Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 25
Filtrar
1.
Infection ; 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38267801

RESUMO

BACKGROUND: Clinical data characterizing invasive Escherichia coli disease (IED) are limited. We assessed the clinical presentation of IED and antimicrobial resistance (AMR) patterns of causative E. coli isolates in older adults. METHODS: EXPECT-2 (NCT04117113) was a prospective, observational, multinational, hospital-based study conducted in patients with IED aged ≥ 60 years. IED was determined by the microbiological confirmation of E. coli from blood; or by the microbiological confirmation of E. coli from urine or an otherwise sterile body site in the presence of requisite criteria of systemic inflammatory response syndrome (SIRS), Sequential Organ Failure Assessment (SOFA), or quick SOFA (qSOFA). The primary outcomes were the clinical presentation of IED and AMR rates of E. coli isolates to clinically relevant antibiotics. Complications and in-hospital mortality were assessed through 28 days following IED diagnosis. RESULTS: Of 240 enrolled patients, 80.4% had bacteremic and 19.6% had non-bacteremic IED. One-half of infections (50.4%) were community-acquired. The most common source of infection was the urinary tract (62.9%). Of 240 patients, 65.8% fulfilled ≥ 2 SIRS criteria, and 60.4% had a total SOFA score of ≥ 2. Investigator-diagnosed sepsis and septic shock were reported in 72.1% and 10.0% of patients, respectively. The most common complication was kidney dysfunction (12.9%). The overall in-hospital mortality was 4.6%. Of 299 E. coli isolates tested, the resistance rates were: 30.4% for trimethoprim-sulfamethoxazole, 24.1% for ciprofloxacin, 22.1% for levofloxacin, 16.4% for ceftriaxone, 5.7% for cefepime, and 4.3% for ceftazidime. CONCLUSIONS: The clinical profile of identified IED cases was characterized by high rates of sepsis. IED was associated with high rates of AMR to clinically relevant antibiotics. The identification of IED can be optimized by using a combination of clinical criteria (SIRS, SOFA, or qSOFA) and culture results.

2.
HIV Med ; 24(7): 785-793, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36883641

RESUMO

OBJECTIVES: Our objective was to assess immune responses and their influencing factors in people living with HIV after messenger RNA (mRNA)-based COVID-19 booster vaccination (third dose). METHODS: This was a retrospective cohort study of people living with HIV who received booster vaccination with BNT-162b2 or mRNA-1273 between October 2021 and January 2022. We assessed anti-spike receptor-binding domain (RBD) immunoglobulin G (IgG), virus neutralizing activity (VNA) titres reported as 100% inhibitory dilution (ID100 ), and T-cell response (using interferon-gamma-release-assay [IGRA]) at baseline and quarterly follow-up visits. Patients with reported COVID-19 during follow-up were excluded. Predictors of serological immune response were analyzed using multivariate regression models. RESULTS: Of 84 people living with HIV who received an mRNA-based booster vaccination, 76 were eligible for analysis. Participants were on effective antiretroviral therapy (ART) and had a median of 670 CD4+ cells/µL (interquartile range [IQR] 540-850). Following booster vaccination, median anti-spike RBD IgG increased by 705.2 binding antibody units per millilitre (BAU/mL) and median VNA titres increased by 1000 ID100 at the follow-up assessment (median 13 weeks later). Multivariate regression revealed that time since second vaccination was a predictor of stronger serological responses (p < 0.0001). No association was found for other factors, including CD4+ status, choice of mRNA vaccine, or concomitant influenza vaccination. In total, 45 patients (59%) had a reactive baseline IGRA, of whom two lost reactivity during follow-up. Of 31 patients (41%) with non-reactive baseline IGRA, 17 (55%) converted to reactive and seven (23%) remained unchanged following booster vaccination. CONCLUSIONS: People living with HIV with ≥500 CD4+ cells/µL showed favourable immune responses to mRNA-based COVID-19 booster vaccination. A longer time (up to 29 weeks) since second vaccination was associated with higher serological responses, whereas choice of mRNA vaccine or concomitant influenza vaccination had no impact.


