Clozapine-Induced Severe Toxicity: Exploring the Pharmacokinetic Profile of Clozapine and Its Significance in Hemodynamic Instability - A Case Report.

Hemodynamic instability in patients with clozapine intoxication can indirectly reflect the serum concentration of clozapine.We have described a case of a 32-year-old pregnant woman who developed life-threatening clozapine toxicity at 28 weeks of gestation. The levels of clozapine and norclozapine in the serum were high. We initiated hemoperfusion(HP) and other detoxification therapies to remove the drug. The patient had severely dilated peripheral blood vessels, which led to cardiac symptoms such as fatal hypotension and uncontrollable tachycardia, resulting in very high cardiac output and elevated Central venous oxygen saturation (ScvO2). Pharmacological intervention significantly improved the hemodynamics.In light of our observations in the ongoing case, we posit that evaluating hemodynamic parameters before and after blood detoxification could serve as a valuable means to gauge effectiveness and provide guidance for treatment.

The pharmacokinetics/pharmacodynamics of ceftazidime/avibactam for central nervous system infections caused by carbapenem-resistant Gram-negatives: a prospective study.

OBJECTIVES: To describe the pharmacokinetics/pharmacodynamics (PK/PD) of ceftazidime/avibactam in critically ill patients with CNS infections. METHODS: A prospective study of critically ill patients with CNS infections who were treated with ceftazidime/avibactam and the steady-state concentration (Css) of ceftazidime/avibactam in serum and/or CSF was conducted between August 2020 and May 2023. The relationship between PK/PD goal achievement, microbial eradication and the clinical efficacy of ceftazidime/avibactam was evaluated. RESULTS: Seven patients were finally included. The ceftazidime/avibactam target attainment in plasma was optimal for three, quasi-optimal for one and suboptimal for three. In three patients with CSF drug concentrations measured, ceftazidime/avibactam target attainment in CSF was 100% (3/3), which was optimal. The AUCCSF/serum values were 0.59, 0.44 and 0.35 for ceftazidime and 0.57, 0.53 and 0.51 for avibactam. Of the seven patients, 100% (7/7) were treated effectively, 71.4% (5/7) achieved microbiological eradication, 85.7% (6/7) survived and 14.3% (1/7) did not survive. CONCLUSIONS: The limited clinical data suggest that ceftazidime/avibactam is effective in the treatment of CNS infections caused by MDR Gram-negative bacilli (MDR-GNB), can achieve the ideal drug concentration of CSF, and has good blood-brain barrier penetration.

A descriptive pharmacokinetic/pharmacodynamic analysis of ceftazidime-avibactam in a case series of critically ill patients with augmented renal clearance.

To describe the pharmacokinetics/pharmacodynamics (PK/PD) of a 2 h infusion of ceftazidime-avibactam (CAZ-AVI) in critically ill patients with augmented renal clearance (ARC). A retrospective review of all critically ill patients with ARC who were treated with CAZ-AVI between August 2020 and May 2023 was conducted. Patients whose 12-h creatinine clearance prior to CAZ-AVI treatment and steady-state concentration (Css) of CAZ-AVI were both monitored were enrolled. The free fraction (fCss) of CAZ-AVI was calculated from Css. The joint PK/PD targets of CAZ-AVI were considered optimal when a Css/minimum inhibitory concentration (MIC) ratio for CAZ ≥4 (equivalent to 100% fT > 4 MIC) and a Css/CT ratio of AVI >1 (equivalent to 100% fT > CT 4.0 mg/L) were reached simultaneously, quasioptimal when only one of the two targets was reached, and suboptimal when neither target was reached. The relationship between PK/PD goal achievement, microbial eradication and the clinical efficacy of CAZ-AVI was evaluated. Four patients were included. Only one patient achieved optimal joint PK/PD targets, while the other three reached suboptimal targets. The patient with optimal PK/PD targets achieved microbiological eradication, while the other three patients did not, but all four patients achieved good clinical efficacy. Standard dosages may not enable most critically ill patients with ARC to reach the optimal joint PK/PD targets of CAZ-AVI. Optimal drug dose adjustment of CAZ-AVI in ARC patients requires dynamic drug concentration monitoring.

Combination of NK and Other Immune Markers at Early Phase Stratify the Risk of Sepsis Patients: A Retrospective Study.

