Ana Arnaiz

Emergence of resistance to daptomycin in a cohort of patients with methicillin-resistant Staphylococcus aureus persistent bacteraemia treated with daptomycin

4 Theoretically estimated AUC 24 /MIC ratios against VRE susceptible to linezolid, according to the EUCAST clinical breakpoint (MIC¼ 4 mg/L), 1 were in the recommended range for the effective treatment of severe infections with linezolid (AUC 24 /MIC ratio of 80 –120) 6 in both cases (.93.76 and .250.96, respectively). In addition , biliary trough levels (C min) of linezolid were above the EUCAST clinical breakpoint against VRE in both cases (7.42 and 37.53 mg/L, respectively), this ensuring a theoretical T .MIC of .100%. The wide interindividual pharmacokinetic variability of linezolid observed between the two patients (patient 1: V ss 31. 5 L, CL 4.2 L/h and t 1/2 5.2 h; patient 2: V ss 67.1 L, CL 1.6 L/h and t 1/2 29.1 h) confirmed previous observations in critically ill patients during treatment with linezolid. 8 This variability is expected to potentially impact more on tolerability than on efficacy. Notably, patient 2 experienced hyperlactacidaemia (an increase in lactate level of 6.2 mmol/L during linezolid treatment), which could have been related to drug overexposure potentially favoured by drug –drug interactions and renal impairment. 8 However, it should not be overlooked that linezolid has generally been shown to be safe and effective in LTx patients. 9 The therapeutic drug monitoring of plasma C min may represent a valuable tool for the optimal management of linezolid in these cases, 8 and has recently been shown to improve safety outcomes in long-term treatment. 10 We recognize that the absence of real biliary pharmacokinetic/ pharmacodynamic data may be a limitation. However, these data confirm the potentially valuable role of linezolid in the treatment of cholangitis due to multidrug-resistant Enterococcus in LTx patients, since they meet the recommendations of good biliary penetration that are given in the Tokyo guidelines. References 1 Asín E, Isla A, Canut A et al. Comparison of antimicrobial pharmacokinetic/pharmacodynamic breakpoints with EUCAST and CLSI clinical breakpoints for Gram-positive bacteria. 4 Cremaschi E, Maggiore U, Maccari C et al. Linezolid levels in a patient with biliary tract sepsis, severe hepatic failure and acute kidney injury on sustained low-efficiency dialysis (SLED). 5 Pea F, Viale P, Lugano M et al. Biliary penetration and pharmacodynamic exposure of linezolid in liver transplant patients. 6 Rayner CR, Forrest A, Meagher AK et al. Clinical pharmacodynamics of linezolid in seriously ill patients treated in a compassionate use programme. 7 Pea F, Viale P, Lugano M et …

Valve surgery in active infective endocarditis: A simple score to predict in-hospital prognosis

AIMS Surgery for infective endocarditis (IE) is associated with high mortality. Our objectives were to describe the experience with surgical treatment for IE in Spain, and to identify predictors of in-hospital mortality. METHODS Prospective cohort of 1000 consecutive patients with IE. Data were collected in 26 Spanish hospitals. RESULTS Surgery was performed in 437 patients (43.7%). Patients treated with surgery were younger and predominantly male. They presented fewer comorbid conditions and more often had negative blood cultures and heart failure. In-hospital mortality after surgery was lower than in the medical therapy group (24.3 vs 30.7%, p=0.02). In patients treated with surgery, endocarditis involved a native valve in 267 patients (61.1%), a prosthetic valve in 122 (27.9%), and a pacemaker lead with no clear further valve involvement in 48 (11.0%). The most common aetiologies were Staphylococcus (186, 42.6%), Streptococcus (97, 22.2%), and Enterococcus (49, 11.2%). The main indications for surgery were heart failure and severe valve regurgitation. A risk score for in-hospital mortality was developed using 7 prognostic variables with a similar predictive value (OR between 1.7 and 2.3): PALSUSE: prosthetic valve, age ≥ 70, large intracardiac destruction, Staphylococcus spp, urgent surgery, sex [female], EuroSCORE ≥ 10. In-hospital mortality ranged from 0% in patients with a PALSUSE score of 0 to 45.4% in patients with PALSUSE score >3. CONCLUSIONS The prognosis of IE surgery is highly variable. The PALSUSE score could help to identify patients with higher in-hospital mortality.

Q fever endocarditis in Spain. Clinical characteristics and outcome.

OBJECTIVES To describe the clinical presentation of a large number of Q fever endocarditis (QFE) and its management considering the role of serology. PATIENTS AND METHODS Eighty-three patients with definite QFE (56 native and 27 prosthetic valve) with a long-term follow-up after stopping treatment (median: 48 months) were included. Final outcome (cure or relapse) was compared according with the serological titre at the end of therapy: less than 1:400 of phase I Ig G antibodies by indirect immunofluorescence (group 1, N=23) or more than 1:400 (group 2, N=30). RESULTS Eleven patients (13.2%) died from QFE and other 8 died for other reasons not related to endocarditis during follow-up. Surgery was performed in 61 (73.5%) patients and combined antimicrobial treatment was long (median: 23 months, IQR: 12 - 36). Seven relapses were observed, but five of them had received an initial incomplete antibiotic regimen. In patients who completed the programmed treatment (range: 12 - 89 months), serological titres at the end of therapy were not useful for predicting the final outcome: one relapse in each group. CONCLUSIONS QFE requires a prolonged antimicrobial treatment, but serological titres are not useful for determining its duration.

