RESUMO
OBJECTIVES: The aim was to analyse the population pharmacokinetics of colistin and to explore the relationship between colistin exposure and time to death. METHODS: Patients included in the AIDA randomized controlled trial were treated with colistin for severe infections caused by carbapenem-resistant Gram-negative bacteria. All subjects received a 9 million units (MU) loading dose, followed by a 4.5 MU twice daily maintenance dose, with dose reduction if creatinine clearance (CrCL) < 50 mL/min. Individual colistin exposures were estimated from the developed population pharmacokinetic model and an optimized two-sample per patient sampling design. Time to death was evaluated in a parametric survival analysis. RESULTS: Out of 406 randomized patients, 349 contributed pharmacokinetic data. The median (90% range) colistin plasma concentration was 0.44 (0.14-1.59) mg/L at 15 minutes after the end of first infusion. In samples drawn 10 hr after a maintenance dose, concentrations were >2 mg/L in 94% (195/208) and 44% (38/87) of patients with CrCL ≤120 mL/min, and >120 mL/min, respectively. Colistin methanesulfonate sodium (CMS) and colistin clearances were strongly dependent on CrCL. High colistin exposure to MIC ratio was associated with increased hazard of death in the multivariate analysis (adjusted hazard ratio (95% CI): 1.07 (1.03-1.12)). Other significant predictors included SOFA score at baseline (HR 1.24 (1.19-1.30) per score increase), age and Acinetobacter or Pseudomonas as index pathogen. DISCUSSION: The population pharmacokinetic model predicted that >90% of the patients had colistin concentrations >2 mg/L at steady state, but only 66% at 4 hr after start of treatment. High colistin exposure was associated with poor kidney function, and was not related to a prolonged survival.
Assuntos
Antibacterianos/farmacocinética , Colistina/farmacocinética , Farmacorresistência Bacteriana , Infecções por Bactérias Gram-Negativas/mortalidade , Antibacterianos/sangue , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias/efeitos dos fármacos , Carbapenêmicos/farmacologia , Colistina/sangue , Colistina/farmacologia , Colistina/uso terapêutico , Estado Terminal , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , HumanosRESUMO
OBJECTIVES: The aim of the study was to measure the impact of antibiotic exposure on the acquisition of colonization with extended-spectrum ß-lactamase-producing Gram-negative bacteria (ESBL-GNB) accounting for individual- and group-level confounding using machine-learning methods. METHODS: Patients hospitalized between September 2010 and June 2013 at six medical and six surgical wards in Italy, Serbia and Romania were screened for ESBL-GNB at hospital admission, discharge, antibiotic start, and after 3, 7, 15 and 30 days. Primary outcomes were the incidence rate and predictive factors of new ESBL-GNB colonization. Random forest algorithm was used to rank antibiotics according to the risk of selection of ESBL-GNB colonization in patients not colonized before starting antibiotics. RESULTS: We screened 10 034 patients collecting 28 322 rectal swab samples. New ESBL-GNB colonization incidence with and without antibiotic treatment was 22/1000 and 9/1000 exposure-days, respectively. In the adjusted regression analyses, antibiotic exposure (hazard ratio (HR) 2.38; 95% CI 1.29-4.40), age 60-69 years (HR 1.19; 95% CI 1.05-1.34), and spring season (HR 1.25; 95% CI 1.14-1.38) were independently associated with new colonization. Monotherapy ranked higher als combination therapy in promoting ESBL-GNB colonization. Among monotherapy, cephalosporins ranked first followed by tetracycline (second), macrolide (fourth) and cotrimoxazole (seventh). Overall the ranking of cephalosporins was lower when used in combination. Among combinations not including cephalosporins, quinolones plus carbapenems ranked highest (eighth). Among sequential therapies, quinolones ranked highest (tenth) when prescribed within 30 days of therapy with cephalosporins. CONCLUSIONS: Impact of antibiotics on selecting ESBL-GNB at intestinal level varies if used in monotherapy or combination and according to previous antibiotic exposure. These finding should be explored in future clinical trials on antibiotic stewardship interventions. CLINICAL TRIAL REGISTRATION: NCT01208519.
