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1.
Am Heart J ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38848985

RESUMO

BACKGROUND: It remains unclear today whether risk scores created specifically to predict early mortality after cardiac operations for infective endocarditis (IE) outperform or not the European System for Cardiac Operative Risk Evaluation II (EuroSCORE II). METHODS: Perioperative data and outcomes from a European multicenter series of patients undergoing surgery for definite IE were retrospectively reviewed. Only the cases with known pathogen and without missing values for all considered variables were retained for analyses. A comparative validation of EuroSCORE II and five specific risk scores for early mortality after surgery for IE - (1) STS-IE (Society of Thoracic Surgeons for IE); (2) PALSUSE (Prosthetic valve, Age ≥70, Large intra-cardiac destruction, Staphylococcus spp, Urgent surgery, Sex (female), EuroSCORE ≥10); (3) ANCLA (Anemia, New York Heart Association class IV, Critical state, Large intra-cardiac destruction, surgery on thoracic Aorta); (4) AEPEI II (Association pour l'Étude et la Prévention de l'Endocardite Infectieuse II); (5) APORTEI (Análisis de los factores PROnósticos en el Tratamiento quirúrgico de la Endocarditis Infecciosa) - was carried out using calibration plot and receiver-operating characteristic curve analysis. Areas under the curve (AUCs) were compared 1:1 according to the Hanley-McNeil's method. The agreement between APORTEI score and EuroSCORE II of the 30-day mortality prediction after surgery was also appraised. RESULTS: A total of 1,012 patients from five European university-affiliated centers underwent 1,036 cardiac operations, with a 30-day mortality after surgery of 9.7%. All IE-specific risk scores considered achieved better results than EuroSCORE II in terms of calibration; AEPEI II and APORTEI score showed the best performances. Despite poor calibration, EuroSCORE II overcame in discrimination every specific risk score (AUC, 0.751 vs. 0.693 or less, p=0.01 or less). For a higher/lesser than 20% expected mortality, the agreement of prediction between APORTEI score and EuroSCORE II was 86%. CONCLUSION: EuroSCORE II discrimination for 30-day mortality after surgery for IE was higher than five established IE-specific risk scores. AEPEI II and APORTEI score showed the best results in terms of calibration.

2.
BMC Infect Dis ; 24(1): 35, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38166743

RESUMO

BACKGROUND: In recent years, Acinetobacter baumannii-calcoaceticus complex (ABC) infections have attracted attention, mainly because of the impact of carbapenem-resistant isolates in hospital-acquired infections. However, acute community-acquired ABC infections are not uncommon in warm and humid countries, where they are responsible for community-acquired infections with specific clinical features. To date, such infection has not been reported in France. CASE PRESENTATION: We report the case of a 55-year-old non-immunocompromised patient living in France with no known risk factors for community-acquired ABC infections who presented pneumonia with bloodstream infection due to wild-type A. pittii. The outcome was favorable after 7 days of antibiotic treatment with cefepime. We confirmed bacterial identification with whole-genome sequencing, and we examined the A. pitii core-genome phylogeny for genomic clusters. CONCLUSIONS: This situation is uncommon in Europe and occurred after a heat wave in France with temperatures above 38 °C. Herein, we discuss the possibility that this pneumonia may be emerging in the current context of global warming.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Acinetobacter , Infecções Comunitárias Adquiridas , Pneumonia , Humanos , Pessoa de Meia-Idade , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Temperatura Alta , Acinetobacter/genética , Antibacterianos/uso terapêutico , Infecções por Acinetobacter/diagnóstico , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Pneumonia/diagnóstico , Pneumonia/tratamento farmacológico , França , Testes de Sensibilidade Microbiana
3.
J Antimicrob Chemother ; 78(11): 2762-2769, 2023 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-37796958

