Impact of a multifaceted educational intervention including serious games to improve the management of invasive candidiasis in critically ill patients.

OBJECTIVES: Infections caused by Candida species are common in critically ill patients and contribute to significant morbidity and mortality. The EPICO Project (Epico 1 and Epico 2.0 studies) recently used a Delphi approach to elaborate guidelines for the diagnosis and treatment of this condition in critically ill adult patients. We aimed to evaluate the impact of a multifaceted educational intervention based on the Epico 1 and Epico 2.0 recommendations. DESIGN: Specialists anonymously responded to two online surveys before and after a multifaceted educational intervention consisting of 60-min educational sessions, the distribution of slide kits and pocket guides with the recommendations, and an interactive virtual case presented at a teleconference and available for online consultation. SETTING: A total of 74 Spanish hospitals. PARTICIPANTS: Specialists of the Intensive Care Units in the participating hospitals. VARIABLES OF INTEREST: Specialist knowledge and reported practices evaluated using a survey. The McNemar test was used to compare the responses in the pre- and post-intervention surveys. RESULTS: A total of 255 and 248 specialists completed both surveys, in both periods, respectively. The pre-intervention surveys showed many specialists to be unaware of the best approach for managing invasive candidiasis. After both educational interventions, specialist knowledge and reported practices were found to be more in line with nearly all the recommendations of the Epico 1 and Epico 2.0 guidelines, except as regards de-escalation from echinocandins to fluconazole in Candida glabrata infections (p=0.055), and the duration of antifungal treatment in both candidemia and peritoneal candidiasis. CONCLUSIONS: This multifaceted educational intervention based on the Epico Project recommendations improved specialist knowledge of the management of invasive candidiasis in critically ill patients.

Prevalence of and risk factors for biliary carriage of bacteria showing worrisome and unexpected resistance traits.

Data on biliary carriage of bacteria and, specifically, of bacteria with worrisome and unexpected resistance traits (URB) are lacking. A prospective study (April 2010 to December 2011) was performed that included all patients admitted for <48 h for elective laparoscopic cholecystectomy in a Spanish hospital. Bile samples were cultured and epidemiological/clinical data recorded. Logistic regression models (stepwise) were performed using bactobilia or bactobilia by URB as dependent variables. Models (P < 0.001) showing the highest R(2) values were considered. A total of 198 patients (40.4% males; age, 55.3 ± 17.3 years) were included. Bactobilia was found in 44 of them (22.2%). The presence of bactobilia was associated (R(2) Cox, 0.30) with previous biliary endoscopic retrograde cholangiopancreatography (ERCP) (odds ratio [OR], 8.95; 95% confidence interval [CI], 2.96 to 27.06; P < 0.001), previous admission (OR, 2.82; 95% CI, 1.10 to 7.24; P = 0.031), and age (OR, 1.09 per year; 95% CI, 1.05 to 1.12; P < 0.001). Ten out of the 44 (22.7%) patients with bactobilia carried URB: 1 Escherichia coli isolate (CTX-M), 1 Klebsiella pneumoniae isolate (OXA-48), 3 high-level gentamicin-resistant enterococci, 1 vancomycin-resistant Enterococcus isolate, 3 Enterobacter cloacae strains, and 1 imipenem-resistant Pseudomonas aeruginosa strain. Bactobilia by URB (versus those by non-URB) was only associated (R(2) Cox, 0.19) with previous ERCP (OR, 11.11; 95% CI, 1.98 to 62.47; P = 0.006). For analyses of patients with bactobilia by URB versus the remaining patients, previous ERCP (OR, 35.284; 95% CI, 5.320 to 234.016; P < 0.001), previous intake of antibiotics (OR, 7.200; 95% CI, 0.962 to 53.906; P = 0.050), and age (OR, 1.113 per year of age; 95% CI, 1.028 to 1.206; P = 0.009) were associated with bactobilia by URB (R(2) Cox, 0.19; P < 0.001). Previous antibiotic exposure (in addition to age and previous ERCP) was a risk driver for bactobilia by URB. This may have implications in prophylactic/therapeutic measures.

