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INTRODUCTION: The effect of remdesivir on COVID-19 mortality remains conflicting. Elderly individuals are at risk for poor COVID-19 outcomes. We aimed to assess the effect of remdesivir on COVID-19 mortality among elderly individuals, using real-world data. METHODS: Retrospective multinational cohort of individuals aged ≥65 years, hospitalized with COVID-19 in six medical centres between January 2020 and May 2021. Associations with in-hospital mortality were evaluated using a multivariable logistic regression model with propensity score adjustment for remdesivir therapy and while implementing generalized estimating equations to control for centre effect. Sensitivity analysis was performed by stratification according to the degree of respiratory support. RESULTS: Of 3010 individuals included, 2788 individuals required either oxygen supplementation or non-invasive/invasive mechanical ventilation, 489 (16%) were treated with remdesivir, and 836 (28%) died. Median age was 77 (IQR 70-84) years and 42% were women. Remdesivir was the only therapeutic intervention associated with decreased mortality [adjusted OR (aOR) 0.49, 95% CI 0.37-0.66, Pâ<â0.001]. This protective effect was shown for individuals requiring oxygen support and non-invasive mechanical ventilation, while no association was found among individuals necessitating invasive mechanical ventilation.Risk factors for mortality included invasive ventilation (aOR 5.18, 95% CI 2.46-10.91, Pâ<â0.001), higher serum creatinine (aOR 1.25, 95% CI 1.09-1.43, Pâ=â0.001) and dyspnoea (aOR 1.40, 95% CI 1.07-1.84, Pâ=â0.015) on presentation, and other non-modifiable factors, such as comorbidities. CONCLUSIONS: Among elderly individuals hospitalized with COVID-19, remdesivir carries survival benefit for those with moderate to severe disease. Its role among individuals with critical illness should be further assessed.
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COVID-19 , Anciano , Humanos , Femenino , Masculino , Tratamiento Farmacológico de COVID-19 , Estudios Retrospectivos , Mortalidad Hospitalaria , Antivirales/uso terapéutico , Alanina/uso terapéuticoRESUMEN
BACKGROUND: Older adults and immunocompromised individulas are often excluded from vaccine trials. AIM: We hypothesised that during the coronavirus disease 2019 (COVID-19) pandemic, the proportion of trials excluding these patients decreased. METHODS: Using the US Food and Drug Administration and and European Medicines Agency search engines, we identified all vaccines approved against pneumococcal disease, influenza (quadrivalent vaccines), and COVID-19 from 2011 to 2021. Study protocols were screened for direct and indirect age exclusion criteria and exclusion of immunocompromised individuals. In addition, we reviewed the studies with no explicit exclusion criteria and investigated the actual inclusion of those individuals. RESULTS: We identified 2024 trial records; 1702 were excluded (e.g., use of other vaccine or risk group); and 322 studies were eligible for our review. Among the pneumococcal and influenza vaccine trials (n = 193), 81 (42%) had an explicit direct age exclusion, and 150 (78%) had an indirect age-related exclusion. In total, 163 trials (84%) trials were likely to exclude older adults. Among the COVID-19 vaccine trials (n = 129), 33 (26%) had direct age exclusion and 82 (64%) had indirect age exclusion; in total, 85 (66%) trials were likely to exclude older adults. Therefore was a 18% decrease in the proportion of trials with age-related exclusion between 2011 and 2021 (only influenza and pneumococcal vaccine trials) and 2020-2021 (only COVID-19 vaccine trials) (p = 0.014). In a sub-analysis assessing observational and randomised trials, the decrease was 25% and 9%, respectively. Immunocompromised individuals were included in 87 (45%) of the pneumococcal and influenza vaccine trials compared with 54 (42%) of the COVID-19 vaccine trials (p = 0.058). CONCLUSIONS: During the COVID-19 pandemic, we found a decrease in the exclusion of older adults from vaccine trials but no significant change in the inclusion of immunocompromised individulas.