RESUMO

BACKGROUND: The new definitions of antimicrobial susceptibility categories proposed by EUCAST in 2020 require the definition of standard and high dosages of antibiotic. For injectable ß-lactams, standard and high dosages have been proposed for short-infusion regimens only. OBJECTIVES: To evaluate dosages for ß-lactams administered by prolonged infusion (PI) and continuous infusion (CI). METHODS: Monte Carlo simulations were performed for seven injectable ß-lactams: aztreonam, cefepime, cefotaxime, cefoxitin, ceftazidime, piperacillin and temocillin. Various dosage regimens based on short infusion, PI or CI were simulated in virtual patients. Pharmacokinetic (PK) profiles and PTAs were obtained based on reference population PK models, as well as PK/pharmacodynamic targets and MIC breakpoints proposed by EUCAST. Alternative dosage regimens associated with PTA values similar to those of recommended dosages up to the breakpoints were considered acceptable. RESULTS: Adequate PTAs were confirmed for most EUCAST short-infusion dosage regimens. A total of 9 standard and 14 high dosages based on PI (3 to 4 h) or CI were identified as alternatives. For cefepime and aztreonam, only PI and CI regimens could achieve acceptable PTAs for infections caused by Pseudomonas spp.: 2 g q8h as PI of 4 h or 6 g/24 h CI for cefepime; 2 g q6h as PI of 3 h or 6 g/24 h CI for aztreonam. CONCLUSIONS: These alternative standard and high dosage regimens are expected to provide antibiotic exposure compatible with new EUCAST definitions of susceptibility categories and associated MIC breakpoints. However, further clinical evaluation is necessary.


Assuntos
Antibacterianos , Aztreonam , Humanos , Cefepima , Antibacterianos/farmacologia , Ceftazidima , Piperacilina , Testes de Sensibilidade Microbiana , Método de Monte Carlo
4.
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
5.
PLoS Pathog ; 17(3): e1009416, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33780519

RESUMO

COVID-19 is characterized by respiratory symptoms of various severities, ranging from mild upper respiratory signs to acute respiratory failure/acute respiratory distress syndrome associated with a high mortality rate. However, the pathophysiology of the disease is largely unknown. Shotgun metagenomics from nasopharyngeal swabs were used to characterize the genomic, metagenomic and transcriptomic features of patients from the first pandemic wave with various forms of COVID-19, including outpatients, patients hospitalized not requiring intensive care, and patients in the intensive care unit, to identify viral and/or host factors associated with the most severe forms of the disease. Neither the genetic characteristics of SARS-CoV-2, nor the detection of bacteria, viruses, fungi or parasites were associated with the severity of pulmonary disease. Severe pneumonia was associated with overexpression of cytokine transcripts activating the CXCR2 pathway, whereas patients with benign disease presented with a T helper "Th1-Th17" profile. The latter profile was associated with female gender and a lower mortality rate. Our findings indicate that the most severe cases of COVID-19 are characterized by the presence of overactive immune cells resulting in neutrophil pulmonary infiltration which, in turn, could enhance the inflammatory response and prolong tissue damage. These findings make CXCR2 antagonists, in particular IL-8 antagonists, promising candidates for the treatment of patients with severe COVID-19.


Assuntos
COVID-19 , Genoma Viral , Metagenômica , SARS-CoV-2 , Células Th1/imunologia , Células Th17/imunologia , Transcriptoma , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/genética , COVID-19/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de Interleucina-8B/genética , Receptores de Interleucina-8B/imunologia , SARS-CoV-2/genética , SARS-CoV-2/imunologia
6.
Emerg Infect Dis ; 27(5): 1540-1543, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33900195

RESUMO

We report a novel severe acute respiratory syndrome coronavirus 2 variant derived from clade 19B (HMN.19B variant or Henri Mondor variant). This variant is characterized by the presence of 18 amino acid substitutions, including 7-8 substitutions in the spike protein and 2 deletions. These variants actively circulate in different regions of France.