Assuntos
Antibacterianos/uso terapêutico , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/epidemiologia , Aprendizado de Máquina , Adolescente , Adulto , Idoso , Quimioterapia Combinada , Feminino , Bactérias Gram-Negativas/enzimologia , Infecções por Bactérias Gram-Negativas/microbiologia , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Itália , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Romênia , Sérvia , Adulto Jovem , beta-LactamasesRESUMO
OBJECTIVES: High-quality diagnosis of bloodstream infections (BSI) is important for successful patient management. As knowledge on current practices of microbiological BSI diagnostics is limited, this project aimed to assess its current state in European microbiological laboratories. METHODS: We performed an online questionnaire-based cross-sectional survey comprising 34 questions on practices of microbiological BSI diagnostics. The ESCMID Study Group for Bloodstream Infections, Endocarditis and Sepsis (ESGBIES) was the primary platform to engage national coordinators who recruited laboratories within their countries. RESULTS: Responses were received from 209 laboratories in 25 European countries. Although 32.5% (68/209) of laboratories only used the classical processing of positive blood cultures (BC), two-thirds applied rapid technologies. Of laboratories that provided data, 42.2% (78/185) were able to start incubating BC in automated BC incubators around-the-clock, and only 13% (25/192) had established a 24-h service to start immediate processing of positive BC. Only 4.7% (9/190) of laboratories validated and transmitted the results of identification and antimicrobial susceptibility testing (AST) of BC pathogens to clinicians 24 h/day. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry from briefly incubated sub-cultures on solid media was the most commonly used approach to rapid pathogen identification from positive BC, and direct disc diffusion was the most common rapid AST method from positive BC. CONCLUSIONS: Laboratories have started to implement novel technologies for rapid identification and AST for positive BC. However, progress is severely compromised by limited operating hours such that current practice of BC diagnostics in Europe complies only partly with the requirements for optimal BSI management.
Assuntos
Testes Diagnósticos de Rotina/métodos , Técnicas Microbiológicas/métodos , Técnicas de Diagnóstico Molecular/métodos , Sepse/diagnóstico , Estudos Transversais , Europa (Continente) , HumanosRESUMO
OBJECTIVES: Intestinal carriage with extended spectrum ß-lactamase Enterobacteriaceae (ESBL-E) and carbapenemase-producing Enterobacteriaceae (CPE) can persist for months. We aimed to evaluate whether oral antibiotics followed by faecal microbiota transplantation (FMT) can eradicate intestinal carriage with ESBL-E/CPE. METHODS: Randomized, open-label, superiority trial in four tertiary-care centres (Geneva (G), Paris (P), Utrecht (U), Tel Aviv (T)). Non-immunocompromised adult patients were randomized 1: 1 to either no intervention (control) or a 5-day course of oral antibiotics (colistin sulphate 2 × 106 IU 4×/day; neomycin sulphate 500 mg 4×/day) followed by frozen FMT obtained from unrelated healthy donors. The primary outcome was detectable intestinal carriage of ESBL-E/CPE by stool culture 35-48 days after randomization (V4). ClinicalTrials.govNCT02472600. The trial was funded by the European Commission (FP7). RESULTS: Thirty-nine patients (G = 14; P = 16; U = 7; T = 2) colonized by ESBL-E (n = 36) and/or CPE (n = 11) were enrolled between February 2016 and June 2017. In the intention-to-treat analysis 9/22 (41%) patients assigned to the intervention arm were negative for ESBL-E/CPE at V4 (1/22 not receiving the intervention imputed as positive) whereas in the control arm 5/17 (29%) patients were negative (one lost to follow up imputed as negative) resulting in an OR for decolonization success of 1.7 (95% CI 0.4-6.4). Study drugs were well tolerated overall but three patients in the intervention group prematurely stopped the study antibiotics because of diarrhoea (all received FMT). CONCLUSIONS: Non-absorbable antibiotics followed by FMT slightly decreased ESBL-E/CPE carriage compared with controls; this difference was not statistically significant, potentially due to early trial termination. Further clinical investigations seem warranted.
