苯扎氯铵增强了加替沙星的抗菌活性，并降低了其选择氟喹诺酮耐药菌株的倾向。

Benzalkonium chloride enhances antibacterial activity of gatifloxacin and reduces its propensity to select for fluoroquinolone-resistant strains.

作者信息

Hesje Christine K, Borsos Shantelle D, Blondeau Joseph M

机构信息

Department of Clinical Microbiology, University of Saskatchewan, Royal University Hospital, 103 Hospital Drive, Saskatoon, Saskatchewan, Canada.

出版信息

J Ocul Pharmacol Ther. 2009 Aug;25(4):329-34. doi: 10.1089/jop.2009.0031.

DOI:10.1089/jop.2009.0031

PMID:19650708

Abstract

PURPOSE

To assess the impact of benzalkonium chloride (BAK) on the minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) of gatifloxacin against Gram-positive pathogens in comparison to gatifloxacin and moxifloxacin alone, moxifloxacin plus BAK, and/or levofloxacin.

METHODS

The MIC was measured following incubation of 10(5) colony-forming units (CFU)/mL of coagulase-negative staphylococci (CNS; n = 20), methicillin-susceptible Staphylococcus aureus (MSSA; n = 20), and methicillin-resistant S. aureus (MRSA; n = 20) with gatifloxacin, levofloxacin, or moxifloxacin. When present, BAK was added from 3.125 microg/mL to 6.25 microg/mL. The MPC was measured following incubation of 10(10) CFU/mL of MRSA (n = 9) and a commercially available MSSA strain with gatifloxacin or moxifloxacin in the absence and presence of BAK at concentrations from 7 microg/mL to 10 microg/mL.

RESULTS

CNS was more susceptible to gatifloxacin (MIC(90) = 2 microg/mL) than levofloxacin (MIC(90) = 8 microg/mL) or moxifloxacin (MIC(90) = 4 microg/mL). MSSA was more susceptible to moxifloxacin (MIC(90) = 1 microg/mL) than gatifloxacin (MIC(90) = 4 microg/mL) or levofloxacin (MIC(90) = 4 microg/mL). MRSA were resistant to gatifloxacin, levofloxacin, and moxifloxacin. In the presence of BAK, however, the MIC(90) of gatifloxacin and moxifloxacin against CNS, MSSA, and MRSA was < or =0.008 microg/mL. Gatifloxacin and moxifloxacin had similar MPCs against MRSA (> or =4 microg/mL). In the presence of BAK, the MPC of gatifloxacin and moxifloxacin against MRSA ranged from < or =0.004 microg/mL to 0.125 microg/mL.

CONCLUSIONS

BAK substantially lowered the MIC and MPC of gatifloxacin and moxifloxacin against Gram-positive staphylococci compared to gatifloxacin alone, moxifloxacin alone, and/or levofloxacin. These findings suggest that the presence of BAK in the ophthalmic formulation of gatifloxacin (Zymar) may serve to enhance the potency of gatifloxacin and decrease its propensity to select for fluoroquinolone-resistant S. aureus strains.

摘要

目的

与单用加替沙星、莫西沙星、莫西沙星加苯扎氯铵（BAK）和/或左氧氟沙星相比，评估苯扎氯铵（BAK）对加替沙星针对革兰氏阳性病原体的最低抑菌浓度（MIC）和突变预防浓度（MPC）的影响。

方法

将10⁵菌落形成单位（CFU）/mL的凝固酶阴性葡萄球菌（CNS；n = 20）、甲氧西林敏感金黄色葡萄球菌（MSSA；n = 20）和甲氧西林耐药金黄色葡萄球菌（MRSA；n = 20）分别与加替沙星、左氧氟沙星或莫西沙星孵育后测量MIC。若存在BAK，则从3.125μg/mL至6.25μg/mL添加。将10¹⁰CFU/mL的MRSA（n = 9）和一种市售MSSA菌株分别与加替沙星或莫西沙星在有无浓度为7μg/mL至10μg/mL的BAK存在下孵育后测量MPC。

结果

CNS对加替沙星（MIC₉₀ = 2μg/mL）比对左氧氟沙星（MIC₉₀ = 8μg/mL）或莫西沙星（MIC₉₀ = 4μg/mL）更敏感。MSSA对莫西沙星（MIC₉₀ = 1μg/mL）比对加替沙星（MIC₉₀ = 4μg/mL）或左氧氟沙星（MIC₉₀ = 4μg/mL）更敏感。MRSA对加替沙星、左氧氟沙星和莫西沙星耐药。然而，在BAK存在下，加替沙星和莫西沙星针对CNS、MSSA和MRSA的MIC₉₀≤0.008μg/mL。加替沙星和莫西沙星针对MRSA的MPC相似（≥4μg/mL）。在BAK存在下，加替沙星和莫西沙星针对MRSA的MPC范围为≤0.004μg/mL至0.125μg/mL。