Attributable mortality of candidemia - Results from the ECMM Candida III multinational European Observational Cohort Study.

INTRODUCTION: Despite antifungal advancements, candidaemia still has a high mortality rate of up to 40%. The ECMM Candida III study in Europe investigated the changing epidemiology and outcomes of candidaemia for better understanding and management of these infections. METHODS: In this observational cohort study, participating hospitals enrolled the first ten consecutive adults with blood culture-proven candidemia. Collected data included patient demographics, risk factors, hospital stay duration (follow-up of 90 days), diagnostic procedures, causative Candida spp., management details, and outcome. Controls were included in a 1:1 fashion from the same hospitals. The matching process ensured similarity in age (10-year range), primary underlying disease, hospitalization in intensive care versus non-ICU ward, and major surgery within 2 weeks before candidemia between cases and controls. Overall and attributable mortality were described, and a survival probability for cases and controls was performed. RESULTS: One hundred seventy-one pairs consisting of patients with candidemia and matched controls from 28 institutions were included. In those with candidemia, overall mortality was 40.4%. Attributable mortality was 18.1% overall but differed between causative Candida species (7.7% for Candida albicans, 23.7% for Candida glabrata/Nakaseomyces glabratus, 7.7% for Candida parapsilosis and 63.6% for Candida tropicalis). Regarding risk factors, the presence of a central venous catheter, total parenteral nutrition and acute or chronic renal disease were significantly more common in cases versus controls. Duration of hospitalization, and especially that of ICU stay, was significantly longer in candidemia cases (20 (IQR 10-33) vs 15 days (IQR 7-28); p = 0.004). CONCLUSIONS: Although overall and attributable mortality in this subgroup analysis of matched case/control pairs remains high, the attributable mortality appears to have decreased in comparison to historical cohorts. This decrease may be driven by improved prognosis of Candida albicans and Candida parapsilosis candidemia; whereas candidemia due to other Candida spp. exhibits a much higher attributable mortality.

A Pathology-based Case Series of Influenza- and COVID-19-associated Pulmonary Aspergillosis: The Proof Is in the Tissue.

Rationale: Invasive pulmonary aspergillosis has emerged as a frequent coinfection in severe coronavirus disease (COVID-19), similarly to influenza, yet the clinical invasiveness is more debated. Objectives: We investigated the invasive nature of pulmonary aspergillosis in histology specimens of influenza and COVID-19 ICU fatalities in a tertiary care center. Methods: In this monocentric, descriptive, retrospective case series, we included adult ICU patients with PCR-proven influenza/COVID-19 respiratory failure who underwent postmortem examination and/or tracheobronchial biopsy during ICU admission from September 2009 until June 2021. Diagnosis of probable/proven viral-associated pulmonary aspergillosis (VAPA) was made based on the Intensive Care Medicine influenza-associated pulmonary aspergillosis and the European Confederation of Medical Mycology (ECMM) and the International Society for Human and Animal Mycology (ISHAM) COVID-19-associated pulmonary aspergillosis consensus criteria. All respiratory tissues were independently reviewed by two experienced pathologists. Measurements and Main Results: In the 44 patients of the autopsy-verified cohort, 6 proven influenza-associated and 6 proven COVID-19-associated pulmonary aspergillosis diagnoses were identified. Fungal disease was identified as a missed diagnosis upon autopsy in 8% of proven cases (n = 1/12), yet it was most frequently found as confirmation of a probable antemortem diagnosis (n = 11/21, 52%) despite receiving antifungal treatment. Bronchoalveolar lavage galactomannan testing showed the highest sensitivity for VAPA diagnosis. Among both viral entities, an impeded fungal growth was the predominant histologic pattern of pulmonary aspergillosis. Fungal tracheobronchitis was histologically indistinguishable in influenza (n = 3) and COVID-19 (n = 3) cases, yet macroscopically more extensive at bronchoscopy in influenza setting. Conclusions: A proven invasive pulmonary aspergillosis diagnosis was found regularly and with a similar histological pattern in influenza and in COVID-19 ICU case fatalities. Our findings highlight an important need for VAPA awareness, with an emphasis on mycological bronchoscopic work-up.

In situ Reconstruction with Autologous Veins for the Treatment of Infected Abdominal Endografts: Single Center Experience.

