In vitro activities of daptomycin and other antimicrobial agents against vancomycin-resistant gram-positive bacteria

Abstract

A comparative evaluation of daptomycin and eight other antimicrobial agents was performed by the agar dilution technique with 56 strains of vancomycin-resistant gram-positive bacteria, including Leuconostoc, Lactobacillus, and Pediococcus spp. Erythromycin, daptomycin, clindamycin, and gentamicin exhibited the greatest activities, whereas penicillin, ampicillin, and cefotaxime showed moderate activities. The organisms were all highly resistant to vancomycin and cefoxitin.Although still uncommon, severe infections due to vancomycin-resistant (V-R) gram-positive bacteria belonging to the genera Leuconostoc (3,[5][6][7]10,13), Lactobacilllus (12), and Pediococcus (4) have recently been reported. Because of this and the relative lack of information in the literature concerning antibiotic susceptibilities and methods for their determination, we undertook the study reported here, which is a comparative evaluation of the activities of daptomycin and eight antimicrobial agents against V-R gram-positive bacteria. Daptomycin (LY146032), a lipopeptide antibiotic derived from a fermentation product, exhibits a high degree of in vitro activity against gram-positive bacteria by inhibiting cell wall peptidoglycan biosynthesis (1).The bacteria used in this study were 56 V-R gram-positive strains belonging to the genera Leuconostoc (n = 13), Lactobacillus (n = 32), or Pediococcus (n = 6) or were strains of indeterminate genus (n = 5). Forty-six strains had been isolated from clinical specimens at Massachusetts General Hospital (11) incubation at 35°C in a 5 to 7% CO2 atmosphere, since some strains exhibited poor growth in an ambient atmosphere. For all strains, lactobacillus Mann, Rogosa, and Sharpe (MRS) broth (Difco Laboratories, Detroit, Mich.) was used to achieve the active growing phase, and the final inoculum dilutions were performed in sterile deionized water.Susceptibilities of the V-R isolates to the agents tested in this study are shown in Tables 1 and 2. All of the organisms were highly resistant to vancomycin and cefoxitin. In contrast, erythromycin, clindamycin, and gentamicin were quite active, with more than 90% of the strains being susceptible Leuconostoc (

Evaluation of New Broth Media for Microdilution Antibiotic Susceptibility Testing of Lactobacilli, Pediococci, Lactococci, and Bifidobacteria

“…A large variety of methods to determine antibiotic susceptibilities of nonenterococcal lactic acid bacteria (LAB) belonging to the genera Lactobacillus, Pediococcus, Lactococcus, and Bifidobacterium based on either agar disk diffusion (4,5,15,20,26,29,32,33,35), E-test (6,9,10,13,15,16,19,21), agar dilution (3,7,11,17,19,22) or broth dilution (1,12,14,18,23,24,25,27,29,30,31,34) has been described. Due to the fact that many of these organisms require special growth conditions in terms of medium acidity and nutrient supplementation, conventional media such as Mueller-Hinton and Iso-Sensitest (IST) agar or broth are not uniformly suitable for susceptibility testing of nonenterococcal LAB.…”

“…A mixed formulation of Iso-Sensitest broth (90%) and deMan-Rogosa-Sharpe broth (10%) with or without supplementation with L-cysteine, referred to as the LAB susceptibility test medium, provided the most optimal medium basis in terms of growth support of nonenterococcal LAB and correct indication of MICs of international control strains.A large variety of methods to determine antibiotic susceptibilities of nonenterococcal lactic acid bacteria (LAB) belonging to the genera Lactobacillus, Pediococcus, Lactococcus, and Bifidobacterium based on either agar disk diffusion (4, 5, 15, 20, 26, 29, 32, 33, 35), E-test (6, 9, 10, 13, 15, 16, 19, 21), agar dilution (3,7,11,17,19,22) or broth dilution (1,12,14,18,23,24,25,27,29,30,31, 34) has been described. Due to the fact that many of these organisms require special growth conditions in terms of medium acidity and nutrient supplementation, conventional media such as Mueller-Hinton and Iso-Sensitest (IST) agar or broth are not uniformly suitable for susceptibility testing of nonenterococcal LAB.…”

Vancomycin Resistant Enterococcus: A Case Report and Review of Literature

“…It could also conjugate to E. faecalis, Streptococcus sanguis, S. pyogenes, S. lactis, and Listeria monocytogenes in which it conferred inducible vancomycin resistance, but not to S. aureus. Although vancomycin-resistant strains of lactobacilli, leuconostocs or pediococci have been isolated occasionally as opportunists from severely compromised patients, their treatment remains relatively uncomplicated because of their susceptibility to clindamycin, erythromycin, and gentamicin [35,36]. Similarly, vancomycinresistant strains of E. rhusiopathiae, S. epidermidis and S. hemolyticus have remained susceptible to commonly used drugs [7,37].…”

Teicoplanin and daptomycin bactericidal activities in the presence of albumin or serum under controlled conditions of pH and ionized calcium

“…Teicoplanin, daptomycin, and vancomycin have similar spectrums of activity against gram-positive aerobic and anaerobic bacteria, including methicillin-resistant staphylococci (6,8,(15)(16)(17)(18). Despite sharing a high degree of protein binding (>90%), teicoplanin and daptomycin have different pharmacodynamic properties.…”

“…Against strain 135, daptomycin again produced the highest BR in B; however, the BRs in BF, BA, and BS were almost identical, indicating that only free daptomycin was active. After correcting for the influence of protein binding, pH, and ionized calcium, teicoplanin appeared to be inhibited by serum, and daptomycin demonstrated enhanced BRs against different S. aureus strains in the presence of albumin or serum.Teicoplanin, daptomycin, and vancomycin have similar spectrums of activity against gram-positive aerobic and anaerobic bacteria, including methicillin-resistant staphylococci (6,8,(15)(16)(17)(18). Despite sharing a high degree of protein binding (>90%), teicoplanin and daptomycin have different pharmacodynamic properties.…”