Vitamin C and thiamine for the treatment of refractory septic shock in surgical critically ill patients: a retrospective before-and-after study.

OBJECTIVE: This study aimed to evaluate whether early vitamin C and thiamine administration was associated with a lower 28-day and in-hospital mortality in surgical critically ill patients with refractory septic shock. METHODS: We performed a retrospective before-and-after study on patients with refractory septic shock. According to local protocol, hydrocortisone is initiated in case of refractory septic shock. In January 2017, the protocol was changed and vitamin C and thiamine were included. Patients who were admitted in 2015-2016 and 2017-2018 were included in the control and treatment groups, respectively. The primary end point was 28-day and in-hospital mortality. Secondary end points were ICU mortality, ICU and hospital length of stay, duration of vasopressors and mechanical ventilation, use of renal replacement therapy (RRT), and the modification in serum procalcitonin and SOFA score during the first 72 h. RESULTS: A total of 120 patients were included (58 in the treatment group and 62 in the control group). Log-rank test in Kaplan-Meier curves showed lower 28-day and in-hospital mortality over time in the treatment group (p=0.021 and p=0.035, respectively) but it not reached statistical significance in ICU mortality over time (p=0.100). The need of RRT was less frequent in treatment group (17.2% vs. 37.1%, p=0.024). There were no differences in other secondary outcomes. CONCLUSIONS: Intravenous vitamin C and thiamine administration in surgical patients with refractory septic shock may be associated with a lower 28-day and in-hospital mortality. Further prospective studies are needed in refractory septic shock.

Controversies in the management of ESBL-producing Enterabacterales. Clinical Implications.

Extended-spectrum ß-lactamases (ESBL)-producing organisms currently represent a major health problem. Although recently published guidelines still consider carbapenems as the treatment of choice for ESBL-producing infections, it is necessary to find non-carbapenem ß-lactams as alternatives to reduce the effects associated with their overutilization. In this review we focus on these alternatives to carbepenem use. It is possible that piperacillin-tazobactam may be an alternative in clinical settings with "low inoculum" infections like urinary tract infections. Newer ß-lactam-ß-lactamase inhibitors (BLBLIs) are potential options too. The current available data support the efficacy of both ceftazidime-avibactam and ceftolozane-tazobactam against susceptible ESBL-producing Enterobacterales (ESBL-E). We are waiting for the results of MERINO-3 study to confirm whether ceftolozane-tazobactam is a good option versus meropenem for treating bloodstream infections caused by ESBL- or AmpC-producing Enterobacterales.

The role of cefiderocol in clinical practice.

Cefiderocol is a new antimicrobial with a chemical structure similar to ceftazidime and cefepime. In this review we will focus on the role of cefiderocol in different clinical scenarios produced by resistant Gram-negative microorganisms, especially to carbapenems. In infections caused by Gram-negative microorganisms, inappropriate antibiotic treatment increased the risk of mortality almost fourfold. In patients with hospital-acquired infection and septic shock; with sepsis and poor functional reserve due to fragility; in immunocompromised patients; and in those with local ecology, individual history of colonization or previous infection and risk factors for carbapenem-resistant Enterobacteriaceae (CRE) such as the presence of chronic multi-morbidities, the best option would be to start an active empirical treatment against gram-negative bacteria resistant to carbapenems and later in 24-36 h with the information obtained from the cultures we could decide on a definitive empirical or directed treatment and avoid unnecessary overuse of these antibiotics. Cefiderocol would be in these cases a good candidate due to its excellent in vitro activity against all classes of beta-lactamase-producing Gram-negatives (including carbapenemase class A, B and D producers), as well as against non-fermenting Gram-negatives such as P. aeruginosa, Acinetobacter spp. and S. maltophilia. It is necessary to optimize the use of new antibiotics such as cefiderocol, guaranteeing the best available treatment to patients while delaying the emergence and spread of resistance.

Clinical management of cUTI, cIAI, and HABP/VABP attributable to carbapenem-resistant Gram-negative infections in Spain.

