Efficacy Of Daptomycin Research Articles

Pharmacokinetic/pharmacodynamic evaluation of the efficacy and safety of daptomycin against Staphylococcus aureus

Daptomycin is a novel lipopeptide exhibiting concentration-dependent bactericidal activity against multidrug-resistant Gram-positive pathogens, including MRSA. Approval of daptomycin is granted at 4–6mg/kg once daily, however off-label use of doses up to 12mg/kg daily has been utilised without evidence of significant toxicity. Our aim was to optimise daptomycin regimens by assessing the probability of bacteriological efficacy (pTA) and toxicity (pTOX) at various MICs using Monte Carlo simulation (MCS) techniques. Population pharmacokinetic, pharmacodynamic and toxicodynamic models were developed based on current literature. MCS was performed for 10000 patients, who were assigned true weight and creatinine clearances, and were infected with four Staphylococcus aureus strains at each MIC. Bacteriostatic and bactericidal %pTA was calculated following administration of 6, 8, 10 and 12mg/kg daptomycin; activity was deemed adequate at %pTA≥90%. Considerable pharmacodynamic variability was observed in derived AUC/MIC targets between strains. Bacteriostatic targets were adequately attained against all strains at MIC≤1mg/L with daptomycin >6mg/kg. However, bactericidal target attainment was only achieved against all strains at the lowest MIC of 0.5mg/L with daptomycin >8mg/kg. At MIC=2mg/kg, bactericidal target attainment was extremely poor even at the highest dose of 12mg/kg. pTOX increased from 3.31% to 17.7% following exposure to 6mg/kg to 12mg/kg daily, respectively. Formal benefit:risk analyses favoured doses of 10mg/kg against infections with MIC<2mg/L, whilst modest improvements in activity at 12mg/kg could not justify the marked increase in pTOX.

The safety and efficacy of high-dose daptomycin combined with rifampicin for the treatment of Gram-positive osteoarticular infections

Treatment of Gram-positive osteoarticular infections requires an adequate surgical approach combined with intensive antimicrobial therapy. The aim of this study was to evaluate the safety and efficacy of a combined regimen of high-dose daptomycin and rifampicin, in patients with various types of Gram-positive osteoarticular infections. This single centre, non-comparative, prospective study evaluated the safety and efficacy of a combined regimen of intravenous daptomycin (8 mg/kg/day) and oral rifampicin (600 mg/day) in patients with Gram-positive osteoarticular infections, with a minimal follow-up of one year. Creatine phosphokinase, transaminases, bilirubinaemia, and serum creatinine, were measured at baseline and regular intervals. The median daily doses of daptomycin and rifampicin, administered for a median duration of 21 (range, 10-122) days to 16 patients (median age, 63.5 years; 11 males, five females) presenting with staphylococcal (n = 15) or streptococcal (n = 1) osteoarticular infections, were 8.15 (range, 6.6-8.9) mg/kg/day and 600 (range, 600-900) mg/day, respectively. The combined regimen of daptomycin and rifampicin was well tolerated by all except one patient, without requiring treatment adjustment or discontinuation. One patient developed allergic responses probably due to rifampicin after 42 days. Fifteen (94 %) patients showed favourable clinical and microbiological outcomes. The combined regimen of high-dose daptomycin and rifampicin was well tolerated and may provide a useful alternative to standard glycopeptide therapy for Gram-positive osteoarticular infections.

Safety and efficacy of high-dose daptomycin as salvage therapy for severe gram-positive bacterial sepsis in hospitalized adult patients