Assuntos
COVID-19 , Infecções por HIV , Influenza Humana , Humanos , Estudos Retrospectivos , COVID-19/prevenção & controle , Vacinação , RNA Mensageiro , Imunidade , Imunoglobulina G , Anticorpos Antivirais
3.
Lancet Infect Dis ; 23(6): 719-731, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36731484

RESUMO

BACKGROUND: Carriers of multidrug-resistant bacteria are at risk of infections with these bacteria; the precise size of this risk is unclear. We aimed to quantify the effect of gut colonisation on subsequent risk of infection with multidrug-resistant bacteria. METHODS: We performed a systematic review and meta-regression analysis. We searched PubMed, Embase, Web of Science Core Collection, and Google Scholar for follow-up studies published from Jan 1, 1995, to March 17, 2022, that measured the incidence of infections with multidrug-resistant Gram-negative bacteria (MDR-GNB) and from Jan 1, 1995, to March 15, 2022, that measured the incidence of infections with vancomycin-resistant enterococci (VRE). We included original cohort studies and case-control studies that used incidence-density sampling, included 50 or more patients with enteric colonisation or positive urinary samples as a surrogate marker of colonisation, or both, and analysed infections clearly preceded by colonisation. We did not use any language restrictions. We excluded studies not reporting length of follow-up. Summary data were extracted and independently cross-verified by two authors. Carriage was defined as MDR-GNB or VRE, detected in faecal or urinary cultures. Our primary outcomes were cumulative incidence and incidence density of infection in patients colonised by multidrug-resistant bacteria. To estimate pooled incidences, general linearised mixed-effects meta-regressions were used, adjusting for varying follow-up durations. This study is registered with PROSPERO, CRD42020222415. FINDINGS: Of the 301 studies identified, 44 studies (26 on MDR-GNB, 14 on VRE, and four on both MDR-GNB and VRE) from 14 countries were retained for qualitative synthesis, 40 of which were analysed with meta-regression, comprising data for 14 049 patients colonised with multidrug-resistant bacteria. The pooled cumulative incidence of infection was 14% (95% CI 10-18; p<0·0001) at a median follow-up time of 30 days for MDR-GNB (845 cases of infection in 9034 patients colonised) and 8% (5-13; p<0·0001) at 30 days for VRE (229 cases of infection in 4747 patients colonised). Infection incidence density (4·26 infections per 1000 patient-days; 95% CI 1·69-6·82) and cumulative incidence of infection (19%, 95% CI 15-25; p<0·0001; 602 cases of infection in 4547 patients colonised) were highest for carbapenem-resistant Gram-negative bacteria at 30 days. Risk of bias was rated low to moderate. INTERPRETATION: The risk of infection was substantial, with the highest risk for patients colonised with carbapenem-resistant Gram-negative bacteria and the lowest in patients with VRE. These data might help to guide prophylactic and treatment decisions and form a valuable resource for planning clinical trials on targeted prevention. FUNDING: The Netherlands Organization for Health Research and Development.


Assuntos
Infecção Hospitalar , Infecções por Bactérias Gram-Negativas , Enterococos Resistentes à Vancomicina , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Incidência , Infecção Hospitalar/prevenção & controle , Farmacorresistência Bacteriana Múltipla , Bactérias Gram-Negativas , Análise de Regressão , Carbapenêmicos/uso terapêutico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico
5.
Euro Surveill ; 27(2)2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35027104

