Carbapenem
Similar to penicillins and cephalosporins, carbapenems are members of the beta-lactam antibiotics drug class, which kill bacteria by binding to penicillin-binding proteins, thus inhibiting bacterial cell wall synthesis.
[8] The carbapenems imipenem and meropenem are recommended by the American Thoracic Society and the Infectious Disease Society of America as one of several first-line therapy options for people with late-onset hospital-acquired or ventilator-associated pneumonia, especially when Pseudomonas, Acinetobacter, or extended spectrum beta-lactamase producing Enterobacteriaceae are suspected pathogens.
[10] A 2015 meta analysis concluded that the anti-pseudomonal penicillin-beta lactamase inhibitor combination piperacillin-tazobactam gives results equivalent to treatment with a carbapenem in patients with sepsis.
[11] In 2015, the National Institute for Health and Care Excellence recommended piperacillin-tazobactam as first line therapy for the treatment of bloodstream infections in neutropenic cancer patients.
[12] For bloodstream infections known to be due to extended spectrum beta-lactamase producing Enterobacteriaceace, carbapenems are superior to alternative treatments.
For empiric therapy (treatment of infections prior to identification of the responsible pathogen) they are often combined with a second drug having broader spectrum gram-positive activity.
Activity is maintained against most strains of E. coli and K. pneumoniae that are resistant to cephalosporins due to the production of extended spectrum beta-lactamases.
[36] The growing prevalence and difficulty of treating such multi-drug resistant Enterobacteriaceae has led to a renaissance of the use of antibiotics such as colistin, which was discovered in the 1950s but rarely used until recently due to unattractive levels of toxicity.
[38] Infections caused by the non-fermenting gram-negative bacteria Pseudomonas aeruginosa and Acinetobacter baumanni are most commonly encountered in hospitalized people.
The combination of inducible AmpC expression, poor membrane permeability, and efflux pumps make Pseudomonas resistant to most beta lactams.
The clinical efficacy of carbapenems in Pseudomonas infection arises in part because, while they are strong inducers of AmpC, they are poor substrates.
Group 2 carbapenems (imipenem, meropenem, and doripenem) are identified by their efficacy with respect to multiresistant gram-negative (MDRGN) bacteria such as Pseudomonas and Acinetobacter species.
Due to their expanded spectra, the desire to avoid generation of resistance and the fact that, in general, they have poor oral bioavailability, they are administered intravenously in hospital settings for more serious infections.
