Evaluation of CO2 removal rate of ECCO2R for a renal replacement therapy platform in an experimental setting.

BACKGROUND: A critical parameter of extracorporeal CO2 removal (ECCO2R) applications is the CO2 removal rate (VCO2). Low-flow venovenous extracorporeal support with large-size membrane lung remains undefined. This study aimed to evaluate the VCO2 of a low-flow ECCO2R with large-size membrane lung using a renal replacement therapy platform in an experimental animal model. METHODS: Twelve healthy pigs were placed under mechanical ventilation and connected to an ECCO2R-CRRT system (surface area = 1.8 m2; OMNIset®, BBraun, Germany). Respiratory settings were reduced to induce two degrees of hypercapnia. VCO2 was recorded under different combinations of PaCO2 (50-69 or 70-89 mm Hg), extracorporeal blood flow (ECBF; 200 or 350 mL/min), and gas flow (4, 6, or 10 L/min). RESULTS: VCO2 increased with ECBF at all three gas flow rates. In severe hypercapnia, the increase in sweep gas flow from 4 to 10 L/min increased VCO2 from 86.38 ± 7.08 to 96.50 ± 8.71 mL/min at an ECBF of 350 mL/min, whereas at ECBF of 200 mL/min, any increase was less effective. But in mild hypercapnia, the increase in sweep gas flow result in significantly increased VCO2 at two ECBF. VCO2 increased with PaCO2 from 50-69 to 70-89 mm Hg at an ECBF of 350 mL/min, but not at ECBF of 200 mL/min. Post-membrane lung PCO2 levels were similar for different levels of premembrane lung PCO2 (p = 0.08), highlighting the gas exchange diffusion efficacy of the membrane lung in gas exchange diffusion. In severe hypercapnia, the reduction of PaCO2 elevated from 11.5% to 19.6% with ECBF increase only at a high gas flow of 10 L/min (p < 0.05) and increase of gas flow significantly reduced PaCO2 only at a high ECBF of 350 mL/min (p < 0.05). CONCLUSIONS: Low-flow venovenous extracorporeal ECCO2R-CRRT with large-size membrane lung is more efficient with the increase of ECBF, sweep gas flow rate, and the degree of hypercapnia. The influence of sweep gas flow on VCO2 depends on the ECBF and degree of hypercapnia. Higher ECBF and gas flow should be chosen to reverse severe hypercapnia.

Prevention of urinary tract infection using a silver alloy hydrogel-coated catheter in critically ill patients: A single-center prospective randomized controlled study.

Background: A new type of silver alloy hydrogel-coated (SAH) catheter has been shown to prevent bacterial adhesion and colonization by generating a microcurrent, and to block the retrograde infection pathway. However, these have only been confirmed in ordinary patients. This study aims to evaluate the effectiveness of a SAH catheter for preventing urinary tract infections in critically ill patients. Methods: This was a prospective single-center, single-blind, randomized, controlled study. A total of 132 patients requiring indwelling catheterization in the intensive care unit (ICU) of the First Affiliated Hospital of the University of Science and Technology of China between October 2022 and February 2023 and who met the study inclusion/exclusion criteria were randomly divided into two groups. Patients in the SAH catheter group received a SAH catheter, while patients in the conventional catheter group received a conventional siliconized latex Foley catheter. The main outcome measure was the incidence of catheter-associated urinary tract infections (CAUTIs). Secondary outcome indicators included urine positivity for white blood cells and positive urine cultures on 3 days, 7 days, 10 days, and 14 days after catheterization, number of viable bacteria in the catheter biofilm on day 14, pathogenic characteristics of positive urine cultures, length of ICU stay, overall hospital stay, ICU mortality, and 28-day mortality. All the data were compared between the two groups. Results: A total of 68 patients in the conventional catheter group and 64 patients in the SAH catheter group were included in the study. On day 7 after catheter placement, the positivity rate for urinary white blood cells was significantly higher in the conventional catheter group than in the SAH catheter group (33.8% vs. 15.6%, P=0.016). On day 10, the rates of positive urine cultures (27.9% vs. 10.9%, P=0.014) and CAUTIs (22.1% vs. 7.8%, P=0.023) were significantly higher in the conventional catheter group than in the SAH catheter group. On day 14, the numbers of viable bacteria isolated from the catheter tip ([3.21±1.91]×106 colony-forming units [cfu]/mL vs. [7.44±2.22]×104 cfu/mL, P <0.001), balloon segment ([7.30±1.99]×107 cfu/mL vs. [3.48±2.38]×105 cfu/mL, P <0.001), and tail section ([6.41±2.07]×105 cfu/mL vs. [8.50±1.46]×103 cfu/mL, P <0.001) were significantly higher in the conventional catheter group than in the SAH catheter group. The most common bacteria in the urine of patients in both groups were Escherichia coli (n=13) and Pseudomonas aeruginosa (n=6), with only one case of Candida in each group. There were no significant differences between the two groups in terms of ICU hospitalization time, total hospitalization time, ICU mortality, and 28-day mortality. Conclusion: SAH catheters can effectively inhibit the formation of catheter-related bacterial biofilms in critically ill patients and reduce the incidence of CAUTIs, compared with conventional siliconized latex Foley catheters; however, regular replacement of the catheter is still necessary.