BackgroundIncreasing the dosage of daptomycin may be advantageous in severe infection by enhancing bactericidal activity and pharmacodynamics. However, clinical data on using daptomycin at doses above 6 mg/kg in Asian population are limited.MethodsA retrospective observational cohort study of all hospitalized adult patients treated with daptomycin (> 6 mg/kg) for at least 72 hours was performed in Taiwan.ResultsA total of 67 patients (40 males) with a median age of 57 years received a median dose of 7.61 mg/kg (range, 6.03-11.53 mg/kg) of daptomycin for a median duration of 14 days (range, 3–53 days). Forty-one patients (61.2%) were in intensive care units (ICU). Sites of infections included complicated skin and soft tissue infections (n = 16), catheter-related bacteremia (n = 16), endocarditis (n = 11), primary bacteremia (n = 10), osteomyelitis and septic arthritis (n = 9), and miscellaneous (n = 5). The median Pitt bacteremia score among the 54 (80.6%) patients with bacteremia was 4. The most common pathogen was methicillin-resistant Staphylococcus aureus (n = 38). Fifty-nine patients (88.1%) were treated with daptomycin after glycopepetide use. Overall, 52 (77.6%) patients achieved clinical success. The all-cause mortality rate at 28 day was 35.8%. In multivariate analysis, the significant predictors of in-hospital mortality in 54 bacteremic patients were malignancies (P = 0.01) and ICU stay (P = 0.02). Adverse effects of daptomycin were generally well-tolerated, leading to discontinuation in 3 patients. Daptomycin-related creatine phosphokinase (CPK) elevations were observed in 4 patients, and all received doses > 8 mg/kg.ConclusionsTreatment with high dose daptomycin as salvage therapy was generally effective and safe in Taiwan. CPK level elevations were more frequent in patients with dose > 8 mg/kg.

Quorum sensing inhibitor FS3-coated vascular graft enhances daptomycin efficacy in a rat model of staphylococcal infection

The aim of the study was to investigate the efficacy of the quorum sensing inhibitor FS3 and daptomycin in preventing prosthesis biofilm in a rat model of staphylococcal vascular graft infection. Graft infections were established in the back subcutaneous tissue of adult male Wistar rats by implantation of Dacron prostheses followed by topical inoculation with 2×107 colony-forming units of Staphylococcus aureus, strain Smith diffuse. The study included a control group, a contaminated group that did not receive any antibiotic prophylaxis and three contaminated groups that received: (i) intraperitoneal daptomycin, (ii) FS3-soacked graft, and (iii) daptomycin plus FS3-soaked graft, respectively. Each group included 15 animals. The infection burden was evaluated by using sonication and quantitative agar culture. Moreover, an in vitro binding-study was performed to quantify the how much FS3 was coated to the surface of the prosthesis. The in vitro studies showed, that minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values for daptomycin were lower in presence of FS3. In in vivo studies, when tested alone, daptomycin and FS3 showed good efficacies. Their combination showed efficacies significantly higher than that of each single compound. Daptomycin is an important candidate for prevention of staphylococcal biofilm related infection and FS3 could serve as an interesting anti-staphylococcal antibiotic enhancer.

Multicenter Evaluation of the Clinical Outcomes of Daptomycin with and without Concomitant β-Lactams in Patients with Staphylococcus aureus Bacteremia and Mild to Moderate Renal Impairment

Patients with underlying renal disease may be vulnerable to vancomycin-mediated nephrotoxicity and Staphylococcus aureus bacteremia treatment failure. In light of recent data demonstrating the successful use of β-lactam plus daptomycin in very difficult cases of S. aureus bacteremia, we examined safety and clinical outcomes for patients who received daptomycin with or without concomitant β-lactams. We identified 106 patients who received daptomycin for S. aureus bacteremia, had mild or moderate renal insufficiency according to FDA criteria, and enrolled in the Cubicin Outcomes Registry and Experience (CORE), a multicenter registry, from 2005 to 2009. Daptomycin treatment success was 81%. Overall treatment efficacy was slightly enhanced with the addition of a β-lactam (87% versus 78%; P = 0.336), but this trend was most pronounced for bacteremia associated with endocarditis or bone/joint infection or bacteremia from an unknown source (90% versus 57%; P = 0.061). Factors associated with reduced daptomycin efficacy (by logistic regression) were an unknown source of bacteremia (odds ratio [OR] = 7.59; 95% confidence interval [CI] = 1.55 to 37.2), moderate renal impairment (OR = 9.11; 95% CI = 1.46 to 56.8), and prior vancomycin failure (OR = 11.2; 95% CI = 1.95 to 64.5). Two patients experienced an increase in creatine phosphokinase (CPK) that resolved after stopping daptomycin. No patients developed worsening renal insufficiency related to daptomycin. In conclusion, daptomycin appeared to be effective and well tolerated in patients with S. aureus bacteremia and mild to moderate renal insufficiency. Daptomycin treatment efficacy might be enhanced with β-lactam combination therapy in primary endovascular and bone/joint infections. Additional studies will be necessary to confirm these findings.