Assuntos
Antibacterianos/uso terapêutico , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Infecções por Enterobacteriaceae/tratamento farmacológico , Transplante de Microbiota Fecal , Administração Oral , Idoso , Portador Sadio/tratamento farmacológico , Portador Sadio/microbiologia , Colistina/uso terapêutico , Esquema de Medicação , Farmacorresistência Bacteriana Múltipla , Fezes/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Centros de Atenção Terciária , beta-LactamasesRESUMO
OBJECTIVES: The rise in carbapenem resistance among Gram-negative bacteria has renewed interest in colistin. Recently, the EUCAST-CLSI Polymyxin Breakpoints Working Group declared that broth microdilution (BMD) is the only valid method for colistin susceptibility testing. BMD is not easily incorporated into the routine work of clinical laboratories, and usually this test is incorporated serially, resulting in delayed susceptibility reporting. We tested a strategy of combining VITEK® 2 with a 2 µg/mL colistin agar dilution (VITEK® 2/AD) screening plate to improve performance and time to reporting of colistin susceptibility. METHODS: Colistin susceptibility for 364 clinical isolates was determined by VITEK® 2/AD and compared with the reference standard BMD according to the ISO 20776-1:2007 and CLSI guidelines. The EUCAST colistin susceptibility breakpoint of ≤2 µg/mL was used. Escherichia coli NCTC 13846 served as quality control strain. Agreement, very major error (VME) and major error rates were determined using ISO 20776-2:2007. RESULTS: The VME rate for VITEK® 2 alone was 30.6% (15/49, 95% CI 18.3-45.4%), and was reduced to 10.2% (5/49, 95% CI 3.4-22.2%) using the VITEK® 2/AD combined testing. The combined testing had categorical agreement with BMD of 97% (354/364, 95% CI 95.0-98.7%), and a major error (ME) rate of 1.6% (5/315, 95% CI 0.5-3.7%). Using the combined testing, even against challenging strains, 349 (95.8%, 95% CI 93.3-97.7%) colistin susceptibility results could be reported, and only 15 isolates required further analysis by BMD. DISCUSSION: Our method is simple to apply and allows rapid reporting of colistin susceptibility.
Assuntos
Antibacterianos/farmacologia , Colistina/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/microbiologia , Programas de Rastreamento/métodos , Testes de Sensibilidade Microbiana/métodos , Ágar , Meios de Cultura , Humanos , Fatores de TempoRESUMO
PURPOSE: There are few data in the literature regarding sepsis or septic shock due to extended-spectrum ß-lactamases (ESBL)-producing Enterobacteriaceae (E). The aim of this study was to assess predictors of outcome in septic patients with bloodstream infection (BSI) caused by ESBL-E. METHODS: Patients with severe sepsis or septic shock and BSI due to ESBL-E were selected from the INCREMENT database. The primary endpoint of the study was the evaluation of predictors of outcome after 30 days from development of severe sepsis or septic shock due to ESBL-E infection. Three cohorts were created for analysis: global, empirical-therapy and targeted-therapy cohorts. RESULTS: 367 septic patients were analysed. Overall mortality was 43.9% at 30 days. Escherichia coli (62.4%) and Klebsiella pneumoniae (27.2%) were the most frequent isolates. ß-lactam/ß-lactamase inhibitor (BLBLI) combinations were the most empirically used drug (43.6%), followed by carbapenems (29.4%). Empirical therapy was active in vitro in 249 (67.8%) patients, and escalation of antibiotic therapy was reported in 287 (78.2%) patients. Cox regression analysis showed that age, Charlson Comorbidity Index, McCabe classification, Pitt bacteremia score, abdominal source of infection and escalation of antibiotic therapy were independently associated with 30-day mortality. No differences in survival were reported in patients treated with BLBLI combinations or carbapenems in empirical or definitive therapy. CONCLUSIONS: BSI due to ESBL-E in patients who developed severe sepsis or septic shock was associated with high 30-day mortality. Comorbidities, severity scores, source of infection and antibiotic therapy escalation were important determinants of unfavorable outcome.
Assuntos
Técnicas de Apoio para a Decisão , Infecções por Enterobacteriaceae/diagnóstico , Infecções por Enterobacteriaceae/mortalidade , Enterobacteriaceae/enzimologia , Sepse/diagnóstico , Sepse/mortalidade , beta-Lactamases/metabolismo , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Quimioterapia Combinada , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Sepse/tratamento farmacológico , Sepse/microbiologia , Análise de Sobrevida , Resultado do Tratamento , Inibidores de beta-Lactamases/uso terapêutico , beta-Lactamas/uso terapêuticoRESUMO
We determined the prevalence of anti-hepatitis B surface antibodies (anti-HBs) among children and adolescents vaccinated for hepatitis B virus in infancy as part of the routine vaccination programme. A representative serum sample of the Israeli population age 0-19 was tested. In a separate pilot study, a booster dose of hepatitis B vaccine was administered to 31 candidates for national service, who were fully vaccinated in infancy and tested negative for hepatitis B surface antibodies at age 17-19 years and anti-HBs antibodies were assessed 8 weeks later. Of the 1273 samples tested, 631 (49·6%) were positive to anti-HBs antibodies. Seropositivity rates were 89·5% among infants aged 6-12 months and declined significantly with age to 20·7% at age 19 years. No differences in seropositivity rates were observed between Jews and Arabs, males and females and those born in Israel and in other countries. Seroconversion rate among the 31 individuals who received a booster dose was 90·3% (95% CI: 75·1-96·6%). We recommend a booster dose for healthcare personnel before starting to work at the health care facility.
