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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.
Perfusion ; : 267659119864813, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31387460

RESUMO

INTRODUCTION: New antibiotics with bactericidal activity against multi-drug-resistant bacteria are increasingly used in the intensive care units. Here, we aimed to evaluate the influence of the extracorporeal membrane oxygenation on plasma levels of ceftolozane. CASE REPORT: A 34-year-old female was admitted to the intensive care unit after bilateral lung transplantation, complicated by primary graft dysfunction and cardiogenic shock needing venoarterial extracorporeal membrane oxygenation. Ceftolozane/tazobactam was started. Plasma ceftolozane levels were monitored on the first and third days of antibiotic treatment. A non-compartment pharmacokinetic analysis was performed and the extraction rate through the oxygenator was calculated. DISCUSSION: The extracorporeal circuit of extracorporeal membrane oxygenation may alter the pharmacokinetics of antibiotics, to varying degrees due to drug sequestration and increased distribution volume. In this case, the extracorporeal membrane oxygenation circuit had little impact on the ceftolozane plasma concentration. CONCLUSION: Plasma levels of ceftolozane are stable in the extracorporeal membrane oxygenation circuit, suggesting that adjustment of standard doses of ceftolozane in patients with extracorporeal membrane oxygenation support may not be needed.

3.
Vet Parasitol ; 271: 31-37, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31303200

RESUMO

The recovery of fenbendazole efficacy against Haemonchus contortus was attempted in a sheep intensive production system, using a strategy of population replacement in which the initial absolute efficacy of fenbendazole was 0%. The strategy was based on managing the parasite populations in refugia. Firstly, the resistant parasite population was reduced by means of anthelmintic treatments with efficacious drugs (Phase I), then a new, susceptible population was introduced in summer by way of artificially infected lambs at weaning, which were left to graze on the experimental pasture for eleven months (Phase II). Lastly, the impact of the replacement strategy, in terms of benzimidazole efficacy, was measured (Phase III). Faecal egg counts from permanent lambs and worm burdens as a measure of pasture infectivity from tracer lambs were determined throughout the study. During Phase I, faecal egg counts diminished from a peak of 2968 (300-7740) epg to 0 epg at the end, while adult worm burdens of H. contortus were reduced from 2625 (800-5100) to 0, which showed that the treatment strategy used in Phase I was effective in reducing the resistant population. These parameters also showed that good levels of pasture contamination and infectivity were achieved in Phase II, as faecal egg counts of up to 7275 (3240-13080) epg and adult worm burdens of 500 (200-800) H. contortus were reached. The absolute benzimidazole efficacy on H. contortus estimated at 16 months post-population replacement (Phase III) was 97.58%. The results lead to the conclusion that the recovery of anthelmintic efficacy of fenbendazole against a resistant population of H. contortus may be achieved by means of a strategy based on management of refugia and a subsequent introduction of a susceptible population. This strategy might be translatable to other resistant nematode genera.


Assuntos
Criação de Animais Domésticos/métodos , Resistência a Medicamentos , Fenbendazol/farmacologia , Hemoncose/veterinária , Haemonchus/efeitos dos fármacos , Criação de Animais Domésticos/normas , Animais , Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico , Benzimidazóis/farmacologia , Benzimidazóis/uso terapêutico , Fenbendazol/uso terapêutico , Hemoncose/tratamento farmacológico , Hemoncose/prevenção & controle , Ovinos
4.
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.

5.
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.

6.
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
7.
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
8.
Ther Drug Monit ; 41(3): 376-382, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30633087

