Mechanism of action Like all beta-lactam antibiotics,<unk>  is bactericidal. It inhibits cross-linking of the peptidoglycan layer of bacterial cell walls by blocking a type of enzymes called penicillin-binding proteins (PBPs). When a bacterial cell tries to synthesize new cell wall in order to grow and divide, the attempt fails, rendering the cell vulnerable to osmotic disruption. Additionally, the surplus of peptidoglycan precursors triggers autolytic enzymes of the bacterium, which disintegrate the existing wall. Bacteria attempting to grow and divide in the presence of<unk>  shed their cell walls, forming fragile spheroplasts. Susceptible bacteria Bacteria that are normally susceptible to<unk>  treatment (at least in Europe) include: * Gram-positive aerobes * Methicillin-susceptible Staphylococcus species (including Staphylococcus aureus) * Streptococcus agalactiae * Streptococcus pneumoniae (not established for penicillin-resistant strains) * Gram-negative aerobes * Escherichia coli * Haemophilus influenzae * Klebsiella pneumoniae * Moraxella catarrhalis * Proteus mirabilis * Anaerobes: * Clostridium species (excluding C. difficile) * Eubacterium species * Fusobacterium species * Peptostreptococcus species * Porphyromonas asaccharolytica * Prevotella species * The US Food and Drug Administration (FDA) label specifies activity against additional anaerobes: * Bacteroides distasonis * Bacteroides fragilis * Bacteroides ovatus * Bacteroides thetaiotaomicron * Bacteroides uniformis Resistance Bacteria that show no clinically relevant response to<unk>  include methicillin-resistant Staphylococcus species (including MRSA) as well as Acinetobacter, Aeromonas, Enterococcus, and Pseudomonas. Microorganisms can become resistant to<unk>  by producing carbapenemases, enzymes that inactivate the drug by opening the beta-lactam ring. Other mechanisms of resistance against carbapenems are development of efflux pumps that transport the antibiotics out of the bacterial cells, mutations of PBPs, and mutations of Gram-negative bacteria's porins which are necessary for carbapenems to enter the bacteria. Pharmacokinetics The main metabolite in humans, which is pharmacologically inactive The route of administration has only a slight effect on the drug's concentrations in the bloodstream: when given as an intramuscular injection, its bioavailability is 90% (as compared to the 100% availability when given directly into a vein), and its highest concentrations in the blood plasma are reached after about 2.3 hours. In the blood, 85–95% of<unk>  are bound to plasma proteins, mostly albumin. Plasma protein binding is higher for lower concentrations, and vice versa. The drug is only partially metabolized, with 94% circulating in form of the parent substance and 6% as metabolites. The main metabolite is the inactive hydrolysis product with the ring opened.<unk>  is mainly eliminated via the kidneys and urine (80%) and to a minor extent via the faeces (10%). Of the 80% found in the urine, 38% is excreted as the parent drug and 37% as the ring-opened metabolite. The biological half-life is about 3.5 hours in women, 4.2 hours in men and 2.5 hours in children up to 12 years of age. Comparison with other antibiotics Like all carbapenem antibiotics,<unk>  has a broader spectrum of activity than other beta-lactams like penicillins and cephalosporins. Similar to doripenem, meropenem and biapenem,<unk>  has slightly better activity against many Gram-negative bacteria than other carbapenems such as imipenem. In contrast to imipenem, doripenem and meropenem, it is not active against Enterococcus, Pseudomonas and Acinetobacter species. For diabetic foot infections,<unk>  as a single treatment or in combination with vancomycin has been found to be more effective and have fewer side effects than tigecycline, but in severe cases it is less effective than piperacillin/tazobactam. Regarding pharmacokinetics, imipenem, doripenem and meropenem have lower plasma protein bindings (up to 25%) and shorter half-lives (about one hour) than<unk> .
Ertapenem
Meropenem
Vancomycin
Resistin
Colistin
Imipenem
Linezolid
Ceftazidime