The Safety and Efficacy of Linezolid and Daptomycin as an Additive in Optisol-GS Against Methicillin-Resistant Staphylococcus aureus

Department of Ophthalmology Konya Training and Research Hospital Konya, Turkey Financial disclosures/conflicts of interest: None reported.

Fosfomycin-Daptomycin and Other Fosfomycin Combinations as Alternative Therapies in Experimental Foreign-Body Infection by Methicillin-Resistant Staphylococcus aureus

The efficacy of daptomycin, imipenem, or rifampin with fosfomycin was evaluated and compared with that of daptomycin-rifampin in a tissue cage model infection caused by methicillin-resistant Staphylococcus aureus (MRSA). Strain HUSA 304 was used. The study yielded the following results for MICs (in μg/ml): fosfomycin, 4; daptomycin, 1; imipenem, 0.25; and rifampin, 0.03. The study yielded the following results for minimum bactericidal concentration (MBC) (in μg/ml): fosfomycin, 8; daptomycin, 4; imipenem, 32; and rifampin, 0.5. Daptomycin-rifampin was confirmed as the most effective therapy against MRSA foreign-body infections. Fosfomycin combinations with high doses of daptomycin and rifampin were efficacious alternative therapies in this setting. Fosfomycin-imipenem was relatively ineffective and did not protect against resistance.

Efficacy and safety of intravenous daptomycin in Japanese patients with skin and soft tissue infections

Daptomycin is a lipopeptide antibiotic active against gram-positive organisms and recently approved for marketing in Japan. This study investigates the efficacy and safety of daptomycin in Japanese patients with skin and soft tissue infections (SSTIs) caused by methicillin-resistant Staphylococcus aureus (MRSA) for regulatory filing in Japan. Overall, 111 Japanese patients with SSTI were randomized in this open-label, randomized, active-comparator controlled, parallel-group, multicenter, phase III study. Patients received intravenous daptomycin 4 mg/kg once daily or vancomycin 1 g twice daily for 7–14 days. Efficacy was determined by a blinded Efficacy Adjudication Committee. Among patients with SSTIs caused by MRSA, 81.8 % (95 % CI, 69.1–90.9) of daptomycin recipients and 84.2 % (95 % CI, 60.4–96.6) of vancomycin recipients achieved a successful clinical response at the test-of-cure (TOC) visit. The microbiological success rate against MRSA at the TOC visit was 56.4 % (95 % CI, 42.3–69.7) with daptomycin and 47.4 % (95 % CI, 24.4–71.1) with vancomycin. Daptomycin was generally well tolerated; most adverse events were of mild to moderate severity. The measurement of daptomycin concentration in plasma revealed that patients with mild or moderate impaired renal function showed similar pharmacokinetics profiles to patients with normal renal function. Clinical and microbiological responses, stratified by baseline MRSA susceptibility, suggested that patients infected with MRSA of higher daptomycin MIC showed a trend of lower clinical success with a P value of 0.052 by Cochran–Armitage test. Daptomycin was clinically and microbiologically effective for the treatment of MRSA-associated SSTIs in Japanese patients.

Daptomycin efficacy in the central nervous system of a patient with disseminated methicillin-resistant Staphylococcus aureus infection: a case report

IntroductionStaphylococcus aureus has emerged as a major nosocomial pathogen in the last decades and also represents the second most common pathogen isolated from patients in outpatient settings. Although methicillin-resistant S.aureus infections were traditionally limited to hospitals, community-associated cases of methicillin-resistant S.aureus infections have been reported. In our case, we observed an unexpected event during treatment.Case presentationA 60-year-old Caucasian man developed fever and multiple muscle and brain abscesses caused by Panton-Valentine leukocidin-negative community-associated methicillin-resistant S. aureus.ConclusionAlthough our patient was given antimicrobials active against the isolated methicillin-resistant S. aureus strain, it was only after the introduction of daptomycin that his skin, soft tissue and muscle lesions and also brain manifestations improved.

