Impact of Aspergillus spp. isolation in the first 24 hours of admission in critically ill patients with severe influenza virus pneumonia.

OBJECTIVE: To determine the incidence and impact of Aspergillus spp. isolation (AI) on ICU mortality in critically ill patients with severe influenza pneumonia during the first 24h of admission. DESIGN: Secondary analysis of an observational and prospective cohort study. SETTING: ICUs voluntary participating in the Spanish severe Influenza pneumonia registry, between June 2009 and June 2019. PATIENTS: Consecutive patients admitted to the ICU with diagnosis of severe influenza pneumonia, confirmed by real-time polymerase chain reaction. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Incidence of AI in respiratory samples. Demographic variables, comorbidities, need for mechanical ventilation and the presence of shock according at admission. Acute Physiology and Chronic Health Evaluation II (APACHE II) scale calculated on ICU admission. RESULTS: 3702 patients were analyzed in this study. AI incidence was 1.13% (n=42). Hematological malignancies (OR 4.39, 95% CI 1.92-10.04); HIV (OR 3.83, 95% CI 1.08-13.63), and other immunosuppression situations (OR 4.87, 95% CI 1.99-11.87) were factors independently associated with the presence of Aspergillus spp. The automatic CHAID decision tree showed that hematologic disease with an incidence of 3.3% was the most closely AI related variable. Hematological disease (OR 2.62 95% CI 1.95-3.51), immunosuppression (OR 2.05 95% CI 1.46-2.88) and AI (OR 3.24, 95% CI 1.60-6.53) were variables independently associated with ICU mortality. CONCLUSIONS: Empirical antifungal treatment in our population may only be justified in immunocompromised patients. In moderate-high risk cases, active search for Aspergillus spp. should be implemented.

Early Stepdown From Echinocandin to Fluconazole Treatment in Candidemia: A Post Hoc Analysis of Three Cohort Studies.

BACKGROUND: There are no clear criteria for antifungal de-escalation after initial empirical treatments. We hypothesized that early de-escalation (ED) (within 5 days) to fluconazole is safe in fluconazole-susceptible candidemia with controlled source of infection. METHODS: This is a multicenter post hoc study that included consecutive patients from 3 prospective candidemia cohorts (2007-2016). The impact of ED and factors associated with mortality were assessed. RESULTS: Of 1023 candidemia episodes, 235 met inclusion criteria. Of these, 54 (23%) were classified as the ED group and 181 (77%) were classified as the non-ED group. ED was more common in catheter-related candidemia (51.9% vs 31.5%; P = .006) and episodes caused by Candida parapsilosis, yet it was less frequent in patients in the intensive care unit (24.1% vs 39.2%; P = .043), infections caused by Nakaseomyces glabrata (0% vs 9.9%; P = .016), and candidemia from an unknown source (24.1% vs 47%; P = .003). In the ED and non-ED groups, 30-day mortality was 11.1% and 29.8% (P = .006), respectively. Chronic obstructive pulmonary disease (odds ratio [OR], 3.97; 95% confidence interval [CI], 1.48-10.61), Pitt score > 2 (OR, 4.39; 95% CI, 1.94-9.20), unknown source of candidemia (OR, 2.59; 95% CI, 1.14-5.86), candidemia caused by Candida albicans (OR, 3.92; 95% CI, 1.48-10.61), and prior surgery (OR, 0.29; 95% CI, 0.08-0.97) were independent predictors of mortality. Similar results were found when a propensity score for receiving ED was incorporated into the model. ED had no significant impact on mortality (OR, 0.50; 95% CI, 0.16-1.53). CONCLUSIONS: Early de-escalation is a safe strategy in patients with candidemia caused by fluconazole-susceptible strains with controlled source of bloodstream infection and hemodynamic stability. These results are important to apply antifungal stewardship strategies.

A clinical predictive model of candidaemia by Candida auris in previously colonized critically ill patients.