RESUMO

BackgroundEvidence supporting the effectiveness of single-room contact precautions (SCP) in preventing in-hospital acquisition of vancomycin-resistant enterococci (haVRE) is limited.AimWe assessed the impact of SCP on haVRE and their transmission.MethodsWe conducted a prospective, multicentre cohort study in German haematological/oncological departments during 2016. Two sites performed SCP for VRE patients and two did not (NCP). We defined a 5% haVRE-risk difference as non-inferiority margin, screened patients for VRE, and characterised isolates by whole genome sequencing and core genome MLST (cgMLST). Potential confounders were assessed by competing risk regression analysis.ResultsWe included 1,397 patients at NCP and 1,531 patients at SCP sites. Not performing SCP was associated with a significantly higher proportion of haVRE; 12.2% (170/1,397) patients at NCP and 7.4% (113/1,531) patients at SCP sites (relative risk (RR) 1.74; 95% confidence interval (CI): 1.35-2.23). The difference (4.8%) was below the non-inferiority margin. Competing risk regression analysis indicated a stronger impact of antimicrobial exposure (subdistribution hazard ratio (SHR) 7.46; 95% CI: 4.59-12.12) and underlying disease (SHR for acute leukaemia 2.34; 95% CI: 1.46-3.75) on haVRE than NCP (SHR 1.60; 95% CI: 1.14-2.25). Based on cgMLST and patient movement data, we observed 131 patient-to-patient VRE transmissions at NCP and 85 at SCP sites (RR 1.76; 95% CI: 1.33-2.34).ConclusionsWe show a positive impact of SCP on haVRE in a high-risk population, although the observed difference was below the pre-specified non-inferiority margin. Importantly, other factors including antimicrobial exposure seem to be more influential.


Assuntos
Infecção Hospitalar , Infecções por Bactérias Gram-Positivas , Enterococos Resistentes à Vancomicina , Estudos de Coortes , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Infecções por Bactérias Gram-Positivas/epidemiologia , Infecções por Bactérias Gram-Positivas/prevenção & controle , Humanos , Tipagem de Sequências Multilocus , Estudos Prospectivos , Enterococos Resistentes à Vancomicina/genética
6.
PLoS One ; 17(1): e0262095, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35030190

RESUMO

BACKGROUND: The understanding of longitudinal changes in the urinary microbiota of healthy women and its relation to intestinal microbiota is limited. METHODS: From a cohort of 15 premenopausal women without known urogenital disease or current symptoms, we collected catheter urine (CU), vaginal and periurethral swabs, and fecal samples on four visits over six months. Additionally, ten participants provided CU and midstream urine (MU) to assess comparability. Urine was subjected to expanded culture. 16S rRNA gene sequencing was performed on all urine, fecal, and selected vaginal and periurethral samples. Sequence reads were processed (DADA2 pipeline) and analyzed using QIIME 2 and R. RESULTS: Relative abundances of urinary microbiota were variable over 6-18 months. The degree of intraindividual variability of urinary microbiota was higher than that found in fecal samples. Still, nearly half of the observed beta diversity of all urine samples could be attributed to differences between volunteers (R2 = 0.48, p = 0.001). After stratification by volunteer, time since last sexual intercourse was shown to be a factor significantly contributing to beta diversity (R2 = 0.14, p = 0.001). We observed a close relatedness of urogenital microbial habitats and a clear distinction from intestinal microbiota in the overall betadiversity analysis. Microbiota compositions derived from MU differed only slightly from CU compositions. Within this analysis of low-biomass samples, we identified contaminating sequences potentially stemming from sequencing reagents. CONCLUSIONS: Results from our longitudinal cohort study confirmed the presence of a rather variable individual urinary microbiota in premenopausal women. These findings from catheter urine complement previous observations on temporal dynamics in voided urine. The higher intraindividual variability of urinary microbiota as compared to fecal microbiota will be a challenge for future studies investigating associations with urogenital diseases and aiming at identifying pathogenic microbiota signatures.


Assuntos
Bactérias/classificação , Pré-Menopausa/urina , RNA Ribossômico 16S/genética , Análise de Sequência de DNA/métodos , Urina/microbiologia , Adulto , Bactérias/genética , Bactérias/isolamento & purificação , DNA Ribossômico/genética , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal , Voluntários Saudáveis , Humanos , Estudos Longitudinais , Filogenia , Projetos Piloto , Uretra/microbiologia , Vagina/microbiologia , Adulto Jovem
7.
Lancet Infect Dis ; 22(5): 731-741, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35065060