Purpose: Immune dysfunction plays a pivotal role in sepsis pathogenesis. Previous studies have revealed the crucial role of T cells and human leukocyte antigen-DR (HLA-DR) in sepsis. However, the function of natural killer (NK) cells remains unclear. This study aimed to investigate whether NK cells are associated with sepsis prognosis. In addition, we aimed to explore the interrelation and influence between NK and other immunological features in patients with sepsis. Patients and Methods: This retrospective, observational study included patients with sepsis from two hospitals in mainland China. The clinical characteristics and immune results during the early phase were collected. Patients were classified according to the level of immune cells to analyze the relationship between immunological features and 28-day mortality. Results: A total of 984 patients were included in this study. Non-survivors were older and had lower levels of lymphocytes, monocytes, NK cells, HLA-DR, and T cells. Patients were classified into eight groups according to their levels of NK cells, HLA-DR, and T cells. Only patients with decreased NK and T cell counts showed a significant increase in 28-day mortality. An increase in CD8+ T cells was correlated with the alleviation of 28-day mortality only among patients with high NK cell levels. Conclusion: This study provides novel insights into the association between NK cells and 28-day mortality as well as the interrelation between NK cells and other immune cells in sepsis. The relationship between CD8+ T cells and 28-day mortality in sepsis is dependent on NK cell count.

Efficacy of initial caspofungin plus trimethoprim/sulfamethoxazole for severe PCP in patients without human immunodeficiency virus infection.

BACKGROUND: The number of pneumocystis pneumonia (PCP) cases is increasing in immunocompromised patients without human immunodeficiency virus infection (HIV), causing serious morbidity with high mortality. Trimethoprim/sulfamethoxazole (TMP/SMZ) monotherapy has limited effectiveness in the treatment of PCP. Clinical data on whether initial caspofungin plus TMP/SMZ for this disease is superior to monotherapy in non-HIV-infected patients are limited. We aimed to compare the clinical effectiveness of these regimens for severe PCP in non-HIV patients. METHODS: A retrospective study reviewed 104 non-HIV-infected patients with confirmed PCP in the intensive care unit between January 2016 and December 2021. Eleven patients were excluded from the study because TMP/SMZ could not be used due to severe hematologic disorders or clinical data were missing. All enrolled patients were divided into three groups according to different treatment strategies: Group 1 received TMP/SMZ monotherapy, Group 2 received caspofungin combined with TMP/SMZ as first-line therapy, and Group 3 initially received TMP/SMZ monotherapy and later received caspofungin as salvage therapy. The clinical characteristics and outcomes were compared among the groups. RESULTS: A total of 93 patients met the criteria. The overall positive response rate of anti-PCP treatment was 58.06%, and the overall 90-day all-cause mortality rate was 49.46%. The median APACHE II score was 21.44. The concurrent infection rate was 74.19%, among whom 15.05% (n = 14) of those patients had pulmonary aspergillosis, 21.05% (n = 20) had bacteremia, and 23.65% (n = 22) had CMV infections. The patients who received initial caspofungin combination with TMP/SMZ had the best positive response rate (76.74%) compared to others (p = 0.001). Furthermore, the group that received initial caspofungin combined with TMP/SMZ had a 90-day all-cause mortality rate (39.53%) that was significantly different from that of the shift group (65.51%, p = 0.024), but this rate showed no statistically significant difference compared with that in the monotherapy group (48.62%, p = 0.322). None of the patients had serious adverse events from caspofungin therapy. CONCLUSIONS: For non-HIV-infected patients with severe PCP, initial combination therapy with caspofungin and TMP/SMZ is a promising first-line treatment option compared with TMP/SMZ monotherapy and combination therapy as salvage therapy.

Pulmonary artery flotation catheter (PAFC) combined with pump-controlled retrograde trial off (PCRTO) as a trial for weaning VA-ECMO patients: A retrospective study.

OBJECTIVES: Pump-controlled retrograde trial off (PCRTO) has been recently proposed as an effective and safe VA-ECMO weaning method. However, reports of haemodynamic monitoring during PCRTO are rare. Therefore, the purpose of this study was to investigate the changes in the left and right heart function during the PCRTO process combined with a pulmonary artery flotation catheter (PAFC). METHODS: Between March 2019 and May 2021, 20 adult VA-ECMO patients who underwent PCRTO in combination with PAFC were enrolled in this study. The patients' general characteristics, PCRTO results, haemodynamic parameters during PCRTO progression, complications, and clinical prognoses were analysed. Those who survived for 48 h after withdrawal and did not require ECMO assistance were defined as the success group, and those who did not survive for 48 h after withdrawal or who required ECMO assistance were defined as the failure group. RESULTS: Of the 20 patients, 13 (65%) were included in the success group, and 7 (35%) were included in the failure group. Compared with the success group, the heart rate (HR) of the failure group was significantly increased 30 min after PCRTO (p < .01), and the pulmonary artery wedge pressure (PAWP) was significantly higher at all time points (p < .01). Compared with pre-PCRTO in the success group, the HR at 2 min in the success group was significantly increased, but decreased to the baseline levels at 15 min and 30 min. The PAWP was also significantly increased at 2 min, but decreased at 15 min and dropped to the baseline level at 30 min in the success group. Compared with pre-PCRTO in the failure group, the HR and PAWP increased significantly at 2 min, 15 min and 30 min in the failure group. No new embolism-related complications were found in the success group after the withdrawal from ECMO. CONCLUSIONS: PCRTO is a safe and reliable VA-ECMO weaning method. Combined with haemodynamic monitoring through PAFC, PCRTO can better assess the cardiac reserve function.