Background: Vascular graft infection is a feared complication with high mortality and morbidity rates. Complete excision with in situ repair is recommended. We report our experience with patients suffering of abdominal aortic endograft infection undergoing excision and in situ reconstruction with autologous vein. Patients and Methods: All patients who underwent excision of an abdominal aortic endograft and in situ reconstruction with autologous superficial femoral veins between April 2005 and June 2021 were retrospectively reviewed. Primary outcome measures were mortality and reinfection. Secondary outcome measure was patient morbidity. Results: Fifteen patients (14 male; 93%) were included. Twenty percent of the index procedures (N = 3) were performed at our hospital, 80% (N = 12) were referred patients. Three aorto-enteric fistulae were seen. Staphylococci and enterococci were the most common pathogens (N = 8; 53%). In two out of six patients (33%) with an endograft with suprarenal fixation, the suprarenal fixation stent was left in situ. 30-day mortality rate was 6.6% (N = 1). Median follow-up time was 12 months (range 0-85). During follow-up, no reinfection was seen. Serious morbidity was witnessed in 2 patients (sepsis due to bowel leakage (N = 1), pneumonia (N = 2), hemodialysis (N = 1)). Eventration was the most common late morbidity observed (N = 5). Conclusions: Surgical treatment of vascular abdominal endograft infection by in situ reconstruction with autologous deep vein is a challenging procedure. If a multidisciplinary approach is applied and patients are centralized in experienced centers, acceptable mortality and morbidity rates can be achieved.

Vascular Graft Infections With Candida: A Factor for Increased Mortality in in-situ Reconstructions.

BACKGROUND: The empiric antibiotic regimen started after deep cultures and explantation of the graft mostly do not cover antifungals. We retrospectively studied the outcome of candida compared to non-candida VGI and assessed whether these results could justify the addition of antifungals to the empiric antibiotics in the early postoperative period. METHODS: All patients treated for infected aorto(ilio)femoral graft with excision and reconstruction at the vascular department of University Hospitals Leuven between January 2010 and 2017 (n = 56) were studied retrospectively. Patients were allocated to the candida group (n = 10) or non-candida group (n = 46) according to the presence of Candida in deep culture isolates. RESULTS: All-cause mortality was significantly higher in the candida group compared to the non-candida group. All-cause 30-day mortality was 40% and 13% for both groups respectively (P = 0.066). At 5 years this was 90% and 46% respectively (P = 0.014). In the candida group 6 patients (60%) had to be revised in the operating room due to bleeding, compared to 5 patients (11%) in the non-candida group (P = 0.002).  Two patients (20%) and 5 patients (11%) had to be readmitted to the ICU, respectively. CONCLUSION: Survival of candida related VGI is significantly worse, especially in the first 5 postoperative months. This could justify the addition of an antifungal to the early empiric postoperative antibiotic cocktail, especially in patients with an aorto-enteric fistula. A cost-benefit analysis could be useful to evaluate the yield.

Pre-clinical In Vitro Models of Vascular Graft Coating in the Prevention of Vascular Graft Infection: A Systematic Review.

OBJECTIVE: Vascular graft infection (VGI) is a feared complication. Prevention is of the utmost importance and vascular graft coatings (VGCs) could offer a potential to do this, with in vitro research a first crucial step. The aim of this study was to summarise key features of in vitro models investigating coating strategies to prevent VGI in order to provide guidance for the setup of future translational research. DATA SOURCES: A comprehensive search was performed in MEDLINE, Embase, and Web of Science. METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. For each database, a specific search strategy was developed. Quality was assessed with the Toxicological data Reliability Assessment Tool (ToxRTool). In vitro models using a VGC and inoculation of the graft with a pathogen were included. The type of graft, coating, and pathogen were summarised. The outcome assessment in each study was evaluated. RESULTS: In total, 4 667 studies were identified, of which 45 papers met the inclusion criteria. The majority used polyester grafts (68.2%). Thirty-one studies (68.9%) included antibiotics, and nine studies (20%) used a commercial silver graft in their protocol. New antibacterial strategies (e.g., proteolytic enzymes) were investigated. A variety of testing methods was found and focused mainly on bacterial adherence, coating adherence and dilution, biofilm formation, and cytotoxicity. Ninety-three per cent of the studies (n = 41) were considered unreliable. CONCLUSION: Polyester is the preferred type of graft to coat on. The majority of coating studies are based on antibiotics; however, new coating strategies (e.g., antibiofilm coating) are coming. Many in vitro setups are available. In vitro studies have great potential, they can limit the use, but cannot replace in vivo studies completely. This paper can be used as a guidance document for future in vitro research.

Pre-clinical in vivo Models of Vascular Graft Coating in the Prevention of Vascular Graft Infection: A Systematic Review.

OBJECTIVE: Vascular graft infection (VGI) remains an important complication with a high mortality and morbidity rate. Currently, studies focusing on the role of vascular graft coatings in the prevention of VGI are scarce. Therefore, the aims of this study were to survey and summarise key features of pre-clinical in vivo models that have been used to investigate coating strategies to prevent VGI and to set up an ideal model that can be used in future preclinical research. DATA SOURCES: A systematic review was conducted in accordance with the Preferred reporting items for Systematic Reviews and Meta-Analysis guidelines. A comprehensive search was performed in MEDLINE (PubMed), Embase, and Web of Science. REVIEW METHODS: For each database, a specific search strategy was developed. Quality was assessed with the Toxicological data Reliability Assessment Tool (ToxRTool). The type of animal model, graft, coating, and pathogen were summarised. The outcome assessment in each study was evaluated. RESULTS: In total, 4 667 studies were identified, of which 94 papers focusing on in vivo testing were included. Staphylococcus aureus was the organism most used (n = 65; 67.7%). Most of the graft types were polyester grafts. Rifampicin was the most frequently used antibiotic coating (n = 43, 48.3%). In the outcome assessment, most studies mentioned colony forming unit count (n = 88; 91.7%) and clinical outcome (n = 72; 75%). According to the ToxRTool, 21 (22.3%, n = 21/94) studies were considered to be not reliable. CONCLUSION: Currently published in vivo models are very miscellaneous. More attention should be paid to the methodology of these pre-clinical reports when transferring novel graft coatings into clinical practice. Variables used in pre-clinical reports (bacterial strain, duration of activity coating) do not correspond well to current clinical studies. Based on the results of this review, a proposal for a complete and comprehensive set up for pre-clinical invivo testing of anti-infectious properties of vascular graft coatings was defined.

The hepatitis C cascade of care in the Belgian HIV population: One step closer to elimination.

OBJECTIVES: The Belgian population of people living with HIV (PLHIV) has unrestricted access to direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection, since 2017. International literature claims that half of the patients remain untreated in high-income countries with unrestricted access to DAA. This study was initiated to provide an overview of the present situation in Belgium and recommendations for HCV care in PLHIV in other regions. METHODS: This was a retrospective, multicenter study of PLHIV in Belgium, from January 1, 2007 to December 31, 2018. The HCV cascade of care was examined. RESULTS: Out of 4607 unique PLHIV, 322 (7.0%) tested positive for HCV antibody and HCV RNA positivity was seen in 289 (6.3%). Of those with a proven HCV infection, 207/289 (71.6%) initiated treatment. Of the 171 (82.6%) persons with a sustained virologic response (SVR), 16 (9.4%) subjects were reinfected. CONCLUSIONS: We present a care cascade of 4607 PLHIV in Belgium. Treatment initiation and SVR rates were high compared to other regions. Implementation of a national HCV register to track progress and yearly screening, especially in PLHIV with high-risk behavior, remains crucial. Identifying reasons for not initiating treatment is necessary to achieve elimination of HCV in PLHIV by 2030.

Immunogenicity and Safety of the 9-Valent Human Papillomavirus Vaccine in Solid Organ Transplant Recipients and Adults Infected With Human Immunodeficiency Virus (HIV).

BACKGROUND: The burden of human papillomavirus (HPV) in human immunodeficiency virus (HIV)-infected persons and solid organ transplant (SOT) recipients is high. Clinical trials on HPV vaccines in persons living with HIV and particularly in SOT recipients have been sparse to date, included low numbers of participants, and none of them assessed the 9-valent HPV (9vHPV) vaccine. We investigated the immunogenicity with respect to HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 and the safety of the 9vHPV vaccine in persons living with HIV and recipients of a kidney, lung, or heart transplant. METHODS: This is a phase III investigator-initiated study in 100 persons living with HIV (age 18-45 years) and 171 SOT recipients (age 18-55 years). The 9vHPV vaccine was administered at day 1, month 2, and month 6. Primary outcome was seroconversion rates to the 9vHPV types at month 7. Secondary outcomes were geometric mean titers (GMTs) and frequency of adverse events (AEs). RESULTS: All HIV-infected participants seroconverted for all HPV types, but seroconversion ranged from 46% for HPV45 to 72% for HPV58 in SOT recipients. GMTs ranged from 180 to 2985 mMU/mL in HIV-positive participants and from 17 to 170 mMU/mL in SOT recipients, depending on the HPV type. Injection-site AEs occurred in 62% of participants but were mostly mild or moderate in intensity. None of the reported serious adverse events were deemed vaccine related. No patients died during the study. CONCLUSIONS: Immunogenicity of the 9vHPV vaccine is high in persons living with HIV but suboptimal in SOT recipients. The vaccine is safe and well tolerated in both groups.

