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1.
J Antimicrob Chemother ; 78(9): 2109-2120, 2023 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-37259598

RESUMO

BACKGROUND: High-risk febrile neutropenia (HR-FN) is a life-threatening complication in patients with haematological malignancies or receiving myelosuppressive chemotherapy. Since the last international guidelines were published over 10 years ago, there have been major advances in the understanding and management of HR-FN, including on antibiotic pharmacokinetics and discontinuation/de-escalation strategies. OBJECTIVES: Summarizing major advances in the field of antibacterial therapy in patients with HR-FN: empirical therapy, pharmacokinetics of antibiotics and antibiotic stewardship. SOURCES: Narrative review based on literature review from PubMed. We focused on studies published between 2010 and 2023 about the pharmacokinetics of antimicrobials, management of antimicrobial administration, and discontinuation/de-escalation strategies. We did not address antimicrobial prophylaxis, viral or fungal infections. CONTENT: Several high-quality publications have highlighted important modifications of antibiotic pharmacokinetics in HR-FN, with standard dosages exposing patients to underdosing. These recent clinical and population pharmacokinetics studies help improve management protocols with optimized initial dosing and infusion rules for ß-lactams, vancomycin, daptomycin and amikacin; they highlight the potential benefits of therapeutic drug monitoring. A growing body of evidence also shows that antibiotic discontinuation/de-escalation strategies are beneficial for bacterial ecology and patients' outcome. We further discuss methods and limitations for implementation of such protocols in haematology. IMPLICATIONS: We highlight recent information about the management of antibacterial therapy in HR-FN that might be considered in updated guidelines for HR-FN management.


Assuntos
Neutropenia Febril , Neoplasias Hematológicas , Humanos , Adulto , Antibacterianos , Vancomicina/uso terapêutico , Amicacina , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/tratamento farmacológico , Neutropenia Febril/etiologia
2.
J Surg Oncol ; 128(2): 344-349, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37010035

RESUMO

BACKGROUND: Pelvic bone and/or soft tissue sarcoma removal surgeries are associated with a high rate of surgical site infection (SSI). The recommended antibiotic prophylaxis (ABP) duration is 24-48 h. We aimed to assess the impact of extended ABP (5 days) on the SSI rate and describe the microbiology of SSI in bone and/or soft tissue pelvic sarcomas. METHODS: We retrospectively included all consecutive patients who underwent pelvic bone and/or soft tissue sarcoma removal surgery between January 2010 and June 2020. RESULTS: We analyzed 146 patients with pelvic bone (45, 31%) or soft tissue (101, 69%). Sixty patients (41%) developed SSI. SSI occurred in 13/28 (46.4%) in the extended ABP group versus 47/118 (39.8%) in the standard group (p = 0.53). In multivariable analysis, risk factors for SSI were surgery duration (OR: 1.94 [1.41-2.92] per h), stay in postoperative ICU for more than 2 days (12.0 [2.8-61.3]), and shred or autologous skin flap (39.3 [5.8-409.5]). Extended ABP was not associated with SSI. SSI were mainly polymicrobial with Enterobacterales (57.4%) and Enterococcus (45%). CONCLUSIONS AND DISCUSSION: Pelvic bone and/or soft tissue sarcoma removal surgery is highly prone to postoperative infection. Extending the ABP to 5 days does not reduce the level of SSI.


Assuntos
Ossos Pélvicos , Sarcoma , Humanos , Antibioticoprofilaxia/efeitos adversos , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Estudos Retrospectivos , Fatores de Risco , Sarcoma/tratamento farmacológico , Antibacterianos/uso terapêutico
3.
J Antimicrob Chemother ; 78(5): 1253-1258, 2023 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-37014800

RESUMO

OBJECTIVES: Data on the efficacy of vancomycin catheter lock therapy (VLT) for conservative treatment of totally implantable venous access port-related infections (TIVAP-RI) due to CoNS are scarce. The aim of this study was to evaluate the effectiveness of VLT in the treatment of TIVAP-RI due to CoNS in cancer patients. METHODS: This prospective, observational, multicentre study included adults with cancer treated with VLT for a TIVAP-RI due to CoNS. The primary endpoint was the success of VLT, defined as no TIVAP removal nor TIVAP-RI recurrence within 3 months after initiation of VLT. The secondary endpoint was 3 month mortality. Risk factors for VLT failure were also analysed. RESULTS: One hundred patients were included [men 53%, median age 63 years (IQR 53-72)]. Median duration of VLT was 12 days (IQR 9-14). Systemic antibiotic therapy was administered in 87 patients. VLT was successful in 44 patients. TIVAP could be reused after VLT in 51 patients. Recurrence of infection after completion of VLT occurred in 33 patients, among which TIVAP was removed in 27. Intermittent VLT (antibiotic solution left in place in the TIVAP lumen part of the time) was identified as a risk factor for TIVAP-RI recurrence. At 3 months, 26 deaths were reported; 1 (4%) was related to TIVAP-RI. CONCLUSIONS: At 3 months, success of VLT for TIVAP-RI due to CoNS was low. However, removing TIVAP was avoided in nearly half the patients. Continuous locks should be preferred to intermittent locks. Identifying factors of success is essential to select patients who may benefit from VLT.


