Opportunities for antimicrobial stewardship in patients with acute bacterial skin and skin structure infections who are unsuitable for beta-lactam antibiotics: a multicenter prospective observational study.

PURPOSE: The objective of this prospective, observational study was to describe the treatment, severity assessment and healthcare resources required for management of patients with acute bacterial skin and skin structure infections who were unsuitable for beta-lactam antibiotic treatments. METHODS: Patients were enrolled across five secondary care National Health Service hospitals. Eligible patients had a diagnosis of acute bacterial skin and skin structure infection and were considered unsuitable for beta-lactam antibiotics (e.g. confirmed/suspected methicillin-resistant Staphylococcus aureus, beta-lactam allergy). Data regarding diagnosis, severity of the infection, antibiotic treatment and patient management were collected. RESULTS: 145 patients with acute bacterial skin and skin structure infection were included; 79% (n = 115) patients received greater than two antibiotic regimens; median length of the first antibiotic regimen was 2 days (interquartile range of 1-5); median time to switch from intravenous to oral antibiotics was 4 days (interquartile range of 3-8, n = 72/107); 25% (n = 10/40) patients with Eron class 1 infection had systemic inflammatory response syndrome, suggesting they were misclassified. A higher proportion of patients with systemic inflammatory response syndrome received treatment in an inpatient setting, and their length of stay was prolonged in comparison with patients without systemic inflammatory response syndrome. CONCLUSION: There exists an urgent need for more focused antimicrobial stewardship strategies and tools for standardised clinical assessment of acute bacterial skin and skin structure infection severity in patients who are unsuitable for beta-lactam antibiotics. This will lead to optimised antimicrobial treatment strategies and ensure effective healthcare resource utilisation.

Daptomycin: an evidence-based review of its role in the treatment of Gram-positive infections.

Infections caused by Gram-positive pathogens remain a major public health burden and are associated with high morbidity and mortality. Increasing rates of infection with Gram-positive bacteria and the emergence of resistance to commonly used antibiotics have led to the need for novel antibiotics. Daptomycin, a cyclic lipopeptide with rapid bactericidal activity against a wide range of Gram-positive bacteria including methicillin-resistant Staphylococcus aureus, has been shown to be effective and has a good safety profile for the approved indications of complicated skin and soft tissue infections (4 mg/kg/day), right-sided infective endocarditis caused by S. aureus, and bacteremia associated with complicated skin and soft tissue infections or right-sided infective endocarditis (6 mg/kg/day). Based on its pharmacokinetic profile and concentration-dependent bactericidal activity, high-dose (>6 mg/kg/day) daptomycin is considered an important treatment option in the management of various difficult-to-treat Gram-positive infections. Although daptomycin resistance has been documented, it remains uncommon despite the increasing use of daptomycin. To enhance activity and to minimize resistance, daptomycin in combination with other antibiotics has also been explored and found to be beneficial in certain severe infections. The availability of daptomycin via a 2-minute intravenous bolus facilitates its outpatient administration, providing an opportunity to reduce risk of health care-associated infections, improve patient satisfaction, and minimize health care costs. Daptomycin, not currently approved for use in the pediatric population, has been shown to be widely used for treating Gram-positive infections in children.

Real-world daptomycin use across wide geographical regions: results from a pooled analysis of CORE and EU-CORE.

BACKGROUND: Pooled data from two large registries, Cubicin(®) Outcomes Registry and Experience (CORE; USA) and European Cubicin(®) Outcomes Registry and Experience (EU-CORE; Europe, Latin America, and Asia), were analyzed to determine the characteristics and clinical outcomes of daptomycin therapy in patients with Gram-positive infections across wide geographical regions. METHODS: Patients receiving at least one dose of daptomycin between 2004 and 2012 for the treatment of Gram-positive infections were included. Clinical success was defined as an outcome of 'cured' or 'improved'. Post-treatment follow-up data were collected for a subset of patients (CORE: osteomyelitis and orthopedic foreign body device infection; EU-CORE: endocarditis, intracardiac/intravascular device infection, osteomyelitis, and orthopedic device infection). Safety was assessed for up to 30 days after daptomycin treatment. RESULTS: In 11,557 patients (CORE, 5482; EU-CORE, 6075) treated with daptomycin (median age, 62 [range, 1-103] years), the most frequent underlying conditions were cardiovascular disease (54.7 %) and diabetes mellitus (28.0 %). The most commonly treated primary infections were complicated skin and soft tissue infection (cSSTI; 31.2 %) and bacteremia (21.8 %). The overall clinical success rate was 77.2 % (uncomplicated SSTI, 88.3 %; cSSTI, 81.0 %; osteomyelitis, 77.7 %; foreign body/prosthetic infection (FBPI), 75.9 %; endocarditis, 75.4 %; and bacteremia, 69.5 %). The clinical success rate was 79.1 % in patients with Staphylococcus aureus infections (MRSA, 78.1 %). An increasing trend of high-dose daptomycin (>6 mg/kg/day) prescribing pattern was observed over time. Clinical success rates were higher with high-dose daptomycin treatment for endocarditis and FBPI. Adverse events (AEs) and serious AEs possibly related to daptomycin therapy were reported in 628 (5.4 %) and 133 (1.2 %) patients, respectively. CONCLUSIONS: The real-world data showed that daptomycin was effective and safe in the treatment of various Gram-positive infections, including those caused by resistant pathogens, across wide geographical regions.