OBJECTIVE: Carbapenem-resistant Gram-negative (CRGN) infections are a major public health problem in Spain, often implicated in complicated, healthcare-associated infections that require the use of potentially toxic antibacterial agents of last resort. The objective of this study was to assess the clinical management of complicated infections caused by CRGN bacteria in Spanish hospitals. METHODS: The study included: 1) a survey assessing the GN infection and antibacterial susceptibility profile in five participating Spanish hospitals and 2) a non-interventional, retrospective single cohort chart review of 100 patients with complicated urinary tract infection (cUTI), complicated intra-abdominal infection (cIAI), or hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia (HABP/VABP) attributable to CRGN pathogens. RESULTS: In the participating hospitals CRGN prevalence was 9.3% amongst complicated infections. In the retrospective cohort, 92% of infections were healthcare-associated, and Klebsiella pneumoniae and Pseudomonas aeruginosa were the most common pathogens. OXA was the most frequently detected carbapenemase type (71.4%). We found that carbapenems were frequently used to treat cUTI, cIAI, HABP/VABP caused by CRGN pathogens. Carbapenem use, particularly in combination with other agents, persisted after confirmation of carbapenem resistance. Clinical cure was 66.0%, mortality during hospitalization 35.0%, mortality at the time of chart review 62.0%, and 6-months-post-discharge readmission 47.7%. CONCLUSIONS: Our results reflect the high burden and unmet needs associated with the management of complicated infections attributable to CRGN pathogens in Spain and highlight the urgent need for enhanced clinical management of these difficult-to-treat infections.

Secondary infections in mechanically ventilated patients with COVID-19: An overlooked matter?

OBJECTIVE: The susceptibility to infection probably increases in COVID-19 patients due to a combination of virusand drug-induced immunosuppression. The reported rate of secondary infections was quite low in previous studies. The objectives of our study were to investigate the rate of secondary infections, risk factors for secondary infections and risk factors for mortality in COVID-19 critically ill patients. METHODS: We performed a single-center retrospective study in mechanically ventilated critically ill COVID-19 patients admitted to our Critical Care Unit (CCU). We recorded the patients' demographic data; clinical data; microbiology data and incidence of secondary infection during CCU stay, including ventilator-associated pneumonia (VAP) and nosocomial bacteremia (primary and secondary). RESULTS: A total of 107 patients with a mean age 62.2 ± 10.6 years were included. Incidence of secondary infection during CCU stay was 43.0% (46 patients), including nosocomial bacteremia (34 patients) and VAP (35 patients). Age was related to development of secondary infection (65.2 ± 7.3 vs. 59.9 ± 12.2 years, p=0.007). Age ≥ 65 years and secondary infection were independent predictors of mortality (OR=2.692, 95% CI 1.068-6.782, p<0.036; and OR=3.658, 95% CI 1.385- 9.660, p=0.009, respectively). The hazard ratio for death within 90 days in the ≥ 65 years group and in patients infected by antimicrobial resistant pathogens was 1.901 (95% CI 1.198- 3.018; p= 0.005 by log-rank test) and 1.787 (95% CI 1.023-3.122; p= 0.036 by log-rank test), respectively. CONCLUSIONS: Our data suggest that the incidence of secondary infection and infection by antimicrobial resistant pathogens is very high in critically ill patients with COVID-19 with a significant impact on prognosis.

Recommendations for antibiotic selection for severe nosocomial infections.

Severe infection and its evolution to sepsis are becoming more prevalent every day and are among the leading causes of critical illness and mortality. Proper management is crucial to improve prognosis. This document addresses three essential points that have a significant impact on this objective: a) early recognition of patients with sepsis criteria, b) identification of those patients who suffer from an infection and have a high risk of progressing to sepsis, and c) adequate selection and optimization of the initial antimicrobial treatment.

Practical recommendations for the perioperative management of the patient with suspection or serious infection by coronavirus SARS-CoV. / Recomendaciones prácticas para el manejo perioperatorio del paciente con sospecha o infección grave por coronavirus SARS-CoV-2.

