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To describe the clinical and microbiological outcomes of patients infected with multidrug-resistant Pseudomonas aeruginosa (MDRP) treated with colistin (colistimethate sodium) and the adverse events observed with this treatment. Retrospective study of MDRP infections treated with colistin from 1997 to 2006. 121 episodes were identified. The median daily intravenous dose was 240 mg/day; 28.9% of patients received intravenous and nebulized colistin. Clinical outcome was favorable in ten cases of bacteremia (62.5%, n = 16), 43 cases of bronchial infection (72.9%, n = 59), 13 cases of pneumonia (65%, n = 20), 11 cases of urinary infection (84.6%, n = 13), eight cases of skin and soft tissues (72.7%, n = 11), and in the one case of arthritis and one case of otitis. Eradication was achieved in 31 (34.8%) of the 89 patients with available bacteriologic data. Factors associated with bacteriological failure were smoking, chronic obstructive pulmonary disease (COPD), and previous infection with P. aeruginosa. Nephrotoxicity occurred in ten cases (8.3%), with the associated factors being previous chronic renal insufficiency, diabetes mellitus, and aminoglycoside use. Crude mortality was 16.5%, and related MDRP was 12.4%, and was higher in patients with pneumonia or bacteremia (36.1%) than in other types of infections (8.2%). Colistin is a safe option for the treatment of MDRP infections, with acceptable clinical outcomes. However, bacteriological eradication is difficult to achieve, especially in COPD patients.

Antibiotic-lock therapy (ALT) has been related to a reduction in the need for catheter withdrawal in patients with catheter-related infection. The stability of the antimicrobial solutions used in ALT has not been sufficiently investigated. A systematic literature review was performed to identify articles including studies on the stability of ALT solutions. Nine studies fulfilled the inclusion criteria requiring specific drug determination techniques, and no apparent drug alterations were observed. The main microorganisms studied were Staphylococcus spp., Pseudomonas aeruginosa, and Klebsiella pneumoniae. The antibiotics included cefazolin, ceftazidime, ciprofloxacin, colistin, gentamicin, ticarcillin/clavulanate, and vancomycin in solution, administered alone or in combinations, with or without heparin. All solutions were fairly stable except for ciprofloxacin at a concentration of 10mg/mL. Few studies applied strict criteria to assess the stability of antibiotic solutions used in ALT; hence, the currently available data are limited. Therefore, it seems advisable to include appropriate stability studies in further research on the use of ALT.

Prescribing antimicrobial treatment should not be considered an action that is performed routinely. The use of antibiotics should be accompanied by in-depth reflection, both at the time of drug sel...

The patients with bacteremia usually require hospital admission. In occasions they are remitted to their home, due to inappropriate diagnosis or rapid clinical improvement. The study describes the evolution and the interventions carried out in patients with community bacteremia that were remitted to their home.Prospective observational study carried out in a university hospital, of 450 beds, from March of 2000 until December of 2003. The hospital has a team that daily evaluated all blood cultures practiced; the patients with bacteremia remitted to home from the Emergency Department with inappropriate antibiotic were identified.During the period of study 1,172 episodes of true bacteremia were diagnosed, of these 247 (21.1%) were remitted to their home. In 50 cases (20.2%) it was considered necessary to contact with the patient: 36 for inappropriate empiric antibiotic treatment, 12 without antibiotic treatment and 2 for lack of information. Antibiotic treatment was initiated or modified in 34 cases, and 10 required hospital admission. Excluding the 66 patients who died in the first 48 h, the crude mortality of the patients remitted to home was inferior (4%) to that of the patients that required hospital admission (11.9%).One fifth of community bacteremia were ambulatory treated, frequently the antibiotic treatment was inappropriate, it is necessary to guarantee an appropriate control of this population.