Assuntos
COVID-19 , SARS-CoV-2 , Substituição de Aminoácidos , França/epidemiologia , Humanos , Glicoproteína da Espícula de Coronavírus/genética
7.
Transpl Infect Dis ; 23(2): e13486, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33047447

RESUMO

BACKGROUND: Data on the risk factors and outcome of intra-abdominal fungal infections (IAFI) following simultaneous pancreas-kidney transplantation (PKT) are scarce. MATERIALS/METHODS: A retrospective monocentric study was conducted on all patients who underwent simultaneous PKT from January 2007 to December 2016. Deep sites positive cultures for fungi during the first post-transplantation year were collected. Clinical, radiological, and microbiological data of proven and probable invasive fungal infections were analysed. RESULTS: Among sixteen PKT patients, 15 were included. Seven patients (47%) developed an invasive fungal infection, exclusively IAFI (six proven, one probable). The proven IAFI included four peritonitis, one pancreatic necrosis with infected hematoma, and one patient with positive preservation fluid only (PF). Candida albicans (n = 4) was the most prevalent species (associated with Galactomyces candidus in one case), C glabrata, C dubliniensis, and C krusei were found in one case each. Three patients had either a positive direct examination and/or culture for renal or pancreatic PF and the culture of PF was positive for the same species that caused IAFI. IAFIs were significantly associated with pancreatic graft arterial thrombosis (5/7 vs 0/8, P = .007) and fungal contamination of PF (3/7 vs 0/8, P = .008). Among patients with IAFI, all required an early surgical revision post-transplantation [1-18 days] and six had early or delayed pancreatic graft removal. One patient died in the first post-transplant year. CONCLUSION: IAFI is a common complication in PKT, associated with pancreatic graft thrombosis or fungal contamination of the graft PF, and can sometimes lead to pancreatic detransplantation.


Assuntos
Transplante de Rim , Micoses , Geotrichum , Humanos , Pâncreas , Estudos Retrospectivos , Fatores de Risco
8.
Crit Care ; 25(1): 241, 2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-34238367

RESUMO

BACKGROUND: Bloodstream infections (BSIs) are frequent on veno-arterial extracorporeal membrane oxygenation (V-A ECMO). Performing routine blood cultures (BCs) may identify early paucisymptomatic BSIs. We investigated the contribution of systematic daily BCs to detect BSIs on V-A ECMO. METHODS: This was a retrospective study including all adult patients requiring V-A ECMO and surviving more than 24 h. Our protocol included routine daily BCs, from V-A ECMO insertion up to 5 days after withdrawal; other BCs were performed on-demand. RESULTS: On the 150 V-A ECMO included, 2146 BCs were performed (1162 routine and 984 on-demand BCs); 190 (9%) were positive, including 68 contaminants. Fifty-one (4%) routine BCs revealed BSIs; meanwhile, 71 (7%) on-demand BCs revealed BSIs (p = 0.005). Performing routine BCs was negatively associated with BSIs diagnosis (OR 0.55, 95% CI [0.38; 0.81], p = 0.002). However, 16 (31%) BSIs diagnosed by routine BCs would have been missed by on-demand BCs. Independent variables for BSIs diagnosis after routine BCs were: V-A ECMO for cardiac graft failure (OR 2.43, 95% CI [1.20; 4.92], p = 0.013) and sampling with on-going antimicrobial therapy (OR 2.15, 95% CI [1.08; 4.27], p = 0.029) or renal replacement therapy (OR 2.05, 95% CI [1.10; 3.81], p = 0.008). Without these three conditions, only two BSIs diagnosed with routine BCs would have been missed by on-demand BCs sampling. CONCLUSIONS: Although routine daily BCs are less effective than on-demand BCs and expose to contamination and inappropriate antimicrobial therapy, a policy restricted to on-demand BCs would omit a significant proportion of BSIs. This argues for a tailored approach to routine daily BCs on V-A ECMO, based on risk factors for positivity.


Assuntos
Hemocultura/normas , Oxigenação por Membrana Extracorpórea/estatística & dados numéricos , Sepse/diagnóstico , Fatores de Tempo , Adulto , Idoso , Hemocultura/métodos , Hemocultura/estatística & dados numéricos , Oxigenação por Membrana Extracorpórea/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Sepse/classificação , Estatísticas não Paramétricas
9.
Infection ; 48(3): 413-420, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32185636