Novel fast pathogen diagnosis method for severe pneumonia patients in the intensive care unit: randomized clinical trial.

Background: Severe pneumonia is one of the common acute diseases caused by pathogenic microorganism infection, especially by pathogenic bacteria, leading to sepsis with a high morbidity and mortality rate. However, the existing bacteria cultivation method cannot satisfy current clinical needs requiring rapid identification of bacteria strain for antibiotic selection. Therefore, developing a sensitive liquid biopsy system demonstrates the enormous value of detecting pathogenic bacterium species in pneumonia patients. Methods: In this study, we developed a tool named Species-Specific Bacterial Detector (SSBD, pronounce as 'speed') for detecting selected bacterium. Newly designed diagnostic tools combining specific DNA-tag screened by our algorithm and CRISPR/Cas12a, which were first tested in the lab to confirm the accuracy, followed by validating its specificity and sensitivity via applying on bronchoalveolar lavage fluid (BALF) from pneumonia patients. In the validation I stage, we compared the SSBD results with traditional cultivation results. In the validation II stage, a randomized and controlled clinical trial was completed at the ICU of Nanjing Drum Tower Hospital to evaluate the benefit SSBD brought to the treatment. Results: In the validation stage I, 77 BALF samples were tested, and SSBD could identify designated organisms in 4 hr with almost 100% sensitivity and over 87% specific rate. In validation stage II, the SSBD results were obtained in 4 hr, leading to better APACHE II scores (p=0.0035, ANOVA test). Based on the results acquired by SSBD, cultivation results could deviate from the real pathogenic situation with polymicrobial infections. In addition, nosocomial infections were found widely in ICU, which should deserve more attention. Conclusions: SSBD was confirmed to be a powerful tool for severe pneumonia diagnosis in ICU with high accuracy. Funding: National Natural Science Foundation of China. The National Key Scientific Instrument and Equipment Development Project. Project number: 81927808. Clinical trial number: This study was registered at https://clinicaltrials.gov/ (NCT04178382).

Correlation between the drug concentration of polymyxin B and polymyxin B-associated acute kidney injury in critically ill patients: A prospective study.

In recent years, polymyxin B-associated acute kidney injury (PB-AKI) in critically ill patients has been reported frequently, but polymyxin B (PB) is mainly cleared through non-renal pathways, and the reasons of PB-AKI remain unclear. The aim of this study was to investigate the relationship between the serum concentration of PB and PB-AKI. We conducted a prospective cohort study in an intensive care unit between May 2019 and July 2021. Over the study period, 52 patients were included and divided into an AKI group (n = 26) and a non-AKI group (n = 26). The loading dose of PB in the AKI group was significantly higher than that in the non-AKI group. The C1/2 , Cmin , and estimated area under the concentration-time curve (AUC)0-24 of PB in the AKI group were dramatically increased compared with those in the non-AKI group, but the Cmax between the two groups showed no differences. Upon obtaining the ROC curve, the areas for the C1/2 , Cmin , and estimated AUC0-24 were 0.742, 0.710, and 0.710, respectively. The sensitivity was ascertained to be 61.54%, and the specificity was 76.92% when the cutoff value for the estimated AUC0-24 of 97.72 mg·h/L was used preferentially. The incidence of PB-AKI is high and related to the loading dose of PB. PB-AKI could be predicted when the estimated AUC0-24 of PB was greater than 97.72 mg·h/L.

[Clinical study on the predictive value of regional cerebral oxygen saturation for the occurrence of sepsis-associated encephalopathy].

