Clinical description and outcome of overall varicella-zoster virus-related organ dysfunctions admitted in intensive care units: the VAZOREA cohort study.

BACKGROUND: Due to aging population and increasing part of immunocompromised patients, a raise in life-threatening organ damage related to VZV can be expected. Two retrospective studies were already conducted on VZV in ICU but focused on specific organ injury. Patients with high-risk of VZV disease still must be identified. The objective of this study was to report the clinical features and outcome of all life-threatening VZV manifestations requiring intensive care unit (ICU) admission. This retrospective cohort study was conducted in 26 French ICUs and included all adult patients with any life-threatening VZV-related event requiring ICU admission or occurring in ICU between 2010 and 2019. RESULTS: One-hundred nineteen patients were included with a median SOFA score of 6. One hundred eight patients (90.8%) were admitted in ICU for VZV disease, leaving 11 (9.2%) with VZV disease occurring in ICU. Sixty-one patients (51.3%) were immunocompromised. Encephalitis was the most prominent organ involvement (55.5%), followed by pneumonia (44.5%) and hepatitis (9.2%). Fifty-four patients (45.4%) received norepinephrine, 72 (60.5% of the total cohort) needed invasive mechanical ventilation, and 31 (26.3%) received renal-replacement therapy. In-hospital mortality was 36.1% and was significantly associated with three independent risk factors by multivariable logistic regression: immunosuppression, VZV disease occurring in ICU and alcohol abuse. Hierarchical clustering on principal components revealed five phenotypically distinct clusters of patients: VZV-related pneumonia, mild encephalitis, severe encephalitis in solid organ transplant recipients, encephalitis in other immunocompromised hosts and VZV disease occurring in ICU. In-hospital mortality was highly different across phenotypes, ranging from zero to 75% (p < 0.001). CONCLUSION: Overall, severe VZV manifestations are associated with high mortality in the ICU, which appears to be driven by immunosuppression status rather than any specific organ involvement. Deciphering the clinical phenotypes may help clinicians identify high-risk patients and assess prognosis.

Antibiotic definitive treatment in ventilator associated pneumonia caused by AmpC-producing Enterobacterales in critically ill patients: a prospective multicenter observational study.

BACKGROUND: Ventilator associated pneumonia (VAP) due to wild-type AmpC-producing Enterobacterales (wtAE) is frequent in intensive care unit (ICU) patients. Despite a low level of evidence, definitive antimicrobial therapy (AMT) with third generation cephalosporins (3GCs) or piperacillin is discouraged. METHODS: Observational prospective study including consecutive wtAE VAP patients in 20 French ICUs. The primary objective was to assess the association of the choice of definitive AMT, i.e. piperacillin ± tazobactam (PTZ), 3GCs or other molecule (4GCs, carbapenems, quinolones, cotrimoxazole; control group), with treatment success at day-7. Recurrence of infection was collected as a secondary outcome, and analyzed accounting for the competing risk of death. RESULTS: From February 2021 to June 2022, 274 patients were included. Enterobacter cloacae was the most prevalent specie (31%). Seventy-eight patients (28%) had PTZ as definitive AMT while 44 (16%) had 3GCs and 152 (56%) were classified in the control group. Day-7 success rate was similar between the 3 groups (74% vs. 73% vs. 68% respectively, p = 0.814). Recurrence probability at day-28 was 31% (95% CI 21-42), 40% (95% CI 26-55) and 21% (95% CI 15-28) for PTZ, 3GCs and control groups (p = 0.020). In multivariable analysis, choice of definitive AMT was not associated with clinical success, but definitive AMT with 3GCs was associated with recurrence at day-28 [csHR(95%CI) 10.9 (1.92-61.91)]. CONCLUSION: Choice of definitive antimicrobial therapy was not associated with treatment success at day 7. However, recurrence of pneumonia at day-28 was higher in patients treated with third generation cephalosporins with no differences in mortality or mechanical ventilation duration.

Albumin versus saline infusion for sepsis-related peripheral tissue hypoperfusion: a proof-of-concept prospective study.