We report a case of pleural effusion, pericardial thickening, and pulmonary involvement in a patient with dry cough, dyspnea, edema, and changes in the skin of the lower limbs. Treatment with cabergoline (Sogilen) had been started 4 months earlier. Pleural effusion, pericardial thickening, and impaired pulmonary function (airflow obstruction, increased airway resistance, and reduced carbon monoxide diffusing capacity) were observed. The Naranjo scale pointed to a probable relationship between cabergoline and these adverse effects. We report on outcome after 2 months of follow-up, during which time there was a slow and incomplete improvement in respiratory function. This is the first case in our practice setting of early pleuropulmonary toxicity associated with cabergoline.

S Grau,1 JC Pozo,2 E Romá,2 M Salavert,3 JA Barrueta,4 C Peral,4 I Rodriguez,5 D Rubio-Rodríguez,6 C Rubio-Terrés6 1Hospital del Mar (IMIM), Barcelona, 2Hospital Universitario Reina Sofía, Córdoba, 3Hospital Universitario y Politécnico La Fe, Valencia, 4Pfizer SLU, Alcobendas, 5Trial Form Support, Madrid, 6Health Value, Madrid, Spain Objective: To estimate the cost-effectiveness of three echinocandins (anidulafungin, caspofungin, and micafungin) and generic fluconazole in the treatment of nonneutropenic adult patients with candidemia and/or invasive candidiasis in intensive care units in Spain. Materials and methods: A decision-tree model was applied. The success and safety (hepatic and renal adverse effects) of first-line treatments were obtained from meta-analyses and systematic reviews of clinical trials. In the case of failure, a second-line treatment (liposomal amphotericin B after the echinocandins, or one of the echinocandins after fluconazole) was administered. The duration of the treatments (14 days total) was established by a panel of clinical experts using the Delphi method and according to Infectious Diseases Society of America guidelines. The cost of the medications and renal toxicity were considered. Deterministic and probabilistic sensitivity analysis using Monte Carlo simulations were carried out. Results: The total cost of the treatment of candidemia and/or invasive candidiasis with anidulafungin, caspofungin, micafungin, and fluconazole was €5,483, €5,968, €6,231, and €2,088, respectively. Anidulafungin was the dominant treatment (more effective, less expensive) compared to micafungin and caspofungin. The cost of achieving one more patient successfully treated with anidulafungin, caspofungin, and micafungin compared to fluconazole was €17,199, €23,962, and €27,339, respectively. The result remained stable, despite modification of the duration of the first-line and second-line treatments, as well as most of the dosing regimens. The probabilistic analysis also remained stable. Conclusion: In accordance with this economic study, anidulafungin would produce savings and would be the dominant treatment compared with micafungin and caspofungin in nonneutropenic adult patients with candidemia and/or invasive candidiasis in intensive care units in Spain. Keywords: invasive candidiasis, candidemia, anidulafungin, micafungin, caspofungin, fluconazole, cost-effectiveness analysis

Background Several factors, such as toxicity, virological failure or low adherence can justify the need for switching antiretroviral therapy (ART) in HIV patients. Purpose To study the reasons for switching ART in an HIV unit in a tertiary hospital. Secondary objectives were to study the number of switches over time and their estimated annual cost (EAC). Material and methods We recorded ART switches performed every 6 months from January 2012–June 2014 in our cohort of 1,550 HIV-infected patients. Date collected: previous and new ART, reason for switching and EAC (difference in the daily acquisition cost between the new and the previous ART calculated for 365 days of treatment). The Spearman test was used for bivariate correlations. Results 685 switches were performed: 117 (7.5%), 98 (6.3%), 130 (8.4%), 157 (10.1%) and 183 (11.8%) in each 6-month period. An increase in the number of changes/6 months over time was observed (Spearman rho: 0.9; p < 0.05). The total number of switches/6 months correlated only with toxicity (Spearman rho: 0.95; p < 0.05). View this table: Abstract CP-065 Table 1 Reasons for switching and EAC (euros) Conclusion References and/or Acknowledgements No conflict of interest.

Background Recent pharmacokinetic studies suggest the administration of higher colistimethate sodium (CMS) doses for treating multidrug resistant Gram-negative (MDR-GNB) infections. Purpose The aim was to compare the efficacy, pharmacokinetics and toxicity of the manufacturer’s recommended CMS doses (RD) versus higher doses (HD). Material and methods Pharmacokinetic study performed at a university hospital in patients with MDR-GNB infections treated with CMS. Data: demographics, severity (APACHE-II), CMS dose, type of infection, colistin plasma concentration (Cmin ss before next CMS dose and at steady state), nephrotoxicity at day 7 (RIFLE criteria), clinical cure and crude mortality. CMS doses were selected by the clinicians’ criteria. All patients treated with higher doses than those recommended by the national manufacturer were considered HD group. Cmin ss was measured by HPLC. Results 102 included patients. Clinical and pharmacokinetic characteristics. Conclusion More than 30% of patients received a higher than recommended CMS dose but they didn’t achieve better clinical outcomes in terms of clinical cure and mortality and they developed nephrotoxicity more frequently, a fact probably related to the higher colistin plasma levels. These findings suggest the need to select which patient’s profile can benefit from higher CMS doses. References and/or acknowledgements None. No conflict of interest.

Monitoring of plasma aminoglycoside and vancomycin concentrations is a measure of good clinical practice in critically ill patients. However, the frequency and application of this practice in Spanish hospitals is unknown.Observational, multicenter study based on a survey designed by the Study Group for Infection in the Critically Ill Patient of the Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC, Spanish Society of Infectious Diseases and Clinical Microbiology). The survey was sent to the 221 general hospitals with a more than 150-bed capacity included in the hospital directory. Questions regarding the antibiotics monitored, hospital services involved, systems used to report the results, and levels of intervention were included.Information was recorded from 56 (25.3%) hospitals with a total of 36,886 beds, among which 933 (2.5%) corresponded to critically ill patients. In 47 (83.9%) hospitals, plasma concentrations of one or two antibiotics were determined: vancomycin in 47 (83.9% of the total), amikacin in 41 (73.2%), and gentamicin in 40 (71.2%). Analyses were performed by the following services: Biochemistry in 34%, Pharmacy in 25.5% and Pharmacology in 8.5%. Only 57.4% of services recommended dose adjustments according to the results obtained, using eight different dose adjustment models.In 16% of the hospitals surveyed, monitoring of antibiotic concentrations was not performed in daily practice. There was considerable variation in all phases of the process, especially with regard to adjustment of plasma antibiotic concentrations. Consensus recommendations established by all the Services implicated are required to standardize monitoring of plasma antibiotic concentrations.

We evaluated the effectiveness and safety of rifampicin addition to clarithromycin in the treatment of Legionnaires' disease. An observational cohort study was conducted on patients assigned to a Legionnaires' disease outbreak. Of 32 patients with confirmed Legionella pneumonia, 11 received clarithromycin monotherapy and 21 received combination therapy of clarithromycin with rifampicin. Both groups had similar baseline characteristics and all patients were cured. Patients who received rifampicin had a 50% longer length of stay (P=0.035) and a trend towards higher bilirubin levels (P=0.053). Length of stay was directly correlated with the duration of rifampicin treatment (P=0.001). Combination therapy of clarithromycin and rifampicin had no additional benefit compared with clarithromycin monotherapy and could prolong the length of stay owing to possible negative drug interactions that could also affect other antibiotics.

Objectives To study the characteristics of the linezolid-associated serotonin syndrome cases. Methods Database search for linezolid-associated serotonin syndrome. Results Twelve cases were found. The mean age of patients was 52.8 years. All patients received linezolid concomitantly with selective serotonin re-uptake inhibitor drugs (SSRID). The onset of syndrome was 9.5 days after linezolid introduction and was directly correlated to patients' age (P = 0.024). The symptoms resolved in 2.9 days. Citalopram was associated with a delayed resolution (P = 0.018). A trend was observed towards longer resolution time the longer the half-life of the interacting drug (P = 0.096). Conclusions Patients are at risk when receiving SSRID concomitant with linezolid. The syndrome onset could be delayed in older patients. The resolution could be delayed when citalopram is involved in the syndrome.

