RESUMO
BACKGROUND: We aimed to assess whether longer indwelling time of peripherally inserted central catheters (PICC) increases risk of central line associated bloodstream infections (CLABSI) in haematology patients. METHODS: Multicentre retrospective cohort study among haematology patients receiving PICCs between 2013 and 2015. Occurrence of CLABSI based on CDC definitions was assessed. We calculated incidence rates, determined risk factors for CLABSI and used Poisson regression models to assess the risk of developing CLABSI as a function of PICC dwell time. We compared diagnoses and treatment characteristics between 2013-2015 and 2015-2020. RESULTS: 455 PICCs placed in 370 patients were included, comprising 19,063 catheter days. Median indwelling time was 26 days (range 0-385) and CLABSI incidence was 4.0 per 1000 catheter days, with a median time to CLABSI of 33 days (range 18-158). Aplastic anaemia (AA) was associated with an increased risk of CLABSI; patients undergoing autologous stem cell transplantation (SCT) were less likely to develop CLABSI. In the unadjusted analysis, PICCs with an indwelling time of 15-28 days, 29-42 days, 43-56 days and > 56 days each had an increased CLABSI incidence rate ratio of 2.4 (1.2-4.8), 2.2 (0.95-5.0), 3.4 (1.6-7.5) and 1.7 (0.9-3.5), respectively, compared to PICCs in place for < 15 days. However, after adjusting for AA and SCT, there was no significant difference in incidence rates between dwell times (p 0.067). CONCLUSIONS: Our study shows that risk of CLABSI does not appear to increase with longer PICC indwelling time. Routine replacement of PICCs therefore is unlikely to prevent CLABSI in this population.
Assuntos
Infecções Relacionadas a Cateter , Cateterismo Venoso Central , Hematologia , Transplante de Células-Tronco Hematopoéticas , Sepse , Infecções Relacionadas a Cateter/prevenção & controle , Cateterismo Venoso Central/efeitos adversos , Catéteres/efeitos adversos , Estudos de Coortes , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Incidência , Estudos Retrospectivos , Sepse/epidemiologia , Transplante Autólogo/efeitos adversosRESUMO
- As yet, with cure rates around 85%, recurrent Clostridium difficile infection is the only definite indication for faecal microbiota transplantation.- Faecal microbiota transplantation induces clinical remission and endoscopic improvements in 24-30% of patients with ulcerative colitis, compared to 5% (water) to 20% (autologous faeces) in placebo-treated patients. Current research focuses on the identification of 'super donors', and subgroups of patients in which faecal microbiota transplantation is effective.- In patients with metabolic syndrome, faecal microbiota transplantation may increase insulin sensitivity. Weight, body mass index, and energy metabolism are not affected by faecal microbiota transplantation in humans.- In addition to the aforementioned indications, faecal microbiota transplantation is an emerging treatment modality for patients with Crohn's disease, irritable bowel syndrome, graft-versus-host-disease, and carriage of multidrug-resistant micro-organisms. Randomized controlled trials, comparing faecal microbiota transplantation with placebo treatment, are required to determine the effectiveness of faecal microbiota transplantation in these patient groups.
Assuntos
Colite Ulcerativa/microbiologia , Colite Ulcerativa/terapia , Doença de Crohn/terapia , Transplante de Microbiota Fecal , Infecções por Clostridium/complicações , Doença de Crohn/microbiologia , Fezes/microbiologia , HumanosRESUMO
OBJECTIVE: To verify the role of proton pump inhibitors (PPI) and nitrofurantoin, which have appeared as novel risk factors for carriage of extended-spectrum ß-lactamase (ESBL) -producing Escherichia coli, as risk factors for ESBL E. coli urinary tract infection (UTI). We included known risk factors to ascertain whether our findings are comparable with those of previous studies. METHODS: Population-based case-control study including 339 cases with community-onset ESBL E. coli UTI in 2007-2012, 3390 non-ESBL E. coli UTI controls and 3390 population controls. We investigated potential risk factors by estimating ORs and 95% CIs adjusting for sex, age and co-morbidity. RESULTS: Comparing cases with non-ESBL E. coli UTI, PPI use yielded an OR of 1.6 (95% CI 1.2-2.0) and antibiotic exposure gave an OR of 1.4 (95% CI 1.1-1.8); these were driven by nitrofurantoin (OR 1.8; 95% CI 1.3-2.6) and macrolides (OR 1.7; 95% CI 1.2-2.3). Other risk factors included previous hospitalization with one or two and more than two hospitalizations versus none yielding ORs of 1.9 (95% CI 1.4-2.5) and 4.6 (95% CI 3.2-6.8), recent surgery (OR 2.0; 95% CI 1.5-2.8), renal disease (OR 2.2; 95% CI 1.4-3.4), chronic pulmonary disease (OR 1.4; 95% CI 1.0-2.0) and cancer (OR 1.5; 95% CI 1.1-2.1). Comparing cases with population controls, we found that most risk factors were also risk factors for non-ESBL UTI. CONCLUSIONS: ESBL E. coli UTI were associated with previous hospitalization and surgery. Nitrofurantoin and macrolides augmented the risk. PPIs had a moderate effect but may be important facilitators of ESBL carriage due to their widespread use.
