RESUMO
RATIONALE: Selective digestive tract decontamination (SDD) and selective oropharyngeal decontamination (SOD) eradicate gram-negative bacteria (GNB) from the intestinal and respiratory tract in intensive care unit (ICU) patients, but their effect on antibiotic resistance remains controversial. OBJECTIVES: We quantified the effects of SDD and SOD on bacterial ecology in 13 ICUs that participated in a study, in which SDD, SOD, or standard care was used during consecutive periods of 6 months (de Smet AM, Kluytmans JA, Cooper BS, Mascini EM, Benus RF, van der Werf TS, van der Hoeven JG, Pickkers P, Bogaers-Hofman D, van der Meer NJ, et al. N Engl J Med 2009;360:20-31). METHODS: Point prevalence surveys of rectal and respiratory samples were performed once monthly in all ICU patients (receiving or not receiving SOD/SDD). Effects of SDD on rectal, and of SDD/SOD on respiratory tract, carriage of GNB were determined by comparing results from consecutive point prevalence surveys during intervention (6 mo for SDD and 12 mo for SDD/SOD) with consecutive point prevalence data in the pre- and postintervention periods. MEASUREMENTS AND MAIN RESULTS: During SDD, average proportions of patients with intestinal colonization with GNB resistant to either ceftazidime, tobramycin, or ciprofloxacin were 5, 7, and 7%, and increased to 15, 13, and 13% postintervention (P < 0.05). During SDD/SOD resistance levels in the respiratory tract were not more than 6% for all three antibiotics but increased gradually (for ceftazidime; P < 0.05 for trend) during intervention and to levels of 10% or more for all three antibiotics postintervention (P < 0.05). CONCLUSIONS: SOD and SDD have marked effects on the bacterial ecology in an ICU, with rising ceftazidime resistance prevalence rates in the respiratory tract during intervention and a considerable rebound effect of ceftazidime resistance in the intestinal tract after discontinuation of SDD.
Assuntos
Antibioticoprofilaxia , Farmacorresistência Bacteriana/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/prevenção & controle , Unidades de Terapia Intensiva , Infecções Respiratórias/prevenção & controle , Antibacterianos/uso terapêutico , Antibioticoprofilaxia/efeitos adversos , Ceftazidima/uso terapêutico , Ciprofloxacina/uso terapêutico , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Infecção Hospitalar/prevenção & controle , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Estudos Longitudinais , Reto/microbiologia , Sistema Respiratório/microbiologia , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/microbiologia , Tobramicina/uso terapêuticoRESUMO
OBJECTIVES: Antimicrobial resistance to ciprofloxacin is increasing. The objective of this study was to reduce the number of inappropriate prescriptions and to improve the quality of ciprofloxacin prescriptions by means of educational intervention. METHODS: In a teaching hospital five units of the Departments of Internal Medicine, Gastro-Enterology, Surgery, Urology and Pulmonary Diseases, selected because of a high rate of ciprofloxacin prescription, participated in a prospective intervention study. The quantity and the quality of prescriptions were reviewed before and after educational intervention and during follow-up. The quality of each ciprofloxacin prescription was independently evaluated by two medical microbiologists. During the intervention period, a medical microbiologist discussed the appropriateness of prescribing ciprofloxacin with prescribing clinicians, and educational presentations were given to clinicians of participating units. Regression analysis was used to analyse trends in time-series data. RESULTS: The number of ciprofloxacin prescriptions decreased from 81 prescriptions/1000 admissions before intervention to 32 prescriptions/1000 admissions after intervention, a significant reduction of 60.5%. Appropriate prescriptions significantly increased. Significantly fewer inappropriate prescriptions were prescribed after intervention and/or during follow-up. At this time, 23 ciprofloxacin prescriptions/1000 admissions were prescribed, a total reduction of 71.3% compared with baseline. CONCLUSIONS: In a hospital with relatively low baseline ciprofloxacin consumption, intervention by direct consultation of a medical microbiologist and educational presentations led to 3-4-fold sustained reduction in the use of ciprofloxacin and significant improvement in quality of ciprofloxacin prescriptions. Close collaboration between clinicians and medical microbiologists can provide a major contribution to the prudent hospital use of antimicrobial agents.