Real-World Treatment of Complicated Skin and Soft Tissue Infections with Daptomycin: Results from a Large European Registry (EU-CORE).

INTRODUCTION: The objective of this analysis was to describe in real-life settings the clinical outcomes and safety associated with daptomycin treatment in a cohort of patients with complicated skin and soft tissues infection (cSSTI). METHODS: All patients with cSSTI who had received at least one dose of daptomycin between January 2006 and April 2012 were identified from a non-interventional, multicenter, retrospective registry (European Cubicin(®) Outcome Registry and Experience; EU-CORE(SM)). RESULTS: Of the 6075 patients included in the EU-CORE registry, 1927 (31.7%) were diagnosed with cSSTI (male, 63.8%; median age, 63 years). The most frequent underlying diseases were cardiovascular disease (58.1%) and diabetes mellitus (40.7%). The most frequent cSSTIs included surgical site infections (34.9%), wound infections (20.2%) and diabetic foot infections (19.9%). The most frequently prescribed doses of daptomycin were 4 mg/kg/day (38.9%) and 6 mg/kg/day (35.2%). A total of 1126 (58.4%) patients received antibiotics prior to daptomycin treatment; treatment failure (53.7%) was the most common reason for switching to daptomycin. The majority of hospitalized patients (61.8%) were treated with concomitant antibiotics. Among patients with positive cultures, Staphylococcus aureus (51.9%; 673/1297) was the most common pathogen. The overall clinical success rate was 84.6%; for infections caused by S. aureus, the success rate was 87.2% (methicillin susceptible, 87.8%; methicillin resistant, 87.0%). Adverse events possibly related to daptomycin treatment were reported in 2.4% of patients and adverse events led to drug discontinuation in 2.4% of patients. CONCLUSION: Daptomycin treatment resulted in high clinical success rates in patients with different cSSTI subtypes, the majority of whom having failed previous antibiotic therapy. Daptomycin was well tolerated and there were no new or unexpected safety findings.

Daptomycin in the Clinical Setting: 8-Year Experience with Gram-positive Bacterial Infections from the EU-CORE(SM) Registry.

INTRODUCTION: The aim of this study was to evaluate the clinical outcomes and safety of daptomycin therapy in patients with serious Gram-positive infections. METHODS: Patients were enrolled in the European Cubicin(®) Outcomes Registry and Experience (EU-CORE(SM)), a non-interventional, multicenter, observational registry. The real-world data were collected across 18 countries (Europe, Latin America, and Asia) for patients who had received at least one dose of daptomycin between January 2006 and April 2012. Two-year follow-up data were collected until 2014 for patients with endocarditis, intracardiac/intravascular device infection, osteomyelitis, or orthopedic device infection. RESULTS: A total of 6075 patients were enrolled. The most common primary infections were complicated skin and soft tissue infection (31.7%) and bacteremia (20.7%). Staphylococcus aureus was the most frequently reported pathogen (42.9%; methicillin-resistant S. aureus [MRSA], 23.2%), followed by Staphylococcus epidermidis and other coagulase-negative staphylococci (CoNS, 28.5%). The most commonly prescribed dose of daptomycin was 6 mg/kg/day (43.6%), and the median duration of therapy was 11 (range 1-300) days. Overall clinical success rate was 80.5%, and was similar whether daptomycin was used as first-line (82.9%) or second-line (79.2%) therapy. Clinical success rates were high in patients with S. aureus (83.9%; MRSA 83.0%) and CoNS (including S. epidermidis, 82.5%) infections. The majority of patients with endocarditis or intracardiac/intravascular device infection (86.7%) or osteomyelitis/orthopedic device infection (85.9%) had a sustained response during the 2-year follow-up period. There were no new or unexpected safety findings. CONCLUSION: Results from real-world clinical experience showed that daptomycin is a valuable therapeutic option in the management of various difficult-to-treat Gram-positive infections. FUNDING: This study was funded by Novartis Pharma AG.

