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The current morbimortality of serious infections is unacceptable and there is a need to promote the increase in the efficacy of empirical and targeted antibiotherapy. This could be achieved by initiatives coming from ASP teams aimed at promoting increased efficacy of antibiotic therapy .In the optimization of the antibiotic therapy there are several critical points in which an adequate timing could achieve benefits in the survival of patients with severe infections: prompt initiation of empirical treatment; de-escalation performance, appropriate targeted treatment; and finally, curtail antibiotic duration.

Background The current treatment for psoriasis depends on the severity of the disease, in mild disease topical therapies alone, and with increasing disease severity in combination with phototherapy and/or traditional systemic therapy (methotrexate, cyclosporine, acitretin) or biologics agents. Apremilast is a selective inhibitor of phosphodiesterase 4, able to down-regulate the inflammatory associated with psoriasis. An oral option for treating chronic moderate/severe plaque psoriasis (PP) in adults whose disease has not responded to other therapies or are contraindicated/not tolerated. Purpose To report the hospital cases of moderate/severe PP treated with apremilast, describing patients’ profile and analysing the efficacy and safety of apremilast. Material and methods A retrospective case series. We reviewed the clinical history of the patients with moderate/severe PP treated with apremilast until August 2018. To assess the severity of the disease: Psoriasis Area and Severity Index (PASI) or% of body surface area (BSA). Moderate disease: PASI≥10 or 5%–10% of BSA; severe disease: PASI>20 or BSA >10%. Adequate response to treatment: 90%, 75% or 50% reduction (improvement) from baseline in PASI score (PASI90, PASI75 or PASI50) at 16 weeks. We investigated previous treatments from the beginning of the disease, analysed the efficacy of apremilast collecting the PASI or BSA scores at the beginning, after 16 and 32 weeks, and collected the adverse events during the treatment. Results Eighteen patients, 83% men, mean age 52 (±12) years. Three patients suffered PP and psoriatic arthritis. Previous treatment: 83% (15) topical therapies and 17% (three) phototherapy. Sixty-seven per cent (12) had received prior systemic therapy with conventional agents and 17% (three) biologic agents. At the start of apremilast: five patients suffered severe disease, nine moderate disease and one without data. Three patients were unmeasurable because of the recent start of apremilast. Sixty per cent (nine) of patients achieved PASI75/PASI90 from baseline at week 16, thirty-three per cent (five) PASI50% and 7% (one) without improvement. Maintenance improvement at week 32 (21% without data): 64%. During treatment six gastrointestinal adverse events, one atrial fibrillation and two cholesterol increased. Conclusion Almost all patients had received prior systemic therapy with conventional agents and/or biologics. The use of premilast has some advantages including oral administration, being well tolerated and with a safer profile. It will likely be of value to these patients and those who may not be candidates for biologics. References and/or acknowledgements No conflict of interest.

Background Nephrogenic diabetes insipidus (NDI) results from the inability of the late distal tubules and collecting ducts to respond to vasopressin. The lack of ability to concentrate urine results in polyuria and polidipsia. NDI is almost always drug-induced, however, there are other causes such as electrolyte abnormalities. Purpose To describe a case of NDI associated with the high-dose and long-term use of liposomal Amphotericin B. Material and methods Data were obtained from electronic medical records. Bibliographic research was conducted to find similar cases. The Nnaranjo algorithm was used to estimate the probability of adverse drug reactions. Results A 39-year-old man diagnosed with diffuse large B-cell non-Hodgkin lymphoma underwent an allogeneic bone marrow transplant. After 2 months, disease progression was detected, and immunosuppressive treatment was withdrawn and rescue treatment initiated. One month later, the patient was diagnosed with graft-versus-host disease grade III (GVHD). Immunosuppressive therapy was started with cyclosporine, micophenolate, sirolimus, methylprednisolone, and oral and rectal beclametasone. Additionally, meropenem, acyclovir, levofloxacine, cotrimoxazole and caspofungine were used as antimicrobial prophylaxis. During hospitalisation, the patient developed invasive pulmonary aspergillosis with isolations of Aspergillus fumigatus and Aspergillus flavus. The patient was treated with liposomal amphotericin B 6 mg/kg (440 mg) for 41 days with a cumulative dose reaching 18.04 g. Voriconazol and Posaconazol were discarded because of concomitant treatment with sirolimus and parenteral nutrition respectively. On day 5, the serum potassium level began to decrease achieving 6 litr/day. The patient was transferred to the medical intensive care unit and treated with vigorous potassium administration. NDI was diagnosed and treated with desmopressin 10 mcg/12 hour nasal drops, hydrochlorothiazide 50 mg/24 hour and spironolactone 50 mg/24 hour. According to the Naranjo algorithm, this event would be classified as a possible reaction because of the temporal correlation between NDI and treatment with liposomal Amphotericin B. Several cases were reported related to NDI induced by Amphotericin B,1 2 regardless of formulation. Conclusion It is very important to understand the etiology and symptoms related with nephrotoxicity and NDI. The association of other nephrotoxic drugs and persistent hypokalaemia also contributed to this event.Specific intervention is required to prevent nephrotoxicity in patients receiving Amphotericin B. References and/or acknowledgements 1. Metzger NL, Gill KLV. Nephrogenic diabetes insipidus induced by two amphotericin B liposomal formulations. Pharmacotherapy2009;29:613–20. 2. Canada TW, Weavind LM, Augustin KM. Possible liposomal amphotericinb-induced nephrogenic diabetes insipidus. Ann Pharmacother2003;37:70–3. No conflict of interest.