Assuntos
Anticorpos Anti-Hepatite B/sangue , Vacinas contra Hepatite B/administração & dosagem , Hepatite B/prevenção & controle , Imunização Secundária , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Feminino , Hepatite B/epidemiologia , Hepatite B/virologia , Vírus da Hepatite B/imunologia , Humanos , Lactente , Recém-Nascido , Israel/epidemiologia , Masculino , Projetos Piloto , Prevalência , Estudos Soroepidemiológicos , Adulto JovemRESUMO
OBJECTIVES: To compare the efficacy, safety and satisfaction from two modes of oral analgesia administration for the treatment of post-caesarean pain in the first 48 h following surgery: on-demand versus fixed time interval administration. DESIGN: Open label parallel-group, randomised-controlled trial from February to December 2013. SETTING: University-affiliated hospital in Israel. POPULATION: Two-hundred women who underwent caesarean delivery with regional anaesthesia. METHODS: Patients were randomly assigned to receive predetermined combinations of tramadol, paracetamol and diclofenac either following patient demand or at predetermined 6-h intervals for the first 48 h. If the patient requested additional analgesia, Percocet (oxycodone and paracetamol) was given as a rescue treatment. MAIN OUTCOME MEASURES: Pain intensity and satisfaction were self-evaluated with visual analogue scale of 0 (no pain/least satisfaction) to 10 (worst pain/highest satisfaction). Breastfeeding, need for supplemental formula, and maternal and neonatal adverse effects were also evaluated. RESULTS: The 'fixed time interval' group, compared with the 'on-demand' group, had lower mean pain score (2.8 ± 0.84 versus 4.1 ± 0.48, respectively; P < 0.0001), higher satisfaction rate (9.1 ± 1.2 versus 8.3 ± 1.5, respectively; P < 0.0001), more breastfeeds (23.7 ± 6.5 versus 19.2 ± 6.2, respectively; P < 0.0001) and less use of supplemental formulas (8.2 ± 5.2 versus 11.9 ± 6.5, respectively; P < 0.0001). The number of times that drugs were given was slightly higher in the 'fixed time interval' group without an increase in maternal adverse effects, which were mild. No adverse effects were reported for the neonates. CONCLUSION: Administration of oral analgesia in fixed time intervals is superior to drug administration following patient demand without increasing maternal or neonatal adverse outcomes. TWEETABLE ABSTRACT: Oral analgesia in fixed time intervals is superior to analgesia following demand.
Assuntos
Analgesia Obstétrica/métodos , Analgésicos/administração & dosagem , Cesárea/efeitos adversos , Dor Pós-Operatória/tratamento farmacológico , Acetaminofen/administração & dosagem , Acetaminofen/efeitos adversos , Administração Oral , Adulto , Analgesia Obstétrica/efeitos adversos , Analgésicos/efeitos adversos , Diclofenaco/administração & dosagem , Diclofenaco/efeitos adversos , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Recém-Nascido , Israel , Oxicodona/administração & dosagem , Oxicodona/efeitos adversos , Manejo da Dor/métodos , Medição da Dor/métodos , Satisfação do Paciente/estatística & dados numéricos , Gravidez , Tramadol/administração & dosagem , Tramadol/efeitos adversos , Resultado do TratamentoRESUMO
We evaluated the sensitivity of surveillance cultures for carbapenem-resistant Acinetobacter baumannii (CRAB) in patients and in their environment. Patients with a CRAB-positive clinical culture were sampled within 7 days; the buccal mucosa and rectum were sampled using swabs, and skin was sampled using pre-moistened sterile sponges. Sponges were also used to sample the surrounding environment. Specimens were inoculated onto CHROMagar MDR Acinetobacter plates both directly and after overnight enrichment. CRAB load was scored semi-quantitatively and composite scores for patient colonization and environmental contamination were calculated. Thirty-four patients were included. Screening sensitivity was 28/34 (82%) for buccal mucosa, 30/34 (88%) for skin, and 25/34 (74%) for rectum. Combined sensitivity was 32/34 (94%). Among patients with CRAB-positive respiratory cultures, sensitivity for buccal mucosa was 20/20 (100%). Direct inoculation had excellent sensitivity: 25/28 (89%) for all three sites combined. In the subgroup of patients who did not have a respiratory source for CRAB, direct inoculation sensitivity was lower than among patients with CRAB-positive respiratory cultures: 5/8 (63%) versus 20/20 (100%). The environment of all patients was contaminated with CRAB. There was a positive correlation between the patient colonization score and the environmental contamination score (r = 0.63, p <0.001; r = 0.4, p 0.04 for buccal mucosa, r = 0.7, p <0.001 for skin, and r = 0.46, p 0.14 for rectum). In conclusion, screening for CRAB carriers can be performed by direct plating of skin and buccal mucosa samples. Environmental contamination is common and can be monitored. Implementing screening may facilitate infection control efforts to limit the spread of CRAB.
Assuntos
Infecções por Acinetobacter/diagnóstico , Acinetobacter baumannii/efeitos dos fármacos , Portador Sadio/microbiologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Microbiologia Ambiental , Feminino , Humanos , Controle de Infecções , Masculino , Testes de Sensibilidade Microbiana , Boca/microbiologia , Reto/microbiologia , Pele/microbiologiaRESUMO
Rapid identification of the causative pathogen in patients with bacteremia allows adjustment of antibiotic therapy and improves patient outcomes. We compared in vitro and real-life time to detection (TTD) of two blood culture media, BacT/Alert FA (FA) and BacT/Alert FA Plus (FA Plus), for the nine most common species of bacterial pathogens recovered from blood samples. Experimental data from simulated cultures was compared with microbiology records of TTD for both culture media with growth of the species of interest in clinical blood cultures. In the experimental conditions, median TTD was 3.8 hours (23.9 %) shorter using FA Plus media. The magnitude of reduction differed between species. Similarly, in real life data, FA Plus had shorter TTD than FA media; however, the difference between culture media was smaller, and median TTD was only 1 hour (8.5 %) less. We found shorter TTD with BacT/Alert FA Plus culture media, both experimentally and in real-life conditions and unrelated to antibiotic neutralization, highlighting the importance of appropriate blood culture media selection.
Assuntos
Bacteriemia/diagnóstico , Hemocultura/métodos , Meios de Cultura/química , Humanos , Estudos Retrospectivos , Fatores de TempoRESUMO
Antibiotic consumption is an easily quantifiable performance measure in hospitals and might be used for monitoring. We conducted a review of published studies and online surveillance reports reporting on antibiotic consumption in acute care hospitals between the years 1997 and 2013. A pooled estimate of antibiotic consumption was calculated using a random effects meta-analysis of rates with 95% confidence intervals. Heterogeneity was assessed through subgroup analysis and metaregression. Eighty studies, comprising data from 3130 hospitals, met the inclusion criteria. The pooled rate of hospital-wide consumption was 586 (95% confidence interval 540 to 632) defined daily doses (DDD)/1000 hospital days (HD) for all antibacterials. However, consumption rates were highly heterogeneous. Antibacterial consumption was highest in intensive care units, at 1563 DDD/1000 HD (95% confidence interval 1472 to 1653). Hospital-wide antibacterial consumption was higher in Western Europe and in medium-sized, private and university-affiliated hospitals. The methods of data collection were significantly associated with consumption rates, including data sources, dispensing vs. purchase vs. usage data, counting admission and discharge days and inclusion of low-consumption departments. Heterogeneity remained in all subgroup analyses. Major heterogeneity currently precludes defining acceptable antibiotic consumption ranges in acute care hospitals. Guidelines on antibiotic consumption reporting that will account for case mix and a minimal set of hospital characteristics recommending standardized methods for monitoring and reporting are needed.
Assuntos
Antibacterianos/uso terapêutico , Cuidados Críticos/métodos , Uso de Medicamentos , Europa (Continente) , Hospitais , Humanos , Projetos de Pesquisa/normasRESUMO
Since 2013, four hospitals in northern Israel have been providing care for Syrian nationals, primarily those wounded in the ongoing civil war. We analyzed carbapenemase-producing Enterobacteriaceae (CPE) isolates obtained from these patients. Isolate identification was performed using the VITEK 2 system. Polymerase chain reaction (PCR) was performed for the presence of bla KPC, bla NDM, and bla OXA-48. Susceptibility testing and genotyping were performed on selected isolates. During the study period, 595 Syrian patients were hospitalized, most of them young men. Thirty-two confirmed CPE isolates were grown from cultures taken from 30 patients. All but five isolates were identified as Klebsiella pneumoniae and Escherichia coli. Nineteen isolates produced NDM and 13 produced OXA-48. Among a further 29 isolates tested, multilocus sequence typing (MLST) showed that ST278 and ST38 were the major sequence types among the NDM-producing K. pneumoniae and OXA-48-producing E. coli isolates, respectively. Most were resistant to all three carbapenems in use in Israel and to gentamicin, but susceptible to colistin and fosfomycin. The source for bacterial acquisition could not be determined; however, some patients admitted to different medical centers were found to carry the same sequence type. CPE containing bla NDM and bla OXA-48 were prevalent among Syrian wounded hospitalized patients in northern Israel. The finding of the same sequence type among patients at different medical centers implies a common, prehospital source for these patients. These findings have implications for public health throughout the region.
Assuntos
Proteínas de Bactérias/genética , Infecções por Enterobacteriaceae/microbiologia , Enterobacteriaceae/enzimologia , Infecção dos Ferimentos/microbiologia , beta-Lactamases/genética , Adolescente , Adulto , Técnicas de Tipagem Bacteriana , Enterobacteriaceae/classificação , Enterobacteriaceae/genética , Enterobacteriaceae/isolamento & purificação , Feminino , Genótipo , Hospitais , Humanos , Israel , Masculino , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Reação em Cadeia da Polimerase , Síria , Guerra , Adulto JovemRESUMO
Antibacterial therapy is one of the most important medical developments of the twentieth century; however, the spread of resistance in healthcare settings and in the community threatens the enormous gains made by the availability of antibiotic therapy. Infections caused by resistant bacteria lead to up to two-fold higher rates of adverse outcomes compared with similar infections caused by susceptible strains. These adverse outcomes may be clinical or economic and reflect primarily the failure or delay of antibiotic treatment. The magnitude of these adverse outcomes will be more pronounced as disease severity, strain virulence, or host vulnerability increases. The negative impacts of antibacterial resistance can be measured at the patient level by increased morbidity and mortality, at the healthcare level by increased resource utilization, higher costs and reduced hospital activity and at the society level by antibiotic treatment guidelines favouring increasingly broad-spectrum empiric therapy. In this review we will discuss the negative impact of antibiotic resistance on patients, the healthcare system and society.
Assuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Farmacorresistência Bacteriana , Infecções Bacterianas/economia , Custos de Cuidados de Saúde , Humanos , Falha de TratamentoRESUMO
In a 2008-2011 survey, 17,945 patients in 18 hospital units in Europe and Israel were screened for carriage of Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae, resulting in identification of 124 positive patients. The isolates were dominated by Klebsiella pneumoniae sequence type 258 (ST258) KPC-2 and ST512 KPC-3, mainly from Greece and Italy, respectively, whereas Israeli isolates were of diverse species, clones, and KPC variants. Various blaKPC platforms were observed, among which IncFIIK-FIBK plasmids with blaKPC-2/-3 genes in the Tn4401a transposon prevailed.
Assuntos
Antibacterianos/uso terapêutico , Proteínas de Bactérias/biossíntese , Proteínas de Bactérias/genética , Carbapenêmicos/uso terapêutico , Infecções por Enterobacteriaceae/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , beta-Lactamases/biossíntese , beta-Lactamases/genética , Citrobacter freundii/efeitos dos fármacos , Citrobacter freundii/genética , Citrobacter freundii/isolamento & purificação , Elementos de DNA Transponíveis/genética , Infecções por Enterobacteriaceae/microbiologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Europa (Continente) , Humanos , Israel , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/isolamento & purificação , Plasmídeos/genéticaRESUMO
OBJECTIVES: The objective of this study was to examine Klebsiella oxytoca clonal and phylogenetic diversity, based on an international collection of carriage isolates non-susceptible to expanded-spectrum cephalosporins (ESCs). METHODS: The study material comprised 68 rectal carriage K. oxytoca isolates non-susceptible to ESCs recovered in 2008-11 from patients in 14 hospitals across Europe and Israel. ESC resistance was tested phenotypically; genes encoding ESBLs, AmpC cephalosporinases and carbapenemases were amplified and sequenced. The isolates were typed by PFGE and MLST, followed by sequencing of blaOXY genes. RESULTS: MLST and PFGE distinguished 34 STs and 47 pulsotypes among the isolates, respectively. Six STs were split into several pulsotypes each. Five STs were more prevalent (nâ=â2-9) and occurred in several countries each, including ST2, ST9 and ST141, which belong to a growing international clonal complex (CC), CC2. Four phylogenetic lineages were distinguished, each with another type of chromosomal OXY-type ß-lactamase. Three of these, with OXY-1/-5, OXY-2 types and OXY-4, corresponded to previously described phylogroups KoI, KoII and KoIV, respectively. A single isolate from Israel represented a distinct lineage with a newly defined OXY-7 type. The phylogroups showed interesting differences in mechanisms of ESC resistance; KoI strains rarely overexpressed the OXY enzymes but commonly produced ESBLs, whereas KoII strains often were OXY hyperproducers and carried ESBLs much less frequently. AmpCs (DHA-1) and carbapenemases (VIM-1) occurred sporadically. CONCLUSIONS: The study confirmed the high genetic diversity of the collection of K. oxytoca ESC-non-susceptible isolates, composed of phylogroups with distinct types of OXY-type ß-lactamases, and revealed some STs of broad geographical distribution.
