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1.
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.

2.
J Infect ; 79(3): 253-261, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31265867

RESUMO

OBJECTIVES: Optimal dosage regimens of colistin for the treatment of urinary tract infections (UTI) are unknown. Colistimethate sodium (CMS), the inactive prodrug of colistin, is mainly excreted in urine and converts to colistin after filtration by glomeruli, suggesting that concentrations of colistin in urine could be much higher than in plasma. Therefore, there is a need to optimize dosage regimens of intravenous CMS for UTI. The aim of this study was to examine the relationship between AUC/MIC of formed colistin and clinical outcomes in patients with UTI caused by extremely drug resistant (XDR) Pseudomonas aeruginosa. METHODS: This prospective, observational cohort study involved patients with UTI caused by XDR P. aeruginosa. Clinical cure, bacteriological clearance and acute kidney injury (AKI) were analyzed. Steady-state colistin plasma concentrations (Css) were measured using HPLC. Based on the PK/PD of colistin in neutropenic mouse thigh infection models with P. aeruginosa, the optimal AUC/MIC should be ≥60 mg·h/L. According to the pharmacokinetics (PK) in critically-ill patients, the Css target of formed colistin in plasma was 2.5 mg/L. RESULTS: Thirty-three patients were included (24 lower UTI and 9 pyelonephritis). The MIC50 and MIC90 values for colistin were 0.5 and 2 mg/L respectively. Nineteen patients (57.6%) received colistin monotherapy (84.2% lower UTI and 15.8% pyelonephritis). Of these, clinical cure was achieved in 89.5% of cases. Among patients with clinical cure and monotherapy, only 5 (29.4%) attained an optimal plasma AUC/MIC and only 1 (5.9%) the therapeutic level of formed colistin (2.5 mg/L). However, 10 (58.8%) patients showed colistin plasma concentrations above the MIC of the isolated P. aeruginosa. Microbiological eradication was achieved in 76.9% of patients. AKI at the end of treatment was present in 29.4% of patients. CONCLUSIONS: The currently recommended dosage regimens of CMS showed high efficacy for the treatment of lower complicated UTI caused by XDR P. aeruginosa in non-critically ill patients and in the case of low MIC values, but also a considerable nephrotoxicity rate. Our data suggest that the use of lower CMS doses for lower UTI should be investigated in future studies to minimize the unnecessary nephrotoxicity.

3.
J Glob Antimicrob Resist ; 18: 37-44, 2019 May 30.
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
5.
Eur J Clin Microbiol Infect Dis ; 38(4): 743-746, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30680575

RESUMO

The incidence of sepsis is disproportionately higher in elderly adults, and age is an independent predictor of mortality. Retrospective analysis was conducted among patients admitted to the emergency department in a tertiary teaching hospital from January 2016 to June 2017. To study the prognosis determinants of sepsis among elderly patients attended in the emergency room of a tertiary care hospital. As secondary objectives, we aimed to describe the causes of sepsis, the general outcome, and the general characteristics of these patients. Two hundred thirty-five episodes data of patients admitted throughout the 15-month study period who were diagnosed with sepsis, severe sepsis or septic shock, were included. Throughout the study cohort, 51 patients (21.7%) fulfilled the criteria of severe sepsis or septic shock. All-cause mortality was 11 patients (4.7%) on day 14 and 27 (11.5%) on day 30. Prognosis factors associated with 30-day mortality were the following: albumin level < 2.6 g/dl (first quartile of the overall population), odds ratio (OR 3.26, 95% CI 12-9.41; p = 0.029), Charlson comorbidity index (OR 1.23, 95% CI 1.04-1.45; p = 0.012), C-reactive protein on admission (OR 1.04, 95% CI 0.99-1.08; p = 0.062), and non-adequacy of the initial antimicrobial therapy (OR 3.3, 95% CI 1.06-10.4; p = 0.039). Among elderly patients with sepsis, strong predictors of mortality such as albumin could be considered as part of prognosis and future potential interventions. Adequacy of antimicrobial therapy at admission must be one of the objectives in the treatment of sepsis, also in the elderly, since it is an independent predictor of mortality.


Assuntos
Mortalidade Hospitalar , Sepse/patologia , Albumina Sérica Humana/análise , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Hospitalização , Hospitais de Ensino , Humanos , Masculino , Razão de Chances , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Sepse/mortalidade
6.
J Infect ; 77(2): 151-157, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29746950

RESUMO

BACKGROUND: Candida periprosthetic joint infection (CPJI) is a rare, difficult-to-treat disease. The purpose of this study was to evaluate the clinical characteristics and outcomes of CPJI treated with various surgical and antifungal strategies. METHODS: We conducted a multicenter retrospective study of all CPJI diagnosed between 2003 and 2015 in 16 Spanish hospitals. RESULTS: Forty-three patients included: median age, 75 years, and median Charlson Comorbidity Index score, 4. Thirty-four (79.1%) patients had ≥1 risk factor for Candida infection. Most common causative species were C. albicans and C. parapsilosis. Thirty-five patients were evaluable for outcome: overall, treatment succeeded in 17 (48.6%) and failed in 18 (51.4%). Success was 13/20 (67%) in patients with prosthesis removal and 4/15 (27%) with debridement and prosthesis retention (p = 0.041). All 3 patients who received an amphotericin B-impregnated cement spacer cured. In the prosthesis removal group, success was 5/6 (83%) with an antibiofilm regimen and 8/13 (62%) with azoles (p = 0.605). In the debridement and prosthesis retention group, success was 3/10 (30%) with azoles and 1/5 (20%) with antibiofilm agents. Therapeutic failure was due to relapse in 9 patients, need for suppressive treatment in 5, persistent infection in 2, and CPJI-related death in 2; overall attributable mortality was 6%. CONCLUSIONS: CPJI is usually a chronic disease in patients with comorbidities and risk factors for Candida infection. Treatment success is low, and prosthesis removal improves outcome. Although there is insufficient evidence that use of antifungals with antibiofilm activity has additional benefits, our experience indicates it may be recommendable.

7.
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
8.
Infect Drug Resist ; 11: 317-321, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29551905

RESUMO

Azole antifungals have frequently been linked to the presence of hepatotoxicity, but there is scarce information on cross-toxicity between these drugs or on the possibility of using some of them when this type of toxicity occurs. We report the case of a 64-year-old man with invasive aspergillosis (IA) leading to spondylodiscitis with neurological involvement. Early management included intravenous (iv) voriconazole, which had to be interrupted after 1 week due to liver damage. Therapeutic drug monitoring (TDM) of voriconazole showed that the plasma concentration was within the therapeutic range. However, it was replaced by a combination therapy of oral posaconazole plus iv caspofungin. Posaconazole allowed normalization of liver enzymes. After finishing posaconazole monotherapy on an outpatient basis, the patient made a full recovery. This case report provides further evidence that oral posaconazole is safe and effective as rescue therapy after the appearance of voriconazole-induced liver toxicity.

9.
J Orthop Surg Res ; 13(1): 58, 2018 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-29554935

RESUMO

BACKGROUND: The objective of this study is to present the results of cement spacer sonication in the second stage of two-stage treatment of shoulder arthroplasty infection and to determine the rate of positive cultures in the second-stage surgery in shoulder arthroplasty and its meaning. METHODS: Twenty-one patients (22 cement spacers) treated with two-stage surgery because of a shoulder arthroplasty infection were included. In the second stage, the cement spacer was sent for sonication and at least four tissue cultures were obtained. Epidemiological data, comorbidities, sensitivity of the microorganisms to the antibiotic loaded in the cement spacer in the first revision surgery, time elapsed since an antibiotic was last administered until second revision procedure, functional shoulder status at last follow-up, and any complication were recorded. RESULTS: Three out of the 22 cases (13.6%) presented positive cultures at the second-stage surgery. Periprosthetic tissue culturing detected the three positive culture cases in the second stage while the cement spacer sonication detected two and missed one. Considering periprosthetic tissue culturing as the standard procedure, the cement spacer sonication showed sensitivity at 66.6%. Recurrent infection over time was considered present in 3 patients; two of them had been previously diagnosed with a positive culture at the second stage (66.6%). CONCLUSIONS: A good number of patients (13.6%) present a positive culture at the second stage of the two-stage surgical procedure for infected shoulder arthroplasty, and those patients seem to be at high risk for recurrent infection. Periprosthetic tissue cultures have a higher sensitivity to detecting a positive culture at the second stage than cement spacer sonication.