RESUMO

BACKGROUND: An optimal antifungal therapy for invasive candidiasis in critically ill patients is essential to reduce the high mortality rates. Acute kidney injury is common, and continuous renal replacement therapies are frequently used. Previous studies have demonstrated a lack of effect from different continuous renal replacement techniques on micafungin clearance. However, the use of high cutoff pore size membranes could potentially allow for the loss of albumin and alter micafungin pharmacokinetics. The objective was to explore the pharmacokinetics of micafungin in critically ill patients undergoing continuous venovenous high cutoff membrane hemodialysis (CVVHD-HCO). METHODS: Prospective observational study performed in critically ill patients treated with 100 mg/d of micafungin and undergoing CVVHD-HCO. CVVHD-HCO sessions were performed using Prisma-Flex monitors and dialyzers with a membrane of polyarylethersulfone of 1.1-m surface area and 45-kDa pore size. Blood samples were collected from arterial prefilter, venous postfilter, and the drainage line ports at 0 (predose), 1, 4, 12, 24 hours after dose, and micafungin concentrations were determined using HPLC-UV. RESULTS: Nine patients (55.6% male; age: 28-80 years) were included. Median (range) of micafungin concentrations in the effluent were <0.2 (<0.2-0.4) mg/L at low (predose) and 0.4 (<0.2-0.7) mg/L at high (1 h) concentrations. The extraction ratio was <12% at each time point. A 2-compartment model best described the time course of plasma concentrations, and body weight was the only covariate that improved the model. CONCLUSIONS: This is the first study demonstrating that CVVHD-HCO does not alter the pharmacokinetics of micafungin, and that standard doses of this antifungal can be used.

9.
Crit Care ; 22(1): 94, 2018 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-29655372

RESUMO

BACKGROUND: Dosing in obese critically ill patients is challenging due to pathophysiological changes derived from obesity and/or critical illness, and it remains fully unexplored. This study estimated the micafungin probability of reaching adequate 24-h area under the curve (AUC0-24h)/minimum inhibitory concentration (MIC) values against Candida spp. for an obese/nonobese, critically ill/noncritically ill, large population. METHODS: Blood samples for pharmacokinetic analyses were collected from 10 critically ill nonobese patients, 10 noncritically ill obese patients, and 11 critically ill morbidly obese patients under empirical/directed micafungin treatment. Patients received once daily 100-150 mg micafungin at the discretion of the treating physician following the prescribing information and hospital guidelines. Total micafungin concentrations were determined by high-performance liquid chromatography (HPLC). Monte-Carlo simulations were performed and the probability of target attainment (PTA) was calculated using the AUC0-24/MIC cut-offs 285 (C. parapsilosis), 3000 (all Candida spp.), and 5000 (nonparapsilosis Candida spp.). Intravenous once-daily 100-mg, 150-mg, and 200-mg doses were simulated at different body weights (45, 80, 115, 150, and 185 kg) and age (30, 50, 70 and 90 years old). PTAs ≥ 90% were considered optimal. Fractional target attainment (FTA) was calculated using published MIC distributions. A dosing regimen was considered successful if the FTA was ≥ 90%. RESULTS: Overall, 100 mg of micafungin was once-daily administered for nonobese and obese patients with body mass index (BMI) ≤ 45 kg/m2 and 150 mg for morbidly obese patients with BMI > 45 kg/m2 (except two noncritically ill obese patients with BMI ~ 35 kg/m2 receiving 150 mg, and one critically ill patient with BMI > 45 kg/m2 receiving 100 mg). Micafungin concentrations in plasma were best described using a two-compartment model. Weight and age (but not severity score) were significant covariates and improved the model. FTAs > 90% were obtained against C. albicans with the 200 mg/24 h dose for all body weights (up to 185 kg), and with the 150 mg/24 h for body weights < 115 kg, and against C. glabrata with the 200 mg/24 h dose for body weights < 115 kg. CONCLUSION: The lack of adequacy for the 100 mg/24 h dose suggested the need to increase the dose to 150 mg/24 h for C. albicans infections. Further pharmacokinetic/pharmacodynamic studies should address optimization of micafungin dosing for nonalbicans Candida infections.


Assuntos
Candidíase/tratamento farmacológico , Relação Dose-Resposta a Droga , Equinocandinas/farmacologia , Equinocandinas/farmacocinética , Lipopeptídeos/farmacologia , Lipopeptídeos/farmacocinética , Obesidade Mórbida/fisiopatologia , Obesidade/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/farmacocinética , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Área Sob a Curva , Índice de Massa Corporal , Estado Terminal/terapia , Equinocandinas/uso terapêutico , Feminino , Humanos , Lipopeptídeos/uso terapêutico , Masculino , Micafungina , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Método de Monte Carlo , Curva ROC , Espanha
10.
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.