COVID-19 and gastrointestinal endoscopy: What should be taken into account?

On March 11, 2020 the World Health Organization declared COVID-19 pandemic, leading to a subsequent impact on the entire world and health care system. Since the causing Severe Acute Respiratory Syndrome Coronavirus 2 houses in the aerodigestive tract, activities in the gastrointestinal outpatient clinic and endoscopy unit should be limited to emergencies only. Health care professionals are faced with the need to perform endoscopic or endoluminal emergency procedures in patients with a confirmed positive or unknown COVID-19 status. With this report, we aim to provide recommendations and practical relevant information for gastroenterologists based on the limited amount of available data and local experience, to guarantee a high-quality patient care and adequate infection prevention in the gastroenterology clinic.

Preoperative joint aspiration culture results and causative pathogens in total hip and knee prosthesis infections: mind the gap.

OBJECTIVES: In prosthetic joint infections (PJIs), there is no consensus about the utility of the preoperative joint aspiration culture to guide antimicrobial treatment. The main objective of this retrospective study was to investigate the value of these preoperative samples to narrow immediate postoperative empirical antimicrobial treatment in patients with a knee or hip PJI. METHODS: Adult patients admitted for an exchange procedure between June 2007 and July 2016 for whom a preoperative joint aspiration within 6 months prior to the procedure was available and with an antibiotic-free interval before sampling, were eligible. Per PJI, taking both preoperative joint aspiration and intraoperative deep samples into account, causative pathogen(s) were assessed by the current Infectious Diseases Society of America (IDSA) guidelines. Per PJI, agreement of preoperative joint aspiration cultures corresponding to the causative pathogen(s) was investigated both on species and on Gram/fungi level. RESULTS: From the 85 PJIs, on species level, the total agreement was found in 58 (68%) PJIs. On Gram/fungi level, when preoperative joint aspiration cultures yielded exclusively Gram-positive microorganisms (n = 61), a 100% predictive value for Gram positive causing pathogens was attained. Insufficient predictive value was observed in PJIs with preoperative joint aspiration yielding Gram-negative microorganisms (n = 4), a fungus (n = 1) or with sterile results (n = 19). CONCLUSION: In the immediate postoperative setting, the treating team might consider a broad spectrum empirical antibiotic regime, guided by the local epidemiology and susceptibility, which can be narrowed to Gram-positive coverage if preoperative joint aspiration cultures yield exclusively Gram-positive microorganisms.

Outcome and Treatment of Nocardiosis After Solid Organ Transplantation: New Insights From a European Study.

BACKGROUND: Solid organ transplant (SOT) recipients are at risk of nocardiosis, a rare opportunistic bacterial infection, but prognosis and outcome of these patients are poorly defined. Our objectives were to identify factors associated with 1-year mortality after nocardiosis and describe the outcome of patients receiving short-course antibiotics (≤120 days). METHODS: We analyzed data from a multicenter European case-control study that included 117 SOT recipients with nocardiosis diagnosed between 2000 and 2014. Factors associated with 1-year all-cause mortality were identified using multivariable conditional logistic regression. RESULTS: One-year mortality was 10-fold higher in patients with nocardiosis (16.2%, 19/117) than in control transplant recipients (1.3%, 3/233, P < .001). A history of tumor (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.1-1.8), invasive fungal infection (OR, 1.3; 95% CI, 1.1-1.5), and donor age (OR, 1.0046; 95% CI, 1.0007-1.0083) were independently associated with 1-year mortality. Acute rejection in the year before nocardiosis was associated with improved survival (OR, 0.85; 95% CI, 0.73-0.98). Seventeen patients received short-course antibiotics (median duration 56 [24-120] days) with a 1-year success rate (cured and surviving) of 88% and a 5.9% risk of relapse (median follow-up 49 [6-136] months). CONCLUSIONS: One-year mortality was 10-fold higher in SOT patients with nocardiosis than in those without. Four factors, largely reflecting general medical condition rather than severity and/or management of nocardiosis, were independently associated with 1-year mortality. Patients who received short-course antibiotic treatment had good outcomes, suggesting that this may be a strategy for further study.

