Weaning from Kidney Replacement Therapy in the Critically Ill Patient with Acute Kidney Injury.

Around 10% of critically ill patients suffer acute kidney injury (AKI) requiring kidney replacement therapy (KRT), with a mortality rate approaching 50%. Although most survivors achieve sufficient renal recovery to be weaned from KRT, there are no recognized guidelines on the optimal period for weaning from KRT. A systematic review was conducted using a peer-reviewed strategy, combining themes of KRT (intermittent hemodialysis, CKRT: continuous veno-venous hemo/dialysis/filtration/diafiltration, sustained low-efficiency dialysis/filtration), factors predictive of successful weaning (defined as a prolonged period without new KRT) and patient outcomes. Our research resulted in studies, all observational, describing clinical and biological parameters predictive of successful weaning from KRT. Urine output prior to KRT cessation is the most studied variable and the most widely used in practice. Other predictive factors, such as urinary urea and creatinine and new urinary and serum renal biomarkers, including cystatin C and neutrophil gelatinase-associated lipocalin (NGAL), were also analyzed in the light of recent studies. This review presents the rationale for early weaning from KRT, the parameters that can guide it, and its practical modalities. Once the patient's clinical condition has stabilized and volume status optimized, a diuresis greater than 500 mL/day should prompt the intensivist to consider weaning. Urinary parameters could be useful in predicting weaning success but have yet to be validated.

Acute kidney injury in critical COVID-19 patients: usefulness of urinary biomarkers and kidney proximal tubulopathy.

Tubular injury is the main cause of acute kidney injury (AKI) in critically ill COVID-19 patients. Proximal tubular dysfunction (PTD) and changes in urinary biomarkers, such as NGAL, TIMP-2, and IGFBP7 product ([TIMP-2]•[IGFBP7]), could precede AKI. We conducted a prospective cohort study from 2020/03/09 to 2020/05/03, which consecutively included all COVID-19 patients who had at least one urinalysis, to assess the incidence of PTD and AKI, and the effectiveness of PTD, NGAL, and [TIMP-2]•[IGFBP7] in AKI and persistent AKI prediction using the area under the receiver operating characteristic curves (AUCs), Kaplan-Meier methodology (log-rank tests), and Cox models. Among the 60 patients admitted to the ICU with proven COVID-19 (median age: 63-year-old (interquartile range: IQR, 55-74), 45 males (75%), median simplified acute physiology score (SAPS) II: 34 (IQR, 22-47) and median BMI: 25.7 kg/m2 (IQR, 23.3-30.8)) analyzed, PTD was diagnosed in 29 patients (48%), AKI in 33 (55%) and persistent AKI in 20 (33%). Urinary NGAL had the highest AUC for AKI prediction: 0.635 (95%CI: 0.491-0.779) and persistent AKI prediction: 0.681 (95%CI: 0.535-0.826), as compared to PTD and [TIMP-2]•[IGFBP7] (AUCs <0.6). AKI was independently associated with higher SAPSII (HR = 1.04, 95%CI: 1.01-1.06, p = 0.005) and BMI (HR = 1.07, 95%CI: 1.00-1.14, p = 0.04) and persistent AKI with higher SAPSII (HR = 1.03, 95%CI: 1.00-1.06, p = 0.048) and nephrotoxic drug use (HR = 3.88, 95%CI: 1.20-12.5, p = 0.02). In conclusion, in critically ill COVID-19 patients, the incidence of PTD and AKI was relatively high. NGAL was the best urinary biomarker for predicting AKI, but only clinical severity was independently associated with its occurrence.

In Vivo-Acquired Resistance to Daptomycin during Methicillin-Resistant Staphylococcus aureus Bacteremia.

Daptomycin (DAP) represents an interesting alternative to treat methicillin-resistant Staphylococcus aureus (MRSA) infections. Different mechanisms of DAP resistance have been described; however, in vivo-acquired resistance is uncharacterized. This study described the phenotypic and genotypic evolution of MRSA strains that became resistant to DAP in two unrelated patients with bacteremia under DAP treatment, in two hospitals in the South of France. DAP MICs were determined using broth microdilution method on the pairs of isogenic (DAP-S/DAP-R) S. aureus isolated from bloodstream cultures. Whole genome sequencing was carried out using Illumina MiSeq Sequencing system. The two cases revealed DAP-R acquisition by MRSA strains within three weeks in patients treated by DAP. The isolates belonged to the widespread ST5 (patient A) and ST8 (patient B) lineages and were of spa-type t777 and t622, respectively. SNP analysis comparing each DAP-S/DAP-R pair confirmed that the isolates were isogenic. The causative mutations were identified in MprF (Multiple peptide resistance Factor) protein: L826F (Patient A) and S295L (Patient B), and in Cls protein: R228H (Patient B). These proteins encoded both proteins of the lipid biosynthetic enzymes. The resistance to DAP is particularly poorly described whereas DAP is highly prescribed to treat MRSA. Our study highlights the non-systematic cross-resistance between DAP and glycopeptides and the importance of monitoring DAP MIC in persistent MRSA bacteremia.