Background Vancomycin is a glycopeptide antibiotic active against gram-positive bacteria. Vancomycin pharmacokinetic parameters can vary widely among individuals. Drug monitoring is recommended if the duration of therapy is expected to be more than 72 hours or for patients receiving other nephrotoxic drugs, obese patients, patients with unstable renal function, central nervous system infections, endocarditis, sepsis etc. Purpose The purpose of this study was to implement the monitoring of vancomycin in specific services. Material and methods A prospective quasi-experimental study during 9 months (1 October 2015 and 30 June 2016) was carried out in a tertiary-care university hospital. Traumatology and rehabilitation, neurosurgery, neurology, and plastic and maxillofacial surgery services were included. Daily, vancomycin prescriptions were selected from electronic records. The interventions were performed by a pharmacist responsible for monitoring. The variables analysed were:type of infection, request for serum vancomycin concentration, number of determinations per patient, rate of administration of loading dose, number of patients who developed an increase of 0.5 mg/L of serum creatinine after starting treatment with vancomycin. The dose adjustment was performed through the Abottbase PKSystem (PKS) program. The optimal trough concentrations were considered as 15 to 20 mg/L. The first measuring was realised before the 4th to 5th dose and every 48 to 72 hours after every change. To achieve this range, monitoring was performed weekly along with serum creatinine levels. The local guideline recommends the administration of 1 g every 12 hours of vancomycin. Results A total of 254 patients were enrolled int the study: 137 (53.9%) were male. The median age was 59 (IQR, 47–72) years, weight 78 (IQR, 69–85) kg. Baseline serum creatinine 0.7 (IQR, 0.64–0.82) mg/L. One hundred and thirty-three patients (52.4%) had osteoarticular infections, 43 (17%) skin and soft tissues infections, 23 (9.1%) central nervous system infections and 55 (21.5%) other infections. 199/254 (78.3%) patients were requested for microbiological cultures and in 95/199 (47.7%) were isolated gram-positive bacteria. In 211 (83.1%) patients the vancomicyn was prescribed as 1 g every 12 hours without considering weight. The loading dose was administered in 28 (11.0%) patients. The median duration of the treatment was 6 days (IQR, 4–9). Vancomycin was monitored in 128 (50.4%) patients. The therapeutic range was achieved in 69/128 (53.9%) patients. The median number of determinations per patient was 1 (IQR, 0–1). Three (1.2%)patients developed nephrotoxicity. The number of recommendations made by a pharmacist for dose adjustment were 73 (28.7%). Conclusion In conclusion, the implementation of monitoring had a favourable uptake. The standard dosage of vancomycin is not enough to achieve the therapeutic range. Loading dosage and patient weight should be considered. No conflict of interest