Clinical presentation, causes and outcome of febrile episodes in a prospective cohort of HIV-infected patients.

BACKGROUND: Fever was frequently caused by opportunistic conditions in HIV-patients in the early years of the epidemic. Little is known about diagnostic spectrum and outcome of febrile episodes in patients with good access to antiretroviral therapy. METHODS: We prospectively studied clinical presentation, diagnosis and outcome of febrile episodes in a contemporary cohort of HIV-patients with good access to antiretroviral therapy. Fever was defined as temperature 38.3 °C or higher, measured by a health care provider. RESULTS: We found 220 febrile episodes in 146 patients. In 25.9% of episodes the patient had a CD4 less than 200/mm³ and in 78.6% the patient was on antiretroviral therapy. There were multiple episodes in 44 patients. A diagnosis was established in 91.8%. Infection accounted for 82.3%, mainly respiratory tract infections, viral syndromes and abdominal infections. Malignancy, drug reactions and inflammatory conditions accounted together for less than 12% of episodes. Fifteen percent were attributed to opportunistic conditions. Episodes in patients with CD4 less than 200 were less likely to be caused by infection, but more likely to be caused by malignancy, drug reactions and opportunistic conditions. In 6.4% the patient died within six months after the onset of fever. Risk factors for death at six months in multivariable analysis were higher age and lower CD4. CONCLUSIONS: HIV-patients with access to antiretroviral therapy present with fever mostly due to conditions common in the general population. HIV-patients with low CD4 remain at risk for fever due to opportunistic conditions and death.

Augmented renal clearance in non-critically ill abdominal and trauma surgery patients is an underestimated phenomenon: A point prevalence study.

BACKGROUND: Augmented renal clearance refers to increased renal elimination of circulating solutes as compared with normal baseline and could lead to underexposure of frequently used renally eliminated antimicrobials. The primary objective was to assess the prevalence of augmented renal clearance in an adult non-critically ill surgery population. Besides, predictors for augmented renal clearance were investigated. A prospective observational single-center point prevalence study was conducted. METHODS: The measured creatinine clearance based on an 8-hour urinary collection was used as primary method for determining kidney function. Augmented renal clearance was defined as measured creatinine clearance of 130 mL/min per 1.73m² or greater. A Poisson regression model was applied to identify predictors for augmented renal clearance. RESULTS: Augmented renal clearance prevalence was 30% and 35% in 103 abdominal and 129 trauma surgery patients, respectively. Younger age (abdominal cohort: relative risk, 0.963 (95% CI, 0.949-0.978); trauma cohort: relative risk, 0.971 [95% CI, 0.960-0.983]) and also for trauma surgery patients, male sex (relative risk, 1.808 [95% CI, 1.026-3.185]) were found to be independent predictors for augmented renal clearance. CONCLUSIONS: Augmented renal clearance is an underestimated phenomenon in adult non-critically ill surgery patients. Especially younger patients, and, in the subset of trauma surgery, males are prone to exhibit augmented renal clearance. Since augmented renal clearance is a risk factor for lower antimicrobial exposure, the impact of augmented renal clearance in relation to antimicrobial underexposure should be investigated in this population. LEVEL OF EVIDENCE: Prognostic/epidemiological study, level III.

Cytomegalovirus serostatus and outcome in nonimmunocompromised critically ill patients.

OBJECTIVE: The impact of cytomegalovirus reactivation during critical illness remains unclear and studies investigating prophylaxis in cytomegalovirus seropositive patients are being considered. This study investigates the association between cytomegalovirus seropositivity and outcome in a large population of nonimmunocompromised critically ill patients. DESIGN: Cytomegalovirus serostatus was determined on prospectively collected serum samples. The primary end point was intensive care unit mortality. The secondary end points were in-hospital mortality, time to alive discharge from intensive care unit and hospital, time to alive weaning from mechanical ventilation, and need for renal replacement therapy. SETTING: This retrospective study was performed in a 17-bed medical and 56-bed surgical intensive care unit in a 1,900-bed referral hospital. PATIENTS: We analyzed serum of 1,504 nonimmunocompromised critically ill patients with an intensive care unit length of stay of 3 days or more. Patients with hematologic malignancy, transplantation, immunosuppressive therapy (calcineurin inhibitors, antitumor necrosis factor-α drugs, antilymphocyte antibodies, or chemotherapeutic agents), or a do-not-resuscitate order were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sixty-four percent of the studied patients were cytomegalovirus seropositive. Multivariable analysis revealed no associated risk for intensive care unit or hospital mortality, or for time to alive discharge from intensive care unit or hospital. The risk for alive weaning from mechanical ventilation and the need for renal replacement therapy were also comparable in seropositive and seronegative groups. CONCLUSION: : No association was found between the cytomegalovirus serostatus and the studied major clinical outcomes. Based on these results, the design of an intervention study assessing the impact of cytomegalovirus prophylaxis in all cytomegalovirus seropositive critically ill patients appears premature.