Usefulness of dynamic regression time series models for studying the relationship between antimicrobial consumption and bacterial antimicrobial resistance in hospitals: a systematic review.

BACKGROUNG: Antimicrobial resistance (AMR) is on the rise worldwide. Tools such as dynamic regression (DR) models can correlate antimicrobial consumption (AMC) with AMR and predict future trends to help implement antimicrobial stewardship programs (ASPs). MAIN BODY: We carried out a systematic review of the literature up to 2023/05/31, searching in PubMed, ScienceDirect and Web of Science. We screened 641 articles and finally included 28 studies using a DR model to study the correlation between AMC and AMR at a hospital scale, published in English or French. Country, bacterial species, type of sampling, antimicrobials, study duration and correlations between AMC and AMR were collected. The use of ß-lactams was correlated with cephalosporin resistance, especially in Pseudomonas aeruginosa and Enterobacterales. Carbapenem consumption was correlated with carbapenem resistance, particularly in Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii. Fluoroquinolone use was correlated with fluoroquinolone resistance in Gram-negative bacilli and methicillin resistance in Staphylococcus aureus. Multivariate DR models highlited that AMC explained from 19 to 96% of AMR variation, with a lag time between AMC and AMR variation of 2 to 4 months. Few studies have investigated the predictive capacity of DR models, which appear to be limited. CONCLUSION: Despite their statistical robustness, DR models are not widely used. They confirmed the important role of fluoroquinolones, cephalosporins and carbapenems in the emergence of AMR. However, further studies are needed to assess their predictive capacity and usefulness for ASPs.

Clinical Features and Outcomes of Enterococcal Bone and Joint Infections and Factors Associated with Treatment Failure over a 13-Year Period in a French Teaching Hospital.

Enterococcal bone and joint infections (BJIs) are reported to have poor outcomes, but there are conflicting results. This study aimed to describe the clinical characteristics and outcomes of patients with enterococcal BJI and to assess the factors associated with treatment failure. We conducted a retrospective cohort study at Nimes University Hospital from January 2007 to December 2020. The factors associated with treatment failure were assessed using a Cox model. We included 90 consecutive adult patients, 11 with native BJIs, 40 with prosthetic joint infections and 39 with orthopedic implant-associated infections. Two-thirds of patients had local signs of infection, but few (9%) had fever. Most BJIs were caused by Enterococcus faecalis (n = 82, 91%) and were polymicrobial (n = 75, 83%). The treatment failure rate was 39%, and treatment failure was associated with coinfection with Staphylococcus epidermidis (adjusted hazard ratio = 3.04, confidence interval at 95% [1.31-7.07], p = 0.01) and with the presence of local signs of inflammation at the time of diagnosis (aHR = 2.39, CI 95% [1.22-4.69], p = 0.01). Our results confirm the poor prognosis of enterococcal BJIs, prompting clinicians to carefully monitor for local signs of infection and to optimize the medical-surgical management in case of coinfections, especially with S. epidermidis.

Continuous infusion of meropenem-vaborbactam for a KPC-3-producing Klebsiella pneumoniae bloodstream infection in a critically ill patient with augmented renal clearance.

PURPOSE: To demonstrate the feasibility of continuous infusion of meropenem-vaborbactam to optimize the treatment of carbapenem-resistant Enterobacterales. METHODS: Report of a case of a Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae bloodstream infection comfirmed by whole genome sequencing and therapeutic drug monitoring (TDM) of meropenem. RESULTS: A patient with augmented renal clearance (ARC) went into septic shock caused by an ST11 KPC-3-producing K. pneumoniae bloodstream infection that was successfully treated with a continuous infusion of meropenem-vaborbactam at a dosage of 1 g/1 g q4h as a 4-h infusion. TDM confirmed sustained concentrations of meropenem ranging from 8 to 16 mg/L throughout the dosing interval. CONCLUSION: Continuous infusion of meropenem-vaborbactam was feasible. It could be appropriate for optimizing the management of critically ill patients with ARC, as it resulted in antibiotic concentrations above the minimum inhibitory concentration for susceptible carbapenem-resistant Enterobacterales (up to 8 mg/L) throughout the dosing interval.

Peripherally Inserted Central Venous Catheter (PICC) Related Bloodstream Infection in Cancer Patients Treated with Chemotherapy Compared with Noncancer Patients: A Propensity-Score-Matched Analysis.

The use of peripherally inserted central catheters (PICCs) has increased in cancer patients. This study aimed to compare the incidence of PICC-related bloodstream infections (PICCR-BSIs) in cancer patients treated with chemotherapy and in noncancer patients. We performed a secondary analysis from a retrospective, single-center, observational cohort. The PICCR-BSI incidence rates in cancer and noncancer patients were compared after 1:1 propensity-score matching. Then, the factors associated with PICCR-BSI were assessed in a Cox model. Among the 721 PICCs (627 patients) included in the analysis, 240 were placed in cancer patients for chemotherapy and 481 in noncancer patients. After propensity-score matching, the PICCR-BSI incidence rate was 2.6 per 1000 catheter days in cancer patients and 1.0 per 1000 catheter days in noncancer patients (p < 0.05). However, after adjusting for variables resulting in an imbalance between groups after propensity-score matching, only the number of PICC lumens was independently associated with PICCR-BSI (adjusted hazard ratio 1.81, 95% confidence interval: 1.01-3.22; p = 0.04). In conclusion, the incidence rate of PICCR-BSI is higher in cancer patients treated with chemotherapy than in noncancer patients, but our results also highlight the importance of limiting the number of PICC lumens in such patients.

Factors associated with meropenem pharmacokinetic/pharmacodynamic target attainment in septic critically ill patients treated with extended intermittent infusion or continuous infusion.

OBJECTIVES: The use of extended intermittent infusion (EII) or continuous infusion (CI) of meropenem is recommended in intensive care unit (ICU) patients, but few data comparing these two options are available. This retrospective cohort study was conducted between 1 January 2019 and 31 March 2020 in a teaching hospital ICU. It aimed to determine the meropenem plasma concentrations achieved with CI and EII. METHODS: The study included septic patients treated with meropenem who had one or more meropenem plasma trough (Cmin) or steady-state concentration (Css) measurement(s), as appropriate. It then assessed the factors independently associated with attainment of the target concentration (Cmin or Css ≥ 10 mg/L) and the toxicity threshold (Cmin or Css ≥ 50 mg/L) using logistic regression models. RESULTS: Among the 70 patients analysed, the characteristics of those treated with EII (n = 33) and CI (n = 37) were balanced with the exception of estimates glomerular filtration rate (eGFR): median 30 mL/min/m2 (IQR 30, 84) vs. 79 mL/min/m2 (IQR 30, 124). Of the patients treated with EII, 21 (64%) achieved the target concentration, whereas 31 (97%) of those treated with CI achieved it (P < 0.001). Factors associated with target attainment were: CI (OR 16.28, 95% CI 2.05-407.5), daily dose ≥ 40 mg/kg (OR 12.23, 95% CI 1.76-197.0; P = 0.03) and eGFR (OR 0.98, 95% CI 0.97-0.99; P = 0.02). Attainment of toxicity threshold was associated with daily dose > 70 mg/kg (OR 35.5, 95% CI 5.61-410.3; P < 0.001). CONCLUSION: The results suggest the use of meropenem CI at 40-70 mg/kg/day, particularly in septic ICU patients with normal or augmented renal clearance.

Prognosis of immune checkpoint inhibitors-induced myocarditis: a case series.

