RESUMO
BACKGROUND: Enterococcus faecalis infective endocarditis (EFIE) is characterized by a higher frequency of relapses than other infective endocarditis. The role of the treatment on its occurrence remains poorly understood. The aim of this study was to investigate whether the antibiotic regimen could impact the risk of relapse in EFIE. MATERIALS: This was a multicenter retrospective study of patients diagnosed with definite EFIE between 2015 and 2019 in 14 French hospitals. The primary endpoint was the occurrence of relapses within the year following endocarditis diagnosis. As death was a competing risk for relapse, Fine and Gray models were used for studying risk factors and impact of treatment. RESULTS: Of the 279 patients included, 83 (29.7%) received the amoxicillin-gentamicin (A-G) combination, 114 (40.9%) amoxicillin-ceftriaxone (A-C), 63 (22.6%) A-G and A-C (A-G/A-C) sequentially, 9 (3.2%) amoxicillin (A), and 10 received other treatments. One-year-relapse rate was 9.3% (26 patients). Relapse occurred after a median delay of 107 days from EFIE diagnosis; 6 occurred after 6 months, and 6 were diagnosed by blood cultures in asymptomatic patients. In multivariate analysis, surgery during treatment was a protective factor against one-year relapse and death.The cumulative incidence of relapse 1 year after endocarditis was 46.2% for patients treated with amoxicillin, 13.4% with A-G, 14.7% with A-C, and 4.3% with A-G/A-C (P≥.05 in multivariate analysis). CONCLUSIONS: Relapses after treatment of EFIE are frequent, frequently asymptomatic, and may occur more than 6 months after the initial episode.
Assuntos
Endocardite Bacteriana , Endocardite , Infecções por Bactérias Gram-Positivas , Humanos , Enterococcus faecalis , Estudos Retrospectivos , Antibacterianos/uso terapêutico , Endocardite/tratamento farmacológico , Endocardite Bacteriana/tratamento farmacológico , Amoxicilina/uso terapêutico , Gentamicinas/uso terapêutico , Quimioterapia Combinada , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , RecidivaRESUMO
BACKGROUND: The optimal duration of antimicrobial therapy for urinary tract infections (UTIs) in men remains controversial. METHODS: To compare 7 days to 14 days of total antibiotic treatment for febrile UTIs in men, this multicenter randomized, double-blind. placebo-controlled noninferiority trial enrolled 282 men from 27 centers in France. Men were eligible if they had a febrile UTI and urine culture showing a single uropathogen. Participants were treated with ofloxacin or a third-generation cephalosporin at day 1, then randomized at day 3-4 to either continue ofloxacin for 14 days total treatment, or for 7 days followed by placebo until day 14. The primary endpoint was treatment success, defined as a negative urine culture and the absence of fever and of subsequent antibiotic treatment between the end of treatment and 6 weeks after day 1. Secondary endpoints included recurrent UTI within weeks 6 and 12 after day 1, rectal carriage of antimicrobial-resistant Enterobacterales, and drug-related events. RESULTS: Two hundred forty participants were randomly assigned to receive antibiotic therapy for 7 days (115 participants) or 14 days (125 participants). In the intention-to-treat analysis, treatment success occurred in 64 participants (55.7%) in the 7-day group and in 97 participants (77.6%) in the 14-day group (risk difference, -21.9 [95% confidence interval, -33.3 to -10.1]), demonstrating inferiority. Adverse events during antibiotic therapy were reported in 4 participants in the 7-day arm and 7 in the 14-day arm. Rectal carriage of resistant Enterobacterales did not differ between both groups. CONCLUSIONS: A treatment with ofloxacin for 7 days was inferior to 14 days for febrile UTI in men and should therefore not be recommended. CLINICAL TRIALS REGISTRATION: NCT02424461; Eudra-CT: 2013-001647-32.