Diagnostic Value and Clinical Application of Metagenomic Next-Generation Sequencing for Infections in Critically Ill Patients.

Objective: To evaluate the diagnostic value and clinical application of metagenomic next-generation sequencing (mNGS) for infections in critically ill patients. Methods: Comparison of diagnostic performance of mNGS and conventional microbiological testing for pathogens was analyzed in 234 patients. The differences between immunocompetent and immunocompromised individuals in mNGS-guided anti-infective treatment adjustment were also analyzed. Results: The sensitivity and specificity of mNGS for bacterial and fungal detection were 96.6% (95% confidence interval [CI], 93.5%-99.6%) and 83.1% (95% CI, 75.2%-91.1%), and 85.7% (95% CI, 71.9%-99.5%) and 93.2% (95% CI, 89.7%-96.7%), respectively. Overall, 152 viruses were detected by mNGS, but in which 28 viruses were considered causative agents. The proportion of mNGS-guided beneficial anti-infective therapy adjustments in the immunocompromised group was greater than in the immunocompetent group (48.5% vs 30.1%; P=0.008). In addition, mNGS-guided anti-infective regimens with peripheral blood and BALF specimens had the highest proportion (39.0%; 40.0%), but the proportion of patients not helpful due to peripheral blood mNGS was also as high as 22.0%. Conclusion: mNGS might be a promising technology to provide precision medicine for critically ill patients with infection.

Comparison of endotracheal aspirate and bronchoalveolar lavage fluid metagenomic next-generation sequencing in severe pneumonia: a nested, matched case-control study.

OBJECTIVES: To compare clinical outcomes in patients with severe pneumonia according to the diagnostic strategy used. METHODS: In this retrospective, nested, case-control study, patients with severe pneumonia who had undergone endotracheal aspirate (ETA) metagenomic next-generation sequencing of (mNGS) testing (n = 53) were matched at a ratio of 1 to 2 (n = 106) by sex, age, underlying diseases, immune status, disease severity scores, and type of pneumonia with patients who had undergone bronchoalveolar lavage fluid (BALF) mNGS. The microbiological characteristics and patient's prognosis of the two groups were compared. RESULTS: An overall comparison between the two groups showed no significant differences in bacterial, fungal, viral, or mixed infections. However, subgroup analysis of 18 patients who received paired ETA and BALF mNGS showed a complete agreement rate for the two specimens of 33.3%. There were more cases for whom targeted treatment was initiated (36.79% vs. 22.64%; P = 0.043) and fewer cases who received no clinical benefit after mNGS (5.66% vs. 15.09%; P = 0.048) in the BALF group. The pneumonia improvement rate in the BALF group was significantly higher than in the ETA group (73.58% vs. 87.74%, P = 0.024). However, there were no significant differences in ICU mortality or 28-day mortality. CONCLUSIONS: We do not recommend using ETA mNGS as the first-choice method for analyzing airway pathogenic specimens from severe pneumonia patients.

Metagenomic next-generation sequencing technology for detection of pathogens in blood of critically ill patients.

