Improved empirical antibiotic treatment of sepsis after an educational intervention: the ABISS-Edusepsis study.

BACKGROUND: Early appropriate antibiotic treatment is essential in sepsis. We aimed to evaluate the impact of a multifaceted educational intervention to improve antibiotic treatment. We hypothesized that the intervention would hasten and improve the appropriateness of empirical antibiotic administration, favor de-escalation, and decrease mortality. METHODS: We prospectively studied all consecutive patients with sepsis/septic shock admitted to 72 intensive care units (ICUs) throughout Spain in two 4-month periods (before and immediately after the 3-month intervention). We compared process-of-care variables (resuscitation bundle and time-to-initiation, appropriateness, and de-escalation of empirical antibiotic treatment) and outcome variables between the two cohorts. The primary outcome was hospital mortality. We analyzed the intervention's long-term impact in a subset of 50 ICUs. RESULTS: We included 2628 patients (age 64.1 ± 15.2 years; men 64.0%; Acute Physiology and Chronic Health Evaluation (APACHE) II, 22.0 ± 8.1): 1352 in the preintervention cohort and 1276 in the postintervention cohort. In the postintervention cohort, the mean (SD) time from sepsis onset to empirical antibiotic therapy was lower (2.0 (2.7) vs. 2.5 (3.6) h; p = 0.002), the proportion of inappropriate empirical treatments was lower (6.5% vs. 8.9%; p = 0.024), and the proportion of patients in whom antibiotic treatment was de-escalated was higher (20.1% vs. 16.3%; p = 0.004); the expected reduction in mortality did not reach statistical significance (29.4% in the postintervention cohort vs. 30.5% in the preintervention cohort; p = 0.544). Gains observed after the intervention were maintained in the long-term follow-up period. CONCLUSIONS: Despite advances in sepsis treatment, educational interventions can still improve the delivery of care; further improvements might also improve outcomes.

Impact of Source Control in Patients With Severe Sepsis and Septic Shock.

OBJECTIVES: Time to clearance of pathogens is probably critical to outcome in septic shock. Current guidelines recommend intervention for source control within 12 hours after diagnosis. We aimed to determine the epidemiology of source control in the management of sepsis and to analyze the impact of timing to source control on mortality. DESIGN: Prospective observational analysis of the Antibiotic Intervention in Severe Sepsis study, a Spanish national multicenter educational intervention to improve antibiotherapy in sepsis. SETTING: Ninety-nine medical-surgical ICUs in Spain. PATIENTS: We enrolled 3,663 patients with severe sepsis or septic shock during three 4-month periods between 2011 and 2013. INTERVENTIONS: Source control and hospital mortality. MEASUREMENTS AND MAIN RESULTS: A total of 1,173 patients (32%) underwent source control, predominantly for abdominal, urinary, and soft-tissue infections. Compared with patients who did not require source control, patients who underwent source control were older, with a greater prevalence of shock, major organ dysfunction, bacteremia, inflammatory markers, and lactic acidemia. In addition, compliance with the resuscitation bundle was worse in those undergoing source control. In patients who underwent source control, crude ICU mortality was lower (21.2% vs 25.1%; p = 0.010); after adjustment for confounding factors, hospital mortality was also lower (odds ratio, 0.809 [95% CI, 0.658-0.994]; p = 0.044). In this observational database analysis, source control after 12 hours was not associated with higher mortality (27.6% vs 26.8%; p = 0.789). CONCLUSIONS: Despite greater severity and worse compliance with resuscitation bundles, mortality was lower in septic patients who underwent source control than in those who did not. The time to source control could not be linked to survival in this observational database.

A review of the factors influencing antimicrobial prescribing.

There are multiple benefits of appropriate antimicrobial prescribing: it has a direct impact on clinical outcomes, avoids adverse effects, is cost effective and, perhaps most importantly, it helps to prevent the emergence of resistance. However, any physician can prescribe antibiotics, which is not the case with other clinically relevant drugs. There is great variability in the prescribing physician's (PP) training, motivation, workload and setting, including accessibility to infectious diseases consultants and/or diagnostic techniques, and therefore there is a high risk of inappropriate prescription. Many antibiotic prescribing errors occur around the selection and duration of treatment. This includes a low threshold for the indication of antibiotics, delayed initiation of treatment when indicated, limited knowledge of local antimicrobial resistance patterns by the PPs, errors in the final choice of dose, route or drug and a lack of de-escalation. Similarly, the prescription of prophylactic antibiotics to prevent surgical site infections, despite being commonly accepted, is suboptimal. Factors that may explain suboptimal use are related to the absence of well-defined protocols, poor knowledge of prophylactic protocols, miscommunication or disagreement between physicians, logistical problems, and a lack of audits. A proper understanding of the prescribing process can guide interventions to improve the PP's practices. Some of the potential interventions included in a stewardship program are education in antimicrobial prescribing, information on the local resistance patterns and accessibility to a qualified infectious diseases consultant.

