[Effect of enteral nutritional support on clinical outcomes of patients with sepsis].

OBJECTIVE: To research whether clinical outcomes of patients with sepsis can be improved by higher enteral nutritional support. METHODS: A retrospective cohort method was applied. 145 patients with sepsis who were hospitalized in intensive care unit (ICU) of Peking University Third Hospital from September, 2015 to August, 2021 and met inclusion criteria as well as exclusion criteria were selected, including 79 males and 66 females, the median age was 68 (61, 73). Researchers evaluated whether there was correlation between improved modified nutrition risk in critically ill score (mNUTRIC), daily energy intake and protein supplement of patients and their clinical outcomes through Poisson log-linear regression analysis and Cox regression analysis. RESULTS: The median of mNUTRIC score of 145 hospitalized patients was 6 (3, 10), wherein 70.3% of patients (102 cases) were in high-score group (≥ 5 scores) and 29.7% of patients (43 cases) were in low-score group (< 5 scores); the average of daily protein intake in ICU was about 0.62 (0.43, 0.79) g×kg-1×d-1, and the average of daily energy intake was about 64.4 (48.1, 86.2) kJ×kg-1×d-1. As shown by Cox regression analysis, increase of mNUTRIC score, sequential organ failure assessment (SOFA), and acute physiology and chronic health evaluation II (APACHE II) were correlated to growth of in-hospital mortality [hazard ratio (HR) = 1.12, 95% confidence interval (95%CI) was 1.08-1.16, P = 0.006; HR = 1.04, 95%CI was 1.01-1.08, P = 0.030; HR = 1.08, 95%CI was 1.03-1.13, P = 0.023]. Higher average daily intake of protein and energy as well as lower mNUTRIC, SOFA, and APACHE II scores were also significantly correlated to lower 30-day mortality (HR = 0.45, 95%CI was 0.25-0.65, P < 0.001; HR = 0.77, 95%CI was 0.61-0.93, P < 0.001; HR = 1.10, 95%CI was 1.07-1.13, P < 0.001; HR = 1.07, 95%CI was 1.02-1.13, P = 0.041; HR = 1.15, 95%CI was 1.05-1.23, P = 0.014); however, there was no significant correlation between gender as well as number of complications and in-hospital mortality. Within 30 days of attack of sepsis, the average daily intake of protein and energy were not correlated to days of non-ventilator (HR = 0.66, 95%CI was 0.59-0.74, P = 0.066; HR = 0.78, 95%CI was 0.63-0.93, P = 0.073). Increase of patients' average daily intake of protein and energy were significantly correlated to a lower in-hospital mortality (HR = 0.41, 95%CI was 0.32-0.50, P < 0.001; HR = 0.87, 95%CI was 0.84-0.92, P < 0.001), shorter ICU stay (HR = 0.46, 95%CI was 0.39-0.53, P < 0.001; HR = 0.82, 95%CI was 0.78-0.86, P < 0.001), and hospital stay (HR = 0.51, 95%CI was 0.44-0.58, P < 0.001; HR = 0.77, 95%CI was 0.68-0.88, P < 0.001). According to correlation analysis, among patients with mNUTRIC score ≥ 5, increasing daily intake of protein and energy can reduce in-hospital mortality (HR = 0.44, 95%CI was 0.32-0.58, P < 0.001; HR = 0.73, 95%CI was 0.69-0.77, P < 0.001), and 30-day mortality (HR = 0.51, 95%CI was 0.37-0.65, P < 0.001; HR = 0.90, 95%CI was 0.85-0.96, P < 0.001); the receiver operator characteristic curve (ROC curve) further confirmed that higher protein intake had good predictive value for inpatient mortality area under the curve (AUC) = 0.96 and 30-day mortality (AUC = 0.94); higher emergy intake had good predictive value for inpatient mortality (AUC = 0.87) and 30-day mortality (AUC = 0.83). By contrast, among patients with mNUTRIC score < 5, it is only discovered that increasing daily intake of protein and energy can reduce 30-day mortality of patients (HR = 0.76, 95%CI was 0.69-0.83, P < 0.001). CONCLUSIONS: The increase of average daily intake of protein and energy for patients with sepsis is significantly correlated to reduction of in-hospital mortality and 30-day mortality, shorter ICU stay, and hospital stay. The correlation is more significant in patients with high mNUTRIC score, and higher intake of protein and energy can bring down in-hospital mortality and 30-day mortality. As for patients with low mNUTRIC score, nutritional support cannot improve prognosis of the patients significantly.

[Incidence of maternal sepsis in ICUs of hospitals in Beijing: a multicenter cohort study].

OBJECTIVE: To investigate the epidemiological data of maternal sepsis in intensive care unit (ICU), analyze the common causes, outcomes of maternal sepsis, and the risk factors of multi-drug resistant (MDR) bacteria. METHODS: A retrospective cohort study. Maternal sepsis cases admitted to ICUs of Peking University Third Hospital, Beijing Chao-Yang Hospital Affiliated to Capital Medical University, and Beijing Friendship Hospital Affiliated to Capital Medical University from January 2008 to September 2022 were enrolled. The following data were recorded: demographic characteristics, sequential organ failure assessment (SOFA) during infection, infection time, infection sites, invasive intervention measures before infection, microbial culture results, blood routine test during infection, body temperature, and clinical outcomes caused by infection. According to the time of sepsis occurrence, the patients were divided into pre-ICU sepsis group and ICU sepsis group, and the causes of sepsis in the two groups were analyzed. According to whether MDR occurred, the patients were divided into MDR group and non-MDR group, and clinical outcomes were analyzed. Multivariate Logistic regression was used to analyze the risk factors of MDR bacteria infection in obstetrics with sepsis. RESULTS: 160 patients were enrolled, among which 104 cases of sepsis happened before ICU and 56 cases of sepsis happened during ICU, 53 cases were with MDR bacteria and 107 cases were without MDR bacteria. The median age of the patients was 30.5 (28.0, 34.0) years old, the median temperature was 38.8 (38.2, 39.5) centigrade, and the median white blood cell count (WBC) was 17.2 (13.2, 21.3)×109/L, the median SOFA score was 5.0 (3.0, 8.0), and 130 cases (81.2%) were referred from other hospitals. The main infection sites were uterine cavity in 64 cases (40.0%), lung in 48 cases (30.0%), abdominal and pelvic cavity in 30 cases (18.8%), urinary system in 27 cases (16.9%). Sepsis led to hysterectomy in 6 cases (3.8%), stillbirth in 8 cases (5.0%), and neonatal death in 2 cases (1.3%). The main surgical intervention measures were cesarean section (44 cases, accounting for 27.5%), followed by exploratory laparotomy (19 cases, 11.9%). The median length of ICU stay was 5.0 (3.0, 10.0) days, and the median hospital length was 14.0 (10.0, 20.8) days. Intrauterine infection was the primary cause of sepsis happened during ICU, accounting for 50.0% (28/56), of which postpartum hemorrhage accounted for 85.7% (24/28). The proportion of diabetes [28.3% (15/53) vs. 14.0% (15/107)], intrauterine operation [41.5% (22/53) vs. 23.4% (25/107)], intrauterine infection [50.9% (27/53) vs. 34.6% (37/107)] and bacteremia [18.9% (10/53) vs. 2.8% (3/107)] in the MDR group were significantly higher than those in the non-MDR group (all P < 0.05). Multivariate Logistic regression analysis showed that diabetes [odds ratio (OR) = 2.348, 95% confidence interval (95%CI) was 1.006-5.480, P = 0.048] and intrauterine operation (OR = 2.541, 95%CI was 1.137-5.678, P = 0.023) were independent risk factors for MDR bacterial infection in obstetrics with sepsis. CONCLUSIONS: Intrauterine infection is the common cause of maternal sepsis in ICU, and postpartum hemorrhage is the common cause of secondary intrauterine infection in ICU. MDR bacteria can lead to serious clinical outcomes. Diabetes and intrauterine operation are independent risk factors for MDR bacteria' infection.

[Analysis of risk factors of hyperpyrexia suffered by post neurosurgical patients after removal of drainage tube].

OBJECTIVE: To analyze the risk factors of hyperthermia after removal of drainage tubes in patients after neurosurgery. METHODS: The clinical data of 146 patients after neurosurgery with indwelling drainage tubes admitted to the department of critical care medicine of Pecking University Third Hospital from January 2019 to July 2021 were analyzed retrospectively. The patients were divided into hyperthermia group (body temperature ≥ 39 centigrade) and non-hyperthermia group (body temperature < 39 centigrade) according to whether their body temperatures within 24 hours after removal of drainage tubes. General clinical data and outcomes of the two groups were collected, and different tendentious scores were matched with the hyperthermia group and non-hyperthermia group based on Glasgow coma score (GCS), respectively. After such matching, the clinical baseline characteristics [age, gender, admission diagnosis, major complications, acute physiology and chronic health evaluation II (APACHE II) at admission, GCS], number of days of drainage tubes retention, location of drainage tubes, microbial culture results before removal of drainage tubes, white blood cell (WBC) and neutrophil ratio (NEU%) before and after removal of drainage tubes as well as clinical outcomes of the cohort patients were analyzed. The primarily outcome was in-hospital mortality, and then the length of intensive care unit (ICU) stay. RESULTS: A total of 146 patients after neurosurgery were included, 28 of which developed hyperthermia after removal of drainage tubes. The GCS scores at admission in the hyperthermia group were significantly lower than that in the non-hyperthermia group, while the proportion of hypertension and diabetes in the hyperthermia group was significantly higher than that in the non-hyperthermia group. Based on GCS scores, the two groups, each of which included 28 patients, were matched with tendentious scores, and there was no significant difference in gender, age, GCS scores and the proportion of hypertension and diabetes between the two groups. The main disease for patients upon admission was cerebral hemorrhage (53.6%, 30/56). The proportion of indwelling ventricular drainage tube retention in the hyperthermia group was significantly higher than that in the non-hyperthermia group [32.1% (9/28) vs. 7.1% (2/28), P < 0.05], but there was no significant difference in the location of other drainage tubes between the two groups. The proportion of lumbar puncture in the hyperthermia group was also significantly higher than that in the non-hyperthermia group [25.0% (7/28) vs. 0 (0/28), P < 0.05]. Compared with the non-hyperthermia group, WBC [×109/L: 13.0 (9.5, 15.2) vs. 11.5 (8.8, 13.3)] of 1 day before removal of drainage tubes, NEU% [0.892 (0.826, 0.922) vs. 0.843 (0.809, 0.909)] after removal of drainage tubes and positive rate of drainage-fluid culture or drainage-tube-tip culture [7.1% (2/28) vs. 0% (0/28)] in the hyperthermia group increased, but there were not significant differences. There was no significant difference in the proportion of pulmonary, urinary system and blood flow infection before removal of drainage tubes in the two groups. In terms of primary outcomes, compared with the non-hyperthermia group, the length of ICU stay [days: 17.0 (8.0, 32.3) vs. 8.5 (1.0, 16.8), P < 0.05] in the hyperthermia group was significantly prolonged, and the in-hospital mortality [35.7% (10/28) vs. 10.7% (3/28), P < 0.05] in the hyperthermia group was obviously increased. The positive rate of carbapenem-resistant bacteria culture [32.1% (9/28) vs. 3.6% (1/28), P < 0.05] in the hyperthermia group during hospitalization was significantly higher than that in the non-hyperthermia group. CONCLUSIONS: Hyperthermia after removal of drainage tubes for patients after neurosurgery can significantly prolong the length of ICU stay and increase the in-hospital mortality, which may be related to the secondary infection caused by indwelling intracranial drainage tubes and the intracranial spread of bacteria caused by removal of drainage tubes, as well as the intracranial multidrug-resistant bacterial infection caused by the drainage tubes.

Features of gut microbiota in patients with anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN) is a psychological disorder, which is characterized by the misunderstanding of body image, food restriction, and low body weight. An increasing number of studies have reported that the pathophysiological mechanism of AN might be associated with the dysbiosis of gut microbiota. The purpose of our study was to explore the features of gut microbiota in patients with AN, hoping to provide valuable information on its pathogenesis and treatment. METHODS: In this cross-sectional study, from August 2020 to June 2021, patients with AN who were admitted into Peking University Third Hospital and Peking University Sixth Hospital ( n   =  30) were recruited as the AN group, and healthy controls (HC) were recruited from a middle school and a university in Beijing ( n   =  30). Demographic data, Hamilton Depression Scale (HAMD) scores of the two groups, and length of stay of the AN group were recorded. Microbial diversity analysis of gut microbiota in stool samples from the two groups was analyzed by 16S ribosomal RNA (rRNA) gene sequencing. RESULTS: The weight (AN vs. HC, [39.31 ±â€Š7.90] kg vs. [56.47 ±â€Š8.88] kg, P  < 0.001) and body mass index (BMI, AN vs. HC, [14.92 ±â€Š2.54] kg/m 2vs. [20.89 ±â€Š2.14] kg/m 2 , P  < 0.001) of patients with AN were statistically significantly lower than those of HC, and HAMD scores in AN group were statistically significantly higher than those of HC. For alpha diversity, there were no statistically significant differences between the two groups; for beta diversity, the two groups differed obviously regarding community composition. Compared to HC, the proportion of Lachnospiraceae in patients with AN was statistically significantly higher (AN vs. HC, 40.50% vs. 31.21%, Z  = -1.981, P  = 0.048), while that of Ruminococcaceae was lower (AN vs. HC, 12.17% vs. 19.15%, Z  = -2.728, P  = 0.007); the proportion of Faecalibacterium (AN vs. HC, 3.97% vs. 9.40%, Z  = -3.638, P  < 0.001) and Subdoligranulum (AN vs. HC, 4.60% vs. 7.02%, Z  = -2.369, P  = 0.018) were statistically significantly lower, while that of Eubacterium_hallii_group was significantly higher (AN vs. HC, 7.63% vs. 3.43%, Z  = -2.115, P  = 0.035). Linear discriminant effect (LEfSe) analysis (LDA score >3.5) showed that o_Lachnospirales, f_Lachnospiraceae, and g_Eubacterium_hallii_group (o, f and g represents order, family and genus respectively) were enriched in patients with AN. Microbial function of nutrient transport and metabolism in AN group were more abundant ( P  > 0.05). In AN group, weight and BMI were significantly negatively correlated with the abundance of Bacteroidota and Bacteroides , while positively correlated with Subdoligranulum . BMI was significantly positively correlated with Firmicutes; HAMD scores were significantly negatively correlated with Faecalibacterium. CONCLUSIONS: The composition of gut microbiota in patients with AN was different from that of healthy people. Clinical indicators have correlations with the abundance of gut microbiota in patients with AN.

Rapid identification of pathogens associated with ventilator-associated pneumonia by Nanopore sequencing.

BACKGROUND: Aetiology detection is crucial in the diagnosis and treatment of ventilator-associated pneumonia (VAP). However, the detection method needs improvement. In this study, we used Nanopore sequencing to build a quick detection protocol and compared the efficiency of different methods for detecting 7 VAP pathogens. METHODS: The endotracheal aspirate (ETA) of 83 patients with suspected VAP from Peking University Third Hospital (PUTH) was collected, saponins were used to deplete host genomes, and PCR- or non-PCR-amplified library construction methods were used and compared. Sequence was performed with MinION equipment and local data analysis methods were used for sequencing and data analysis. RESULTS: Saponin depletion effectively removed 11 of 12 human genomes, while most pathogenic bacterial genome results showed no significant difference except for S. pneumoniae. Moreover, the average sequence time decreased from 19.6 h to 3.62 h. The non-PCR amplification method and PCR amplification method for library build has a similar average sensitivity (85.8% vs. 86.35%), but the non-PCR amplification method has a better average specificity (100% VS 91.15%), and required less time. The whole method takes 5-6 h from ETA extraction to pathogen classification. After analysing the 7 pathogens enrolled in our study, the average sensitivity of metagenomic sequencing was approximately 2.4 times higher than that of clinical culture (89.15% vs. 37.77%), and the average specificity was 98.8%. CONCLUSIONS: Using saponins to remove the human genome and a non-PCR amplification method to build libraries can be used for the identification of pathogens in the ETA of VAP patients within 6 h by MinION, which provides a new approach for the rapid identification of pathogens in clinical departments.

[Clinical characteristics of critically ill pregnant women with different admission methods to intensive care unit: data analysis from 2006 to 2019 in the university hospital].

OBJECTIVE: To compare the clinical characteristics of critically ill pregnant women admitted to the intensive care unit (ICU) with different admission methods, in order to make more effective and rational use of ICU resources. METHODS: A retrospective study was conducted. The clinical data of critically ill pregnant women admitted to ICU of Peking University Third Hospital from January 2006 to July 2019 were analyzed. According to the admission mode to ICU, the pregnant women were divided into emergency admission group (transferred to ICU on the same day or the next day due to critical illness) and planned admission group (transferred to ICU 2 days after admitting in obstetric ward). The clinical characteristics of ICU critical pregnant women, such as the incidence, causes of admission, severity of the disease, main treatment measures, mortality, and medical expenses were collected, and a comparative analysis between the two groups was performed. RESULTS: During the nearly 14 years, a total of 576 critical pregnant women in ICU were enrolled, accounting for 0.8% (576/71 790) of the total number of obstetric inpatients and 4.6% (576/12 412) of the total number of ICU inpatients. Seven maternal deaths accounted for 1.2% of all critically pregnant women transferred to ICU, and the overall mortality of pregnant women was 10/100 thousand. Of the 576 critically pregnant women, there were 327 patients (56.8%) in the emergency admission group and 249 patients (43.2%) in the planned admission group. Compared with the planned admission group, the proportion of elective cesarean section in the emergency admission group was significantly lower (17.7% vs. 94.0%, P < 0.01), and the proportion of emergency cesarean section was significantly higher (65.1% vs. 2.4%, P < 0.01), the acute physiology and chronic health evaluation (APACHE II, APACHE III) scores, simplified acute physiology score II (SAPS II) and Marshall score were significantly higher [APACHE II score: 6.0 (4.0, 9.8) vs. 4.0 (3.0, 7.0), APACHE III score: 14.0 (11.0, 20.3) vs. 12.0 (9.0, 16.0), SAPS II score: 8 (0, 12) vs. 3 (0, 8), Marshall score: 2 (1, 4) vs. 1 (1, 3), all P < 0.01]. The length of ICU stay in the emergency admission group was significantly longer than that in the planned admission group [days: 2 (1, 5) vs. 2 (1, 3), P < 0.01], and the total length of hospital stay was significantly shorter [days: 9 (7, 13) vs. 13 (10, 18), P < 0.01]. Both in the emergency admission group and the planned admission group, obstetric factors were the main reason for admission, 60.9% (199/327) and 70.3% (175/249), respectively. The proportion of postpartum hemorrhage was the highest [35.2% (115/327) and 57.0% (142/249)], followed by preeclampsia/eclampsia [7.0% (23/327) and 7.6% (19/249)]. Only 7 of the 19 critically pregnant women with puerperal infection were planned admission. All 21 patients with acute fatty liver of pregnancy (AFLP) during pregnancy were emergency admission. Among the emergency and planned admission patients, 73 patients (22.3%) and 42 patients (16.9%) required mechanical ventilation (duration of mechanical ventilation > 24 hours), 99 patients (30.3%) and 35 patients (14.1%) needed vasoactive agents, 67 patients (20.5%) and 20 patients (8.0%) received hemodynamic monitoring, and 123 patients (37.6%) and 154 patients (61.8%) were given anticoagulation therapy, respectively. In terms of severity score of critical pregnant women, there were significant differences in APACHE II, APACHE III, SAPS II and Marshall scores of pregnant women with different diseases. Among them, the APACHE III, SAPS II and Marshall scores of AFLP were the highest [21.0 (15.0, 32.5), 12.0 (6.0, 16.5) and 6.0 (3.5, 8.0), respectively]. The APACHE II and APACHE III scores of postpartum hemorrhage were the lowest [4.0 (3.0, 7.0), 12.0 (10.0, 16.0)]. The SAPS II score of pneumonia was the lowest [2.0 (0, 14.0)]. The Marshall score for puerperal infection was the lowest [1.0 (0, 3.0)]. In terms of the total medical expenses, the cost in the emergency admission group was significantly lower than that in the planned admission group [10 thousand Yuan: 3.1 (2.0, 4.7) vs. 4.1 (2.9, 5.8), P < 0.05]. CONCLUSIONS: Compared with the critically ill pregnant women who planned to be admitted to ICU, the patients emergency admitted to ICU were more complicated and urgent, and the severity of the condition was scored higher. At present, the severity scoring system commonly used in ICU can only partly evaluate the severity of critically ill pregnant women, therefore, it is necessary to design the specific severity scoring system for critically ill pregnant women to effectively and rationally use the precious ICU resources.

Disseminated intravascular coagulation associated organ failure in obstetric patients admitted to intensive care units: a multicenter study in China.

We aimed to determine disseminated intravascular coagulation (DIC)-associated organ failure and underlying diseases based on data from three ICU wards in tertiary hospitals in China from 2008 to 2016. The diagnosis of DIC was confirmed by an International Society of Thrombosis and Hemostasis score greater than or equal to 5. The maternal outcomes included the changes in organ function 24 h after ICU admission. The durations of hospital stay and ICU stay were recorded as secondary outcomes. Among 297 ICU admissions (median Sequential Organ Failure Assessment score, 4) for obstetric diseases, there were 87 DIC cases, with an estimated DIC incidence of 87 per 87,580 deliveries. Postpartum hemorrhage was the leading disease associated with DIC (71, 81.6%), followed by hypertensive disorders (27, 31.0%), sepsis (15, 17.2%), acute fatty liver of pregnancy (11, 12.6%) and amniotic fluid embolism (10, 11.5%). Compared with patients without DIC, those with DIC had higher rates of multiple organ dysfunction syndrome/death (27.6% vs 4.8%, p = 0.000), organ failure (36.8% vs 24.3%, p = 0.029), among which organ failure included acute renal failure (32.2% vs 10.0%, p = 0.000), respiratory failure (16.1% vs 8.6%, p = 0.057), disturbance of consciousness (12.6% vs 2.4%, p = 0.000) and DIC group also had higher rates of massive transfusion (52.9% vs 21.9%, p = 0.000), hysterectomy (32.2% vs 15.7%, p = 0.001), longer ICU (4 days vs 2 days, p = 0.000) and hospital stays (14 days vs 11 days, p = 0.005). DIC and amniotic fluid embolism were independent risk factors for organ failure in patients admitted to the ICU. Postpartum hemorrhage was the leading cause of DIC associated organ failure in obstetrics admitted to the ICU. The control of obstetric bleeding in a timely manner may improve obstetric prognoses.

Pharmacokinetic-pharmacodynamic analysis of ciprofloxacin in elderly Chinese patients with lower respiratory tract infections caused by Gram-negative bacteria.

BACKGROUND: Ciprofloxacin is usually used in the treatment of lower respiratory tract infections (LRTIs). Recent studies abroad have shown ciprofloxacin is inadequately dosed and might lead to worse outcomes. The aim of this study was to perform pharmacokinetic and pharmacodynamic analyses of ciprofloxacin in elderly Chinese patients with severe LRTIs caused by Gram-negative bacteria. METHODS: From September 2012 to June 2014, as many as 33 patients were empirically administered beta-lactam and ciprofloxacin combination therapy. Patients were infused with 200 or 400 mg of ciprofloxacin every 12 h, which was determined empirically by the attending physician based on the severity of the LRTI and the patient's renal condition. Ciprofloxacin serum concentrations were determined by high-performance liquid chromatography. Bacterial culture was performed from sputum samples and/or endotracheal aspirates, and the minimum inhibitory concentrations (MICs) of ciprofloxacin were determined. The ratios of the area under the serum concentration-time curve to the MIC (AUC/MIC) and of the maximum serum concentration of the drug to the MIC (Cmax/MIC) were calculated. The baseline data and pharmacokinetic parameters were compared between clinical success group and clinical failure group, bacteriologic success group and bacteriologic failure group. RESULTS: Among the 33 patients enrolled in the study, 17 were infected with Pseudomonas aeruginosa, 14 were infected with Acinetobacter baumannii, and two were infected with Klebsiella pneumoniae. The mean age of the patients was 76.9 ± 6.7 years. Thirty-one patients (93.4%) did not reach the target AUC/MIC value of >125, and 29 patients (87.9%) did not reach the target Cmax/MIC value of >8. The AUC/MIC and Cmax/MIC ratios in the clinical success group were significantly higher than those in the clinical failure group (61.1 [31.7-214.9] vs. 10.4 [3.8-66.1], Z = -4.157; 9.6 [4.2-17.8] vs. 1.3 [0.4-4.7], Z = -4.018; both P < 0.001). The AUC/MIC and Cmax/MIC ratios in the patients for whom the pathogens were eradicated were significantly higher than those in the patients without the pathogens eradicated (75.3 [31.7-214.9] vs. 10.5 [3.8-66.1], Z = -3.938; 11.4 [4.2-17.8] vs. 1.4 [0.4-5.4], Z = -3.793; P < 0.001 for both). Receiver operating characteristic curve analysis showed that the AUC/MIC and Cmax/MIC values were closely associated with clinical and bacteriologic efficacies (P < 0.001 in both). CONCLUSIONS: Ciprofloxacin is inadequately dosed against Gram-negative bacteria, especially for those with relatively high MIC values. Consequently, the target values, AUC/MIC > 125 and Cmax/MIC > 8, cannot be reached.

[Population pharmacokinetics of ciprofloxacin in Chinese elderly patients with lower respiratory tract infection].

OBJECTIVE: To analyse population pharmacokinetic (PPK) parameter values of ciprofloxacin in Chinese elderly patients with lower respiratory tract infection. METHODS: Hospitalized in Respiratory Intensive Care Unit (RICU) due to severe lower respiratory tract infection and at high risks of Pseudomonas aeruginosa. 43 consecutive elderly patients received an intravenous infusion of ciprofloxacin at a dose of 200/400 mg every 12/24 h empirically. Plasma samples were drawn from Day 4 and at 1, 2, 3, 4, 6, 8 and 12 h after infusion. The serum concentrations of ciprofloxacin were determined by high-performance liquid chromatography (HPLC). Ciprofloxacin population pharmacokinetic analysis was conducted by the NONMEM 7.3.0 software. RESULTS: Forty patients aged (78 ± 9) years completed the study. A total of 210 serum concentrations were detected. The mean values of clearance and volume of distribution (V1) were 17.8 L/h and 49.8 L respectively. The serum creatinine level influenced ciprofloxacin according to the equation: Clearance - 17.8 × [1 - 0.001 3 × (serum creatinine - 67)] × e(η1i) × 0.659(n) (at a dose of 200 mg, n - 1, at a dose of 400 mg, n - 0; ηi for inter individual random variation). The values of clearance and V1 were multiplied by 0.659 at a dose of 200 mg. At the doses of 200 and 400 mg, the maximum steady-state concentrations (C(max)) were (4.2 ± 1.1) and (5.3 ± 1.21) mg/L, the minimum steady-state concentrations (C(min)) (1.1 ± 1.1) and (0.8 ± 0.4) mg/L and the area under concentration-time curve measured in steady-state up to 24 h after dosing (AUC(0-24 h)) were (45.5 ± 28.1) and (47.2 ± 11.3) mg · h · L⁻¹ respectively. CONCLUSIONS: The clearance of ciprofloxacin in elderly patients significantly decreases as compared with adult patients. Ciprofloxacin PPK model shows a significant influence of serum creatinine level on ciprofloxacin clearance. A single dose of 400 mg may increase serum drug concentration, but causes no in vivo drug retention.

[Pharmacokinetics of meropenem administered with prolonged infusion time in patients receiving continuous veno-venous hemofiltration].

OBJECTIVE: To demonstrate the pharmacokinetic profile of meropenem when administered by 3-hour infusion in patients undergoing continuous veno-venous hemofiltration (CVVH). METHODS: The study was conducted in 10 patients, who were treated with CVVH. Each subject received meropenem in 3-hour infusion of 500 mg every 6 hours. Blood samples were collected before infusion (0 hour) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6 hours (just before the infusion of the next dose) after the beginning of the fourth infusion. The concentrations of meropenem in plasma were measured by high-performance liquid chromatography method, and mean serum meropenem concentration-time curve was plotted. RESULTS: Peak plasma drug concentrations measured 3 hours post-infusion were (25.05 ± 5.64) mg/L, and trough levels after 6 hours of infusion were (13.03 ± 3.01) mg/L. The area under the plasma concentration-time curve (AUC) was (118.42 ± 26.78) mg x h⁻¹ x L⁻². The elimination half-life (T1/2) was (3.74 ± 0.55) hours. The mean residence time (MRT) was (4.99 ± 0.84) hours. The volume of distribution (Vb) was (22.85 ± 9.85) L and clearance of meropenem (CL) was (4.49 ± 1.32) L/h. The percentage of time that the serum drug concentration was above the minimum inhibitory concentration (MIC) accounting for the interval time of infusion (%T>MIC) was 100% (MIC 8 mg/L) in all the 10 patients. CONCLUSION: Based on these data, we concluded that satisfactory pharmacodynamic parameters could be attained in CVVH patients treated with meropenem by a prolonged infusion time of 3 hours with a dosage of 500 mg for every 6 hours.

Relationship between time to positivity of blood culture with clinical characteristics and hospital mortality in patients with Escherichia coli bacteremia.

BACKGROUND: Previous studies indicated that the time to positivity (TTP) of blood culture is a parameter correlating with degree of the bacteremia and outcome in patients with bloodstream infections caused by Escherichia coli (E. coli). The objective of this study was to further investigate the diagnostic and prognostic power of using TTP to predict E. coli bacteremia. METHODS: A retrospective cohort study at two university hospitals was conducted. We retrieved all the medical records of those with E. coli bloodstream infection according to the records generated by their microbiology departments. Univariate and multivariate analyses were applied to identify clinical factors correlating with fast bacterial growth and significant prognostic factors for hospital mortality. RESULTS: Medical records of 353 episodes of E. coli bacteremia diagnosed between January 1, 2007 and December 31, 2009 were retrieved in the investigation. Univariate analysis demonstrated that the TTP ≤ 7 hours group is associated with higher incidence of active malignancies (41.7% vs. 27.2%, P = 0.010), neutropenia (30% vs.14.3%, P = 0.007), primary bacteremia (55.0% vs. 33.4%, P = 0.002), and poorer outcome (hospital mortality 43.3% vs.11.9%, P = 0.000) than the TTP > 7 hours group. Multivariate analysis revealed that the significant predictors of hospital mortality, in rank order from high to low, were TTP (for TTP ≤ 7 hours, odds ratio (OR): 4.886; 95% confidence interval (CI): 2.572 - 9.283; P = 0.000), neutropenia (OR: 2.800; 95%CI: 1.428 - 5.490; P = 0.003), comedication of steroids or immunosuppressive agents (OR: 2.670; 95%CI: 0.971 - 7.342; P = 0.057). CONCLUSIONS: Incidence of malignancies, neutropenia and primary bacteremia correlates with fast bacterial growth in patients with E. coli bacteremia. The parameter of TTP has been identified as a variable of highest correlation to hospital mortality and therefore can be potentially utilized as a mortality prognostic marker.