Assuntos
Infecções por Escherichia coli/etiologia , Infecções Urinárias/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Estudos de Casos e Controles , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/etiologia , Infecções Comunitárias Adquiridas/microbiologia , Dinamarca/epidemiologia , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/epidemiologia , Infecções Urinárias/microbiologia , Adulto Jovem , Resistência beta-LactâmicaRESUMO
Multiple body site screening and pre-emptive isolation of patients at risk for methicillin-resistant Staphylococcus aureus (MRSA) carriage are considered essential for control of nosocomial spread. The relative importance of extranasal screening when using rapid diagnostic testing (RDT) is unknown. Using data from a multicentre study evaluating BD GeneOhm™ MRSA PCR (IDI), Xpert MRSA (GeneXpert) and chromogenic agar, added to conventional cultures, we determined cost-effectiveness assuming isolation measures would have been based on RDT results of different hypothetical screening regimes. Costs per isolation day avoided were calculated for regimes with single or less extensive multiple site RDT, regimes without conventional back-up cultures and when PCR would have been performed with pooling of swabs. Among 1764 patients at risk, MRSA prevalence was 3.3% (n = 59). In all scenarios the negative predictive value is above 98.4%. With back-up cultures of all sites as a reference, the costs per isolation day avoided were 15.19, 30.83 and 45.37 with 'nares only' screening using chromogenic agar, IDI and GeneXpert, respectively, as compared with 19.95, 95.77 and 125.43 per isolation day avoided when all body sites had been screened. Without back-up cultures costs per isolation day avoided using chromogenic agar would range from 9.24 to 76.18 when costs per false-negative RDT range from 5000 up to 50 000; costs for molecular screening methods would be higher in all scenarios evaluated. In conclusion, in a low endemic setting chromogenic agar screening added to multiple site conventional cultures is the most cost-effective MRSA screening strategy.
Assuntos
Técnicas Bacteriológicas/economia , Técnicas Bacteriológicas/métodos , Portador Sadio/diagnóstico , Programas de Rastreamento/economia , Programas de Rastreamento/métodos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/diagnóstico , Portador Sadio/microbiologia , Análise Custo-Benefício , Humanos , Valor Preditivo dos Testes , Prevalência , Estudos Prospectivos , Infecções Estafilocócicas/microbiologiaRESUMO
Infection of biomedical devices is characterized by biofilm formation and colonization of surrounding tissue by the causative pathogens. To investigate whether bacteria detected microscopically in tissue surrounding infected devices were viable, we used bromodeoxyuridine (BrdU), a nucleotide analogue that is incorporated into bacterial DNA and can be detected with antibodies. Infected human tissue was obtained postmortem from patients with intravascular devices, and mouse biopsy specimens were obtained from mice with experimental biomaterial infection. In vitro experiments showed that Staphylococcus epidermidis incorporated BrdU, as judged from staining of the bacteria with anti-BrdU antibodies. After incubation of bacteria with BrdU and subsequent staining of microscopic sections with anti-BrdU antibodies, bacteria could be clearly visualized in the tissue surrounding intravascular devices of deceased patients. With this staining technique, relapse of infection could be visualized in mice challenged with a low dose of S. epidermidis and treated with dexamethasone between 14 and 21 days after challenge to suppress immunity. This confirms and extends our previous findings that pericatheter tissue is a reservoir for bacteria in biomaterial-associated infection. The pathogenesis of the infection and temporo-spatial distribution of viable, dividing bacteria can now be studied at the microscopic level by immunolabeling with BrdU and BrdU antibodies.
