daptomycin
Fuentes regulatorias consultadas
Indicaciones aprobadas
- Infecciones complicadas de piel y tejidos blandos y bacteriemia por Staphylococcus aureus, incluida endocarditis derecha; no está indicada para neumonía.
Contraindicaciones
Absolutas
- Hipersensibilidad a daptomicina.
Advertencias clínicas
- Controla CPK al menos semanalmente y con mayor frecuencia en insuficiencia renal o con estatinas. Suspende si hay síntomas con CPK >5 veces el límite superior o sin síntomas con CPK >10 veces. — CIMA/AEMPS, ficha técnica 05328001
- Puede causar neumonía eosinofílica, habitualmente a las 2–4 semanas, además de DRESS, nefritis tubulointersticial y neuropatía; suspende y evalúa ante fiebre, disnea o infiltrados. — CIMA/AEMPS, ficha técnica 05328001
Interacciones medicamentosas
- SeveraEstatinas
Mecanismo: Aumentan el riesgo de miopatía y rabdomiólisis.
Recomendación: Considera suspender temporalmente la estatina y controla CPK con mayor frecuencia.
CIMA/AEMPS, ficha técnica 05328001
- ModeradaReactivos de PT/INR
Mecanismo: Puede causar una prolongación falsa dependiente del reactivo.
Recomendación: Obtén la muestra cerca del valle y usa un reactivo alternativo si el resultado no concuerda.
CIMA/AEMPS, ficha técnica 05328001
Eventos adversos
Comunes (≥1%)
Reacciones en el lugar de perfusión, cefalea, náuseas y elevación de CPK
Raros pero graves
Rabdomiólisis, neumonía eosinofílica, DRESS y nefritis tubulointersticial
Embarazo y lactancia
Usa durante el embarazo solo si es claramente necesario. Decide entre suspender lactancia o tratamiento.
Bibliografía reciente (PubMed)
Staphylococcus aureus, a gram-positive bacterium, is the leading cause of death from bacteremia worldwide, with a case fatality rate of 15% to 30% and an estimated 300 000 deaths per year. Staphylococcus aureus bacteremia causes metastatic infection in more than one-third of cases, including endocarditis (≈12%), septic arthritis (7%), vertebral osteomyelitis (≈4%), spinal epidural abscess, psoas abscess, splenic abscess, septic pulmonary emboli, and seeding of implantable medical devices. Patients with S aureus bacteremia commonly present with fever or symptoms from metastatic infection, such as pain in the back, joints, abdomen or extremities, and/or change in mental status. Risk factors include intravascular devices such as implantable cardiac devices and dialysis vascular catheters, recent surgical procedures, injection drug use, diabetes, and previous S aureus infection. Staphylococcus aureus bacteremia is detected with blood cultures. Prolonged S aureus bacteremia (≥48 hours) is associated with a 90-day mortality risk of 39%. All patients with S aureus bacteremia should undergo transthoracic echocardiography; transesophageal echocardiography should be performed in patients at high risk for endocarditis, such as those with persistent bacteremia, persistent fever, metastatic infection foci, or implantable cardiac devices. Other imaging modalities, such as computed tomography or magnetic resonance imaging, should be performed based on symptoms and localizing signs of metastatic infection. Staphylococcus aureus is categorized as methicillin-susceptible (MSSA) or methicillin-resistant (MRSA) based on susceptibility to β-lactam antibiotics. Initial treatment for S aureus bacteremia typically includes antibiotics active against MRSA such as vancomycin or daptomycin. Once antibiotic susceptibility results are available, antibiotics should be adjusted. Cefazolin or antistaphylococcal penicillins should be used for MSSA and vancomycin, daptomycin, or ceftobiprole for MRS
Vancomycin-resistant enterococci (VRE) are common causes of bloodstream infections (BSIs) with high morbidity and mortality rates. They are pathogens of global concern with a limited treatment pipeline. Significant challenges exist in the management of VRE BSI, including drug dosing, the emergence of resistance, and the optimal treatment for persistent bacteremia and infective endocarditis. Therapeutic drug monitoring (TDM) for antimicrobial therapy is evolving for VRE-active agents; however, there are significant gaps in the literature for predicting antimicrobial efficacy for VRE BSIs. To date, TDM has the greatest evidence for predicting drug toxicity for the three main VRE-active antimicrobial agents daptomycin, linezolid, and teicoplanin. This article presents an overview of the treatment options for VRE BSIs, the role of antimicrobial dose optimization through TDM in supporting clinical infection management, and challenges and perspectives for the future.