BACKGROUND: Albumin has potential endothelial protective effects through antioxidant and anti-inflammatory properties. However, the effect of albumin on peripheral tissue perfusion in human sepsis remains poorly known. METHODS: Bi-centric prospective study included patients with sepsis with or without shock and prolonged CRT > 3 s despite initial resuscitation. Clinicians in charge of the patients were free to infuse either saline 500 mL or human serum albumin 20% 100 mL over 15 min. Global hemodynamic parameters as well as peripheral tissue perfusion were analyzed after 1 (H1) and 4 h (H4). The primary endpoint was CRT normalization (< 3 s) at H1. RESULTS: 62 patients were screened, and 50 patients (13 sepsis and 37 septic shock) were included, 21 in the saline group and 29 in the albumin group. SOFA score was 8 [5-11], and SAPS II was 53 [45-70]. Median age was 68 [60-76] years with a higher proportion of men (74%). The primary sources of infection were respiratory (54%) and abdominal (24%). At baseline, comorbidities, clinical and biological characteristics were similar between groups. At H1, CRT normalization (< 3 s) was more frequent in patients receiving albumin as compared to patients treated by saline (63 vs 29%, P = 0.02). The decrease in fingertip CRT was more important in the albumin group when compared to saline group (- 1.0 [- 0.3; - 1.5] vs - 0.2 [- 0.1; - 1.1] seconds, P = 0.04) as well as decrease in mottling score. At H4, beneficial effects of albumin on peripheral tissue perfusion were maintained and urinary output trended to be higher in the albumin group (1.1 [0.5-1.8] vs 0.7 [0.5-0.9] ml/kg/h, P = 0.08). Finally, arterial lactate level did not significantly change between H0 and H4 in the saline group but significantly decreased in the albumin group (P = 0.03). CONCLUSION: In patients with resuscitated sepsis, albumin infusion might lead to greater improvement of tissue hypoperfusion compared to saline. CLINICALTRIALS: gov Identifier: NCT05094856.

Prediction of esophagogastroduodenoscopy therapeutic usefulness for in-ICU suspected upper gastrointestinal bleeding: the SUGIBI score study.

BACKGROUND: Suspected upper gastrointestinal bleeding (SUGIB) is a common issue during ICU stay. In the absence of specific guidelines on the indication and timing of esophagogastroduodenoscopy (EGD), there is substantial variability in EGD indication depending on accessibility and clinical presentation. This study aimed to investigate factors associated with the need for per-EGD hemostatic therapy and to create a score predicting therapeutic benefit of emergency bedside EGD in ICU patients with SUGIB. METHODS: We conducted a retrospective study in our ICU to identify factors associated with the need for hemostatic procedure during EGD performed for SUGIB. From this observational cohort, we derived a score predicting the need for hemostasis during EGD, the SUGIBI score. This score was subsequently validated in a retrospective multicenter cohort. RESULTS: Two hundred fifty-five patients not primarily admitted for GI bleeding who underwent a bedside EGD for SUGIB during their ICU stay were analyzed. The preeminent EGD indication were anemia (79%), melena (19%), shock (14%), and hematemesis (13%). EGD was normal in 24.7% of cases, while primary lesions reported were ulcers (23.1%), esophagitis (18.8%), and gastritis (12.5%). Only 12.9% of patients underwent hemostatic endotherapy during EGD. A SUGIBI score < 4 had a negative predictive value of 95% (91-99) for hemostatic endotherapy [AUC of 0.81; 0.75-0.91 (p < 0.0001)]. The SUGIBI score for predicting the need for an EGD-guided hemostatic procedure was next validated in a multicenter cohort with an AUC of 0.75 (0.66-0.85) (p < 0.0001), a score < 4 having a negative predictive value of 95% (92-97). CONCLUSIONS: Our study shows that the therapeutic usefulness of bedside emergency EGD for SUGIB in critically ill patients is limited to a minority of patients. The SUGIBI score should help clinicians stratify the probability of a therapeutic EGD.

Corticosteroids induce an early but limited decrease in IL-6 dependent pro-inflammatory responses in critically ill COVID-19 patients.