Randomized Controlled Trial of the Safety and Efficacy of Daptomycin versus Standard-of-Care Therapy for Management of Patients with Osteomyelitis Associated with Prosthetic Devices Undergoing Two-Stage Revision Arthroplasty

The prevalence of Staphylococcus aureus causing prosthetic joint infection (PJI) supports investigation of higher doses of daptomycin in the management of PJI. This was a prospective, randomized controlled trial studying safety and efficacy of daptomycin (6 and 8 mg/kg of body weight) compared with standard-of-care therapy for PJI. This open-label study randomized 75 patients undergoing 2-stage revision arthroplasty to daptomycin at 6 or 8 mg/kg or a comparator (vancomycin, teicoplanin, or semisynthetic penicillin). After prosthesis removal, patients received 6 weeks of antibiotic treatment and a 2- to 6-week antibiotic-free period before implantation of a new prosthesis. Test of cure (TOC) was within 1 to 2 weeks after reimplantation. The primary objective was evaluation of creatine phosphokinase (CPK) levels. Secondary objectives were clinical efficacy and microbiological assessments. Of 73 CPK safety population patients, CPK elevation of >500 U/liter occurred in 4 of 25 (16.0%) (daptomycin, 6 mg/kg) and 5 of 23 (21.7%) (daptomycin, 8 mg/kg) daptomycin-treated patients and 2 of 25 (8.0%) comparator patients. Adverse-event rates were similar among daptomycin and comparator groups. Among modified intent-to-treat patients at TOC, clinical success rates were 14 of 24 (58.3%) for 6 mg/kg daptomycin, 14 of 23 (60.9%) for 8 mg/kg daptomycin, and 8 of 21 (38.1%) for the comparator. Overall microbiological success at TOC was 12 of 24 (50.0%) for 6 mg/kg daptomycin, 12 of 23 (52.2%) for 8 mg/kg daptomycin, and 8 of 21 (38.1%) for comparator patients. In conclusion, daptomycin at 6 and 8 mg/kg given for up to 6 weeks was safe and appeared to be effective in managing staphylococcal PJI using a 2-stage revision arthroplasty technique in a total of 49 patients.

Efficacy of Daptomycin-Cloxacillin Combination in Experimental Foreign-Body Infection Due to Methicillin-Resistant Staphylococcus aureus

Despite the use of daptomycin alone at high doses (greater than 6 mg/kg of body weight/day) against difficult-to-treat infections, clinical failures and resistance appeared. Recently, the combination daptomycin-cloxacillin showed enhanced efficacy in clearing bacteremia caused by methicillin-resistant Staphylococcus aureus (MRSA). The aim of this study was to evaluate the efficacy of daptomycin at usual and high doses (equivalent to 6 and 10 mg/kg/day in humans, respectively) in combination with cloxacillin in a rat tissue cage infection model by MRSA and to compare its efficacy to that of daptomycin-rifampin. We used MRSA strain ATCC BAA-39. In the log- and stationary-phase kill curves, daptomycin-cloxacillin improved the bactericidal activity of daptomycin, especially in log phase. For in vivo studies, therapy was administered intraperitoneally for 7 days with daptomycin at 100 mg/kg/day and 45/mg/kg/day (daptomycin 100 and daptomycin 45), daptomycin 100-cloxacillin at 200 mg/kg/12 h, daptomycin 45-cloxacillin, and daptomycin 100-rifampin at 25 mg/kg/12 h. Daptomycin-rifampin was the best therapy (P < 0.05). Daptomycin 45 was the least effective treatment and did not protect against the emergence of resistant strains. There were no differences between the two dosages of daptomycin plus cloxacillin in any situation, and both protected against resistance. The overall effect of the addition of cloxacillin to daptomycin was a significantly greater cure rate (against adhered bacteria) than that for daptomycin alone. In conclusion, daptomycin-cloxacillin enhanced modestly the in vivo efficacy of daptomycin alone against foreign-body infection by MRSA and was less effective than daptomycin plus rifampin. The benefits of adding cloxacillin to daptomycin should be especially evaluated against infections by rifampin-resistant MRSA and for protection against the emergence of daptomycin nonsusceptibility.