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COVID-19 , Vacunas contra la Influenza , Gripe Humana , Humanos , Anciano , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Vacunas contra la Influenza/uso terapéutico , Vacunas contra la COVID-19/uso terapéutico , Pandemias/prevención & control , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas Neumococicas/uso terapéuticoRESUMEN
Acute myeloid leukemia is characterized by the accumulation of clonal myeloid blast cells unable to differentiate into mature leukocytes. Chemotherapy induces remission in the majority of patients, but relapse rates are high and lead to poor clinical outcomes. Because this is primarily caused by chemotherapy-resistant leukemic stem cells (LSCs), it is essential to eradicate LSCs to improve patient survival. LSCs have predominantly been studied at the transcript level, thus information about posttranscriptionally regulated genes and associated networks is lacking. Here, we extend our previous report on LSC proteomes to healthy age-matched hematopoietic stem and progenitor cells (HSPCs) and correlate the proteomes to the corresponding transcriptomes. By comparing LSCs to leukemic blasts and healthy HSPCs, we validate candidate LSC markers and highlight novel and potentially targetable proteins that are absent or only lowly expressed in HSPCs. In addition, our data provide strong evidence that LSCs harbor a characteristic energy metabolism, adhesion molecule composition, as well as RNA-processing properties. Furthermore, correlating proteome and transcript data of the same individual samples highlights the strength of proteome analyses, which are particularly potent in detecting alterations in metabolic pathways. In summary, our study provides a comprehensive proteomic and transcriptomic characterization of functionally validated LSCs, blasts, and healthy HSPCs, representing a valuable resource helping to design LSC-directed therapies.
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Leucemia Mieloide Aguda/metabolismo , Células Madre Neoplásicas/metabolismo , Animales , Metabolismo Energético , Regulación Leucémica de la Expresión Génica , Humanos , Leucemia Mieloide Aguda/genética , Ratones , Proteoma/genética , Proteoma/metabolismo , Proteómica , TranscriptomaRESUMEN
The purpose of this survey is to explore changes in the management of COVID-19 during the first versus the second wave, with particular emphasis on therapies, antibiotic prescriptions, and elderly care. An internet-based questionnaire survey was distributed to European Society of Clinical Microbiology and Infectious Diseases (ESCMID) members. Therapeutic approach to patients with mild-to-moderate (PiO2/FiO2 200-350) and severe (PiO2/FiO2 < 200) COVID-19, antibiotic use, and reasons for excluding patients from the intensive care unit (ICU) were investigated. A total of 463 from 21 countries participated in the study. Most representatives were infectious disease specialists (68.3%). During the second wave of pandemic, physicians abandoned the use of hydroxychloroquine, lopinavir/ritonavir, and azithromycin in favor of dexamethasone, low-molecular weight heparin (LMWH), and remdesivir in mild-to-moderate COVID-19. In critically ill patients, we detected an increased use of high-dose steroids (51%) and a decrease in tocilizumab use. The use of antibiotics at hospital admission decreased but remained high in the second wave. Age was reported to be a main consideration for exclusion of patients from ICU care by 25% of responders; a third reported that elderly were not candidates for ICU admission in their center. The decision to exclude patients from ICU care was based on the individual decision of an intensivist in 59.6% of cases. The approach of physicians to COVID-19 changed over time following evidence accumulation and guidelines. Antibiotic use at hospital admission and decision to exclude patients from ICU care remain critical aspects that should be better investigated and harmonized among clinicians.
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Tratamiento Farmacológico de COVID-19 , COVID-19 , Pandemias , COVID-19/epidemiología , Combinación de Medicamentos , Humanos , Hidroxicloroquina/uso terapéutico , Unidades de Cuidados Intensivos , Lopinavir , Ritonavir , Encuestas y CuestionariosRESUMEN
PURPOSE: Arthrodesis of the knee joint is still a salvage procedure after recurrent prosthetic joint infections (PJI) of total knee arthroplasties (TKA) with substantial bone loss and seems to be a good solution to avoid amputation. Until now, intramedullary arthrodesis has increasingly been performed; no study has yet been published to compare these techniques after septic removal of TKA in terms of functional assessment and quality of daily life. METHODS: In a single-centre retrospective setting, clinical and radiographic evaluation of consecutive patients after knee arthrodesis using intramedullary and external fixation for infected knee joints was performed. All patients were evaluated clinically, with x-ray and questionnaire including analysis regarding any complications at latest follow-up of a minimum 12 months postoperatively. RESULTS: We included 152 patients (75 females, 77 males) in this study. The mean age of the patients at surgery was 63.6 years (range 12 to 90 years). The minimum follow-up was 12 months (mean 3.1 years, range 12 to 49 months). Arthrodesis with external fixator (83 patients, 52.2%) showed less blood loss and less peri-operative complications (1.6%) but a high rate of post-operative, pin-track infections (35.5%); loose pins (12.7%); and pin fractures (4.8%), and therefore risk factors for instability and nonunion (30.9%). Revision rate was 22.6% for arthrodesis with external fixator, and the primary union rate was 65.6%. Intramedullary arthrodesis (69 patients, 43.4%) showed a similar re-infection rate to external fixation (16.1% and 15.9%, respectively) but a significantly lower revision rate (5.4%, p < 0.001). Eighty percent of patients with intramedullary arthrodesis showed very good patient-related outcomes regarding pain, function and daily life activities in the questionnaire. CONCLUSION: Despite similar results regarding patient satisfaction and everyday competences in questionnaires, intramedullary arthrodesis of the knee is superior to the external fixator, as it results in fewer complications, lower revision rate, and union rates/loosening.