BACKGROUND: Corticosteroids have become standard of care for COVID-19 but their effect on the systemic immune-inflammatory response has been little investigated. METHODS: Multicenter prospective cohort, including critically ill COVID-19 patients between March and November 2020. C-reactive protein (CRP), lymphocyte count and fibrinogen levels were collected upon hospital admission before initiation of steroid treatment and at ICU admission, three days and seven days later, along with interleukin (IL)-6, IL-10 and tumor necrosis factor-alpha (TNF-α) plasma levels. RESULTS: A hundred and fifty patients were included, 47 received corticosteroids, 103 did not. Median age was 62 [53-70], and 96 (65%) patients were mechanically ventilated. Propensity score matching rendered 45 well-balanced pairs of treated and non-treated patients, particularly on pre-treatment CRP levels. Using a mixed model, CRP (P=0.019), fibrinogen (P=0.003) and lymphocyte counts (P=0.006) remained lower in treated patients over ICU stay. Conversely, there was no significant difference over the ICU stay for Il-6 (P=0.146) and IL-10 (0.301), while TNF- α levels were higher in the treated group (P=0.013). Among corticosteroid-treated patients, CRP (P=0.012), fibrinogen (P=0.041) and lymphocyte count (P=0.004) over time were associated with outcome, whereas plasma cytokine levels were not. CONCLUSIONS: Steroid treatment was associated with an early and sustained decrease in the downstream IL-6-dependent inflammatory signature but an increase in TNF-α levels. In corticosteroid-treated patients, CRP and lymphocyte count were associated with outcome, conversely to plasma cytokine levels. Further research on using these biomarker's kinetics to individualize immunomodulatory treatments is warranted.

Epidemiology and Clinical Patterns of Lung Abscesses in ICU: A French Multicenter Retrospective Study.

BACKGROUND: Data are scarce regarding epidemiology and management of critically ill patients with lung abscesses. RESEARCH QUESTION: What are the clinical and microbiological characteristics of critically ill patients with lung abscesses, how are they managed in the ICU, and what are the risk factors of in-ICU mortality? STUDY DESIGN AND METHODS: This was a retrospective observational multicenter study, based on International Classification of Diseases, 10th Revision, codes, between 2015 and 2022 in France. In-ICU mortality-associated factors were determined by multivariate logistic regression. RESULTS: We analyzed 171 ICU patients with pulmonary abscesses. Seventy-eight percent were male, with a mean age of 56.5 ± 16.4 years; 20.4% misused alcohol, 25.2% had a chronic lung disease (14% COPD), and 20.5% had a history of cancer. Overall, 40.9% were immunocompromised and 38% qualified for nosocomial infection. Presenting symptoms included fatigue or weight loss in 62%, fever (50.3%), and dyspnea (47.4%). Hemoptysis was reported in 21.7%. A polymicrobial infection was present in 35.6%. The most frequent pathogens were Enterobacteriaceae in 31%, Staphylococcus aureus in 22%, and Pseudomonas aeruginosa in 19.3%. Fungal infections were found in 10.5%. Several clusters of clinicoradiologic patterns were associated with specific microbiological documentation and could guide empiric antibiotic regimen. Percutaneous abscess drainage was performed in 11.7%; surgery was performed in 12.7%, and 12% required bronchial artery embolization for hemoptysis. In-ICU mortality was 21.5%, and age (OR: 1.05 [1.02-1.91], P = .007], renal replacement therapy during ICU stay (OR, 3.56 [1.24-10.57], P = .019), and fungal infection (OR, 9.12 [2.69-34.5], P = .0006) were independent predictors of mortality after multivariate logistic regression, and drainage or surgery were not. INTERPRETATION: Pulmonary abscesses in the ICU are a rare but severe disease often resulting from a polymicrobial infection, with a high proportion of Enterobacteriaceae, S aureus, and P aeruginosa. Percutaneous drainage, surgery, or arterial embolization was required in more than one-third of cases. Further prospective studies focusing on first-line antimicrobial therapy and source control procedure are warranted to improve and standardize patient management.

Prospective evaluation of bleeding risk among thrombocytopenic patients admitted in intensive care unit.

