Activity of Cefiderocol Alone and in Combination with Levofloxacin, Minocycline, Polymyxin B, or Trimethoprim-Sulfamethoxazole against Multidrug-Resistant Stenotrophomonas maltophilia
Activity of Cefiderocol Alone and in Combination with Levofloxacin, Minocycline, Polymyxin B, or Trimethoprim-Sulfamethoxazole against Multidrug-Resistant Stenotrophomonas maltophilia
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DOI：
10.1128/aac.00559-20
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发表时间：
2020-09-01
影响因子：
4.9
通讯作者：
Wenzler, E.
中科院分区：
文献类型：
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作者：
Biagi, M.;Vialichka, A.;Wenzler, E.
L1金属β -内酰胺酶和L2丝氨酸活性位点β -内酰胺酶的产生排除了β -内酰胺用于治疗嗜麦芽寡养单胞菌感染。临床前数据表明，头孢地罗是第一个被批准的抗嗜麦芽葡萄球菌活性可靠的β -内酰胺类药物，但目前一线药物耐药菌株的数据有限，而且没有研究评估头孢地罗的联合用药。本研究的目的是评估和比较头孢地罗单独使用和与左氧氟沙星、米诺环素、多粘菌素B或甲氧苄啶-磺胺甲恶唑（TMP-SMZ）联合使用对高度耐药的临床嗜麦芽葡萄球菌分离株的体外活性。为此，对37株对左氧氟沙星和/或TMP-SMZ不敏感的嗜麦芽葡萄球菌进行了头孢地罗、头孢他啶、左氧氟沙星、米诺环素、多粘菌素B和TMP-SMZ的mic测定。用头孢地罗单用和联合比较物对9株具有头孢地罗不同mic的菌株进行时间杀伤实验。敏感率超过40%的药物只有头孢地罗（100%）和米诺环素（97.3%）。Cefiderocol的MIC50和MIC90值最低，分别为0.125和0.5 mg/l。在时间杀伤实验中，头孢地罗与左氧氟沙星、米诺环素、多粘菌素B或TMP-SMZ联用分别对4/9（44.4%）、6/9（66.7%）、5/9（55.5%）和6/9（66.7%）菌株有协同作用。这些数据表明，头孢地罗在体外对嗜麦芽葡萄球菌显示出强大的活性，包括对目前首选药物耐药的菌株。未来对头孢地罗单用和联用的动态和体内研究有必要进一步确定头孢地罗的协同能力及其在嗜麦芽葡萄球菌感染治疗中的地位。
The production of an L1 metallo-beta-lactamase and an L2 serine active-site beta-lactamase precludes the use of beta-lactams for the treatment of Stenotrophomonas maltophilia infections. Preclinical data suggest that cefiderocol is the first approved beta-lactam with reliable activity against S. maltophilia, but data on strains resistant to current first-line agents are limited, and no studies have assessed cefiderocol-based combinations. The objective of this study was to evaluate and compare the in vitro activity of cefiderocol alone and in combination with levofloxacin, minocycline, polymyxin B, or trimethoprim-sulfamethoxazole (TMP-SMZ) against a collection of highly resistant clinical S. maltophilia isolates. For this purpose, the MICs of cefiderocol, ceftazidime, levofloxacin, minocycline, polymyxin B, and TMP-SMZ for 37 S. maltophilia isolates not susceptible to levofloxacin and/or TMP-SMZ were determined. Nine strains with various cefiderocol MICs were then tested in time-kill experiments with cefiderocol alone and in combination with comparators. The only agents for which susceptibility rates exceeded 40% were cefiderocol (100%) and minocycline (97.3%). Cefiderocol displayed the lowest MIC50 and MIC90 values (0.125 and 0.5 mg/liter, respectively). In time-kill experiments, synergy was observed when cefiderocol was combined with levofloxacin, minocycline, polymyxin B, or TMP-SMZ against 4/9 (44.4%), 6/9 (66.7%), 5/9 (55.5%), and 6/9 (66.7%) isolates, respectively. These data suggest that cefiderocol displays potent in vitro activity against S. maltophilia, including strains resistant to currently preferred agents. Future dynamic and in vivo studies of cefiderocol alone and in combination are warranted to further define cefiderocol's synergistic capabilities and its place in therapy for S. maltophilia infections.