Epidemiology, diagnosis and treatment of fungal respiratory infections in the critically ill patient.

OBJECTIVE: To elaborate practical recommendations based on scientific evidence, when available, or on expert opinions for the diagnosis, treatment and prevention of fungal respiratory infections in the critically ill patient, including solid organ transplant recipients. METHODS: Twelve experts from two scientific societies (The Spanish Society for Chemotherapy and The Spanish Society of Intensive Care and Coronary Units) reviewed in a meeting held in March 2012 epidemiological issues and risk factors as basis for a document about prevention, diagnosis and treatment of respiratory fungal infections caused by Candida spp., Aspergillus spp or Zygomycetes. RESULTS: Despite the frequent isolation of Candida spp. from respiratory tract samples, antifungal treatment is not recommended since pneumonia by this fungal species is exceptional in non-neutropenic patients. In the case of Aspergillus spp., approximately 50% isolates from the ICU represent colonization, and the remaining 50% cases are linked to invasive pulmonary aspergillosis (IPA), an infection of high mortality. Main risk factors for invasive disease in the ICU are previous treatment with steroids and chronic obstructive pulmonary disease (COPD). Collection of BAL sample is recommended for culture and galactomannan determination. Voriconazole and liposomal amphotericin B have the indication as primary therapy while caspofungin has the indication as salvage therapy. Although there is no solid data supporting scientific evidence, the group of experts recommends combination therapy in the critically ill patient with sepsis or severe respiratory failure. Zygomycetes cause respiratory infection mainly in neutropenic patients, and liposomal amphotericin B is the elective therapy. CONCLUSIONS: Presence of fungi in respiratory samples from critically ill patients drives to different diagnostic and clinical management approaches. IPA is the most frequent infection and with high mortality.

Value of ß-D-glucan and Candida albicans germ tube antibody for discriminating between Candida colonization and invasive candidiasis in patients with severe abdominal conditions.

PURPOSE: To assess the value of (1→3)-ß-D: -glucan (BDG), Candida albicans germ tube antibody (CAGTA), C-reactive protein (CRP), and procalcitonin (PCT) levels for the diagnosis of invasive candidiasis (IC) and for differentiating Candida spp. colonization from infection in ICU patients with severe abdominal conditions (SAC). METHODS: Prospective study of 176 non-neutropenic patients, with SAC at ICU admission, and expected to stay at least 7 days. Surveillance cultures and BDG, CAGTA, CRP, and PCT levels were performed on the third day of ICU stay and twice a week for four consecutive weeks. Patients were grouped into invasive candidiasis (IC), Candida colonization, and neither colonized/nor infected. The classification and regression tree (CART) analysis was used to predict IC in colonized patients. The discriminatory ability of the obtained prediction rule was assessed by the area under the ROC curve (AUC). RESULTS: The probabilities of IC were 59.3 % for the terminal node of BDG greater than 259 pg/mL and 30.8 % for BDG less than 259 pg/mL and CAGTA positivity, whereas there was a 93.9 % probability in predicting the absence of IC for BDG less than 259 pg/mL and negative CAGTA. Using a cutoff of 30 % for IC probability, the prediction rule showed 90.3 % sensitivity, 54.8 % specificity, 42.4 % positive predictive value, and 93.9 % negative predictive value with an AUC of 0.78 (95 % confidence interval 0.76-0.81). Significant differences in CRP (p = 0.411) and PCT (p = 0.179) among the studied groups were not found. CONCLUSIONS: BDG with a positive test for CAGTA accurately differentiated Candida colonization from IC in patients with SAC, whereas CRP and PCT did not.

[Persistent candidemia in a renal-pancreatic transplant patient]. / Candidemia persistente en una paciente receptora de trasplante renopancreático.

BACKGROUND: In recent decades, there has been an increase in the survival of recipients of solid organ transplants related to the improvement of the surgical technique, the introduction of protocols for immunosuppressive therapy, and the use of antimicrobial prophylaxis. Nonetheless, invasive fungal infection (IFI) is currently the major cause of morbidity and mortality in this group of patients. Invasive candidiasis is the most common IFI found after renal transplantation and is usually associated with total parenteral nutrition, broad-spectrum antibiotic therapy and abdominal surgery. CLINICAL CASE: We report the case of a recent kidney-pancreas transplant recipient who developed a persistent catheter-related candidemia caused by Candida glabrata. The patient was treated with anidulafungin and had a good clinical course with no significant drug interactions. We discuss the possible causes and diagnostic and therapeutic alternatives of this kind of infection.

[Programs for optimizing the use of antibiotics (PROA) in Spanish hospitals: GEIH-SEIMC, SEFH and SEMPSPH consensus document]. / Programas de optimización de uso de antimicrobianos (PROA) en hospitales españoles: documento de consenso GEIH-SEIMC, SEFH y SEMPSPH.

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.