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Infecciones Relacionadas con Prótesis , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Artrodesis/efectos adversos , Clavos Ortopédicos , Niño , Fijadores Externos , Femenino , Humanos , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/cirugía , Masculino , Persona de Mediana Edad , Infecciones Relacionadas con Prótesis/epidemiología , Infecciones Relacionadas con Prótesis/cirugía , Reoperación , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVES: To provide evidence-based recommendations for vaccination against influenza virus and S. pneumoniae in patients with autoimmune rheumatic diseases (ARDs). METHODS: A Consensus Committee including physicians with expertise in rheumatic and infectious diseases was established by two Italian scientific societies, Società Italiana di Reumatologia (SIR) and Società Italiana di Malattie Infettive e Tropicali (SIMIT). The experts were invited to develop evidence-based recommendations concerning vaccinations in ARDs patients, based on their clinical status before and after undergoing immunosuppressive treatments. Key clinical questions were formulated for the systematic literature reviews, based on the clinical pathway. A search was made in Medline (via PubMed) according to the original MeSH strategy from October 2009 and a keyword strategy from January 2016 up to December 2017, updating existing EULAR recommendations. Specific recommendations were separately voted and scored from 0 (no agreement with) to 100 (maximal agreement) and supporting evidence graded. The mean and standard deviation of the scores were calculated to determine the level of agreement among the experts' panel for each recommendation. Total cumulative agreement ≥70 defined consensus for each statement. RESULTS: Nine recommendations, based on 6 key clinical questions addressed by the expert committee, were proposed. The aim of this work is to integrate the 2011 EULAR recommendations on vaccination against influenza and S. pneumoniae in ARDs patients. An implementation plan was proposed to improve the vaccination status of these patients and their safety during immunosuppressive treatments. CONCLUSIONS: Influenza and pneumococcus vaccinations are effective and safe in patients with ARDs. More efforts should be made to translate the accumulated evidence into practice.
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Vacunas contra la Influenza/administración & dosificación , Vacunas Neumococicas/administración & dosificación , Enfermedades Reumáticas/inmunología , Vacunación , Adulto , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/tratamiento farmacológico , Consenso , Medicina Basada en la Evidencia/métodos , Femenino , Humanos , Inmunosupresores/efectos adversos , Vacunas contra la Influenza/inmunología , Gripe Humana/inmunología , Gripe Humana/prevención & control , Italia , Masculino , Vacunas Neumococicas/inmunología , Neumonía Estafilocócica/inmunología , Neumonía Estafilocócica/prevención & control , Enfermedades Reumáticas/complicaciones , Enfermedades Reumáticas/tratamiento farmacológico , Vacunación/normasRESUMEN
PURPOSE: Staphylococcus aureus is an important cause of infections in hospitalized neonates. Preterm or low birthweight infants are especially at risk to develop a S. aureus infection due to the immaturity of the immune system, length of hospital stay and invasive procedures. Exfoliative toxin (ET)-producing S. aureus is often responsible for neonatal infections, causing clinical manifestations such as staphylococcal scalded skin syndrome, characterized by both localized blisters or generalized exfoliation of the skin. METHODS: We describe an outbreak due to an S. aureus strain producing ETA occurring in a local hospital in Northern Italy. Molecular typing of the isolates included spa typing and multilocus sequence typing. DNA microarray hybridization was also performed on one representative strain. RESULTS: In the period from July 2013 to February 2014, 12 neonates presented with skin infections, mainly bullae or pustules. Cultures of skin swabs yielded methicillin-susceptible S. aureus (MSSA). By molecular typing, an epidemic strain (t1393/ST5) was identified in nine neonates; microarray analysis and PCR revealed that it contained the ETA encoding gene. Screening of staff, mothers and healthy neonates and environmental cultures did not reveal the presence of the epidemic strain. However, the father of an infected neonate was found to be a carrier of MSSA t1393 five months after the outbreak started. CONCLUSION: Implementation of hygiene procedures and sanitization of the ward twice terminated the outbreak. Timely surveillance of infections, supported by molecular typing, is fundamental to prevent similar episodes among neonates.