OBJECTIVES: Candida auris is an emerging multidrug-resistant fungus that has been associated with nosocomial outbreaks with high rates of mortality and transmission. The aim of this study was to perform a retrospective cohort analysis of risk factors and to build a scoring method for estimating the risk of candidaemia in colonized critically ill patients. METHODS: We performed a retrospective observational cohort study of patients aged ≥15 years colonized by C. auris in the 3-year period between March 2016 and March 2019. Epidemiological, clinical, laboratory and microbiological data were collected. We developed a predictive model for candidaemia using elastic net multivariable logistic regression techniques, assessed its discriminative capacity, and internally validated it using bootstrap resampling. RESULTS: Two-hundred and six patients were enrolled in the cohort for derivation and internal validation. Thirty-seven out of 206 patients developed candidaemia. Total parenteral nutrition was the foremost risk factor (adjusted OR 3.73); previous surgery (adjusted OR 1.03), sepsis (adjusted OR 1.75), previous exposure to antifungal agents (adjusted OR 1.17), arterial catheters (adjusted OR 1.46), central venous catheters (adjusted OR 1.21), presence of advanced chronic kidney disease (adjusted OR 1.35) and multifocal colonization (adjusted OR of unifocal colonization 0.46) were proven to be independent predictors of candidaemia in our cohort. The corresponding area under the curve (AUC) of the elastic net regularized predictive model was 0.89 (95%CI 0.826; 0.951). After performing the internal validation by generating 500 bootstrap replications, the model still showed great accuracy, with a resulting AUC of 0.84. CONCLUSION: Our study provides evidence on the independent predisposing factors for candidaemia. It may help predict its estimated risk and may identify a high-risk population that could benefit from early or prophylactic antifungal treatment after external validation in other cohorts.

Incidence and risk factors of post-engraftment invasive fungal disease in adult allogeneic hematopoietic stem cell transplant recipients receiving oral azoles prophylaxis.

Studies that analyze the epidemiology and risk factors for invasive fungal disease (IFD) after engraftment in alloSCT are few in number. This single-center retrospective study included 404 alloSCT adult recipients surviving >40 days who engrafted and were discharged without prior IFD. All patients who received ⩾20 mg/day of prednisone were assigned to primary oral prophylaxis (itraconazole or low-dose voriconazole). The primary end point was the cumulative incidence (CI) of probable/proven IFD using the European Organization for Research and Treatment of Cancer and Mycoses Study Group (EORTC/MSG) criteria. The independent prognostic factors after multivariate analyses were used to construct a post-engraftment IFD risk score. The 1-year CI of IFD was 11%. The non-relapse mortality was 40% in those developing IFD and 16% in those who did not. The intent-to-treat analysis showed that 17% of patients abandoned the assigned prophylaxis. Age >40 years, ⩾1 previous SCT, pre-engraftment neutropenia >15 days, extensive chronic GVHD and CMV reactivation were independent risk factors. The post-engraftment IFD score stratified patients into low risk (0-1 factor, CI 0.7%), intermediate risk (2 factors, CI 9.9%) and high risk (3-5 factors, CI 24.7%) (P<0.0001). The antifungal prophylaxis strategy failed to prevent post-engraftment IFD in 11% of alloSCT. Our risk score could be useful to implement risk-adapted strategies using antifungal prophylaxis after engraftment.

Invasive Candida infections in surgical patients in intensive care units: a prospective, multicentre survey initiated by the European Confederation of Medical Mycology (ECMM) (2006-2008).