Assuntos
Anti-Infecciosos , Infecções Urinárias , Masculino , Humanos , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/complicações , Antibacterianos/efeitos adversos , Anti-Infecciosos/uso terapêutico , Febre/tratamento farmacológico , Febre/complicações , Método Duplo-Cego , Ofloxacino/uso terapêuticoRESUMO
OBJECTIVES: Limited pharmacokinetics data support dalbavancin long-term use in off-label indications and the optimal dosing regimen is debated. We aimed to describe dalbavancin concentrations in an observational retrospective multicentre study. METHODS: Patients from 13 French hospitals, treated with 1500â mg doses of dalbavancin and for whom therapeutic drug monitoring was performed from June 2018 to March 2021 were included. Dalbavancin plasma concentrations were described at peak and 1, 2, 3, 4, 6 and 8â weeks after the last 1500â mg dose. Concentrations in patients weighing more or less than 75â kg and with a GFR greater or less than 60â mL/min were compared. Microbiological data were collected and dalbavancin MIC was measured when possible. RESULTS: One hundred and thirty-three patients were included (69% treated for bone and joint infections, 16% for endocarditis). Thirty-five patients received a single dose of dalbavancin and 98 received several administrations. Two, 3 and 4â weeks after the last dose, median plasma concentrations were respectively 25.00, 14.80 and 9.24â mg/L for the first doses and 34.55, 22.60 and 19.20â mg/L for the second or subsequent doses. Weight and renal function had an impact on pharmacokinetics. Infection was documented in 105 patients (Staphylococcus spp. in 68% of cases). Staphylococcus aureus was isolated in 32.5% of cases (median MIC: 0.047â mg/L) and Staphylococcus epidermidis in 27% of cases (median MIC of 0.047â mg/L). CONCLUSIONS: Plasma concentrations of dalbavancin were consistent with those described in clinical trials and those sought during the industrial development of the molecule.
Assuntos
Antibacterianos , Infecções Estafilocócicas , Humanos , Teicoplanina/farmacocinética , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureusRESUMO
BACKGROUND: Early antibiotic discontinuation according to the Fourth European Conference on Infections in Leukaemia (ECIL-4) recommendations is not systematically applied in high-risk neutropenic patients with haematological malignancies. METHODS: A retrospective multicentre observational study was conducted over 2â years to evaluate the safety of early antibiotic discontinuation for fever of unknown origin (FUO) during neutropenia after induction chemotherapy or HSCT, in comparison with a historical cohort. We used Cox proportional hazards models, censored on neutropenia resolution, to analyse factors associated with febrile recurrence. RESULTS: Among 147 included patients in the ECIL-4 cohort, mainly diagnosed with acute leukaemia (nâ=â104, 71%), antibiotics were discontinued during 170 post-chemotherapy neutropenic episodes. In comparison with the historical cohort of 178 episodes of neutropenia without antibiotic discontinuation, no significant differences were observed regarding febrile recurrences [71.2% (121/170) versus 71.3% (127/178), Pâ=â0.97], admission in ICUs [6.5% (11/170) versus 11.2% (20/178), Pâ=â0.17], septic shock [0.6% (1/170) versus 3.9% (7/178), Pâ=â0.07] and 30â day mortality [1.4% (2/147) versus 2.7% (4/150), Pâ=â0.084]. In the ECIL-4 cohort, the rate of bacteraemia in case of febrile recurrence was higher [27.1% (46/170) versus 11.8% (21/178), Pâ<â0.01] and antibiotic consumption was significantly lower (15.5 versus 19.9â days, Pâ<â0.001). After early antibiotic discontinuation according to ECIL-4 recommendations, enterocolitis was associated with febrile recurrence [HRâ=â2.31 (95% CIâ=â1.4-3.8), Pâ<â0.001] and stage III-IV oral mucositis with bacteraemia [HRâ=â2.26 (95% CIâ=â1.22-4.2), Pâ=â0.01]. CONCLUSIONS: After an FUO episode in high-risk neutropenia, compliance with ECIL-4 recommendations for early antibiotic discontinuation appears to be safe and mucosal damage was associated with febrile recurrence and bacteraemia. Prospective interventional studies are warranted to assess this strategy in high-risk neutropenic patients.