OBJECTIVE: To evaluate the predictive value of regional cerebral oxygen saturation (rScO2) for the occurrence of sepsis-associated encephalopathy (SAE). METHODS: The data of 94 patients with sepsis admitted to the intensive care unit of Nanjing Drum Tower Hospital from September 2019 to June 2021 were collected. The patients were divided into SAE group and non-SAE group according to the evaluation results of daily intensive care unit confusion assessment method (CAM-ICU) during ICU treatment. The general data such as age and gender of the patients, rScO2 on 1, 2, 3, 5, and 7 days of ICU admission, and prognostics were recorded. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of rScO2 on SAE during ICU stay. RESULTS: All 94 patients were enrolled in the analysis, of whom 59.6% (56/94) were male, and the mean age was (50.1±15.1) years old; the incidence of SAE was 31.9% (30/94). The levels of rScO2 within first 3 days of ICU admission in the SAE group were significantly lower than those in the non-SAE group (1 day: 0.601±0.107 vs. 0.675±0.069, 2 days: 0.592±0.090 vs. 0.642±0.129, 3 days: 0.662±0.109 vs. 0.683±0.091, all P < 0.05). However, there was no significant difference in rScO2 level on the 5th or the 7th day between the SAE and non-SAE groups (5 days: 0.636±0.065 vs. 0.662±0.080, 7 days: 0.662±0.088 vs. 0.690±0.077, both P > 0.05). ROC curve analysis showed that 1-day rScO2 had the greatest predictive value for SAE [1 day: area under the ROC curve (AUC) = 0.77, 95% confidence interval (95%CI) was 0.65-0.89, P < 0.01; 2 days: AUC = 0.60, 95%CI was 0.48-0.72, P > 0.05; 3 days: AUC = 0.55, 95%CI was 0.41-0.68, P > 0.05]; with 1-day rScO2 = 0.640 as the diagnostic threshold, the sensitivity was 73.4%, the specificity was 80.0%. Compared with the non-SAE group, the length of ICU stay and hospital stay in the SAE group were significantly longer [length of ICU stay (days): 13.6±7.1 vs. 9.0±4.3, length of hospital stay (days): 20.1±8.0 vs. 15.8±6.1, both P < 0.05], but the ICU mortality between the two groups was not statistically different. CONCLUSIONS: The incidence of SAE is relatively high in ICU patients, and the occurrence of SAE can be predicted by monitoring rScO2. The rScO2 value on the first day of ICU admission is closely related to the occurrence of SAE, and may be the target of sepsis resuscitation to guide the treatment and improve the long-term prognosis.

Clinical feature of severe fever with thrombocytopenia syndrome (SFTS)-associated encephalitis/encephalopathy: a retrospective study.

BACKGROUND/OBJECTIVE: Severe fever with thrombocytopenia syndrome (SFTS) cause encephalitis/encephalopathy, but few reports were available. We aimed to investigate the incidence of encephalitis/encephalopathy in SFTS patients and to summarize clinical characteristics, laboratory findings and imaging features. METHODS: We conducted a retrospective review of all patients with confirmed SFTS admitted to Nanjing Drum Tower Hospital, a tertiary hospital in Nanjing City, China, between January 2016 and July 2020. The patients were divided into two groups according to whether they had encephalitis/encephalopathy: encephalitis/encephalopathy group and non- encephalitis/encephalopathy group. Clinical data, laboratory findings, imaging characteristics, treatments and outcomes of these patients were collected and analyzed. RESULTS: A total of 109 SFTS patients with were included, of whom 30 (27.5 %) developed encephalitis/encephalopathy. In-hospital mortality (43.3 %) was higher in encephalitis/encephalopathy group than non-encephalitis/encephalopathy group (12.7 %). Univariate logistic regression showed that cough, wheezing, dyspnoea, respiratory failure, vasopressors use, bacteremia, invasive pulmonary aspergillosis (IPA) diagnoses, PCT > 0.5 ug/L, CRP > 8 mg/L, AST > 200 U/L and serum amylase level > 80 U/L were the risk factors for the development of encephalitis/encephalopathy for SFTS patients. Multivariate logistic regression analysis identified bacteremia, PCT > 0.5 mg/L and serum amylase level > 80 U/L as independent predictors of encephalitis/ encephalopathy development for SFTS patients. CONCLUSIONS: SFTS-associated encephalitis/encephalopathy has high morbidity and mortality. it was necessary to strengthen the screening of CSF testing and brain imaging after admission for SFTS patients who had symptoms of encephalitis/encephalopathy. SFTS patients with bacteremia, PCT > 0.5 ug/L or serum amylase level > 80 U/L should be warned to progress to encephalopathy.

[Application of extracorporeal membrane oxygenation in critically ill pregnant women].

