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22 AntimicrobialsCarbapenems
Carbapenems have the broadest spectrum of any class of antimicrobial covering
gram-positive and gram-negative aerobic and anaerobic organisms. They do not
cover MRSA orE.faecalisand if used in isolation tend to generate Pseudomonas
resistance; however, they still prove useful when treating neutropenic fever or life-
threatening multi-resistant gram-negative sepsis.Imipenem
This bactericidal carbapenem has a very broad spectrum of activity including many
aerobic and anaerobic organisms especially Legionella,Streptococcus faecium(Strep.
Faecium), Yersinia and all types of Pseudomonas (exceptPseudomonas maltophilia
(P.maltophilia). It is resistant toβ-lactamase-producing organisms but is only mod-
erately effective againstClostridia perfringens(C. perfringens). In spite of imipenem’s
broad spectrum some strains of Citrobacter, Enterobacter and Serratia are resistant
(though not through the application ofβ-lactamase). Imipenem also induces
β-lactamase expression in Pseudomonas which, does not alter susceptibility to
imipenem but does impart substantial protection from otherβ-lactams.Kinetics
Imipenem is partially metabolized by renal dehydropeptidase-I and is presented
in combination withcilastatin(itself devoid of antimicrobial activity) to prevent
this metabolism. As a result plasma and urine concentration are increased. It is
mainly excreted unchanged in the urine and will accumulate in renal failure. When
imipenem/cilastatin is used in patients on CVVHDF the dose must be halved and
the dose-interval doubled to 12 hourly.Side effects
Imipenem is generally well tolerated but may cause vomiting and diarrhoea (includ-
ing pseudomembranous colitis), a positive Coombs’ test, allergic reactions and con-
vulsions. Imipenem has similar convulsive potential to benzylpenicillin but only
presents problems in people with pre-existing CNS disorders or cases of relative
overdose (renal insufficiency or concurrent probenecid use).Meropenem
Meropenem is similar to imipenem but is not metabolized by renal dehy-
dropeptidase-I and does not require combination with cilastatin. It is very resistant
toβ-lactamases although Pseudomonas has been reported to produce protective
enzymes. Meropenem is less active than imipenem against gram-positive organ-
isms but more active against gram-negative organisms that are moderately resistant
to imipenem, however, the clinical significance of this is negligible.