Abstract
Infections in the ICU are often caused by Gram-negative bacteria. When these microorganisms are resistant to third-generation cephalosporines (due to extended-spectrum (ESBL) or AmpC beta-lactamases) or to carbapenems (for example carbapenem producing Enterobacteriales (CPE)), the treatment options become limited. In the last six years, fortunately, there have been new antibiotics approved by the U.S. Food and Drug Administration (FDA) with predominant activities against Gram-negative bacteria. We aimed to review these antibiotics: plazomicin, eravacycline, temocillin, cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, meropenem/vaborbactam, and imipenem/relebactam. Temocillin is an antibiotic that was only approved in Belgium and the UK several decades ago. We reviewed the in vitro activities of these new antibiotics, especially against ESBL and CPE microorganisms, potential side effects, and clinical studies in complicated urinary tract infections (cUTI), intra-abdominal infections (cIAI), and hospital-acquired pneumonia/ventilator-associatedpneumonia (HAP/VAP). All of these new antibiotics are active against ESBL, and almost all of them are active against CPE caused by KPC beta-lactamase, but only some of them are active against CPE due to MBL or OXA beta-lactamases. At present, all of these new antibiotics are approved by the U.S. Food and Drug Administration for cUTI (except eravacycline) and most of them for cIAI (eravacycline, ceftazidime/avibactam, ceftolozane/tazobactam, and imipenem/relebactam) and for HAP or VAP (cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, and imipenem/relebactam).
Highlights
Two-thirds of the infections in intensive care units (ICUs) are caused by Gram-negative bacteria [1], and resistance of these bacteria to certain antibiotics poses a significant problem.Several multidrug resistant, Gram-negative microorganisms such as carbapenem-resistantAcinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacterales are duly included in the recent WHO list of high-priority pathogens [2].Beta-lactam antibiotics—penicillins, cephalosporins, carbapenems, and to a lesser extent monobactams—are often the antibiotics of choice in the ICU, but they can be inactivated by beta-lactamase enzymes
Plazomicin is active against > 95% of Enterobacterales isolates, but only in 30 to 40% of Acinetobacter spp. or P. aeruginosa isolates originated from North America and Europe [12,13]
The eight antibiotics reviewed here add to the armamentarium of antibiotics against carbapenem-resistant Gram-negative microorganisms
Summary
Two-thirds of the infections in intensive care units (ICUs) are caused by Gram-negative bacteria [1], and resistance of these bacteria to certain antibiotics poses a significant problem.Several multidrug resistant, Gram-negative microorganisms such as carbapenem-resistantAcinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacterales are duly included in the recent WHO list of high-priority pathogens [2].Beta-lactam antibiotics—penicillins, cephalosporins, carbapenems, and to a lesser extent monobactams—are often the antibiotics of choice in the ICU, but they can be inactivated by beta-lactamase enzymes (the most common and important mechanism of resistance inGram-negative bacteria). Two-thirds of the infections in intensive care units (ICUs) are caused by Gram-negative bacteria [1], and resistance of these bacteria to certain antibiotics poses a significant problem. Beta-lactam antibiotics—penicillins, cephalosporins, carbapenems, and to a lesser extent monobactams—are often the antibiotics of choice in the ICU, but they can be inactivated by beta-lactamase enzymes These beta-lactamases can be classified into four molecular classes:. Among the beta-lactam antibiotics, carbapenems have the widest spectrum of activity and are often the antibiotic class of choice when Gram-negative bacteria produce 4.0/). The distinction is important from the infection-prevention point of view because carbapenemase production refers to resistance caused by beta-lactamase production encoded by transmissible genes, and not due to, for example, efflux pumps
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