OBJECTIVE: To investigate the safety and effectiveness of extracorporeal membrane oxygenation (ECMO) in emergency treatment of critically ill pregnant women. METHODS: Clinical data of 8 pregnant women with severe cardiopulmonary dysfunction during the perinatal period treated by ECMO in the department of intensive care unit (ICU) of Nanjing Drum Tower Hospital, the Affiliated Hospital to Nanjing University Medical School from September 2017 to November 2020 were retrospectively analyzed. RESULTS: For the 8 pregnant women, the mean age was (32.5±6.3) years old. Body weight was (73.5±8.1) kg. Gestational age was (31.0±4.4) weeks. Acute physiology and chronic health evaluation II (APACHE II) score was 13.0±6.6, and sequential organ failure assessment (SOFA) score was 8.3±3.8. Among them, 5 pregnant women suffered from severe pneumonia and were treated with venous-venous ECMO (VV-ECMO). Another 3 pregnant women with heart failure underwent venous-arterial ECMO (VA-ECMO). The initial ECMO flow rate was set to 2.0-3.0 L/min. Then the highest flow rate was (3.1±0.6) L/min, and the average ECMO running time was (174±36) hours. The length of ICU stay was (16.0±5.4) days. Six pregnant women (5 with severe pneumonia and 1 with peripartum cardiomyopathy) successfully evacuated from ECMO and survived. Two pregnant women with pulmonary hypertension showed poor prognosis. In total, seven babies survived. Two of them were delivered after ECMO evacution, and one underwent emergency cesarean section with ECMO support. In another case, the fetus could not be delivered due to under-gestational weeks. During this period, there were no serious bleeding complications. One pregnant woman developed heparin-induced thrombocytopenia and thrombosis (HITT), then she received another anticoagulant treatment. One pregnant woman got sequential anticoagulation therapy for 3 months on account of thrombosis in the puncture vessel. CONCLUSIONS: ECMO has played an active role in the rescue of critically ill pregnant women. For those with reversible severe cardiopulmonary dysfunction, it is necessary to evaluate the application of ECMO as early as possible to improve the survival rate of mothers and infants.

Invasive pulmonary aspergillosis is a frequent complication in patients with severe fever with thrombocytopenia syndrome: A retrospective study.

OBJECTIVES: Invasive pulmonary aspergillosis (IPA) usually occurs in immunocompromised hosts. It has recently been reported that patients with severe fever with thrombocytopenia syndrome (SFTS) can also develop IPA. The aim of this study was to determine the incidence of IPA in SFTS patients and to investigate the relevant clinical, imaging, and laboratory characteristics. METHODS: A retrospective review was conducted of all patients with SFTS admitted to Nanjing Drum Tower Hospital, a tertiary hospital in Nanjing City, China, between January 2016 and December 2019. The patients were divided into two groups according to whether they had IPA: the IPA group and the non-IPA group. Data on clinical manifestations, laboratory findings, imaging characteristics, treatments, and outcomes were collected and analysed. RESULTS: A total of 91 SFTS patients were included, of whom 29 (31.9%) developed IPA. In-hospital mortality (22.0%) was higher in the IPA group than in the non-IPA group. Univariate logistic regression showed that diabetes, cough, wheezing, amylase level, vasopressor use, encephalopathy, and intensive care unit transfer were risk factors for the development of IPA. Multivariate logistic regression analysis identified wheezing as an independent predictor of IPA in SFTS patients. CONCLUSIONS: SFTS combined with IPA is associated with high morbidity and mortality. It is necessary to strengthen screening for fungal infections after admission in SFTS patients. However, whether early antifungal prophylaxis should be administered needs further investigation.

Metagenomic next-generation sequencing in the diagnosis of severe pneumonias caused by Chlamydia psittaci.

PURPOSE: Chlamydia psittaci infection in humans can lead to serious clinical manifestations, including severe pneumonia, adult respiratory distress syndrome, and, rarely, death. Implementation of metagenomic next-generation sequencing (mNGS) gives a promising new tool for diagnosis. The clinical spectrum of severe psittacosis pneumonia is described to provide physicians with a better understanding and to highlight the rarity and severity of severe psittacosis pneumonia. METHODS: Nine cases of severe psittacosis pneumonia were diagnosed using mNGS. Retrospective analysis of the data on disease progression, new diagnosis tool, treatments, and outcomes, and the findings were summarised. RESULTS: Frequent symptoms included chills and remittent fever (100%), cough and hypodynamia (100%), and headache and myalgia (77.8%). All patients were severe psittacosis pneumonia developed respiratory failure, accompanied by sepsis in 6/9 patients. mNGS takes 48-72 h to provide the results, and help to identify diagnosis of psittacosis. Laboratory data showed normal or slightly increased leucocytes, neutrophils, and procalcitonin but high C-reactive protein levels. Computed tomography revealed air-space consolidation and ground-glass opacity, which began in the upper lobe of one lung, and spread to both lungs, along with miliary, nodular, or consolidated shadows. One patient died because of secondary infection with Klebsiella pneumoniae, while the other eight patients experienced complete recoveries. CONCLUSIONS: The use of mNGS can improve accuracy and reduce the delay in diagnosis of psittacosis. Severe psittacosis pneumonia responds well to the timely use of appropriate antibiotics.

Evaluation of the ratio of the estimated area under the concentration-time curve to minimum inhibitory concentration (estimated AUIC) as a predictor of the outcome for tigecycline treatment for pneumonia due to multidrug-resistant bacteria in an intensive care unit.

