Penicillins

Narrow-spectrum penicillins

Narrow-spectrum penicillins are active mainly against Gram-positive organisms, but they are inactivated by beta-lactamases.

Benzylpenicillin (penicillin G) is administered parenterally and remains the treatment of choice for susceptible infections if parenteral treatment is warranted.

Procaine penicillin is an intramuscular preparation designed to extend the half-life of benzylpenicillin. It provides blood levels for up to 24 hours, but these are adequate only against highly susceptible organisms.

Benzathine penicillin is given intramuscularly and provides low levels of benzylpenicillin for up to 4 weeks.

Phenoxymethylpenicillin (penicillin V) is acid-stable, so it can be given orally, although food impairs absorption. It is intrinsically less active than benzylpenicillin.

Narrow-spectrum penicillins with antistaphylococcal activity

Dicloxacillin, flucloxacillin and methicillin are stable to beta-lactamase produced by staphylococci. Flucloxacillin and dicloxacillin are reliably absorbed by the oral route; however, food reduces absorption and they are best taken half to one hour before food. Methicillin, the parent drug, is not used in clinical practice. Laboratories test with either oxacillin or cefoxitin rather than methicillin to determine susceptibility to antistaphylococcal drugs.

Flucloxacillin is generally well tolerated, but is occasionally associated with cholestatic jaundice, particularly in older patients on prolonged therapy. This may occur after oral or intravenous administration and up to 6 weeks after treatment. It may last for months, can be irreversible and, rarely, may be fatal. Dicloxacillin appears to cause less irreversible hepatotoxicity but results in more infusion phlebitis (see Intravenous administration of antimicrobials) and interstitial nephritis. Dicloxacillin may be preferable to flucloxacillin for oral therapy or in patients requiring prolonged therapy. In these guidelines, di/flucloxacillin refers to dicloxacillin or flucloxacillin.

MRSA should be regarded as clinically resistant to all beta lactams.

Moderate-spectrum penicillins

The aminopenicillins, amoxycillin and ampicillin, have greater activity than benzylpenicillin against some Gram-negative organisms (eg Escherichia coli, Haemophilus influenzae), but are destroyed by beta-lactamase–producing strains. They are drugs of choice for enterococcal infections. Amoxycillin is better absorbed orally than ampicillin, is not affected significantly by food and requires fewer oral doses per day, but when administered parenterally they are equivalent. In these guidelines, amoxy/ampicillin refers to amoxycillin or ampicillin.

Broad-spectrum penicillins (beta-lactamase inhibitor combinations)

The beta-lactamase inhibitors clavulanate, sulbactam and tazobactam inhibit the enzymes produced by Staphylococcus aureus and Bacteroides fragilis and also the beta-lactamase enzymes found in Escherichia coli, Klebsiella species, Neisseria gonorrhoeae and Haemophilus influenzae. These three drugs possess little inherent antibacterial activity, but significantly extend the spectra of activity of amoxycillin, ticarcillin and piperacillin when given with them. Reserve these combinations for the treatment of infections due to organisms in which resistance to the beta lactam is due to enzymes that the beta-lactamase inhibitors are able to inhibit. The combinations are often more expensive than the beta-lactam antimicrobials alone.

Amoxycillin+clavulanate can cause diarrhoea and hepatotoxicity, which occur more frequently than with amoxycillin.

Broad-spectrum penicillins with antipseudomonal activity

Piperacillin and ticarcillin are the only penicillins that have activity against Pseudomonas aeruginosa, but high doses are required. The addition of clavulanate to ticarcillin and tazobactam to piperacillin extends their spectra of activity, with piperacillin+tazobactam having greater in vitro activity against enterococci and Klebsiella species. Piperacillin+tazobactam is more expensive than ticarcillin+clavulanate, and both are more expensive than most other penicillins.