Antibacterial treatment scheme and risk factors of bloodstream infection with carbapenem-resistant Klebsiella pneumoniae / 中国综合临床

Objective:To investigate the relationship between antibacterial treatment scheme and prognosis, and to analyze the mortality risk factors of bloodstream infection with carbapenem-resistant Klebsiella pneumoniae(CRKP).Methods:A retrospective case-control study was conducted. The CRKP isolated from clinical venous blood samples in the First Medical Center, Chinese PLA General Hospital between January 1, 2013 and December 31, 2018(not included from January 1, 2016 to December 31, 2017) was collected. According to relevant standards, a total of 50 patients with bloodstream infection with CRKP were included. The patients were divided into death (19 cases) or survival (31 cases) group according to their hospitalization outcomes, and clinical data and antibacterial treatment scheme after infection were collected. The clinical features of the two groups and the correlation between different antibacterial treatment regimens and prognosis were compared. Logistics regression model was used to analyze the risk factors for death in CRKP-infected patients.Results:The all-cause mortality rate of patients with CRKP bloodstream infection during hospitalization was 38%(19/50). The age ((66.89±18.13) vs. (55.06±14.39) years old, t=2.555, P=0.014), charlson's comorbidity index ((6.11±2.87) vs. (3.19±1.97), t=4.256, P<0.001) of the death group was higher than that of the survival group. The proportion of patients with chronic obstructive pulmonary disease (42.1%(8/19) vs. 3.2%(1/31), χ2=9.574, P=0.002), Charlson's comorbidity index ≥5 (68.4%(13/19) vs. 22.6%(7/31), χ2=10.314, P=0.001), septic shock (36.8%(7/19) vs. 6.5%(2/31), χ2=5.456, P=0.020), source of lung infection (36.8%(7/19) vs. 9.7%(3/31), χ2=3.868, P=0.049) was higher in death group than those in survival group. Kaplan-meier survival curve showed that the 30-day mortality of appropriate targeted treatment was lower than that of inappropriate targeted treatment ( χ2=8.138, P=0.004). Multivariate analysis showed that septic shock ( OR=56.363, 95% CI: 4.309-737.273, P=0.002) and charlson's comorbidity index ≥5 ( OR=18.605,95% CI: 1.813-190.896, P=0.014) were independent risk factors for mortality in patients with bloodstream CRKP infection. Conclusion:Appropriate targeted therapy can reduce 30-day mortality in patients with CRKP bloodstream infection. In order to reduce the risk of mortality, we should prevent the occurrence of septic shock and strengthen the diagnosis and treatment of patients with Chalson's comorbidity index ≥5.

Preliminary evaluation of the safety and efficacy of oral human antimicrobial peptide LL-37 in the treatment of patients of COVID-19, a small-scale, single-arm, exploratory safety study

Background& AimsThe Coronavirus Disease 2019 (COVID-19) has become a global epidemic and has caused a lasting and huge loss of life security, economic development and social stability in more than 180 countries around the world. Unfortunately, there is still no specific treatment for COVID-19 till now, therefore, at this point, all potential therapies need to be critically considered. LL-37 is one of the best-studied human antimicrobial peptide (AMPs) that has a broad-spectrum activity against bacteria and viruses. The use of living, genetically modified organisms (GMOs) is an effective approach for delivery of therapeutic proteins. The aim of this study was to determine the safety and efficacy of the Lactococcus lactis which has been genetically modified to produce the therapeutic human antimicrobial peptide LL-37 (herein after referred to cas001) in the patients of COVID-19. MethodsFirstly we constructed genetically modified food-grade probiotic, Lactococcus lactis, with sequence of seven tandem repeats of mature human LL-37 under control of the nisin-inducible nisA promoter to produce the cas001. A total of 20 healthy SD rats, half male and half female (There were five male and five female in the control group, the same in treatment group) were used to observe the acute toxic reaction and death after daily administration of cas001 for three weeks, which helps to provide necessary reference basis for clinical dose selection, verificaition of toxic reaction and possible target organs. According to the estimated clinical dosage of 1 x 108CFU /kg/day, considering the conversion of body surface area, the dose for rats should be multiplied by 6.17 to 6 x 108 CFU/kg/day. We administrated 100 times higher dose at 6 x 1010 CFU/ /kg/day to rats. In order to investigate the pharmacokinetics of cas001, male SD rats (body weight 250-300g, 1 x 1010 /animal, n=3) were given oral administration of LL-37 bacteria powder. The concentration of LL-37 in the blood before and after gavage was detected by ELISA kit (Hycult biotechnology Cat# HK321). Human clinical study was approved by Ethics committee of Chinese PLA General Hospital (S2020-074-04) and a total of 11 patients with mild symptoms were enrolled in Wuhan hankou hospital and Huoshenshan hospital. They were enrolled voluntarily and all patients signed informed consent. Among them, there were 5 males and 6 females, aged 55 {+/-} 12 (36-70) years old, and the duration from onset to medication enrollment was 35 {+/-} 19 (5-68) days. 6 patients were nucleic acid positive and 5 patients were nucleic acid negative when they were enrolled. All patients received the oral drug cas001 treatment according to requirement(1 x 109 CFU/capsule, 3 capsules/time, three times a day for 3weeks), with an average follow-up time of 33 {+/-} 15 days (see table 1 for the results). O_TBL View this table: org.highwire.dtl.DTLVardef@1845d29org.highwire.dtl.DTLVardef@1004b38org.highwire.dtl.DTLVardef@4a741aorg.highwire.dtl.DTLVardef@c73d5org.highwire.dtl.DTLVardef@188b563_HPS_FORMAT_FIGEXP M_TBL O_FLOATNOTable 1.C_FLOATNO O_TABLECAPTIONSerum biochemical detection in rats two weeks after gavage Serum biochemistry detection of rats at the end of two weeks (Vehicle[male] v.s. LL-37[male], n=5; Vehicle[female] v.s. LL-37[female], n=5). *represent p value<0.05. C_TABLECAPTION C_TBL FindingsWestern blot analysis shows that reasonable amount of LL-37 were induced by different concentrations of nisin, which means we have successfully constructed cas001. In the pre-clinical safety evaluation test, after three weeks administration of cas001, no adverse effects were observed on the rats body weight, food and water intake, hematological or serum biochemical parameters. The results showed that the LD50 of cas001 was higher than that of the 100 times of the expected clinical dose of 6 x 1010 CFU/day. These results showed that cas001 could be safe in animal experiments. In addition, rat pharmacokinetics results showed that the serum concentration of LL-37 reached peak 2 hours after gavage of cas001 and returned to basal level 6 hours after gavage. During study period, the volunteers did not feel any discomfort while taking the cas001 capsules, and two hours after oral administration, the concentration of LL-37 were increased in healthy volunteers. cas001 shows definite effect in the improvement of gastrointestinal symptoms and is possible to have effects in improving the systemic symptoms and respiratory symptoms and may play a role in the improvement of results of nucleic acid test and lung CT test. 11 patients enrolled showed good compliance, tolerance, subjective feeling and actively interacted with the doctors. None of the patients had any adverse reactions. ConclusionsBased on above observations, we conclude here that as an oral anti-viral agent, cas001 displayed good safety profiles. It is very hard to reach conclusion of clinical outcomes related to the cas001, although changes of several symptoms indicate encouraging findings.

Assisting Scalable Diagnosis Automatically via CT Images in the Combat against COVID-19

Introductory paragraphThe pandemic of coronavirus Disease 2019 (COVID-19) caused enormous loss of life globally. 1-3 Case identification is critical. The reference method is using real-time reverse transcription PCR (rRT-PCR) assays, with limitations that may curb its prompt large-scale application. COVID-19 manifests with chest computed tomography (CT) abnormalities, some even before the onset of symptoms. We tested the hypothesis that application of deep learning (DL) to the 3D CT images could help identify COVID-19 infections. Using the data from 920 COVID-19 and 1,073 non-COVID-19 pneumonia patients, we developed a modified DenseNet-264 model, COVIDNet, to classify CT images to either class. When tested on an independent set of 233 COVID-19 and 289 non-COVID-19 patients. COVIDNet achieved an accuracy rate of 94.3% and an area under the curve (AUC) of 0.98. Application of DL to CT images may improve both the efficiency and capacity of case detection and long-term surveillance.

Prevalence and Resistant Characteristics of Clinical Isolates of Enterobacter cloacae / 中华医院感染学杂志

OBJECTIVE To study the prevalance and resistance characteristics of clinical isolates of Enterobacter cloacae.METHODS Clinical isolates of E.cloacae were studied by K-B methods,and the data of MIC were(analyzed ) by WHONET 5.3 software.RESULTS Totally 416 clinical isolates of E.cloacae isolated from 2000 to 2004 were studied and they were mainly isolated from department of respiration,surgical ICU and department of(neurology) and their rate was 25.2%,9.6%,and 8.6%,respectively.The E.cloacae strain was(resistant) to ciprofloxacin,amikacin and most of penicillins,cephalosporins and ?-lactams combined with the(?-lactamase) inhibitors.It was susceptible to cefepime,imipenem and etrapenem.CONCLUSIONS The E.cloacae is resistant to many commonly used antibiotics in clinics and it is important to control antibiotic(resistance) by using antibiotics reasonably.