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1.
Anal Chim Acta ; 1177: 338760, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34482897

RESUMO

Beta-lactam antibiotics are of vital importance for the treatment of infections in a broad range of patients. Although most systemically administered antibiotics will be excreted renally, a fraction will reach the gastro-intestinal tract, affecting the intestinal microbiome by eradicating a wide range of bacterial species while facilitating the growth of antimicrobial-resistant species. A better understanding of the kinetics of beta-lactam antibiotics in the gastro-intestinal tract is essential to study their role in the development of antibiotic resistance in bacteria and to help develop future therapies to prevent damage to, or restore, the intestinal microbiome. Analysis of beta-lactam antibiotics in faeces is particularly challenging due to the heterogeneous nature of the matrix, rapid degradation of some beta-lactam antibiotics in faeces and very strong ion suppression when using mass spectrometry. Sample preparation was optimized using a sequential strategy of experimental designs. It resulted in lyophilization, a MOPS buffer system and the addition of the beta-lactamase inhibitor avibactam to minimize degradation of antibiotics allowing sensitive quantification. The developed liquid chromatography method with high-resolution mass spectrometric detection was successfully validated according to bioanalytical EMA guidelines and had a linear range of 1-200 µg g-1 lyophilized faeces for amoxicillin, piperacillin and meropenem; and 0.5-100 µg g-1 lyophilized faeces for tazobactam. Despite the highly complex and heterogeneous composition of faeces, the accuracy (0.1-15%) and precision (1.7-12.1%) were in line with those obtained for quantification methods of beta-lactam antibiotics in plasma, the golden standard matrix for therapeutic drug monitoring. The applicability of the method was illustrated by successful quantification of piperacillin and tazobactam in faeces from an intensive care unit patient receiving piperacillin/tazobactam in a continuous intravenous infusion. Both piperacillin and tazobactam were still present six days after discontinuation of the therapy.


Assuntos
Amoxicilina , Piperacilina , Antibacterianos , Cromatografia Líquida , Fezes , Humanos , Espectrometria de Massas , Meropeném , Projetos de Pesquisa , Tazobactam
2.
Acta Clin Belg ; : 1-5, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34152944

RESUMO

INTRODUCTION: The high variability of SARS-CoV-2 serological response after COVID-19 infection hampers its use as indicator of the timing of infection. A potential alternative method is the determination of affinity maturation of SARS-CoV-2 IgG, expressed as the SARS-CoV-2 IgG avidity. METHODS: SARS-CoV-2 IgG concentration and avidity were measured in sera of hospitalized COVID-19 patients sampled at two weeks and ≥12 weeks post symptom onset using an in-house developed protocol based on EUROIMMUN (anti-spike) and EDI™ (anti-nucleocapsid) SARS-CoV-2 IgG ELISA protocols. RESULTS: We included 68 confirmed COVID-19 patients that tested positive for SARS-CoV-2 IgG in both the initial and follow-up specimen sampled at a median of 14 (range 10-18) days and 120 (range 84-189) days, respectively, post symptom onset. The median anti-spike and anti-nucleocapsid SARS-CoV-2 IgG avidity response was 40% (range 9-93%) and 72% (range 27-104%), respectively, for the first sample, and 66% (range 28-90%) and 57% (range 25-94%), respectively, for the second sample. The proportion of SARS-CoV-2 IgG avidity results ≥60% was significantly lower for anti-spike compared to anti-nucleocapsid IgG for initial samples (p< 0.01) and vice versa for follow-up samples (p< 0.01). CONCLUSION: Anti-nucleocapsid SARS-CoV-2 IgG maturation occurs faster and avidity decreases faster than anti-spike IgG, indicating different kinetics of anti-spike and anti-nucleocapsid IgG. Further, affinity maturation after SARS-CoV-2 infection is frequently incomplete.

