Practical information on using beta lactams: carbapenems
Carbapenems are broad-spectrum antibacterial drugs with activity against many strains of gram-negative bacteria that are resistant to other drug classes. However, widespread use of carbapenems is linked to an increasing prevalence of infections caused by methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), multidrug-resistant gram-negative bacteria and Clostridioides difficile (formerly known as Clostridium difficile). Furthermore, carbapenem resistance is emerging worldwide, often due to the production of various carbapenemase enzymes, which also confer resistance to other antibiotics. Therefore, the use of carbapenems should be reserved.
Imipenem and meropenem have broad activity against Enterobacterales (enteric gram-negative bacilli), including isolates that produce extended-spectrum beta-lactamase enzymes (ESBLs), and Pseudomonas aeruginosa; this activity is comparable to that of aminoglycosides. They also have excellent activity against anaerobic gram-negative bacteria (including Bacteroides fragilis), and many gram-positive bacteria (including Nocardia species).
Imipenem is formulated in combination with the renal dipeptidase enzyme inhibitor, cilastatin, to prevent inactivation.
High-dose meropenem achieves adequate concentrations in the cerebrospinal fluid and has a lower incidence of seizures than imipenem.
In these guidelines, a higher initial dosage of meropenem, is recommended for critically ill patients with suspected or confirmed infection with P. aeruginosa, Burkholderia pseudomallei or Acinetobacter baumannii. Adequate drug exposure is less likely to be achieved with standard dosing in this situation because these pathogens may have a high minimum inhibitory concentration (MIC) and these patients may have augmented renal clearance1Hong, 2023.
In these guidelines, meropenem administered by an extended infusion is recommended for patients who have septic shock or who require intensive care support to ensure adequate drug exposure. A recent study2 observed a reduction in mortality with the use of meropenem administered as a loading dose followed by a continuous infusion (given as 3 consecutive 8-hourly infusions) when compared with dosing meropenem intermittentlyAbdul-Aziz, 2024. It is the consensus opinion of the Antibiotic expert group that although high-quality clinical evidence to support this practice in children is lacking, this recommendation is still relevant to children.
Ertapenem has a similar spectrum of activity to the other carbapenems, but has poor activity against P. aeruginosa, E. faecalis and Acinetobacter species.
Carbapenems are inactive against MRSA, VRE, Enterococcus faecium, Mycoplasma species, Chlamydia species and Stenotrophomonas maltophilia.