[The challenge in colistin dosing: Updating available recommendations]. / El desafio en la dosificación de colistin: actualización de las recomendaciones disponibles.

Polymyxins have been available since the 1960s, however, because of their adverse effects, their use has been reserved for the treatment of infections caused by multiresistant bacteria. The increase in the clinical experience acquired in recent years and the published medical literature have raised doubts about the information provided by the product, indicating the need to update dosage recommendations, pharmacokinetics and pharmacokinetic/pharmacodynamic information (PK/PD). In addition, differences in concentration and dose between the different products of colistin may lead to errors of indication/administration and pose a risk to patients. In 2013, the European Medicines Agency (EMA) commissioned the Committee for Medicinal Products for Human Use (CHPM) to review available data and to make updated recommendations on the use of colistin. This procedure yielded a first report in 2014. This review highlights critical safety and efficacy aspects, reviews the recent pharmacokinetic and stability advances, the available pharmaceutical forms in Chile, providing the schemes currently recommended by health care agencies and experts in the field.

El desafio en la dosificación de colistin: actualización de las recomendaciones disponibles / The challenge in colistin dosing: updating available recommendations

Resumen Las polimixinas están disponibles desde la década de los 60; sin embargo, debido a sus efectos adversos su uso ha sido reservado para el tratamiento de infecciones provocadas por bacterias multi-resistentes. El aumento en la experiencia clínica adquirida en los últimos años y la literatura médica publicada han planteado dudas respecto de la información entregada del producto, poniendo en manifiesto la necesidad de actualizar las recomendaciones posológicas, su farmacocinética y la información farmacocinética/farmacodinámica. Además, las diferencias en cuanto a concentración y dosis entre los distintos productos del colistín pueden dar lugar a errores de indicación/administración y suponer un riesgo para los pacientes. El año 2013, la Agencia Europea de Medicamento (EMA) encargó al Comité de Productos Medicinales para uso Humano (CHPM) la revisión de los datos disponibles y que formulara recomendaciones actualizadas del uso de colistín. Dicho procedimiento arrojó un primer informe en 2014. Esta revisión destaca los aspectos críticos de seguridad y eficacia, revisa los recientes avances farmacocinéticos y de estabilidad, las formas farmacéuticas disponibles en Chile, proporcionando los esquemas actualmente recomendados por agencias sanitarias y expertos en el tema para distintos escenarios clínicos.

Polymyxins have been available since the 1960s, however, because of their adverse effects, their use has been reserved for the treatment of infections caused by multiresistant bacteria. The increase in the clinical experience acquired in recent years and the published medical literature have raised doubts about the information provided by the product, indicating the need to update dosage recommendations, pharmacokinetics and pharmacokinetic/pharmacodynamic information (PK/PD). In addition, differences in concentration and dose between the different products of colistin may lead to errors of indication/administration and pose a risk to patients. In 2013, the European Medicines Agency (EMA) commissioned the Committee for Medicinal Products for Human Use (CHPM) to review available data and to make updated recommendations on the use of colistin. This procedure yielded a first report in 2014. This review highlights critical safety and efficacy aspects, reviews the recent pharmacokinetic and stability advances, the available pharmaceutical forms in Chile, providing the schemes currently recommended by health care agencies and experts in the field.

Predictive value of superficial cultures to anticipate tunneled hemodialysis catheter-related bloodstream infection.

We performed a prospective study in patients with tunneled catheters to assess the validity of Gram stain and superficial culture for anticipating catheter exit-site infection and hemodialysis catheter-related bloodstream infection. The sensitivity and negative predictive value were high, and we succeeded in identifying a subpopulation at low risk of infection.

Vancomycin MICs do not predict the outcome of methicillin-resistant Staphylococcus aureus bloodstream infections in correctly treated patients.