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Infección Hospitalaria/epidemiología , Dermotoxinas/metabolismo , Brotes de Enfermedades , Exfoliatinas/metabolismo , Enfermedades Cutáneas Infecciosas/epidemiología , Infecciones Estafilocócicas/epidemiología , Infección Hospitalaria/microbiología , Femenino , Humanos , Recién Nacido , Italia/epidemiología , Masculino , Tipificación de Secuencias Multilocus , Enfermedades Cutáneas Infecciosas/microbiología , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/aislamiento & purificaciónRESUMEN
INTRODUCTION: Although open procedures are the gold standard, the alternative approach of minimal invasive reduction using percutaneous screws for thoracic and lumbar spine fractures is under discussion. Aim of this study was to investigate the results of reduction and the accuracy of screw placement in minimally invasive percutaneous posterior instrumentation for these fractures. MATERIALS AND METHODS: One hundred and twenty-seven patients with thoraco-lumbar and lumbar burst fractures and minimal invasive dorsal instrumentation were analyzed retrospectively in terms of the accuracy of pedicle screw placement and results of fracture reduction. RESULTS: In total, 542 screws were placed. Thirty-four (6.3%) screws of 22 patients (17.3%) were misplaced, but misplacement was minimal, replacement of any screw position due to instability was not necessary, and no new neurological deficit occurred. In thoraco-lumbar fractures (82/64.5%), reduction succeeded from 2.5 ± 6° kyphosis to 5.6 ± 5.7° lordosis (p < 0.001) and in lumbar spine fractures from 6.9° ± 10.3° lordosis to 14.5° ± 8.8° lordosis (p < 0.001). CONCLUSION: Minimal invasive percutaneous dorsal instrumentation of burst fractures of the thoraco-lumbar and lumbar spine provides adequate reduction and reliable regular screw placement. LEVEL OF EVIDENCE: Level IV (retrospective series).
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Vértebras Lumbares/cirugía , Fracturas de la Columna Vertebral/cirugía , Vértebras Torácicas/cirugía , Adulto , Anciano , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Femenino , Fijación Interna de Fracturas/instrumentación , Fijación Interna de Fracturas/métodos , Humanos , Cifosis/cirugía , Lordosis/cirugía , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Tempo Operativo , Tornillos Pediculares , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE: The aim of the current study is to analyze perioperative data and complications of open vs. percutaneous dorsal instrumentation after dorsal stabilization in patients suffering from fractures of the thoracic or lumbar spine. METHODS: In the time period from 01/2007 to 06/2009, open surgical approach was used for dorsal stabilization. The percutaneous surgical approach was used from 05/2009 to 03/2014. In every time period, all types of fractures were treated only by open or by percutaneous approach, respectively, to avoid any selection bias. Retrospectively, epidemiological data, complications and perioperative data were documented and statistically analyzed. RESULTS: A total of 491 patients met the inclusion criteria. Open surgery procedure was carried out on 169 patients, and percutaneous surgery procedure was carried out on 322 patients. Fracture level ranged from T1 to L5, and fractures were classified types A, B, and C. In 91.4% of all patients, no complication occured following dorsal stabilization after traumatic spine fracture during their hospital stay. However, 42 complications related to dorsal stabilization have been documented during the hospital stay. The complication rate was 14.8% if open surgical approach has been used and was significantly reduced to 5.3% using percutaneous surgical approach. Post-operative hospital stay was also reduced significantly using the percutaneous surgical approach. CONCLUSIONS: According to the current study, percutaneous dorsal stabilization of the spine could also be safely used in trauma cases and is not restricted to degenerative spinal surgery.
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Vértebras Lumbares , Procedimientos Ortopédicos , Complicaciones Posoperatorias/epidemiología , Fracturas de la Columna Vertebral/cirugía , Vértebras Torácicas , Adulto , Anciano , Femenino , Humanos , Vértebras Lumbares/lesiones , Vértebras Lumbares/cirugía , Masculino , Persona de Mediana Edad , Procedimientos Ortopédicos/efectos adversos , Procedimientos Ortopédicos/instrumentación , Procedimientos Ortopédicos/métodos , Procedimientos Ortopédicos/estadística & datos numéricos , Estudios Retrospectivos , Vértebras Torácicas/lesiones , Vértebras Torácicas/cirugíaRESUMEN
PURPOSE: Diagnosing periprosthetic infection remains a challenge. Multiplex-PCR and biomarkers such as alpha-defensin are potentially useful and fast methods for detecting periprosthetic infection. This study compared these new methods with clinical assessment, conventional microbiological methods and histo-pathological examination. METHODS: Twenty-eight consecutive patients with 30 joints and a mean age of 67.7 years (range 39 to 88) with removal of total hip arthroplasty (THA) or total knee replacement (TKR) were included in this study. Patients were classified according to the modified Musculoskeletal Infection Society score (MSIS) for infected joints. Punction fluid and tissue specimens were taken for conventional microbiological examination, alphadefensin test was performed, a synovial membrane specimen was used for multiplex-PCR and histopathological examination was carried out. RESULTS: The alpha-defensin test and multiplex-PCR showed a sensitivity of 76.9 vs. 30.8% and a specificity of 82.4 vs. 100%, respectively. We found a significant difference between the positive and negative results (p = 0.0023). The conventional microbiological methods were not significantly different from the alpha-defensin test (p = 0.244) with a sensitivity of 84.6% and a specificity of 100% but did differ significantly from the multiplex PCR (p = 0.0030). There was a significant difference between modified MSIS classification and multiplex PCR (p = 0.0007). CONCLUSIONS: Neither alpha-defensin test nor multiplex-PCR could detect periprosthetic infection immediately and reliably. Multiplex-PCR was suitable for detecting the non-infected but not the truly infected. Alpha-defensin test was helpful but showed no satisfactory results. Conventional microbiological methods remain the most reliable for periprosthetic infection diagnosis.