Assuntos
Antibacterianos/provisão & distribuição , Ciprofloxacina/provisão & distribuição , Prescrições de Medicamentos/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Ciprofloxacina/administração & dosagem , Ciprofloxacina/uso terapêutico , Farmacorresistência Bacteriana , Feminino , Gastroenterite/tratamento farmacológico , Hospitais de Ensino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Infecções Respiratórias/tratamento farmacológico , Sepse/tratamento farmacológicoRESUMO
Human L-ficolin (FCN) is a serum lectin characterized by a collagen-like and a fibrinogen-like domain that can activate the lectin pathway of complement. Structural and functional similarities to mannose-binding lectin (MBL) suggest a role for L-ficolin in innate immunity. Structural polymorphisms in the MBL2 gene lead to functional deficiency of MBL. Polymorphisms in the FCN2 gene have not been studied previously. We developed 10 denaturing gradient gel electrophoresis (DGGE) assays to screen a total of 188 Dutch Caucasians for polymorphisms in FCN2. Total gene screening in this large cohort revealed 10 single nucleotide polymorphisms (SNPs). Interestingly, two conserved coding SNPs were found in exon 8, leading to amino acid substitutions within the fibrinogen-like domain. Fibrinogen-like domains are highly conserved among several proteins in many species. As this domain is responsible for binding of L-ficolin, these newly found coding polymorphisms could alter the affinity of the protein for its substrates and possibly alter the ability of L-ficolin to recognize invading microorganisms.
Assuntos
Doadores de Sangue , Lectina de Ligação a Manose da Via do Complemento/genética , Lectinas/genética , Programas de Rastreamento/métodos , Polimorfismo de Nucleotídeo Único , Substituição de Aminoácidos/genética , Sequência de Bases , Bancos de Sangue , Sequência Conservada , DNA/química , Eletroforese em Gel de Poliacrilamida/métodos , Humanos , Países Baixos , Desnaturação de Ácido Nucleico , Fases de Leitura Aberta/genética , FicolinasRESUMO
An outbreak of psittacosis in a veterinary teaching hospital was recognized in December 2004. Outbreak management was instituted to evaluate the extent of the outbreak and to determine the avian source. Real-time PCR, serologic testing and sequencing of the ompA gene of Chlamydophila psittaci were performed. Sputum samples from patients, throat-swab samples from exposed students and staff, and faecal specimens from parrots and pigeons were tested. In this outbreak, 34 % (10/29) of the tested individuals were infected. The clinical features of the infection ranged from none to sepsis with multi-organ failure requiring intensive-care-unit admission. C. psittaci genotype A was identified as the outbreak strain. Parrots, recently exposed to a group of cockatiels coming from outside the teaching facility, which were used in a practical class, appeared to be the source of the outbreak. One of the tested pigeons harboured an unrelated C. psittaci genotype B strain. The microbiological diagnosis by real-time PCR on clinical specimens allowed for rapid outbreak management; subsequent genotyping of the isolates identified the avian source. Recommendations are made to reduce the incidence and extent of future outbreaks.
Assuntos
Chlamydophila psittaci/crescimento & desenvolvimento , Surtos de Doenças , Psitacose/epidemiologia , Zoonoses/microbiologia , Adulto , Amazona , Animais , Anticorpos Antibacterianos/sangue , Proteínas da Membrana Bacteriana Externa/química , Proteínas da Membrana Bacteriana Externa/genética , Sequência de Bases , Doenças das Aves/microbiologia , Chlamydophila psittaci/genética , Testes de Fixação de Complemento , DNA Bacteriano/química , DNA Bacteriano/genética , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Países Baixos/epidemiologia , Reação em Cadeia da Polimerase , Psitacose/microbiologia , Zoonoses/epidemiologia , Zoonoses/transmissãoRESUMO
OBJECTIVE: In this study we evaluate the value of baseline concentrations of acute-phase reactants on prognosis after percutaneous coronary intervention (PCI). METHODS: Blood samples were drawn immediately before PCI to measure baseline concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), lipoprotein(a) (Lp(a)), and fibrinogen. Follow-up data were collected at 8 months. Repeat PCI, CABG, myocardial infarction, and death were recorded as major adverse clinical events (MACE). Furthermore the recurrence of angina pectoris was noted. RESULTS: The study included 600 consecutive patients after a successful PCI. Sixty-four percent of the patients were stented. The mean age was 61.6 years and 68.9% were male. CRP levels were significantly higher in patients who were to have repeat angina as compared with those who were not (P=0.0322). IL-6 levels were not correlated with angina or MACE. Lp(a) and fibrinogen concentrations were both significantly related to MACE (P=0.0337 and P=0.0253, respectively). CONCLUSION: Our study clearly supports the role of inflammation in restenosis after PCI as measured in statistically higher levels of Lp(a) and fibrinogen in patients with MACE and CRP in patients with repeat angina.