RESUMO

BACKGROUND: The burden of bloodstream infections remains high worldwide and cannot be confined to short-term in-hospital mortality. We aimed to develop scores to predict short-term and long-term mortality in patients with bloodstream infections. METHODS: The Bloodstream Infection due to Multidrug-resistant Organisms: Multicenter Study on Risk Factors and Clinical Outcomes (BLOOMY) study is a prospective, multicentre cohort study at six German tertiary care university hospitals to develop and validate two scores assessing 14-day and 6-month mortality in patients with bloodstream infections. We excluded patients younger than 18 years or who were admitted to an ophthalmology or psychiatry ward. Microbiological, clinical, laboratory, treatment, and survival data were prospectively collected on day 0 and day 3 and then from day 7 onwards, weekly. Participants were followed up for 6 months. All patients in the derivation cohort who were alive on day 3 were included in the analysis. Predictive scores were developed using logistic regression and Cox proportional hazards models with a machine-learning approach. Validation was completed using the C statistic and predictive accuracy was assessed using sensitivity, specificity, and predictive values. FINDINGS: Between Feb 1, 2017, and Jan 31, 2019, 2568 (61·5%) of 4179 eligible patients were recruited into the derivation cohort. The in-hospital mortality rate was 23·75% (95% CI 22·15-25·44; 610 of 2568 patients) and the 6-month mortality rate was 41·55% (39·54-43·59; 949 of 2284). The model predictors for 14-day mortality (C statistic 0·873, 95% CI 0·849-0·896) and 6-month mortality (0·807, 0·784-0·831) included age, body-mass index, platelet and leukocyte counts, C-reactive protein concentrations, malignancy (ie, comorbidity), in-hospital acquisition, and pathogen. Additional predictors were, for 14-day mortality, mental status, hypotension, and the need for mechanical ventilation on day 3 and, for 6-month mortality, focus of infection, in-hospital complications, and glomerular filtration rate at the end of treatment. The scores were validated in a cohort of 1023 patients with bloodstream infections, recruited between Oct 9, 2019, and Dec 31, 2020. The BLOOMY 14-day score showed a sensitivity of 61·32% (95% CI 51·81-70·04), a specificity of 86·36% (83·80-88·58), a positive predictive value (PPV) of 37·57% (30·70-44·99), and a negative predictive value (NPV) of 94·35% (92·42-95·80). The BLOOMY 6-month score showed a sensitivity of 69·93% (61·97-76·84), a specificity of 66·44% (61·86-70·73), a PPV of 40·82% (34·85-47·07), and a NPV of 86·97% (82·91-90·18). INTERPRETATION: The BLOOMY scores showed good discrimination and predictive values and could support the development of protocols to manage bloodstream infections and also help to estimate the short-term and long-term burdens of bloodstream infections. FUNDING: DZIF German Center for Infection Research. TRANSLATION: For the German translation of the abstract see Supplementary Materials section.


Assuntos
Sepse , Adulto , Estudos de Coortes , Humanos , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Prospectivos
8.
Nat Commun ; 12(1): 2240, 2021 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-33854064

RESUMO

Trial enrichment using gut microbiota derived biomarkers by high-risk individuals can improve the feasibility of randomized controlled trials for prevention of Clostridioides difficile infection (CDI). Here, we report in a prospective observational cohort study the incidence of CDI and assess potential clinical characteristics and biomarkers to predict CDI in 1,007 patients ≥ 50 years receiving newly initiated antibiotic treatment with penicillins plus a beta-lactamase inhibitor, 3rd/4th generation cephalosporins, carbapenems, fluoroquinolones or clindamycin from 34 European hospitals. The estimated 90-day cumulative incidences of a first CDI episode is 1.9% (95% CI 1.1-3.0). Carbapenem treatment (Hazard Ratio (95% CI): 5.3 (1.7-16.6)), toxigenic C. difficile rectal carriage (10.3 (3.2-33.1)), high intestinal abundance of Enterococcus spp. relative to Ruminococcus spp. (5.4 (2.1-18.7)), and low Shannon alpha diversity index as determined by 16 S rRNA gene profiling (9.7 (3.2-29.7)), but not normalized urinary 3-indoxyl sulfate levels, predicts an increased CDI risk.