3.
Clin Infect Dis ; 73(4): e976-e980, 2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-33575791

RESUMO

BACKGROUND: The Democratic Republic of the Congo (DRC) has one of the highest neonatal death rates (between 14% and 28%) in the world. In the DRC, neonatal sepsis causes 15.6% of this mortality, but data on the bacterial etiology and associated drug susceptibility are lacking. METHODS: Hemocultures of 150 neonates with possible early-onset neonatal sepsis (pEOS) were obtained at the Hôpital Provincial Général de Référence de Bukavu (Bukavu, DRC). The newborns with pEOS received an empirical first-line antimicrobial treatment (ampicillin, cefotaxime, and gentamicin) based on the synopsis of international guidelines for the management of EOS that are in line with World Health Organization (WHO) recommendations. Isolates were identified using matrix-assisted laser desorption/ ionization time-of-flight mass spectrophotometry. Antibiotic resistance was assessed using the disk diffusion method. RESULTS: Fifty strains were obtained from 48 patients and identified. The 3 most prevalent species were Enterobacter cloacae complex (42%), Klebsiella pneumoniae (18%), and Serratia marcescens (12%). Enterobacter cloacae isolates were resistant to all first-line antibiotics. All K. pneumoniae and S. marcescens isolates were resistant to ampicillin, and the majority of the K. pneumoniae and half of the S. marcescens isolates were resistant to both cefotaxime and gentamicin. All E. cloacae complex strains, 89% of K. pneumoniae, and half of S. marcescens had an extended-spectrum ß-lactamase phenotype. CONCLUSIONS: The most prevalent pathogens causing EOS in Bukavu were E. cloacae complex, K. pneumoniae, and S. marcescens. Most of these isolates were resistant to the WHO-recommended antibiotics.


Assuntos
Sepse Neonatal , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , República Democrática do Congo/epidemiologia , Resistência Microbiana a Medicamentos , Humanos , Recém-Nascido , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana , Sepse Neonatal/tratamento farmacológico , Sepse Neonatal/epidemiologia , beta-Lactamases
4.
BMC Microbiol ; 21(1): 31, 2021 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-33482729

RESUMO

BACKGROUND: Early 2020, a COVID-19 epidemic became a public health emergency of international concern. To address this pandemic broad testing with an easy, comfortable and reliable testing method is of utmost concern. Nasopharyngeal (NP) swab sampling is the reference method though hampered by international supply shortages. A new oropharyngeal/nasal (OP/N) sampling method was investigated using the more readily available throat swab. RESULTS: 35 patients were diagnosed with SARS-CoV-2 by means of either NP or OP/N sampling. The paired swabs were both positive in 31 patients. The one patient who tested negative on both NP and OP/N swab on admission, was ultimately diagnosed on bronchoalveolar lavage fluid. A strong correlation was found between the viral RNA loads of the paired swabs (r = 0.76; P < 0.05). The sensitivity of NP and OP/N analysis in hospitalized patients (n = 28) was 89.3% and 92.7% respectively. CONCLUSIONS: This study demonstrates equivalence of NP and OP/N sampling for detection of SARS-CoV-2 by means of rRT-PCR. Sensitivity of both NP and OP/N sampling is very high in hospitalized patients.


Assuntos
Teste de Ácido Nucleico para COVID-19 , COVID-19/diagnóstico , Pandemias , SARS-CoV-2/isolamento & purificação , Manejo de Espécimes/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nasofaringe/virologia , Orofaringe/virologia , Estudos Prospectivos , Sensibilidade e Especificidade , Adulto Jovem
5.
Gastroenterology ; 160(1): 145-157.e8, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32681922

RESUMO

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder associated with intestinal dysbiosis. Given the reported promising results of open-label fecal microbiota transplantation (FMT) therapy in patients with predominant abdominal bloating, we studied efficacy of this treatment in a randomized, placebo-controlled trial. METHODS: Patients with refractory IBS, defined as failure of ≥3 conventional therapies, were randomly assigned to single-dose nasojejunal administration of donor stools (n = 43) or autologous stools (n = 19) in a double-blind study, performed from December 2015 through October 2017, and were followed up for 1 year. IBS-related symptoms were assessed by using a daily symptom diary to determine general abdominal discomfort, abdominal bloating, abdominal pain, and flatulence on a scale of 1-6. Number of daily bowel movements, consistency of the stools, and abdominal circumference were also recorded. Patients completed the IBS-specific quality of life questionnaire. Primary endpoints were improvement of IBS symptoms and bloating at 12 weeks (response). Secondary endpoints were changes in IBS symptom scores and quality of life. Stool samples were collected for microbiota amplicon sequencing. Open-label retransplantation was offered after the trial. RESULTS: At week 12, 56% of patients given donor stool reported improvement in both primary endpoints compared with 26% of patients given placebo (P = .03). Patients given donor stool had significant improvements in level of discomfort (mean reduction, 19%; median score before FMT, 3.98; range, 2.13-6.00; median score after FMT, 3.1; range, 951.29-5.90), stool frequency (mean reduction, 13%; median score before FMT, 2.10; range, 0.57-14.29; median score after FMT 1.7; range, 0.71-4.29), urgency (mean reduction, 38%; median score before FMT, 0.61; range, 0.00-1.00; median score after FMT, 0.37; range, 0.00-1.00), abdominal pain (mean reduction, 26%; median score before FMT, 3.88; range, 1.57-5.17; median score after FMT, 2.80; range, 1.14-4.94), flatulence (mean reduction, 10%; median score before FMT, 3.42; range, 0.71-6.00; median score after FMT, 3.07; range, 0.79-4.23), and quality of life (mean increase, 16%; median score before FMT 32.6; range, 11-119; median score after FMT, 43.1; range, 32.25-99). A significantly higher proportion of women given donor stool (69%) had a response than men (29%) (P = .01). Fecal samples from responders had higher diversity of microbiomes before administration of donor material than fecal samples from nonresponders (P = .04) and distinct baseline composition (P = .04), but no specific marker taxa were associated with response. After single FMT, 21% of patients given donor stool reported effects that lasted for longer than 1 year compared with 5% of patients given placebo stool. A second FMT reduced symptoms in 67% of patients with an initial response to donor stool but not in patients with a prior nonresponse. CONCLUSIONS: In a randomized trial of patients with treatment-refractory IBS with predominant bloating, FMT relieved symptoms compared with placebo (autologous transplant), although the effects decreased over 1 year. A second FMT restored the response patients with a prior response. Response was associated with composition of the fecal microbiomes before FMT; this might be used to as a biomarker to select patients for this treatment. ClinicalTrials.gov, Number: NCT02299973.