Assuntos
Técnicas Bacteriológicas/métodos , Bromodesoxiuridina/metabolismo , Infecções Relacionadas a Cateter/diagnóstico , Viabilidade Microbiana , Infecções Relacionadas à Prótese/diagnóstico , Infecções Estafilocócicas/diagnóstico , Staphylococcus epidermidis/isolamento & purificação , Animais , Materiais Biocompatíveis , Infecções Relacionadas a Cateter/microbiologia , Humanos , Imuno-Histoquímica/métodos , Camundongos , Microscopia/métodos , Infecções Relacionadas à Prótese/microbiologia , Coloração e Rotulagem/métodos , Infecções Estafilocócicas/microbiologia , Staphylococcus epidermidis/crescimento & desenvolvimento , Staphylococcus epidermidis/metabolismoRESUMO
Pathogenic mycobacteria have the ability to persist in phagocytic cells and to suppress the immune system. The glycolipid lipoarabinomannan (LAM), in particular its mannose cap, has been shown to inhibit phagolysosome fusion and to induce immunosuppressive IL-10 production via interaction with the mannose receptor or DC-SIGN. Hence, the current paradigm is that the mannose cap of LAM is a crucial factor in mycobacterial virulence. However, the above studies were performed with purified LAM, never with live bacteria. Here we evaluate the biological properties of capless mutants of Mycobacterium marinum and M. bovis BCG, made by inactivating homologues of Rv1635c. We show that its gene product is an undecaprenyl phosphomannose-dependent mannosyltransferase. Compared with parent strain, capless M. marinum induced slightly less uptake by and slightly more phagolysosome fusion in infected macrophages but this did not lead to decreased survival of the bacteria in vitro, nor in vivo in zebra fish. Loss of caps in M. bovis BCG resulted in a sometimes decreased binding to human dendritic cells or DC-SIGN-transfected Raji cells, but no differences in IL-10 induction were observed. In mice, capless M. bovis BCG did not survive less well in lung, spleen or liver and induced a similar cytokine profile. Our data contradict the current paradigm and demonstrate that mannose-capped LAM does not dominate the Mycobacterium-host interaction.
Assuntos
Cápsulas Bacterianas/fisiologia , Lipopolissacarídeos/metabolismo , Manose/metabolismo , Mycobacterium/fisiologia , Animais , Cápsulas Bacterianas/metabolismo , Elementos de DNA Transponíveis/genética , Células Dendríticas/metabolismo , Células Dendríticas/microbiologia , Eletroforese em Gel de Poliacrilamida , Feminino , Teste de Complementação Genética , Interações Hospedeiro-Patógeno , Humanos , Immunoblotting , Interleucina-10/metabolismo , Macrófagos/metabolismo , Macrófagos/microbiologia , Manose/química , Manose/fisiologia , Manosiltransferases/genética , Manosiltransferases/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Modelos Biológicos , Modelos Moleculares , Mutagênese Insercional , Mutação , Mycobacterium/metabolismo , Infecções por Mycobacterium/metabolismo , Infecções por Mycobacterium/microbiologia , Peixe-ZebraRESUMO
An open-label randomised clinical trial was designed to compare the efficacy and tolerance of levofloxacin and ciprofloxacin plus phenethicillin for the prevention of bacterial infections in patients with high-risk neutropenia, and to monitor the emergence of antimicrobial resistance. Adult patients (n = 242) scheduled to receive intensive treatment for haematological malignancies were assigned randomly to receive oral prophylaxis with either levofloxacin 500 mg once-daily (n = 122), or ciprofloxacin 500 mg twice-daily plus phenethicillin 250 mg four-times-daily (n = 120). The primary endpoint was failure of prophylaxis, defined as the first occurrence of either the need to change the prophylactic regimen or the initiation of intravenous broad-spectrum antibiotics. This endpoint was observed in 89 (73.0%) of 122 levofloxacin recipients and in 85 (70.8%) of 120 ciprofloxacin plus phenethicillin recipients (RR 1.03, 95% CI 0.88-1.21, p 0.71). No differences were noted between the two groups with respect to secondary outcome measures, including time to endpoint, occurrence of fever, type and number of microbiologically documented infections, and administration of intravenous antibiotics. A questionnaire revealed that levofloxacin was tolerated significantly better than ciprofloxacin plus phenethicillin. Surveillance cultures indicated the emergence of viridans group (VG) streptococci resistant to levofloxacin in 17 (14%) of 122 levofloxacin recipients; in these cases, the prophylactic regimen was adjusted. No bacteraemia with VG streptococci occurred. It was concluded that levofloxacin and ciprofloxacin plus phenethicillin are equally effective in the prevention of bacterial infections in neutropenic patients, but that levofloxacin is tolerated better. Emergence of levofloxacin-resistant VG streptococci is of concern, but appears to be a manageable problem.