Assuntos
Antibacterianos/uso terapêutico , Clostridioides difficile/efeitos dos fármacos , Infecções por Clostridium/tratamento farmacológico , Idoso , Biomarcadores/análise , Carbapenêmicos/uso terapêutico , Cefalosporinas/uso terapêutico , Clostridioides difficile/genética , Clostridioides difficile/fisiologia , Infecções por Clostridium/microbiologia , Quimioterapia Combinada , Feminino , Fluoroquinolonas/uso terapêutico , Seguimentos , Microbioma Gastrointestinal , Hospitalização , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Penicilinas/uso terapêutico , Estudos Prospectivos
10.
Am J Infect Control ; 49(5): 586-592, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32966854

RESUMO

BACKGROUND: Contamination of the catheter hub is an important source of central line-associated bloodstream infections (CLABSI); catheter hub caps incorporating a 70% isopropyl alcohol aim are designed to reduce contamination and hence CLABSI rates. Supporting data in high-risk hematological and oncological patients on the clinical effectiveness of this approach are sparse. METHODS: We conducted a before-after single center study accompanying the introduction of such caps at our department. Retrospective data from the year prior to the introduction were compared to 1 year of prospective data. RESULTS: The control and antiseptic barrier cap (ABC) groups consisted of 309 and 289 patients presenting a CLABSI rate of 15.28 and 10.38 per 1,000 catheter days (P= .042), respectively. However, after multivariate analysis, ABCs were not identified as a statistically significant independent protective factor for the occurrence of CLABSI (hazard ratio 0.69, P= .120). There was no significant difference between the groups with respect to time to CLABSI (P= .681), nor the proportion of catheters removed due to suspicion of infection (P= .076). CONCLUSIONS: The introduction of ABCs in this high-risk population did not significantly alter CLABSI rates.


Assuntos
Bacteriemia , Infecções Relacionadas a Cateter , Cateterismo Venoso Central , Cateteres Venosos Centrais , Sepse , Bacteriemia/epidemiologia , Bacteriemia/prevenção & controle , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/prevenção & controle , Cateterismo Venoso Central/efeitos adversos , Cateteres Venosos Centrais/efeitos adversos , Humanos , Estudos Prospectivos , Melhoria de Qualidade , Estudos Retrospectivos , Sepse/epidemiologia , Sepse/prevenção & controle
11.
Antibiotics (Basel) ; 9(10)2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33028048

RESUMO

Mobile genetic elements (MGEs), especially multidrug-resistance plasmids, are major vehicles for the dissemination of antimicrobial resistance determinants. Herein, we analyse the MGEs in three extensively drug-resistant (XDR) Klebsiella pneumoniae isolates from Germany. Whole genome sequencing (WGS) is performed using Illumina and MinION platforms followed by core-genome multi-locus sequence typing (MLST). The plasmid content is analysed by conjugation, S1-pulsed-field gel electrophoresis (S1-PFGE) and Southern blot experiments. The K. pneumoniae isolates belong to the international high-risk clone ST147 and form a cluster of closely related isolates. They harbour the blaOXA-181 carbapenemase on a ColKP3 plasmid, and 12 antibiotic resistance determinants on an multidrug-resistant (MDR) IncR plasmid with a recombinogenic nature and encoding a large number of insertion elements. The IncR plasmids within the three isolates share a high degree of homology, but present also genetic variations, such as inversion or deletion of genetic regions in close proximity to MGEs. In addition, six plasmids not harbouring any antibiotic resistance determinants are present in each isolate. Our study indicates that genetic variations can be observed within a cluster of closely related isolates, due to the dynamic nature of MGEs. The mobilome of the K. pneumoniae isolates combined with the emergence of the XDR ST147 high-risk clone have the potential to become a major challenge for global healthcare.