Assuntos
Infecções Relacionadas a Cateter , Cateterismo Venoso Central , Neoplasias , Masculino , Adulto , Humanos , Pessoa de Meia-Idade , Vancomicina/uso terapêutico , Cateterismo Venoso Central/efeitos adversos , Coagulase , Estudos Prospectivos , Cateteres de Demora/efeitos adversos , Infecções Relacionadas a Cateter/tratamento farmacológico , Infecções Relacionadas a Cateter/complicações , Antibacterianos/uso terapêutico , Neoplasias/tratamento farmacológico , Staphylococcus
4.
Antibiotics (Basel) ; 12(1)2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36671286

RESUMO

(1) Background: Cephalosporins (CA) are the first-line antibiotic prophylaxis recommended to prevent surgical site infection (SSI) after cardiac surgery. The combination of vancomycin/gentamicin (VGA) might represent a good alternative, but few studies have evaluated its efficacy in SSI prevention. (2) Methods: A single-centre retrospective study was conducted over a 13-year period in all consecutive adult patients undergoing elective cardiac surgery. Patients were stratified according to the type of antibiotic prophylaxis. CA served as the first-line prophylaxis, and VGA was used as the second-line prophylaxis. The primary endpoint was SSI occurrence at 90 days, which was defined as the need for reoperation due to SSI. (3) Results: In total, 14,960 adult patients treated consecutively from 2006 to 2019 were included in this study, of whom 1774 (12%) received VGA and 540 (3.7%) developed SSI. VGA patients had higher severity with increased 90-day mortality. Nevertheless, the frequency of SSI was similar between CA and VGA patients. However, the microbiological aetiologies were different, with more Gram-negative bacteria noted in the VGA group. (4) Conclusions: VGA seems to be as effective as CA in preventing SSI.

5.
Antimicrob Resist Infect Control ; 11(1): 52, 2022 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-35346373

RESUMO

BACKGROUND: The 2011 4th European Conference on Infections in Leukemia (ECIL4) guidelines recommend antibiotics de-escalation/discontinuation in selected febrile neutropenia (FN) patients. We aimed to assess the impact of an antimicrobial stewardship (AMS) program based on these guidelines on antibiotics use and clinical outcomes in high-risk FN patients. METHODS: We conducted an observational study in the hematology department of Cochin University Hospital in Paris, France. An ECIL4-based antibiotics de-escalation and discontinuation strategy was implemented jointly by the hematologists and the AMS team. The pre-intervention (January-October 2018) and post-intervention (January-October 2019) periods were compared. We retrospectively collected clinical and microbiological data. We compiled antibiotics consumptions via hospital pharmacy data and standardized them by calculating defined daily doses per 1000 patient-days. We analyzed the two-monthly antibiotic consumption using an interrupted time series method and built a composite endpoint for clinical outcomes based on transfer to the intensive care unit (ICU) and/or hospital death. RESULTS: Overall, 273 hospital stays (164 patients) in the pre-intervention and 217 (148 patients) in the post-intervention periods were analyzed. Patients were mainly hospitalized for intensive chemotherapy for acute leukemia or autologous stem-cell transplant for myeloma. Patients were slightly younger in the pre-intervention compared to the post-intervention period (median age 60.4 vs 65.2 years, p = 0.049), but otherwise comparable. After implementation of the AMS program, glycopeptide and carbapenem use decreased by 85% (p = 0.03) and 72% (p = 0.04), respectively. After adjustment on confounders, the risk of transfer to the ICU/death decreased significantly after implementation of the AMS program (post-intervention period: odds-ratio = 0.29, 95% Confidence Interval: 0.15-0.53, p < 0.001). CONCLUSION: Implementation of a multidisciplinary AMS program for high-risk neutropenic patients was associated with lower carbapenem and glycopeptide use and improved clinical outcomes.


Assuntos
Gestão de Antimicrobianos , Neutropenia Febril , Antibacterianos/uso terapêutico , Gestão de Antimicrobianos/métodos , Carbapenêmicos , Neutropenia Febril/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos
6.
Arthritis Care Res (Hoboken) ; 74(5): 809-817, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-33278067