BACKGROUND: Recent studies have reported a greater probability of vancomycin treatment failure in methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections caused by strains with a vancomycin MIC ≥ 1.5 mg/L. However, previous reports included patients treated without adjustments based on vancomycin serum levels and with different methods to evaluate MICs, which may render different results. METHODS: Over a 5 year period (2005-09), vancomycin MICs were determined for 361 MRSA isolates recovered from 309 patients with bloodstream infection using microdilution and the Etest simultaneously. The relationship between the vancomycin MICs determined by each method was assessed. To assess the outcome of patients treated with vancomycin, 104 patients for whom serum vancomycin levels had been determined were selected. RESULTS: The percentage of MRSA strains with MIC values ≥ 1.5 mg/L according to the Etest was 66.5% compared with only 3.6% according to microdilution. No correlation between mortality and any MIC value obtained with either method was observed, independently of the vancomycin serum levels measured. CONCLUSIONS: There is a poor correlation between vancomycin MIC values obtained by microdilution and by Etest. No association between mortality rate and any MIC value was observed, not even in patients with suboptimal vancomycin trough serum levels. These data do not support replacing or complementing the standard microdilution test with the Etest for determination of MICs of vancomycin in microbiology laboratories.

Poor compliance with antifungal drug use guidelines by transplant physicians: a framework for educational guidelines and an international consensus on patient safety.

The rate of compliance with antifungal drug use guidelines by transplant physicians is mostly unknown. We performed a nationwide electronic survey to assess antifungal use by different types of transplant physicians. Sixty-one percent (53/87) of the transplant programs responded (accounting for 85% of heart transplant procedures, 65% of kidney transplantations, and 71.5% of liver transplantations). Antifungal prophylaxis was used in 41.5% programs (liver 93.3%, heart 30.8%, and kidney 16%). Prophylaxis was universal in 32% of the programs and targeted only to selected patients in 68%, mainly indicated after re-transplantation (73.3%), re-intervention (66.7%) and hemodialysis (60%). Main drugs for universal prophylaxis were fluconazole and itraconazole (42.9% each), while fluconazole (60%), L-amphotericin B (AMB), and caspofungin (13.4% each) were preferred for targeted prophylaxis. Overall, 84.9% of the programs used galactomannan for the diagnosis of invasive aspergillosis (only 34% in BAL) and 66.6% used voriconazole as first-line monotherapy. Combination first-line therapy for invasive aspergillosis was used by 31.3%, mainly with voriconazole with caspofungin (40%) or anidulafungin (26.7%) or L-AMB-caspofungin (26.7%). Adherence of transplant physicians to current recommendations on antifungal treatment and prophylaxis is poor. An international consensus that responds to differences in patients and centers and emphasizes patient safety is clearly needed.

Listeriosis: An emerging public health problem especially among the elderly.

OBJECTIVES: To analyze the incidence trend of listeriosis, its present epidemiology and the potential benefit of aminoglycosides during the last two decades. METHODS: We reviewed all cases of invasive listeriosis detected during a 22-year period in a large tertiary hospital. Two equal periods of 11 years were compared. RESULTS: We detected 111 cases of listeriosis (32 during the first 11-year period and 79 during the second). Incidence of listeriosis increased significantly (from 4.66/10(6) inhabitants to 10.39/10(6) inhabitants; P = .001). In the second period, there were more patients >65 years (21.9%-45.6%; P = .02) and with no significant underlying diseases (0 vs. 16.5%; P = .02). Comparing clinical presentations between the two periods, primary bacteremia increased (40.6% vs. 55.7%), while central nervous system infections decreased (34.4% vs. 27.8%). Cotrimoxazole (SXT) use increased significantly in the second period (from 6.3% to 40.5%, P = .001) while the administration of aminoglycosides decreased (from 40.6% to 21.5%, P = .04). The use of combination therapy did not have any impact on mortality, however it did increase toxicity. CONCLUSIONS: Listeriosis should be considered an emerging health problem, especially among the elderly, including those with no underlying medical conditions. The use of aminoglycosides does not seem to be justified according to our data.

New antifungal agents for the treatment of candidaemia.

Suspected or proven invasive candidiasis is an important indication for antifungal drugs and a leading cause of death. Prompt initiation of effective therapy has a marked effect on survival, but the indiscriminate application of different risk-factor-based prediction models is massively increasing the number of patients treated unnecessarily. Fluconazole resistance levels are <5% in most European centres and the use of low doses is still common. Candins are fungicidal, have efficacy against device-related infections, have few interactions and are well tolerated. Accordingly, the use of newer, more expensive drugs must be carefully balanced in each case. Campaigns directed towards stewardship in antifungal drug use must take into consideration the choice of the drug, the dose and route of administration, and the length of therapy. Early microbiological information and medical education may contribute to better use of these important drugs. We review the characteristics of the new antifungals used for the treatment of candidaemia.