[Correlation between in vitro bacterial growth velocity of blood of patients with clinical parameters and prognosis in patients with Escherichia coli bacteremia].

OBJECTIVE: To identify the clinical and laboratory parameters correlating with speed of bacterial growth in culture and independent risk factors of in-hospital mortality in patients with Escherichia coli bacteremia. METHODS: This retrospective study was conducted at Beijing University Third Hospital. The medical records and microbiological database of the patients diagnosed as Escherichia coli bacteremia between January 2007 and December 2009 were collected. The parameter of time to positivity (TTP) was used to be a surrogate marker of bacterial growth. Univariate analysis was used to identify relationship between clinical parameters and the speed of bacterial growth. Logistic multivariate analysis was used to identify risk factors of in-hospital mortality. RESULTS: The medical records of 112 patients during the study period were collected, 25 patients died during hospital stay, the overall in-hospital mortality rate was 22.3%. Univariate analysis indicated the rapid-growth (TTP≤7 hours) group (n=20) had higher incidence of neutropenia (40.0% vs. 15.2%), higher incidence of primary bacteremia (40.0% vs. 18.5%) and higher in-hospital mortality rate (45.0% vs. 17.4%) than those with slow bacterial growth (TTP>7 hours) group (n =92, all P<0.05). The death group (n=25) was found to have a higher incidence of TTP≤7 hours (36.0% vs. 12.6%), higher incidence of active malignancies (44.0% vs. 24.1%), higher incidence of neutropenia (36.0% vs. 14.9%), higher rate of isolation of extended spectrum ß lactamases (ESBL)-producing strains (48.0% vs. 24.1%) than the survival group (n=87, all P<0.05). Logistic multivariate analysis suggested the significant predictors of in-hospital mortality included TTP≤7 hours [odds ratio (OR)=3.412, 95% confidence interval (95% CI)=1.1819.856, P=0.023], ESBL-producing strains (OR=2.545, 95% CI=0.9776.625, P=0.056). CONCLUSION: In vitro Escherichia coli growth speed in the blood culture correlates with the incidence of neutropenia and primary bacteremia, and TTP≤7 hours and ESBL-producing strains may be the strong, independent risk factors of a worse prognosis in patients with Escherichia coli bacteremia.

[Assessment of severity of acute pancreatitis in early stage].

OBJECTIVE: To assess the accuracy of indexes for predicting severe acute pancreatitis (SAP). METHODS: Thirty-nine patients suffering from acute pancreatitis (AP) were randomly selected, including 20 SAP cases and 19 mild acute pancreatitis (MAP) cases. The levels of polymorphonuclear leucocyte-elastase (PMN-E), serum phospholipase A2 (PLA2), pancreatic PLA2 (Pan-PLA2), PLA2 catalytic activity (CA-PLA2), amylase, as well as C-reactive protein (CRP) were determined Acute Physiology and chronic health evaluation II (APACHE II) was scored in every patient. Sensitivity and specificity of all the parameters were assessed, and receiver operator characteristic curve (ROC) was plotted. Positive predictive value, negative predictive value, and overall accuracy were then analyzed. RESULTS: PMN-E, CRP and CA-PLA2 were obviously higher in SAP than in MAP, and were indicative of the severity of the disease (all P < 0.01). Pan-PLA2 and amylase of AP patients raised at the onset of the disease, and they showed no difference between the SAP groups and MAP groups. When SAP was predicted by PMN-E, sensitivity was 94.5%, specificity was 99.4%, positive predictive value was 97.8%, negative predictive value was 99.4%, overall accuracy was 98.7%, higher than other indexes. When SAP was Predicted by CRP, the overall accuracy was also high and reached 84.0%. CONCLUSION: PMN-E, CA-PLA2, CRP, and APACHE II are all indexes for the diagnosis of SAP. PMN-E is found to be the best index in predicting SAP.