Spiramycin

Spiramycin belongs to the macrolide family, whose name comes from their large central ring: this one has sixteen atoms. It is produced by a soil bacterium, Streptomyces ambofaciens, isolated in 1951 in Péronne, France. Its classification code is J01FA02. Like the other macrolides, it does not act by killing the bacterium directly, but by preventing it from making its proteins.

To multiply, a bacterium must synthesise proteins on its ribosomes. Spiramycin binds to the 50S subunit of the bacterial ribosome and blocks the translocation step, the moment when the protein chain moves forward one notch to lengthen. Synthesis stops, and the bacterium can no longer proliferate. Resistance to this class appears when the bacterium methylates its 23S ribosomal RNA: the target is modified, and the macrolide can no longer attach to it.

In France, oral spiramycin covers a wide range of respiratory tract and ear, nose and throat infections. It is prescribed for group A streptococcal sore throat, as an alternative to beta-lactams, for acute sinusitis, superinfections of acute bronchitis and exacerbations of chronic bronchitis, as well as certain community-acquired pneumonias.

Its indications extend to skin and dental infections, non-gonococcal genital infections and the prevention of meningococcal meningitis. Its strong diffusion into tissues explains this range: it concentrates in the lungs, the tonsils, the infected sinuses and bone, and accumulates in phagocytes, the cells that carry it to the site of intracellular bacteria. It does not penetrate the cerebrospinal fluid.

Spiramycin holds a particular place in pregnant women. When toxoplasmosis is contracted early in pregnancy, it is used to reduce the risk of transmission to the fetus during the first eighteen weeks. Its wide use over the years has not revealed any malformative or fetotoxic effect, which makes it possible to consider during pregnancy.

It does not cross the placenta and remains less active than the pyrimethamine plus sulfonamide combination. It is therefore continued until infection of the fetus is confirmed or ruled out, around the eighteenth week, by amniocentesis and detection of the parasite by PCR. Breastfeeding, however, is not advised during treatment, because spiramycin passes into breast milk in significant amounts.

In adults with normal kidney function, the usual dose ranges from six to nine million international units per day, that is four to six tablets, divided into two or three intakes. The tablets are swallowed whole with a glass of water. The absorption of spiramycin is not changed by food: it can therefore be taken during or apart from meals, according to what helps you not to forget anything.

Regularity makes effectiveness: an antibiotic is taken to the end of the set duration, even when symptoms fade, so as not to let the most resistant bacteria survive. Spiramycin has a plasma half-life of about eight hours and binds little to blood proteins. The liver transforms it into active metabolites and eliminates it mainly through the bile, very little through the urine: no dose adjustment is needed in case of kidney failure.

Some effects are expected and most often mild. Paraesthesia, that passing tingling, is very common and affects more than one person in ten, but it remains occasional and transient. Digestive disorders are common, in one to ten people in a hundred: abdominal pain, nausea, vomiting, stomach ache and diarrhoea. A passing alteration of taste and skin rashes fall within the same frequency.

Abnormal liver test results are very rare, below one person in ten thousand. Macrolides can cause liver damage, most often a cholestatic hepatitis that appears one to three weeks after the start of treatment, and a symptomless rise in transaminases is seen in about one to five per cent of patients treated with this class. More rarely still, at an undetermined frequency, spiramycin has been associated with serious skin reactions, anaphylactic shock and a prolongation of the QT interval that can go as far as torsades de pointes.

The cardiac side deserves attention in predisposed people. QT prolongation becomes more likely when the potassium or magnesium level is too low and uncorrected, in cases of congenital long QT, heart disease or simultaneous intake of other medicines that prolong the QT. Correcting a potassium and magnesium deficit is part of the points to watch before and during treatment.

Several combinations call for monitoring. With levodopa and carbidopa, spiramycin hinders the absorption of carbidopa and lowers levodopa concentrations, which may require a dose adjustment. Like other antibiotics, it can unbalance the INR of patients on vitamin K antagonist anticoagulants, whose INR must then be checked. Finally, in people with G6PD deficiency, very rare haemolytic anaemias have been reported, and spiramycin is not recommended there.