Indications for the use of antimicrobials in critically ill patients are similar to those for other hospitalised patients. However, the selection of agents depends on the particular characteristics of patients in the intensive care unit (ICU), the form of presentation of infection, the type of infection and the bacteriological features of the causative pathogens. The use of antimicrobials in patients admitted to medical-surgical ICUs varies between 33 and 53%. The selection of empirical antimicrobials to be included in treatment protocols of the most common infections depends on the strong interrelationship between patient characteristics, predominant pathogens in each focus. and antimicrobials used for treatment. Epidemiological studies carried out in the past have identified the microorganisms most frequently responsible for community-acquired and nosocomial infections in patients admitted to ICUs. Susceptibility to antimicrobial agents may be different between each geographical area, between each hospital and even within the same hospital service. In addition, susceptibility patterns may change temporarily in relation to the use of particular antimicrobials or in association with other unknown factors so that assessment of endemic antimicrobial resistance patterns is very useful in order to tailor the antimicrobial regimens of therapeutic protocols. Antimicrobial use should not be a routine procedure. The clinical course of the patient (an indicator of effectiveness) should be closely monitored as well as the possible appearance of adverse effects and/or multiresistant pathogens. Controls are based on the assessment of plasma drug concentrations and microbiological surveillance to detect the presence of multiresistant strains or new antibacterial-resistant pathogens. Prevention of the development of multiresistant pathogens is the main goal of the ICU antimicrobial policy. Although a series of general strategies to reduce the presence of multiresistant pathogens have been proposed, the implementation of these recommendations in ICUs requires the cooperation of a member of the intensive care team.

Background Body mass index (BMI) is a factor related to the disposition of aminoglycosides (AMG). Dosage is based on total body weight (TBW) or adjusted body weight (ABW) according to patients’ BMI. Purpose To assess if the amikacin dosage prescribed to patients matches with the dosage based on BMI. To calculate the optimal cut-off point of BMI that predicts a 10% discrepancy between dosage based on TBW or ABW. Materials and Methods Retrospective study January 2003–December 2010 performed in a 450-bed tertiary hospital. Dosage of 15 mg/TBW was considered except for patients with TBW > 30% over ideal body weight (IBW). That dose was calculated according to ABW: ABW(kg) = IBW + 0.4(TBW–IBW) as recommended. Patients included: intravenous amikacin treatment of respiratory tract infections in an extended-interval dosing regimen with therapeutic drug monitoring of amikacin. Patients excluded: Data collected: demographics, TBW, height, BMI, renal function. Amikacin levels: fluorescence polarisation immunoassay (TDX, Abbott Lab) Pharmacokinetic analysis: Bayesian estimation compartmental model (PKS programme) Statistical analysis: ROC curve. Results 133 patients (79.70% men). Mean (±SD): age: 62.12 years (±15.48); TBW: 65.52kg (±13.43); height: 166.89 cm (±7.44); serum creatinine baseline: 0.68 (±0.19) and CrCl: 97.32 mL/min (±34.67). Difference between TBW dose vs. ABW dose (mg)(%): BMI[ 40]: 1 patient. A ROC curve was built to determine the best cut off point of BMI: 26 mg/m 2 Difference between recommended dosage and prescribed dosage (mg): BMI[ 40]: 1 patient. Conclusions Considerable variation between the dosage of amikacin based on TBW and ABW was observed with a reduction of recommended dose in patients with BMI ≥ 25 kg/m2 and an overdose in patients with BMI A reduction of 10% or more of the adjusted calculated dose of amikacin was observed in patients with BMI ≥ 26 kg/m 2 . No conflict of interest.