A prospective, observational, multicentre study of invasive candidosis (IC) in surgical patients in intensive care units (ICUs) was conducted from 2006 to 2008 in 72 ICUs in 14 European countries. A total of 779 patients (62.5% males, median age 63 years) with IC were included. The median rate of candidaemia was 9 per 1000 admissions. In 10.8% the infection was already present at the time of admission to ICU. Candida albicans accounted for 54% of the isolates, followed by Candida parapsilosis 18.5%, Candida glabrata 13.8%, Candida tropicalis 6%, Candida krusei 2.5%, and other species 5.3%. Infections due to C. krusei (57.9%) and C. glabrata (43.6%) had the highest crude mortality rate. The most common preceding surgery was abdominal (51.5%), followed by thoracic (20%) and neurosurgery (8.2%). Candida glabrata was more often isolated after abdominal surgery in patients ≥60 years, and C. parapsilosis was more often isolated in neurosurgery and multiple trauma patients as well as children ≤1 year of age. The most common first-line treatment was fluconazole (60%), followed by caspofungin (18.7%), liposomal amphotericin B (13%), voriconazole (4.8%) and other drugs (3.5%). Mortality in surgical patients with IC in ICU was 38.8%. Multivariate analysis showed that factors independently associated with mortality were: patient age ≥60 years (hazard ratio (HR) 1.9, p 0.001), central venous catheter (HR 1.8, p 0.05), corticosteroids (HR 1.5, p 0.03), not receiving systemic antifungal treatment for IC (HR 2.8, p <0.0001), and not removing intravascular lines (HR 1.6, p 0.02).

Unexpected postmortem diagnosis of Acanthamoeba meningoencephalitis following allogeneic peripheral blood stem cell transplantation.

Meningoencephalitis caused by pathogenic free-living amebas is usually fatal. Only a few cases of Acanthamoeba meningoencephalitis, diagnosed at autopsy, have been reported following hematopoietic stem cell transplantation. We here report a case of Acanthamoeba meningoencephalitis following allogeneic peripheral blood stem cell transplantation with rapidly evolving neurologic symptoms that remained unexplained. Magnetic resonance imaging failed to show brain lesions and cerebrospinal fluid was negative for microbiological cultures. Definite diagnosis was an unexpected autopsy finding. As overall and teaching hospital autopsy rates are declining worldwide, we must emphasize the need of autopsy exams if we want to improve our knowledge as the best way to care for our patients.

Epidemiology of candidaemia in Europe: results of 28-month European Confederation of Medical Mycology (ECMM) hospital-based surveillance study.

In order to update the epidemiological and mycological profile of candidaemia in Europe, the European Confederation of Medical Mycology conducted a prospective, sequential, hospital population-based study from September 1997 to December 1999. A total of 2,089 cases were documented by 106 institutions in seven European countries. Rates of candidaemia ranging from 0.20 to 0.38 per 1,000 admissions were reported. Candida albicans was identified in 56% of cases. Non-albicans Candida species were most frequently isolated from patients with haematological malignancies (65%). With increasing age, an increasing incidence of Candida glabrata was seen. The 30-day mortality rate was 37.9%. The survey results underline the burden of candidaemia in a wide range of patient populations, confirm the importance of non- albicans species, and provide baseline data for future surveillance studies at a European level.

Infectious complications in patients undergoing unrelated donor bone marrow transplantation: experience from a single institution.

OBJECTIVE: To analyze the incidence and characteristics of documented infections in patients with hematologic malignancies undergoing unrelated donor bone marrow transplantation (UD-BMT). METHODS: We studied the occurrence of infections in 22 patients with hematologic malignancies or severe aplastic anemia who underwent UD-BMT from April 1990 to December 2000. The median age was 26 years (range 13-46). Acyclovir-ganciclovir, co-trimoxazole, fluconazole-nystatin and ciprofloxacin were administered for anti-infectious prophylaxis. RESULTS: We registered 61 infectious episodes. During the early post-transplant period, there were eight clinically documented infections (CDIs), four cases of fever of unknown origin (FUO), seven cases of bacteremia, two cases of cytomegalovirus (CMV) antigenemia, and one case of CMV disease. In the intermediate period (days 30-100 after BMT), there were nine cases of CMV antigenemia, three bacterial infections, two fungal infections, one case of disseminated toxoplasmosis, and one case of FUO. In the late period (day 100 and later), we documented 13 viral infections, eight bacterial infections, one CDI, and one case of invasive aspergillosis. Infections contributed to death in 10 of 17 patients. Citrobacter bacteremia and sepsis of unknown origin were the main causes of infectious mortality in the early period. Infection was the main cause of death in six of seven patients in the late period. CONCLUSION: A high incidence of life-threatening infections and infection-related mortality was observed. A high rate of CMV infection in the early period, and death caused by multiresistant Gram-negative microorganisms in the late period, were the main findings in this series.

Two cases of fungemia due to Candida lusitaniae and a literature review.

Reported here are two cases of candidemia caused by Candida lusitaniae that occurred in two immunocompromised patients at Hospital Universitario "La Fe" in Valencia, Spain. Case 1 involved a low-birth-weight premature infant with congenital nephrotic syndrome who was successfully treated with amphotericin B, and case 2 involved a 50-year old woman with a high-grade malignancy lymphoma who succumbed to the infection. Antifungal susceptibility testing of the Candida lusitaniae isolates recovered from both patients revealed sensitivity to amphotericin, 5-flucytosine and fluconazole. Results are presented and discussed together with a comprehensive review of the literature, covering all previously reported cases of fungemia caused by this emerging pathogen.

In vitro susceptibility of Candida dubliniensis to current and new antifungal agents.

BACKGROUND: Candida dubliniensis is a recently described Candida species closely related to Candida albicans, which has been associated with oral candidiasis in HIV-infected patients. Fluconazole-resistant strains of C. dubliniensis are easily obtained in vitro and this fact could be a complication if this resistance develops during treatment with this drug. METHODS: In the present study, the in vitro antifungal susceptibilities of 36 C. dubliniensis clinical isolates and culture strains to current and new antifungal agents, such as amphotericin B (AMB), amphotericin B lipid complex (ABLC), amphotericin B colloidal dispersion (ABCD), 5-fluorocytosine (5FC), fluconazole (FLC), itraconazole (ITC), ketoconazole (KTC), liposomal amphoteri- cin B (LAMB), liposomal nystatin (LNYT), LY303366 (LY), SCH56592 (SCH), and voriconazole (VRC), were determined according to the National Committee for Clinical Laboratory Standards M27-A broth microdilution method for yeasts. RESULTS: Most isolates of C. dubliniensis were susceptible to both new and current antifungal drugs, with 75.9% isolates susceptible to KTC, 86.2% to FLC and to ITC, and approximately 100% to the other antifungal agents tested. The cross-resistance phenotypes are detailed. Four isolates were resistant (MIC > or =64 microg/ml) to FLC. These 4 isolates were also resistant to KTC, and 3 of them were also resistant to ITC (MIC > or =1 microg/ml for both agents). However, these isolates were highly susceptible to 5FC and all polyene formulations (AMB, ABLC, ABCD, LAMB, and LNYT), triazole (SCH and VRC) and echinocandin (LY) antifungal agents. CONCLUSION: The new liposomal and lipidic formulations of AMB, LNYT, and the new triazoles and echinocandins may provide new alternatives to FLC for the treatment of infections by C. dubliniensis.

Killing of gram-negative bacteria by ciprofloxacin within both healthy human neutrophils and neutrophils with inactivated O2-dependent bactericidal mechanisms.

The intraphagocytic killing of Escherichia coli, Serratia marcescens, Pseudomonas aeruginosa, and Salmonella typhi by ciprofloxacin (0.1, 1 and 5 microg/ml) within human neutrophils with intact and impaired (by phenylbutazone treatment) O2-dependent killing mechanisms was studied and compared with the extracellular killing in the same medium of the intraphagocytic killing, but omitting neutrophils. The MIC/MBC of ciprofloxacin in vitro (assays performed according to NCCLS specifications) were: 0.015/0.06 for E. coli, 0.12/32 for S. marcescens, 1/16 for P. aeruginosa, and 0.007/0.06 for S. typhi. Ciprofloxacin showed bactericidal activity both extracellular and within phenylbutazone-treated and untreated neutrophils. The minimum concentration of ciprofloxacin to kill 90% of phagocytosed bacteria within neutrophils with normal O2-dependent killing power after 30 min was: 0.1 microg/ml for E. coli, and S. typhi, 1 microg/ml for P. aeruginosa, and 5 microg/ml for S. marcescens. In contrast, exposure for 60 min was required to reach this percentage within phenylbutazone treated neutrophils. The minimum concentration to kill 90% of extracellular bacteria after 30 min was: 0.1 microg/ml for E. coli, P. aeruginosa and S. typhi, and 5 microg/ml, for S. marcescens. A positive interaction between ciprofloxacin and the O2-dependent mechanisms of phagocytes was found. The reactive oxygen metabolites produced in the respiratory burst did not affect the intraphagocytic activity of ciprofloxacin. Phenylbutazone treatment of phagocytes would be a good experimental model to study the intraphagocytic killing of drugs in situations such as AIDS and chronic granulomatous disease where inefficient oxidative mechanisms of neutrophils exist.