Assuntos
Artroplastia do Ombro , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/cirurgia , Prótese de Ombro/efeitos adversos , Sonicação/métodos , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Cimentos para Ossos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Relacionadas à Prótese/etiologia , Recidiva , Estudos Retrospectivos , Prótese de Ombro/microbiologia
11.
Artigo em Inglês | MEDLINE | ID: mdl-28874376

RESUMO

This study assessed the molecular epidemiology, resistance mechanisms, and susceptibility profiles of a collection of 150 extensively drug-resistant (XDR) Pseudomonas aeruginosa clinical isolates obtained from a 2015 Spanish multicenter study, with a particular focus on resistome analysis in relation to ceftolozane-tazobactam susceptibility. Broth microdilution MICs revealed that nearly all (>95%) of the isolates were nonsusceptible to piperacillin-tazobactam, ceftazidime, cefepime, aztreonam, imipenem, meropenem, and ciprofloxacin. Most of them were also resistant to tobramycin (77%), whereas nonsusceptibility rates were lower for ceftolozane-tazobactam (31%), amikacin (7%), and colistin (2%). Pulsed-field gel electrophoresis-multilocus sequence typing (PFGE-MLST) analysis revealed that nearly all of the isolates belonged to previously described high-risk clones. Sequence type 175 (ST175) was detected in all 9 participating hospitals and accounted for 68% (n = 101) of the XDR isolates, distantly followed by ST244 (n = 16), ST253 (n = 12), ST235 (n = 8), and ST111 (n = 2), which were detected only in 1 to 2 hospitals. Through phenotypic and molecular methods, the presence of horizontally acquired carbapenemases was detected in 21% of the isolates, mostly VIM (17%) and GES enzymes (4%). At least two representative isolates from each clone and hospital (n = 44) were fully sequenced on an Illumina MiSeq. Classical mutational mechanisms, such as those leading to the overexpression of the ß-lactamase AmpC or efflux pumps, OprD inactivation, and/or quinolone resistance-determining regions (QRDR) mutations, were confirmed in most isolates and correlated well with the resistance phenotypes in the absence of horizontally acquired determinants. Ceftolozane-tazobactam resistance was not detected in carbapenemase-negative isolates, in agreement with sequencing data showing the absence of ampC mutations. The unique set of mutations responsible for the XDR phenotype of ST175 clone documented 7 years earlier were found to be conserved, denoting the long-term persistence of this specific XDR lineage in Spanish hospitals. Finally, other potentially relevant mutations were evidenced, including those in penicillin-binding protein 3 (PBP3), which is involved in ß-lactam (including ceftolozane-tazobactam) resistance, and FusA1, which is linked to aminoglycoside resistance.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/genética , Aminoglicosídeos/farmacologia , Proteínas de Bactérias/genética , Cefalosporinas/farmacologia , Fluoroquinolonas/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Epidemiologia Molecular , Ácido Penicilânico/análogos & derivados , Ácido Penicilânico/farmacologia , Polimixinas/farmacologia , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/epidemiologia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/isolamento & purificação , Espanha/epidemiologia , Tazobactam , Resistência beta-Lactâmica/genética , beta-Lactamases/genética
13.
Artigo em Inglês | MEDLINE | ID: mdl-28559275

RESUMO

Limited information is available on the urinary excretion of colistin in infected patients. This study aimed to investigate the pharmacokinetics of colistimethate sodium (CMS) and formed colistin in urine in patients with multidrug-resistant (MDR) Gram-negative bacterial infections. A pharmacokinetic study was conducted on 12 patients diagnosed with an infection caused by an extremely drug-resistant (XDR) P. aeruginosa strain and treated with intravenous CMS. Fresh urine samples were collected at 2-h intervals, and blood samples were collected predose (Cmin ss) and at the end of the CMS infusion (Cmax ss) for measurement of concentrations of CMS and formed colistin using high-performance liquid chromatography (HPLC). CMS urinary recovery was determined as the summed amount of CMS and formed colistin recovered in urine for each 2-h interval divided by the CMS dose. There were 12 enrolled patients, 9 of whom were male (75%). Data [median (range)] were as follows: age, 65.5 (37 to 86) years; colistimethate urinary recovery 0 to 6 h, 42.6% (2.9% to 72.8%); range of concentrations of colistin in urine, <0.1 to 95.4 mg/liter; Cmin ss and Cmax ss of colistin in plasma, 0.9 (<0.2 to 1.4) and 0.9 (<0.2 to 1.4) mg/liter, respectively. In 6/12 (50%) patients, more than 40% of the CMS dose was recovered in the urine within the first 6 h after CMS administration. This study demonstrated rapid urinary excretion of CMS in patients within the first 6 h after intravenous administration. In all but one patient, the concentrations of formed colistin in urine were above the MIC for the most predominant isolate of P. aeruginosa in our hospital. Future studies are warranted for optimizing CMS dosage regimens in urinary tract infection (UTI) patients.


Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Antibacterianos/farmacocinética , Antibacterianos/urina , Colistina/análogos & derivados , Infecções por Pseudomonas/tratamento farmacológico , Infecções Urinárias/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Cromatografia Líquida de Alta Pressão , Colistina/farmacocinética , Colistina/uso terapêutico , Colistina/urina , Farmacorresistência Bacteriana Múltipla , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Infecções Urinárias/microbiologia
15.
Rev. esp. quimioter ; 30(3): 224-228, jun. 2017. tab, graf
Artigo em Inglês | IBECS | ID: ibc-163235

RESUMO

The use of colistin for the treatment of multiresistant bacteria has led to the emergence of colistin-resistant strains of Gram-negative bacilli. Treatment of infections caused by these pan–drug-resistant bacteria is difficult owing to the paucity of effective antibiotics. We report two cases of ventilator-associated respiratory infection caused by pan–drug-resistant, colistin-resistant Pseudomonas aeruginosa that were successfully treated with ceftolozane-tazobactam (AU)


La utilización de colistina para el tratamiento de bacterias multirresistentes ha favorecido la aparición de cepas de bacilos gramnegativos resistentes a dicho antibiótico. El tratamiento de las infecciones producidas por estas bacterias panresistentes es difícil dada la escasez de antibióticos que se pueden emplear en esta situación. Se presentan dos pacientes con infecciones respiratorias relacionadas con ventilación mecánica producidas por una Pseudomonas aeruginosa panresistente y resistente a colistina que fueron tratadas con ceftolozano/tazobactam con buenos resultados (AU)


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Colistina/uso terapêutico , Resistência beta-Lactâmica , Pseudomonas aeruginosa , Pseudomonas aeruginosa/isolamento & purificação , Infecções Respiratórias/tratamento farmacológico , Respiração Artificial/efeitos adversos , Infecções Respiratórias/prevenção & controle , Respiração Artificial , Cuidados Críticos/métodos
16.
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
17.
BMC Infect Dis ; 17(1): 11, 2017 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-28056821

RESUMO

BACKGROUND: Colistin has a narrow therapeutic window with nephrotoxicity being the major dose-limiting adverse effect. Currently, the optimal doses and therapeutic plasma levels are unknown. METHODS: Prospective observational cohort study, including patients infected by colistin-susceptible P. aeruginosa treated with intravenous colistimethate sodium (CMS). Clinical data and colistin plasma levels at steady-state (Css) were recorded. The primary and secondary end points were clinical cure and 30-day all-cause mortality. RESULTS: Ninety-one patients were included. Clinical cure was observed in 72 (79%) patients. The mean (SD) Css was 1.49 (1.4) mg/L and 2.42 (1.5) mg/L (p = 0.01) in patients who achieved clinical cure and those who not, respectively. Independent risk factors for clinical failure were male sex (OR 5.88; 95% CI 1.09-31.63), APACHE II score (OR 1.15; 95% CI 1.03-1.27) and nephrotoxicity at the EOT (OR 9.13; 95% CI 95% 2.06-40.5). The 30-day mortality rate was 30.8%. Risk factors for 30-day mortality included the APACHE II score (OR 1.98; 95% CI 1-1.20), the McCabe score (OR 2.49; 95% CI 1.14-5.43) and the presence of nephrotoxicity at the end of treatment (EOT) (OR 3.8; 95% CI 1.26-11.47). CONCLUSION: In this series of patients with infections caused by XDR P. aeruginosa infections, Css is not observed to be related to clinical outcome.


Assuntos
Antibacterianos/sangue , Colistina/sangue , Farmacorresistência Bacteriana Múltipla , Infecções por Pseudomonas/sangue , Pseudomonas aeruginosa , Administração Intravenosa , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Antibacterianos/farmacocinética , Disponibilidade Biológica , Colistina/administração & dosagem , Colistina/efeitos adversos , Colistina/análogos & derivados , Colistina/farmacocinética , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Feminino , Humanos , Nefropatias/sangue , Nefropatias/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
18.
Enferm. infecc. microbiol. clín. (Ed. impr.) ; 35(1): 5-11, ene. 2017. tab, graf, ilus
Artigo em Inglês | IBECS | ID: ibc-160155

RESUMO

Objective: To describe a clonal outbreak due to vancomycin-resistant Enterococcus faecium (VREF) in the nephrology and renal transplant unit of a tertiary teaching hospital in Barcelona, Spain, and to highlight how active patient and environment surveillance cultures, as well as prompt and directed intervention strategies, mainly environmental, helped to successfully bring it under control. Patients and methods: A study was conducted on patients admitted to the nephrology ward with any culture positive for VREF over a 6-month period (August 2012–January 2013). Based on the identification of a clonal link between the isolates, weekly rectal screening using swabs was implemented for all patients, as well as environmental cultures and cleaning of medical equipment and the ward. VREF isolates were identified by MicroScan and confirmed by Etest. Bacterial identification was confirmed by MALDI-TOF MS. The presence of van genes, and esp and hyl virulence genes was determined using PCR. The clonal relationship between the isolates was studied first with DiversiLab (bioMérieux), and then by PFGE-Smal and MLST. A two-tier sequence of infection control measures was implemented. Results: During the study period, VREF was isolated from 13 patients. All cases were colonized with no criteria for infection. VREF isolates were also extensively recovered from the environment and medical equipment. Isolates carried the vanA gene, and were multidrug-resistant, including high-level resistance (MIC >16mg/L) to vancomycin and teicoplanin. Molecular analysis showed that all VREF isolates belonged to sequence type 17 (ST17) carrying hyl virulence genes. After implementing infection control measures in a two-tier sequence, and reinforcing particularly environmental and medical equipment cleaning, no further cases were detected in the follow-up year. Conclusion: A clonal outbreak of VREF-ST17 involving only colonization is reported. The prompt implementation of aggressive infection control measures in patients and the environment was effective in controlling the outbreak and avoided the potential emergence of infection among patients (AU)


Objetivo: Describir un brote clonal de Enterococcus faecium resistente a vancomicina (VREF) en la unidad de trasplante renal de un hospital universitario en Barcelona (España) y destacar que los controles ambientales, así como las estrategias de intervención dirigidas y tempranas, principalmente ambientales, fueron suficientes para controlar el brote. Pacientes y métodos: Se estudiaron todos los pacientes ingresados en la unidad de nefrología con un cultivo positivo para VREF en un periodo de 6 meses (Agosto de 2012 a Enero de 2013). Basados en la identificación de una relación clonal entre las cepas, se implementaron frotis rectales de cribado para todos los pacientes, así como frotis ambientales y limpieza de todo el material médico y de la unidad. Se identificaron las cepas de VREF por MicroScan y se confirmaron con Etest. La identificación bacteriana se confirmó con MALDI-TOF MS. La presencia de genes van, y de genes de virulencia esp y hyl, se investigó por PCR. La relación clonal entre las cepas se estudió con DiversiLab (bioMérieux), y después con PFGE-Smal y MLST. Resultados: Durante el periodo estudiado, se aislaron cepas de VREF de 13 pacientes. Todos fueron casos de colonización sin casos de infección. Se aislaron numerosas cepas del ambiente y del equipo médico. Las cepas presentaban el gen VanA y eran multirresistentes. El análisis molecular mostró que todas las cepas pertenecían a la secuencia tipo17 (ST17), portando genes de virulencia hyl. Tras la implementación de medidas de control de infección de 2 niveles, e incrementando sobretodo la limpieza del ambiente y del equipo médico, no se detectaron nuevos casos en el año posterior. Conclusión: Se informa de un brote clonal de VREF-ST17. La pronta implementación de medidas agresivas de control de infección en pacientes y en el ambiente fue efectiva para el control del brote (AU)