12.
Dtsch Arztebl Int ; 117(3): 31-38, 2020 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-32031511

RESUMO

BACKGROUND: Fecal microbiota transfer (FMT) is increasingly being used in Ger- many, as in other countries, for the treatment of recurrent Clostridioides difficile infection (rCDI). FMT is now being performed both for research and in individual patients outside of clinical trials. No compulsory standards have been established to date for donor screening or for the method of fecal transfer. Given the potential dangers of FMT, this would seem to be urgently necessary. METHODS: This review is based on pertinent literature retrieved by a selective search, including the reports of consensus conferences from Germany and abroad. RESULTS: Because of its high efficacy, FMT is the treatment of choice for rCDI. It is largely free of adverse side effects, even in immune-deficient patients, as long as comprehensive and repeated donor screening has been carried out, with extensive clinical and microbiological testing and with the use of structured questionnaires. The ingestion of frozen, encapsulated microbiota is just as effective as other modes of delivery for the treatment of rCDI. CONCLUSION: Encapsulation of the fecal microbiome (FM) and storage at -20°C is the method of choice, because it can be standardized with the necessary quality controls and it is readily available. Patients with rCDI should undergo FMT by orally ingesting the capsules. There are ongoing research efforts to identify the active e FM. It is not yet clear when the ultimate goal of recombinant production can be achieved.


Assuntos
Clostridioides difficile , Infecções por Clostridium/terapia , Transplante de Microbiota Fecal , Alemanha , Humanos , Resultado do Tratamento
15.
BMC Biol ; 17(1): 76, 2019 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533707

RESUMO

BACKGROUND: The selection pressure exercised by antibiotic drugs is an important consideration for the wise stewardship of antimicrobial treatment programs. Treatment decisions are currently based on crude assumptions, and there is an urgent need to develop a more quantitative knowledge base that can enable predictions of the impact of individual antibiotics on the human gut microbiome and resistome. RESULTS: Using shotgun metagenomics, we quantified changes in the gut microbiome in two cohorts of hematological patients receiving prophylactic antibiotics; one cohort was treated with ciprofloxacin in a hospital in Tübingen and the other with cotrimoxazole in a hospital in Cologne. Analyzing this rich longitudinal dataset, we found that gut microbiome diversity was reduced in both treatment cohorts to a similar extent, while effects on the gut resistome differed. We observed a sharp increase in the relative abundance of sulfonamide antibiotic resistance genes (ARGs) by 148.1% per cumulative defined daily dose of cotrimoxazole in the Cologne cohort, but not in the Tübingen cohort treated with ciprofloxacin. Through multivariate modeling, we found that factors such as individual baseline microbiome, resistome, and plasmid diversity; liver/kidney function; and concurrent medication, especially virostatic agents, influence resistome alterations. Strikingly, we observed different effects on the plasmidome in the two treatment groups. There was a substantial increase in the abundance of ARG-carrying plasmids in the cohort treated with cotrimoxazole, but not in the cohort treated with ciprofloxacin, indicating that cotrimoxazole might contribute more efficiently to the spread of resistance. CONCLUSIONS: Our study represents a step forward in developing the capability to predict the effect of individual antimicrobials on the human microbiome and resistome. Our results indicate that to achieve this, integration of the individual baseline microbiome, resistome, and mobilome status as well as additional individual patient factors will be required. Such personalized predictions may in the future increase patient safety and reduce the spread of resistance. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02058888 . Registered February 10 2014.


Assuntos
Antibacterianos/efeitos adversos , Ciprofloxacina/efeitos adversos , Resistência Microbiana a Medicamentos , Microbioma Gastrointestinal/efeitos dos fármacos , Plasmídeos/efeitos dos fármacos , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Antibacterianos/uso terapêutico , Ciprofloxacina/uso terapêutico , Estudos de Coortes , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Resistência Microbiana a Medicamentos/genética , Genes Bacterianos/efeitos dos fármacos , Alemanha , Humanos , Estudos Longitudinais , Metagenômica/métodos , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
16.
J Antimicrob Chemother ; 74(7): 2065-2074, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31220256