Assuntos
Dor Abdominal/prevenção & controle , Transplante de Microbiota Fecal , Flatulência/prevenção & controle , Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/terapia , Dor Abdominal/etiologia , Adolescente , Adulto , Método Duplo-Cego , Feminino , Flatulência/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
6.
Acta Clin Belg ; : 1-6, 2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33350362

RESUMO

Background: Molecular detection of SARS-CoV-2 in respiratory samples is the gold standard for COVID-19 diagnosis but it has a long turnaround time and struggles to detect low viral loads. Serology could help to diagnose suspected cases which lack molecular confirmation. Two case reports are presented as illustration.Objectives: The aim of this study was to evaluate the performance of several commercial assays for COVID-19 serology. We illustrated the added value of COVID-19 serology testing in suspect COVID-19 cases with negative molecular test.Study design: Twenty-three sera from 7 patients with a confirmed molecular diagnosis of SARS-CoV-2 were tested using 14 commercial assays. Additionally, 10 pre-pandemic sera and 9 potentially cross-reactive sera were selected. We calculated sensitivity and specificity. Furthermore, we discuss the diagnostic relevance of COVID-19 serology in a retrospective cohort of 145 COVID-19 cases in which repetitive molecular and serological SARS-CoV-2 tests were applied.Results: The interpretation of the pooled sensitivity of IgM/A and IgG resulted in the highest values (range 14-71% on day 2-7; 88-94% on day 8-18). Overall, the specificity of the assays was high (range 79-100%). Among 145 retrospective cases, 3 cases (2%) remained negative after sequential molecular testing but positive on final SARS-CoV-2 serology.Conclusion: Sensitivity of COVID-19 serological diagnosis was variable but consistently increased at >7 days after symptom onset. Specificity was high. Our data suggest that serology can complement molecular testing for diagnosis of COVID-19, especially for patients presenting the 2nd week after symptom onset or later.

7.
Clin Chem Lab Med ; 58(10): 1759-1767, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32649292

RESUMO

Objectives In this study, the possibilities of Fourier-transformed infrared spectroscopy (FTIR) for analysis of urine sediments and for detection of bacteria causing urinary tract infections (UTIs) were investigated. Methods Dried urine specimens of control subjects and patients presenting with various nephrological and urological conditions were analysed using mid-infrared spectroscopy (4,000-400 cm-1). Urine samples from patients with a UTI were inoculated on a blood agar plate. After drying of the pure bacterial colonies, FTIR was applied and compared with the results obtained by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Chemometric data analysis was used to classify the different species. Results Due to the typical molecular assignments of lipids, proteins, nucleic acids and carbohydrates, FTIR was able to identify bacteria and showed promising results in the detection of proteins, lipids, white and red blood cells, as well as in the identification of crystals. Principal component analysis (PCA) allowed to differentiate between Gram-negative and Gram-positive species and soft independent modelling of class analogy (SIMCA) revealed promising classification ratios between the different pathogens. Conclusions FTIR can be considered as a supplementary method for urine sediment examination and for detection of pathogenic bacteria in UTI.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32500040

RESUMO

Objectives: Pneumocystis jirovecii pneumonia (PCP) is an AIDS-defining illness. In patients with HIV, the benefit of PCP prophylaxis is well-defined when the CD4 T-cell count decreases below 200 cells/µL. In other immunocompromised patients, the value of PCP prophylaxis is not always as well-established. This study aimed to describe the epidemiology of PCP in recent years and assess how many patients with PCP did or did not receive prophylaxis in the month preceding the infection. Material and Methods: A multicenter retrospective study was performed in 3 tertiary care hospital. A list of patients that underwent broncho-alveolar lavage sampling and Pneumocystis jirovecii (PJ) PCR testing was retrieved from the microbiology laboratories. An in-house PJ quantitative PCR (qPCR) was used in each center. A cycle threshold (Ct) value of ≤ 28.5-30 was considered a probable PCP. For patients with a positive PJ qPCR but above this threshold, a predefined case definition of possible PCP was defined as a qPCR Ct value ≤ 34-35 and both of the following criteria: 1. Clinical and radiological features compatible with PCP and 2. The patient died or received PCP therapy and survived. Patient files from those with a qPCR Ct value ≤ 35 were reviewed to determine whether the patient fulfilled the case definition and if PCP prophylaxis had been used in the weeks preceding the PCP. Disease-specific guidelines, as well as hospital-wide guidelines, were used to evaluate if prophylaxis could be considered indicated. Results: From 2012 to 2018, 482 BAL samples were tested. Two hundred and four had a qPCR Ct value ≤ 35 and were further evaluated: 90 fulfilled the definition of probable and 63 of possible PCP while the remaining 51 were considered colonized. Seventy-four percentages of the patients with PCP were HIV-negative. Only 11 (7%) of the 153 patients had received prophylaxis, despite that in 133 (87%) cases prophylaxis was indicated according to guidelines. Conclusion: In regions where HIV testing and treatment is available without restrictions, PCP is mainly diagnosed in non-HIV immunocompromised patients. More than four out of five patients with PCP had not received prophylaxis. Strategies to improve awareness of antimicrobial prophylaxis guidelines in immunocompromised patients are urgently needed.


Assuntos
Pneumocystis carinii , Pneumonia por Pneumocystis , Humanos , Hospedeiro Imunocomprometido , Pneumocystis carinii/genética , Pneumonia por Pneumocystis/epidemiologia , Pneumonia por Pneumocystis/prevenção & controle , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos
9.
Expert Rev Anti Infect Ther ; 18(11): 1155-1164, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32597263

RESUMO

INTRODUCTION: Individualizing antibiotic therapy is paramount to improve clinical outcomes while minimizing the risk of toxicity and antimicrobial therapy. ß-lactam antibiotics are amongst the drugs most commonly prescribed in the Intensive Care Unit (ICU). The pharmacokinetics of ß-lactam antibiotics are profoundly altered in critically ill patients, leading to the failure of standard drug dosing regimens to result in adequate drug concentrations. Therapeutic Drug Monitoring (TDM) of ß-lactam antibiotics is a promising tool to help optimize ß-lactam antibiotic therapy. AREAS COVERED: The rationale behind TDM for ß-lactam antibiotics is explained, as well as some more practical aspects such as when to sample, what concentrations to strive for and how to use it in clinical practice. We also discuss microbiological and analytical considerations, knowledge gaps, and future perspectives of ß-lactam antibiotics TDM in ICU patients. EXPERT OPINION: TDM of ß-lactam antibiotics has been studied intensively in recent years. While TDM may not yet be widely available, and targets need to be further refined, TDM of ß-lactam antibiotics will help to optimize antibiotic therapy in the critically ill patient, as an integrated part of an antimicrobial stewardship program.


Assuntos
Antibacterianos/administração & dosagem , Monitoramento de Medicamentos/métodos , beta-Lactamas/administração & dosagem , Antibacterianos/farmacocinética , Gestão de Antimicrobianos , Cuidados Críticos/métodos , Estado Terminal , Humanos , Unidades de Terapia Intensiva , Medicina de Precisão , beta-Lactamas/farmacocinética
10.
Curr Opin Anaesthesiol ; 33(2): 156-161, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31904697

RESUMO

PURPOSE OF REVIEW: Antimicrobial resistance (AMR) is increasing in ICUs around the world, but the prevalence is variable. We will review recent literature and try to answer the question whether this is a myth or a new reality, as well as discuss challenges and potential solutions. RECENT FINDINGS: AMR is diverse, and currently Gram-negative multidrug-resistant organisms (MDROs) are the main challenge in ICUs worldwide. Geographical variation in prevalence of MDROs is substantial, and local epidemiology should be considered to assess the current threat of AMR. ICU patients are at a high risk of infection with MDRO because often multiple risk factors are present. Solutions should focus on reducing the risk of cross-transmission in the ICU through strict infection prevention and control practices and reducing exposure to antimicrobials as the major contributor to the development of AMR. SUMMARY: AMR is a reality in most ICUs around the world, but the extent of the problem is clearly highly variable. Infection prevention and control as well as appropriate antimicrobial use are the cornerstones to turn the tide.


