ABSTRACT
VEXAS syndrome is a recently described autoinflammatory syndrome caused by the somatic acquisition of UBA1 mutations in myeloid precursors and is frequently associated with hematologic malignancies, chiefly myelodysplastic syndromes. Disease presentation can mimic several rheumatologic disorders, delaying the diagnosis. We describe a case of atypical presentation resembling late-onset axial spondylarthritis, later progressing to a systemic inflammatory syndrome with chondritis, cutaneous vasculitis, and transfusion-dependent anemia, requiring high doses of steroids. Ruxolitinib was used as the first steroid-sparing strategy without response. However, azacitidine showed activity in controlling both inflammation and the mutant clone. This case raises the question of whether azacitidine's anti-inflammatory effects are dependent on or independent of clonal control. We discuss the potential relevance of molecular remission in VEXAS syndrome and highlight the importance of a multidisciplinary team for the care of such complex patients.
Subject(s)
Azacitidine , Sacroiliitis , Ubiquitin-Activating Enzymes , Humans , Azacitidine/therapeutic use , Sacroiliitis/drug therapy , Sacroiliitis/diagnosis , Sacroiliitis/genetics , Ubiquitin-Activating Enzymes/genetics , Mutation , Male , Middle Aged , Treatment Outcome , Myelodysplastic Syndromes/drug therapy , Myelodysplastic Syndromes/genetics , Myelodysplastic Syndromes/diagnosisSubject(s)
Aerococcus , Endocarditis, Bacterial , Gram-Positive Bacterial Infections , Recurrence , Urinary Tract Infections , Humans , Urinary Tract Infections/microbiology , Urinary Tract Infections/diagnosis , Urinary Tract Infections/drug therapy , Aerococcus/isolation & purification , Endocarditis, Bacterial/microbiology , Endocarditis, Bacterial/diagnosis , Endocarditis, Bacterial/drug therapy , Gram-Positive Bacterial Infections/diagnosis , Gram-Positive Bacterial Infections/microbiology , Gram-Positive Bacterial Infections/drug therapy , MaleABSTRACT
Introduction Pseudomonas aeruginosa displays resistance to several available antibiotics. Infections caused by this pathogen are associated with a high mortality, morbidity, and considerable healthcare resource utilization and costs. This study was aimed at describing the use of ceftolozane/tazobactam (C/T) for the treatment of patients with P. aeruginosa infections. Methods Case series analysis of hospitalized patients treated with C/T for P. aeruginosa infections in five public Portuguese hospitals. Patients presenting with infections caused by this pathogen and receiving C/T for at least 72h during hospitalization were eligible. Results Sixty-four hospitalized patients with P. aeruginosa infections treated with C/T were evaluated between December 2016 and July 2019. Most patients were aged between 60 and 79 years (53.9%). Patients presented a total of 68 P. aeruginosa infections, with respiratory infections being the most common (28.1%, 18 out of 64). Most P. aeruginosa strains (85.9%, 55 out of 64) were extensively drug-resistant (XDR). C/T was mostly used as targeted therapy (98.4%, 63 out of 64 patients) and as monotherapy (72.7%, 47 out of 64 patients). Combination therapy was used in 47.4% (9 out of 19) of patients with bacteriemia. Most patients had successful microbiological (79.2%, 42 out of 53) and clinical (78.7%, 48 out of 61) outcomes. All-cause in-hospital mortality rate was 34.4%. Conclusion The present case series contributes to the body of evidence suggesting that C/T is an effective and safe option for treating P. aeruginosa infections, namely those caused by XDR strains, both when used as mono- or combination therapy (AU)
Introducción Pseudomonas aeruginosa presenta mecanismos de resistencia a diversos antibióticos. Las infecciones causadas por este patógeno aumentan la morbimortalidad, el uso de recursos y los costos asociados. Este estudio tuvo como objetivo describir el uso de ceftolozano/tazobactam (C/T) para el tratamiento de pacientes con infecciones por P. aeruginosa. Métodos Serie de casos de pacientes hospitalizados con infecciones por P. aeruginosa que fueron tratados con C/T en 5 hospitales portugueses. Fueron incluidos pacientes que presentaban infecciones por este patógeno y recibían terapéutica con C/T durante al menos 72 horas. Resultados Entre diciembre de 2016 y julio de 2019 fueron analizados 64 pacientes hospitalizados con infecciones por P. aeruginosa tratados con C/T. La mayoría tenían entre 60 y 79 años (53,9%). Se aislaron 68 infecciones por P. aeruginosa, siendo más frecuentes las respiratorias (28,1%; 18/64). La mayoría de las cepas de P. aeruginosa (85,9%; 55764) eran extremadamente resistentes. El C/T se utilizó principalmente como terapia dirigida (98,4%; 63/64 pacientes) y en monoterapia (72,7%; 47/64 pacientes). La terapia combinada se utilizó en el 47,4% (9/19) de los pacientes con bacteriemia. La mayoría de los pacientes tuvieron resultados microbiológicos (79,2%; 42/53) y clínicos (78,7%; 48/61) satisfactorios. La tasa de mortalidad intrahospitalaria por todas las causas fue del 34,4%. Conclusión La presente serie de casos sustenta que la terapéutica con C/T es una alternativa efectiva y segura para las infecciones por P. aeruginosa, particularmente por cepas extremadamente resistentes, en monoterapia o en terapia combinada (AU)
Subject(s)
Humans , Male , Female , Adolescent , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Cross Infection/drug therapy , Cross Infection/microbiology , Pseudomonas Infections/drug therapy , Tazobactam/administration & dosage , Cephalosporins/administration & dosage , Anti-Bacterial Agents/administration & dosage , Drug Resistance, Multiple, Bacterial , Retrospective StudiesABSTRACT
INTRODUCTION: Pseudomonas aeruginosa displays resistance to several available antibiotics. Infections caused by this pathogen are associated with a high mortality, morbidity, and considerable healthcare resource utilization and costs. This study was aimed at describing the use of ceftolozane/tazobactam (C/T) for the treatment of patients with P. aeruginosa infections. METHODS: Case series analysis of hospitalized patients treated with C/T for P. aeruginosa infections in five public Portuguese hospitals. Patients presenting with infections caused by this pathogen and receiving C/T for at least 72h during hospitalization were eligible. RESULTS: Sixty-four hospitalized patients with P. aeruginosa infections treated with C/T were evaluated between December 2016 and July 2019. Most patients were aged between 60 and 79 years (53.9%). Patients presented a total of 68 P. aeruginosa infections, with respiratory infections being the most common (28.1%, 18 out of 64). Most P. aeruginosa strains (85.9%, 55 out of 64) were extensively drug-resistant (XDR). C/T was mostly used as targeted therapy (98.4%, 63 out of 64 patients) and as monotherapy (72.7%, 47 out of 64 patients). Combination therapy was used in 47.4% (9 out of 19) of patients with bacteriemia. Most patients had successful microbiological (79.2%, 42 out of 53) and clinical (78.7%, 48 out of 61) outcomes. All-cause in-hospital mortality rate was 34.4%. CONCLUSION: The present case series contributes to the body of evidence suggesting that C/T is an effective and safe option for treating P. aeruginosa infections, namely those caused by XDR strains, both when used as mono- or combination therapy.