RESUMO

OBJECTIVES: We assessed the efficacy and safety of an oral antimicrobial regimen for short- and long-term intestinal eradication of ESBL-producing Escherichia coli and Klebsiella pneumoniae (ESBL-EC/KP) in immunocompromised patients. METHODS: We performed a randomized (2:1), double-blind multicentre Phase II study in four haematology-oncology departments. Patients colonized with ESBL-EC/KP received a 7 day antimicrobial regimen of oral colistin (2 × 106 IU 4×/day), gentamicin (80 mg 4×/day) and fosfomycin (three administrations of 3 g every 72 h), or placebo. Faecal, throat and urine specimens were collected on day 0, 6 ± 2, 11 ± 2, 28 ± 4 and 42 ± 4 after treatment initiation, and the quantitative burden of ESBL-EC/KP, resistance genes and changes in intestinal microbiota were analysed. Clinicaltrials.gov: NCT01931592. RESULTS: As the manufacture of colistin powder was suspended worldwide, the study was terminated prematurely. Overall, 29 (18 verum/11 placebo) out of 47 patients were enrolled. The short-term intestinal eradication was marginal at day 6 (verum group 15/18, 83.3% versus placebo 2/11, 18.2%; relative risk 4.58, 95% CI 1.29-16.33; Fisher's exact test P = 0.001) and not evident at later timepoints. Quantitative analysis showed a significant decrease of intestinal ESBL-EC/KP burden on day 6. Sustained intestinal eradication (day 28 + 42) was not achieved (verum, 38.9% versus placebo, 27.3%; P = 0.299). In the verum group, mcr-1 genes were detected in two faecal samples collected after treatment. Microbiome analysis showed a significant decrease in alpha diversity and a shift in beta diversity. CONCLUSIONS: In this prematurely terminated study of a 7 day oral antimicrobial eradication regimen, short-term ESBL-EC/KP suppression was marginal, while an altered intestinal microbiota composition was clearly apparent.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Enterobacteriaceae/etiologia , Infecções por Enterobacteriaceae/prevenção & controle , Doenças Hematológicas/complicações , Controle de Infecções , Adulto , Idoso , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Farmacorresistência Bacteriana , Feminino , Microbioma Gastrointestinal , Humanos , Hospedeiro Imunocomprometido , Controle de Infecções/métodos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade
17.
PLoS One ; 14(4): e0215428, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30986251

RESUMO

OBJECTIVES: Large-scale clinical studies investigating associations between intestinal microbiota signatures and human diseases usually rely on stool samples. However, the timing of repeated stool sample collection cannot be predefined in longitudinal settings. Rectal swabs, being straightforward to obtain, have the potential to overcome this drawback. Therefore, we assessed the usability of rectal swabs for microbiome sampling in a cohort of hematological and oncological patients. STUDY DESIGN: We used a pipeline for intestinal microbiota analysis from deep rectal swabs which was established and validated with test samples and negative controls. Consecutively, a cohort of patients from hematology and oncology wards was established and weekly deep rectal swabs taken during their admissions and re-admissions. RESULTS: Validation of our newly developed pipeline for intestinal microbiota analysis from rectal swabs revealed consistent and reproducible results. Over a period of nine months, 418 rectal swabs were collected longitudinally from 41 patients. Adherence to the intended sampling protocol was 97%. After DNA extraction, sequencing, read pre-processing and filtering of chimeric sequences, 405 of 418 samples (96.9%) were eligible for further analyses. Follow-up samples and those taken under current antibiotic exposure showed a significant decrease in alpha diversity as compared to baseline samples. Microbial domination occurred most frequently by Enterococcaceae (99 samples, 24.4%) on family level and Enterococcus (90 samples, 22.2%) on genus level. Furthermore, we noticed a high abundance of potential skin commensals in 99 samples (24.4%). SUMMARY: Deep rectal swabs were shown to be reliable for microbiome sampling and analysis, with practical advantages related to high sampling adherence, easy timing, transport and storage. The relatively high abundance of putative skin commensals in this patient cohort may be of potential interest and should be further investigated. Generally, previous findings on alpha diversity dynamics obtained from stool samples were confirmed.