Assuntos
Farmacorresistência Bacteriana Múltipla , Unidades de Terapia Intensiva , Humanos
11.
Clin Chem Lab Med ; 58(4): 597-604, 2020 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-31860463

RESUMO

Background Diagnosis of upper urinary tract infections (UTI) is challenging. We evaluated the analytical and diagnostic performance characteristics of renal tubular epithelial cells (RTECs) and transitional epithelial cells (TECs) on the Sysmex UF-5000 urine sediment analyzer. Methods Urinary samples from 506 patients presenting with symptoms of a UTI were collected. Only samples for which a urinary culture was available were included. Analytical (imprecision, accuracy, stability and correlation with manual microscopy) and diagnostic performance (sensitivity and specificity) were evaluated. Results The Sysmex UF-5000 demonstrated a good analytical performance. Depending on the storage time, storage conditions (2-8 °C or 20-25 °C) and urinary pH, RTECs and TECs were stable in urine for at least 4 h. Using Passing-Bablok and Bland-Altman analysis, an acceptable agreement was observed between the manual and automated methods. Compared to TECs, RTECs demonstrated an acceptable diagnostic performance for the diagnosis of upper UTI. Conclusions While TECs do not seem to serve as a helpful marker, increased urinary levels of RTECs add value in the diagnosis of upper UTI and may be helpful in the discrimination between upper and lower UTIs.


Assuntos
Urinálise/métodos , Infecções Urinárias/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Cistite/diagnóstico , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Feminino , Humanos , Túbulos Renais/citologia , Masculino , Pessoa de Meia-Idade , Prostatite/diagnóstico , Pielonefrite/diagnóstico , Curva ROC , Sensibilidade e Especificidade , Urinálise/instrumentação , Urina/química , Urina/microbiologia , Adulto Jovem
12.
BMC Infect Dis ; 19(1): 1061, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31847834

RESUMO

BACKGROUND/OBJECTIVES: Assessing the clinical relevance of non-tuberculous mycobacteria (NTM) isolated from respiratory samples can be challenging. The epidemiology and pathogenicity of NTM species vary geographically. We aimed to outline the clinical relevance and associated radiological patterns of NTM species isolated in Belgium. METHODS: We performed a retrospective multicentre analysis of all patients identified from the laboratory database with > 1 respiratory sample growing NTM from January 2010 through December 2017. We collected clinical, radiological and microbiological data through medical record review and assessed clinical relevance according to ATS/IDSA criteria for NTM pulmonary disease (NTM-PD). RESULTS: Of the 384 unique patients, 60% were male, 56% had a smoking history and 61% had pre-existing lung disease. Mycobacterium avium complex (MAC), M. gordonae and M. xenopi were the most frequently isolated species: 53, 15 and 8% respectively. 43% of patients met ATS/IDSA criteria, of whom 28% presented with fibrocavitary disease. Weight loss, fever, nodular bronchiectatic and fibrocavitary lesions on chest CT, and a positive acid-fast bacilli (AFB) stain were significantly associated with NTM-PD. The species with the highest pathogenic potential were M. abscessus (11/12), M. malmoense (6/7) and M. intracellulare (41/64). CONCLUSION: In our study, MAC was the most commonly isolated NTM species, but M. abscessus and M. malmoense showed the highest probability of being clinically relevant. Clinical relevance varied not only by species but also by radiological findings on chest CT and AFB staining. Clinicians should consider these elements in their treatment decision making. Prospective data including clinical outcome are needed to provide more robust evidence.


Assuntos
Bronquiectasia/complicações , Fibrose Cística/complicações , Infecções por Mycobacterium não Tuberculosas/etiologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Complexo Mycobacterium avium/isolamento & purificação , Doença Pulmonar Obstrutiva Crônica/complicações , Idoso , Bélgica , Testes Diagnósticos de Rotina , Suscetibilidade a Doenças , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
13.
Artigo em Inglês | MEDLINE | ID: mdl-31548884