Assuntos
Bacteriemia , Febre de Causa Desconhecida , Neoplasias Hematológicas , Leucemia Mieloide Aguda , Neoplasias , Neutropenia , Antibacterianos/efeitos adversos , Bacteriemia/complicações , Bacteriemia/tratamento farmacológico , Febre de Causa Desconhecida/induzido quimicamente , Febre de Causa Desconhecida/complicações , Febre de Causa Desconhecida/tratamento farmacológico , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/tratamento farmacológico , Humanos , Leucemia Mieloide Aguda/complicações , Neoplasias/complicações , Neutropenia/induzido quimicamente , Neutropenia/complicações , Neutropenia/tratamento farmacológico , Estudos ProspectivosRESUMO
Chronic meningococcemia is defined by blood culture(s) positive for Neisseria meningitidis, symptoms duration > 7 days, and neither meningitis nor shock on admission. This series of 26 consecutive cases illustrates that this is a rare disease (< 5% of meningococcemia, < 0.05 cases per 100,000 inhabitants per year), mostly affecting young adults, males, with no predisposing condition. Major symptoms include fever, rash, and arthralgia. Median time between symptoms onset, and diagnosis is 28 days. Most patients fully recover with a 1-week course of parenteral betalactams.
Assuntos
Antibacterianos/uso terapêutico , Infecções Meningocócicas/diagnóstico , Infecções Meningocócicas/tratamento farmacológico , beta-Lactamas/uso terapêutico , Adolescente , Adulto , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Doença Crônica/epidemiologia , Feminino , França/epidemiologia , Humanos , Incidência , Infusões Parenterais , Masculino , Infecções Meningocócicas/epidemiologia , Infecções Meningocócicas/microbiologia , Pessoa de Meia-Idade , Prognóstico , Adulto JovemRESUMO
Candidemia remains a major cause of disease worldwide and is associated with a high mortality rate. We conducted a retrospective study of candidemia at Nantes Hospital, France, between 2004 and 2010. A total of 191 episodes (n = 188 patients) were reviewed. Incidence, demographics, risk factors, antifungal management, species identification, in vitro susceptibility and 12 weeks survival were analysed. Global incidence of candidemia was 0.37 admissions. Higher incidences were observed in haematology (6.65) and intensive care units (2). Central venous catheter and antibiotic exposure were the most frequent risk factors (77% and 76% respectively). Candida albicans was the predominant species (51.8%) followed by C. parapsilosis (14.5%), C. glabrata (9.8%), C. tropicalis (9.8%) and C. krusei (4.1%). However, species distribution differed significantly between medical units with frequency of C. tropicalis being higher in haematology compared to other medical units. Fluconazole and caspofungin were the main antifungals given as first-line therapy. Although not significant, 12 weeks mortality rate was 30.9%, being higher for C. tropicalis (44.4%) than for C. parapsilosis (16%). Acquired azole or echinocandin resistance was noted in some isolates, underlining the need for systematic antifungal susceptibility testing in patients with candidemia. These epidemiological findings will be of interest for antifungal stewardship at our hospital.
Assuntos
Antifúngicos/farmacologia , Candida/classificação , Candidemia/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/uso terapêutico , Candida/efeitos dos fármacos , Candida/isolamento & purificação , Candidemia/tratamento farmacológico , Candidemia/microbiologia , Criança , Pré-Escolar , Farmacorresistência Fúngica , Equinocandinas/farmacologia , Equinocandinas/uso terapêutico , Feminino , Fluconazol/farmacologia , Fluconazol/uso terapêutico , França/epidemiologia , Unidades Hospitalares/estatística & dados numéricos , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: Acute graft pyelonephritis (AGPN) is the most frequent infectious complication in kidney transplant recipients (KTR). The treatment of acute community-acquired (CA) pyelonephritis is based on third-generation cephalosporins (3GC) and fluoroquinolones. Cefepime or a piperacillin-tazobactam combination are more often used in healthcare-associated (HCA) infections. However, these recommendations do not consider the resistance observed in KTRs. The objective of our study was to define the most appropriate empirical antibiotherapy for AGPN in KTRs according to the CA and HCA settings. To answer this question, we assessed the prevalence of resistance to different antibiotics usually recommended for urinary tract infections (UTIs) in the general population. METHODS: Observational, retrospective, multicenter study covering all episodes of AGPN occurring in hospitalized KTRs in 2019. RESULTS: A total of 210 patients were included in 7 centers and 244 episodes of AGPN were analyzed (158 CA-AGPN and 86 HCA-AGPN). The prevalence of 3GC and fluoroquinolone resistance was 23 % (n = 36) and 30 % (n = 50) in CA infections (n = 158), and 47 % (n = 40) and 31 % (n = 27) in HCA infections (n = 86), respectively. Cefepime resistance rate was 19 % (n = 30) in CA-AGPN and 29 % (n = 25) in HCA-AGPN. Piperacillin-tazobactam combination had resistance rates > 15 % in both CA and HCA infections. The only antimicrobials with resistance rates < 10 % were aminoglycosides and carbapenems. CONCLUSION: None of the antibiotics recommended in empirical treatment in UTIs has shown a resistance rate of less than 10% with regard to AGPN. Therefore, none of them should be used as monotherapy. A combination therapy including amikacin could be an appropriate strategy in this setting.