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Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Reacción en Cadena de la Polimerasa/métodos , Infecciones Relacionadas con Prótesis/diagnóstico , Membrana Sinovial/microbiología , alfa-Defensinas/análisis , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/análisis , Remoción de Dispositivos , Femenino , Humanos , Prótesis Articulares/microbiología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Reproducibilidad de los Resultados , Líquido Sinovial/químicaRESUMEN
INTRODUCTION: Distal biceps brachii tendon rupture can lead to 30-40% power loss of elbow flexion and up to 50% of forearm supination. Re-fixation of the distal biceps brachii tendon is recommended to warrant an adequate quality of the patient's life. This study reports the isometric and isokinetic results after anchor re-fixation 2.5 years after surgery. PATIENTS AND METHODS: Between 2007 and 2010, 69 patients with distal biceps brachii tendon tear underwent a suture anchor reattachment. During the follow-up examination, a questionnaire and DASH score were filled in, the circumferences of the arm were measured, range of motion was collected, and different trials were conducted at the BTE Primus RS™ (Baltimore Therapeutic Equipment) on both arms. RESULTS: 49 patients (71%) were reinvestigated with a follow-up of 32 months (11-58 months). A significant difference was found in the ability of elbow flexion between the affected arm and the opposite side as well as in pronation and supination. In elbow flexion and extension as well as in pronation and supination of the forearm, the strength was significantly diminished. CONCLUSIONS: 32 months after surgical re-fixation of the distal biceps brachii tendon rupture, strength in all exercises is marginally reduced in comparison to the opposite arm. Re-fixation of the distal biceps brachii tendon is an adequate method to return the range of motion and the strength in the elbow joint to an almost normal level and that gives rise to a high level of patient satisfaction. LEVEL OF EVIDENCE: Level III, case-control study.
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Lesiones de Codo , Tendones Isquiotibiales/lesiones , Traumatismos de los Tendones/cirugía , Adulto , Anciano , Estudios de Casos y Controles , Articulación del Codo/cirugía , Tendones Isquiotibiales/cirugía , Humanos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Rango del Movimiento Articular , Encuestas y Cuestionarios , Anclas para Sutura , Traumatismos de los Tendones/diagnóstico por imagen , Traumatismos de los Tendones/rehabilitación , Resultado del TratamientoRESUMEN
A 42-year-old woman, living in a nursing home for the mentally disabled, with congenital ventricular septal defect and multiple comorbidities, developed endocarditis with vegetations of the interventricular septum and the right coronary aortic leaflet. The main feature of this case was the metastatic embolism leading to multiple and muscular abscesses. Methicillin-sensitive S. aureus, spa type 253 and ST30, producing toxin shock syndrome toxin-1 was isolated from blood cultures. The patient was initially treated with beta-lactam antibiotics without showing clinical response and subsequently with daptomycin and linezolid that improved the patient's clinical symptoms. The effectiveness of treatment with daptomycin and linezolid was partly due to the ability of linezolid to reduce TSST-1 secretion. The portal of entry of the infection was not recognized. TSST-1 production by the strain might have favoured the formation of large cardiac vegetations and the subsequent metastatic dissemination to the muscles.