Assuntos
Enterobacteriaceae , Enterococcus , Fezes/microbiologia , Microbioma Gastrointestinal , Neoplasias Hematológicas/microbiologia , Manejo de Espécimes , Estudos de Coortes , Enterobacteriaceae/classificação , Enterobacteriaceae/crescimento & desenvolvimento , Enterococcus/classificação , Enterococcus/genética , Feminino , Humanos , Masculino
18.
Infection ; 47(1): 7-11, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30178076

RESUMO

In recent years, an increase in invasive VRE infections has been reported worldwide, including Germany. The most common gene encoding resistance to glycopeptides is VanA, but predominant VanB clones are emerging. Although neither the incidence rates nor the exact routes of nosocomial transmission of VRE are well established, screening and strict infection control measures, e.g. single room contact isolation, use of personal protective clothing by hospital staff and intensified surface disinfection for colonized individuals, are implemented in many hospitals. At the same time, the impact of VRE infection on mortality remains unclear, with current evidence being weak and contradictory. In this short review, we aim to give an overview on the current basis of evidence on the clinical effectiveness of infection control measures intended to prevent transmission of VRE and to put these findings into a larger perspective that takes further factors, e.g. VRE-associated mortality and impact on patient care, into account.


Assuntos
Infecções por Bactérias Gram-Positivas/prevenção & controle , Controle de Infecções/métodos , Assistência ao Paciente/métodos , Resistência a Vancomicina , Enterococos Resistentes à Vancomicina/fisiologia , Infecções por Bactérias Gram-Positivas/mortalidade , Infecções por Bactérias Gram-Positivas/transmissão , Humanos , Enterococos Resistentes à Vancomicina/efeitos dos fármacos
19.
Infection ; 46(6): 871-874, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30109576

RESUMO

PURPOSE: We report on a kidney transplant recipient treated with fecal microbiota transplantation (FMT) for recurrent urinary tract infections. METHODS: FMT was administered via frozen capsulized microbiota. Before and after FMT, urinary, fecal and vaginal microbiota compositions were analyzed. RESULTS: The patient remained without symptoms after FMT. CONCLUSIONS: Underlying mechanisms of action need to be addressed in depth by future research.


Assuntos
Transplante de Microbiota Fecal , Transplante de Rim , Transplantados , Infecções Urinárias/terapia , Feminino , Alemanha , Humanos , Pessoa de Meia-Idade , Recidiva , Resultado do Tratamento
20.
Am J Infect Control ; 46(9): 992-997, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29661631

RESUMO

BACKGROUND: A recent study reported a reduction in probable/definite central venous catheter (CVC)-related bloodstream infections (CRBSIs) in neutropenic high-risk patients using CVC dressings with a chlorhexidine-containing gel pad. METHODS: Based on published data, a health-economic analysis was performed to analyze the economic effect of using CVC dressings with a chlorhexidine-containing gel pad compared to non-chlorhexidine control dressings. A micro-costing approach was used to determine CRBSI-related direct treatment cost factors. RESULTS: Between February 2012 and September 2014, 356 patients (178 patients in both groups) were analyzed. Distribution of probable and definite CRBSI in the chlorhexidine group and control group were 12 (7%) vs 18 (10%) and 9 (5%) vs 21 (12%), respectively (P = .011). Median overall length of stay (25 vs 27.5 days; P = .630) and days on treatment with antibacterials (10 vs 12 days; P = .140) were similar between the chlorhexidine and control groups. The most important cost driver in both groups was treatment on general ward (€4275 [US$ 5173], interquartile range [IQR]: €592 - €6504 [US$ 716 - US$ 7871] vs €4560 [US$ 5518], IQR: €1227 - €8567 [US$ 1485 - US$ 10,367]; P = .120), resulting in median overall direct treatment costs of €13,881 (US$ 16,798) [IQR: €10,922 - €25,457 (US$ 13,217 - US$ 30,807) vs €13,929 [US$ 16,856] [IQR: €11,295 - €23,561 (US$ 13,669 - US$ 28,512); P = .640]). CONCLUSION: Our study shows similar results in overall direct treatment costs, meaning that higher acquisition costs of chlorhexidine-containing dressings did not translate into higher costs. Expenses were primarily outweighed by a lower rate of probable/definite CRBSI and reduced associated costs.


Assuntos
Anti-Infecciosos Locais/administração & dosagem , Bandagens/economia , Cateteres Venosos Centrais/efeitos adversos , Clorexidina/administração & dosagem , Custos e Análise de Custo , Desinfecção/métodos , Sepse/prevenção & controle , Adulto , Idoso , Desinfecção/economia , Feminino , Custos de Cuidados de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Sepse/economia , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA