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1.
J Antimicrob Chemother ; 74(11): 3268-3273, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31495877

RESUMO

OBJECTIVES: To assess the pharmacokinetics of formed colistin in plasma and the safety of two different high doses of colistimethate sodium administered via nebulization in critically ill surgical patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP). PATIENTS AND METHODS: Formed colistin plasma concentrations were measured in critically ill surgical patients with pneumonia treated with two different doses of nebulized colistimethate sodium (3 MIU/8 h versus 5 MIU/8 h). Adverse events possibly related to nebulized colistimethate sodium were recorded. RESULTS: Twenty-seven patients (15 in the 3 MIU/8 h group and 12 in the 5 MIU/8 h group) were included. Colistin plasma concentrations were unquantifiable (<0.1 mg/L) in eight (53.3%) patients in the 3 MIU/8 h group and in seven patients (58.3%) in the 5 MIU/8 h group. Median (IQR) quantifiable colistin plasma concentrations before nebulization and at 1, 4 and 8 h were 0.17 (0.12-0.33), 0.20 (0.11-0.24), 0.17 (0.12-0.23) and 0.17 (0.11-0.32) mg/L, respectively, in the 3 MIU/8 h group and 0.20 (0.11-0.35), 0.24 (0.12-0.44), 0.24 (0.10-0.49) and 0.23 (0.11-0.44) mg/L, respectively, in the 5 MIU/8 h group, with no differences between the two groups at any time. Renal impairment during nebulized treatment was observed in three patients in each group, but was unlikely to be related to colistimethate sodium treatment. Nebulized colistimethate sodium therapy was well tolerated and no bronchospasms or neurotoxicity events were observed. CONCLUSIONS: In this limited observational case series of critically ill patients with HAP or VAP treated with high doses of nebulized colistimethate sodium, systemic exposure was minimal and the treatment was well tolerated.

2.
Clin Microbiol Rev ; 32(4)2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31462403

RESUMO

SUMMARYIn recent years, the worldwide spread of the so-called high-risk clones of multidrug-resistant or extensively drug-resistant (MDR/XDR) Pseudomonas aeruginosa has become a public health threat. This article reviews their mechanisms of resistance, epidemiology, and clinical impact and current and upcoming therapeutic options. In vitro and in vivo treatment studies and pharmacokinetic and pharmacodynamic (PK/PD) models are discussed. Polymyxins are reviewed as an important therapeutic option, outlining dosage, pharmacokinetics and pharmacodynamics, and their clinical efficacy against MDR/XDR P. aeruginosa infections. Their narrow therapeutic window and potential for combination therapy are also discussed. Other "old" antimicrobials, such as certain ß-lactams, aminoglycosides, and fosfomycin, are reviewed here. New antipseudomonals, as well as those in the pipeline, are also reviewed. Ceftolozane-tazobactam has clinical activity against a significant percentage of MDR/XDR P. aeruginosa strains, and its microbiological and clinical data, as well as recommendations for improving its use against these bacteria, are described, as are those for ceftazidime-avibactam, which has better activity against MDR/XDR P. aeruginosa, especially strains with certain specific mechanisms of resistance. A section is devoted to reviewing upcoming active drugs such as imipenem-relebactam, cefepime-zidebactam, cefiderocol, and murepavadin. Finally, other therapeutic strategies, such as use of vaccines, antibodies, bacteriocins, anti-quorum sensing, and bacteriophages, are described as future options.

3.
J Glob Antimicrob Resist ; 18: 37-44, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31154007

RESUMO

BACKGROUND: Extensively drug-resistant (XDR) Pseudomonas aeruginosa (P. aeruginosa) and particularly P. aeruginosa high-risk clones, are of growing concern because treatment options are limited. For years, colistin monotherapy has been the only available treatment, but is well known that is not an optimal treatment. A combination of colistin with another antibiotic could be a possible therapeutic option. OBJECTIVES: This study aimed to investigate effective antibiotic combinations against 20 XDR P. aeruginosa isolates obtained in a Spanish multicentre study (2015). METHODS: Forty-five checkerboards with six antipseudomonal antibiotics (amikacin, aztreonam, ceftazidime, meropenem, colistin, and ceftolozane/tazobactam) were performed to determine whether combinations were synergic or additive by fractional inhibitory concentration indices. On average, 15 different regimens were evaluated in duplicate against the three most prevalent high-risk clones (ST175, ST235, ST111) by time-kill analyses over 24h. The combination showing synergism in the three high-risk clones was validated in all studied XDR isolates. RESULTS: In time-kill curves, the untreated control failed, as did each study regimen when administered alone. Two combinations were synergistic in the three high-risk clones that were initially studied: amikacin plus ceftazidime and colistin plus meropenem, with the second being the most effective combination. The efficacy of colistin plus meropenem was then tested in all 20 isolates. A synergistic bacterial density reduction for the duration of the study occurred in 80% of the entire XDR collection. CONCLUSIONS: These data suggest that colistin plus meropenem may be a useful combination for the treatment of infections due to XDR P. aeruginosa, including high-risk clones, which warrants evaluation in a clinical trial.

4.
Molecules ; 24(3)2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30717123

RESUMO

Colistin is administered as its inactive prodrug colistimethate (CMS). Selection of an individualized CMS dose for each patient is difficult due to its narrow therapeutic window, especially in patients with chronic kidney disease (CKD). Our aim was to analyze CMS use in patients with CKD. Secondary objectives were to assess the safety and efficacy of CMS in this special population. In this prospective observational cohort study of CMS-treated CKD patients, CKD was defined as the presence of a glomerular filtration rate (GFR) < 60 mL/min/m² for more than 3 months. The administered doses of CMS were compared with those recently published in the literature. Worsened CKD at the end of treatment (EOT) was evaluated with the RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) criteria. Colistin plasma concentrations (Css) were measured using high-performance liquid chromatography. Fifty-nine patients were included. Thirty-six (61.2%) were male. The median age was 76 (45⁻95) years and baseline GFR was 36.6 ± 13.6. The daily mean CMS dosage used was compared with recently recommended doses (3.36 vs. 6.07; p < 0.001). Mean Css was 0.9 (0.2⁻2.9) mg/L, and Css was <2 mg/L in 50 patients (83.3%). Clinical cure was achieved in 43 (72.9%) patients. Worsened renal function at EOT was present in 20 (33.9%) patients and was reversible in 10 (52.6%). The CMS dosages used in this cohort were almost half those currently recommended. The mean achieved Css were under the recommended target of 2 mg/dL. Despite this, clinical cure rate was high. In this patient cohort, the incidence of nephrotoxicity was similar to those found in other recent studies performed in the general population and was reversible in 52.6%. These results suggest that CMS is safe and effective in patients with CKD and may encourage physicians to adjust dosage regimens to recent recommendations in order to optimize CMS treatments.


Assuntos
Antibacterianos/farmacocinética , Bronquite/tratamento farmacológico , Colistina/análogos & derivados , Pneumonia Bacteriana/tratamento farmacológico , Infecções por Pseudomonas/tratamento farmacológico , Insuficiência Renal Crônica/tratamento farmacológico , Infecções Urinárias/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/sangue , Antibacterianos/farmacologia , Bronquite/sangue , Bronquite/complicações , Bronquite/fisiopatologia , Colistina/sangue , Colistina/farmacocinética , Colistina/farmacologia , Esquema de Medicação , Cálculos da Dosagem de Medicamento , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/sangue , Pneumonia Bacteriana/complicações , Pneumonia Bacteriana/fisiopatologia , Estudos Prospectivos , Infecções por Pseudomonas/sangue , Infecções por Pseudomonas/complicações , Infecções por Pseudomonas/fisiopatologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/crescimento & desenvolvimento , Pseudomonas aeruginosa/patogenicidade , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia , Resultado do Tratamento , Infecções Urinárias/sangue , Infecções Urinárias/complicações , Infecções Urinárias/fisiopatologia
6.
Rev. esp. quimioter ; 31(2): 110-117, abr. 2018. tab
Artigo em Inglês | IBECS | ID: ibc-174505

RESUMO

Objective. To analyze the clinical and economic impact of an antimicrobial stewardship program (ASP) targeting urinary tract infections (UTI) caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli. Methods. An observational retrospective study that included adults with a diagnosis of UTI caused by ESBL-producing E. coli admitted to a tertiary care hospital in Barcelona, Spain, between January 2014 and December 2015. The impact of the ASP was analyzed in terms of clinical and economic outcomes. Results. A total of 222 patients met the inclusion criteria and an intervention was made by the ASP team in 104 cases (47%). ASP intervention was an independent variable related to clinical cure (p = 0.008). Other variables influencing clinical outcomes were the McCabe Jackson score (p = 0.005) and outpatient status (p < 0.001). The ASP interventions in this study had no economic impact. Conclusion. Antimicrobial stewardship has a positive clinical impact on UTIs caused by ESBL-producing E. coli. Further prospective studies are needed to assess the economic impact of ASPs on UTI caused by ESBL-producing E. col


Objetivo. Analizar el impacto clínico y económico de un Programa de Optimización de Antimicrobianos (PROA) en las infecciones del tracto urinario (ITU) causadas por Escherichia coli productor de β-lactamasas de espectro extendido (BLEE). Métodos. Estudio observacional retrospectivo que incluye adultos con ITU por E. coli BLEE diagnosticados en un hospital terciario en Barcelona, España, entre enero de 2014 y diciembre de 2015. El impacto del PROA se analizó en términos de evolución clínica y consumo de recursos sanitarios. Resultados. Se incluyeron un total de 222 pacientes, de los cuales se realizó algún tipo de intervención por parte del equipo de PROA en 104 casos (47%). La intervención del PROA resultó ser una variable independiente relacionada con la curación clínica (p = 0,008). Otras variables relacionadas con la evolución clínica fueron la clasificación de McCabe Jackson (p = 0,005) y el manejo ambulatorio (p < 0,001). Las intervenciones del PROA no demostraron tener un impacto económico en este estudio. Conclusión. Las intervenciones de los PROA tienen un impacto positivo en la evolución clínica de los pacientes con ITU por E. coli productor de BLEE. Se necesitan más estudios prospectivos para determinar el impacto económico de los PROA en las ITU por E. coli productor de BLEE


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudo Observacional , Escherichia coli , Escherichia coli/enzimologia , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Infecções Urinárias/epidemiologia , Infecções Urinárias/microbiologia , beta-Lactamases/metabolismo , Antibacterianos/uso terapêutico , Bacteriemia/microbiologia , Farmacorresistência Bacteriana , Estudos Retrospectivos , Espanha/epidemiologia , Infecções Urinárias/tratamento farmacológico
7.
Artigo em Inglês | MEDLINE | ID: mdl-29530842

RESUMO

The aim of this study was to investigate the efficacy of ceftolozane-tazobactam in combination with meropenem against an extensively drug-resistant (XDR) Pseudomonas aeruginosa high-risk clone, sequence type 175, isolated in a Spanish university hospital. A 14-day hollow-fiber infection model was used to simulate clinical exposure of the two drug regimens alone and in combination, and serial samples were collected to determine drug concentrations and CFU counts. The untreated control failed, as did each study regimen when administered alone. However, when ceftolozane-tazobactam was administered in combination with meropenem, there was a >4-log10 CFU/ml bacterial density reduction and suppression of resistance for the duration of the study. These data suggest that ceftolozane-tazobactam plus meropenem may be a useful combination for treating XDR P. aeruginosa.

8.
JAMA ; 319(8): 788-799, 2018 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-29486041

RESUMO

Importance: Meropenem-vaborbactam is a combination carbapenem/beta-lactamase inhibitor and a potential treatment for severe drug-resistant gram-negative infections. Objective: To evaluate efficacy and adverse events of meropenem-vaborbactam in complicated urinary tract infection (UTI), including acute pyelonephritis. Design, Setting, and Participants: Phase 3, multicenter, multinational, randomized clinical trial (TANGO I) conducted November 2014 to April 2016 and enrolling patients (≥18 years) with complicated UTI, stratified by infection type and geographic region. Interventions: Eligible patients were randomized 1:1 to receive meropenem-vaborbactam (2g/2g over 3 hours; n = 274) or piperacillin-tazobactam (4g/0.5g over 30 minutes; n = 276) every 8 hours. After 15 or more doses, patients could be switched to oral levofloxacin if they met prespecified criteria for improvement, to complete 10 days of total treatment. Main Outcomes and Measures: Primary end point for FDA criteria was overall success (clinical cure or improvement and microbial eradication composite) at end of intravenous treatment in the microbiologic modified intent-to-treat (ITT) population. Primary end point for European Medicines Agency (EMA) criteria was microbial eradication at test-of-cure visit in the microbiologic modified ITT and microbiologic evaluable populations. Prespecified noninferiority margin was -15%. Because the protocol prespecified superiority testing in the event of noninferiority, 2-sided 95% CIs were calculated. Results: Among 550 patients randomized, 545 received study drug (mean age, 52.8 years; 361 [66.2%] women; 374 [68.6%] in the microbiologic modified ITT population; 347 [63.7%] in the microbiologic evaluable population; 508 [93.2%] completed the trial). For the FDA primary end point, overall success occurred in 189 of 192 (98.4%) with meropenem-vaborbactam vs 171 of 182 (94.0%) with piperacillin-tazobactam (difference, 4.5% [95% CI, 0.7% to 9.1%]; P < .001 for noninferiority). For the EMA primary end point, microbial eradication in the microbiologic modified ITT population occurred in 128 of 192 (66.7%) with meropenem-vaborbactam vs 105 of 182 (57.7%) with piperacillin-tazobactam (difference, 9.0% [95% CI, -0.9% to 18.7%]; P < .001 for noninferiority); microbial eradication in the microbiologic evaluable population occurred in 118 of 178 (66.3%) vs 102 of 169 (60.4%) (difference, 5.9% [95% CI, -4.2% to 16.0%]; P < .001 for noninferiority). Adverse events were reported in 106 of 272 (39.0%) with meropenem-vaborbactam vs 97 of 273 (35.5%) with piperacillin-tazobactam. Conclusions and Relevance: Among patients with complicated UTI, including acute pyelonephritis and growth of a baseline pathogen, meropenem-vaborbactam vs piperacillin-tazobactam resulted in a composite outcome of complete resolution or improvement of symptoms along with microbial eradication that met the noninferiority criterion. Further research is needed to understand the spectrum of patients in whom meropenem-vaborbactam offers a clinical advantage. Trial Registration: clinicaltrials.gov Identifier: NCT02166476.


Assuntos
Antibacterianos/administração & dosagem , Ácidos Borônicos/administração & dosagem , Ácido Penicilânico/análogos & derivados , Pielonefrite/tratamento farmacológico , Tienamicinas/administração & dosagem , Infecções Urinárias/tratamento farmacológico , Doença Aguda , Adulto , Idoso , Antibacterianos/efeitos adversos , Ácidos Borônicos/efeitos adversos , Combinação de Medicamentos , Feminino , Humanos , Análise de Intenção de Tratamento , Masculino , Meropeném , Pessoa de Meia-Idade , Ácido Penicilânico/administração & dosagem , Ácido Penicilânico/efeitos adversos , Piperacilina/administração & dosagem , Piperacilina/efeitos adversos , Combinação Piperacilina e Tazobactam , Guias de Prática Clínica como Assunto , Tienamicinas/efeitos adversos , Urina/microbiologia
9.
Shock ; 50(5): 504-510, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29293175

RESUMO

PURPOSE: The integrated analysis of changes in the metabolic profile could be critical for the discovery of biomarkers of lung injury, and also for generating new pathophysiological hypotheses and designing novel therapeutic targets for the acute respiratory distress syndrome (ARDS). This study aimed at developing a nuclear magnetic resonance (NMR)-based approach for the identification of the metabolomic profile of ARDS in patients with H1N1 influenza virus pneumonia. METHODS: Serum samples from 30 patients (derivation set) diagnosed of H1N1 influenza virus pneumonia were analyzed by unsupervised principal component analysis to identify metabolic differences between patients with and without ARDS by NMR spectroscopy. A predictive model of partial least squares discriminant analysis (PLS-DA) was developed for the identification of ARDS. PLS-DA was trained with the derivation set and tested in another set of samples from 26 patients also diagnosed of H1N1 influenza virus pneumonia (validation set). RESULTS: Decreased serum glucose, alanine, glutamine, methylhistidine and fatty acids concentrations, and elevated serum phenylalanine and methylguanidine concentrations, discriminated patients with ARDS versus patients without ARDS. PLS-DA model successfully identified the presence of ARDS in the validation set with a success rate of 92% (sensitivity 100% and specificity 91%). The classification functions showed a good correlation with the Sequential Organ Failure Assessment score (R = 0.74, P < 0.0001) and the PaO2/FiO2 ratio (R = 0.41, P = 0.03). CONCLUSIONS: The serum metabolomic profile is sensitive and specific to identify ARDS in patients with H1N1 influenza A pneumonia. Future studies are needed to determine the role of NMR spectroscopy as a biomarker of ARDS.

10.
Electrophoresis ; 38(18): 2341-2348, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28714069

RESUMO

Acute respiratory distress syndrome (ARDS) is a serious complication of influenza A (H1N1) virus infection. Its pathogenesis is unknown and biomarkers are lacking. Untargeted metabolomics allows the analysis of the whole metabolome in a biological compartment, identifying patterns associated with specific conditions. We hypothesized that LC-MS could help identify discriminant metabolites able to define the metabolic alterations occurring in patients with influenza A (H1N1) virus infection that developed ARDS. Serum samples from patients diagnosed with 2009 influenza A (H1N1) virus infection with (n = 25) or without (n = 32) ARDS were obtained on the day of hospital admission and analyzed by LC-MS/MS. Metabolite identification was determined by MS/MS analysis and analysis of standards. The specificity of the patterns identified was confirmed in patients without 2009 influenza A(H1N1) virus pneumonia (15 without and 17 with ARDS). Twenty-three candidate biomarkers were found to be significantly different between the two groups, including lysophospholipids and sphingolipids related to inflammation; bile acids, tryptophan metabolites, and thyroxine, related to the metabolism of the gut microflora. Confirmation results demonstrated the specificity of major alterations occurring in ARDS patients with influenza A (H1N1) virus infection.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/sangue , Metabolômica/métodos , Síndrome do Desconforto Respiratório do Adulto/sangue , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Influenza Humana/virologia , Masculino , Metaboloma , Pessoa de Meia-Idade , Síndrome do Desconforto Respiratório do Adulto/virologia , Espectrometria de Massas em Tandem/métodos
11.
PLoS One ; 12(4): e0173802, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28388647

RESUMO

Dysbalance in gut microbiota has been linked to increased microbial translocation, leading to chronic inflammation in HIV-patients, even under effective HAART. Moreover, microbial translocation is associated with insufficient reconstitution of CD4+T cells, and contributes to the pathogenesis of immunologic non-response. In a double-blind, randomised, placebo-controlled trial, we recently showed that, compared to placebo, 12 weeks treatment with probiotic Saccharomyces boulardii significantly reduced plasma levels of bacterial translocation (Lipopolysaccharide-binding protein or LBP) and systemic inflammation (IL-6) in 44 HIV virologically suppressed patients, half of whom (n = 22) had immunologic non-response to antiretroviral therapy (<270 CD4+Tcells/µL despite long-term suppressed viral load). The aim of the present study was to investigate if this beneficial effect of the probiotic Saccharomyces boulardii is due to modified gut microbiome composition, with a decrease of some species associated with higher systemic levels of microbial translocation and inflammation. In this study, we used 16S rDNA gene amplification and parallel sequencing to analyze the probiotic impact on the composition of the gut microbiome (faecal samples) in these 44 patients randomized to receive oral supplementation with probiotic or placebo for 12 weeks. Compared to the placebo group, in individuals treated with probiotic we observed lower concentrations of some gut species, such as those of the Clostridiaceae family, which were correlated with systemic levels of bacterial translocation and inflammation markers. In a sub-study of these patients, we observed significantly higher parameters of microbial translocation (LBP, soluble CD14) and systemic inflammation in immunologic non-responders than in immunologic responders, which was correlated with a relative abundance of specific gut bacterial groups (Lachnospiraceae genus and Proteobacteria). Thus, in this work, we propose a new therapeutic strategy using the probiotic yeast S. boulardii to modify gut microbiome composition. Identifying pro-inflammatory species in the gut microbiome could also be a useful new marker of poor immune response and a new therapeutic target.


Assuntos
Infecções por HIV/microbiologia , Intestinos/microbiologia , Microbiota , Probióticos , Saccharomyces boulardii , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placebos
12.
Int Orthop ; 41(7): 1315-1319, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28321490

RESUMO

BACKGROUND: Periprosthetic tissue cultures, sonication and synovial fluid cultures remain the gold standard for prosthetic joint infection (PJI) diagnosis. However, some 15-20% culture-negative PJI are still reported. Therefore, there is the need for other diagnostic criteria. One point of concern relative to the different definitions of PJI is as to the inclusion of the c-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) as diagnostic criteria for PJI despite them being non-specific inflammatory blood tests. PURPOSE: The purpose of the present study was to determine the relevance of CRP and the ESR in the diagnosis of PJI. METHODS: All PJI with positive cultures over a two-year period in two hospitals were reviewed. The main variables of the present study were the type of prosthesis and the CRP level. More information was recorded in those patients with normal CRP: radiographs, physical examination records and the ESR. RESULTS: Seventy-three patients were included in study. Pre-operative CRP levels were normal (lower than 0.8 mg/dl) in 23 patients, representing 32% of all PJI with positive cultures. Low virulence micro-organisms, 12 coagulase-negative staphylococci and four P. acnes, grew in most of them. They represented 70% of all PJI with normal CRP levels. In addition, 17 patients (23% of all PJI with positive cultures) had a normal ESR, a normal physical examination (they only presented with pain) and no clear loosening was observed in the radiographs. CONCLUSIONS: Per the American Association of Orthopaedic Surgeons (AAOS) guidelines or the Musculoskeletal Infection Society (MSIS), 23% of the patients in the present study with PJI would never have been identified. Blood inflammatory markers such as the CRP level and ESR may not be accurate as diagnostic tools in PJI, particularly to identify low-grade and chronic PJI.


Assuntos
Artroplastia de Substituição/efeitos adversos , Sedimentação Sanguínea , Proteína C-Reativa/análise , Erros de Diagnóstico/prevenção & controle , Infecções Relacionadas à Prótese/diagnóstico , Idoso , Bactérias/patogenicidade , Biomarcadores/sangue , Candida/patogenicidade , Doença Crônica , Feminino , Humanos , Masculino , Técnicas Microbiológicas , Pessoa de Meia-Idade , Infecções Relacionadas à Prótese/imunologia , Infecções Relacionadas à Prótese/microbiologia , Estudos Retrospectivos , Líquido Sinovial/imunologia , Líquido Sinovial/microbiologia
13.
Diagn Microbiol Infect Dis ; 86(4): 442-445, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27745737

RESUMO

BACKGROUND: Culture negative prosthetic joint infections (PJI) still remain an issue even with the advantages of the new diagnostic tools for PJI. This is why some orthopedic surgeons have reservations relative to the use of preoperative antibiotic prophylaxis when a PJI is suspected. The purpose of the present study was to evaluate the influence of preoperative antibiotic prophylaxis on intraoperative cultures. MATERIAL AND METHODS: An enhanced diagnostic protocol for PJI (Zimmerli criteria) was used for the inclusion criteria in order to collect all PJI that were seen in a university hospital. Patients were prospectively randomized into two groups. The control group received the classical preoperative antibiotic prophylaxis. The study group did not receive prophylaxis prior to surgery. RESULTS: There were 14 patients in each group. They correspond to 13 total hip arthroplasty infections, 12 total knee arthroplasty infections and 3 reverse shoulder prosthesis infections. There were 10 patients in the study group and 10 patients in the control group with at least one positive microbiological criterion (P > 0.05). There were 4 patients in each group with a culture negative PJI (P > 0.05). CONCLUSIONS: Preoperative antibiotic prophylaxis does not affect intraoperative cultures in suspected or confirmed PJI. Therefore it is essential to deliver antibiotic prophylaxis in any patient in which a prosthesis is to be implanted in order to protect the prosthesis from infection.


Assuntos
Antibioticoprofilaxia/métodos , Bactérias/isolamento & purificação , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/cirurgia , Osteoartrite/cirurgia , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/cirurgia , Idoso , Idoso de 80 Anos ou mais , Bactérias/classificação , Técnicas Bacteriológicas , Feminino , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Distribuição Aleatória , Sensibilidade e Especificidade
14.
Int J Antimicrob Agents ; 48(6): 725-727, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28128096

RESUMO

Nephrotoxicity limits the effective use of colistin for the treatment of multidrug-resistant Gram-negative bacteria (MDR-GNB) infections. We previously defined a steady-state colistin plasma concentration (Css) of 2.42 mg/L that predicted nephrotoxicity at end of treatment (EOT). The objective of this study was to validate this breakpoint in a prospective cohort. This was a multicentre, prospective, observational study conducted at three hospitals with a cohort of patients treated for MDR-GNB infection with colistin methanesulfonate from September 2011 until January 2015. Nephrotoxicity was evaluated at Day 7 and at EOT using the RIFLE criteria. Css values were measured and analysed using HPLC. Taking the previously defined breakpoint for colistin concentration as a criterion, patients were divided into two groups (Css, ≤2.42 mg/L vs. >2.42 mg/L). Sixty-four patients were included. Seven patients (10.9%) had a Css > 2.42 mg/L and were compared with the remaining patients. Bivariate analysis showed that patients with a Css > 2.42 mg/L were older and had a significantly higher incidence of nephrotoxicity at Day 7 and EOT. Although not statistically significant, nephrotoxicity occurred earlier in these patients (6.2 days vs. 9.2 days in patients with lower Css; P = 0.091). Multivariate analysis of nephrotoxicity showed that Css > 2.42 mg/L was the only predictive factor. Nephrotoxicity was more frequent and occurred earlier in patients with colistin plasma concentrations higher than the previously defined breakpoint (2.42 mg/L). Colistin therapeutic drug monitoring should be routinely considered to avoid reaching this toxicity threshold and potential clinical consequences.


Assuntos
Lesão Renal Aguda , Antibacterianos/efeitos adversos , Antibacterianos/análise , Colistina/análogos & derivados , Plasma/química , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Cromatografia Líquida de Alta Pressão , Colistina/administração & dosagem , Colistina/efeitos adversos , Colistina/análise , Monitoramento de Medicamentos , Feminino , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
15.
J Clin Microbiol ; 53(5): 1622-7, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25740775

RESUMO

Sonication improved the diagnosis of orthopedic implant-associated infections (OIAI). We investigated the diagnostic performance of sonication fluid inoculated into blood culture bottles in comparison with that of intraoperative tissue and sonication fluid cultures. Consecutive patients with removed orthopedic hardware were prospectively included and classified as having OIAI or aseptic failure (AF) according to standardized criteria. The diagnostic procedure included the collection of five intraoperative tissue cultures and sonication of the removed device, followed by conventional culture of the sonication fluid. Cultures were incubated for 7 days (aerobic) or 14 days (anaerobic). In addition, 10 ml of sonication fluid was inoculated into each aerobic and anaerobic BacT/Alert FAN blood culture bottle and incubated in the automated blood culture system for 5 days. Of 75 included patients, 39 had OIAI and 36 AF. The sensitivity of sonication fluid inoculated into blood culture bottles (100%) was higher than that of conventional sonication fluid (87%; P = 0.05) or intraoperative tissue cultures (59%; P < 0.01). Previous antibiotic therapy reduced the culture sensitivity of conventional sonication fluid to 77% and that of intraoperative tissue to 55%, while it remained 100% for blood culture-inoculated sonication fluid. The time to positivity was shorter in blood culture-inoculated sonication fluid, with detection of 72% of microorganisms after 1 day of incubation, than for intraoperative tissue and conventional sonication fluid cultures, with detection of 18% and 28% of microorganisms, respectively. In conclusion, compared to conventional sonication fluid and intraoperative tissue cultures, sonication fluid inoculated into blood culture bottles improved the diagnosis of OIAI and considerably reduced the time to culture positivity.


Assuntos
Técnicas Microbiológicas/métodos , Próteses e Implantes/microbiologia , Infecções Relacionadas à Prótese/diagnóstico , Sonicação , Manejo de Espécimes/métodos , Adulto , Aerobiose , Idoso , Idoso de 80 Anos ou mais , Anaerobiose , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Ortopédicos/efeitos adversos , Sensibilidade e Especificidade , Fatores de Tempo
16.
J Acquir Immune Defic Syndr ; 68(3): 256-63, 2015 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-25469528

RESUMO

BACKGROUND: Microbial translocation has been associated with an increase in immune activation and inflammation in HIV infection despite effective highly active antiretroviral therapy. It has been shown that some probiotics have a beneficial effect by reducing intestinal permeability and, consequently, microbial translocation. OBJECTIVES: To assess changes in microbial translocation and inflammation after treatment with probiotics (Saccharomyces boulardii) in HIV-1-infected patients with virologic suppression. METHODS: A double-blind, randomized, placebo-controlled trial was conducted in 44 nonconsecutive HIV-1-infected patients with viral load of <20 copies per milliliter for at least 2 years. Patients were randomized to oral supplementation with probiotics or placebo during 12 weeks. Markers of microbial translocation (lipopolysaccharide-binding protein [LBP] and soluble CD14), inflammation (interleukin 6 [IL-6], tumor necrosis factor alpha, interferon gamma, high-sensitivity C-reactive protein), and immunological and clinical data were determined before and after the intervention and 3 months after treatment discontinuation. Quantitative variables were compared using the Mann-Whitney U test, and categorical variables were compared using the Fisher exact test. RESULTS: After 12 weeks of treatment, differences between the probiotic arm and the placebo arm were observed in LBP values (-0.30 vs +0.70 pg/mL) and IL-6 (-0.60 vs +0.78 pg/mL). These differences were also noted at 3 months after treatment withdrawal. Qualitative analysis was performed, defining a variable as "decreased" or "increased" from baseline LBP. A significant decrease of LBP at 12 weeks of treatment was observed (57.9% patients in the probiotic group vs 6.2% in the placebo group, P = 0.002). CONCLUSIONS: Treatment with S. boulardii decreases microbial translocation (LBP) and inflammation parameters (IL-6) in HIV-1-infected patients with long-term virologic suppression.


Assuntos
Translocação Bacteriana , Infecções por HIV/complicações , Inflamação/prevenção & controle , Probióticos/uso terapêutico , Saccharomyces/fisiologia , Proteínas da Fase Aguda , Administração Oral , Proteína C-Reativa/análise , Proteínas de Transporte/sangue , Citocinas/sangue , Método Duplo-Cego , Feminino , Infecções por HIV/terapia , Humanos , Receptores de Lipopolissacarídeos/sangue , Masculino , Glicoproteínas de Membrana/sangue , Placebos/administração & dosagem , Saccharomyces/crescimento & desenvolvimento , Resultado do Tratamento
17.
Curr Infect Dis Rep ; 16(11): 439, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25230606

RESUMO

Infective endocarditis (IE) continues to be a serious disease with a poor prognosis and high mortality. Neither incidence rates nor mortality have decreased in recent decades. Because of this, it is important to prevent IE in patients at risk. In the past, prevention of IE has focused on antimicrobial prophylaxis, mainly for dental procedures. However, recent major changes in epidemiology, the most significant being the growing frequency and high mortality rate of health care-associated valve endocarditis (HAIE), mean that preventive strategies against IE must also change. Since intravascular catheters are the most common source of bacteremia among patients with HAIE, significant efforts must be made to minimize the risk of catheter-related bloodstream infections. Measures for preventing the infection of prosthetic valves and cardiac implantable devices at the time of implantation also need to be implemented.

18.
J Infect ; 69(1): 35-41, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24631778

RESUMO

OBJECTIVES: The sensitivity of periprosthetic tissue culture is inadequate for the diagnosis of prosthetic joint infection (PJI). We investigated and compared the values of sonication fluid culture and periprosthetic tissue culture for diagnosing PJI. METHODS: Included were patients whose joint prosthesis had been removed for any reason. The resulting sonication fluid and periprosthetic tissues were cultured for 14 days. RESULTS: Of 231 explanted prostheses, aseptic failure was diagnosed in 162 cases (70%) and PJI in 69 (30%). In PJI cases, sonication fluid culture detected 62 microorganisms and periprosthetic tissue culture detected 45. Tissue and sonication fluid cultures showed sensitivities of 61% and 81%, respectively (p < 0.01), with specificity of 100% and 99%, respectively. On day 1, tissue and sonication fluid cultures were positive in 13% and 28% (p = 0.013) of PJI cases respectively, and on day 2, in 26% and 48% (p = 0.002) of cases. Four anaerobes grew in sonication fluid culture after 7-13 days incubation, whereas tissue culture missed 3 of these. Prolonged incubation of sonication fluid did not detect any organisms in the cases of aseptic failure. CONCLUSIONS: Sonication fluid culture provides a more rapid diagnosis and detects about 30% more pathogens, although anaerobic organisms require up to 2 weeks of incubation.


Assuntos
Artrite/diagnóstico , Técnicas Microbiológicas/métodos , Próteses e Implantes/microbiologia , Infecções Relacionadas à Prótese/diagnóstico , Sonicação/métodos , Manejo de Espécimes/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade , Fatores de Tempo
19.
Expert Rev Mol Diagn ; 14(1): 83-96, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24308408

RESUMO

An accurate diagnosis of prosthetic joint infection (PJI) is the mainstay for an optimized clinical management. This review analyzes different diagnostic strategies of PJI, with special emphasis on molecular diagnostic tools and their current and future applications. Until now, the culture of periprosthetic tissues has been considered the gold standard for the diagnosis of PJI. However, sonication of the implant increases the sensitivity of those cultures and is being increasingly adopted by many centers. Molecular diagnostic methods compared with intraoperative tissue culture, especially if combined with sonication, have a higher sensitivity, a faster turnaround time and are not influenced by previous antimicrobial therapy. However, they still lack a system for detection of antimicrobial susceptibility, which is crucial for an optimized and less toxic therapy of PJI. More studies are needed to assess the clinical value of these methods and their cost-effectiveness.


Assuntos
Infecções Bacterianas/diagnóstico , Prótese de Quadril/efeitos adversos , Prótese do Joelho/efeitos adversos , Técnicas de Diagnóstico Molecular , Infecções Relacionadas à Prótese/diagnóstico , Infecções Bacterianas/microbiologia , DNA Bacteriano/genética , Humanos , Reação em Cadeia da Polimerase , Infecções Relacionadas à Prótese/microbiologia , Líquido Sinovial/microbiologia
20.
BMC Infect Dis ; 13: 380, 2013 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-23957376

RESUMO

BACKGROUND: Data regarding the most efficacious and least toxic schedules for the use of colistin are scarce. The aim of this study was to determine the incidence and the potential risk factors of colistin-associated nephrotoxicity including colistin plasma levels. METHODS: A prospective observational cohort study was conducted for over one year in patients receiving intravenous colistin methanesulfonate sodium (CMS). Blood samples for colistin plasma levels were collected immediately before (Cmin) and 30 minutes after CMS infusion (Cmax). Renal function was assessed at baseline, on day 7 and at the end of treatment (EOT). Severity of acute kidney injury (AKI) was defined by the RIFLE (risk, injury, failure, loss, and end-stage kidney disease) criteria. RESULTS: One hundred and two patients met the inclusion criteria. AKI related to CMS treatment on day 7 and at the end of treatment (EOT) was observed in 26 (25.5%) and 50 (49.0%) patients, respectively. At day 7, Cmin (OR, 4.63 [2.33-9.20]; P < 0.001) was the only independent predictor of AKI. At EOT, the Charlson score (OR 1.26 [1.01-1.57]; P = 0.036), Cmin (OR 2.14 [1.33-3.42]; P = 0.002), and concomitant treatment with ≥ 2 nephrotoxic drugs (OR 2.61 [1.0-6.8]; P = 0.049) were independent risk factors for AKI. When Cmin was evaluated as a categorical variable, the breakpoints that better predicted AKI were 3.33 mg/L (P < 0.001) on day 7 and 2.42 mg/L (P < 0.001) at EOT. CONCLUSIONS: When using the RIFLE criteria, colistin-related nephrotoxicity is observed in a high percentage of patients. Cmin levels are predictive of AKI. Patients who receive intravenous colistin should be closely monitored and Cmin might be a new useful tool to predict AKI.


Assuntos
Antibacterianos/sangue , Colistina/sangue , Nefropatias/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/toxicidade , Colistina/toxicidade , Feminino , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Humanos , Nefropatias/sangue , Nefropatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Espanha/epidemiologia
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