Serum (1-3)-beta-D-glucan as a tool for diagnosis of Pneumocystis jirovecii pneumonia in patients with human immunodeficiency virus infection or hematological malignancy.

(1-3)-Beta-D-Glucan (BG) reactivity was tested in serum samples from 28 patients with human immunodeficiency virus infection or a hematological malignancy and Pneumocystis jirovecii pneumonia (PCP) and 28 control patients. The sensitivity and specificity of BG detection with the Fungitell assay for PCP were 100 and 96.4%, respectively, using a cutoff value of 100 pg/ml. Serum BG testing looks promising for the noninvasive diagnosis of PCP. Our data suggest that a higher cutoff value for the diagnosis of PCP than for the diagnosis of invasive aspergillosis or candidiasis could be used safely and will improve the specificity of the test.

Galactomannan in bronchoalveolar lavage fluid: a tool for diagnosing aspergillosis in intensive care unit patients.

RATIONALE: Invasive aspergillosis (IA) is an important cause of mortality in patients with hematologic malignancies. However, IA appears to be gaining a foothold in the intensive care unit (ICU) in patients without classical risk factors. A recent study described 89 cases of IA in patients in a medical ICU without leukemia or cancer. The diagnosis of IA remains difficult and is often established too late. Galactomannan (GM) is an exo-antigen released from Aspergillus hyphae while they invade host tissue. OBJECTIVES: This prospective single-center study was conducted to investigate the role of GM in bronchoalveolar lavage (BAL) fluid as a tool for early diagnosis of IA in the ICU. METHODS: All patients with risk factors identified in our earlier study were evaluated. BAL for culture and GM detection, serum GM levels, and computed tomography scan were obtained for all included patients with signs of pneumonia. Patients were classified as having proven, probable, or possible IA. MEASUREMENTS AND MAIN RESULTS: A total of 110 patients out of 1,109 admissions were eligible. There were 26 proven IA cases. Using a cutoff index of 0.5, the sensitivity and specificity of GM detection in BAL fluid was 88 and 87%, respectively. The sensitivity of serum GM was only 42%. In 11 of 26 proven cases, BAL culture and serum GM remained negative, whereas GM in BAL was positive. CONCLUSIONS: IA is common in immunocompromised, critically ill patients. GM detection in BAL fluid seems to be useful in establishing or excluding the diagnosis of IA in the ICU.

Rapidly fatal Acanthamoeba encephalitis and treatment of cryoglobulinemia.

We describe a 66-year-old woman with therapy-refractory cryoglobulinemia treated with rituximab, plasmapheresis, and steroids; a case of fatal meningoencephalitis caused by Acanthamoeba spp. then developed. Such infections are rare and show an unusually rapid course (possibly related to rituximab).

Invasive aspergillosis in the intensive care unit.

Data regarding the incidence of invasive aspergillosis (IA) in the intensive care unit (ICU) are scarce, and the incidence varies. An incidence of 5.8% in a medical ICU has been reported. The majority of patients did not have a hematological malignancy, and conditions such as chronic obstructive pulmonary disease and liver failure became recognized as risk factors. Diagnosis of IA remains difficult. Mechanical ventilation makes it difficult to interpret clinical signs, and radiological diagnoses are clouded by underlying lung pathologies. The significance of a positive respiratory culture result is greatly uncertain, because cultures of respiratory specimens have low sensitivity (50%) and specificity (20%-70%, depending on whether the patient is immunocompromised). The use of serologic markers has never been validated in an ICU population. Limited experience with the detection of galactomannan in bronchoalveolar lavage fluid specimens has yielded promising results. Because of a delay in the diagnosis of IA, the mortality rate exceeds 50%. Recently, our therapeutic armamentarium against IA has improved. Data concerning the safety and efficacy of new antifungal agents in the ICU setting, however, are lacking.