Assuntos
Proteínas de Fase Aguda/análise , Angioplastia Coronária com Balão , Doença das Coronárias/sangue , Doença das Coronárias/terapia , Idoso , Biomarcadores/sangue , Proteína C-Reativa/análise , Doença das Coronárias/mortalidade , Feminino , Fibrinogênio/análise , Seguimentos , Humanos , Interleucina-6/sangue , Lipoproteína(a)/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Stents , Taxa de SobrevidaRESUMO
BACKGROUND: The aim of our study was to investigate the influence of prior cytomegalovirus (CMV) or Chlamydia pneumoniae (CP) infection on prognosis after percutaneous coronary intervention (PCI). METHODS: Using the enzyme-linked immunosorbent assay technique preprocedural anti-CMV immunoglobulin G and anti-CP immunoglobulin A (CP IgA), immunoglobulin M, and immunoglobulin G antibodies were measured. Repeat anginal complaints and major adverse clinical events (MACE), including PCI, coronary artery bypass grafting, myocardial infarction, and death, were recorded at 8-month follow-up. RESULTS: Six hundred consecutive patients were included after successful PCI. Sixty-four percent of the patients were stented. The mean age was 61.6 years, and 68.9% were male. The rate of seropositivity for CP IgA in patients with MACE as compared with patients without MACE was 50.9% versus 35.4% (P =.0276). In patients with repeat anginal complaints, CP IgA seropositivity was 41.6% versus 34.6% in patients without repeat angina (P =.1057). The negative effect of CP on prognosis was confirmed after calculating the odds ratios for MACE (1.9, 95% CI 1.1-3.3). The rates of seropositivity for anti-CMV immunoglobulin G were not significantly different between both groups, although we found an association between infectious burden and repeat angina pectoris (odds ratio 1.8, 95% CI 1.1-3.0). CONCLUSIONS: We conclude that preprocedural seropositivity of CP IgA is a risk factor for MACE and angina pectoris after PCI. Although no such relation was found for CMV alone, the cumulative infectious burden was also related to these clinical manifestations of restenosis.
Assuntos
Angioplastia Coronária com Balão , Infecções por Chlamydophila/complicações , Chlamydophila pneumoniae , Doença das Coronárias/terapia , Reestenose Coronária/etiologia , Infecções por Citomegalovirus/complicações , Angina Pectoris/etiologia , Chlamydophila pneumoniae/isolamento & purificação , Ponte de Artéria Coronária , Doença das Coronárias/complicações , Citomegalovirus/isolamento & purificação , Intervalo Livre de Doença , Feminino , Fibrinolíticos/uso terapêutico , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Prognóstico , RecidivaAssuntos
Coccidiostáticos/uso terapêutico , Toxoplasmose Ocular/diagnóstico , Quimioterapia Combinada , Feminino , Ácido Fólico/uso terapêutico , Humanos , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Pirimetamina/uso terapêutico , Sulfadiazina/uso terapêutico , Toxoplasmose Ocular/tratamento farmacológico , Toxoplasmose Ocular/patologia , Resultado do TratamentoRESUMO
BACKGROUND: Previously, we assessed selective digestive tract decontamination (SDD) and selective oropharyngeal decontamination (SOD) on survival and prevention of bacteraemia in patients in intensive-care units. In this analysis, we aimed to assess effectiveness of these interventions for prevention of respiratory tract colonisation and bacteraemia with highly resistant microorganisms acquired in intensive-care units. METHODS: We did an open-label, clustered group-randomised, crossover study in 13 intensive-care units in the Netherlands between May, 2004, and July, 2006. Participants admitted to intensive-care units with an expected duration of mechanical ventilation of more than 48 h or an expected stay of more than 72 h received SOD (topical tobramycin, colistin, and amphotericin B in the oropharynx), SDD (SOD antibiotics in the oropharynx and stomach plus 4 days' intravenous cefotaxime), or standard care. The computer-randomised order of study regimens was applied by an independent clinical pharmacist who was masked to intensive-care-unit identity. We calculated crude odds ratios (95% CI) for rates of bacteraemia or respiratory tract colonisation with highly resistant microorganisms in patients who stayed in intensive-care