Assuntos
Antibacterianos , Transplante de Rim , Pielonefrite , Humanos , Estudos Retrospectivos , Antibacterianos/uso terapêutico , Pielonefrite/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Transplante de Rim/efeitos adversos , Adulto , Doença Aguda , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Urinárias/tratamento farmacológico , Combinação Piperacilina e Tazobactam/uso terapêutico , Idoso , Fluoroquinolonas/uso terapêutico , Cefalosporinas/uso terapêutico , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana , Infecção Hospitalar/tratamento farmacológicoRESUMO
Hormographiella aspergillata is a basidiomycete exceptionally involved in invasive fungal infections (IFI). We report a case of H. aspergillata pulmonary infection in a 30-year-old female in a context of pancytopenia and relapsed of acute myeloid leukemia (AML). She presented with fever, thoracic pain, left pleural effusion and pneumonia, diagnosed on chest X-ray and CT-scan. Direct examination of a bronchoalveolar lavage (BAL) specimen performed on day (d) 10 was negative, while the culture was positive on d30. H. aspergillata was suspected, considering macroscopic and microscopic examination. Its identification was confirmed using Microflex® Bruker mass spectrometry and pan-fungal (PF)-PCR assay followed by DNA sequencing. After this initial diagnosis, the patient was monitored for 2.8 years. She was treated with liposomal amphotericin B and/or voriconazole until switching to isavuconazole on d298 due to side-effects. This antifungal treatment was maintained until d717 and then discontinued, the patient being considered as cured. Over this follow-up period, the patient was submitted to recurrent pulmonary sampling. Each time, cultures were negative, while PF - PCR assays and DNA sequencing confirmed the presence of H. aspergillata. The present case-report is the 32nd observation of H. aspergillata invasive infection showing that this IFI is still infrequent. Fifteen have occurred in patients with AML, which appears as the most frequent underlying disease favoring this IFI. Six recent case-reports in addition to ours highlight PF-PCR assays and DNA sequencing as relevant diagnostic tools that must be included in routine diagnosis and monitoring of IFI, specifically those due to rare basidiomycetes.
Assuntos
Agaricales , Basidiomycota , Leucemia Mieloide Aguda , Pneumopatias Fúngicas , Pneumonia , Adulto , Feminino , Humanos , Antifúngicos/uso terapêutico , Basidiomycota/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Pneumopatias Fúngicas/diagnóstico , Pneumopatias Fúngicas/tratamento farmacológico , Pneumopatias Fúngicas/microbiologia , Reação em Cadeia da Polimerase , Análise de Sequência de DNARESUMO
BACKGROUND: Staphylococcus aureus bloodstream infection is treated with at least 14 days of intravenous antimicrobials. We assessed the efficacy and safety of an early switch to oral therapy in patients at low risk for complications related to S aureus bloodstream infection. METHODS: In this international, open-label, randomised, controlled, non-inferiority trial done in 31 tertiary care hospitals in Germany, France, the Netherlands, and Spain, adult patients with low-risk S aureus bloodstream infection were randomly assigned after 5-7 days of intravenous antimicrobial therapy to oral antimicrobial therapy or to continue intravenous standard therapy. Randomisation was done via a central web-based system, using permuted blocks of varying length, and stratified by study centre. The main exclusion criteria were signs and symptoms of complicated S aureus bloodstream infection, non-removable foreign devices, and severe comorbidity. The composite primary endpoint was the occurrence of any complication related to S aureus bloodstream infection (relapsing S aureus bloodstream infection, deep-seated infection, and mortality attributable to infection) within 90 days, assessed in the intention-to-treat population by clinical assessors who were masked to treatment assignment. Adverse events were assessed in all participants who received at least one dose of study