Self-administered outpatient parenteral antimicrobial therapy (S-OPAT) for infective endocarditis: A safe and effective model

The safety and efficacy of treatment of infectious endocarditis (IE) was evaluated within a program of hospital-in-home (HIH) based on self-administered outpatient parenteral antimicrobial therapy (S-OPAT). IE episodes (n=48 in 45 patients; 71% middle-aged males) were recruited into the HIH program between 1998 and 2012. Following treatment stabilization at the hospital they returned home for HIH in which a physician and/or a nurse supervised the S-OPAT. Safety and efficacy were evaluated as mortality, re-occurrence, and unexpected re-admission to hospital. Of the episodes of IE, 83.3% had comorbidities with a mean score of 2.3 on the Charlson index and 1.5 on the Profund index; 60.4% had pre-existing valve disease (58.6% having had surgical intervention); 8.3% of patients had suffered a previous IE episode; 62.5% of all episodes affected a native valve; 45.8% being mitral; 70.8% of infection derived from the community. In 75% of the episodes there was micro-organism growth, of which 83.3% were Gram positive. Overall duration of antibiotic treatment was 4.8 weeks; 60.4% of this time corresponding to HIH. Re-admission occurred in 12.5% of episodes of which 33.3% returned to HIH to complete the S-OPAT. No deaths occurred during HIH. One year after discharge, 2 patients had recurrence and 5 patients died, in 2 of whom previous IE as cause-of-death could not be excluded. In conclusion, the S-OPAT schedule of hospital-in-home is safe and efficacious in selected patients with IE.

Clinical characteristics, treatment and outcomes of MRSA bacteraemia in the elderly.

OBJECTIVES To compare clinical and microbiological characteristics, treatment and outcomes of MRSA bacteraemia among elderly and younger patients. MATERIAL AND METHODS Prospective study conducted at 21 Spanish hospitals including patients with MRSA bacteraemia diagnosed between June/2008 and December/2009. Episodes diagnosed in patients aged 75 or more years old (≥75) were compared with the rest of them (<75). RESULTS Out of 579 episodes of MRSA bacteraemia, 231 (39.9%) occurred in patients ≥75. Comorbidity was significantly higher in older patients (Charlson score ≥4: 52.8 vs. 44%; p = .037) as was the severity of the underlying disease (McCabe ≥1: 61.9 vs. 43.4%; p < .001). In this group the acquisition was more frequently health-care related (43.3 vs. 33.9%, p = .023), mostly from long-term care centers (12.1 vs. 3.7%, p < .001). An unknown focus was more frequent among ≥75 (19.9 vs. 13.8%; p = .050) while severity at presentation was similar between groups (Pitt score ≥3: 31.2 vs. 27.6%; p = .352). The prevalence of vancomycin resistant isolates was similar between groups, as was the appropriateness of empirical antibiotic therapy. Early (EM) and overall mortality (OM) were significantly more frequent in the ≥75 group (EM: 12.1 vs. 6%; p = .010 OM: 42.9 vs. 23%; p < .001). In multivariate analysis age ≥75 was an independent risk factor for overall mortality (aOR: 2.47, CI: 1.63-3.74; p < .001). CONCLUSION MRSA bacteraemia was frequent in patients aged ≥75 of our cohort. This group had higher comorbidity rates and the source of infection was more likely to be unknown. Although no differences were seen in severity or adequacy of empiric therapy, elderly patients showed a higher overall mortality.

Efficiency of a self-administered outpatient parenteral antimicrobial therapy (s-opat) for infective endocarditis within the context of a shortened hospital admission based on hospital at home program

ABSTRACT Objective: This study aimed to evaluate the efficiency of treatment of infectious endocarditis (IE) via Self-administered Outpatient Parenteral Antimicrobial Therapy (S-OPAT) supported by a shortening hospital admission program in a hospitalization-at-home unit (HAH), including a short review of the literature. Methods: Ambispective cohort study of 57 episodes of IE in 54 patients treated in an HAH unit between 1988 and 2014 who receive S-OPAT after prior intra-hospital clinical stabilization. Characteristics of each episode of IE, safety and efficiency of the care model, were analyzed. Results: Forty-three (76%) patients were males with a median age of 61 years (SD = 16.5). A total of 37 (65%) episodes affected the native valve (42% the aortic valve). In 75%, a micro-organism was isolated, of which 88% were Gram-positive bacteria. No deaths occurred during HAH program, clinical complications appeared in 30% of episodes, only 6 patients were re-admitted to hospital although no patient died. In the 12 months’ follow-up 3 cases had a recurrence. The average cost of a day stay in HAH was €174 while in traditional cardiology hospitalization was €1100. The total average cost of treatment of each episode of IE managed entirely in hospital was calculated as €54,723. Application of the S-OPAT model based on HAH meant a cost reduction of 32.72%. Conclusions: In suitably selected patients, treatment of IE based on S-OPAT supported by a shortening hospital admission care program by means of referral to a HAH unit is a safe and efficient care model which entails a significant cost saving for the public healthcare system.

8. Costo-eficacia de un programa de alta temprana en el tratamiento de la endocarditis infecciosa apoyado en una unidad de hospitalizacion a domicilio

Pajarón, M1, Fernández-Miera M1, Dueñas JC2, Allende I3, Arnaiz-García AM4, Fernández-Sampedro M4, Gutiérrez-Cuadra M4, Armiñanzas C4, Sanroma-Mendizábal P1, Berrazueta JR5, Fariñas MC4. 1Unidad de Hospitalización Domiciliaria, 2Subdirección de Gestión, 3Atención Primaria (Centro de Salud Bezana), 4Unidad de Enfermedades Infecciosas, 5Cardiología Hospital Universitario Marqués de Valdecilla (Santander, Cantabria)