RESUMO

OBJECTIVE: Systemic sclerosis (SSc) is an autoimmune connective tissue disorder characterized by skin fibrosis, vasculopathy, and dysimmunity. Data regarding osteitis in SSc are scarce. METHODS: We performed a nationwide multicenter, retrospective, case-control study including patients with SSc, according to the 2013 American College of Rheumatology/European Alliance of Associations for Rheumatology classification, with a diagnosis of osteitis. The objectives of the study were to describe, to characterize, and to identify associated factors for osteitis in patients with SSc. RESULTS: Forty-eight patients were included. Twenty-six patients (54.1%) had osteitis beneath digital tip ulcers. Physical symptoms included pain (36 of 48, 75%), erythema (35 of 48, 73%), and local warmth (35 of 48, 73%). Thirty-one (65%) patients had median (interquartile range) C-reactive protein levels >2 mg/liter of 8 (2.7-44.3) mg/liter. On radiography, computed tomography, or magnetic resonance imaging, osteitis was characterized by swelling or abscess of soft tissues, with acro-osteolysis or lysis in 28 patients (58%). Microbiological sampling was performed in 45 (94%) patients. Most pathogens were Staphylococcus aureus (43.8%), anaerobes and Enterobacteriaceae (29.1%), and Pseudomonas aeruginosa (10.4%). Management comprised antibiotics in 37 (77.1%) patients and/or surgery in 26 (54.2%). Fluoroquinolones were used in 22 (45.8%) patients, and amoxicillin plus ß-lactamase inhibitor in 7 (14.6%). Six (12.6%) patients relapsed, 6 (12.6%) patients had osteitis recurrence, 15 (32%) sequelae, and 2 patients had septic shock and died. CONCLUSION: This study confirmed digital tip ulcers as an associated factor for osteitis and revealed a high rate of functional sequelae. Antimicrobial therapy with oral fluoroquinolone or intravenous amoxicillin and ß-lactamase inhibitor are used as first-line antibiotic therapy in SSc patients with osteitis.


Assuntos
Osteíte , Escleroderma Sistêmico , Úlcera Cutânea , Amoxicilina , Estudos de Casos e Controles , Humanos , Osteíte/complicações , Osteíte/etiologia , Estudos Retrospectivos , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico , Úlcera/complicações , Inibidores de beta-Lactamases
7.
Lancet Infect Dis ; 22(3): 341-348, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34843662

RESUMO

BACKGROUND: Mass indoor gatherings were banned in early 2020 to prevent the spread of SARS-CoV-2. We aimed to assess, under controlled conditions, whether infection rates among attendees at a large, indoor gathering event would be similar to those in non-attendees, given implementation of a comprehensive prevention strategy including antigen-screening within 3 days, medical mask wearing, and optimised ventilation. METHODS: The non-inferiority, prospective, open-label, randomised, controlled SPRING trial was done on attendees at a live indoor concert held in the Accor Arena on May 29, 2021 in Paris, France. Participants, aged 18-45 years, recruited via a dedicated website, had no comorbidities, COVID-19 symptoms, or recent case contact, and had had a negative rapid antigen diagnostic test within 3 days before the concert. Participants were randomly allocated in a 2:1 ratio to the experimental group (attendees) or to the control group (non-attendees). The allocation sequence was computer-generated by means of permuted blocks of sizes three, six, or nine, with no stratification. The primary outcome measure was the number of patients who were SARS-CoV-2-positive by RT-PCR test on self-collected saliva 7 days post-gathering in the per-protocol population (non-inferiority margin <0·35%). This trial is registered with ClinicalTrials.gov, NCT04872075. FINDINGS: Between May 11 and 25, 2021, 18 845 individuals registered on the dedicated website, and 10 953 were randomly selected for a pre-enrolment on-site visit. Among 6968 who kept the appointment and were screened, 6678 participants were randomly assigned (4451 were assigned to be attendees and 2227 to be non-attendees; median age 28 years; 59% women); 88% (3917) of attendees and 87% (1947) of non-attendees complied with follow-up requirements. The day 7 RT-PCR was positive for eight of the 3917 attendees (observed incidence, 0·20%; 95% CI 0·09-0·40) and three of the 1947 non-attendees (0·15%; 0·03-0·45; absolute difference, 95% CI -0·26% to 0·28%), findings that met the non-inferiority criterion for the primary endpoint. INTERPRETATION: Participation in a large, indoor, live gathering without physical distancing was not associated with increased SARS-CoV-2-transmission risk, provided a comprehensive preventive intervention was implemented. FUNDING: French Ministry of Health. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.


Assuntos
COVID-19 , Eventos de Massa , Programas de Rastreamento , SARS-CoV-2/isolamento & purificação , Adulto , COVID-19/prevenção & controle , COVID-19/terapia , Feminino , França , Humanos , Masculino , Estudos Prospectivos , Saliva/citologia
8.
J Allergy Clin Immunol ; 149(2): 550-556.e2, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34800432

RESUMO

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) is characterized by impaired type I interferon activity and a state of hyperinflammation leading to acute respiratory distress syndrome. The complement system has recently emerged as a key player in triggering and maintaining the inflammatory state, but the role of this molecular cascade in severe COVID-19 is still poorly characterized. OBJECTIVE: We aimed at assessing the contribution of complement pathways at both the protein and transcriptomic levels. METHODS: To this end, we systematically assessed the RNA levels of 28 complement genes in the circulating whole blood of patients with COVID-19 and healthy controls, including genes of the alternative pathway, for which data remain scarce. RESULTS: We found differential expression of genes involved in the complement system, yet with various expression patterns: whereas patients displaying moderate disease had elevated expression of classical pathway genes, severe disease was associated with increased lectin and alternative pathway activation, which correlated with inflammation and coagulopathy markers. Additionally, properdin, a pivotal positive regulator of the alternative pathway, showed high RNA expression but was found at low protein concentrations in patients with a severe and critical disease, suggesting its deposition at the sites of complement activation. Notably, low properdin levels were significantly associated with the use of mechanical ventilation (area under the curve = 0.82; P = .002). CONCLUSION: This study sheds light on the role of the alternative pathway in severe COVID-19 and provides additional rationale for the testing of drugs inhibiting the alternative pathway of the complement system.