In December 2019, the Wuhan Municipal Health and health Commission (Hubei Province, China) reported a series of cases of pneumonia of unknown etiology. On January 7, 2020, the Chinese authorities identified as a causative agent of the outbreak a new type of virus of the Coronaviridiae family, called SARS-CoV-2. Since then, thounsands of cases have been reported with global dissemination. Infections in humans cause a broad clinical spectrum ranging from mild upper respiratory tract infection, to severe acute respiratory distress syndrome and sepsis. There is not specific treatment for SARS-CoV-2, which is why the fundamental aspects are to establish adequate prevention measures and support treatment and management of complications.

Recommendations for the diagnosis and treatment of Clostridioides difficile infection: An official clinical practice guideline of the Spanish Society of Chemotherapy (SEQ), Spanish Society of Internal Medicine (SEMI) and the working group of Postoperative Infection of the Spanish Society of Anesthesia and Reanimation (SEDAR).

This document gathers the opinion of a multidisciplinary forum of experts on different aspects of the diagnosis and treatment of Clostridioides difficile infection (CDI) in Spain. It has been structured around a series of questions that the attendees considered relevant and in which a consensus opinion was reached. The main messages were as follows: CDI should be suspected in patients older than 2 years of age in the presence of diarrhea, paralytic ileus and unexplained leukocytosis, even in the absence of classical risk factors. With a few exceptions, a single stool sample is sufficient for diagnosis, which can be sent to the laboratory with or without transportation media for enteropathogenic bacteria. In the absence of diarrhoea, rectal swabs may be valid. The microbiology laboratory should include C. difficile among the pathogens routinely searched in patients with diarrhoea. Laboratory tests in different order and sequence schemes include GDH detection, presence of toxins, molecular tests and toxigenic culture. Immediate determination of sensitivity to drugs such as vancomycin, metronidazole or fidaxomycin is not required. The evolution of toxin persistence is not a suitable test for follow up. Laboratory diagnosis of CDI should be rapid and results reported and interpreted to clinicians immediately. In addition to the basic support of all diarrheic episodes, CDI treatment requires the suppression of antiperistaltic agents, proton pump inhibitors and antibiotics, where possible. Oral vancomycin and fidaxomycin are the antibacterials of choice in treatment, intravenous metronidazole being restricted for patients in whom the presence of the above drugs in the intestinal lumen cannot be assured. Fecal material transplantation is the treatment of choice for patients with multiple recurrences but uncertainties persist regarding its standardization and safety. Bezlotoxumab is a monoclonal antibody to C. difficile toxin B that should be administered to patients at high risk of recurrence. Surgery is becoming less and less necessary and prevention with vaccines is under research. Probiotics have so far not been shown to be therapeutically or preventively effective. The therapeutic strategy should be based, rather than on the number of episodes, on the severity of the episodes and on their potential to recur. Some data point to the efficacy of oral vancomycin prophylaxis in patients who reccur CDI when systemic antibiotics are required again.

Patient characteristics, clinical course and factors associated to ICU mortality in critically ill patients infected with SARS-CoV-2 in Spain: A prospective, cohort, multicentre study. / Características, evolución clínica y factores asociados a la mortalidad en UCI de los pacientes críticos infectados por SARS-CoV-2 en España: estudio prospectivo, de cohorte y multicéntrico.