Assuntos
Humanos , Enterococos Resistentes à Vancomicina/patogenicidade , Infecção Hospitalar/prevenção & controle , Transplante de Rim , Controle de Infecções/organização & administração , Resistência a Vancomicina , Enterococcus faecalis/patogenicidade , Surtos de Doenças/prevenção & controle
19.
Enferm Infecc Microbiol Clin ; 35(1): 5-11, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27156245

RESUMO

OBJECTIVE: To describe a clonal outbreak due to vancomycin-resistant Enterococcus faecium (VREF) in the nephrology and renal transplant unit of a tertiary teaching hospital in Barcelona, Spain, and to highlight how active patient and environment surveillance cultures, as well as prompt and directed intervention strategies, mainly environmental, helped to successfully bring it under control. PATIENTS AND METHODS: A study was conducted on patients admitted to the nephrology ward with any culture positive for VREF over a 6-month period (August 2012-January 2013). Based on the identification of a clonal link between the isolates, weekly rectal screening using swabs was implemented for all patients, as well as environmental cultures and cleaning of medical equipment and the ward. VREF isolates were identified by MicroScan and confirmed by Etest. Bacterial identification was confirmed by MALDI-TOF MS. The presence of van genes, and esp and hyl virulence genes was determined using PCR. The clonal relationship between the isolates was studied first with DiversiLab (bioMérieux), and then by PFGE-Smal and MLST. A two-tier sequence of infection control measures was implemented. RESULTS: During the study period, VREF was isolated from 13 patients. All cases were colonized with no criteria for infection. VREF isolates were also extensively recovered from the environment and medical equipment. Isolates carried the vanA gene, and were multidrug-resistant, including high-level resistance (MIC >16mg/L) to vancomycin and teicoplanin. Molecular analysis showed that all VREF isolates belonged to sequence type 17 (ST17) carrying hyl virulence genes. After implementing infection control measures in a two-tier sequence, and reinforcing particularly environmental and medical equipment cleaning, no further cases were detected in the follow-up year. CONCLUSION: A clonal outbreak of VREF-ST17 involving only colonization is reported. The prompt implementation of aggressive infection control measures in patients and the environment was effective in controlling the outbreak and avoided the potential emergence of infection among patients.


Assuntos
Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Surtos de Doenças/prevenção & controle , Enterococcus faecium/efeitos dos fármacos , Infecções por Bactérias Gram-Positivas/epidemiologia , Infecções por Bactérias Gram-Positivas/prevenção & controle , Unidades Hospitalares , Transplante de Rim , Resistência a Vancomicina , Adulto , Idoso , Microbiologia Ambiental/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Espanha/epidemiologia , Fatores de Tempo
20.
AIDS Res Treat ; 2016: 5120831, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27699068

RESUMO

Hypovitaminosis D and secondary hyperparathyroidism are frequent among HIV-infected patients. As there are no data about the best supplementation therapy both in treatment and in maintenance, we conducted an observational study of 300 HIV-infected patients for whom vitamin D and parathormone (PTH) had been measured in order to validate a protocol of vitamin D supplementation in patients with HIV-infection. Patients with vitamin D deficiency (defined as 25(OH)D < 10 ng/mL), insufficiency (defined as 25(OH)D < 20 ng/mL), or hyperparathyroidism (PTH > 65 pg/mL) were supplemented with cholecalciferol 16.000IU (0.266 mg) weekly (if deficiency) or fortnightly (if insufficiency or high PTH levels). Rates of normalization of 25(OH)D (levels above 20 ng/mL) and PTH levels (<65 pg/mL) were analyzed. Multivariate analysis of factors related to normalization was carried out. With a median follow-up of 2 years, 82.1% of patients with deficiency and 83.9% of cases with insufficiency reached levels above 20 ng/mL. However, only 67.2% of individuals with hyperparathyroidism at baseline reached target levels (<65 pg/mL). Independent factors for not achieving PTH objective were tenofovir (TDF) and protease inhibitors use. In HIV-infected patients with hypovitaminosis, the protocol of cholecalciferol supplementation normalized vitamin D levels regardless of antiretroviral regimen in a high proportion of patients but it was less effective to correct hyperparathyroidism.

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