Conference Coverage

Daptomycin beats infective endocarditis caused by several pathogens




AMSTERDAM – Daptomycin successfully treated infective endocarditis in 90% of patients who developed it after undergoing heart valve replacement, according to a report presented at the annual congress of the European Society of Clinical Microbiology and Infectious Diseases.

Dr. Achyut Guleri, clinical director of laboratory medicine at Blackpool Victoria Hospital, Lancashire, England, said the lipopeptide antibiotic was equally effective against methicillin- and penicillin-resistant Staphylococcus aureus, coagulase-negative staphylococcus, and enterococci.

“This is particularly good to know because sometimes in real life, on the shop floor, you don’t always have a very clear insight into what you’re trying to treat,” said Dr. Guleri. “It’s reassuring to see that the success rate is similar in all these infections.”

Dr. Achyut Guleri

Dr. Achyut Guleri

He presented a subgroup analysis of patients enrolled in European Cubicin Outcomes Registry and Experience (EUCORE), a retrospective, noninterventional, postmarketing registry. The 4-year study reported real-world clinical experience of daptomycin use for the treatment of Gram-positive infections in patients with infective endocarditis who had undergone heart valve replacement.

Typically, Dr. Guleri said, vancomycin, either alone or with rifampicin, is recommended for the infection. “However, with increasing antibiotic resistance, vancomycin doesn’t inspire much confidence, especially for MRSA infections,” he noted.

Daptomycin is increasingly employed as an alternative treatment. It exhibits rapid bactericidal activity against a wide range of Gram-positive pathogens, including MRSA. It’s approved for the treatment of right-sided infective endocarditis due to S. aureus, at a dose of 6 mg/kg per day. However, higher doses are now recommended by several international guidelines and are often used for hard-to-treat infections, Dr. Guleri said.

EUCORE comprised 6,075 patients from 18 countries who were enrolled from 2006 to 2012. Patients were followed until 2014. Of this group, 610 had infective endocarditis and 198 underwent valve replacement. Most were male (70%); mean age was 58 years. Medical comorbidities were common and included renal disease, sepsis, diabetes, pulmonary disease, gastrointestinal disease, cerebrovascular disease and inflammatory diseases.

Culture results were available for 87%. Of these, 68% were positive. The most common pathogen was S. aureus (37%). Half of these isolates were penicillin resistant and 35% were methicillin resistant. Enterococci were responsible for 14% of the infections, and coagulase-negative staph for 32%. The rest were caused by other pathogens.

Before trying daptomycin, most patients (83%) had already been treated with an antibiotic, which was employed in conjunction with another antibiotic in 77% of cases. The concomitant medications included rifampicin (31%), aminoglycosides (29%) and carbapenems (18%).

The overall clinical cure rate at 2 years was 90%. Daptomycin was equally effective in left- and right-sided disease, and was more effective in penicillin-resistant staph (95%) than methicillin-resistant staph (80%). The cure rate was also good in coagulase-negative staph (81%) and enterococci (75%).

High doses were more effective than low doses. At 4 mg/kg per day, the cure rate was 61%. At 6 mg/kg per day, it was 86%, and at more than 6 mg/kg per day, it was 90%.

Adverse events were rare (3%). Three patients developed increased creatine phosphokinase levels; one patient developed rhabdomyolysis and one developed cholestasis. Agranulocytosis developed in three patients and eosinophilic pneumonia in three. One patient developed a rash. No one discontinued the drug due to a side effect.

Dr. Guleri had no financial disclosures.

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