Saturday, August 27, 2011

Carbapenem Use for Pseudomonas treatment

Carbapenems consist of a series of β-lactam antibiotics with a unique nuclear structure that differs from the penam nucleus of the penicillins in having a carbon atom replacing sulphur at position 1 and in having an unsaturated bond between carbon atoms 2 and 3 in the 5-membered ring (fig. 1 and 2). The first two types of carbapenems (the olivanic acids and thienamycin) were discovered almost at the same time in the mid-1970s. The olivanic acids produced by Streptomyces olivaceus were discovered as part of the systematic screening program that also led to the discovery of the oxapenam, clavulanic acid (Brown et al., 1976). Thienamycin (fig. 3) was found in the course of a soil-screening program looking for antibiotics that inhibit cell wall synthesis (Kahan et al., 1983). It was produced by a previously unknown Streptomyces species which was named Str. cattleya because the pigment in its aerial mycelium resembled the colour of the cattleya orchid. Its structure was determined by Albers-Schonberg (Albers-Schonberg et al., 1978).
Not only is its nuclear structure remarkable but it also contains a unique hydroxyethyl side chain in the trans (α) configuration at position 6. The classic
penicillins (penams) and cephalosporins (cephems) have side chains in the cis (β) configuration at positions 6 and 7 relative to one another. Subsequent studies confirmed that it is trans configuration accounts for the unique resistance of thienamycin to a wide variety of β-lactamases. The side chain at position 2 (a basic alkylthio group) has been shown to be responsible for the striking activity of thienamycin against Ps. aeruginosa (Christensen, 1981). In addition to the olivanic acids and thienamycins, a number of naturally occurring carbapenems have been discovered in the past decade and a variety of semi-synthetic derivatives have been synthesized (Wise, 1986).
Need more Information Read Manual of Antibiotics: Method of Actions, Mechanisms of Resistan…

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