BACKGROUND: Immune checkpoint inhibitors (ICI) have transformed cancer treatment over the last decade. Alongside this therapeutic improvement, a new variety of side effects has emerged, called immune-related adverse events (irAEs), potentially affecting any organ. Among these irAEs, myocarditis is rare but life-threatening. METHODS: We conducted a multicenter cross-sectional retrospective study with the aim of better characterizing ICI-related myocarditis. Myocarditis diagnosis was based on the recent consensus statement of the International Cardio-Oncology Society. RESULTS: Twenty-nine patients were identified, from six different referral centers. Most patients (55%) were treated using anti-programmed-death 1, rather than ICI combination (35%) or anti-programmed-death-ligand 1 (10%). Transthoracic echocardiography was abnormal in 52% of them, and cardiac magnetic resonance showed abnormal features in 14/24 patients (58%). Eleven patients (38%) were classified as severe. Compared with other patients, they had more frequently pre-existing systemic autoimmune disease (45% vs 6%, p=0.018), higher troponin level on admission (42-fold the upper limit vs 3.55-fold, p=0.001), and exhibited anti-acetylcholine receptor autoantibodies (p=0.001). Seven patients (24%) had myocarditis-related death, and eight more patients died from cancer progression during follow-up. Twenty-eight patients received glucocorticoids, 10 underwent plasma exchanges, 8 received intravenous immunoglobulins, and 5 other immunosuppressants. ICI rechallenge was performed in six patients, with only one myocarditis relapse. DISCUSSION: The management of ICI-related myocarditis may be challenging and requires a multidisciplinary approach. Prognostic features are herein described and may help to allow ICI rechallenge for some patients with smoldering presentation, after an accurate evaluation of benefit-risk balance.

Effect of antimicrobial consumption on Escherichia coli resistance: assessment and forecasting using Dynamic Regression models in a French university hospital (2014-2019).

INTRODUCTION: The aim of this study was to determine the correlation between antimicrobial consumption (AMC) and antimicrobial resistance (AMR) in Escherichia coli at a hospital level, and assess the capacity of dynamic regression (DR) models to predict AMR for their use in deployment of antimicrobial stewardship programs (ASPs). METHODS: A retrospective epidemiological study was conducted in a French tertiary hospital between 2014 and 2019. DR models were used to assess the correlation between AMC and AMR from 2014 to 2018. The predictive abilities of the models were estimated by comparing the predicted data with those observed in 2019. RESULTS: Rates of fluoroquinolone and cephalosporin resistance decreased. AMC increased overall but decreased for fluoroquinolone. DR models highlighted that the decrease in use of fluoroquinolone and the increase in use of anti-pseudomonal activity penicillin with beta-lactamase inhibitor (AAPBI) explained 54% of the decrease in fluoroquinolone resistance and 15% of the decrease in cephalosporin resistance. In addition, penicillin/beta-lactamase inhibitor (PBI) consumption explained 53% of PBI resistance, and beta-lactam use explained 36% of penicillin resistance, with both remaining stable over time. DR models had predictive capabilities with margins of error from 8% to 34%. CONCLUSION: Over a six-year period in a French tertiary hospital, decreasing rates of resistance to fluoroquinolones and cephalosporins were correlated with decreasing use of fluoroquinolone and increasing use of AAPBI, whereas rates of resistance to penicillin remained high and stable. The results indicate that DR models should be used with caution for AMR forecasting and ASP implementation.

Epidemiology, clinical presentation, and outcomes of 620 patients with eosinophilia in the intensive care unit.

PURPOSE: Although eosinophil-induced manifestations can be life-threatening, studies focusing on the epidemiology and clinical manifestations of eosinophilia in the intensive care unit (ICU) are lacking. METHODS: A retrospective, national, multicenter (14 centers) cohort study over 6 years of adult patients who presented with eosinophilia ≥ 1 × 109/L on two blood samples performed from the day before admission to the last day of an ICU stay. RESULTS: 620 patients (0.9% of all ICU hospitalizations) were included: 40% with early eosinophilia (within the first 24 h of ICU admission, ICU-Eo1 group) and 56% with delayed (> 24 h after ICU admission, ICU-Eo2 group) eosinophilia. In ICU-Eo1, eosinophilia was mostly due to respiratory (14.9%) and hematological (25.8%) conditions, frequently symptomatic (58.1%, mainly respiratory and cardiovascular manifestations) requiring systemic corticosteroids in 32.2% of cases. In ICU-Eo2, eosinophil-related organ involvement was rare (25%), and eosinophilia was mostly drug-induced (46.8%). Survival rates at day 60 (D60) after ICU admission were 21.4% and 17.2% (p = 0.219) in ICU-Eo1 and ICU-Eo2 patients, respectively. For ICU-Eo1 patients, in multivariate analysis, risk factors for death at D60 were current immunosuppressant therapy at ICU admission, eosinophilia of onco-hematological origin and the use of vasopressors at ICU admission, whereas older age and the use of vasopressors or mechanical ventilation at the onset of eosinophilia were associated with a poorer prognosis for ICU-Eo2 patients. CONCLUSION: Eosinophilia ≥ 1 × 109/L is not uncommon in the ICU. According to the timing of eosinophilia, two subsets of patients requiring different etiological workups and management can be distinguished.