BACKGROUND: The clinical course of COVID-19 critically ill patients, during their admission in the intensive care unit (UCI), including medical and infectious complications and support therapies, as well as their association with in-ICU mortality has not been fully reported. OBJECTIVE: This study aimed to describe clinical characteristics and clinical course of ICU COVID-19 patients, and to determine risk factors for ICU mortality of COVID-19 patients. METHODS: Prospective, multicentre, cohort study that enrolled critically ill COVID-19 patients admitted into 30 ICUs from Spain and Andorra. Consecutive patients from March 12th to May 26th, 2020 were enrolled if they had died or were discharged from ICU during the study period. Demographics, symptoms, vital signs, laboratory markers, supportive therapies, pharmacological treatments, medical and infectious complications were reported and compared between deceased and discharged patients. RESULTS: A total of 663 patients were included. Overall ICU mortality was 31% (203 patients). At ICU admission non-survivors were more hypoxemic [SpO2 with non-rebreather mask, 90 (IQR 83 to 93) vs. 91 (IQR 87 to 94); P<.001] and with higher sequential organ failure assessment score [SOFA, 7 (IQR 5 to 9) vs. 4 (IQR 3 to 7); P<.001]. Complications were more frequent in non-survivors: acute respiratory distress syndrome (ARDS) (95% vs. 89%; P=.009), acute kidney injury (AKI) (58% vs. 24%; P<10-16), shock (42% vs. 14%; P<10-13), and arrhythmias (24% vs. 11%; P<10-4). Respiratory super-infection, bloodstream infection and septic shock were higher in non-survivors (33% vs. 25%; P=.03, 33% vs. 23%; P=.01 and 15% vs. 3%, P=10-7), respectively. The multivariable regression model showed that age was associated with mortality, with every year increasing risk-of-death by 1% (95%CI: 1 to 10, P=.014). Each 5-point increase in APACHE II independently predicted mortality [OR: 1.508 (1.081, 2.104), P=.015]. Patients with AKI [OR: 2.468 (1.628, 3.741), P<10-4)], cardiac arrest [OR: 11.099 (3.389, 36.353), P=.0001], and septic shock [OR: 3.224 (1.486, 6.994), P=.002] had an increased risk-of-death. CONCLUSIONS: Older COVID-19 patients with higher APACHE II scores on admission, those who developed AKI grades ii or iii and/or septic shock during ICU stay had an increased risk-of-death. ICU mortality was 31%.

[Recommendations in the empiric anti-infective agents of intra-abdominal infection]. / Recomendaciones en el tratamiento antibiótico empírico de la infección intraabdominal.

A significant number of patients with abdominal infection develop advanced stages of infection and mortality is still above 20%. Failure is multifactorial and is associated with an increase of bacterial resistance, inappropriate empirical treatment, a higher comorbidity of patients and poor source control of infection. These guidelines discuss each of these problems and propose measures to avoid the failure based on the best current scientific evidence.

New evidence on the use of fosfomycin for bacteremia and infectious endocarditis.

There is growing concern regarding the increased resistance rates of numerous pathogens and the limited availability of new antibiotics against these pathogens. In this context, fosfomycin is of considerable interest due to its activity against a wide spectrum of these microorganisms. We will review the encouraging data on this issue regarding the use of fosfomycin in treating Gram-negative bacterial infections. We will also cover fosfomycin's role against 2 of the main causal agents of bacteremia and endocarditis worldwide (nosocomial and community-acquired): enterococci, whose growing resistance to glycopeptides and aminoglycosides represents a serious threat, and methicillin-resistant Staphylococcus aureus, whose infection, despite efforts, continues to be associated with high morbidity and mortality and a high risk of complications. Thanks also to its considerable synergistic capacity with various antibiotics, fosfomycin is a tool for extending the therapeutic arsenal against these types of infections.

[Septic shock due to community-acquired complicated intra-abdominal infection treated with ertapenem: outcome in 25 cases]. / Resultados en 25 pacientes con shock séptico por infección intraabdominal complicada adquirida en la comunidad tratados con ertapenem.

OBJECTIVES: To assess the effectiveness of ertapenem in patients admitted to a surgical intensive care unit with septic shock due to community-acquired complicated intra-abdominal infection. PATIENTS AND METHODS: Patients undergoing emergency surgery for community-acquired complicated intra-abdominal infection were enrolled prospectively. All patients were given intravenous ertapenem at a rate of 1 g/24 h and the guidelines of the Surviving Sepsis Campaign were applied. Outcome measures were duration of antibiotic therapy, mean length of stay in the surgical intensive care unit (ICU), antibiotic failure, and death while in the surgical ICU. RESULTS: Twenty-five patients with a mean (SD) age of 74 (14) years were enrolled. The origin of infection was the colon in 56% of the cases; most patients (76%) had generalized peritonitis. The mean stay in the surgical ICU was 10 (7) days. The mean duration of antibiotic therapy was 5.8 (1.26) days. Antibiotic failure occurred in 12%. Mortality in the surgical ICU was 28%. CONCLUSIONS: Our findings suggest that patients with community-acquired intra-abdominal infection and septic shock have a good chance of survival when treated according to the guidelines of the Surviving Sepsis Campaign. Ertapenem seems to give good results when used in this setting.