[Invasive fungal infections in patients with blood disorders]. / Infecciones fúngicas invasoras en pacientes con hemopatías.

BACKGROUND: Invasive fungal infections (IFI) are severe infectious complications frequently observed in patients with hematological disorders. The aims of this study were to analyse the characteristics of this particular type of infection in a large series of a single institution and to determine the factors associated with the outcome and therapeutic response. PATIENTS AND METHODS: This study reviews the clinical and microbiological features of 155 IFI occurred among 144 patients with hematologic disorders throughout a period of 17 years in a single institution. RESULTS: In 118 cases (82%) the diagnosis was acute leukemia. The main risk factors for developing IFI included a persistent and profound granulocytopenia, the use of broad-spectrum antibacterial agents, indwelling central venous catheters and the damage of normal host barriers following intensive cytotoxic chemotherapy. Candida (65 cases [44%]) and Aspergillus (38 cases [26%]) species were the most common fungal species isolated. An increasing number of IFI were caused by fungi previously considered as contaminants or harmless colonizers. The outcome of IFI was favourable in 78 cases (50%). The most important prognostic factors for the outcome of the IFI were the phase of cytotoxic chemotherapy (p = 0.005), the response of the underlying disease to the cytotoxic chemotherapy (p < 0.00001), and the recovery of neutropenia during the infection course (p < 0.00001). An earlier use of empirical antifungal therapy was also associated with a better outcome. CONCLUSIONS: In spite of earlier treatment and regardless the development of new antifungal agents, the prognosis of IFI in patients with hematological malignancies remains poor. The use of hematopoietic growth factors, through their impact in the duration and severity of neutropenia, may prove valuable the management of IFI in this setting.

Laparoscopic pelvic lymphadenectomy for prostatic cancer.

Development of laparoscopic techniques has converted lymphadenectomy into a real alternative to current laparotomy technique. The limitation of diagnostic imaging methods to know ganglion involvement in prostate cancer as well the high incidence of false negatives in frozen intrasurgical biopsies following open-surgery lymphadenectomy has pushed us since november of 1990 to develop laparoscopic lymphadenectomy with staging. This study analyses the diverse diagnostic imaging methods and continues with a precise description of the laparoscopic technique. The authors summarize the results of our series and finish the article with a review of the most controversial aspects as well as the diagnostic value, advantages and disadvantages with respect to open surgery techniques, complications and indications of this technique at the present moment.

Intraphagocytic killing of gram-positive bacteria by ciprofloxacin.

The intraphagocytic killing of Staphylococcus aureus, Streptococcus pyogenes, and Corynebacterium group D2 by ciprofloxacin (0.1, 1 and 5 mg/L) within human neutrophils was determined. The organisms showed different susceptibility to neutrophil killing mechanisms. The neutrophils with intact and impaired (by phenylbutazone treatment) O2-dependent killing mechanisms were studied. The minimum concentrations of ciprofloxacin to kill 90% of phagocytosed bacteria within untreated neutrophils after 2 h were 1 mg/L for S. aureus and Corynebacterium group D2, and 0.1 mg/L for S. pyogenes. In contrast, exposure for 3 h was required to achieve similar cidal effects within phenylbutazone treated neutrophils. Synergic interaction between ciprofloxacin and the O2-dependent mechanisms of phagocytes was found. The reactive oxygen metabolites produced in the respiratory burst did not affect the intraphagocytic activity of ciprofloxacin. Phenylbutazone treatment of phagocytes would be a good experimental model to study intraphagocytic killing by drugs in situations where the oxidative mechanisms of neutrophils are impaired (for example AIDS and chronic granulomatous disease).