medication (safety population). Due to slow recruitment, the scientific advisory committee decided on Jan 15, 2018, to stop the trial after 215 participants were randomly assigned (planned sample size was 430 participants) and to convert the planned interim analysis into the final analysis. The decision was taken without knowledge of outcome data, at a time when 126 participants were enrolled. The new sample size accommodated a non-inferiority margin of 10%; to claim non-inferiority, the upper bound of the 95% CI for the treatment difference (stratified by centre) had to be below 10 percentage points. The trial is closed to recruitment and is registered with ClinicalTrials.gov (NCT01792804), the German Clinical trials register (DRKS00004741), and EudraCT (2013-000577-77). FINDINGS: Of 5063 patients with S aureus bloodstream infection assessed for eligibility, 213 were randomly assigned to switch to oral therapy (n=108) or to continue intravenous therapy (n=105). Mean age was 63·5 (SD 17·2) years and 148 (69%) participants were male and 65 (31%) were female. In the oral switch group, 14 (13%) participants met the primary endpoint versus 13 (12%) in the intravenous group, with a treatment difference of 0·7 percentage points (95% CI -7·8 to 9·1; p=0·013). In the oral switch group, 36 (34%) of 107 participants in the safety population had at least one serious adverse event compared with 27 (26%) of 103 participants in the intravenous group (p=0·29). INTERPRETATION: Oral switch antimicrobial therapy was non-inferior to intravenous standard therapy in participants with low-risk S aureus bloodstream infection. However, it is necessary to carefully assess patients for signs and symptoms of complicated S aureus bloodstream infection at the time of presentation and thereafter before considering early oral switch therapy. FUNDING: Deutsche Forschungsgemeinschaft. TRANSLATIONS: For the German, Spanish, French and Dutch translations of the abstract see Supplementary Materials section.
Assuntos
Antibacterianos , Infecções Estafilocócicas , Staphylococcus aureus , Humanos , Feminino , Masculino , Infecções Estafilocócicas/tratamento farmacológico , Pessoa de Meia-Idade , Administração Oral , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Antibacterianos/efeitos adversos , Idoso , Bacteriemia/tratamento farmacológico , Resultado do Tratamento , Adulto , Administração IntravenosaRESUMO
BACKGROUND: Infective endocarditis (IE) caused by non-HACEK gram-negative bacilli (GNB) is poorly characterised and may be emerging as a consequence of medical progress. METHODS: We performed an observational retrospective case-control study. Cases were non-HACEK GNB IE, definite or possible (modified Duke criteria), diagnosed in adults between 2007 and 2020 in six French referral hospitals. Two controls were included for each case (IE due to other bacteria, matched by sites and diagnosis date). RESULTS: Non-HACEK GNB were identified in 2.4% (77/3230) of all IE during the study period, with a mean age of 69.2 ± 14.6 years, and a large male predominance (53/77, 69%). Primary pathogens were Escherichia coli (n = 33), Klebsiella sp. (n = 12) and Serratia marcescens (n = 9), including eight (10%) multidrug-resistant GNB. Compared to controls (n = 154: 43% Streptococcus sp., 41% Staphylococcus sp. and 12% Enterococcus sp.), non-HACEK GNB IE were independently associated with intravenous drug use (IVDU, 8% vs. 2%, p = .003), active neoplasia (15% vs. 6%, p = .009), haemodialysis (9% vs. 3%, p = .007) and healthcare-associated IE (36% vs. 18%, p = .002). Urinary tract was the main source of infection (n = 25, 33%) and recent invasive procedures were reported in 29% of cases. Non-HACEK GNB IE were at lower risk of embolism (31% vs. 47%, p = .002). One-year mortality was high (n = 28, 36%). Comorbidities, particularly malignant hemopathy and cirrhosis, were associated with increased risk of death. CONCLUSIONS: Non-HACEK GNB are rarely responsible for IE, mostly as healthcare-associated IE in patients with complex comorbidities (end-stage renal disease, neoplasia), or in IVDUs.