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Absceso/microbiología , Toxinas Bacterianas/metabolismo , Endocarditis Bacteriana/microbiología , Enterotoxinas/metabolismo , Enfermedades Musculares/microbiología , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/aislamiento & purificación , Superantígenos/metabolismo , Absceso/tratamiento farmacológico , Acetamidas/uso terapéutico , Adulto , Antibacterianos/uso terapéutico , Daptomicina/uso terapéutico , Endocarditis Bacteriana/tratamiento farmacológico , Femenino , Humanos , Linezolid , Enfermedades Musculares/tratamiento farmacológico , Oxazolidinonas/uso terapéutico , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/genética , Staphylococcus aureus/metabolismoRESUMEN
OBJECTIVE: To identify predictors of 30-day survival in elderly patients with coronavirus disease 2019 (COVID-19). METHODS: Retrospective cohort study including patients with COVID-19 aged ≥65 years hospitalized in six European sites (January 2020 to May 2021). Data on demographics, comorbidities, clinical characteristics, and outcomes were collected. A predictive score (FLAMINCOV) was developed using logistic regression. Regression coefficients were used to calculate the score. External validation was performed in a cohort including elderly patients from a major COVID-19 centre in Israel. Discrimination was evaluated using the area under the receiver operating characteristic curve (AUC) in the derivation and validation cohorts. Survival risk groups based on the score were derived and applied to the validation cohort. RESULTS: Among 3010 patients included in the derivation cohort, 30-day survival was 74.5% (2242/3010). The intensive care unit admission rate was 7.6% (228/3010). The model predicting survival included independent functional status (OR, 4.87; 95% CI, 3.93-6.03), a oxygen saturation to fraction of inspired oxygen (SpO2/FiO2) ratio of >235 (OR, 3.75; 95% CI, 3.04-4.63), a C-reactive protein level of <14 mg/dL (OR, 2.41; 95% CI, 1.91-3.04), a creatinine level of <1.3 (OR, 2.02; 95% CI, 1.62-2.52) mg/dL, and absence of fever (OR, 1.34; 95% CI, 1.09-1.66). The score was validated in 1174 patients. The FLAMINCOV score ranges from 0 to 15 and showed good discrimination in the derivation (AUC, 0.79; 95% CI, 0.77-0.81; p < 0.001) and validation cohorts (AUC, 0.79; 95% CI, 0.76-0.81; p < 0.001). Thirty-day survival ranged from 39.4% (203/515) to 95.3% (634/665) across four risk groups according to score quartiles in the derivation cohort. Similar proportions were observed in the validation set. DISCUSSION: The FLAMINCOV score identifying elderly with higher or lower chances of survival may allow better triage and management, including intensive care unit admission/exclusion.
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COVID-19 , Anciano , Humanos , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , HospitalesRESUMEN
Ceftazidime-avibactam (CAZ-AVI) is an active antibiotic combination of a ß-lactam-ß-lactamase inhibitor against carbapenemase-producing Enterobacterales. Reports of resistance to CAZ-AVI other than metallo-ß-lactamases have increased in recent years. The aim of this study was to analyze KPC-Klebsiella pneumoniae (KP) isolates resistant to CAZ-AVI from the intestinal carriage of hospitalized elderly patients in Italy, in February 2018-January 2020. Characterization of CAZ-AVI-resistant KP isolates, including MLST, resistome, virulome and plasmid content, was performed by WGS analysis. Out of six CAZ-AVI-resistant KP isolates, three belonged to ST101 and three to ST512; two isolates produced KPC-3 (both ST512), four had mutated KPC-3 (KPC-31, in ST101 and ST512, and KPC-46, both ST101). All CAZ-AVI-resistant KP isolates were multidrug-resistant and carried several resistance genes. The yersiniabactin ybt9 gene cluster was present in all ST101 isolates, while, in ST512 isolates, no virulence genes were detected. Several plasmids were detected: IncF was present in all isolates, as well as IncR and Col440 in ST101 and IncX3 in ST512 isolates. In conclusion, it is important to monitor the circulation of K. pneumoniae resistant to CAZ-AVI to prevent the spread of clones causing difficult-to-treat infections. The presence of mutated KPC-3 in high-risk K. pneumoniae clones resistant to CAZ-AVI in hospitalized patients deserves attention.