Assuntos
COVID-19/imunologia , Ativação do Complemento/genética , Via Alternativa do Complemento/genética , Proteínas do Sistema Complemento/genética , Coagulação Intravascular Disseminada/imunologia , SARS-CoV-2/patogenicidade , COVID-19/genética , COVID-19/terapia , COVID-19/virologia , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/terapia , Doenças Cardiovasculares/virologia , Estudos de Casos e Controles , Comorbidade , Proteínas do Sistema Complemento/imunologia , Diabetes Mellitus/genética , Diabetes Mellitus/imunologia , Diabetes Mellitus/terapia , Diabetes Mellitus/virologia , Coagulação Intravascular Disseminada/genética , Coagulação Intravascular Disseminada/terapia , Coagulação Intravascular Disseminada/virologia , Feminino , Regulação da Expressão Gênica , Humanos , Hipertensão/genética , Hipertensão/imunologia , Hipertensão/terapia , Hipertensão/virologia , Lectinas/genética , Lectinas/imunologia , Masculino , Pessoa de Meia-Idade , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/terapia , Neoplasias/virologia , Properdina/genética , Properdina/imunologia , Respiração Artificial , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Índice de Gravidade de Doença
9.
Nutr Metab Cardiovasc Dis ; 31(9): 2605-2611, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34348875

RESUMO

BACKGROUND AND AIMS: To analyze lifestyle habits and weight evolution during the COVID-19 pandemic-associated lockdown, in diabetes and overweight/obesity patients (body mass index (BMI) [25-29.9] and ≥30 kg/m2, respectively). METHODS AND RESULTS: We collected information on participants' characteristics and behavior regarding lifestyle before and during the lockdown, through the CoviDIAB web application, which is available freely for people with diabetes in France. We stratified the cohort according to BMI (≥25 kg/m2vs < 25 kg/m2) and examined the determinants of weight loss (WL), WL > 1 kg vs no-WL) in participants with a BMI ≥25 kg/m2, in both univariate and multivariate analyses. Of the 5280 participants (mean age, 52.5 years; men, 49%; diabetes, 100% by design), 69.5% were overweight or obese (mean BMI, 28.6 kg/m2 (6.1)). During the lockdown, patients often quit or decreased smoking; overweight/obese participants increased alcohol consumption less frequently as compared with normal BMI patients. In addition, overweight/obese patients were more likely to improve other healthy behaviors on a larger scale than patients with normal BMI: increased intake of fruits and vegetables, reduction of snacks intake, and reduction of total dietary intake. WL was observed in 18.9% of people with a BMI ≥25 kg/m2, whereas 28.6% of them gained weight. Lifestyle favorable changes characterized patients with WL. CONCLUSIONS: A significant proportion of overweight/obese patients with diabetes seized the opportunity of lockdown to improve their lifestyle and to lose weight. Identifying those people may help clinicians to personalize practical advice in the case of a recurrent lockdown.


Assuntos
COVID-19/prevenção & controle , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 2/terapia , Estilo de Vida Saudável , Obesidade/terapia , Comportamento de Redução do Risco , Redução de Peso , Adulto , Idoso , Índice de Massa Corporal , COVID-19/epidemiologia , COVID-19/transmissão , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Dieta Saudável , Exercício Físico , Feminino , França/epidemiologia , Hábitos , Comportamentos Relacionados com a Saúde , Conhecimentos, Atitudes e Prática em Saúde , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Nutritivo , Obesidade/diagnóstico , Obesidade/epidemiologia , Prevalência , Medição de Risco , Fatores de Risco , Abandono do Hábito de Fumar , Fatores de Tempo , Aumento de Peso
10.
Eur J Clin Microbiol Infect Dis ; 40(11): 2379-2388, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34342768