OBJECTIVES: Based on pharmacokinetics/pharmacodynamics (PK/PD) and the minimum inhibitory concentration (MIC) of tigecycline (TGC), dose increases have been advocated to maximize the efficacy against pneumonia that is suspected to be due to multidrug-resistant (MDR) bacteria in an intensive care unit. This practice-based study explored the relationship between the predicted PK parameter, the ratio of the area under the concentration-time curve to the 24 h of dosing/minimum inhibitory concentration (AUC0-24/MIC or AUIC), and the clinical and microbiological outcomes in critically ill patients with pneumonia due to MDR bacteria. METHODS: We conducted a prospective cohort study of the treatment of pneumonia due to MDR bacteria in an intensive care unit. The study patients were recruited and assigned to either TGC standard dose (SD, 50 mg q12 h) or high dose (HD, 100 mg q12 h) for the treatment of pneumonia due to MDR bacteria depending on the doctors' decisions. The relationships between the PK/PD parameters and outcomes were examined. RESULTS: Over the study period, 105 patients were included in the study. Whereas C1/2, Cmin, MIC and AUC were dramatically higher in the HD group than in the SD group (all P < 0.05), the Cmax and AUIC had no difference in both groups (all P > 0.05). The patients in the HD group had a higher clinical cure rate than those in the SD group (P = 0.029), but the bacterial eradication rate and survival rate of the patients in the HD group were not better than those in SD group (P = 0.279 and 0.416, respectively). The Cmax, C1/2, Cmin and AUC in the cured group were higher than those in failure group (all P < 0.05). The MICs were dramatically higher in the failure group than those in cure group (P = 0.0001), which led to significantly lower AUICs (P = 0.0001). In the ROC analysis, the areas of Cmax, C1/2, Cmin, AUC, negative-MIC and AUIC under the ROC curve were 0.64, 0.69, 0.67, 0.66, 0.73 and 0.82, respectively. The sensitivity was ascertained to be 75% and the specificity was 89% when the AUIC cut-off value was considered to be 10.12. Moreover, the sensitivity was ascertained to be 63% and the specificity was 80% when the MIC cut-off value was considered to be 1.75 mg/L. CONCLUSIONS: The AUIC and MIC are associated with tigecycline treatment outcomes in pneumonia due to MDR bacteria, and aiming to achieve an individualized AUIC ≥ 10.12 when MIC < 1.75 mg/L could improve outcomes.

[Clinical study of vancomycin for appropriate dosing in severe infective patients with augmented renal clearance].

OBJECTIVE: To explore the impact of augmented renal clearance (ARC) on vancomycin pharmacokinetic target attainment in severe infective patients, and to analyze the initial dose of vancomycin based on the measured 12-hour urinary creatinine clearance (12 h-CLCR). METHODS: A retrospective observational study was conducted. The patients with severe infection, who receiving vancomycin empiric or targeted therapy, admitted to intensive care unit (ICU) of the Affiliated Drum Tower Hospital of Nanjing University Medical School from February 2013 to December 2017 were enrolled. All patients were treated with vancomycin intravenously by intermittent bolus every 6-12 hours. After four or five doses, blood samples were drawn before the next dosage for serum trough vancomycin concentration (Cmin), and target concentration was defined between 15 mg/L and 20 mg/L. The urine creatinine (UCr) was measured, and CLCR was calculated. ARC was defined as 12 h-CLCR > 130 mL×min-1×1.73 m-2. According to 12 h-CLCR before treatment, the patients were divided into ARC group and non-ARC group. The basic renal function of the patients was monitored, and the dosage of vancomycin and the dosage of vancomycin when the blood concentration reached the target were recorded. The correlations between 12 h-CLCR and the dosage of vancomycin when the blood concentration reached the target as well as the blood concentration of vancomycin were analyzed by Spearman correlation analysis. Dosage stratification analysis was carried out according to different 12 h-CLCR. The predictive value of 12 h-CLCR for vancomycin dosage when the blood concentration reached the target was evaluated by using the receiver operator characteristic curve (ROC). RESULTS: Data was provided from a total of 135 patients with severe infection, in which 102 patients met the inclusion criteria. The patients with vancomycin treatment duration less than 72 hours, chronic kidney disease V phase, vancomycin treatment before entering ICU and those with incomplete data were excluded. The mean 12 h-CLCR was (114.31±73.38) mL×min-1×1.73 m-2. The 12 h-CLCR in ARC group (n = 44, 43.14%) was significantly higher than that in non-ARC group (n = 58, 56.86%) (mL×min-1×1.73 m-2: 179.37±59.04 vs. 65.95±35.71, P < 0.01). Target Cmin of vancomycin was achieved in 50.98% of patients (52/102), the target rate in ARC group was significantly lower than that in non-ARC group [29.55% (13/44) vs. 67.24% (39/58), P < 0.01], and the Cmin of vancomycin in ARC group was significantly lower than that in non-ARC group (mg/L: 10.98±6.09 vs. 14.67±6.20, P < 0.01). Spearman correlation analysis showed that there was a significantly negative correlation between 12 h-CLCR and initial Cmin of vancomycin (n = 102, r = -0.436, P < 0.001), but a positive correlation was found between 12 h-CLCR and vancomycin dosage when the blood concentration reached the target (n = 52, r = 0.275, P = 0.048). The patients with ARC need higher dosage for blood concentration reaching the target than those without ARC (mg×kg-1×d-1: 42.47±13.17 vs. 31.53±14.43, P < 0.01). According to 12 h-CLCR, the patients with initial treatment reaching the target were divided into five subgroups, < 40, 40-70, 71-100, 101-130 and > 130 mL×min-1×1.73 m-2. The results showed that as 12 h-CLCR increased, the attained dosage of vancomycin was also increased correspondingly. ROC curve analysis showed that when 12 h-CLCR≥69.83 mL×min-1×1.73 m-2, the attained dose of vancomycin when the blood concentration reached the target was greater than conventional dosage of 30 mg×kg-1×d-1. CONCLUSIONS: Patients with ARC have low concentrations of vancomycin and often fail to achieve therapeutic target. The initial dose of vancomycin can be selected according to 12 h-CLCR, the higher the 12 h-CLCR, the more the dosage of vancomycin is. When 12 h-CLCR is greater than or equal to 69.83 mL×min-1×1.73 m-2, the dosage of vancomycin should be higher than the conventional dosage.