Assuntos
Endocardite Bacteriana , Endocardite , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Estudos Retrospectivos , Estudos de Casos e Controles , Endocardite Bacteriana/tratamento farmacológico , Bactérias Gram-NegativasRESUMO
The term phaeohyphomycosis refers to a rare group of fungal infections characterized by the presence of dark-walled hyphae or yeast-like cells in affected tissues. Herein, we report on the clinical and epidemiological characteristics of six cases of phaeohyphomycosis due to Alternaria spp. that occurred in our hospital over a 30-month period (from January 2008 to June 2010). Interestingly, whereas histopathological examinations were positive and fungal cultures yielded molds in all cases, mycological identification using conventional phenotypic methods was never possible despite prolonged incubation of the isolates. Identification of Alternaria infectoria species complex was obtained for each isolate by amplification and sequencing of the internal transcribed spacer of the ribosomal DNA (ITS rDNA). All patients had favourable outcomes following the introduction of azole-based antifungal therapy. This case series describes the clinical course of these six patients and highlights the utility of molecular identification to help in the identification of the etiologic agent when classical mycological methods have failed.
Assuntos
Alternaria/patogenicidade , Feoifomicose/microbiologia , Adulto , Idoso , Alternaria/classificação , Alternaria/genética , Alternaria/isolamento & purificação , Antifúngicos/uso terapêutico , Sequência de Bases , Biópsia/métodos , DNA Fúngico/análise , DNA Fúngico/genética , DNA Espaçador Ribossômico/genética , Feminino , Hospitais , Humanos , Itraconazol/farmacologia , Masculino , Pessoa de Meia-Idade , Técnicas de Tipagem Micológica , Feoifomicose/diagnóstico , Feoifomicose/tratamento farmacológico , Feoifomicose/epidemiologia , Análise de Sequência de DNARESUMO
OBJECTIVE: We aimed to investigate whether anakinra, an interleukin-1receptor inhibitor, could improve outcome in moderate COVID-19 patients. METHODS: In this controlled, open-label trial, we enrolled adults with COVID-19 requiring oxygen. We randomly assigned patients to receive intravenous anakinra plus optimized standard of care (oSOC) vs. oSOC alone. The primary outcome was treatment success at day 14 defined as patient alive and not requiring mechanical ventilation or extracorporeal membrane oxygenation. RESULTS: Between 27th April and 6th October 2020, we enrolled 71 patients (240 patients planned to been enrolled): 37 were assigned to the anakinra group and 34 to oSOC group. The study ended prematurely by recommendation of the data and safety monitoring board due to safety concerns. On day 14, the proportion of treatment success was significantly lower in the anakinra group 70% (n = 26) vs. 91% (n = 31) in the oSOC group: risk difference-21 percentage points (95% CI, -39 to -2), odds ratio 0.23 (95% CI, 0.06 to 0.91), p = 0.027. After a 28-day follow-up, 9 patients in the anakinra group and 3 in the oSOC group had died. Overall survival at day 28 was 75% (95% CI, 62% to 91%) in the anakinra group versus 91% (95% CI, 82% to 100%) (p = 0.06) in the oSOC group. Serious adverse events occurred in 19 (51%) patients in the anakinra group and 18 (53%) in the oSOC group (p = 0·89). CONCLUSION: This trial did not show efficacy of anakinra in patients with COVID-19. Furthermore, contrary to our hypothesis, we found that anakinra was inferior to oSOC in patients with moderate COVID-19 pneumonia.
