RESUMO
Background: Consensus guidelines for dosing and monitoring of vancomycin recommend collection of 2 serum concentrations to estimate an area under the curve/minimum inhibitory concentration ratio (AUC/MIC). Use of Bayesian software for AUC estimation and model-informed precision dosing (MIPD) enables pre-steady state therapeutic drug monitoring using a single serum concentration; however, data supporting this approach are limited. Methods: Adult patients with culture-proven gram-positive infections treated with vancomycin ≥72â hours receiving either trough-guided or AUC-guided therapy were included in this retrospective study. AUC-guided therapy was provided using MIPD and single-concentration monitoring. Treatment success, vancomycin-associated acute kidney injury (VA-AKI), and inpatient mortality were compared using a desirability of outcome ranking analysis. The most desirable outcome was survival with treatment success and no VA-AKI, and the least desirable outcome was death. Results: The study population (N = 300) was comprised of an equal number of patients receiving AUC-guided or trough-guided therapy. More patients experienced the most desirable outcome in the AUC-guided group compared to the trough-guided group (58.7% vs 46.7%, P = .037). Rates of VA-AKI were lower (21.3% vs 32.0%, P = .037) and median hospital length of stay was shorter (10 days [interquartile range {IQR}, 8-20] vs 12 days [IQR, 8-25]; P = .025) among patients receiving AUC-guided therapy. Conclusions: AUC-guided vancomycin therapy using MIPD and single-concentration monitoring improved outcomes in patients with culture-proven gram-positive infections. Safety was improved with reduced incidence of VA-AKI, and no concerns for reduced efficacy were observed. Moreover, MIPD allowed for earlier assessment of AUC target attainment and greater flexibility in the collection of serum vancomycin concentrations.
RESUMO
OBJECTIVES: This study aimed to evaluate both efficacy and safety of combination therapy with daptomycin plus ceftaroline (DAP/CPT) versus alternative therapy in the treatment of persistent methicillin-resistant Staphylococcus aureus bacteraemia (MRSAB). METHODS: This retrospective, single-centre study investigated adult patients who underwent a change in antibiotic therapy for persistent MRSAB. Daptomycin plus ceftaroline was compared with alternative therapy after initial treatment with vancomycin or DAP monotherapy was modified. The primary outcome was in-hospital mortality, and several secondary efficacy and safety outcomes were evaluated. RESULTS: A total of 68 patients with persistent MRSAB had initial therapy switched to DAP/CPT (n = 43) or alternative therapy (n = 25). In-hospital mortality was similar with DAP/CPT versus alternative therapy (16.3% vs. 16%; P = 1.0). On average, the total duration of bacteraemia was numerically 1 day less in patients switched to DAP/CPT (11.4 days vs. 12.5 days; P = 0.5). Daptomycin plus ceftaroline was de-escalated in 81% of patients after receiving combination therapy for an average of 12.5 days. Secondary outcomes, including rates of adverse events and emergence of antimicrobial resistance, were similar between the two groups. CONCLUSIONS: Switching to DAP/CPT after approximately 1 week of persistent MRSA bacteraemia may result in similar clinical outcomes when compared with alternative therapy. Rates of adverse events and emergence of antimicrobial resistance were low without a statistically significant difference observed between DAP/CPT and alternative therapy. These findings, as well as the impact of earlier switch or prolonged treatment with the combination, require further investigation.
Assuntos
Bacteriemia , Daptomicina , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Adulto , Humanos , Daptomicina/uso terapêutico , Bacteriemia/tratamento farmacológico , Estudos Retrospectivos , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus , Antibacterianos/uso terapêutico , Testes de Sensibilidade Microbiana , CeftarolinaRESUMO
BACKGROUND: Over the past 25 years, researchers have performed >120 randomized controlled trials (RCTs) illustrating short courses to be non-inferior to long courses of antibiotics for common bacterial infections. OBJECTIVE: We sought to determine whether clinical data from RCTs affirm the mantra of 'shorter is better' for antibiotic durations in 7 common infections: pneumonia, urinary tract infection, intra-abdominal infection, bacteraemia, skin and soft tissue infection, bone and joint infections, pharyngitis and sinusitis. SOURCES: Published RCTs comparing short- versus long-course antibiotic durations were identified through searches of PubMed and clinical guideline documents. CONTENT: Short-course antibiotic durations consistently result in similar treatment success rates as longer antibiotic courses among patients with community-acquired pneumonia, complicated urinary tract infections in women, gram-negative bacteraemia, and skin and soft tissue infections when the diagnosis is confirmed, appropriate antimicrobials are used, and patients show clinical signs of improvement. For patients with osteomyelitis, 6 weeks of antibiotics is adequate for the treatment of osteomyelitis in the absence of implanted foreign bodies and surgical debridement. Whether durations can be further shortened with debridement is unclear, although small studies are promising. IMPLICATIONS: With few exceptions, short courses were non-inferior to long courses; future research should focus on appropriately defining the patient population, ensuring the correct choice and dose of antimicrobials and developing meaningful outcomes relevant for frontline clinicians.
Assuntos
Bacteriemia , Osteomielite , Pneumonia , Infecções dos Tecidos Moles , Infecções Urinárias , Feminino , Humanos , Antibacterianos/uso terapêutico , Infecções Urinárias/tratamento farmacológico , Osteomielite/tratamento farmacológico , Osteomielite/microbiologia , Infecções dos Tecidos Moles/tratamento farmacológico , Pneumonia/tratamento farmacológico , Bacteriemia/tratamento farmacológicoRESUMO
The use of fecal microbiota transplantation (FMT) was first described in China in the 4th century by Ge Hong when "yellow soup," a fecal slurry, was administered for the treatment of severe food poisoning and diarrhea, a practice that continued for centuries. Bedouin groups also consumed stools of their camels as a remedy for dysentery. FMT was also applied in veterinary medicine in Europe in the 16th century. Additional therapeutic use of human excretions was described in Europe in the 18th and 19th century and in World War II, when gut bacteria were administered to German soldiers suffering from dysentery in the North African campaign. More scientifically, Eismann, in 1958, utilized fecal transplantation via enema in 4 patients for the treatment of severe pseudomembranous colitis with success. Following this report a number of isolated cases were published describing the use of FMT by different delivery routes for the treatment of a variety of illnesses.
Assuntos
Clostridioides difficile/fisiologia , Infecções por Clostridium/história , Transplante de Microbiota Fecal/história , Infecções por Clostridium/terapia , Enterocolite Pseudomembranosa/história , Enterocolite Pseudomembranosa/terapia , História do Século XV , História do Século XVI , História do Século XVII , História do Século XVIII , História do Século XIX , História do Século XX , História do Século XXI , História Antiga , História Medieval , HumanosRESUMO
We report the use of fecal microbiota transplantation in a single heart-kidney transplant recipient with recurrent Clostridium difficile, vancomycin-resistant Enterococcus (VRE) fecal dominance, and recurrent VRE infections. Fecal microbiota transplantation resulted in the reconstruction of a diverse microbiota with (1) reduced relative abundance of C difficile and VRE and (2) positive clinical outcome.