Dalbavancin

Dalbavancin belongs to the lipoglycopeptide family. It targets the building of the bacterial wall, the rigid envelope that protects the bacterium and gives it its shape. In practical terms, it binds to the D-alanyl-D-alanine end of the pentapeptide of the nascent peptidoglycan, the basic building block of this wall. By occupying this end, it prevents the assembly of the chains.

This assembly relies on two reactions, transpeptidation and transglycosylation, which link the chains together to form a solid mesh. Dalbavancin blocks this cross-linking: the wall no longer closes and the bacterium does not withstand the internal pressure. In vitro, it proves bactericidal, meaning that it kills the bacteria, against Staphylococcus aureus and Streptococcus pyogenes.

Dalbavancin is indicated in acute bacterial infections of the skin and soft tissues, referred to by the abbreviation ABSSSI. It is intended for adults as well as children, when the infection is due to susceptible Gram-positive bacteria. This group of bacteria shares a thick wall, precisely the target of the antibiotic.

Its spectrum covers Staphylococcus aureus, including strains resistant to methicillin, known as MRSA, which escape several common antibiotics. It also includes Streptococcus species and Enterococcus faecalis. This activity against germs that are sometimes difficult to treat explains its place in the management of severe skin infections.

Dalbavancin is given only by intravenous infusion, over thirty minutes, and never by the oral route. Two regimens coexist: a single dose of 1,500 mg, or a first injection of 1,000 mg followed by an injection of 500 mg one week later. Because the product is infused, the dose does not depend on meals.

This administration in one or two times is explained by a particular pharmacokinetics. The terminal half-life of the molecule reaches about 346 hours, with an effective half-life of about 8.5 days, that is 204 hours. The medicine therefore remains active for a long time after the infusion, which avoids daily dosing. When the two-injection regimen is chosen, the second-week appointment is part of the treatment and is not skipped.

In the blood, dalbavancin circulates bound to plasma proteins at about 93 percent, mainly to albumin. It is then eliminated by two routes: the urine, which removes about 33 percent of it in unchanged form, and the faeces, for about 20 percent. The renal share of this elimination justifies attention to kidney function.

When renal function is greatly reduced, with a creatinine clearance below 30 mL/min in a patient not on dialysis, the dose is lowered: 1,125 mg as a single dose, or 750 mg followed by 375 mg one week later. In people treated with regular haemodialysis, no adjustment is needed. These adjustments are the prescriber’s decision, based on the renal assessment.

The most frequent adverse effects in adults were quantified in the clinical trials. Nausea is noted in 5.5 percent of patients, headache in 4.7 percent, diarrhoea in 4.4 percent, vomiting in 2.8 percent, skin rash in 2.7 percent and itching in 2.1 percent. These disorders most often remain moderate.

The liver deserves particular monitoring. Among the patients whose level of ALT, a liver enzyme, was normal at the start, 17, that is 0.8 percent, saw this value exceed three times the upper limit of normal, including five above ten times; these elevations were reversible. In addition, an infusion that is too fast can trigger infusion-related reactions, such as flushing, hives, itching, a rash or back pain. Slowing down or stopping the infusion makes these symptoms subside.

Dalbavancin is neither a substrate, nor an inhibitor, nor an inducer of the isoenzymes of cytochrome P450, the enzyme system through which many medicines interact with one another. No formal drug interaction study has been conducted, and the potential for interaction with substrates, inhibitors or inducers of this cytochrome is judged to be minimal. The risk of interference with other treatments therefore appears low.

Vigilance concerns above all the digestive tract and the liver. Like almost all antibiotics by the systemic route, dalbavancin can encourage Clostridioides difficile diarrhoea, of variable intensity up to severe colitis, and this diarrhoea can appear more than two months after administration: any diarrhoea that persists after the treatment should be reported to the doctor. Monitoring of transaminases completes this surveillance, echoing the liver elevations observed.