RESUMO

Background: We report a recurrent outbreak of postoperative infections with extended-spectrum ß-lactamase (ESBL)-producing E. cloacae complex in cardiac surgery patients, describe the outbreak investigation and highlight the infection control measures. Methods: Cases were defined as cardiac surgery patients in Ghent University Hospital who were not known preoperatively to carry ESBL-producing E. cloacae complex and who postoperatively had a positive culture for this multiresistant organism between May 2017 and January 2018. An epidemiological investigation, including a case-control study, and environmental investigation were conducted to identify the source of the outbreak. Clonal relatedness of ESBL-producing E. cloacae complex isolates collected from case patients was assessed using whole-genome sequencing-based studies. Results: Three separate outbreak episodes occurred over the course of 9 months. A total of 8, 4 and 6 patients met the case definition, respectively. All but one patients developed a clinical infection with ESBL-producing E. cloacae complex, most typically postoperative pneumonia. Overall mortality was 22% (4/18). Environmental cultures were negative, but epidemiological investigation pointed to transesophageal echocardiography (TEE) as the outbreak source. Of note, four TEE probes showed a similar pattern of damage, which very likely impeded adequate disinfection. The first and second outbreak episode were caused by the same clone, whereas a different strain was responsible for the third episode. Conclusions: Health professionals caring for cardiac surgery patients and infection control specialists should be aware of TEE as possible infection source. Caution must be exercised to prevent and detect damage of TEE probes.


Assuntos
Surtos de Doenças , Ecocardiografia Transesofagiana/instrumentação , Enterobacter cloacae/isolamento & purificação , Infecções por Enterobacteriaceae/epidemiologia , Equipamentos e Provisões/microbiologia , Complicações Pós-Operatórias/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Serviço Hospitalar de Cardiologia , Estudos de Casos e Controles , Enterobacter cloacae/genética , Infecções por Enterobacteriaceae/mortalidade , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mortalidade , Complicações Pós-Operatórias/mortalidade , Recidiva , Sequenciamento Completo do Genoma , beta-Lactamases/metabolismo
16.
Crit Care ; 22(1): 241, 2018 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-30268142

RESUMO

BACKGROUND: Preparing an antibiotic stewardship program requires detailed information on overall antibiotic use, prescription indication and ecology. However, longitudinal data of this kind are scarce. Computerization of the patient chart has offered the potential to collect complete data of high resolution. To gain insight in our global antibiotic use, we aimed to explore antibiotic prescription in our intensive care unit (ICU) from various angles over a prolonged time period. METHODS: We studied all adult patients admitted to Ghent University Hospital ICU from 1 January 2013 until 31 December 2016. Antibiotic prescription data were prospectively merged with diagnostic (suspected focus, severity and probability of infection at the time of prescription, or prophylaxis) and microbiology data by ICU physicians during daily workflow through dedicated software. Definite focus of infection and probability of infection (classified as high/moderate/low) were reassessed by dedicated ICU physicians at patient discharge. RESULTS: During the study period, 8763 patients were admitted and overall antibiotic consumption amounted to 1232 days of therapy (DOT)/1000 patient days. Antibacterial DOT (84% of total DOT) were linked with infection in 80%; the predominant foci were the respiratory tract (49%) and the abdomen (19%). A microbial cause was identified in 56% (3169/5686). Moderate/low probability infections accounted for 42% of antibacterial DOT prescribed for respiratory tract infections; for abdominal infections, this figure was 15%. The median treatment duration of moderate/low probability respiratory infections was 4 days (IQR 3-7). Antifungal DOT (16% of total DOT) were linked with infection in 47% of total antifungal DOT. Antifungal prophylaxis was primarily administered in the surgical ICU (76%), with a median duration of 4 DOT (IQR 2-9). CONCLUSIONS: By prospectively combining antibiotic, microbiology and clinical data we were able to construct a longitudinal, multifaceted dataset on antibiotic use and infection diagnosis. A complete overview of this kind may allow the identification of antibiotic prescription patterns that require future antibiotic stewardship attention.


Assuntos
Antibacterianos/uso terapêutico , Uso de Medicamentos/estatística & dados numéricos , Infecções/diagnóstico , APACHE , Adolescente , Adulto , Idoso , Antibacterianos/farmacologia , Gestão de Antimicrobianos/métodos , Feminino , Humanos , Infecções/tratamento farmacológico , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estatísticas não Paramétricas
17.
JAMA ; 320(20): 2087-2098, 2018 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-30347072