Los antimicrobianos son fármacos distintos al resto. Su eficacia en la reducción de la morbilidad y la mor talidad es muy superior a la de otros grupos de medicamentos. Por otra parte, son los únicos fármacos con efectos ecológicos, de manera que su administración puede contribuir a la aparición y diseminación de resistencias microbianas. Finalmente, son utilizados por médicos de prácticamente todas las especialidades. La actual complejidad en el manejo de las enfermedades infecciosas y del aumento de las resistencias hace imprescindible el establecimiento de programas de optimización del uso de antimicrobianos en los hospitales (PROA). Este documento de consenso define los objetivos de los PROA (mejorar los resultados clínicos de los pacientes con infecciones, minimizar los efectos adversos asociados a la utilización de antimicrobianos, incluyendo aquí las resistencias, y garantizar la utilización de tratamientos coste-eficaces) y establece recomendaciones para su implantación en los hospitales españoles. Las líneas maestras de las recomendaciones son: la constitución de un equipo multidisciplinario de antibióticos, dependiente de la Comisión de Infecciones. Los PROA necesitan ser considerados programas institucionales de los hospitales donde se desarrollen. Deben incluir objetivos específicos y resultados cuantificables en función de indicadores, y basarse en la realización de actividades encaminadas a mejorar el uso de antimicrobianos, principalmente mediante actividades formativas y medidas no impositivas de ayuda a la prescripción. The antimicrobial agents are unique drugs for several reasons. First, their efficacy is higher than other drugs in terms of reduction of morbidity and mortality. Also, antibiotics are the only group of drugs associated with ecological effects, because their administration may contribute to the emergence and spread of microbial resistance. Finally, they are used by almost all medical specialties. Appropriate use of antimicrobials is very complex because of the important advances in the management of infectious diseases and the spread of antibiotic resistance. Thus, the implementation of programs for optimizing the use of antibiotics in hospitals (called PROA in this document) is necessary. This consensus document defines the objectives of the PROA (namely, to improve the clinical results of patients with infections, to minimise the adverse events associated to the use of antimicrobials including the emergence and spread of antibiotic resistance, and to ensure the use of the most cost-efficacious treatments), and provides recommendations for the implementation of these programs in Spanish hospitals. The key aspects of the recommendations are as follows. Multidisciplinary antibiotic teams should be formed, under the auspices of the Infection Committees. The PROA need to be considered as part of institutional programs and the strategic objectives of the hospital. The PROA should include specific objectives based on measurable indicators, and activities aimed at improving the use of antimicrobials, mainly through educational activities and interventions based more on training activities directed to prescribers than just on restrictive measures.

Background We aimed to assess the hospital economic costs of nosocomial multi-drug resistant Pseudomonas aeruginosa acquisition. Methods A retrospective study of all hospital admissions between January 1, 2005, and December 31, 2006 was carried out in a 420-bed, urban, tertiary-care teaching hospital in Barcelona (Spain). All patients with a first positive clinical culture for P. aeruginosa more than 48 h after admission were included. Patient and hospitalization characteristics were collected from hospital and microbiology laboratory computerized records. According to antibiotic susceptibility, isolates were classified as non-resistant, resistant and multi-drug resistant. Cost estimation was based on a full-costing cost accounting system and on the criteria of clinical Activity-Based Costing methods. Multivariate analyses were performed using generalized linear models of log-transformed costs. Results Cost estimations were available for 402 nosocomial incident P. aeruginosa positive cultures. Their distribution by antibiotic susceptibility pattern was 37.1% non-resistant, 29.6% resistant and 33.3% multi-drug resistant. The total mean economic cost per admission of patients with multi-drug resistant P. aeruginosa strains was higher than that for non-resistant strains (15,265 vs. 4,933 Euros). In multivariate analysis, resistant and multi-drug resistant strains were independently predictive of an increased hospital total cost in compared with non-resistant strains (the incremental increase in total hospital cost was more than 1.37-fold and 1.77-fold that for non-resistant strains, respectively). Conclusions P. aeruginosa multi-drug resistance independently predicted higher hospital costs with a more than 70% increase per admission compared with non-resistant strains. Prevention of the nosocomial emergence and spread of antimicrobial resistant microorganisms is essential to limit the strong economic impact.

