Antimicrobial Activity Of Daptomycin Research Articles

Effect of High Blood Glucose Level on the Antimicrobial Activity of Daptomycin against Staphylococcus aureus in Streptozotocin-Induced Diabetic Mice.

Daptomycin is active against Staphylococcus aureus including methicillin-resistant S. aureus (MRSA), demonstrating efficacy in the treatment of infections in diabetic patients. However, daptomycin degrades in 5% glucose solution, and data on the efficacy of daptomycin in hyperglycemic patients are limited. Therefore, we investigated the effect of high levels of blood glucose on the efficacy and concentration of daptomycin. The efficacy of simulated human exposure to daptomycin against S. aureus was compared in a neutropenic murine thigh model, with and without hyperglycemia. A clinically isolated MRSA strain and S. aureus ATCC25923 standard strain were used. Daptomycin concentrations, in the serum and at the infected site, were preliminarily analyzed using the high-performance liquid chromatography assay. Even in hyperglycemic mice, the mean concentration of daptomycin in hyperglycemic mice was equivalent to that in untreated mice within the physiological blood glucose levels. Additionally, the efficacy of daptomycin against MRSA was equal to that observed in the untreated and hyperglycemic mice. Based on similar studies using S. aureus ATCC25923, the efficacy in hyperglycemic mice was equal to or greater than that observed in untreated mice. In conclusion, daptomycin is an alternative therapeutic option in diabetic mice with serious staphylococcal infections, regardless of blood glucose control in this animal model.

A Versatile Boc Solid Phase Synthesis of Daptomycin and Analogues Using Site Specific, On-Resin Ozonolysis to Install the Kynurenine Residue.

A de novo solid-phase synthesis of the cyclic lipodepsipeptide daptomycin via Boc chemistry was achieved. The challenging ester bond formation between the nonproteinogenic amino acid kynurenine was achieved by esterification of a threonine residue with a protected tryptophan. Subsequent late-stage on-resin ozonolysis, inspired by the biomimetic pathway, afforded the kynurenine residue directly. Synthetic daptomycin possessed potent antimicrobial activity (MIC100 =1.0 μg mL-1 ) against S. aureus, while five other daptomycin analogues containing (2R,3R)-3-methylglutamic acid, (2S,4S)-4-methylglutamic acid or canonical glutamic acid at position twelve prepared using this new methodology were all inactive, clearly establishing that the (2S,3R)-3-methylglutamic acid plays a key role in the antimicrobial activity of daptomycin.

Antimicrobial activity of daptomycin in comparison to glycopeptides and other antimicrobials when tested against numerous species of coagulase-negative Staphylococcus

Coagulase-negative Staphylococcus spp. (CoNS) represent a major cause of bloodstream infections, especially in patients with prosthetic devices and intravenous catheters. We evaluated the activity of daptomycin in comparison to vancomycin and teicoplanin against a large collection of 22,024 CoNS isolates causing clinically significant infections from 283 medical centers over 9 years (2002–2010) and tested for susceptibility by broth microdilution methods against daptomycin and numerous comparators. Overall, daptomycin (MIC50/90, 0.25/0.5 μg/mL) inhibited 99.8% of CoNS at the susceptible breakpoint of ≤1 μg/mL and was 4- to 16-fold more active than vancomycin (MIC50/90, 1/2 μg/mL; >99.9% susceptible). All species showed ≥99.6% susceptibility to daptomycin, except Staphylococcus auricularis (95.1%), S. capitis (99.0%), S. warneri (98.8%), and S. sciuri. S.sciuri represented only 0.2% of the collection (46 strains) and exhibited decreased susceptibility to daptomycin (MIC50/90, 1/2 μg/mL; 71.7% susceptible). In contrast, S. sciuri exhibited high susceptibility to vancomycin and teicoplanin (highest MIC at 2 μg/mL for both drugs). In summary, daptomycin exhibited species-specific activity among CoNS, especially versus S. sciuri. No correlation between decreased susceptibility to daptomycin and the glycopeptides tested was observed.

Antimicrobial Activity of Daptomycin Tested Against Gram-Positive Strains Collected in European Hospitals: Results from 7 Years of Resistance Surveillance (2003-2009)

Daptomycin is a cyclic lipopeptide approved by the European medicines Agency (EMEA) for the treatment of complicated skin and soft tissue infections (cSSTI) and Staphylococcus aureus bacteremia and endocarditis. We evaluated the in vitro activity of daptomycin and comparators tested against clinical isolates from European hospitals over a 7-year period (2003-2009). A total of 36,769 consecutive isolates were collected in 34 medical centers located in 13 European countries, turkey and Israel. the collection included S. aureus (18,352; 27.2% oxacillin-resistant [MRSA]); coagulase-negative staphylo-cocci (CoNS; 6,874), Enterococcus spp. (7,241; 9.4% vancomycin-resistant),β-hemolytic (3,009), viridans group streptococci (1,176), and Streptococcus bovis/gallolyticus (107). The organisms were isolated mainly from patients with bloodstream infection (56%) or cSSTI (23%). Daptomycin was very active against S. aureus and CoNS (MIC50/90, 0.25/0.5 mg/L for both organisms), and its activity was not adversely influenced by oxacillin resistance. All Enterococcus faecalis strains were susceptible to daptomycin (MIC50/90, 1/1 mg/L). Daptomycin (MIC50/90, 2/2 mg/L; 100.0% susceptible) and linezolid (MIC50/90, 1/2 mg/L; 99.7% susceptible) were the most active agents tested against vancomycin-resistant E. faecium. Vancomycin-resistant and -susceptible enterococcal strains were equally susceptible to daptomycin. Daptomycin was also active against β-hemolytic streptococci (MIC50/90, 0.06/0.25 mg/L; 100.0% susceptible), viridans group streptococci (MIC50/90, 0.25/0.5 mg/L; 99.8% susceptible) and S. bovis (MIC50/90, 0.06/0.12 mg/L; 100.0% susceptible).In summary, daptomycin was very potent against this large collection (36,769) of Gram-positive organisms isolated in European hospitals, and its activity remained stable across the 7-year period evaluated (2003-2009), using reference methods and interpretive criteria. Decreases in daptomycin potency were not observed since EMEA approval and widespread clinical use, and emerging resistance to other compounds did not adversely influence daptomycin activity against contemporary Gram-positive species.