RESUMO

Importance: The effects of chlorhexidine (CHX) mouthwash, selective oropharyngeal decontamination (SOD), and selective digestive tract decontamination (SDD) on patient outcomes in ICUs with moderate to high levels of antibiotic resistance are unknown. Objective: To determine associations between CHX 2%, SOD, and SDD and the occurrence of ICU-acquired bloodstream infections with multidrug-resistant gram-negative bacteria (MDRGNB) and 28-day mortality in ICUs with moderate to high levels of antibiotic resistance. Design, Setting, and Participants: Randomized trial conducted from December 1, 2013, to May 31, 2017, in 13 European ICUs where at least 5% of bloodstream infections are caused by extended-spectrum ß-lactamase-producing Enterobacteriaceae. Patients with anticipated mechanical ventilation of more than 24 hours were eligible. The final date of follow-up was September 20, 2017. Interventions: Standard care was daily CHX 2% body washings and a hand hygiene improvement program. Following a baseline period from 6 to 14 months, each ICU was assigned in random order to 3 separate 6-month intervention periods with either CHX 2% mouthwash, SOD (mouthpaste with colistin, tobramycin, and nystatin), or SDD (the same mouthpaste and gastrointestinal suspension with the same antibiotics), all applied 4 times daily. Main Outcomes and Measures: The occurrence of ICU-acquired bloodstream infection with MDRGNB (primary outcome) and 28-day mortality (secondary outcome) during each intervention period compared with the baseline period. Results: A total of 8665 patients (median age, 64.1 years; 5561 men [64.2%]) were included in the study (2251, 2108, 2224, and 2082 in the baseline, CHX, SOD, and SDD periods, respectively). ICU-acquired bloodstream infection with MDRGNB occurred among 144 patients (154 episodes) in 2.1%, 1.8%, 1.5%, and 1.2% of included patients during the baseline, CHX, SOD, and SDD periods, respectively. Absolute risk reductions were 0.3% (95% CI, -0.6% to 1.1%), 0.6% (95% CI, -0.2% to 1.4%), and 0.8% (95% CI, 0.1% to 1.6%) for CHX, SOD, and SDD, respectively, compared with baseline. Adjusted hazard ratios were 1.13 (95% CI, 0.68-1.88), 0.89 (95% CI, 0.55-1.45), and 0.70 (95% CI, 0.43-1.14) during the CHX, SOD, and SDD periods, respectively, vs baseline. Crude mortality risks on day 28 were 31.9%, 32.9%, 32.4%, and 34.1% during the baseline, CHX, SOD, and SDD periods, respectively. Adjusted odds ratios for 28-day mortality were 1.07 (95% CI, 0.86-1.32), 1.05 (95% CI, 0.85-1.29), and 1.03 (95% CI, 0.80-1.32) for CHX, SOD, and SDD, respectively, vs baseline. Conclusions and Relevance: Among patients receiving mechanical ventilation in ICUs with moderate to high antibiotic resistance prevalence, use of CHX mouthwash, SOD, or SDD was not associated with reductions in ICU-acquired bloodstream infections caused by MDRGNB compared with standard care. Trial Registration: ClinicalTrials.gov Identifier: NCT02208154.


Assuntos
Anti-Infecciosos/uso terapêutico , Bacteriemia/prevenção & controle , Clorexidina/uso terapêutico , Desinfecção/métodos , Infecções por Bactérias Gram-Negativas/prevenção & controle , Antissépticos Bucais/uso terapêutico , Respiração Artificial , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecção Hospitalar/prevenção & controle , Farmacorresistência Bacteriana , Feminino , Trato Gastrointestinal/microbiologia , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Orofaringe/microbiologia , Adulto Jovem
18.
Eur J Clin Microbiol Infect Dis ; 37(12): 2253-2260, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30187248

RESUMO

For patients with bloodstream infections, rapid initiation of the appropriate antimicrobial therapy is essential in reducing mortality and morbidity. New developments and automation in clinical microbiology labs speed up the identification and susceptibility results but are expensive. To gain insight in the added value of the new workflows, we simulated the possible impact of rapid identification and susceptibility tests on a real-life cohort of 158 positive blood culture episodes. Our routine workflow was theoretically challenged against two new workflows, one based on rapid identification with MALDI-TOF MS and one based on molecular testing. First, we observed an important role of the rapid communication of the gram stain results, as about one third of patients needed an adaptation of the antimicrobial therapy based on these results. Antibiotic adaptation based on the microorganism identification was necessary in 10% and in another 25% of cases after the availability of the susceptibility results. The added value of the newer workflow methods lies mainly in the field of the rapid identification and was rather limited in our cohort. In conclusion, for optimizing the blood culture workflow, each microbiology lab should critically scan its own workflow and know its own blood culture epidemiology, before investing in expensive or time-consuming processes.