PURPOSE: Bleeding risk evaluation of thrombocytopenic patients admitted in ICU has been poorly investigated. METHODS: A prospective observational study conducted in an 18-bed medical ICU. Consecutive patients with thrombocytopenia (<150 Giga/L) and no bleeding at admission were included. RESULTS: Over one year, 91 patients were included, mainly men (63%), with an age of 61 [46-68] years and a SOFA score of 6 [3-8]. Twenty-three patients (25%) had an hemorrhagic event during ICU stay, mainly digestive (n = 9; 39%) and urological (n = 6; 26%). The time between ICU admission and bleeding was 8 [2-19] days. Almost half of bleeding events required vasopressor infusion and a hemostatic procedure. At admission, two variables were significantly different between the Bleeding and No-Bleeding groups: plasma urea level was significantly higher in the Bleeding group (9 [5.1; 13] vs. 13 [8.9; 31] mmol/L; p < 0.001) and the presence of skin purpura was associated with a 3-fold higher risk for bleeding during ICU stay (HR: 3.4 [1.3-8.3]; p < 0.05). In contrast, admission platelet count was not significantly different between the 2 groups (90 [32; 128] vs 62 [36; 103] G/L; p = 0.26). CONCLUSION: Plasma urea levels and the presence of skin purpura are helpful in identifying thrombocytopenic patients at high-risk of bleeding during ICU stay.

Permissive Hypotension Has No Deleterious Impact on Fluid Balance or Kidney Function.

OBJECTIVES: Mean arterial hypotension between 55 and 65 mm Hg could be tolerated safely in the absence of tissue hypoperfusion, but the consequences on fluid balance and kidney function remain unknown. DESIGN: During a 1-year period, we retrospectively collected data of consecutive septic patients admitted for sepsis with a mean arterial pressure (MAP) less than 65 mm Hg despite fluid resuscitation. SETTING: Medical 18-bed ICU in a tertiary teaching hospital. PATIENTS: Septic patients with a MAP less than 65 mm Hg despite initial resuscitation. INTERVENTIONS: In our ICU, MAP between 55 and 65 mm Hg was tolerated in the absence of peripheral hypoperfusion (permissive hypotension) or corrected using norepinephrine (septic shock group) when peripheral tissue hypoperfusion was present. MEASUREMENTS AND MAIN RESULTS: Ninety-four consecutive septic patients were included, 15 in the permissive hypotension group and 79 in the septic shock group. Median age was 66 years (57-77 yr) and 42% were women. The main sources of infection were respiratory (45%) and abdominal (18%). Severity was more important in septic shock group with higher Sequential Organ Failure Assessment score (7 [5-10] vs. 4 [1-6]; p < 0.0001), more frequent organ support therapy and ultimately higher mortality (38 vs. 0%; p < 0.01). The total volume of crystalloids infused before ICU admission was not different between groups (1930 ± 250 vs. 1850 ± 150 mL; p = 0.40). Within the 6 first hours of ICU stay, patients in the permissive hypotension group received less fluids (530 ± 170 vs. 1100 ± 110 mL; p = 0.03) and had higher urinary output (1.4 mL [0.88-2.34 mL] vs. 0.47 mL/kg/hr [0.08-1.25 mL/kg/hr]; p < 0.001). In addition, kidney injury evaluated using KDIGO score was lower in the permissive hypotension group at 48 hours (0 hr [0-1 hr] vs. 1 hr [0-2 hr]; p < 0.05). CONCLUSIONS: In septic patients without clinical peripheral hypoperfusion, mean arterial hypotension between 55 and 65 mm Hg could be tolerated safely without vasopressor infusion and was not associated with excessive fluid administration or kidney damage.

Sonometric assessment of cough predicts extubation failure: SonoWean-a proof-of-concept study.