Assuntos
Antibacterianos/farmacologia , Cefalosporinas/farmacologia , Genótipo , Infecções por Klebsiella/microbiologia , Klebsiella oxytoca/classificação , Klebsiella oxytoca/efeitos dos fármacos , Resistência beta-Lactâmica , Portador Sadio/epidemiologia , Portador Sadio/microbiologia , Europa (Continente)/epidemiologia , Fezes/microbiologia , Variação Genética , Hospitais , Humanos , Israel/epidemiologia , Infecções por Klebsiella/epidemiologia , Klebsiella oxytoca/genética , Klebsiella oxytoca/isolamento & purificação , Testes de Sensibilidade Microbiana , Tipagem Molecular , Filogenia , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , beta-Lactamases/genéticaRESUMO
BACKGROUND: Israel has been the destination of large numbers of illegal migrants from East African countries in recent years. Despite efforts to detect and treat active tuberculosis (TB) at the border, 75% of all active TB cases diagnosed in our hospital were illegal migrants. In 2012, there was a large-scale TB exposure in our maternity ward, neonatal, and paediatric intensive care units following the admission of an infectious but apparently asymptomatic migrant who was in labour. A hospital-wide screening programme was subsequently implemented to prevent exposure of patients and staff to TB. AIM: To report the results of the first year of this intervention in the maternity hospital. METHODS: All illegal migrants from countries where TB is highly prevalent were screened by chest radiography (CR) upon admission to the maternity hospital. The results were immediately categorized by a radiologist as either 'suggestive of active pulmonary TB' or 'non-suggestive'. Patients with CR suggestive of TB were placed in airborne isolation and underwent further evaluation. FINDINGS: Four hundred and thirty-one apparently asymptomatic migrant women underwent CR screening. Most (363, 84%) presented in labour. Eleven women (2.6%) had a CR suggestive of active pulmonary TB which was confirmed in three (0.7% of screened women). No TB cases were missed by the CRs. Neither patients nor hospital staff were exposed to TB. CONCLUSION: Targeted CR screening for TB among high-risk women upon their admission to a maternity hospital had a high yield and was an effective strategy to prevent in-hospital transmission of TB.
Assuntos
Transmissão de Doença Infecciosa/prevenção & controle , Programas de Rastreamento/métodos , Migrantes/estatística & dados numéricos , Tuberculose/prevenção & controle , Adulto , Antibioticoprofilaxia/métodos , Antituberculosos/uso terapêutico , Feminino , Maternidades/estatística & dados numéricos , Humanos , Recém-Nascido , Isoniazida/uso terapêutico , Israel/epidemiologia , Masculino , Mycobacterium tuberculosis/isolamento & purificação , Isolamento de Pacientes , Valor Preditivo dos Testes , Gravidez , Prevalência , Radiografia , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Tuberculose/transmissão , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/diagnóstico por imagem , Tuberculose Pulmonar/transmissãoRESUMO
OBJECTIVES: The objective of this study was to perform a multinational survey of patients' colonization by metallo-ß-lactamase (MBL)-producing Enterobacteriaceae, including their molecular characterization. METHODS: Patients in 18 hospital units across Europe and Israel (nâ=â17â945) were screened between mid-2008 and mid-2011. MBL-producing isolates were typed by PFGE and MLST. MBL genes were amplified and sequenced within their integrons. Plasmids with MBL genes were analysed by nuclease S1 plus hybridization profiling, mating and transformation assays, and by PCR-based replicon typing. RESULTS: Ninety-one patients in nine centres (six countries), including 62 patients in two Greek ICUs, carried 94 non-duplicate MBL-producing organisms. Klebsiella pneumoniae isolates from Greece dominated (nâ=â57) and belonged mainly to ST147, ST36 and ST383. All but one of the isolates expressed VIM-1-type MBLs. Isolates of Greek origins produced five enzymes, including new VIM-39, encoded by class 1 integrons of four types. In-e541-like elements prevailed, comprising six variants located on IncR, IncFIIK, IncRâ+âFIIK, IncRâ+âA/C or non-typeable plasmids. The other group were new In4873 and In4863, being the first In416-like elements identified in Greece, which were present on IncA/C or non-typeable plasmids. Isolates from other countries produced only VIM-1 and the major integron was In916, identified in 16 organisms from France, Italy and Spain. In916 was carried by four plasmid types, including IncA/C, IncFIIK and IncHI2. Other integrons included a new element, In3103, in Spain and In110 identified only in Latvia. CONCLUSIONS: This study provided fully comparable data on the occurrence and molecular characteristics of VIM-producing Enterobacteriaceae in a group of hospital units across Europe, documenting recent changes in their epidemiology.