Effect of Tocilizumab on Mortality in Patients with SARS-CoV-2 Pneumonia Caused by Delta or Omicron Variants: A Propensity-Matched Analysis in Nimes University Hospital, France.

We aimed to assess the factors associated with mortality in patients treated with tocilizumab for a SARS-CoV-2 pneumonia due to the delta or omicron variants of concern (VOC) and detect an effect of tocilizumab on mortality. We conducted a prospective cohort study in a tertiary hospital from 1 August 2021 to 31 March 2022 including patients with severe COVID-19, treated with tocilizumab. Factors associated with mortality were assessed in a Cox model; then, the 60-day mortality rates of COVID-19 patients treated with standard of care (SoC) +/- tocilizumab were compared after 1:1 propensity score matching. The mortality rate was 22% (N = 26/118) and was similar between delta and omicron cases (p = 0.6). The factors independently associated with mortality were age (HR 1.06; 95% CI (1.02-1.11), p = 0.002), Charlson index (HR 1.33; 95% CI (1.11-1.6), p = 0.002), WHO-CPS (HR 2.56; 95% CI (1.07-6.22) p = 0.03), and tocilizumab infusion within the first 48 h following hospital admission (HR 0.37, 95% CI (0.14-0.97), p = 0.04). No significant differences in mortality between the tocilizumab plus SoC and SoC alone groups (p = 0.5) were highlighted. However, the patients treated with tocilizumab within the 48 h following hospital admission had better survival (p = 0.04). In conclusion, our results suggested a protective effect on mortality of the early administration of tocilizumab in patients with severe COVID-19 regardless of the VOC involved.

Analytical Performances of the Novel i-STAT Alinity Point-of-Care Analyzer.

Many Point-of-Care devices have been released over the past decade. However, data regarding their analytical performances in real-world situations remains scarce. Herein, we aimed to assess the analytical performances of the i-STAT Alinity system. We conducted an analytical performances study with the i-STAT Alinity device using cartridges CG4+ (pH, Pco2, Po2, lactate, bicarbonate and base excess); CHEM8+ (Na, K, Cl, ionized Ca, urea, creatinine, glucose, hematocrit and hemoglobin) and PT/INR (prothrombin time and international normalized ratio). We assessed the imprecision and compared the results to those obtained on existing instruments in the central laboratory. We found that the within-lab coefficients of variation (CV) were very low (<2%) or low (2−5%), except for creatinine and PT (CV = 5.2% and CV = 6.3%, respectively). For almost all the parameters, the results were strongly (R2 = 90−95%) or very strongly (R2 > 95%) correlated with those of the existing laboratory instruments, and the biases were very low (<2%) or low (2−5%). However, correlations of the PT and INR measurements with existing instruments were lower (R2 = 86.0% and 89.7%), and biases in the Po2 (7.9%), creatinine (5.4%) and PT (−6.6%) measurements were higher. The i-STAT Alinity appeared as a convenient device for measurements of numerous parameters. However, clinicians should interpret Po2, creatinine and PT results with caution.

Clinical factors associated with peripherally inserted central catheters (PICC) related bloodstream infections: a single centre retrospective cohort.

BACKGROUND: Despite their spread in daily practice, few data is available on clinical factors associated with peripherally inserted central catheter (PICC)-related bloodstream infections (PR-BSI). We aimed to assess the PR-BSI incidence, microbiology, and factors associated with PR-BSI with a focus on clinical symptoms. METHODS: We conducted a retrospective cohort study in a French university hospital. We screened all PICC insertions performed from April 1st, 2018, to April 1st, 2019, and included PICC insertions in adult patients. We assessed the PR-BSI incidence, the factors associated with PR-BSI using a Cox model, and negative and positive predictive values (NPVs and PPVs) of each clinical sign for PR-BSI. RESULTS: Of the 901 PICCs inserted in 783 patients (38,320 catheters days), 214 PICCs (24%) presented with a complication. The most prevalent complication was PR-BSI (1.9 per 1000 catheter days; 8.1% of inserted PICCs ). Enterobacterales (N = 27, 37%) and coagulase negative Staphylococci (N = 24, 33%), were the main microorganisms responsible for PR-BSI. Factors independently associated with occurrence of PR-BSI were fever (hazard ratio 13.21, 95% confidence interval 6.00-29.11, p < 0.001) and chills (HR 3.66, 95%CI 1.92-6.99, p < 0.001). All clinical signs and a duration of PICC maintenance ≥ 28 days, had a low PPVs (≤ 67.1%) but high NPVs (≥ 92.5%) for PR-BSI. CONCLUSIONS: Monitoring of clinical signs, especially fever and chills, with caution and limitation of device maintenance duration, could improve PICC management.