Prognosis and predictors of mortality in critically ill elderly patients. / Pronóstico y predictores de mortalidad de los pacientes ancianos críticos.

OBJECTIVES: to evaluate mortality of patients≥80 years admitted to the Surgical Intensive Care Unit (SICU), global hospital mortality and factors related to it. MATERIAL AND METHODS: observational retrospective study of patients≥80 years admitted to SICU between June 2012 and June 2015. RESULTS: a total of 299 patients were included, 54 of them died in the SICU (18.1%) and 80 patients (26.8%) died during their hospital stay. SICU mortality was independently related to age (OR=1.125; 95%CI: 1.042-1.215; P=.003), SAPS II (OR=1.026; 95% CI: 1.008-1.044; P=.004), need for renal replacement therapy (RRT) (OR=1.960; 95%CI: 1.046-3.671; P=.036) and need for mechanical ventilation for more than 24hours (OR=2.834; 95%CI: 1.244-6.456; P=.013). Factors independently related to hospital mortality were age (OR=1.125; 95%CI: 1.054-1.192; P<.001), SOFA score (OR=1.154; 95% CI: 1.079-1.235; P<.001), need for RRT (OR=1.924; 95%CI: 1.121-3.302; p=0.018) and need for mechanical ventilation for more than 24hours (OR=3.144; 95% CI: 1.771-5.584; P<.001). CONCLUSIONS: In critically ill patients over 80 years hospital mortality was independently related to age, SOFA score, RRT need and need for mechanical ventilation for more than 24hours. Our results raise important issues about end-of-life care and life-sustaining interventions in elderly, critically ill patients.

Current aspects in sepsis approach. Turning things around.

The incidence and prevalence of sepsis depend on the definitions and records that we use and we may be underestimating their impact. Up to 60% of the cases come from the community and in 30-60% we obtain microbiological information. Sometimes its presentation is ambiguous and there may be a delay in its detection, especially in the fragile population. Procalcitonin is the most validated biomarker for bacterial sepsis and the one that best discriminates the non-infectious cause. Presepsin and pro-adrenomedullin are useful for early diagnosis, risk stratification and prognosis in septic patients. The combination of biomarkers is even more useful to clarify an infectious cause than any isolated biomarker. Resuscitation with artificial colloids has worse results than crystalloids, especially in patients with renal insufficiency. The combination of saline solution and balanced crystalloids is associated with a better prognosis. Albumin is only recommended in patients who require a large volume of fluids. The modern molecular methods on the direct sample or the identification by MALDI-TOF on positive blood culture have helped to shorten the response times in diagnosis, to optimize the antibiotic treatment and to facilitate stewardship programs. The hemodynamic response in neonates and children is different from that in adults. In neonatal sepsis, persistent pulmonary hypertension leads to an increase in right ventricular afterload and heart failure with hepatomegaly. Hypotension, poor cardiac output with elevated systemic vascular resistance (cold shock) is often a terminal sign in septic shock. Developing ultra-fast Point-of-Care tests (less than 30 minutes), implementing technologies based on omics, big data or massive sequencing or restoring "healthy" microbiomes in critical patients after treatment are the main focuses of research in sepsis. The main benefits of establishing a sepsis code are to decrease the time to achieve diagnosis and treatment, improve organization, unify criteria, promote teamwork to achieve common goals, increase participation, motivation and satisfaction among team members, and reduce costs.

Antibiotic selection in the treatment of acute invasive infections by Pseudomonas aeruginosa: Guidelines by the Spanish Society of Chemotherapy.

