New β-Lactam-β-Lactamase Inhibitor Combinations

被引:345
作者
Yahav, Dafna [1 ,2 ]
Giske, G. Christian [3 ,4 ]
Gramatniece, Alise [3 ,4 ,5 ]
Abodakpi, Henrietta [6 ,8 ]
Tam, H. Vincent [6 ]
Leibovici, Leonard [2 ,7 ]
机构
[1] Beilinson Med Ctr, Infect Dis Unit, Rabin Med Ctr, Petah Tiqwa, Israel
[2] Tel Aviv Univ, Sackler Fac Med, Ramat Aviv, Israel
[3] Karolinska Inst, Dept Lab Med, Clin Microbiol, Stockholm, Sweden
[4] Karolinska Univ Hosp, Stockholm, Sweden
[5] Univ Latvia, Pauls Stradins Univ Hosp, Riga, Latvia
[6] Univ Houston, Coll Pharm, Dept Pharm Practice & Translat Res, Houston, TX 77030 USA
[7] Beilinson Med Ctr, Rabin Med Ctr, Med E, Petah Tiqwa, Israel
[8] US FDA, Off Clin Pharmacol, Silver Spring, MD USA
基金
美国国家卫生研究院;
关键词
beta-lactam; beta-lactamase inhibitor combinations; ceftazidime-avibactam; ceftolozane-tazobactam; meropenem-vaborbactam; imipenem-relebactam; IN-VITRO ACTIVITY; URINARY-TRACT-INFECTIONS; COMPLICATED INTRAABDOMINAL INFECTIONS; RESISTANT-PSEUDOMONAS-AERUGINOSA; ANTIMICROBIAL SURVEILLANCE PROGRAM; CEFTAZIDIME-AVIBACTAM ACTIVITY; GRAM-NEGATIVE BACILLI; CARE-ASSOCIATED INFECTIONS; US MEDICAL-CENTERS; CARBAPENEMASE-PRODUCING ENTEROBACTERIACEAE;
D O I
10.1128/CMR.00115-20
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The limited armamentarium against drug-resistant Gram-negative bacilli has led to the development of several novel beta-lactam-beta-lactamase inhibitor combinations (BLBLIs). In this review, we summarize their spectrum of in vitro activities, mechanisms of resistance, and pharmacokinetic-pharmacodynamic (PK-PD) characteristics. A summary of available clinical data is provided per drug. Four approved BLBLIs are discussed in detail. All are options for treating multidrug-resistant (MDR) Enterobacterales and Pseudomonas aeruginosa. Ceftazidime-avibactam is a potential drug for treating Enterobacterales producing extended-spectrum beta-lactamase (ESBL), Klebsiella pneumoniae carbapenemase (KPC), AmpC, and some class D beta-lactamases (OXA-48) in addition to carbapenem-resistant Pseudomonas aeruginosa. Ceftolozane-tazobactam is a treatment option mainly for carbapenem-resistant P. aeruginosa (non-carbapenemase producing), with some activity against ESBL-producing Enterobacterales. Meropenem-vaborbactam has emerged as treatment option for Enterobacterales producing ESBL, KPC, or AmpC, with similar activity as meropenem against P. aeruginosa. Imipenem-relebactam has documented activity against Enterobacterales producing ESBL, KPC, and AmpC, with the combination having some additional activity against P. aeruginosa relative to imipenem. None of these drugs present in vitro activity against Enterobacterales or P. aeruginosa producing metallo-beta-lactamase (MBL) or against carbapenemase-producing Acinetobacter baumannii. Clinical data regarding the use of these drugs to treat MDR bacteria are limited and rely mostly on nonrandomized studies. An overview on eight BLBLIs in development is also provided. These drugs provide various levels of in vitro coverage of carbapenem-resistant Enterobacterales, with several drugs presenting in vitro activity against MBLs (cefepime-zidebactam, aztreonam-avibactam, meropenem-nacubactam, and cefepime-taniborbactam). Among these drugs, some also present in vitro activity against carbapenem-resistant P. aeruginosa (cefepime-zidebactam and cefepime-taniborbactam) and A. baumannii (cefepime-zidebactam and sulbactam-durlobactam).
引用
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页码:1 / 61
页数:61
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