The Safety and Efficacy of Linezolid and Daptomycin as an Additive in Optisol-GS Against Methicillin-Resistant Staphylococcus aureus

To evaluate the efficacy of adding either linezolid or daptomycin to Optisol-GS donor storage medium in reducing methicillin-resistant Staphylococcus aureus (MRSA) contamination of donor corneas. Optisol-GS was supplemented with either linezolid at 2×, 4×, or 10× minimum inhibitory concentration (MIC) or daptomycin and calcium at 5× or 50× MIC. Unsupplemented control groups were also used. Gentamicin-sensitive and gentamicin-resistant isolates of MRSA were added, and vials were refrigerated for 48 hours followed by sampling for viable colony counts immediately upon removal from refrigeration and after warming to room temperature for 3 hours. Safety studies of Optisol-GS supplemented with 50× MIC daptomycin and calcium were performed by evaluating the central corneal thickness and endothelial cell density of the donor cornea. Stability of daptomycin in Optisol-GS at storage was also tested. No added benefit was observed with linezolid supplementation to Optisol-GS against gentamicin-sensitive MRSA, with reduction in viable colony counts by >90% in all groups. No benefit was observed with linezolid supplementation against gentamicin-resistant MRSA, with the majority of inocula remaining viable in all groups. Viable counts of gentamicin-sensitive MRSA and gentamicin-resistant MRSA were effectively reduced with both 5× MIC and 50× MIC daptomycin supplementation. 50× MIC daptomycin-supplemented Optisol-GS had no appreciable effect on the central corneal thickness or endothelial cell density of the donor cornea and was stable at storage for 14 days. The addition of daptomycin to Optisol-GS significantly increases the anti-MRSA activity of the medium without any apparent negative effects on donor corneal tissue.

Clinical experience with daptomycin for the treatment of patients with knee and hip periprosthetic joint infections

To investigate the clinical efficacy and safety of daptomycin in the treatment of hip and knee periprosthetic joint infections (PJIs). We completed a retrospective review of all patients in our institution (n=20) who were treated with daptomycin for hip or knee PJI, over the 36 month period from January 2008 until December 2010. Infection types included eight cases with acute infections, nine cases of chronic infection and three cases of positive intraoperative cultures. Methicillin-resistant coagulase-negative Staphylococcus was the most frequent microorganism found in surgical cultures (40%). Our patients, on average, received daptomycin as salvage therapy at a dose of 6.6 mg/kg/day for 44.9 days. The overall success rate was 78.6% after a median follow-up period of 20 months. In the subgroup of patients with acute PJIs, treatment with daptomycin, debridement and implant retention was successful in all cases. We found two cases of severe side effects (one case of acute renal failure due to massive rhabdomyolysis and one of eosinophilic pneumonia) and two cases of asymptomatic transient creatine phosphokinase (CPK) level elevation. The combination of high daptomycin doses with an adequate surgical approach could be a viable alternative in cases of difficult-to-treat Gram-positive PJIs. Due to the risk of potentially serious adverse events, serum CPK level should be closely monitored.

Daptomycin and Tigecycline Have Broader Effective Dose Ranges than Vancomycin as Prophylaxis against a Staphylococcus aureus Surgical Implant Infection in Mice

Vancomycin is widely used for intravenous prophylaxis against surgical implant infections. However, it is unclear whether alternative antibiotics used to treat methicillin-resistant Staphylococcus aureus (MRSA) infections are effective as prophylactic agents. The aim of this study was to compare the efficacies of vancomycin, daptomycin, and tigecycline as prophylactic therapy against a methicillin-sensitive S. aureus (MSSA) or MRSA surgical implant infection in mice. MSSA or MRSA was inoculated into the knee joints of mice in the presence of a surgically placed medical-grade metallic implant. The efficacies of low- versus high-dose vancomycin (10 versus 110 mg/kg), daptomycin (1 versus 10 mg/kg), and tigecycline (1 versus 10 mg/kg) intravenous prophylaxis were compared using in vivo bioluminescence imaging, ex vivo bacterial counts, and biofilm formation. High-dose vancomycin, daptomycin, and tigecycline resulted in similar reductions in bacterial burden and biofilm formation. In contrast, low-dose daptomycin and tigecycline were more effective than low-dose vancomycin against the implant infection. In this mouse model of surgical implant MSSA or MRSA infection, daptomycin and tigecycline prophylaxis were effective over a broader dosage range than vancomycin. Future studies in humans will be required to determine whether these broader effective dose ranges for daptomycin and tigecycline in mice translate to improved efficacy in preventing surgical implant infections in clinical practice.

