新型乙內醯胺類抗生素治療抗藥性革蘭氏陰性菌腦膜炎的療效

The Effectiveness of Newer Beta-Lactams for the Treatment of Antimicrobial-Resistant Gram-Negative Meningitis

治療對傳統乙內醯胺（β-lactam）與氟喹諾酮（fluoroquinolone）類抗生素皆具抗性的革蘭氏陰性菌感染，即難治型抗藥性（difficult-to-treat resistance, DTR）具有挑戰性，因為可用且仍具活性的抗生素選擇非常有限。當DTR革蘭氏陰性菌感染發生在中樞神經系統時，治療難度更高，主要因為藥物在腦脊髓液（CSF）與腦實質中的濃度可能不足。目前已有多種對DTR革蘭氏陰性菌具活性的較新乙內醯胺類藥物，包括ceftazidime-avibactam、aztreonam、ceftolozane-tazobactam、imipenem-cilastatin-relebactam、meropenem-vaborbactam、cefiderocol、sulbactamdurlobactam。本篇文章檢視影響抗生素治療細菌性腦膜炎療效的藥物因子與宿主因子，並回顧上述藥物在治療細菌性腦膜炎方面的臨床證據。

Managing DTR (difficult-to-treat resistance) gram-negative infections is challenging and even more complex when present in the central nervous system due to the difficulty in achieving sufficient concentrations of agents in the cerebrospinal fluid and brain parenchyma. Several newerβ-lactam agents with activity against DTR gram-negatives are available, including ceftazidime-avibactam, aztreonam, ceftolozanetazobactam, imipenem-cilastatin-relebactam, meropenem-vaborbactam, cefiderocol and sulbactam-durlobactam. This article reviews the drug factors, preclinical and clinical data of the aforementioned agents for the treatment of bacterial meningitis.