Assuntos
Bacteriemia/diagnóstico , Hemocultura , Fluxo de Trabalho , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Técnicas Bacteriológicas , Bélgica , Humanos , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
19.
Cell Tissue Bank ; 19(4): 697-704, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30159825

RESUMO

Autotransplantation is a versatile technique for the replacement of a missing tooth and cryopreservation can expand its scope. The aim of this in vitro study is to compare the antimicrobial effect of different transport protocols on procured teeth prior to cryopreservation. Streptococcus oralis biofilms were grown on ten sterile premolars, incubated for 48 h and subjected to the following transport procedures: an untreated (contaminated) control group, a group rinsed with phosphate buffered saline (PBS), a group transported in PBS, a group transported in Dulbecco's Modified Eagle's medium (DMEM) supplemented with fetal calf serum (FCS), and a group transported in DMEM supplemented with FCS and antibiotics (AB). The effect of cryopreservation as such, as well as the combination with a transport medium (DMEM + FCS + AB) on the contamination was also tested. The surviving bacteria were harvested, and determined by plate counting. There was no significant reduction in contamination after rinsing the tooth, after transport in PBS or after transport in DMEM with FCS. Significant reductions were observed for transport in DMEM with AB when compared to the control group (p = 0.003). Cryopreservation as such reduced the biofilm significantly (p < 0.001). No cumulative effect could be found when transport in DMEM + FCS + AB was followed by cryopreservation. Within the limitations of this laboratory set-up, DMEM + FCS + AB was the most effective transport medium in S. oralis biofilm elimination. It could not be concluded that rinsing of the tooth gives an additional reduction. Cryopreservation as such decontaminated the teeth more effectively than any tested transport procedure.


Assuntos
Dente Pré-Molar/efeitos dos fármacos , Criopreservação , Meios de Cultura/farmacologia , Extração Dentária , Transportes , Dente Pré-Molar/microbiologia , Contagem de Colônia Microbiana , Humanos , Transplante Autólogo
20.
Lancet Respir Med ; 6(10): 782-792, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30076119

RESUMO

BACKGROUND: Invasive pulmonary aspergillosis typically occurs in an immunocompromised host. For almost a century, influenza has been known to set up for bacterial superinfections, but recently patients with severe influenza were also reported to develop invasive pulmonary aspergillosis. We aimed to measure the incidence of invasive pulmonary aspergillosis over several seasons in patients with influenza pneumonia in the intensive care unit (ICU) and to assess whether influenza was an independent risk factor for invasive pulmonary aspergillosis. METHODS: We did a retrospective multicentre cohort study. Data were collected from adult patients with severe influenza admitted to seven ICUs across Belgium and The Netherlands during seven influenza seasons. Patients were older than 18 years, were admitted to the ICU for more than 24 h with acute respiratory failure, had pulmonary infiltrates on imaging, and a confirmed influenza infection based on a positive airway PCR test (influenza cohort). We used logistic regression analyses to determine if influenza was independently associated with invasive pulmonary aspergillosis in non-immunocompromised (ie, no European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group [EORTC/MSG] host factor) influenza-positive patients (influenza case group) compared with non-immunocompromised patients with severe community-acquired pneumonia who had a negative airway influenza PCR test (control group). FINDINGS: Data were collected from patients admitted to the ICU between Jan 1, 2009, and June 30, 2016. Invasive pulmonary aspergillosis was diagnosed in 83 (19%) of 432 patients admitted with influenza (influenza cohort), a median of 3 days after admission to the ICU. The incidence was similar for influenza A and B. For patients with influenza who were immunocompromised, incidence of invasive pulmonary aspergillosis was as high as 32% (38 of 117 patients), whereas in the non-immunocompromised influenza case group, incidence was 14% (45 of 315 patients). Conversely, only 16 (5%) of 315 patients in the control group developed invasive pulmonary aspergillosis. The 90-day mortality was 51% in patients in the influenza cohort with invasive pulmonary aspergillosis and 28% in the influenza cohort without invasive pulmonary aspergillosis (p=0·0001). In this study, influenza was found to be independently associated with invasive pulmonary aspergillosis (adjusted odds ratio 5·19; 95% CI 2·63-10·26; p<0·0001), along with a higher APACHE II score, male sex, and use of corticosteroids. INTERPRETATION: Influenza was identified as an independent risk factor for invasive pulmonary aspergillosis and is associated with high mortality. Future studies should assess whether a faster diagnosis or antifungal prophylaxis could improve the outcome of influenza-associated aspergillosis. FUNDING: None.


Assuntos
Aspergillus , Vírus da Influenza A , Vírus da Influenza B , Influenza Humana/epidemiologia , Aspergilose Pulmonar Invasiva/epidemiologia , APACHE , Idoso , Bélgica/epidemiologia , Feminino , Humanos , Incidência , Influenza Humana/microbiologia , Unidades de Terapia Intensiva/estatística & dados numéricos , Aspergilose Pulmonar Invasiva/microbiologia , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Razão de Chances , Admissão do Paciente/estatística & dados numéricos , Estudos Retrospectivos
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