Assuntos
Tratamento Farmacológico da COVID-19 , Adulto , Humanos , Proteína Antagonista do Receptor de Interleucina 1/efeitos adversos , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Respiração Artificial , SARS-CoV-2 , Resultado do TratamentoRESUMO
OBJECTIVES: Pulmonary tularemia is a rare and little-known disease, whose clinical and radiological presentation can be confused with those of much more frequent pathologies, such as lung cancer or B-cell lymphoma (46,000 and 5,000 new cases respectively per year in France). Furthermore, PET/CT is a powerful tool for the diagnosis of malignancies or the exploration of fever of unknown origin. The objective of this study was to describe the characteristics of pulmonary tularemia and to determine whether its PET/CT aspect could help distinguish it from neoplasia. METHODS: Retrospective observational study collecting all pulmonary tularemia cases for which a PET/CT was performed between 2016 and 2020. RESULTS: Twenty-seven cases of pulmonary tularemia were analyzed. The sex ratio was 4.4, and the median age was 60 years. Clinical manifestations were mainly represented by fever (n=23), arthralgia (n=7) and cough (n=6). PET/CT revealed intensely hypermetabolic mediastinal adenopathies in all cases, associated with parenchymal (n=20) or pleural (n=6) lesions, suggesting neoplastic pathology in 15 patients. Cytopuncture or lymph node biopsy was performed in 16 patients, revealing non-specific adenitis (n=8), necrotic epithelio-gigantocellular granuloma (n=3), or were non-contributory (n=5). All patients reported significant environmental exposure. The outcome was favorable for all patients, spontaneously for 8 of them and after antibiotic therapy with either doxycycline or ciprofloxacin for the other 19. CONCLUSIONS: Depending on the epidemiological setting, pulmonary tularemia may be considered an alternative diagnosis to lung cancer, lymphoma, or tuberculosis, in the presence of infectious symptoms and hypermetabolic pulmonary lesions and mediastinal lymphadenopathies on PET/CT.
Assuntos
Neoplasias Pulmonares , Tularemia , Fluordesoxiglucose F18 , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Tularemia/diagnósticoRESUMO
We report a case of disseminated Scedosporium/Pseudallescheria infection due to Pseudallescheria boydii sensu stricto after lung transplantation in a patient with cystic fibrosis. Dissemination occurred under voriconazole. Despite surgery and combination therapy with voriconazole, caspofungin, and terbinafine, the patient died 8 months after transplantation. Previously reported cases are reviewed.
Assuntos
Fibrose Cística/terapia , Pneumopatias Fúngicas/diagnóstico , Transplante de Pulmão/efeitos adversos , Pseudallescheria/isolamento & purificação , Scedosporium/isolamento & purificação , Adulto , Antifúngicos/uso terapêutico , Encéfalo/diagnóstico por imagem , Caspofungina , Quimioprevenção/métodos , DNA Fúngico/química , DNA Fúngico/genética , Equinocandinas/uso terapêutico , Evolução Fatal , Feminino , Humanos , Lipopeptídeos , Pneumopatias Fúngicas/tratamento farmacológico , Pneumopatias Fúngicas/microbiologia , Pneumopatias Fúngicas/cirurgia , Imageamento por Ressonância Magnética , Testes de Sensibilidade Microbiana , Microscopia , Dados de Sequência Molecular , Naftalenos/uso terapêutico , Pseudallescheria/classificação , Pseudallescheria/citologia , Pseudallescheria/genética , Pirimidinas/uso terapêutico , RNA Fúngico/genética , RNA Ribossômico 28S/genética , Radiografia , Scedosporium/classificação , Scedosporium/citologia , Scedosporium/genética , Análise de Sequência de DNA , Terbinafina , Triazóis/uso terapêutico , VoriconazolRESUMO
BACKGROUND: We describe the epidemiological, clinical, and prognostic aspects of 177 tularemia cases diagnosed at the National Reference Center for rickettsioses, coxiellosis, and bartonelloses between 2008 and 2017. METHODS: All patients with a microbiological diagnosis of tularemia made in the laboratory were included. Clinical and epidemiological data were collected retrospectively from clinicians in charge of patients using a standardized questionnaire. Diagnostic methods used were indirect immunofluorescence serology, real-time polymerase chain reaction (PCR), and universal PCR targeting the 16S ribosomal ribonucleic acid gene. RESULTS: The series included 54 females and 123 males (sex ratio, 2.28; mean age, 47.38 years). Eighty-nine (50.2%) were confirmed as having tularemia on the basis of a positive Francisella tularensis PCR or seroconversion, and 88 (49.8%) were considered as probable due to a single positive serum. The regions of France that were most affected included Pays de la Loire (22% of cases), Nouvelle Aquitaine (18.6% of cases), and Grand Est (12.4% of cases). Patients became infected mainly through contact with rodents or game (38 cases, 21.4%), through tick-bites (23 cases, 12.9%), or during outdoor leisure activities (37 cases, 20.9%). Glandular and ulceroglandular forms were the most frequent (109 cases, 61.5%). Two aortitis, an infectious endocarditis, a myocarditis, an osteoarticular infection, and a splenic hematoma were also diagnosed. Tularemia was discovered incidentally in 54.8% of cases. Seventy-eight patients were hospitalized, and no deaths were reported. CONCLUSIONS: Our data suggest that in an endemic area and/or in certain epidemiological contexts, tularemia should be sought to allow an optimized antibiotic therapy and a faster recovery.