Ceftobiprole is a cephalosporin that may be effective for treating complicated Staphylococcus aureus bacteremia, including methicillin-resistant S. aureus. In this phase 3, double-blind, double-dummy, noninferiority trial, adults with complicated S. aureus bacteremia were randomly assigned in a 1:1 ratio to receive ceftobiprole at a dose of 500 mg intravenously every 6 hours for 8 days and every 8 hours thereafter, or daptomycin at a dose of 6 to 10 mg per kilogram of body weight intravenously every 24 hours plus optional aztreonam (at the discretion of the trial-site investigators). The primary outcome, overall treatment success 70 days after randomization (defined as survival, bacteremia clearance, symptom improvement, no new S. aureus bacteremia-related complications, and no receipt of other potentially effective antibiotics), with a noninferiority margin of 15%, was adjudicated by a data review committee whose members were unaware of the trial-group assignments. Safety was also assessed. Of 390 patients who underwent randomization, 387 (189 in the ceftobiprole group and 198 in the daptomycin group) had confirmed S. aureus bacteremia and received ceftobiprole or daptomycin (modified intention-to-treat population). A total of 132 of 189 patients (69.8%) in the ceftobiprole group and 136 of 198 patients (68.7%) in the daptomycin group had overall treatment success (adjusted difference, 2.0 percentage points; 95% confidence interval [CI], -7.1 to 11.1). Findings appeared to be consistent between the ceftobiprole and daptomycin groups in key subgroups and with respect to secondary outcomes, including mortality (9.0% and 9.1%, respectively; 95% CI, -6.2 to 5.2) and the percentage of patients with microbiologic eradication (82.0% and 77.3%; 95% CI, -2.9 to 13.0). Adverse events were reported in 121 of 191 patients (63.4%) who received ceftobiprole and 117 of 198 patients (59.1%) who received daptomycin; serious adverse events were reported in 36 patients (18.8%) and 45
This paper discusses the mechanisms of S. aureus drug resistance including: (1) introduction. (2) resistance to beta-lactam antibiotics, with particular emphasis on the mec genes found in the Staphylococcaceae family, the structure and occurrence of SCCmec cassettes, as well as differences in the presence of some virulence genes and its expression in major epidemiological types and clones of HA-MRSA, CA-MRSA, and LA-MRSA strains. Other mechanisms of resistance to beta-lactam antibiotics will also be discussed, such as mutations in the gdpP gene, BORSA or MODSA phenotypes, as well as resistance to ceftobiprole and ceftaroline. (3) Resistance to glycopeptides (VRSA, VISA, hVISA strains, vancomycin tolerance). (4) Resistance to oxazolidinones (mutational and enzymatic resistance to linezolid). (5) Resistance to MLS-B (macrolides, lincosamides, ketolides, and streptogramin B). (6) Aminoglycosides and spectinomicin, including resistance genes, their regulation and localization (plasmids, transposons, class I integrons, SCCmec), and types and spectrum of enzymes that inactivate aminoglycosides. (7). Fluoroquinolones (8) Tetracyclines, including the mechanisms of active protection of the drug target site and active efflux of the drug from the bacterial cell. (9) Mupirocin. (10) Fusidic acid. (11) Daptomycin. (12) Resistance to other antibiotics and chemioterapeutics (e.g., streptogramins A, quinupristin/dalfopristin, chloramphenicol, rifampicin, fosfomycin, trimethoprim) (13) Molecular epidemiology of MRSA.
To review recently published evidence relevant to Staphylococcus aureus bacteremia (SAB). Staphylococcus aureus is the most common pathogen causing co-infections and superinfections in patients with COVID-19. Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia ratios have sharply risen during the pandemic. SAB mortality is 18% at 1 month and 27% at 3 months but has gradually decreased over the last 30 years. Recurrences and reinfections are common (9%). Standardised items to define complicated SAB, and a new cut-off defining persisting bacteremia after 2 days with positive blood cultures have been proposed. Multiple antibiotic combinations have been trialled including vancomycin or daptomycin with β-lactams, fosfomycin, or clindamycin, without significant results. In the recently published guidelines, vancomycin remains the first line of treatment for MRSA bacteremia. For the management of methicillin-susceptible Staphylococcus aureus , cefazolin less frequently causes acute kidney injury than flucloxacillin, and when susceptibility is demonstrated, de-escalation to penicillin G is suggested. Our review confirms that Staphylococcus aureus represents a special aetiology among all causes of bloodstream infections. Pending results of platform and larger trials, its distinct epidemiology and determinants mandate careful integration of clinical variables and best available evidence to optimize patient outcomes.