A Current Perspective on Daptomycin for the Clinical Microbiologist

Abstract

SUMMARY Daptomycin is a lipopeptide antimicrobial with in vitro bactericidal activity against Gram-positive bacteria that was first approved for clinical use in 2004 in the United States. Since this time, significant data have emerged regarding the use of daptomycin for the treatment of serious infections, such as bacteremia and endocarditis, caused by Gram-positive pathogens. However, there are also increasing reports of daptomycin nonsusceptibility, in Staphylococcus aureus and, in particular, Enterococcus faecium and Enterococcus faecalis . Such nonsusceptibility is largely in the context of prolonged treatment courses and infections with high bacterial burdens, but it may occur in the absence of prior daptomycin exposure. Nonsusceptibility in both S. aureus and Enterococcus is mediated by adaptations to cell wall homeostasis and membrane phospholipid metabolism. This review summarizes the data on daptomycin, including daptomycin's unique mode of action and spectrum of activity and mechanisms for nonsusceptibility in key pathogens, including S. aureus , E. faecium , and E. faecalis . The challenges faced by the clinical laboratory in obtaining accurate susceptibility results and reporting daptomycin MICs are also discussed.

β-Lactams Enhance Daptomycin Activity against Vancomycin-Resistant Enterococcus faecalis and Enterococcus faecium in In Vitro Pharmacokinetic/Pharmacodynamic Models

“…Treatment of VRE infections can prove problematic, as available treatment options are potentially limited by static activity and/or platelet suppression with long-term use (6)(7)(8). Daptomycin (DAP) is a bactericidal lipopeptide often used against resistant enterococci (9). Mechanistically, it binds with calcium to form a cationic moiety that disrupts membrane potential to confer its antimicrobial effects, similar to endogenous, cationic antimicrobial peptides (10,11).…”

Precision of Vancomycin and Daptomycin MICs for Methicillin-Resistant Staphylococcus aureus and Effect of Subculture and Storage

“…Daptomycin is expensive and may not be available in all institutions. Further, some isolates, such as those observed in our study, develop daptomycin and vancomycin resistance in parallel (33,34). As there are no clear molecular targets associated with reduced susceptibility to vancomycin, it is clear that the generation of an accurate vancomycin MIC is imperative for patient care.…”

“…Alternative therapies to vancomycin for bacteremia due to MRSA are limited. Daptomycin has been shown to be effective for the treatment of MRSA bacteremia, with the exception of that caused by leftsided endocarditis, and it may retain bactericidal activity in spite of slightly elevated MICs (33,34,36). Daptomycin is expensive and may not be available in all institutions.…”

Small molecules targeting at the bacterial cell division protein FtsZ as potential antimicrobial agents

“…Nowadays, the treatment of bacterial infections has become more difficult because bacteria can develop resistance to antibiotics at an alarming speed [1][2][3][4]. Vancomycin-resistant Enterococcus faecium (VREF) and methicillin-resistant Staphylococcus aureus (MRSA) are two typical representatives of gram-positive bacteria that are resistant to conventional antibiotics including vancomycin and methicillin [5,6]. This situation is even more alarming in gram-negative bacteria.…”