RESUMO
INTRODUCTION: Immediate empirical antibiotic therapy is mandatory in febrile chemotherapy-induced neutropenia, but its optimal duration is unclear, especially in patients with fever of unknown origin (FUO). OBJECTIVES: The primary objective of this 20-month prospective observational study was to evaluate the feasibility and safety of short-term antibiotic treatment in afebrile or febrile patients exhibiting FUO, irrespective of their neutrophil count. The secondary objective was to describe the epidemiology of all episodes of febrile neutropenia. METHODS: In the first phase of the study, empirical antibiotic therapy in FUO patients was stopped after 48 h of apyrexia, in accordance with European Conference on Infections in Leukaemia guidelines (n = 45). In the second phase of the study, antibiotics were stopped no later than day 5 for all FUO patients, regardless of body temperature or leukocyte count (n = 37). RESULTS: Two hundred and thirty-eight cases of febrile neutropenia in 123 patients were included. Neither the composite endpoint (p = .11), nor each component (in-hospital mortality (p = .80), intensive care unit admission (p = 0.48), relapse of infection ≤48 h after discontinuation of antibiotics (p = .82)) differed between the two FUO groups. Violation of protocol occurred in 17/82 episodes of FUO without any major impact on statistical results. Twenty-six (57.3%) and 22 (59.5%) FUO episodes did not relapse during hospital-stay (p = 1), and nine (20%) and five (13.5%) presented another FUO, respectively. One hundred and fifty-six episodes of febrile neutropenia (65.5%) were clinically or microbiologically documented, including 85 bacteremia. CONCLUSIONS: These results suggest that early discontinuation of empirical antibiotics in FUO is safe for afebrile neutropenic patients.
Assuntos
Antibacterianos/administração & dosagem , Neutropenia Febril/tratamento farmacológico , Febre de Causa Desconhecida/tratamento farmacológico , Suspensão de Tratamento , Adolescente , Adulto , Idoso , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Neutropenia Febril Induzida por Quimioterapia/tratamento farmacológico , Neutropenia Febril Induzida por Quimioterapia/epidemiologia , Quimioterapia Combinada , Estudos de Viabilidade , Neutropenia Febril/epidemiologia , Neutropenia Febril/mortalidade , Feminino , Febre de Causa Desconhecida/epidemiologia , Febre de Causa Desconhecida/mortalidade , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Negativas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Segurança , Fatores de Tempo , Adulto JovemRESUMO
Three months after a kidney transplant, a man experienced an internuclear ophthalmoplegia. Magnetic resonance imaging found a punctuate hyperintensity of the brainstem. Afterwards, the patient presented with peripheral facial paralysis. A complete morphologic assessment showed an increase of the brainstem lesion, together with an excavated pulmonary nodule. Combination therapy with high-dose liposomal amphotericin B and voriconazole was begun for the putative aspergillosis. Owing to its atypical clinical presentation and negative detection of Aspergillus galactomannan antigen on sera, a biopsy specimen of the lung lesion was obtained. Histopathological and mycological investigations allowed the diagnosis of mucormycosis owing to Rhizopus microsporus. Accordingly, voriconazole was replaced with posaconazole. After 5 months, regression of the cerebral lesion was noted. Disseminated mucormycosis in solid-organ recipients is uncommon and mycological diagnosis is challenging. Mortality is high and is increased by diagnostic delay. Treating mucormycosis requires surgical debridement and appropriate antifungal therapy (usually intravenous liposomal amphotericin B). This report suggests that a combination of liposomal amphotericin B and posaconazole can be a therapeutic option in patients with a poor prognosis.