In-vitro postantibiotic effect of sparfloxacin and ciprofloxacin against Pseudomonas aeruginosa and Enterococcus faecalis.

The effect of concentration and exposure time on the postantibiotic effect (PAE) of sparfloxacin and ciprofloxacin against Pseudomonas aeruginosa Psa-1 and Enterococcus faecalis SD-63 was evaluated by the colony counting method using centrifugation to remove the antibiotic. The microorganisms were exposed for 15, 30 and 60 min to drug concentrations ranging from 1 x MIC to 31 x MIC. The PAE was calculated as the difference in time required by test and control cultures to increase 1 log10 after the drug was removed. The MICs of sparfloxacin for P. aeruginosa and E. faecalis were 0.50 mg/L and 0.25 mg/L, respectively, whereas the MICs of ciprofloxacin were 0.25 mg/L for P. aeruginosa and 0.50 mg/L for E. faecalis. PAEs increased as a function of concentration and exposure time. Against E. faecalis no point of maximal response was reached. On the contrary, against P. aeruginosa this point was reached at 8 x MIC of ciprofloxacin and 16 x MIC of sparfloxacin PAE values of sparfloxacin for P. aeruginosa and E. faecalis ranged from 7 to 96 min and from 0 to 112 min, respectively, and those of ciprofloxacin from 8.5 to 82.33 min and from 0 to > 136 min, respectively. Significant PAEs for P. aeruginosa were obtained after 60 min exposure at 4 x MIC (62.6 min) and 2 x MIC (52.6 min) of ciprofloxacin and sparfloxacin, respectively, and at 8 x MIC (81.5 min) and 16 x MIC (81.6 min) for E. faecalis.(ABSTRACT TRUNCATED AT 250 WORDS)

[Current indications for laparoscopic surgery in urology]. / Indicaciones actuales de cirugía laparoscópica en urología.

More than four years have elapsed since the first laparoscopic pelvian lymphadenectomy for the staging of prostate cancer was performed. The early impact of the procedure involved the broadening and gradual application of laparoscopy to the group of organs and diseases of our specialty, mainly with therapeutical purposes. Urologists are able to reproduce nowadays many of the traditional surgical procedures through these methods. The present paper tries to conduct an update of the different techniques applied up to now on the different structures (genitalia, prostate, bladder, ureter, kidney, adrenals, pelvian nodes and other) and to analyze objectively some specific indications based on the experience gathered by several authors and our own.

[Laparoscopic surgery instrumentation]. / Instrumental en cirugía laparoscópica.

Today the urologist can perform many of the conventional surgical procedures by laparoscopic methods, which could not have been developed and improved without technological support. Industry has continued to provide solutions to each new requirement of laparoscopic surgery through more ergonomic materials and instruments. The different equipment and instruments for performing laparoscopic procedures are analyzed and described in the present article.

[Laparoscopic lymphadenectomy]. / Linfadenectomía laparoscópica.

The limitations of the diagnostic imaging methods in determining lymph node involvement in pelvic tumors (prostatic cancer) and the high incidence of false negatives in the intraoperative frozen biopsies done during open lymphadenectomy have prompted us to develop laparoscopic staging lymphadenectomy since November, 1990. The different imaging and invasive diagnostic methods are briefly analyzed in the present article. The laparoscopic lymphadenectomy procedure is described in detail and a summary of our series is presented.

[Laparoscopic nephrectomy: a case report]. / Nefrectomía laparoscópica: caso report.

Presentation and clinical picture outline of a patient who underwent transperitoneal laparoscopy-assisted nephrectomy. The procedure lasted 4 hours and the patient was discharged 72 hours later without incidence or complications. The paper describes the technique (presently unique and for selective indications), as well as the resources that the extensive laparoscopic experience of our group put into practice to perform the first successful laparoscopic nephrectomy in humans in our country.