Background The emergence of highly-resistant gram-negative bacteria, in particular acinetobacter baumanii pseudomonas aeruginosa, and carbapenem-resistant klebsiella species has been associated with high rates of morbidity and mortality. Therapeutic options for these pathogens are limited. Because of the lack of newer antimicrobial agents, colistimethate sodium (CMS) has been recently reused for the treatment of infections caused by this microorganism. Purpose The study aimed to assess CMS prescriptions and analyse the occurrence of nephrotoxicity after CMS administration. Material and methods A retrospective observational study was performed at a tertiary-care university hospital between 1 January 2016 and 31 July 2017 including every patient who had received intravenous CMS for at least 48 hours. Clinical data were obtained from electronic medical records. Only one treatment per patient was considered in the analysis. The following variables were collected: patient characteristics, site of infection, type of microorganism, daily dosage and duration of CMS used and concomitant antimicrobial treatment, and laboratory data: serum creatinine (at day 1 and during the therapy), albumin, haemoglobin and leukocytes. Nephrotoxicity was defined as at least two consecutive serum creatinine measurements with an increase of 0.5 mg/dl from the baseline after 2 or more days of CMS therapy. Results A total of 75 patients received CMS therapy, 53 (70.7%) were male. The median age of the patients was 69 (IQR, 57–79) years, Charlson index 2 (1–3)and eGFR (CKD-EPI) was 91. 1 (IQR, 78.9–113.2) ml/min/1.73 m 2 . Nephrotoxicity developed in 35 (46.7%) patients. The median onset time for nephrotoxicity was 7 days (IQR, 3–12). Patients with nephrotoxicity were older than those without it (74 years vs 64 years, p=0.025) and had lower median serum albumin and haemoglobin levels 2.9 vs 3.1 (p=0.501) and 9.4 vs 10.1 (p=0.069) respectively. The median daily dose of CMS was 9 MU, the loading dose was administered in 25 (33.3%) patients. In 24 patients (32.0%) the dosage was adjusted according to eGFR. The median duration of treatment was 10 (IQR, 6–15) days. Bloodstream infections occurred in 19 (25.3%) patients. Principal infectious sources were: respiratory (38.7%), urinary (25.3%) and skin and soft tissue (17.3%). Pathogens were A. baumanii 73.3%, P. aeruginosa 17.3% and carbapenem-resistant enterobacteriaceae 10.7%. In 41 patients (54.7%) CMS was administered in combination therapy. Causes for the end of treatment were clinical resolution (56.0%), change to other (13.3%), toxicity (13.4%) and death (17.3%). Conclusion In conclusion, very low rates of adjustment of the dosage by eGFR were observed. Almost half of the patients developed nephrotoxicity due to the CMS therapy, which was significantly associated with the age of patients. No conflict of interest

Background Dalbavancin (DBV) is an antibiotic from the lipoglycopeptide family that is active against Gram +cocci (GPC) that reaches adequate concentrations to allow dosing once a week. It is currently only approved for skin and soft tissue infections, although its PK/PD properties could allow a potential use for infectious endocarditis (IE) and/or bloodstream infections caused by GPC. The estimated duration of bloodstream infections is 10 to 14 days and 28 to 42 days for IE, both requiring intravenous treatments and prolongued hospital stay, all of which entails a high use of hospital and economic resources. Purpose The purpose of this study was to evaluate the economic impact of switching to dalbavancin from standard antibiotic treatment Material and methods Observational,restrospective,single-centre study. All patients with IE and/or bloodstream infections caused by GPC who had received at least one dose of DBV were included. The proportion of patients presenting clinical resolution was calculated, as well as the reduction in days of hospital stay and associated costs. For the estimate of reduction of costs, public prices provided by the health system were used. Results Thirty patients were included: 22 (73.3%) were males,with a median age of 66 (IQR 47.5–75.5),Charlson Index 1 (IQR 1–3). Twenty-two patients (73.3%) had IE and 8 (26.7%) had a bloodstream infection. The isolated microbiological agent was coagulase-negative staphyloccoci in 46.7% of patients; 13.3% streptococus spp, 10% enterococcus spp; and 10% SAMS y 3.3% SAMR. The reason for administering DBV was: 83.3% early discharge, 10% failure of previous treatment and 6.6% toxicity. The median length of stay was 27 (IQR 18–38) days. The initial dose of DBV was 1500 mg in 21 (70%) patients;1000 mg in eight (26.7%) patients and in one patient the dose was 750 mg adjusted for renal function. Four patients (13.3%) received an extra dose of 1000 mg on day 14. 73.3% of patients had previously received treatment with daptomycin, and 24 (80%) presented clinical resolution at the time of the analysis. Hospital stay was reduced in 24 (80%) patients by a median of 11 days (IQR 1–14), leading to average savings of €6830.96 per patient. The average cost of treatment with dalbavancin was €1341.9 compared to €1475.63 for 14 days of treatment with daptomycin (€133.73). Conclusion In conclusion, the administration of DBV for patients with a positive clinical evolution could be an effective alternative treatment, with an important reduction in health costs. No conflict of interest