RESUMO

Nasopharyngeal sampling for nucleic acid amplification testing (NAAT) is the standard diagnostic test of coronavirus disease 2019. Our objectives were to assess, in real-life conditions, the diagnostic accuracy of a nasopharyngeal point-of-care antigen (Ag) test and of saliva NAAT for detection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in ambulatory care. This was a prospective cohort study from 19 October through 18 December 2020 in two community COVID-19 screening centers in Paris, France. Two nasopharyngeal swabs and one saliva sample were simultaneously collected. Diagnostic accuracies of nasopharyngeal Ag testing and of three saliva NAAT methods were assessed as compared to nasopharyngeal NAAT. A total of 1452 ambulatory children and adults were included. Overall, 129/1443 (9%) participants tested positive on nasopharyngeal NAAT (102/564 [18%] in symptomatic and 27/879 [3%] in asymptomatic participants). Sensitivity was 94%, 23%, 96%, and 94% for the three different protocols of saliva NAAT and for the nasopharyngeal Ag test, respectively. Estimates of specificity were above 95% for all methods. Diagnostic accuracy was similar in symptomatic and asymptomatic individuals. Diagnostic accuracy of nasopharyngeal Ag testing and of saliva NAAT is similar to that of nasopharyngeal NAAT, subject to compliance with specific protocols for saliva. Registration number: NCT04578509.


Assuntos
Teste para COVID-19/métodos , COVID-19/diagnóstico por imagem , Nasofaringe/virologia , SARS-CoV-2/isolamento & purificação , Saliva/virologia , Manejo de Espécimes/métodos , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Técnicas de Amplificação de Ácido Nucleico/métodos , Paris , Testes Imediatos , Estudos Prospectivos , Sensibilidade e Especificidade
11.
Stem Cell Rev Rep ; 17(1): 296-299, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33403488

RESUMO

We report the case of an HIV-1-infected patient, treated with anti-CD20 monoclonal antibody for a B-cell lymphoma previously treated by autologous stem cell transplant. He suffered from chronic COVID19 and we monitored by plasma SARS-CoV-2 RNA by highly sensitive droplet-based digital PCR technology (ddPCR). Under tocilizumab therapy and despite a first clinical improvement biologically associated with decreasing inflammatory markers, a slight increase of SARS-CoV-2 RNAaemia quantified by ddPCR was highlighted, confirming the absence of viral efficacy of this treatment and predicting the subsequent observed deterioration. As expected, his complete recovery, finally achieved after COVID-19 convalescent plasmatherapy, strictly paralleled plasma SARS-CoV-2 RNA clearance. With these results, we confirmed the interest of SARS-CoV-2 RNAaemia monitoring by ddPCR in COVID-19 patients, particularly during treatment, and firstly showed that this new and specific biomarker could be helpful to select eligible patient for anti-IL6 receptors therapy considering the variable levels of efficacy recently observed with such therapy.


Assuntos
COVID-19/sangue , Infecções por HIV/sangue , Linfoma de Células B/tratamento farmacológico , RNA Viral/sangue , Anticorpos Monoclonais Humanizados/uso terapêutico , COVID-19/complicações , COVID-19/genética , COVID-19/virologia , Infecções por HIV/genética , Infecções por HIV/terapia , Infecções por HIV/virologia , HIV-1/patogenicidade , Humanos , Linfócitos/virologia , Linfoma de Células B/complicações , Linfoma de Células B/genética , Linfoma de Células B/virologia , RNA Viral/efeitos dos fármacos , SARS-CoV-2/genética , SARS-CoV-2/patogenicidade , Carga Viral/efeitos dos fármacos
12.
Science ; 369(6504): 718-724, 2020 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-32661059

RESUMO

Coronavirus disease 2019 (COVID-19) is characterized by distinct patterns of disease progression that suggest diverse host immune responses. We performed an integrated immune analysis on a cohort of 50 COVID-19 patients with various disease severity. A distinct phenotype was observed in severe and critical patients, consisting of a highly impaired interferon (IFN) type I response (characterized by no IFN-ß and low IFN-α production and activity), which was associated with a persistent blood viral load and an exacerbated inflammatory response. Inflammation was partially driven by the transcriptional factor nuclear factor-κB and characterized by increased tumor necrosis factor-α and interleukin-6 production and signaling. These data suggest that type I IFN deficiency in the blood could be a hallmark of severe COVID-19 and provide a rationale for combined therapeutic approaches.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Interferon alfa-2/metabolismo , Interferon-alfa/metabolismo , Interferon beta/metabolismo , Pneumonia Viral/imunologia , Adulto , Idoso , Betacoronavirus/fisiologia , COVID-19 , Infecções por Coronavirus/virologia , Estado Terminal , Estudos Transversais , Feminino , Perfilação da Expressão Gênica , Humanos , Imunidade Inata , Inflamação , Interleucina-6/metabolismo , Masculino , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Pandemias , Pneumonia Viral/virologia , SARS-CoV-2 , Transdução de Sinais , Subpopulações de Linfócitos T/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Carga Viral
13.
Ann Thorac Surg ; 108(1): 196-202, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30853591

