Carbapenems Imipenem Meropenem and Ertapenem

Imipenem, a thienamycin, is a beta-lactam antibiotic that is effective against a wide variety of aerobic and anaerobic gram-positive and gram-negative organisms including normally multiresistant species such as P. aeruginosa, Serratia spp., Enterobacter spp., Acinetobacter spp., and enterococcus (41,42). It also possesses excellent activity against beta-lactamase-producing Bacteroides. It has the lowest MIC for B. fragilis group and is also most effective against Entero-bacteriaceae. About 10-25% of Pseudomonas spp. have shown resistance. The pharmacokinetics of imipenem are characterized by poor absorption from the gastrointestinal tract, high plasma concentration after intravenous administration, a small degree of systemic metabolism, and renal excretion. In the kidney, imipenem is metabolized by breakage of the beta-lactamase bond in the proximal tubular cells. The result is low urinary excretion of active imipenem, which may

TABLE 3 Incidence of Bacteroides fragilis Group in Intra-abdominal Infection in Adults (185 isolates) and Children (100 isolates)

Incidence (%) Adults Children

Bacteroides fragilis Bacteroides thetaiotaomicron Bacteroides distasonis Bacteroides vulgatus Bacteroides ovatus Bacteroides uniformis

impair its ability to inhibit certain urinary pathogens. To overcome the problem of renal metabolism of imipenem, it is combined at a 1:1 ratio with an inhibitor of the renal dipeptidase, cilastatin. This increases the urinary excretion of the active drug and its half-life in the serum. This agent is an effective single agent for the therapy of mixed aerobic-anaerobic infections.

Meropenem is a carbapenem antibiotic that has a very broad-spectrum of activity against aerobic and anaerobic bacteria, similar to that of imipenem. Imipenem has more activity than meropenem against staphylococci and enterococci, but meropenem provides better coverage of gram-negative bacteria such as Pseudomonas, Enterobacter, Klebsiella, Providencia, Morganella, Aeromonas, Alcaligenes, Moraxella, Kingella, Actinobacillus, Pasteurella, and Haemophilus spp. (43,44). Meropenem has been effective in abdominal infections, meningitis in children and adults, community-acquired and nosocomial pneumonia, and neutropenic fever (45).

Ertapenem is a new 1-beta-methyl carbapenem, stable to dehydropeptidase. It has a broad antibacterial spectrum for penicillin-susceptible Streptococcus pneumoniae, Streptococcus pyogenes, methicillin-sensitive Staphylococcus aureus, Haemophilis influenzae, Moraxella catarrhalis, Escherichia coli, Citrobacter spp., Klebsiella spp., Serratia spp., Proteus spp., C. perfringens, Fuso-bacterium spp., Peptostreptococcus spp., and AGNB (46).

In comparison to other available carbapenems, ertapenem has a long half-life of 4.5 hours and is given in a single daily dose. It is less effective than other carbapenems for P. aeruginosa, Enterococcus spp., and Acinetobacter spp.

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