Carbapenems for Cystic Fibrosis

Carbapenems, a class of beta-lactam, broad-spectrum antibiotics that include imipenem and meropenem for the treatment of Pseudomonas aeruginosa or Staphylococcus aureus infections in people with cystic fibrosis (CF). Carbapenems inhibit synthesis of the bacterial cell wall by attaching to the penicillin binding proteins and interfering with the formation of the cell wall.

History of carbapenems

As carbapenems possess a broad spectrum of activity against gram-positive and gram-negative bacteria, they are used as last-line agents when other antibiotics don’t work or may be resistant bacteria.

These antibiotics were discovered in the 1970s after bacterial beta-lactamases appeared and threatened the use of penicillin. The first beta-lactamase inhibitors, olivanic acids, had a “carbapenem backbone,” but were chemically unstable. Later, thienamycin was produced by Streptomyces cattleya and was the first carbapenem that served as a model compound for all carbapenems.

Enthusiasm for this compound grew rapidly, since it showed inhibitory microbiological activity against gram-negative bacteria, including P. aeruginosa, as well as anaerobes and gram-positive bacteria, such as methicillin- or oxacillin-susceptible Staphylococcus aureus and streptococci.

Unfortunately, thienamycin was unstable in aqueous solutions and reactive to other compounds, so the search for stable analogous derivatives increased, with imipenem being the first to be developed in 1985. Later, meropenem and others were developed.

How carbapenems work

Carbapenems halt synthesis of the bacterial wall by attaching to the penicillin binding proteins, inhibiting the key enzyme in bacterial wall synthesis. They also appear to activate one or more cell wall enzymes that lead to the destruction of the bacteria.

Other details

Imipenem and meropenem are injections that come as a powder to be mixed with liquid to be injected intravenously over a period of 20 minutes to one hour every six or eight hours, or into the muscles of the buttocks or thigh every 12 hours.

Common side effects include pain where the medicine was injected, dizziness and drowsiness, nausea, vomiting and diarrhea, itching, rash or a swollen tongue.

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