RESUMO

BACKGROUND: Postoperative pneumonia (POP) is a severe complication of major lung resection. The objective of this study was to describe the current epidemiology and appropriateness of antibiotic prescriptions in severe POP, 4 years after implementation of an antimicrobial stewardship program that was based on weekly multidisciplinary review of all antibiotic therapies. METHODS: This study was a retrospective analysis of a prospectively collected database. It included all cases of severe POP occurring within 30 days after major lung resection of in a 1,500-bed hospital between 2013 and 2015. Criteria for severe POP were acute respiratory failure, severe sepsis, or a rapidly extensive pulmonary infiltrate. The study collected data on incidence, clinical outcomes, and microbiological analyses. Appropriateness of antibiotic prescribing was assessed by quality indicators previously validated in the literature. RESULTS: Over the study period, 1,555 patients underwent major lung surgery. Severe POP occurred in 91 patients (5.8%; confidence interval, 4.7%; 7.0%), with a mortality rate of 9.0% (8 of 91; confidence interval, 3.0%; 14.6%). In POP with positive microbiological results, the proportion of gram-negative bacteria other than Haemophilus was 76% (50 of 66 cases). All patients (91 of 91) had respiratory samples taken within 24 hours after the start of antibiotics; empiric therapy was concordant with the guideline in 80% (69 of 86), and it was switched to pathogen-directed therapy in 74% (46 of 62). In 71 of 91 patients (78%), the antibiotic duration was up to 7 days. CONCLUSIONS: This study reported a high proportion of gram-negative bacteria in severe POP. Four years after implementation of the program, quality indicators of antibiotic prescribing were all >70%. The rate of de-escalation to pathogen-directed therapy could be improved, however.


Assuntos
Antibacterianos/uso terapêutico , Pneumonectomia/efeitos adversos , Pneumonia Bacteriana/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Gestão de Antimicrobianos , Bactérias/isolamento & purificação , Farmacorresistência Bacteriana , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/epidemiologia , Pneumonia Bacteriana/etiologia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos
14.
Int J Infect Dis ; 64: 93-95, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28951103

RESUMO

An unusual case of pleural empyema related to Nocardia farcinica and Ureaplasma urealyticum, occurring after autologous haematopoietic stem cell transplantation in a 30-year-old patient with lymphoma, is reported. This case illustrates the role of repeated and comprehensive microbiological investigations and the contribution of molecular techniques in reaching the aetiological diagnosis.


Assuntos
Linfoma de Células B/complicações , Nocardiose/diagnóstico , Pleuropneumonia/diagnóstico , Reação em Cadeia da Polimerase , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Infecções por Ureaplasma/diagnóstico , Ureaplasma urealyticum , Adulto , DNA Bacteriano/análise , Humanos , Masculino , Tipagem Molecular , Nocardia , Nocardiose/complicações , Nocardiose/diagnóstico por imagem , Nocardiose/microbiologia , Pleuropneumonia/complicações , Pleuropneumonia/microbiologia , RNA Ribossômico 16S/análise , Infecções por Ureaplasma/complicações , Ureaplasma urealyticum/genética
15.
Int J Clin Pharmacol Ther ; 54(11): 923-927, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27509826

RESUMO

We report two cases of treatment failure in patients with osteoarticular infection associated with Staphylococcus aureus bacteremia and receiving daptomycin. Using a published population-pharmacokinetic model and daptomycin blood level in these patients, area under the curve (AUC) was calculated and compared to the pharmacological target. For the first patient, treated with 6 mg/kg every 48 hours due to acute renal failure and then every 24 hours, the AUC was 820 mg×h×L-1, with a minimal concentration of 23.5 mg/L confirming the right dose adjustment and the absence of underdosing. The methicillin-resistant Staphylococcus aureus (MRSA) strain was still susceptible to daptomycin, but it was not sufficient to observe a favorable outcome. For the second patient, treated with 10 mg/kg/d, the steady state residual concentration was 10.4 mg/L, and the calculated AUC value was 550 mg×h×L-1. AUC/MIC values evolved during treatment to be under the cut-off for bactericidal effects (> 800 hours), and the Staphylococcus aureus (SA) strain became daptomycin resistant. This study highlights the inter-individual pharmacokinetic variation leading sometimes to drug underdosing. Drug monitoring should be encouraged in order to avoid treatment failure.


Assuntos
Antibacterianos/sangue , Antibacterianos/uso terapêutico , Doenças Ósseas Infecciosas/tratamento farmacológico , Doenças Ósseas Infecciosas/microbiologia , Doenças das Cartilagens/tratamento farmacológico , Doenças das Cartilagens/microbiologia , Cartilagem Articular , Daptomicina/sangue , Daptomicina/uso terapêutico , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas/tratamento farmacológico , Idoso de 80 Anos ou mais , Antibacterianos/farmacocinética , Área Sob a Curva , Daptomicina/farmacocinética , Monitoramento de Medicamentos , Feminino , Humanos , Masculino , Osteomielite/tratamento farmacológico , Osteomielite/microbiologia , Falha de Tratamento , Vancomicina/uso terapêutico
16.
Clin Exp Rheumatol ; 34(3 Suppl 97): S89-92, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27214210