BACKGROUND: Extubation failure is associated with increased mortality. Cough ineffectiveness may be associated with extubation failure, but its quantification for patients undergoing weaning from invasive mechanical ventilation (IMV) remains challenging. METHODS: Patients under IMV for more than 24 h completing a successful spontaneous T-tube breathing trial (SBT) were included. At the end of the SBT, we performed quantitative sonometric assessment of three successive coughing efforts using a sonometer. The mean of the 3-cough volume in decibels was named Sonoscore. RESULTS: During a 1-year period, 106 patients were included. Median age was 65 [51-75] years, mainly men (60%). Main reasons for IMV were acute respiratory failure (43%), coma (25%) and shock (17%). Median duration of IMV at enrollment was 4 [3-7] days. Extubation failure occurred in 15 (14%) patients. Baseline characteristics were similar between success and failure extubation groups, except percentage of simple weaning which was lower and MV duration which was longer in extubation failure patients. Sonoscore was significantly lower in patients who failed extubation (58 [52-64] vs. 75 [70-78] dB, P < 0.001). After adjustment on MV duration and comorbidities, Sonoscore remained associated with extubation failure. Sonoscore was predictive of extubation failure with an area under the ROC curve of 0.91 (IC95% [0.83-0.99], P < 0.001). A threshold of Sonoscore < 67.1 dB predicted extubation failure with a sensitivity of 0.93 IC95% [0.70-0.99] and a specificity of 0.82 IC95% [0.73-0.90]. CONCLUSION: Sonometric assessment of cough strength might be helpful to identify patients at risk of extubation failure in patients undergoing IMV.

Improvement of central vein ultrasound-guided puncture success using a homemade needle guide-a simulation study.

BACKGROUND: Out-of-plane (OOP) approach is frequently used for ultrasound-guided insertion of central venous catheter (CVC) owing to its simplicity but does not avoid mechanical complication. In-plane (IP) approach might improve safety of insertion; however, it is less easy to master. We assessed, a homemade needle guide device aimed to improve CVC insertion using IP approach. METHOD: We evaluated in a randomized simulation trial, the impact of a homemade needle guide on internal jugular, subclavian and femoral vein puncture, using three approaches: out-of-plane free hand (OOP-FH), in-plane free hand (IP-FH), and in-plane needle guided (IP-NG). Success at first pass, the number of needle redirections and arterial punctures was recorded. Time elapsed (i) from skin contact to first skin puncture, (ii) from skin puncture to successful venous puncture and (iii) from skin contact to venous return were measured. RESULTS: Thirty operators performed 270 punctures. IP-NG approach resulted in high success rate at first pass (jugular: 80%, subclavian: 95% and femoral: 100%) which was higher than success rate observed with OOP-FH and IP-FH regardless of the site (p = .01). Compared to IP-FH and OOP-FH, the IP-NG approach decreased the number of needle redirections at each site (p = .009) and arterial punctures (p = .001). Compared to IP-FH, the IP-NG approach decreased the total procedure duration for puncture at each site. CONCLUSION: In this simulation study, IP approach using a homemade needle guide for ultrasound-guided central vein puncture improved success rate at first pass, reduced the number of punctures/redirections and shortened the procedure duration compared to OOP and IP free-hand approaches.

Severe skin infections.

PURPOSE OF REVIEW: The incidence of necrotizing soft-tissue infections (NSTI) has increased during recent decades. These infections are still associated with high morbidity and mortality, underlining a need for continued education of the medical community. This review will focus on practical approaches to management of NSTI focusing on antibiotic therapies and optimizing the management of group A streptococcus (GAS)-associated NSTIs. RECENT FINDINGS: Antibiotic therapy for NSTI patients faces several challenges as the rapid progression of NSTIs mandates broad-spectrum agents with bactericidal action. Current recommendations support using clindamycin in combination with penicillin in case of GAS-documented NSTIs. Linezolide could be an alternative in case of clindamycin resistance. SUMMARY: Reducing the time to diagnosis and first surgical debridement, initiating early broad-spectrum antibiotics and early referral to specialized centres are the key modifiable factors that may impact the prognosis of NSTIs. Causative organisms vary widely according to the topography of the infection, underlying conditions, and geographic location. Approximately one third of NSTIs are monomicrobial, involving mainly GAS or Staphylococcus aureus . Data for antibiotic treatment specifically for necrotizing soft-tissue infections are scarce, with guidelines mainly based on expert consensus.

Impact of immunosuppressive regimen on ICU acquired pneumonia in critically ill COVID-19.

