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22 Antimicrobialsbeing fundamentally different from the gram-negative types. Gram-negativeβ-
lactamase is encoded on bacterial chromosomes and plasmids, which may be
disseminated; the basis of acquired resistance.Kinetics
Intestinal absorption is variable and certain penicillins are only available as par-
enteral preparations. Plasma half-lives are short (benzylpenicillin, 30 min; ampi-
cillin, 2 hrs) and protein binding widely variable (ampicillin, 20%; flucloxacillin,
93%). Tissue penetration is generally good although inflammation is necessary for
penicillins to pass into bone and through the blood-brain barrier. Penicillins are
excreted by the kidneys in the unchanged form (60–90%), mainly by renal tubular
secretion, but they are also excreted in bile (10%) and up to 20% is metabolized.
Probenecidblocks renal tubular secretion so that when given in combination with
penicillin the plasma concentration of the latter doubles. In addition probenecid
inhibits active removal of penicillin from the CSF via the choroid plexus so that there
is increased risk of CNS toxicity.Use during continuous veno-venous haemodiafiltration (CVVHDF)
Penicillin dose adjustment is unnecessary for patients on CVVHDF with the excep-
tion of benzylpenicillin – the dose of which should be reduced by 30%. Peni-
cillins combined with clavulanic acid (AugmentinTM,TimentinTM)ortazobactam
(TazocinTM)require no dose adjustment for CVVHDF. However, if an anuric patient
remains without filtration for a prolonged period then dose frequency reduction
should be considered.Side effects
Hypersensitivity – allergy to penicillins occurs in up to 10% of the popula-
tion, anaphylaxis occurs in 0.01%. Cross-reactivity exists between penicillins,
cephalosporins and carbapenems in up to 10% of allergic people. Patients with
ahistory of immediate reaction (urticaria, anaphylaxis or interstitial nephritis)
should therefore avoid any of theseβ-lactams.
Encephalopathy – benzylpenicillin is the most pro-convulsantβ-lactam. Toxic CSF
levels can be reached by intrathecal injection (maximum dose of benzylpenicillin
is 12 mg), by using large doses in meningitic patients with renal impairment and
byconcomitant probenecid use.
Gut–diarrhoea is common during oral therapy. Ampicillin is also associated with
alowrisk of pseudomembranous colitis (0.3–0.7%).
Miscellaneous – ampicillin produces a maculopapular rash in 10% of all patients
and 95% of patients with infectious mononucleosis. Bone marrow suppression has
also been reported with penicillins.