Daptomycin lock therapy for grampositive long-term catheter-related bloodstream infections

To evaluate the efficacy of Daptomycin (DPT) lock therapy in the treatment of Grampositive long-term catheter-related bloodstream infections (LT-CRBI). A retrospective review of all patients receiving DPT lock therapy for the treatment of LT-CRBI from December 2009 to May 2010 was conducted. The primary endpoint used in this study was failure to cure the episode of LT-CRBI. Cure was defined as fever disappearance, negative blood cultures within 1 month after the end of treatment, and catheter salvage. Thirteen subjects (seven men, mean age 62 years) were evaluated. There were six Staphylococcus epidermidis, two Staphylococcus hominis, one Staphylococcus haemolyticus, two Enterococcus faecalis and two polymicrobial (S. epidermidis and S. hominis) bloodstream infections. DPT lock therapy was administered for a mean of 14 days (interquartilic range 10-14). Intravenous DPT was administered in nine patients for a mean of 10 days (interquartilic range 5-11). Clinical cure and blood culture sterilisation occurred in 11 of 13 patients (85%). Two patients had fever during treatment and catheters were removed. Median length of follow-up in patients with therapeutic success was 67 days (interquartilic range 14-88). DPT lock therapy demonstrated good in vivo efficacy in LT-CRBI caused by coagulase negative staphylococci and Enterococcus species.

El registro EUCORE: objetivos y resultados generales

The European Cubicin Outcomes Registry and Experience (EUCORE) is an ongoing, retrospective, European, post-marketing, non-comparative database of daptomycin use in patients that have received at least one daptomycin dose. The primary objective is to evaluate the clinical outcomes of patients treated with this drug. This article presents the analysis of patients included in Spanish institutions from January 2006 to March 2010. A total of 726 patients were included: 66% males, 48.6% aged more than 65 years old, and 70% with comorbidities. Daptomycin was administered in the outpatient setting in 20.3% of the patients. More than 50% of the patients received a dose of 6mg/kg/day and in 80% daptomycin was administered as a rescue therapy. The median treatment duration was 14 days. The infections treated were bacteremia (32.51%), skin and soft tissue infections (31.4%), infectious endocarditis (14.33%), infections associated with prosthetic materials (10.9%), osteoarticular infections (6.1%), and others. Infections were caused by Staphylococcus aureus (40.5%; 14.4% methicilllin-resistant), coagulase-negative staphylococci (34.5%), enterococci (11.7%) and group viridans streptococci (2.9%). The overall rate of clinical success was 78.4% (81.5% when administered as first-line therapy and 77.6% when administered as rescue therapy). In patients with renal failure, the efficacy of daptomycin was lower. At the end of therapy, 8.7% of patients showed a decrease in creatinine clearance, and in 25 patients creatine kinase values were more than 10 times higher than normal values. Daptomycin is a safe and effective antimicrobial agent for the treatment of severe infections caused by Gram-positive bacteria.

Tratamiento con daptomicina en pacientes diabéticos

In diabetic patients, there is a high prevalence of skin or nasal carriage of Staphylococcus aureus, which is associated with an increased risk of local or systemic infections and consequently with greater morbidity and mortality. The microorganisms causing most infections in diabetic ulcers and diabetic foot are S. aureus and Streptococcus pyogenes, although chronic diabetic foot infections are generally polymicrobial, including Pseudomonas aeruginosa and enterobacteria. The present article describes experience with daptomycin in the treatment of the most frequent infectious complications in diabetic patients. The Cubicin Outcomes Registry and Experience (CORE) registry contains information on 60 patients with skin and soft tissue infections treated with daptomycin, with a success rate of 83%. Other recent studies comparing daptomycin with vancomycin or semi-synthetic penicillins have also shown the efficacy and safety of daptomycin with cure rates of between 70% and 80%. In the European version of the CORE registry, the EUROCORE, diabetic patients who developed bacteremia or endocarditis due to Gram-positive pathogens and who received daptomycin showed success rates of 76.8% and 72%, respectively. No significant differences were found in a study comparing daptomycin or standard therapy with vancomycin in methicillin-resistant S. aureus (MRSA) or antistaphylococcal penicillin in methicillin-susceptible S. aureus (MSSA) in diabetic patients with bacteremia or endocarditis. Because of its rapid bactericidal action and scarce adverse effects, daptomycin is an attractive antimicrobial agent in the treatment of Gram-positive infections in diabetic patients, whether in monotherapy or in association with other agents.