units for more than 3 days (ie, acquired infection). This trial is registered at http://isrctn.org, number ISRCTN35176830. FINDINGS: Data were available for 5927 (>99%) of 5939 patients, of whom 5463 (92%) were in intensive-care units for more than 3 days. 239 (13%) of 1837 patients in standard care acquired bacteraemia after 3 days, compared with 158 (9%) of 1758 in SOD (odds ratio 0·66, 95% CI 0·53-0·82), and 124 (7%) of 1868 in SDD (0·48, 0·38-0·60). Eight patients acquired bacteraemia with highly resistant microorganisms during SDD, compared with 18 patients (with 19 episodes) during standard care (0·41, 0·18-0·94; rate reduction [RR] 59%, absolute risk reduction [ARR] 0·6%) and 20 during SOD (0·37, 0·16-0·85; RR 63%, ARR 0·7%). Of the patients staying in intensive-care units for more than 3 days, we obtained endotracheal aspirate cultures for 881 (49%) patients receiving standard care, 886 (50%) receiving SOD, and 828 (44%) receiving SDD. 128 (15%) patients acquired respiratory tract colonisation with highly resistant microorganisms during standard care, compared with 74 (8%) during SDD (0·58, 0·43-0·78; RR 38%, ARR 5·5%) and 88 (10%) during SOD (0·65, 0·49-0·87; RR 32%, ARR 4·6%). Acquired respiratory tract colonisation with Gram-negative bacteria or cefotaxime-resistant and colistin-resistant pathogens was lowest during SDD. INTERPRETATION: Widespread use of SDD and SOD in intensive-care units with low levels of antibiotic resistance is justified. FUNDING: None.
Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Descontaminação/métodos , Farmacorresistência Bacteriana , Trato Gastrointestinal/microbiologia , Orofaringe/microbiologia , Bactérias/efeitos dos fármacos , Estudos Cross-Over , Farmacorresistência Fúngica , Humanos , Unidades de Terapia IntensivaRESUMO
Polymorphisms leading to deficiency of mannose-binding lectin (MBL) are associated with predisposition to infection. However, MBL deficiency can be protective against intracellular pathogens that use MBL to enter host cells. The role of MBL genotype and activity in infection with the intracellular pathogen Legionella pneumophila was studied in a large outbreak of legionellosis at a Dutch flower show. A total of 141 patients, 65 exposed asymptomatic exhibition staff members and 670 unexposed blood bank donors were included for the study of MBL2 genotypes and MBL-mediated complement activation. Genotypic MBL deficiency was equally prevalent in patients and controls. Deficient MBL-mediated complement activation was more prevalent in patients. Even in patients with genotypes that confer MBL sufficiency, 20.6% lacked MBL-mediated complement activation. In most patients with MBL-sufficient genotypes who lacked MBL-mediated activation at the acute phase of disease, lectin pathway functionality was restored at convalescence. In conclusion, genotypic MBL deficiency was not a risk factor for legionellosis. However, patients with legionellosis displayed deficient MBL-mediated complement activation even with MBL-sufficient genotypes. Together, these genotypical and functional data suggest that the observed deficiency of lectin pathway activation is an effect of legionellosis rather than a risk factor for acquiring it.
Assuntos
Doença dos Legionários/fisiopatologia , Lectina de Ligação a Manose/genética , Lectina de Ligação a Manose/metabolismo , Pneumonia Bacteriana/fisiopatologia , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Doadores de Sangue , Estudos de Casos e Controles , Ativação do Complemento/genética , Surtos de Doenças , Feminino , Genótipo , Humanos , Doença dos Legionários/genética , Masculino , Lectina de Ligação a Manose/sangue , Lectina de Ligação a Manose/deficiência , Pessoa de Meia-Idade , Pneumonia Bacteriana/genéticaRESUMO
A real-time PCR for the ABI Prism 7000 system targeting the 23S-5S spacer of Legionella spp. was developed. Simultaneous detection and differentiation of Legionella spp. and Legionella pneumophila within 90 min and without post-PCR melting-curve analysis was achieved using two TaqMan probes. In sputum samples from 23 controls and 17 patients with legionellosis, defined by positive culture, urinary antigen testing, or seroconversion, 94% sensitivity and 100% specificity were observed.