Assuntos
Antibacterianos/uso terapêutico , Antibioticoprofilaxia/métodos , Ciprofloxacina/uso terapêutico , Infecção Hospitalar/prevenção & controle , Neoplasias Hematológicas/microbiologia , Levofloxacino , Ofloxacino/uso terapêutico , Penicilina V/análogos & derivados , Adolescente , Adulto , Idoso , Antibioticoprofilaxia/efeitos adversos , Farmacorresistência Bacteriana/efeitos dos fármacos , Quimioterapia Combinada , Feminino , Febre/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Neutropenia/microbiologia , Penicilina V/uso terapêutico , Resultado do Tratamento , Estreptococos Viridans/efeitos dos fármacosRESUMO
In the Netherlands, less than 1% of clinical isolates of Staphylococcus aureus are methicillin-resistant (MRSA). A national search and destroy policy prevents MRSA from becoming endemic. Some MRSA outbreaks cannot be related to patients at risk for MRSA carriage. This study was designed to measure the prevalence of MRSA among patients without risk factors for MRSA carriage at the time of admission to the hospital. In four Dutch hospitals, patients admitted to non-surgical departments in the period 1999-2000 were screened for MRSA nasal carriage. Nasal swabs were streaked on 5% sheep blood agar (BA), submerged in a selective broth, and incubated for two to three days at 35 degrees C. Colonies suspected of being S. aureus were identified with an agglutination test. Susceptibility testing was performed by an automated system and additional oxacillin disk diffusion. Methicillin resistance was confirmed by a DNA hybridization test and mecA PCR. MRSA strains were genotyped by pulsed-field gel electrophoresis (PFGE). Twenty-four percent (2332/9859) of the patients were S. aureus nasal carriers. Only three (0.03%) patients were MRSA carriers. These patients were not repatriated, nor known to be MRSA carriers before screening. Genotyping revealed that the strains were not clonally related and were not related to MRSA outbreaks in the hospital where the patients were admitted. We conclude that at routine admission to a Dutch hospital (excluding high-risk foreign admissions) the MRSA prevalence is low (0.03%), due to the Dutch search and destroy policy and restrictive antibiotic prescribing.
Assuntos
Portador Sadio/diagnóstico , Resistência a Meticilina , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus/isolamento & purificação , Portador Sadio/tratamento farmacológico , Humanos , Programas de Rastreamento/métodos , Países Baixos/epidemiologia , Admissão do Paciente , Prevalência , Fatores de RiscoRESUMO
Gram-positive breakthrough infections pose a major drawback to the use of quinolones for antibacterial prophylaxis in neutropenic patients. Levofloxacin offers the advantage of an augmented Gram-positive spectrum and may potentially overcome this problem. In an open-label, clinical pilot study, we investigated the effects on throat and bowel microflora and pharmacokinetics of a once-daily oral dose of 500 mg levofloxacin, during neutropenia in 20 patients with haematological malignancies. Gram-negative bowel flora and Staphylococcus aureus were successfully eradicated. No Gram-negative infections occurred. Minimal inhibitory concentration values for viridans group (VG) streptococci tended to increase, in four patients over 8 mg/l, indicating resistance to levofloxacin. Four patients developed blood-stream infections with levofloxacin-resistant Gram-positive cocci. No significant changes in numbers of anaerobic microorganisms were observed. Pharmacokinetic parameters of levofloxacin, including the maximum serum concentration (C(max)), time to C(max) (T(max)), area under the concentration-time curve (AUC), volume of distribution at steady state (V(ss)/F) and clearance (CL/F) were not statistically different at first dose and during neutropenia. In conclusion, levofloxacin eradicates Gram-negative microorganisms and S. aureus and spares the anaerobic flora. Its pharmacokinetic profile is unaltered during neutropenia. However, prolonged administration of levofloxacin as antibacterial prophylaxis may be hampered by the emergence of levofloxacin-resistant VG streptococci.