Pseudomonas aeruginosa is characterized by a notable intrinsic resistance to antibiotics, mainly mediated by the expression of inducible chromosomic ß-lactamases and the production of constitutive or inducible efflux pumps. Apart from this intrinsic resistance, P. aeruginosa possess an extraordinary ability to develop resistance to nearly all available antimicrobials through selection of mutations. The progressive increase in resistance rates in P. aeruginosa has led to the emergence of strains which, based on their degree of resistance to common antibiotics, have been defined as multidrug resistant, extended-resistant and panresistant strains. These strains are increasingly disseminated worldwide, progressively complicating the treatment of P. aeruginosa infections. In this scenario, the objective of the present guidelines was to review and update published evidence for the treatment of patients with acute, invasive and severe infections caused by P. aeruginosa. To this end, mechanisms of intrinsic resistance, factors favoring development of resistance during antibiotic exposure, prevalence of resistance in Spain, classical and recently appeared new antibiotics active against P. aeruginosa, pharmacodynamic principles predicting efficacy, clinical experience with monotherapy and combination therapy, and principles for antibiotic treatment were reviewed to elaborate recommendations by the panel of experts for empirical and directed treatment of P. aeruginosa invasive infections.

Antimicrobial management in nosocomial peritonitis: microbiota, drug and time.

Complicated intra-abdominal infection requires surgical treatment and broad-spectrum empiric antibiotic treatment used early. The rapid spread of multidrug-resistant bacteria has become a serious threat, especially in critical care units. The excessive use of carbapenems has led to carbapenemase-producing Enterobacteriaceae, leaving tigecycline and colistin as therapeutical options. The new antimicrobials, ceftazidime-avibactam and ceftolozane-tazobactam open new horizons in the treatment of multi-drug resistant Enterobacteriaceae. Candida peritonitis causes a high mortality in the critical patient. Diagnosis and early treatment are associated with a better prognosis, the administration of an echinocandin being of choice in these patients.

Update on management of invasive candidiasis.

Given the growing incidence of invasive candidiasis in critically ill and haemato-oncological patients and its poor outcomes, an early diagnosis and treatment are need for get a better prognosis. This document reviews the current ap-proaches that help in diagnosis of invasive candidiasis based on culture-independent microbiological tests. The combination of clinical prediction scores with fungal serological markers could facilitate the approach in antifungal therapy, optimiz-ing it. This article also reviews the epidemiology and primary risk factors for invasive candidiasis in these patients, updating the therapeutic approach algorithms in both clinical contexts based on the main evidence and international guidelines.

[Candidemia and invasive candidiasis approach in critically ill patients: role of the echinocandins]. / Abordaje de la candidemia y la candidiasis invasiva en el paciente crítico: papel de las equinocandinas.

OBJECTIVE: Invasive infections caused by Candida spp. in critically ill patients may significantly worsen their prognosis, so it is of great importance to establish an early detection and a suitable therapeutic strategy. The objective of this study was to define the differential role of echinocandins in treating certain critical patient profiles. METHODS: A scientific committee of 9 experts in infectious diseases, critical care, microbiology, and hospital pharmacy reviewed the existing evidence on the treatment of candidemia and invasive candidiasis in critically ill patients. After that, a questionnaire with 35 items was elaborated to be agreed by 26 specialists in the aforementioned disciplines using a modified Delphi method. RESULTS: After two rounds of evaluation, a consensus was reached in terms of agreement in 66% of the items. Some of the consensuses achieved included: it is not necessary to adjust the dose of echinocandins during renal replacement therapy; the echinocandins are the empirical and/or directed treatment of choice for candidemia and invasive candidiasis associated with biofilms; these drugs may be used in the antifungal prophylaxis of high-risk liver transplantation. In the absence of additional clinical data, it should be noted that micafungin is the echinocandin with the most available scientific evidence. CONCLUSIONS: The experts consulted showed a high degree of agreement on some of the most controversial aspects regarding the management of candidemia and invasive candidiasis in critical patients, which could inform of practical recommendations for their treatment.