BACKGROUND: Immunosuppressors (IS) such as Dexamethasone (DXM), Tocilizumab, and high-dose methylprednisolone boli (HDMB), are used in COVID-19-related acute respiratory distress syndrome (ARDS). This study aimed to determine whether COVID-19 ARDS-related combined IS therapy was associated with an increased incidence of ICU-acquired pneumonia (IAP). METHODS: We retrospectively analyzed COVID-19-ARDS admitted to ICU from March 2020 to April 2022. Patients' and IAP characteristics were analyzed according to five IS regimens: No IS, DXM alone, DXM+HDMB, DXM+tocilizumab, and DXM+tocilizumab+HDMB. To investigate the role of IS on IAP incidence, we performed a multivariate logistic regression and built a propensity score. Ultimately, we used a conditional logistic regression after pairing on the propensity score. RESULTS: The study included 496 COVID-19-ARDS. Regarding the IS therapy, 12.7% received no IS, 43% DXM alone, 21.6% DXM+HDMB, 15.5% DXM+tocilizumab and 5.4% DXM+tocilizumab+HDMB. 37% presented at least one IAP, and the IAP incidence was higher with DXM+HDMB (66.4%) compared to no IS (P<0.0001), DXM (P<0.0001) and DXM+tocilizumab (P<0.0001). HDMB and probabilistic antibiotherapy at admission were independent IAP predictors after adjustment on the propensity score (respectively OR:2.44; P<0.0001 and OR:2.85; P<0.001). CONCLUSIONS: In critically ill COVID-19, HDMB significantly increases the risk of IAP whereas DXM alone, nor in combination with tocilizumab, did not.

High-Dose Steroids for Nonresolving Acute Respiratory Distress Syndrome in Critically Ill COVID-19 Patients Treated With Dexamethasone: A Multicenter Cohort Study.

OBJECTIVES: To determine the impact of high doses of corticosteroids (HDCT) in critically ill COVID-19 patients with nonresolving acute respiratory distress syndrome (ARDS) who had been previously treated with dexamethasone as a standard of care. DESIGN: Prospective observational cohort study. Eligible patients presented nonresolving ARDS related to severe acute respiratory syndrome coronavirus 2 infection and had received initial treatment with dexamethasone. We compared patients who had received or not HDCT during ICU stay, consisting of greater than or equal to 1 mg/kg of methylprednisolone or equivalent for treatment of nonresolving ARDS. The primary outcome was 90-day mortality. We assessed the impact of HDCT on 90-day mortality using univariable and multivariable Cox regression analysis. Further adjustment for confounding variables was performed using overlap weighting propensity score. The association between HDCT and the risk of ventilator-associated pneumonia was estimated using multivariable cause-specific Cox proportional hazard model adjusting for pre-specified confounders. SETTING: We included consecutive patients admitted in 11 ICUs of Great Paris area from September 2020 to February 2021. PATIENTS: Three hundred eighty-three patients were included (59 in the HDCT group, 324 in the no HDCT group). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: At day 90, 30 of 59 patients (51%) in the HDCT group and 116 of 324 patients (35.8%) in the no HDCT group had died. HDCT was significantly associated with 90-day mortality in unadjusted (hazard ratio [HR], 1.60; 95% CI, 1.04-2.47; p = 0.033) and adjusted analysis with overlap weighting (adjusted HR, 1.65; 95% CI, 1.03-2.63; p = 0.036). HDCT was not associated with an increased risk of ventilator-associated pneumonia (adjusted cause-specific HR, 0.42; 95% CI, 0.15-1.16; p = 0.09). CONCLUSIONS: In critically ill COVID-19 patients with nonresolving ARDS, HDCT result in a higher 90-day mortality.

Necrotizing soft tissue infections in critically ill neutropenic patients: a French multicentre retrospective cohort study.