11.
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
12.
Farm. hosp ; 41(2): 187-203, mar.-abr. 2017. graf, tab
Artigo em Inglês | IBECS | ID: ibc-160949

RESUMO

Introduction: Community-acquired pneumonia (CAP) is associated with high morbidity and mortality rates. Despite methicillin-resistant Staphylococcus aureus (MRSA) having often been associated with nosocomial pneumonia, the condition of some MRSA CAP patients is severe enough to warrant their being admitted to ICU. Objective: The purpose of this study is to conduct a systematic review of the literature on antibiotic treatment of MRSA CAP in critically-ill patients. Material and methods: An online search was conducted for locating articles on MRSA CAP in critically ill patients. Relevant publications were identified in PUBMED, the BestPractice database, UpToDate database and the Cochrane Library for articles published in English within the December 2001 - April 2016 time frame. Results: A total of 70 articles were found to have been published, 13 (18.8%) having been included and 57 (81.4%) excluded. Cohort studies were predominant, having totaled 16 in number (20.7%) as compared to one sole cross-sectional study (3.5%). Conclusions: The experience in the treatment of MRSA CAP in patients requiring admission to ICU is quite limited. Vancomycin or linezolid seem to be the treatments of choice for MRSA CAP, although there not be any specific recommendation in this regard. It may be useful to use alternative routes, such as administration via aerosolized antibiotics, continuous infusion or in association with other antibiotics (AU)


Introducción: La neumonía adquirida en la comunidad (NAC) está relacionada con unas tasas elevadas de morbi-mortalidad. A pesar de que Staphylococcus aureus resistente a meticilina (SARM) se ha relacionado frecuentemente con la neumonía nosocomial, algunos pacientes con NAC por este microorganismo revisten la suficiente gravedad como para precisar su ingreso en la UCI. Objetivos: Efectuar una revisión sistemática de la literatura sobre el tratamiento antibiótico de la NAC por SARM en pacientes críticos. Material y métodos: Se realizó una búsqueda de artículos sobre NAC por SARM en el paciente crítico. Se identificaron las publicaciones pertinentes en PUBMED, BestPractice database, UpToDate database y Cochrane Plus Library para artículos publicados en inglés desde diciembre del 2001 hasta abril del 2016. Resultados: Se encontraron 70 publicaciones, incluyendo 13 (18,8%) y excluyendo 57 (81,4%). Predominaron los estudios de cohortes con un total de 6 (20,7%), frente a una única publicación en forma de estudio transversal (3,5%). Conclusiones: La experiencia en el tratamiento de la NAC por SARM en pacientes que precisen ingreso en la UCI es muy limitada. La vancomicina o el linezolid parecen ser las terapias en las que se dispone de una mayor experiencia, aunque no existe ninguna recomendación específica al respecto. Puede ser útil la utilización de vías alternativas como la nebulizada, administración en perfusión continua o en asociación con otros antibióticos (AU)


Assuntos
Humanos , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Pneumonia Estafilocócica/epidemiologia , Infecções Estafilocócicas/epidemiologia , Antibacterianos/administração & dosagem , Infecções Comunitárias Adquiridas/epidemiologia , Cuidados Críticos/estatística & dados numéricos , Unidades de Terapia Intensiva/estatística & dados numéricos
13.
Farm Hosp ; 41(2): 187-203, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28236797

RESUMO

INTRODUCTION: Community-acquired pneumonia (CAP) is associated with high morbidity and mortality rates. Despite methicillin-resistant Staphylococcus aureus (MRSA) having often been associated with nosocomial pneumonia, the condition of some MRSA CAP patients is severe enough to warrant their being admitted to ICU. OBJECTIVE: The purpose of this study is to conduct a systematic review of the literature on antibiotic treatment of MRSA CAP in critically-ill patients. MATERIAL AND METHODS: An online search was conducted for locating articles on MRSA CAP in critically ill patients. Relevant publications were identified in PUBMED, the BestPractice database, UpToDate database and the Cochrane Library for articles published in English within the December 2001 - April 2016 time frame. RESULTS: A total of 70 articles were found to have been published, 13 (18.8%) having been included and 57 (81.4%) excluded. Cohort studies were predominant, having totaled 16 in number (20.7%) as compared to one sole cross-sectional study (3.5%). CONCLUSIONS: The experience in the treatment of MRSA CAP in patients requiring admission to ICU is quite limited. Vancomycin or linezolid seem to be the treatments of choice for MRSA CAP, although there not be any specific recommendation in this regard. It may be useful to use alternative routes, such as administration via aerosolized antibiotics, continuous infusion or in association with other antibiotics.