Antimicrobial Activity of Daptomycin and Comparator Agents Tested Against Gram-positive Organisms from Hong Kong, Indonesia, Philippines, Singapore and Thailand

Antimicrobial Activity of Daptomycin and Comparator Agents Tested Against Gram-positive Organisms from Hong Kong, Indonesia, Philippines, Singapore and Thailand

Antimicrobial activity of daptomycin and selected comparators tested against bloodstream Staphylococcus aureus isolates from hemodialysis patients

Patients on long-term hemodialysis are at a significantly higher risk for catheter-related bloodstream infections (BSI) than the general population. These infections are generally caused by gram-positive organisms, especially Staphylococcus aureus. In the present study, we evaluated the antimicrobial susceptibility patterns of S. aureus causing BSI in dialysis patients compared to those causing BSI in other patient populations. The potencies of daptomycin and various comparator agents were evaluated by reference broth microdilution methods for S. aureus bloodstream isolates from dialysis patients (606 strains) in 43 hospitals in North America and Europe. Susceptibility patterns for the dialysis isolate set were compared to those S. aureus causing BSI in other patient populations in the same hospitals and time period. Daptomycin was highly potent against S. aureus causing bacteremia in dialysis patients (MIC(50)/MIC(90), 0.25/0.5 microg/ml). Vancomycin (MIC(50)/MIC(90), 1/1 microg/ml) and linezolid (MIC(50)/MIC(90), 2/2 microg/ml) showed similar potency, and overall susceptibility rates for the three antibiotics were 99.8-100.0% susceptible. Linezolid and vancomycin were four- to eight-fold less potent than daptomycin. The overall susceptibility patterns of S. aureus strains from dialysis patients were very similar to those of non-dialysis patients.

In vitro Activity of Daptomycin versus Linezolid and Vancomycin against Gram-Positive Uropathogens and Ampicillin against Enterococci, Causing Complicated Urinary Tract Infections

Objectives: The existing therapeutic options for complicated urinary tract infections (UTI) caused by gram-positive uropathogens are not always optimal. Therefore, newer antimicrobials have to be assessed. Methods: The antimicrobial activity of daptomycin was tested versus linezolid, vancomycin, and ampicillin (enterococci on ly), against pathogens from three different collections: (1) Uropathogens from hospitalized urological patients with complicated and/or hospital-acquired UTIs of the Urologic Clinic, Hospital St. Elisabeth, Straubing. (2) Uropathogens from a multicenter study comprising 37 urological centers throughout Germany. (3) Methicillin-resistant Staphylococcus aureus (MRSA) isolates of patients and staff within the Hospital St. Elisabeth, Straubing. Genotyping of the latter isolates was performed by pulsed-field gel electrophoresis. The minimal inhibitory concentrations (MIC) of daptomycin, linezolid, vancomycin, and ampicillin (only tested against enterococci) were determined by an agar dilution method using a multipointer with an inoculum of 10⁴ CFU per point. Results: For all methicillin-susceptible Staphylococcus aureus (n = 25), MRSA (n = 49), methicillin-susceptible coagulase-negative staphylococci (n = 129), methicillin-resistant coagulase-negative staphylococci (n = 33), for Enterococcus faecalis (n = 289), and for Enterococcus faecium (n = 4) the MICs ranged up to 2 mg/l (daptomycin, linezolid), up to 4 mg/l (vancomycin), and up to 8 mg/l (ampicillin, enterococci only) indicating that all strains were susceptible to the antibiotics tested. Conclusions: According to the in vitro activity daptomycin may be considered a promising antibacterial agent for the treatment of complicated UTI caused by gram-positive uropathogens. Thus, daptomycin should be evaluated in a clinical study

Antimicrobial activity of daptomycin against multidrug-resistant gram-positive strains collected worldwide

Daptomycin is a cyclic lipopeptide recently released for clinical use in the treatment of serious Gram-positive infections in hospitalized patients. We evaluated the in vitro activity of daptomycin tested against recently isolated multidrug-resistant Gram-positive clinical strains. A total of 386 isolates were selected from a large collection of strains from more than 70 centers located in Europe, North America, and South America. The strains were tested by reference broth microdilution methods in Mueller–Hinton broth with 50 mg/L Ca ++ against daptomycin. Daptomycin was the most potent compound tested against penicillin-resistant Streptococcus pneumoniae with MIC 50/90 values at ≤0.12 and 0.25 μg/mL, respectively. Daptomycin was also highly active against vancomycin-resistant enterococci and staphylococcal strains with various resistance patterns. Enterococcus faecium showed higher daptomycin MIC values (MIC 90, 4 μg/mL) when compared to E. faecalis (MIC 90, 1 μg/mL). In summary, resistance to vancomycin, teicoplanin, quinupristin/dalfopristin, or penicillin among the Gram-positive isolates did not adversely influence daptomycin activity. Daptomycin showed a significant potency and spectrum against Gram-positive species, including multidrug-resistant strains, and may represent a reasonable therapeutic option for infections caused by these important pathogens.