RESUMO

OBJECTIVES: To estimate the impact of vaccinations, infections and traumatic life events on the disease activity of a web-based cohort of systemic necrotising vasculitis (SNV) patients. METHODS: Adults diagnosed with SNV self-reported vaccinations, infectious episodes and traumatic life events every 3 months during follow-up on a secure dedicated website. Participants reported information on disease activity assessed with 3 scores: the French version of the Medical Outcome Study Short Form-36 (SF-36), the visual numerical scale for Patient Global Assessment (PGA) and the modified Disease Extent Index (mDEI). RESULTS: Between December 2005 and October 2008, 145 participants (mean ± SD age 53±13 years; 57% males) were included. Mean follow-up was 445±325 days. SNVs were distributed as follows: 46% granulomatosis with polyangiitis (Wegener's), 22% eosinophilic granulomatosis with polyangiitis (Churg-Strauss), 18% polyarteritis nodosa and 8% microscopic polyangiitis. During follow-up, 94 vaccinations, 57 acute infectious episodes and 274 traumatic life events were reported. In univariate and multivariate analyses, only traumatic life events were significantly associated with decreased SF-36 mental and physical component scores. No significant SF-36, PGA and mDEI scores variations were reported during the 3 months following acute infectious episode or vaccine administration. CONCLUSIONS: No significant clinical impact of vaccinations on SNV activity was found in this prospective observational study.


Assuntos
Vasculite Sistêmica/complicações , Vacinação , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Infecções/complicações , Internet , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
17.
Vaccine ; 34(20): 2390-6, 2016 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-27013430

RESUMO

INTRODUCTION: Pregnancy is a risk factor for severe influenza. However, data on influenza incidence during pregnancy are scarce. Likewise, no data are available on influenza vaccine coverage in France since national recommendation in 2012. We aimed to assess these points using a novel nationwide web-based surveillance system, G-GrippeNet. METHODS: During the 2014/2015 influenza season, pregnant women living in metropolitan France were enrolled through a web platform (https://www.grippenet.fr/). Throughout the season, participants were asked to report, on a weekly basis, if they had experienced symptoms of influenza-like-illness (ILI). ILI episodes reported were used to calculate incidence density rates based on period of participation from each participant. Vaccination coverage was estimated after weighing on age and education level from national data on pregnant women. Factors associated with higher vaccination coverage were obtained through a logistic regression with Odds Ratio (OR) corrected with the Zhang and Yu method. RESULTS: A total of 153 women were enrolled. ILI incidence density rate was 1.8 per 100 person-week (95% CI, 1.5-2.1). This rate was higher in women older than 40 years (RR = 3.0, 95% CI [1.1-8.3], p = 0.03) and during first/second trimesters compared to third trimester (RR = 4.0, 95% CI [1.4-12.0], p = 0.01). Crude vaccination coverage was 39% (95% CI, 31-47) and weighted vaccination coverage was estimated at 26% (95% CI, 20-34). Health care provider recommendation for vaccination (corrected OR = 7.8; 95% CI [3.0-17.1]) and non-smoking status (cOR = 2.1; 95% CI [1.2-6.9]) were associated with higher vaccine uptake. CONCLUSION: This original web based longitudinal surveillance study design proved feasible in pregnant women population. First results are of interest and underline that public health policies should emphasize the vaccination promotion through health care providers.


Assuntos
Influenza Humana/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Vacinação/estatística & dados numéricos , Adulto , Feminino , França/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Incidência , Influenza Humana/prevenção & controle , Internet , Estudos Longitudinais , Pessoa de Meia-Idade , Vigilância da População , Gravidez , Complicações Infecciosas na Gravidez/prevenção & controle , Vacinação/psicologia , Adulto Jovem
18.
Rev Prat ; 66(3): 275-279, 2016 03.
Artigo em Francês | MEDLINE | ID: mdl-30512637

RESUMO

Meningococcal vaccines in france. In France in 2015, several vaccines against invasive meningococcal disease (IMD) are available: non-conjugated polysaccharide vaccines (bivalent AC and tetravalent ACYW135) conjugate vaccines (monovalent A monovalent C and quadrivalent ACYW135) and a novel multicomponent meningococcal B vaccine. These vaccines have a very satisfactory safety profile. Currently in France, universal vaccination against serogroup C meningococcal disease is recommended for all infants at the age of 12 months with catch up till the age of 24 years. Vaccination against IMD B and C are also recommended to persons with specific individual risk factors (mainly asplenia, complement deficiency, hematopoietic stem cells) or travel in endemic areas. Despite recommendations, vaccination coverage remains below recommended levels in most of the targeted populations.


