活性（71.4%‒85.7%）。有趣的是，本研究中测试的葡萄球菌中有82.14%携带mecA基因。此外，耐氟喹诺酮革兰氏阴性菌分离株中的gyrA和parC基因表现出不同的突变（替换和缺失）。在此，我们表明，与环丙沙星和左氧氟沙星等其他氟喹诺酮类药物相比，德拉氟沙星是对葡萄球菌（包括耐甲氧西林金黄色葡萄球菌）和铜绿假单胞菌活性最高的氟喹诺酮类药物。