Effectiveness and safety of daptomycin in complicated skin and soft-tissue infections and bacteraemia in clinical practice: results of a large non-interventional study.

This retrospective analysis of patients from eight countries included in the European Cubicin(®) Outcomes Registry and Experience (EU-CORE(SM)) captures the first post-approval years of clinical experience with daptomycin in its licensed indications. Of the total 1127 patients enrolled in EU-CORE between 2006 and 2008, 373 had a primary complicated skin and soft-tissue infection (cSSTI), most commonly surgical-site infection (48%), and 244 had bacteraemia, 55% of which were catheter-related. The most common pathogens were Staphylococcus aureus in cSSTIs (43%) and coagulase-negative staphylococci in bacteraemia (36%). The most frequently prescribed daptomycin doses were 4 mg/kg and 6 mg/kg for cSSTIs, and 6 mg/kg for bacteraemia. The median duration of inpatient and outpatient treatment, respectively, was 13 days and 8 days for cSSTIs and 8 days and 10 days for bacteraemia. Clinical success was reported for 81% of patients with cSSTIs and 77% with bacteraemia, with 82% success overall for infections caused by S. aureus. A trend towards higher clinical success was noted with higher daptomycin doses in bacteraemia (78% for 6 mg/kg vs. 90% for doses >6 mg/kg). Daptomycin demonstrated a favourable safety profile. Adverse events regardless of relationship to study drug were reported for 11% of patients with cSSTIs and 24% with bacteraemia, most commonly septic shock [7 patients (2%) with cSSTIs and 5 patients (2%) with bacteraemia]. These results demonstrate that daptomycin is effective and well tolerated in the treatment of cSSTIs and bacteraemia caused by Gram-positive bacteria in clinical practice.

Clinical experience with daptomycin in Europe: the first 2.5 years.

OBJECTIVES: To describe the patient populations and infections being treated with daptomycin, as well as the efficacy and safety outcomes. PATIENTS AND METHODS: Data from the European Cubicin Outcomes Registry and Experience (EU-CORESM), retrospectively collected at 118 institutions between January 2006 and August 2008, were analysed. RESULTS: Daptomycin treatment was documented in 1127 patients with diverse infections, including complicated skin and soft tissue infections (33%), bacteraemia (22%), endocarditis (12%) and osteomyelitis (6%). It was used empirically, before microbiological results became available, in 53% of patients. Staphylococcus aureus was the most common pathogen (34%), with 52% of isolates resistant to methicillin; coagulase-negative staphylococci and enterococci were also frequent, with 22% of Enterococcus faecium isolates resistant to vancomycin. Daptomycin was used as first-line therapy in 302 (27%) patients. When used second line, the most common reasons for discontinuation of previous antibiotic were treatment failure and toxicity or intolerance. The use of concomitant antibiotics was reported in 65% of patients. Most frequent doses were 6 mg/kg (47%) and 4 mg/kg (32%). The median duration of daptomycin therapy was 10 days (range 1-246 days) in the inpatient setting and 13 days (range 2-189 days) in the outpatient setting. The overall clinical success rate was 79%, with a clinical failure rate of <10% for all infection types. Low failure rates were observed in first- and second-line therapy (6% and 8%, respectively). Daptomycin demonstrated a favourable safety and tolerability profile regardless of treatment duration. CONCLUSIONS: Daptomycin has a relevant role in the treatment of Gram-positive infections.

Cefalosporinas de tercera generación: las dos caras de la moneda / Third generation cephalosporins: the 2 faces of a coin

En este artículo se revisan las principales características farmacológicas e indicaciones de las cefalosporinas de tercera generación, así como los mecanismos de resistencia bacteriana a estos antibióticos, poniendo particular interés en el problema epidemiológico que significa su uso empírico e indiscriminado, dada la capacidad que tienen de inducir la producción de beta-lactamasas y resistencia a otros antibióticos. Ante el uso cada vez más frecuente de las nuevas cefalosporinas en nuestro país, consideramos que este es un momento oportuno para hacer una llamada de atención a la comunidad médica, antes de que esto se vuelva un problema grave en México, por lo que se proponen algunas medidas para limitar su prescripción a aquellas situaciones clínicas, en las que no existen otras alternativas terapéuticas más adecuadas