OBJECTIVE: To explore the applicability of metagenomic next-generation sequencing (mNGS) technology for the detection of blood pathogens in intensive care unit patients. METHODS: The clinical data of 63 critically ill patients who could not be diagnosed with blood culture (BC) and who underwent mNGS blood sample testing were retrospectively analyzed. The diagnostic efficacy of mNGS was compared with that of traditional detection methods; the distribution of the pathogens identified by mNGS was analyzed; and the differences in laboratory tests, comorbidities, treatment, and prognosis between the mNGS-positive and mNGS-negative groups were compared. RESULTS: The positive rate of mNGS was 41.3% (26/63), and 16 patients were found to have mixed infections. However, the positive rate of BCs performed simultaneously with mNGS was only 7.9% (5/63). The results of univariate analysis showed that the average length of intensive care unit stay (ß, -8.689 [95% CI, -16.176, -1.202]; P = 0.026) and the time from onset to sequencing (ß, -5.816 [95% CI,-9.936, -1.696]; P = 0.007) of the mNGS-positive group were significantly shorter than those of the mNGS-negative group. More patients in the positive group were adjusted for anti-infective treatment after mNGS (OR, 3.789 [95% CI,1.176, 12.211]; P < 0.001). CONCLUSIONS: Detection of blood pathogens by mNGS has good applicability for critically ill patients who cannot be diagnosed by BC in the early stages of infection, and mNGS should be performed as early as possible to obtain higher pathogen detection rates.

Diagnostic Value of Metagenomic Next-Generation Sequencing for the Detection of Pathogens in Bronchoalveolar Lavage Fluid in Ventilator-Associated Pneumonia Patients.

Objective: To evaluate the diagnostic performance of metagenomic next-generation sequencing (mNGS) using bronchoalveolar lavage fluid (BALF) in patients with ventilator-associated pneumonia (VAP). Methods: BALF samples of 72 patients with VAP were collected from August 2018 to May 2020. The diagnostic performance of conventional testing (CT) and mNGS methods were compared based on bacterial and fungal examinations. The diagnostic value of mNGS for viral and mixed infections was also analyzed. Results: The percentage of mNGS positive samples was significantly higher than that estimated by the CT method [odds ratio (OR), 4.33; 95% confidence interval (CI), 1.78-10.53; p < 0.001]. The sensitivity and specificity of mNGS for bacterial detection were 97.1% (95% CI, 93.2-101.0%) and 42.1% (95 CI, 30.7-53.5%), respectively, whereas the positive predictive value (PPV) and the negative predictive value (NPV) were 60.0% (95% CI, 48.7-71.3%) and 94.1% (95% CI, 88.7-99.6%), respectively. A total of 38 samples were negative for bacterial detection as determined by the CT method, while 22 samples were positive as shown by the mNGS method. Conflicting results were obtained for three samples between the two methods of bacterial detection. However, no significant differences were noted between the mNGS and CT methods (OR, 1.42; 95% CI, 0.68-2.97; p = 0.46) with regard to fungal infections. The sensitivity and specificity of mNGS were 71.9% (95% CI, 61.5-82.3%) and 77.5% (95% CI, 67.9-87.1%), respectively. mNGS exhibited a PPV of 71.9% (95% CI, 61.5-82.3%) and an NPV of 77.5% (95% CI, 67.9-87.1%). A total of 9 out of 40 samples were found positive for fungi according to mNGS, whereas the CT method failed to present positive results in these samples. The mNGS and CT methods produced conflicting results with regard to fungal detection of the two samples. A total of 30 patients were virus-positive using mNGS. Furthermore, 42 patients (58.3%) were identified as pulmonary mixed infection cases. Conclusions: mNGS detection using BALF improved the sensitivity and specificity of bacterial identification in patients who developed VAP. In addition, mNGS exhibited apparent advantages in detecting viruses and identifying mixed infections.

Hemophagocytic lymphohistiocytosis is associated with Bartonella henselae infection in a patient with multiple susceptibility genes.