Vaccination antiméningococcique en france. En France en 2015, plusieurs vaccins contre les infections invasives à méningocoques (IIM) sont disponibles : des vaccins polyosidiques non conjugués (bivalent AC et tétravalent ACYW135), des vaccins conjugués (monovalent C et tétravalent ACYW135) et le vaccin protéique contre le méningocoques de sérogroupe B. Tous ces vaccins ont un profil de tolérance très satisfaisant. À l'heure actuelle, en France, une vaccination universelle contre les infections à méningocoque de sérogroupe C est recommandée pour tous les nourrissons à 12 mois avec rattrapage jusqu'à l'âge de 24 ans. Il existe également des recommandations de vaccination contre les infections à méningocoques C et B en fonction de facteurs de risque particuliers (principalement asplénie, déficit en complément, greffe de cellules souches hématopoïétiques) ou de voyage en zone d'endémie. Malgré ces recommandations, la couverture vaccinale reste cependant inférieure aux préconisations dans la plupart des populations ciblées.


Assuntos
Infecções Meningocócicas , Vacinas Meningocócicas , Neisseria meningitidis Sorogrupo C , França , Humanos , Lactente , Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/uso terapêutico , Vacinas Conjugadas
19.
Hum Vaccin Immunother ; 12(2): 528-33, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26309144

RESUMO

In France, vaccination against human papilloma virus (HPV) was recommended in 2007 for all 14-year-old girls as well as "catch-up" vaccination for girls between 15-23 y of age either before or within one year of becoming sexually active. We evaluated the vaccine coverage according to the eligibility for vaccination in a sample of young girls aged 14 to 23 years, who were seen in general practices. A survey was proposed to 706 general practitioners (GPs) and carried out from July to September 2010. GPs, also called "family doctor," are physicians whose practice is not restricted to a specific field of medicine but instead covers a variety of medical problems in patients of all ages. Each participating GP included, retrospectively, the last female patient aged 14-17 y and the last female patient aged 18-23 y whom he had seen. A questionnaire collected information regarding the GP and the patients' characteristics. The vaccine coverage was determined according to the eligibility for vaccination, i.e. the coverage among younger women (14-17) and among those sexually active in the second age range (18-23). Sexual activity status was assessed by GP, according to information stated in the medical record. The 363 participating physicians (response rate 51.4%) included 712 patients (357 in the 14- to 17-year-old group and 355 in the 15- to 23-year-old group) in their responses. The rate of the vaccination coverage in the 14- to 17-year-old group was 55%. Among the girls in the 18- to 23-year-old group, 126 were eligible, and their vaccination coverage rate was 82%. The evaluation of the eligibility by the GPs was incorrect in 36% of the cases. Of the 712 patients, 6% of the girls had been vaccinated without a need for the vaccination, and 26% of the girls had not been vaccinated, although they needed to be vaccinated. Regarding the vaccine uptake, vaccination at the age of 14 was not as effective as vaccinating the older population for which vaccination was indicated as a catch-up program, based on sexual history. However, in more than one-third of the older population, difficulties remained regarding the determination of eligibility, according to the sexual history of the patient.


Assuntos
Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/imunologia , Neoplasias do Colo do Útero/prevenção & controle , Vacinação/estatística & dados numéricos , Adolescente , Adulto , Feminino , França , Medicina Geral , Humanos , Masculino , Pessoa de Meia-Idade , Médicos , Estudos Retrospectivos , Comportamento Sexual , Inquéritos e Questionários , Adulto Jovem
20.
Vaccine ; 33(31): 3703-8, 2015 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-26073016

RESUMO

BACKGROUND: Immunocompromised patients are at increased risk for severe influenza and invasive pneumococcal diseases. Population-specific vaccine recommendations are thus warranted. This study aimed to estimate the prevalence and predictors of influenza and pneumococcal vaccine uptake in a large cohort of patients with secondary immune deficiency. METHODS: An anonymous online survey was submitted to the members of 11 French associations of immunocompromised patients. The questionnaire included questions concerning underlying disease, care and treatment, flu and pneumococcal vaccine uptake, attitudes and knowledge about vaccination. Factors associated with vaccine uptake were assessed by multivariate logistic regression. RESULTS: Among the 10,897 solicited patients, 3653 agreed to participate (33.5%): 75% were female, 20% aged 65+, 79% were followed for an autoimmune disease, 13% were solid organ recipients or waiting for transplantation and 8% were treated for hematological malignancies. 3109 (85%) participants were treated with immunosuppressive therapy. Self-reported vaccine uptake was 59% (95%CI [57-60]) against seasonal influenza and 49% (95%CI [47-50]) against pneumococcal diseases. Better knowledge of and favorable attitudes toward vaccination were positively associated with vaccine uptake while being treated with a biological therapy was negatively associated. CONCLUSION: Despite specific recommendations regarding immunocompromised patients, influenza and pneumococcal vaccination rates do not reach recommended levels. Targeted information campaigns on vaccination toward these populations should be implemented to improve vaccine coverage and thus reduce the burden of infections.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/administração & dosagem , Vacinação/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , França/epidemiologia , Humanos , Hospedeiro Imunocomprometido , Síndromes de Imunodeficiência , Vacinas contra Influenza/imunologia , Influenza Humana/epidemiologia , Masculino , Pessoa de Meia-Idade , Infecções Pneumocócicas/epidemiologia , Vacinas Pneumocócicas/imunologia , Inquéritos e Questionários , Adulto Jovem
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