Retos en el tratamiento antimicrobiano de la endocarditis infecciosa. Papel de la daptomicina

Infections caused by Gram-positive organisms are currently a therapeutic problem because of the emergence and spread of strains with multiple resistance to antibiotics used as first-line therapeutic options. Glycopeptides, considered as alternative drugs, have limited effectiveness in the treatment of serious infections caused by these microorganisms, including infective endocarditis. Among the new antimicrobial agents recently licensed for use in human therapy, daptomycin offers a good clinical efficacy profile in both clinical trials and in experiences of clinical use registered after approval. Because of its bactericidal activity and potential synergy with other antimicrobial agents, such as beta-lactams, fosfomycin and aminoglycosides, daptomycin is among the first-line options in the treatment of infections caused by staphylococci and probably enterococci with multiple resistance to antibiotics. Daptomycin also offers an excellent safety profile and a very low rate of resistance. Further studies, including many patients with this serious infection, should precisely determine the clinical efficacy of daptomycin in this indication.

Safety and efficacy of daptomycin for the treatment of hospitalized adult patients in Taiwan with severe staphylococcal infections

The safety and efficacy of treating serious infections caused by Staphylococcus aureus with daptomycin in a Taiwanese population were studied. A retrospective, multicenter study was performed in Taiwan between December 2007 and June 2009. This study included adult hospitalized patients who had received intravenous daptomycin therapy for infections caused by S aureus. All patients were followed until discharge from the hospital or death. A total of 52 patients (males, n=44; median age: 62 years) were evaluated. Infections included complicated skin and soft-tissue infections (n=14), catheter-related bacteremia (n=14), osteomyelitis and septic arthritis (n=12), endovascular infections and endocarditis (n=11), and urinary tract infections (n=1). Overall, 47 (90.4%) patients were successfully treated and their clinical symptoms were resolved. Adverse effects related to daptomycin were detected in nine patients, but none were required to discontinue daptomycin. The results support daptomycin as an effective and safe treatment for staphylococcal infections in Taiwanese populations.

Efficacy of Daptomycin versus Vancomycin in an Experimental Model of Foreign-Body and Systemic Infection Caused by Biofilm Producers and Methicillin-Resistant Staphylococcus epidermidis

Staphylococcus epidermidis is a frequent cause of device-associated infections. In this study, we compared the efficacy of daptomycin versus vancomycin against biofilm-producing methicillin-resistant S. epidermidis (MRSE) strains in a murine model of foreign-body and systemic infection. Two bacteremic biofilm-producing MRSE strains were used (SE284 and SE385). The MIC of daptomycin was 1 mg/liter for both strains, and the MICs of vancomycin were 4 and 2 mg/liter for SE284 and for SE385, respectively. The in vitro bactericidal activities of daptomycin and vancomycin were evaluated by using time-kill curves. The model of foreign-body and systemic infection of neutropenic female C57BL/6 mice was used to ascertain in vivo efficacy. Animals were randomly allocated into three groups (n = 15): without treatment (controls) or treated with daptomycin at 50 mg/kg/day or vancomycin at 440 mg/kg/day. In vitro, daptomycin showed concentration-dependent bactericidal activity, while vancomycin presented time-dependent activity. In the experimental in vivo model, daptomycin and vancomycin decreased liver and catheter bacterial concentrations (P < 0.05) and increased the survival and the number of sterile blood cultures (P < 0.05) using both strains. Daptomycin produced a reduction in the bacterial liver concentration higher than 2.5 log(10) CFU/g compared to vancomycin using both strains, with this difference being significant (P < 0.05) for infection with SE385. For the catheter bacterial concentrations, daptomycin reduced the concentration of SE284 3.0 log(10) CFU/ml more than did vancomycin (P < 0.05). Daptomycin is more effective than vancomycin for the treatment of experimental foreign-body and systemic infections by biofilm-producing methicillin-resistant S. epidermidis.