Assuntos
Antibacterianos/uso terapêutico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Estado Terminal/terapia , Staphylococcus aureus Resistente à Meticilina , Pneumonia Estafilocócica/tratamento farmacológico , Cuidados Críticos , Humanos
14.
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
15.
Enferm. infecc. microbiol. clín. (Ed. impr.) ; 34(10): 652-654, dic. 2016. tab
Artigo em Inglês | IBECS | ID: ibc-158738

RESUMO

In this prospective observational study performed in 12 hospitalized patients with proven or suspected invasive fungal infection treated for a mean of 14 days with micafungin (MCF), 8 of whom with pre-existing liver function impairment, plasma levels of MCF at steady state were not correlated with liver function tests at the beginning of treatment. Liver function remained stable or even improved in all patients, except in one in which MCF was discontinued due to liver toxicity (AU)


Se trata de un estudio prospectivo observacional en 12 pacientes ingresados en un hospital con sospecha o infección fúngica confirmada tratados con micafungina (MCF) durante una media de 14 días, 8 de los cuales con presencia de alteración hepática preexistente. Los niveles plasmáticos de MCF en el estado estacionario no se correlacionaron con los valores basales de las pruebas hepáticas al inicio del tratamiento. La función hepática permaneció estable o incluso mejoró en todos los pacientes excepto en uno de ellos en el que el tratamiento con MCF fue interrumpido debido a la presencia de toxicidad hepática (AU)


Assuntos
Humanos , Antifúngicos/farmacocinética , Fungemia/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Estudos Prospectivos , Testes de Função Hepática , Monitoramento de Medicamentos/métodos
16.
Cuad. psiquiatr. psicoter. niño adolesc ; (61): 17-33, ene.-jun. 2016. tab
Artigo em Espanhol | IBECS | ID: ibc-158144

RESUMO

El Hospital de Día Infanto Juvenil (HDDIJ) basa su modelo de intervención en la terapia institucional. Este recurso ha sido ampliamente validado en el tratamiento de diferentes trastornos mentales de la infancia y adolescencia, y se propone para la intervención de la patología mental grave en esta población. Sin embargo, la estructura óptima de este dispositivo no ha sido bien establecida. En este trabajo presentamos a modo de ejemplo un posible esquema para estructurar la guía de actuación interna de un hospital de día infanto juvenil y del plan de intervención individualizado de trabajo con cada niño, basado en la experiencia del Hospital Mancha Centro. Así mismo, presentamos el proyecto de investigación actualmente en marcha en nuestra unidad de elaboración de un algoritmo de evaluación neuropsicológica para Trastornos del Espectro Autista en el HDDIJ. Abrimos igualmente el debate para la propuesta de posibles indicadores clínicos de evolución en HDDIJ (AU)


Child and Adolescent psychiatric Day Hospital (CAPDH)bases its intervention model in institutional therapy. This intervention has been extensively validated in the treatment of various mental disorders in childhood and adolescence, and it has been proposed for the intervention of severe mental illness in this population. However , the optimal structure of this device has not been well established. We present a possible structural scheme for a clinical actuation guide in child and adolescent day hospital and individual action plan work, based on the experience of the Hospital Mancha Centro. Also , we present the research project currently underway in our unit developing a neuropsychological evaluation algorithm for Autism Spectrum Disorders in (CAPDH). Also we opened the discussion for the proposed clinical indicators of possible developments in HDDIJ (AU)


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Adulto Jovem , Hospital Dia/métodos , Hospital Dia/psicologia , Transtorno Autístico/complicações , Transtorno Autístico/psicologia , Psicoterapia/métodos , Psicologia da Criança/métodos , Desenvolvimento da Personalidade , Neuropsicologia/métodos , Indicadores de Serviços/métodos , Indicadores de Serviços/organização & administração , Apoio Social
17.
J Antimicrob Chemother ; 71(3): 696-702, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26702922

