Cloxacillin

Cloxacillin belongs to the penicillins, the large family of beta-lactam antibiotics. At the heart of the molecule, a chemical ring called the beta-lactam binds to a bacterial enzyme, the DD-transpeptidase, also known as the penicillin-binding protein. This enzyme normally assembles the meshes of peptidoglycan, the rigid net that forms the wall of the bacterium. By binding to it irreversibly, cloxacillin inactivates it and blocks the cross-linking of this wall.

A poorly assembled wall no longer holds. Cloxacillin then leaves the way open to bacterial enzymes, the autolysins and hydrolases, which finish degrading the envelope. Deprived of this protection, the bacterium is subjected to osmotic pressure: water enters until it bursts. The effect is therefore bactericidal, the antibiotic kills the bacterium instead of merely slowing its growth.

Many bacteria defend themselves by producing an enzyme, the beta-lactamase, also called penicillinase, which cuts the beta-lactam ring and destroys the penicillin before it acts. Cloxacillin is one of the penicillins described as penicillinase-resistant, or second generation. These are semi-synthetic versions of the natural penicillins, modified to withstand this enzyme. That is what allows them to act where penicillin G is destroyed.

This advantage directly guides their use. Cloxacillin, like its close relatives dicloxacillin, oxacillin and nafcillin, is used to treat moderate to severe infections caused by penicillinase-producing staphylococci, when the strain remains sensitive to the product. The doctor prescribes it after establishing that the causative organism does indeed fall within this scope.

These penicillins are better absorbed on an empty stomach. The summary of product characteristics for flucloxacillin, the antistaphylococcal agent closest to cloxacillin, states that it should be taken on an empty stomach: one hour before a meal or two hours after. Taken with food, the absorption of these isoxazolyl penicillins decreases. Respecting this timing increases the amount of antibiotic that passes into the blood.

The molecule acts quickly but does not stay long: the half-life of flucloxacillin is short, in the order of 53 minutes. The treatment is therefore divided into several doses per day, at regular intervals, to maintain an effective concentration. The prescribed duration is followed through to the end, without stopping as soon as one feels better, because interrupting too early leaves bacteria to survive. The dose is not changed on one’s own, it is discussed with the doctor.

The most common effects concern digestion. Diarrhoea and nausea are frequent and generally remain minor. Skin reactions, rash, urticaria or purpura, are uncommon. As with any penicillin, an allergy remains possible and warrants prompt medical advice.

Serious effects are rare. Cholestatic-type liver injury, with jaundice, may appear 1 to 6 weeks after the start of treatment; it remains rare and most often resolves on its own once treatment stops. Cholestatic jaundice attributed to cloxacillin has been reported in the literature. Hepatitis, cholestatic jaundice and pseudomembranous colitis are among the very rare effects of this class.

These penicillins are given in the form of a sodium salt. Injectable flucloxacillin at 1 g provides about 2.26 mmol of sodium per vial, an amount to be counted in the intake of people on a low-salt diet. Caution is required when high doses of sodium salts are given in cases of kidney or heart failure.

At high doses, these penicillins can also lower blood potassium, a hypokalaemia that is sometimes serious and may resist potassium supplementation. Regular monitoring of blood potassium is recommended during treatment with high doses. Vigilance is heightened in cases of combination with diuretics, of undernutrition or of a disorder of the renal tubules.

Several medicines interact with this class. Probenecid slows the renal elimination of penicillin and increases its concentrations in the blood. The risk of methotrexate toxicity increases in combination. Under warfarin, the INR may change, which calls for monitoring. The oral typhoid vaccine, finally, may be inactivated by the antibiotic.

Follow-up completes the prescription. The elimination of cloxacillin passes mainly through the kidney and its binding to blood proteins is high, around 95 % for flucloxacillin, so that kidney function deserves attention in frail people. During breastfeeding, cloxacillin is acceptable, because it passes little into the milk. After a single 500 mg intramuscular dose in two women, the levels measured in the milk ranged from 0.1 to 0.3 mg/L between one and six hours after the dose.