Antipseudomonal Penicillins

Carboxypenicillins

These in general have the same antibacterial spectrum as ampicillin (and are susceptible to P-lactamases), but have the additional capacity to destroy Pseudomonas aeruginosa and indole-positive Proteus spp.

Ticarcillin (t'/21 h) is presented in combination with clavulanic acid (as Timentin), so to provide greater activity against P-lactamase-producing organisms. It is given by i.m. or slow i.v. injection or by rapid i.v. infusion. Note that ticarcillin is presented as its disodium salt and each 1 g delivers about 5.4 mmol of sodium, which should be borne in mind when treating patients with impaired cardiac or renal function. Carboxypenicillins inactivate aminoglycosides if both drugs are administered in the same syringe or intravenous infusion system.

Ureidopenicillins

These are adapted from the ampicillin molecule, with a side-chain derived from urea. Their major advantages over the carboxypenicillins are higher efficacy against Pseudomonas aeruginosa and the fact that as monosodium salts they deliver on average about 2 mmol of sodium per gram of antimicrobial (see above) and are thus safer where sodium overload should particularly be avoided. They are degraded by many p-lactamases. Ureidopenicillins must be administered parenterally and are eliminated mainly in the urine. Accumulation in patients with poor renal function is less than with other penicillins as 25% is excreted in the bile. An unusual feature of their kinetics is that, as the dose is increased, the plasma concentration rises disproportionately, i.e. they exhibit saturation (zero-order) kinetics.

For pseudomonas septicaemia, a ureidopenicil-lin plus an aminoglycoside provides a synergistic effect but the co-administration in the same fluid results in inactivation of the aminoglycoside (as with carboxypenicillins, above).

Azlocillin (iY2 1 h), highly effective against Pseudomonas aeruginosa infections, is less so than other

OTHER p - LACTAM ANTIBACTERIALS

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