Assuntos
Portador Sadio/epidemiologia , Infecções por Enterobacteriaceae/epidemiologia , Enterobacteriaceae/enzimologia , beta-Lactamases/metabolismo , Portador Sadio/microbiologia , DNA Bacteriano/química , DNA Bacteriano/genética , Eletroforese em Gel de Campo Pulsado , Enterobacteriaceae/classificação , Enterobacteriaceae/genética , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/microbiologia , Europa (Continente)/epidemiologia , Genes Bacterianos , Hospitais , Humanos , Unidades de Terapia Intensiva , Epidemiologia Molecular , Tipagem de Sequências Multilocus , Plasmídeos/análise , Reação em Cadeia da Polimerase , Análise de Sequência de DNARESUMO
Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae is a pathogen causing an epidemic of carbapenem-resistant Enterobacteriaceae (CRE) in healthcare settings in developed countries. The spread is primarily by patient-to-patient transmission. Understanding the mode of spread is important for designing effective control measures. We studied CRE dissemination by quantifying environmental contamination from the vicinity of 34 carriers using selective contact plates. We examined rectal CRE concentrations and clinical characteristics and correlated these with environmental contamination. Eight (24%) carriers were non-spreaders: no CRE was detected in their vicinity. Faecal continence was the only independent predictor of being a non-spreader. Among the 26 spreaders, we identified a distinct group of six (18%) super-spreaders who accounted for 79% of environmental colonies detected. Super-spreaders were likely to have high rectal CRE concentrations and to have been admitted with respiratory disease. CRE spread to the environment follows the 20/80 rule: 20% of carriers are responsible for 80% of shedding and may play a central role in CRE transmission.
Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/análise , Carbapenêmicos/farmacologia , Infecção Hospitalar/epidemiologia , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/enzimologia , Resistência beta-Lactâmica , beta-Lactamases/análise , Idoso , Idoso de 80 Anos ou mais , Portador Sadio/epidemiologia , Portador Sadio/microbiologia , Infecção Hospitalar/microbiologia , Infecção Hospitalar/transmissão , Transmissão de Doença Infecciosa , Microbiologia Ambiental , Feminino , Humanos , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/transmissão , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Reto/químicaRESUMO
Little is known about the molecular epidemiology of Klebsiella pneumoniae carbapenemase-producing Escherichia coli (KPCEC). We aimed to describe the clonal structure and resistance mechanisms of KPCEC in a multicenter study. The study included 88 isolates from four medical centres in Israel: Tel Aviv Medical Center (n = 17), Laniado Medical Center (n = 12), Sha'are-Zedek Medical Center (n = 38), and Rambam Medical Center (n = 21). Twelve (14%) KPCEC were from clinical sites and 86% from surveillance cultures. The clonal structure was studied by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) and was highly diverse, with 79 and 45 different PFGE types and STs, respectively. The most common clones were ST-131 and ST-410, identified in 21 isolates (23%). Dominant clonal complexes (CCs) were CC131 (n = 16), CC410 (n = 14), CC10 (n = 17), and CC-69 (n = 6). The blaKPC-2 and blaKPC-3 genes were identified in 68 and 20 isolates, respectively. All isolates were non-susceptible to ertapenem; 16 (18%) and 35 (40%) isolates were susceptible (minimal inhibitory concentration ≤1 mg/L) to imipenem and meropenem, respectively. Isolates were susceptible to colistin, amikacin, ciprofloxacin, gentamicin, and trimethoprim-sulfamethoxazole in 100%, 87%, 28%, 27%, and 21% of the cases, respectively. blaKPC-Harbouring plasmids from Tel Aviv Medical Center as well as from six CC-131 isolates from the other centres were studied by Inc and pMLST typing. Sixteen of the 20 blaKPC2-harbouring plasmids were of identical type, IncN-pMLST ST-15. In conclusion, the clonal structure of KPCEC in Israel is characterized by the predominance of known international extended-spectrum ß-lactamase-producing clones and by high intra- and inter-institutional diversity. This suggests that in Israel, clonal spread does not play a major role in the dissemination of KPCEC.