Carbapenems are parenteral bactericidal beta-lactam antibiotics Overview of Antibacterial Drugs Antibacterial drugs are derived from bacteria or molds or are synthesized de novo. Technically, “antibiotic” refers only to antimicrobials derived from bacteria or molds but is often (including... read more that have an extremely broad spectrum. They are active against
Most Enterobacteriaceae (including those that produce AmpC beta-lactamase and extended-spectrum beta-lactamase [ESBL], although Proteus mirabilis Proteeae Infections The Proteeae are normal fecal flora that often cause infection in patients whose normal flora have been disturbed by antibiotic therapy. The Proteeae constitute at least 3 genera of gram-negative... read more tends to have a higher imipenem minimum inhibitory concentration [MIC])
Methicillin-sensitive staphylococci Staphylococcal Infections Staphylococci are gram-positive aerobic organisms. Staphylococcus aureus is the most pathogenic; it typically causes skin infections and sometimes pneumonia, endocarditis, and osteomyelitis... read more and streptococci Streptococcal Infections Streptococci are gram-positive aerobic organisms that cause many disorders, including pharyngitis, pneumonia, wound and skin infections, sepsis, and endocarditis. Symptoms vary with the organ... read more , including Streptococcus pneumoniae (except possibly strains with reduced penicillin sensitivity)
Most Enterococcus faecalis Enterococcal Infections Enterococci are gram-positive, facultative anaerobic organisms. Enterococcus faecalis and E. faecium cause a variety of infections, including endocarditis, urinary tract infections, prostatitis... read more and many Pseudomonas aeruginosa Pseudomonas and Related Infections Pseudomonas aeruginosa and other members of this group of gram-negative bacilli are opportunistic pathogens that frequently cause hospital-acquired infections, particularly in ventilator patients... read more strains, including those resistant to broad-spectrum penicillins and cephalosporins, are susceptible to imipenem, meropenem, and doripenem but are resistant to ertapenem. However, meropenem and doripenem are less active against E. faecalis than imipenem. Carbapenems are active synergistically with aminoglycosides against P. aeruginosa. However, E. faecium, Stenotrophomonas maltophilia, and methicillin-resistant staphylococci are resistant.
Many multidrug-resistant hospital-acquired bacteria are sensitive only to carbapenems.
Imipenem and meropenem penetrate into cerebrospinal fluid when meninges are inflamed. Meropenem is used for gram-negative bacillary meningitis Acute Bacterial Meningitis Acute bacterial meningitis is rapidly progressive bacterial infection of the meninges and subarachnoid space. Findings typically include headache, fever, and nuchal rigidity. Diagnosis is by... read more ; imipenem is not used in meningitis because it may cause seizures. Most seizures occur in patients who have central nervous system abnormalities or renal insufficiency and who are given inappropriately high doses.
Doripenem has a black box warning stating that when used to treat patients with ventilator-associated bacterial pneumonia Hospital-Acquired Pneumonia Hospital-acquired pneumonia (HAP) develops at least 48 hours after hospital admission. The most common pathogens are gram-negative bacilli and Staphylococcus aureus; antibiotic-resistant organisms... read more , it has an increased risk of death compared with imipenem. Also, clinical response rates were lower with doripenem. Doripenem is not approved for the treatment of pneumonia.
Expanded use of carbapenems has resulted in some carbapenem resistance. This development is concerning because carbapenems are often the last resort for treating multidrug-resistant gram-negative organisms, particularly those that produce AmpC and extended-spectrum beta-lactamases, which destroy most beta-lactams except for carbapenems.
The most common mechanism of carbapenem resistance is
However, carbapenem resistance may also be mediated by the loss or alteration of porin channels, the expression of efflux pumps, or penicillin-binding protein (PBP) modification.
Many carbapenemases are encoded on plasmids, facilitating the spread of resistance genes among organisms of the same species or even different bacterial species. If carbapenemase-producing pathogens are identified in a patient, infection control precautions and enhanced environmental cleaning should be instituted to prevent further transmission.
The novel beta-lactamase inhibitors, avibactam, relebactam, and vaborbactam, can inhibit most carbapenemases but are ineffective against metallo-beta-lactamases (a type of carbapenemase that uses reactive zinc to destroy the carbapenem). The coformulation of avibactam with ceftazidime, vaborbactam with meropenem, or relebactam with imipenem increases activity against certain carbapenemase-producing pathogens.
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