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Beta-lactam antibiotics (penicillins, cephalosporins, carbapenems, aztreonam) are among the most commonly prescribed drugs in hospitalized patients with sepsis. These antibiotics can inhibit the cell wall mucopeptide synthase, namely penicillin-binding proteins (PBPs), thereby hindering the synthesis of cell wall mucopeptides, causing the bacterial cell wall to be defective and the bacteria to expand and lyse. The most important mechanism of resistance of Gram-negative bacteria and a few Gram-positive bacteria to β-lactam antibiotics is the production of various β-lactamases. Beta-lactam antibiotics are an important choice for clinical treatment of β-lactamase-producing bacterial infections.
Beta-lactamase production
In most hospitalized patients, the spectrum of beta-lactamase production ranges from minimal to moderate induction of resistance. In some cases, Enterobacteriaceae, such as Klebsiella pneumoniae and Escherichia coli, produce extended-spectrum beta-lactamases (ESLBLs) that generally require carbapenem therapy. Carbapenemases (eg, Klebsiella pneumoniae carbapenemase [KPC] or New Delhi metallo-beta-lactamase [NDM]) may also be produced in rare cases, and are resistant to carbapenems medicine. Carbapenemase-producing bacteria need to be treated with cefdil or a combination of beta-lactamase inhibitors (eg, meropenem/faborbactam).
Cefoperazone/sulbactam and piperacillin/tazobactam are the main drugs for the treatment of ESBLs-producing Enterobacteriaceae, which can be used for mild cases caused by ESBLs-producing Enterobacteriaceae. Treatment of moderate infections (including urinary tract infections, liver abscesses, biliary tract infections, peritonitis, hospital-acquired pneumonia (HAP), etc.).
Cephalosporins
Cephalosporins are divided into five generations based on their spectrum of antimicrobial activity, and the newer iron-containing cephalosporins (ceftil) are classified as other cephalosporins. First-generation cephalosporins (cefazolin, cephalexin) are commonly used to treat cellulitis, urinary tract infections (UTIs), and methicillin-susceptible Staphylococcus aureus (MSSA); second-generation cephalosporins (cephalosporins) Cefaclor) can cover anaerobic bacteria and can be used to treat pelvic inflammatory disease (PID); third-generation cephalosporins (ceftriaxone, cefotaxime) are less active against staphylococci than first-generation cephalosporins Bacteriocin, but with higher activity against pneumococcal infection. Clinical use of third-generation cephalosporins for the treatment of cephalosporinase-producing (AmpC) bacterial infections should be avoided because drug resistance develops rapidly during treatment. A fourth-generation cephalosporin (cefepime) is more active against Gram-negative bacteria that produce the AmpC enzyme β-lactamase. Notably, the neurotoxicity caused by cefepime occurred mainly in patients with renal insufficiency, and clinically manifested as altered mental status, nonconvulsive status epilepticus, and forced-clonic seizures. Therefore, patients with renal insufficiency need to adjust the dose appropriately when using cefepime. The fifth-generation cephalosporin ceftaroline is active against methicillin-resistant Staphylococcus aureus (MRSA) but inactive against Pseudomonas; ceftoloza/tazobactam is active against Pseudomonas but not against MRSA active. Cefepime is active against MRSA and Pseudomonas.
Cefdil is an iron-containing cephalosporin that inhibits most Gram-negative bacteria, including ESBL, carbapenemase-producing Monomonas, Acinetobacter, Stenotrophomonas and Burkholderia.
Carbapenems
Carbapenems (imipenem/cilastatin, meropenem, doripenem, and ertapenem) are effective against beta-lactamase-producing gram-negative bacteria ( including ESBL) and anaerobic bacteria have broad activity. It should be noted that the resistance of Enterobacteriaceae to carbapenems has been increasing worldwide; the use of these drugs in patients with renal insufficiency requires dose adjustment; the use of imipenem and the central nervous system Toxicity is related and should not be used in the treatment of meningitis. Ertapenem has a narrower spectrum of antimicrobial activity (ineffective against Pseudomonas, Acinetobacter, Enterococcus, and Listeria) and can be used to treat most ESBL infections.
Single amide rings
Aztreonam is a new type of β-lactam antibiotic of monoamide ring class, which has little activity against Gram-positive bacteria or anaerobic bacteria. Empirical use of aztreonam is discouraged in septic patients allergic to penicillin. Since aztreonam is mainly excreted by the kidneys, the dosage should be reduced in patients with renal insufficiency.
References:
1. Reddy P (August 30, 2022) Clinical Approach to Nosocomial Bacterial Sepsis. Cureus 14(8): e28601. doi:10.7759/cureus.28601.
5. Expert consensus on the clinical application of β-lactam antibiotics/β-lactamase inhibitor compound preparations. Expert group for compiling. β-lactam antibiotics/β-lactamase inhibition Expert consensus on clinical application of compound preparations (2020 edition)[J]. Chinese Medical Journal, 2020, 100(10):738-747.