The incidence and mortality rates of severe infections are still very high. Moreover, the growing threat of bacterial resistance and the progressive reduction of research into new antibiotics, overshadows the future of the fight against infections. We need to preserve the effectiveness of available antibiotics. This can only be achieved if we minimize the development of bacterial resistance. We have sufficient evidence to show that reducing the duration of antibiotic treatment can minimize the potential development of bacterial resistance, without worsening the prognosis of infections. So, we think that the proposal to shorten the antibiotic treatment should become a key element of our antibiotic stewardship programs.

Background Therapeutic de-escalation enables us to improve the effectiveness of empirical antimicrobial therapy and avoids the development of resistance. Purpose To analyse the preliminary results of a pilot project of pharmacy interventions to achieve de-escalation of treatment with carbapenems, within a programme of optimisation of antibiotics use. Materials and Methods Prospective study of pharmacy interventions aimed at de-escalation in patients starting treatment with carbapenems, over three months (from March to June 2012) in a tertiary hospital, based on available microbiology results. The de-escalation suggestion was made through the electronic prescribing software. The variables analysed were: number of patients prescribed carbapenems, prescribing speciality, request for cultures, microorganisms isolated and interventions performed. De-escalations carried out without pharmacy intervention were also assessed. Results Total number of prescriptions was 433. The most prescribed carbapenem was ertapenem (37.6%) followed by meropenem (36%). The carbapenem most used in Internal Medicine was meropenem (58.2%) and in Urology, imipenem (75%). Ertapenem was used more frequently in General Surgery (53.7%) and Vascular Surgery (86.0%). Out of a total of 316 requested tests, 172 (54.4%) were positive. The most common pathogen isolated was Escherichia Coli (24.7%) 20.8% of which were Extended-Spectrum Beta-Lactamase (ESBL)-producing, 60% of which were sensitive to piperacillin-tazobactam or fosfomycin. Klebsiella spp. were isolated in 3.6%, of which 33.3% were ESBL-producing and 50% were sensitive to piperacillin-tazobactam. Total treatments subject to de-escalation were 96 (55.8%), out of 172 showing this possibility, where 74 (77.1%) were carried out by initiatives of medical teams and 22 (22.9%) after pharmacy interventions. The Services with a higher degree of acceptance of pharmacy interventions were Internal Medicine (36.4%) and General Surgery (27.3%). Conclusions Although the therapeutic de-escalation of empirical treatments with carbapenems was a low percentage, nevertheless pharmacy interventions achieved an increase of this practise, with the more receptive specialties being Internal Medicine and General Surgery. No conflict of interest.

The authors followed up 20 full-term and 52 premature neonates given breast milk and substitutes differing in the character of the fatty component: "Malyutka", "Malyutka with a new fatty composition", and "similac". In the full-term children, the level of vitamin E in the blood serum was higher than that in the premature children and remained greater whatever the type of feeding. In the premature children, the tocopherol content in the blood serum depended on the child's age and was higher in children of a 36-37 week gestation age. Both the full-term and premature children showed sufficient supply with vitamin E during natural feeding and during feeding with "Similac" and "Malyutka" mixtures. Upon feeding with a "Malyutka with a new fatty composition" all the neonates had a lower content of vitamin E in the blood serum as compared to that in children given a different type of feeding. This is likely to be related to the high content of polyunsaturated fatty acids and to a relatively little content of vitamin E in the mixture under consideration.

The efficacy and adequacy of fat component depending on the feeding type (breast milk, Malyutka, Malyutka with a new fatty composition and Similak mixtures) were defined in the course of feeding 90 premature infants aged 33 to 37 weeks on the basis of clinical observations, determination of fat assimilation and the main indicators of lipid metabolism. All the mixtures were shown to be tolerated well. No significant differences were revealed in the mean daily weight gain and in the monthly body length gain. The children fed breast milk showed a higher assimilation of fats and an increase in the cholesterol level in the blood serum. The indicators of fat retention in children fed Similak and Malyutka with a new fatty composition mixtures were similar to those in children on natural feeding. The milk mixtures under consideration are found to be effective enough and thus can be used for feeding premature children born to mothers with hypo- and agalactia.