Clinical features of fatal severe fever with thrombocytopenia syndrome that is complicated by invasive pulmonary aspergillosis.

INTRODUCTION: Severe fever with thrombocytopenia syndrome (SFTS) has been prevalent in parts of Asia during recent years. However, SFTS with invasive pulmonary aspergillosis (IPA) is rare, and it is important to understand its clinical features. MATERIALS AND METHODS: Total four cases of SFTS with IPA are reviewed and detailing the disease progression, treatment options, and prognosis were summarized and analyzed. RESULTS: The patients with SFTS-associated IPA first presented with fever, gastrointestinal symptoms, thrombocytopenia, leukopenia, and multiple organ failure. After 1-2 weeks, the patients developed mild polypnea and wheezing rales, and quickly developed dyspnea and respiratory failure. Tracheal intubation was usually performed, but did not relieve the intractable airway spasm and pulmonary ventilation failure. Bronchoscopy confirmed that the antifungal treatment was ineffective and the aspergillosis had worsened. All patients died of type 2 respiratory failure caused by continued airway obstruction and spasticity. CONCLUSIONS: Given the high mortality rate in this series, there is a need for increased awareness of SFTS-associated IPA. Additional examinations should be performed in these cases, and early-stage antifungal treatment with organ support may be helpful.

Profiles of acute cytokine and antibody responses in patients infected with avian influenza A H7N9.

The influenza A H7N9 virus outbreak in Eastern China in the spring of 2013 represented a novel, emerging avian influenza transmission to humans. While clinical and microbiological features of H7N9 infection have been reported in the literature, the current study investigated acute cytokine and antibody responses in acute H7N9 infection. Between March 27, 2013 and April 23, 2013, six patients with confirmed H7N9 influenza infection were admitted to Drum Tower Hospital, Nanjing, China. Acute phase serum cytokine profiles were determined using a high-throughput multiplex assay. Daily H7 hemagglutinin (HA)-specific IgG, IgM, and IgA responses were monitored by ELISA. Neutralizing antibodies specific for H7N9 viruses were determined against a pseudotyped virus expressing the novel H7 subtype HA antigen. Five cytokines (IL-6, IP-10, IL-10, IFNγ, and TNFα) were significantly elevated in H7N9-infected patients when compared to healthy volunteers. Serum H7 HA-specific IgG, as well as IgM and IgA responses, were detected within 8 days of disease onset and increased in a similar pattern during acute infection. Neutralizing antibodies developed shortly after the appearance of binding antibody responses and showed similar kinetics as a fraction of the total H7 HA-specific IgG responses. H7N9 infection resulted in hallmark serum cytokine increases, which correlated with fever and disease persistence. The novel finding of simultaneous development of IgG, IgM, and IgA responses in acute H7N9 infection points to the potential for live influenza viruses to elicit fast and potent protective antibodies to limit the infection.

Human infection with a novel avian-origin influenza A (H7N9) virus: serial chest radiographic and CT findings.