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OBJECTIVES: To assess risk factors for acquiring extended-spectrum ß-lactamase-producing Gram-negative bacteria (ESBL+ GN) causing urinary tract infections (UTIs) in long-term care facilities (LTCFs). METHODS: A prospective case-case-control study was carried out. In the first study, cases were defined as patients harbouring ESBL+ GN, while, in the second study, cases were defined as patients harbouring ESBL-negative (ESBL-) GN. Controls were selected by simple random sampling from patients without GN infection. ESBL determinants were characterized by hybridization, and confirmed by PCR and sequencing. RESULTS: The study involved 297 LTCF patients (99 with ESBL+ GN UTI, 99 with ESBL- GN UTI and 99 without GN infection). ESBL+ GN UTIs were due to Escherichia coli (64%), Proteus mirabilis (25%) and Klebsiella pneumoniae (11%). The CTX-M-type enzymes were the most prevalent (73% of isolates), whereas TEM- and SHV-type ESBLs and AmpC-type enzymes were less prevalent (10%, 2% and 15% of isolates, respectively). Patients with ESBL+ GN UTI were more likely to have a permanent urinary catheter (OR 15, 95% CI 6.9-30.5) and to have received antimicrobial therapy in the previous 30 days (OR 4, 95% CI 1.2-10.9). After adjusting for type, dosage and duration of antibiotic, exposure to ≥7 days of quinolones and third-generation cephalosporins was associated with the highest risk of ESBL+ GN UTI development (OR 7, 95% CI 1.2-40). Independent risk factors for acquiring ESBL- GN UTIs were previous surgical procedures (OR 2, 95% CI 1.1-4) and the presence of a urinary catheter (OR 8, 95% CI 4-16). No specific antibiotics remained a significant risk for ESBL- GN UTI after adjusting for demographic and clinical risk factors. CONCLUSIONS: Exposure to ≥7 days of quinolones and third-generation cephalosporins significantly increases the risk of ESBL+ GN UTI. Interventions aimed at improving compliance with antimicrobial stewardship principles should be further developed and implemented in LTCFs.
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Infección Hospitalaria/epidemiología , Bacterias Gramnegativas/aislamiento & purificación , Infecciones por Bacterias Gramnegativas/epidemiología , Cuidados a Largo Plazo , Infecciones Urinarias/epidemiología , beta-Lactamasas/genética , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Estudios de Casos y Controles , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/microbiología , ADN Bacteriano/química , ADN Bacteriano/genética , Femenino , Genotipo , Bacterias Gramnegativas/clasificación , Bacterias Gramnegativas/genética , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/microbiología , Humanos , Masculino , Hibridación de Ácido Nucleico , Reacción en Cadena de la Polimerasa , Estudios Prospectivos , Factores de Riesgo , Análisis de Secuencia de ADN , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/microbiología , beta-Lactamasas/metabolismoAsunto(s)
Antibacterianos/administración & dosificación , Monitoreo de Drogas , Linezolid/administración & dosificación , Anciano , Anciano de 80 o más Años , Antibacterianos/farmacocinética , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Linezolid/farmacocinética , Masculino , Estudios RetrospectivosRESUMEN
The spread of carbapenemase-producing (CP) Enterobacterales is currently a worldwide concern, especially in the elderly. Twelve CP-E. coli isolated from rectal swabs of colonized inpatients aged ≥65 years from four hospitals in two Italian cities (Milan and Rome) were analyzed by whole genome sequencing (WGS) to obtain multi-locus sequence typing (MLST), identification of carbapenemase-encoding genes, resistome, plasmid content, and virulence genes. MLST analysis showed the presence of 10 unrelated lineages: ST410 (three isolates from three different hospitals in two cities) and ST12, ST38, ST69, ST95, ST131, ST189, ST648, ST1288, and ST1598 (one isolate each). Most isolates (9/12, 75%) contained a serine-ß-lactamase gene (5 blaKPC-3, 2 blaKPC-2, and 2 blaOXA-181), while three isolates harbored a metallo-ß-lactamase gene (two blaNDM-5 and one blaVIM-1). In most CP-E. coli, the presence of more than one plasmid was observed, with the predominance of IncF. Several virulence genes were detected. All isolates contained genes enhancing the bacterial fitness, such as gad and terC, and all isolates but one, fimH, encoding type 1 fimbriae. In conclusion, CP-E. coli clones colonizing elderly patients showed heterogeneous genetic backgrounds. We recommend strict surveillance to monitor and prevent the spread of successful, high-risk clones in healthcare settings.
RESUMEN
Carbapenemase-producing Enterobacterales (CPE) represent a serious threat to public health worldwide. Elderly patients are at increased risk of colonisation/infection with CPE. This study aimed to evaluate the persistence of CPE colonisation and the genotypic characteristics of persistent strains in elderly people discharged from Italian hospitals. A longitudinal study was conducted in two Italian cities (March 2018 to September 2020) enrolling 137 patients aged ≥65 years with CPE intestinal colonisation at hospital discharge. CPE colonisation was evaluated after 4, 8 and 12 months. Competing risk analysis was used to explore the association between baseline characteristics and persistence at 4 months. For all isolates, carbapenemase typing and multilocus sequence typing were performed. Persistent isolates underwent whole-genome sequencing. Of 137 patients, 91% carried carbapenemase-producing Klebsiella pneumoniae (CP-KP) and 8.8% carried carbapenemase-producing Escherichia coli. Although a large number of patients were lost to follow-up owing to death or withdrawal, 28/65 patients (43.1%) remained colonised at Month 4; 16/42 (38.1%) and 5/28 (17.9%) were found colonised up to Months 8 and 12, respectively. Colonisation persistence was more frequent in patients with bacteraemia or complicated urinary tract infection while in hospital and in those staying in long-term care facilities (LTCFs). Clonal characteristics of CP-KP isolates did not appear to influence persistence. Isolates obtained from each persistent carrier were identical or highly related by SNP phylogenetic analysis. Identification of patients at higher risk of persistent intestinal carriage after hospital discharge can prompt control measures to limit the transmission of CPE in the community, especially in LTCF settings.