BACKGROUND: Necrotizing soft tissue infections (NSTIs) are rare life-threatening bacterial infections. Few data are available regarding neutropenic patients with NSTIs. Our objectives were to describe the characteristics and management of neutropenic patients with NSTIs in intensive care units (ICUs). We conducted a retrospective multicentre cohort study in 18 ICUs between 2011 and 2021. Patients admitted with NSTIs and concomitant neutropenia at diagnosis were included and compared to non-neutropenic patients with NSTIs. The relationship between therapeutic interventions and outcomes was assessed using Cox regression and propensity score matching. RESULTS: 76 neutropenic patients were included and compared to 165 non-neutropenic patients. Neutropenic patients were younger (54 ± 14 vs 60 ± 13 years, p = 0.002) and had less lower limb (44.7% vs 70.9%, p < 0.001) and more abdomino-perineal NSTIs (43.4% vs 18.8%, p < 0.001). Enterobacterales and non-fermenting gram-negative bacteria were the most frequently isolated microorganisms in neutropenic patients. In-hospital mortality was significantly higher in neutropenic than in non-neutropenic patients (57.9% vs 28.5%, p < 0.001). Granulocyte colony-stimulating factor (G-CSF) administration was associated with a lower risk of in-hospital mortality in univariable Cox (hazard ratio (HR) = 0.43 95% confidence interval (CI) [0.23-0.82], p = 0.010) and multivariable Cox (adjusted HR = 0.46 95% CI [0.22-0.94], p = 0.033) analyses and after overlap propensity score weighting (odds ratio = 0.25 95% CI [0.09; 0.68], p = 0.006). CONCLUSIONS: Critically ill neutropenic patients with NSTIs present different clinical and microbiological characteristics and are associated with a higher hospital mortality than non-neutropenic patients. G-CSF administration was associated with hospital survival.

Quantitation of 10 antibiotics in plasma: Sulfosalicylic acid combined with 2D-LC-MS/MS is a robust assay for beta-lactam therapeutic drug monitoring.

Therapeutic drug monitoring (TDM) of antibiotics is particularly important in populations with high pharmacokinetic variabilities, such as critically ill patients, leading to unpredictable plasma concentrations and clinical outcomes. Here, we i) describe an original method for the simultaneous quantification of ten antibiotics (cefepime, ceftazidime, ampicillin, piperacillin/tazobactam, cefotaxime, amoxicillin, cloxacillin, oxacillin, linezolid) using 5-sulfosalicylic acid dihydrate (SSA) solution for protein precipitation together with 2D-LC-MS/MS, and ii) evaluate its impact in a one-year retrospective study. The method involved simple dilution with an aqueous mix of deuterated internal standards and plasma protein precipitation with SSA. Twenty microliters of the supernatant was injected into a C8 SPE online cartridge (30 × 2.1 mm) without any evaporation step and back-flushed onto a C18 UHPLC (100 × 2.1 mm) analytical column. Mass spectrometry detection (Xevo TQD) was performed in positive electrospray, in scheduled MRM mode. Overall analytical runtime was 7 min. Due to analytical constraints and the physicochemical properties of the antibiotics, protein precipitation using organic solvents could not be applied. As an alternative, SSA used with 2D-LC offered various advantages: i) lack of dilution resulting in better assay sensitivity, and ii) good chromatography of hydrophilic compounds. Ten microliters of 30% SSA in water eliminated>90% of plasma proteins, including the most abundant high molecular weight proteins at 55 and 72 kDa. The assay was successfully validated according to FDA and EMA guidelines for all the antibiotics, and the coefficients of variation of the quality control (QC) run during sample analysis over one year were below 10%, whatever the QC levels or the antibiotics. The use of 2D-LC combined with SSA precipitation allowed development of a robust, sensitive and rapid quantification assay. Feedback to clinicians was reduced to 24 h, thus allowing rapid dosage adjustment. During one year, 3,304 determinations were performed in our laboratory: 41% were not in the therapeutic range, 58% of which were sub-therapeutic, underlining the importance of early TDM of antibiotics to limit therapeutic failures and the emergence of bacterial resistance.

SARS-CoV-2 variants and mutational patterns: relationship with risk of ventilator-associated pneumonia in critically ill COVID-19 patients in the era of dexamethasone.

We aimed to explore the relationships between specific viral mutations/mutational patterns and ventilator-associated pneumonia (VAP) occurrence in COVID-19 patients admitted in intensive care units between October 1, 2020, and May 30, 2021. Full-length SARS-CoV-2 genomes were sequenced by means of next-generation sequencing. In this prospective multicentre cohort study, 259 patients were included. 222 patients (47%) had been infected with pre-existing ancestral variants, 116 (45%) with variant α, and 21 (8%) with other variants. 153 patients (59%) developed at least one VAP. There was no significant relationship between VAP occurrence and a specific SARS CoV-2 lineage/sublineage or mutational pattern.