RESUMO

PURPOSE: Corynebacterium spp. (C. spp.) is commonly considered as a contaminant in respiratory specimens. No study has ever focused on its clinical relevance in the lower respiratory tract of patients admitted to the intensive care unit (ICU) and requiring mechanical ventilation. The aims were to describe the characteristics of ICU patients with a C. spp. positive deep respiratory specimen, to investigate the impact of C. spp. on the occurrence of pneumonia, and to evaluate the outcomes of these pneumonia. METHODS: We retrospectively included all adult patients admitted to ICU in a 1000-bed University Hospital (2007-2017) who had a C. spp. positive lower respiratory tract specimen at a significant quantitative level. We used clinical, radiological, and microbiological criteria to classify the likelihood of such pneumonia. RESULTS: Among the 31 patients included, acute respiratory failure and postoperative care after major surgery were the main reasons of admission. SAPS II was 47 [34-60]. C. spp. pneumonia was considered as probable, possible and unlikely in 10, 14, and 7 patients, respectively. Fifty-two and 94% of C. spp. strains were sensitive to amoxicillin, and vancomycin/linezolid, respectively. Seventeen patients had a complete course of antibiotic against C. spp. The overall ICU mortality was 58%. CONCLUSION: Corynebacterium spp seems to be responsible for authentic pneumonia in mechanically ventilated patients. It should be considered as clinically relevant when predominantly present in respiratory specimen from patients suspected with pneumonia in ICU, and empirically treated.


Assuntos
Infecções por Corynebacterium/terapia , Corynebacterium/isolamento & purificação , Unidades de Terapia Intensiva/estatística & dados numéricos , Pneumonia/mortalidade , Respiração Artificial/estatística & dados numéricos , Infecções Respiratórias/terapia , Idoso , Estudos de Coortes , Infecções por Corynebacterium/microbiologia , Estado Terminal/epidemiologia , Estado Terminal/terapia , Feminino , França/epidemiologia , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia/microbiologia , Infecções Respiratórias/microbiologia , Estudos Retrospectivos
10.
Artigo em Inglês | MEDLINE | ID: mdl-29263078

RESUMO

An increase in amoxicillin-induced crystal nephropathy (AICN) incidence has been recently suggested. The aims of this study were to investigate the trend of AICN incidence through Paris' regional centers of pharmacovigilance (Paris RCPVs) and better describe this rare adverse drug reaction. Forty-five AICN cases were identified between 1985 and 2016. All cases, except one, were reported since 2010. Amoxicillin (AMX) was administered intravenously (65 [interquartile range {IQR}, 43 to 110] mg/kg of body weight/day) in all patients, either for treating infection (n = 15) or as surgical prophylaxis (n = 30). Delay between AMX administration and AICN onset was 1 (IQR, 1 to 3) day; 30, 4, and 11 patients developed KDIGO stage 1, 2, and 3 acute kidney injury, respectively. Delay between AICN onset and kidney function recovery was 4 (IQR, 2 to 6) days. Precipitating factors were identified in only one-third of cases. Twelve patients required intensive care unit admission, and 8 needed renal replacement therapy. Neither chronic kidney disease nor death was observed. We confirmed the recent and dramatic increase of AICN in the Paris RCPVs since 2010. The absence of precipitating factors in the majority of cases and the onset of AICN in apparent routine indications, such as surgical prophylaxis, are alarming and justify a high vigilance from all AMX prescribers.


Assuntos
Amoxicilina/efeitos adversos , Injúria Renal Aguda/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Farmacovigilância , Estudos Retrospectivos
11.
Eur J Clin Microbiol Infect Dis ; 37(10): 1931-1940, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30051357

RESUMO

Febrile neutropenia (FN) is the main reason for antibiotic prescription in hematology wards where, on the other hand, antibiotic stewardship (AS) is poorly explored. The objectives of the present study were to evaluate (1) the impact of an AS intervention on antibiotic consumption and (2) the applicability and acceptance rate of the intervention and its clinical impact. A persuasive AS intervention based on European Conference on Infection in Leukaemia (ECIL) guidelines for FN was implemented in a high-risk hematology ward in a tertiary referral public university hospital. This included the creation and diffusion of flow charts on de-escalation and discontinuation of antibiotics for FN, and the introduction in the team of a doctor dedicated to the implementation of flow charts and to antibiotic prescription revision. All consecutive patients receiving antibiotics during hospitalization were included. A segmented linear regression model was performed for the evaluation of antibiotic consumption, taking into account 1-year pre-intervention period and 6-month intervention period. Overall, 137 consecutive antibiotic prescriptions were re-evaluated, 100 prescriptions were for FN. A significant reduction of the level of carbapenem consumption was observed during the intervention period (level change (estimate coefficient ± standard error) = - 135.28 ± 59.49; p = 0.04). Applicability and acceptability of flow charts were high. No differences in terms of intensive care unit transfers, bacteremia incidence, and mortality were found. A persuasive AS intervention in hematology significantly reduced carbapenem consumption without affecting outcome and was well accepted. This should encourage further applications of ECIL guidelines for FN.


Assuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Uso de Medicamentos/estatística & dados numéricos , Neutropenia/tratamento farmacológico , Adulto , Idoso , Antibacterianos/economia , Infecções Bacterianas/microbiologia , Feminino , Febre/tratamento farmacológico , Febre/microbiologia , França , Hematologia , Hospitalização , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Análise de Séries Temporais Interrompida , Masculino , Pessoa de Meia-Idade , Neutropenia/microbiologia , Resultado do Tratamento , Suspensão de Tratamento/estatística & dados numéricos
17.
Open Forum Infect Dis ; 11(7): ofae327, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38957691

RESUMO

Background: The advent of anti-tumor necrosis factor α (anti-TNFα) has revolutionized the treatment of inflammatory bowel disease (IBD). However, susceptibility to active tuberculosis (TB) is associated with this therapy and requires its discontinuation. The risk of immune reconstitution inflammatory syndrome (IRIS) in this population is poorly understood, as is the safety of resuming anti-TNFα. Methods: This French retrospective study (2010-2022) included all TB cases in patients with IBD who were treated with anti-TNFα in 6 participating centers. A systematic literature review was performed on TB-IRIS and anti-TNFα exposure. Results: Thirty-six patients were included (median age, 35 years; IQR, 27-48). TB was disseminated in 86% and miliary in 53%. IRIS occurred in 47% after a median 45 days (IQR, 18-80). Most patients with TB-IRIS (93%) had disseminated TB. Miliary TB was associated with IRIS risk in univariate analysis (odds ratio, 7.33; 95% CI, 1.60-42.82; P = .015). Anti-TB treatment was longer in this population (median [IQR], 9 [9-12] vs 6 [6-9] months; P = .049). Anti-TNFα was resumed in 66% after a median 4 months (IQR, 3-10) for IBD activity (76%) or IRIS treatment (24%), with only 1 case of TB relapse. Fifty-two cases of TB-IRIS in patients treated with anti-TNFα were reported in the literature, complicating disseminating TB (85%) after a median 42 days (IQR, 21-90), with 70% requiring anti-inflammatory treatment. Forty cases of TB-IRIS or paradoxical reaction treated with anti-TNFα were also reported. IRIS was neurologic in 64%. Outcome was mostly favorable (93% recovery). Conclusions: TB with anti-TNFα treatment is often complicated by IRIS of varying severity. Restarting anti-TNFα is a safe and effective strategy.

18.
Lancet Infect Dis ; 24(5): 523-534, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38244557

RESUMO

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 Intravenosa
19.
Antimicrob Agents Chemother ; 57(3): 1488-95, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23318796

RESUMO

Intestinal flora contains a reservoir of Gram-negative bacilli (GNB) resistant to cephalosporins, which are potentially pathogenic for intensive care unit (ICU) patients; this has led to increasing use of carbapenems. The emergence of carbapenem resistance is a major concern for ICUs. Therefore, in this study, we aimed to assess the intestinal carriage of imipenem-resistant GNB (IR-GNB) in intensive care patients. For 6 months, 523 consecutive ICU patients were screened for rectal IR-GNB colonization upon admission and weekly thereafter. The phenotypes and genotypes of all isolates were determined, and a case control study was performed to identify risk factors for colonization. The IR-GNB colonization rate increased regularly from 5.6% after 1 week to 58.6% after 6 weeks in the ICU. In all, 56 IR-GNB strains were collected from 50 patients: 36 Pseudomonas aeruginosa strains, 12 Stenotrophomonas maltophilia strains, 6 Enterobacteriaceae strains, and 2 Acinetobacter baumannii strains. In P. aeruginosa, imipenem resistance was due to chromosomally encoded resistance (32 strains) or carbapenemase production (4 strains). In the Enterobacteriaceae strains, resistance was due to AmpC cephalosporinase and/or extended-spectrum ß-lactamase production with porin loss. Genomic comparison showed that the strains were highly diverse, with 8 exceptions (4 VIM-2 carbapenemase-producing P. aeruginosa strains, 2 Klebsiella pneumoniae strains, and 2 S. maltophilia strains). The main risk factor for IR-GNB colonization was prior imipenem exposure. The odds ratio for colonization was already as high as 5.9 (95% confidence interval [95% CI], 1.5 to 25.7) after 1 to 3 days of exposure and increased to 7.8 (95% CI, 2.4 to 29.8) thereafter. In conclusion, even brief exposure to imipenem is a major risk factor for IR-GNB carriage.


Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/efeitos adversos , Enterobacteriaceae/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Imipenem/efeitos adversos , Pseudomonas aeruginosa/efeitos dos fármacos , Stenotrophomonas maltophilia/efeitos dos fármacos , Resistência beta-Lactâmica/efeitos dos fármacos , Acinetobacter baumannii/enzimologia , Acinetobacter baumannii/crescimento & desenvolvimento , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Técnicas de Tipagem Bacteriana , Estudos de Casos e Controles , Colo/microbiologia , Enterobacteriaceae/enzimologia , Enterobacteriaceae/crescimento & desenvolvimento , Feminino , Expressão Gênica/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Imipenem/administração & dosagem , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Pseudomonas aeruginosa/enzimologia , Pseudomonas aeruginosa/crescimento & desenvolvimento , Stenotrophomonas maltophilia/enzimologia , Stenotrophomonas maltophilia/crescimento & desenvolvimento , beta-Lactamases/genética , beta-Lactamases/metabolismo
20.
Microbiol Spectr ; : e0454522, 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37747184

RESUMO

Enterococcus faecium, a common resident of the human gastrointestinal tract, is also a major pathogen. Prompt initiation of appropriate treatment is essential to improve patient outcome in disseminated E. faecium infections. However, ampicillin resistance is frequent in this species, rendering treatment difficult. We used a comprehensive approach, including clinical data review, whole-genome sequencing, and mass spectrometry, to characterize ampicillin-susceptible (EFM-S) and ampicillin-resistant (EFM-R) isolates. We included all patients with culture-confirmed E. faecium infection attending our hospital over a 16-month period. A comparison of 32 patients infected with EFM-S strains and 251 patients infected with EFM-R strains revealed that EFM-R isolates were strongly associated with a longer hospital stay, history of prior hospitalization, and the carriage of multidrug-resistant organisms. An analysis of the genomes of 26 EFM-S and 26 EFM-R isolates from paired patients revealed a population structure almost perfectly matching ampicillin susceptibility, with resistant isolates in clade A1, and susceptible isolates in clades A2 and B. The clade B and A2 isolates mostly came from digestive or biliary tract samples, whereas clade A1 isolates were mostly obtained from urine and blood. Finally, we built a custom database for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), which differentiated between clade B and clade A1/A2 strains with high-positive and high-negative predictive values (95.6% and 100%, respectively). This study provides important new insight into the clinical features and clades associated with EFM-S and EFM-R isolates. In combination with MALDI-TOF MS, these data could facilitate the rapid initiation of the most appropriate treatment.IMPORTANCEEnterococcus faecium is an important human pathogen in which the prevalence of ampicillin resistance is high. However, little is known about the clinical characteristics of patients infected with ampicillin-resistant and ampicillin-susceptible strains. Indeed, current knowledge is based on genus-wide studies of Enterococcus or studies of very small numbers of susceptible isolates, precluding robust conclusions. Our data highlight specific clinical features related to the epidemiology of EFM-S and EFM-R strains, such as length of hospital stay, history of prior hospitalization, carriage of multidrug-resistant organisms, and type of sample from which the isolate was obtained. The use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry with a custom-built database may make it possible to distinguish clade B isolates, which are typically susceptible to ampicillin, from clade A1/A2 isolates (A1 being typically resistant), thereby facilitating the management of these infections.

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