BACKGROUND: Adult-onset hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening condition, which is often triggered by certain types of infection, cancer and numerous autoimmune diseases; however, of the numerous infectious triggers associated with HLH, the consequences of Bartonella henselae infection have been rarely reported. CASE PRESENTATION: A 48-year-old female presented with a 20-day history of intermittent fever accompanied by systemic rash, fatigue, anorexia and weight loss later she developed shock and unconsciousness. Blood tests showed a reduction of leukocyte, anemia and thrombocytopenia, and pathological results of a bone marrow biopsy confirmed hemophagocytic activity. Metagenomic next-generation sequencing (mNGS) analysis of the lymph node detected the presence of B. henselae. Whole exome sequencing revealed two gene variants, STXBP2 and IRF5, in this adult patient with secondary HLH. Then, she received minocycline and rifampin combination anti-infective therapy. Intravenous immunoglobulin for 5 days followed by a high dose of methylprednisolone were also administered. The patient was successfully discharged from the intensive care unit and remained in good condition after 2 months of follow-up. CONCLUSIONS: mNGS served crucial roles in obtaining an etiological diagnosis, which suggested that screening for B. henselae should be considered in patients with HLH, especially those with a cat at home. In addition, the genetic defects were discovered to not only be present in primary HLH, but also in secondary HLH, even in the elderly.

[In vitro activity of ceftazidime-avibactam combined with colistin against extensively drug-resistant Pseudomonas aeruginosa].

OBJECTIVE: To evaluate the in vitro activity of ceftazidime-avibactam (CAZ-AVI) alone or in combination with colistin (COL) against clinically isolated extensively drug-resistant Pseudomonas aeruginosa (XDR-PA). METHODS: Minimum inhibitory concentration (MIC) of 16 clinical XDR-PA isolates was determined by broth dilution method and chessboard design when CAZ-AVI and COL were used alone or in combination, then the combined inhibitory concentration index (FICI) was calculated. Class A [Klebsiella pneumoniae carbapenemase ß-lactamase (blaKPC), Guiana extended-spectrum ß-lactamase (blaGES)], Class B [imipenemase ß-lactamase (blaIMP), Verona-Integronmetallo ß-lactamase (blaVIM), New Delhi metallo ß-lactamase (blaNDM), German imipenemase ß-lactamase (blaGIM), Sao Paulo metallo-ß-lactamase (blaSPM)], Class C [AmpC ß-lactamase (blaAmpC)], Class D [oxacillinase ß-lactamase (blaOXA)] ß-lactamase-related resistance genes were detected by polymerase chain reaction. Drug-resistant mutation frequencies of each strain were determined on a drug-containing plate. The time kill curves of three XDR-PA were plotted by colony counting method. A biofilm model was established in vitro, and the synergistic effect of CAZ-AVI and COL on biofilm inhibition was detected by methythiazolyl tetrazolium assay (MTT). RESULTS: The MICs of 16 XDR-PA for CAZ-AVI ranged from 1 mg/L to 128 mg/L, and three of the isolates showed resistance (MIC > 8 mg/L). The FICI range of CAZ-AVI combined with COL was 0.312-1.000. Four isolates were synergistic, while the other 12 isolates were additive. Three isolates resistant to CAZ-AVI contained Class B resistance genes such as blaIMP and blaVIM, while 13 susceptible isolates carried resistance genes belonging to Class A, C or D. The logarithm values of mutation frequencies of drug resistance in CAZ-AVI group, COL group and combination group were -4.81±0.88, -7.06±0.69 and -9.70 (-9.78, -9.53), respectively. There were significant differences among the three groups (H = 33.601, P < 0.001), and between every two groups (adjusted P < 0.05). In time kill curves, the phytoplankton load of three XDR-PA decreased more than 6 log CFU/L when these two drugs were used together, and number of PA1819 planktonic bacteria decreased more than 5.1 log CFU/L compared with monotherapy group. Viable quantity in biofilm (A490) of normal saline group, CAZ-AVI group, COL group and CAZ-AVI-COL group were 0.665±0.068, 0.540±0.072, 0.494±0.642 and 0.317±0.080, respectively. There was significant difference between the other two groups (all P < 0.001), except for that between CAZ-AVI group and COL group (P = 0.109). CONCLUSIONS: CAZ-AVI combined with COL can effectively improve the bactericidal effect of each drug alone on XDR-PA. The regimen can also reduce the production of drug-resistant bacteria and inhibit the formation of biofilm. Therefore, it is a potential treatment for XDR-PA infection.