BACKGROUND: Rapidly progressive pneumonia infection with H7N9 virus is a novel disease, and limited information is available concerning serial chest radiographic and computed tomography (CT) findings. The aim of this study was to evaluate the changes in serial radiologic findings in patients with H7N9 pneumonia. METHODS: The two institutional ethics review boards approved this retrospective study. This study included 10 patients with H7N9 pneumonia. All patients underwent chest radiologic examinations at different time points. Serial radiologic images were systematically analyzed. RESULTS: All patients showed abnormal results on initial chest radiography and CT. The initial radiographic abnormalities were unilateral (n = 9) and bilateral (n = 1), including ground-glass opacities (GGOs) (n = 5) and consolidation (n = 5). The initial CT findings consisted of unilateral (n = 6) and bilateral (n = 4), including consolidation (n = 10), GGOs (n = 10), reticular opacities (n = 2), and pleural effusion (n = 3). Follow-up radiologic findings showed rapid development of consolidation or GGOs within two weeks after illness onset. Pneumomediastinum with secondary subcutaneous emphysema and pneumothorax were noted in two patients. Follow-up high resolution computed tomography (HRCT) after two weeks showed slow improvement in both size and opacity of the lesions. On HRCT after discharge, patients had substantial residual lesions such as irregular linear opacities, reticular opacities, parenchymal bands, traction bronchiectasis, and cystic lesions. CONCLUSIONS: The most common radiologic findings at presentation are multifocal or diffuse areas of consolidation and GGOs in H7N9 pneumonia. HRCT in sequence can show more changes in rapid progression of disease and a slow decrease of both size and opacity of the lesions plays an important role in the evaluation of H7N9 pneumonia.

Epidemiological and clinical characteristics and risk factors for death of patients with avian influenza A H7N9 virus infection from Jiangsu Province, Eastern China.

BACKGROUND: A novel avian influenza A (H7N9) virus has caused great morbidity as well as mortality since its emergence in Eastern China in February 2013. However, the possible risk factors for death are not yet fully known. METHODS AND FINDINGS: Patients with H7N9 virus infection between March 1 and August 14, 2013 in Jiangsu province were enrolled. Data were collected with a standard form. Mean or percentage was used to describe the features, and Fisher's exact test or t-test test was used to compare the differences between fatal and nonfatal cases with H7N9 virus infection. A total of 28 patients with H7N9 virus infection were identified among whom, nine (32.1%) died. The median age of fatal cases was significant higher than nonfatal cases (P<0.05). Patients with older age were more strongly associated with increased odds of death (OR = 30.0; 95% CI, 2.85-315.62). Co-morbidity with chronic lung disease and hypertension were risk factors for mortality (OR = 14.40; 95% CI, 1.30-159.52, OR = 6.67; 95% CI, 1.09-40.43, respectively). Moreover, the presence of either bilateral lung inflammation or pulmonary consolidation on chest imaging on admission was related with fatal outcome (OR = 7.00; 95%CI, 1.10-44.61). Finally, dynamic monitoring showed that lymphopenia was more significant in fatal group than in nonfatal group from day 11 to week five (P<0.05). The decrease in oxygenation indexes were observed in most cases and more significantly in fatal cases after week three (P<0.05), and the value of nearly all fatal cases were below 200 mmHg during our evaluation period. CONCLUSIONS: Among cases with H7N9 virus infection, increased age accompanied by co-morbidities was the risk of death. The severity of lung infection at admission, the persistence of lymphocytopenia, and the extended duration of lower oxygenation index all contributed to worsened outcomes of patients with H7N9 virus infection.

[Effects of lung recruitment maneuver on oxygenation and hemodynamics after open endotracheal suctioning in acute respiratory distress syndrome].

OBJECTIVE: To evaluate the treatment value of lung recruitment (LR) maneuver on oxygenation and hemodynamics in acute respiratory distress syndrome (ARDS) patients after open endotracheal suctioning (ETS). METHODS: Twenty ARDS/acute lung injury (ALI) patients requiring mechanical ventilation support were randomized into two groups after stabilizing for 30 minutes. Group 1: LRs were performed immediately after ETS (ETS+LR), and then ETS was repeated after 60 minutes without LR. Group 2: the first ETS was performed without LR (ETS-LR), and the second ETS was combined with LR after 60 minutes. Partial pressure of oxygen in artery (PaO(2)), central venous pressure (CVP), heart rate (HR) and mean arterial pressure (MAP) were serially measured during the procedure. RESULTS: The hemodynamic parameters were stable in all patients, and no arrhythmia occurred. PaO(2) decreased significantly after ETS, but recovered rapidly in 5 and 15 minutes after LR (both P<0.05). CONCLUSION: LR is effective in rapidly counteracting the deterioration in PaO(2) caused by open ETS in ARDS/ALI patients without interfering the hemodynamics.