We assessed the adherence to the prescribing hospital protocol for tigecycline and factors associated with noncompliance. A total of 103 patients were included in the study. In 23 (22.3%) patients, tigecycline was not administered according to the protocol, mostly because of the availability of other therapeutic alternatives and prescription for indications that were not included in the guidelines. factors independently associated with nonadherence to the protocol were community-acquired infection (OR, 14.01; 95% CI, 1.54-127.12; P=0.019), and empirical tigecycline treatment (OR, 6.97; 95% CI, 0.88-55.40; P=0.066). penicillin allergy (OR, 0.004; 95% CI, 0.000-0.071; P=0.001) and previous antibiotic treatment (OR, 0.025; 95% CI, 0.003-0.233; P=0.001) were factors associated with adherence to the hospital protocol. A positive time trend between total number of prescriptions and non-compliant prescriptions with the protocol was observed (Spearman's rho coefficient 0.971; P=0.001). Adherence to tigecycline protocol could be improved by focusing on protocols for community-acquired infections, mainly skin and soft tissue infections.

Filiació URV: SIInclòs a la memòria: SIAfegir al títol: [EPICO 3.0Recomendaciones para el manejo de la candidiasis invasiva en pacientes críticos con infección intraabdominal complicada y pacientes quirúrgicos de larga estancia en la UCI] Background Although in the last decade the management of invasive fungal infections has improved, a number of controversies persist regarding the management of complicated intra-abdominal infection and surgical extended length-of-stay (LOS) patients in intensive care unit (ICU). Aims To identify the essential clinical knowledge and elaborate a set of recommendations, with a high level of consensus, necessary for the management of postsurgical patients with complicated intra-abdominal infection and surgical patients with ICU extended stay. Methods A Spanish prospective questionnaire, which measures consensus through the Delphi technique, was anonymously answered and e-mailed by 30 multidisciplinary national experts, all of them specialists in fungal invasive infections from six scientific national societies; these experts were intensivists, anesthesiologists, microbiologists, pharmacologists and specialists in infectious diseases. They answered 11 questions drafted by the coordination group after conducting a thorough review of the literature published in the last few years. For a category to be selected, the level of agreement among the experts in each should be equal to or greater than 70%. In a second round, 73 specialists attended a face-to-face meeting which was held after extracting recommendations from the chosen topics and in which they validated the pre-selected recommendations and derived algorithm. Results After the second Delphi round, the following 11 recommendations with high degree of consensus were validated. For “surgica

**Objective:** The aim of this study was to evaluate, from the Spanish National Health System perspective, the cost-effectiveness of rivaroxaban (20 mg/day) versus use of acenocoumarol (5 mg/day) for the treatment of patients with non-valvular atrial fibrillation (NVAF) at moderate to high risk for stroke. **Methods:** A Markov model was designed and populated with local cost estimates, efficacy and safety of rivaroxaban in stroke prevention in NVAF compared with adjusted-dose warfarin clinical results from the pivotal phase III ROCKET AF trial and utility values obtained from the literature. Warfarin and acenocoumarol were assumed to have therapeutic equivalence. **Results:** Rivaroxaban treatment was associated with fewer ischemic strokes and systemic embolisms (0.289 vs. 0.300 events), intracranial bleeds (0.051 vs. 0.067), and myocardial infarctions (0.088 vs. 0.102) per patient compared with acenocoumarol. Over a lifetime time horizon, rivaroxaban led to a reduction of 0.041 life-threatening events per patient, and increases of 0.103 life-years and 0.155 quality-adjusted lifeyears (QALYs) versus acenocoumarol treatment. This resulted in an incremental cost-effectiveness ratio of €7045 per QALY and €10 602 per life-year gained. Sensitivity analysis indicated that these results were robust and that rivaroxaban is cost-effective compared with acenocoumarol in 89.4% of cases should a willingness-to-pay threshold of €30 000/QALY gained be considered. **Conclusions:** The present analysis suggests that rivaroxaban is a cost-effective alternative to acenocoumarol therapy for the prevention of stroke and systemic embolisms in patients with NVAF in the Spanish healthcare setting.