Asunto(s)
Enterobacteriaceae Resistentes a los Carbapenémicos , Infecciones por Enterobacteriaceae , Anciano , Proteínas Bacterianas/genética , Infecciones por Enterobacteriaceae/epidemiología , Escherichia coli , Hospitales , Humanos , Klebsiella pneumoniae , Estudios Longitudinales , Alta del Paciente , Filogenia , beta-Lactamasas/genéticaRESUMEN
Management of patients with infections caused by multidrug-resistant organisms is challenging and requires a multidisciplinary approach to achieve successful clinical outcomes. The aim of this paper is to provide recommendations for the diagnosis and optimal management of these infections, with a focus on targeted antibiotic therapy. The document was produced by a panel of experts nominated by the five endorsing Italian societies, namely the Italian Association of Clinical Microbiologists (AMCLI), the Italian Group for Antimicrobial Stewardship (GISA), the Italian Society of Microbiology (SIM), the Italian Society of Infectious and Tropical Diseases (SIMIT) and the Italian Society of Anti-Infective Therapy (SITA). Population, Intervention, Comparison and Outcomes (PICO) questions about microbiological diagnosis, pharmacological strategies and targeted antibiotic therapy were addressed for the following pathogens: carbapenem-resistant Enterobacterales; carbapenem-resistant Pseudomonas aeruginosa; carbapenem-resistant Acinetobacter baumannii; and methicillin-resistant Staphylococcus aureus. A systematic review of the literature published from January 2011 to November 2020 was guided by the PICO strategy. As data from randomised controlled trials (RCTs) were expected to be limited, observational studies were also reviewed. The certainty of evidence was classified using the GRADE approach. Recommendations were classified as strong or conditional. Detailed recommendations were formulated for each pathogen. The majority of available RCTs have serious risk of bias, and many observational studies have several limitations, including small sample size, retrospective design and presence of confounders. Thus, some recommendations are based on low or very-low certainty of evidence. Importantly, these recommendations should be continually updated to reflect emerging evidence from clinical studies and real-world experience.
Asunto(s)
Acinetobacter baumannii , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Programas de Optimización del Uso de los Antimicrobianos , Carbapenémicos , Farmacorresistencia Bacteriana Múltiple , HumanosRESUMEN
OBJECTIVE: Dorsal stabilization is a frequently used procedure in the treatment of acute traumatic vertebral body fractures. Besides the traditional open surgical procedure, the percutaneous positioning of pedicle screws is now widely used. The aim of the current study is to compare pedicle screw misplacement following open vs. percutaneous dorsal instrumentation after traumatic spinal fracture of the thoracic and lumbar spine and to assess possible risk factors associated with pedicle screw misplacement. METHODS: All patients who suffered a traumatic spinal fracture that were treated with dorsal stabilization in our level I trauma center in the period from 01/2007 to 03/2014 were included in this retrospective therapeutic cohort study. From 01/2007 to 06/2009, an open surgical procedure was used, and from 06/2009 to 03/2014, the percutaneous procedure was used for all types of fractures. Retrospectively, the positioning of every single pedicle screw was evaluated in the post-operative computed tomography scan and classified. Epidemiological data were also documented to compare the two treatment groups. RESULTS: A total of 491 patients with 681 vertebral body fractures were included. Of 733 pedicle screws placed during the open surgery procedure, 96.0% were within the safe zone. There was no significant difference compared with pedicle screws placed percutaneously (95.3% of 1884 screws). In all other categories, the number of misplaced pedicle screws also showed no differences between the two treatment groups. There is a positive correlation between pedicle screw misplacement and duration of the operation. Most pedicle screws are misplaced at the levels T12, L1 and T7, T8. CONCLUSION: The current study shows that percutaneous surgery using dorsal stabilization allows the positioning of pedicle screws in an equivalently safe manner compared with an open surgical procedure in the acute care of spinal trauma.