Sodium flux during hemodialysis and hemodiafiltration treatment of acute kidney injury: Effects of dialysate and infusate sodium concentration at 140 and 145 mmol/L.

BACKGROUND: A higher sodium (Na) dialysate concentration is recommended during renal replacement therapy (RRT) of acute kidney injury (AKI) to improve intradialytic hemodynamic tolerance, but it may lead to Na loading to the patient. We aimed to evaluate Na flux according to Na dialysate and infusate concentrations at 140 and 145 mmol/L during hemodialysis (HD) and hemodiafiltration (HDF). METHODS: Fourteen AKI patients that underwent consecutive HD or HDF sessions with Na dialysate/infusate at 140 and 145 mmol/L were included. Per-dialytic flux of Na was estimated using mean sodium logarithmic concentration including diffusive and convective influx. We compared the flux of sodium between HD140 and 145, and between HDF140 and 145. RESULTS: Nine HD140, ten HDF140, nine HD145, and 11 HDF145 sessions were analyzed. A Na gradient from the dialysate/replacement fluid to the patient was observed with dialysate/infusate Na at 145 mmol/L in both HD and HDF (p = 0.01). The comparison of HD145 to HD140 showed that higher Na dialysate induced a diffusive Na gradient to the patient (163 mmol vs. -25 mmol, p = 0.004) and that of HDF145 to -140 (211 vs. 36 mmol, p = 0.03) as well. Intradialytic hemodynamic tolerance was similar across all RRT sessions. CONCLUSIONS: During both HD and HDF, a substantial Na loading occurred with a Na dialysate and infusate at 145 mmol/L. This Na loading is smaller in HDF with Na dialysate and infusate concentration at 140 mmol/L and inversed with HD140. Clinical and intradialytic hemodynamic tolerance was fair regardless of Na dialysate and infusate.

Adverse Events and Infectious Complications in the Critically Ill Treated by Plasma Exchange: A Five-Year Multicenter Cohort Study.

OBJECTIVES: The aim of this study was to determine, in critically ill patients treated with therapeutic plasma exchange (TPE), the incidence of adverse events as well as the incidence of secondary infections and its predictive factors. DESIGN: A multicenter retrospective cohort study of an intensive care population treated with TPE to collect adverse events and infectious complications. The characteristics of patients who developed an infection after plasma exchange were compared with those of patients who did not. SETTING: Four ICUs of French university hospitals. PATIENTS: All adults admitted between January 1, 2015, and December 31, 2019, who received at least one plasma exchange session were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 711 TPE sessions were performed on 124 patients. The most frequent TPE indications were thrombotic microangiopathies (n = 32, 26%), myasthenia gravis (n = 25, 20%), and acute polyradiculoneuropathy (n = 12, 10%). Among the 124 patients, 22 (21%) developed arterial hypotension, 12 (12%) fever, and 9 (9%) electrolyte disturbance during TPE. Moreover, 60 (48%) presented at least one infectious complication: ventilator-associated pneumonia 42, pneumonia 13, bacteremia 18 (of which 6 catheter-related infections) viral reactivation 14. Independent risk factors for ICU-acquired infection were the ICU length of stay (24 vs. 7 d; hazard ratio [HR]: 1.09 [1.04-1.15], p < 0.001) and invasive mechanical ventilation (92% vs. 35%; HR: 16.2 [5.0-53.0], p < 0.001). CONCLUSIONS: In critically ill patients treated with TPE, adverse events occurring during the procedure remain moderately frequent and are mostly not life-threatening. Infectious complications, mainly ventilation-associated pneumonia, are frequent in this population. The need of mechanical ventilation and longer ICU stay is associated with an increased risk of infection.