RESUMO

OBJECTIVES: The objectives of this study were to determine the effects of obesity on unbound trough concentrations and on the achievement of pharmacokinetic (PK)/pharmacodynamic (PD) targets of piperacillin and meropenem in critically ill patients. METHODS: This study retrospectively analysed therapeutic-drug-monitoring data from ICU databases in Australia, Germany and Spain, as well as from a large PK study. The presence of obesity was defined as a BMI ≥30 kg/m(2), and patients were also categorized based on level of renal function. The presence of obesity was compared with unbound piperacillin and meropenem trough concentrations. We also used logistic regression to describe factors associated with the achievement of the PK/PD targets, an unbound concentration maintained above the MIC breakpoint (100% fT>MIC and 100% fT>4×MIC) of Pseudomonas aeruginosa. RESULTS: In all, 1400 patients were eligible for inclusion in the study. The median age and weight were 67 years (IQR 52-76 years) and 79 kg (69-90 kg), respectively, and 65% of participants were male. Significantly lower median piperacillin trough concentrations [29.4 mg/L (IQR 17.0-58.0 mg/L)] were found in obese patients compared with non-obese patients [42.0 mg/L (21.5-73.5 mg/L)] (P = 0.001). There was no difference for meropenem trough concentrations [obese 10.3 mg/L (IQR 4.8-16.0 mg/L) versus non-obese 11.0 mg/L (4.3-18.5 mg/L); P = 0.296]. Using logistic regression, we found that the presence of obesity was not associated with achievement of 100% fT>MIC, but the use of prolonged infusion, a creatinine clearance ≤100 mL/min, increasing age and female gender were for various PK/PD targets for both piperacillin and meropenem (P < 0.05). CONCLUSIONS: This large dataset has shown that the presence of obesity in critically ill patients may affect piperacillin, but not meropenem, unbound trough concentrations.


Assuntos
Antibacterianos/farmacocinética , Estado Terminal , Obesidade , Piperacilina/farmacocinética , Plasma/química , Tienamicinas/farmacocinética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Austrália , Feminino , Alemanha , Humanos , Masculino , Meropeném , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Piperacilina/administração & dosagem , Pseudomonas aeruginosa/efeitos dos fármacos , Estudos Retrospectivos , Espanha , Tienamicinas/administração & dosagem , Adulto Jovem
18.
AIDS Behav ; 20(5): 1068-75, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26427376

RESUMO

Continuous HIV treatment is necessary to ensure successful combined antiretroviral therapy (cART). The aim of this study was to evaluate the incidence of patient-initiated non-structured treatment interruptions in HIV-infected persons who inject drugs and who received a multidisciplinary comprehensive program, including medical HIV care, drug-dependence treatment and psychosocial support, at a drug outpatient addiction center. Non-structured treatment interruptions were defined as ≥30 consecutive days off cART without medical indication. During a median follow-up of 53.8 months, 37/132 (28 %) patients experienced the first non-structured treatment interruptions. The cumulative probability of cART interruption at 5 years was 31.2 % (95 % CI 22.4-40.0). Current drug use injection ≥1/day (HR 14.77; 95 % CI 5.90-36.96) and cART naive patients (HR 0.35, 95 % CI 0.14-0.93) were predictive factors for non-structured treatment interruptions. HIV care provided at a drug addiction center is a useful strategy to sustain continuous cART, however, drug abstinence is essential for the long-term maintenance of cART.


Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Metadona/administração & dosagem , Tratamento de Substituição de Opiáceos/estatística & dados numéricos , Abuso de Substâncias por Via Intravenosa/complicações , Adulto , Comorbidade , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/psicologia , Infecções por HIV/virologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Espanha/epidemiologia , Centros de Tratamento de Abuso de Substâncias , Abuso de Substâncias por Via Intravenosa/tratamento farmacológico , Abuso de Substâncias por Via Intravenosa/epidemiologia , Resultado do Tratamento
19.
Enferm Infecc Microbiol Clin ; 34(10): 652-654, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25882063

RESUMO

In this prospective observational study performed in 12 hospitalized patients with proven or suspected invasive fungal infection treated for a mean of 14 days with micafungin (MCF), 8 of whom with pre-existing liver function impairment, plasma levels of MCF at steady state were not correlated with liver function tests at the beginning of treatment. Liver function remained stable or even improved in all patients, except in one in which MCF was discontinued due to liver toxicity.


Assuntos
Antifúngicos/farmacocinética , Equinocandinas/farmacocinética , Infecções Fúngicas Invasivas/metabolismo , Lipopeptídeos/farmacocinética , Hepatopatias/complicações , Antifúngicos/uso terapêutico , Equinocandinas/uso terapêutico , Feminino , Humanos , Infecções Fúngicas Invasivas/tratamento farmacológico , Lipopeptídeos/uso terapêutico , Masculino , Micafungina , Pessoa de Meia-Idade , Estudos Prospectivos
20.
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
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