Effect of prior receipt of antibiotics on the pathogen distribution: a retrospective observational cohort study on 27,792 patients.

BACKGROUND: There have been no systematic studies of microbiological differences before and after antibiotics treatment. The aim of this study was to evaluate the effect of prior receipt of antibiotics on the microorganism distribution. METHODS: A retrospective, observational cohort study was conducted in a 3200-bed tertiary, referral, teaching hospital in eastern China. During a 2-year period, all hospitalized patients treated with antimicrobial agents were enrolled in this study. Among 48,692 patients evaluated, the 27,792 (57.1%) who were sampled within 2 days before or after administration of the first dose of antimicrobial agents were included. Distribution of clinical specimens and the microorganism were compared between before and after antibiotic drug treatment groups. RESULTS: Compared to specimens taken after antibiotics exposure, specimens taken before antibiotics exposure had a higher proportion of blood and urine specimens and a higher culture positive rate (all P < 0.001). Higher percentages of Staphylococcus aureus (9.9% vs. 8.5%, P = 0.041), non-fermenting bacteria (27.7% vs. 19.9%, P < 0.001), and fungi (8.4% vs. 4.0%, P < 0.001) were isolated from the group after antibiotics exposure, while the percentages of Streptococcus spp. (4.8% vs. 2.7%, P < 0.001), Haemophilus influenzae (2.3% vs. 0.8%, P < 0.001), and Moraxella catarrhalis (0.7% vs. 0.1%, P < 0.001) were higher in the group before antibiotics exposure. Further analysis found significant differences of microbes derived from respiratory secretions, blood or urine samples. We found, after antibiotics exposure, the separation rate of non-fermenting bacteria was significantly increased (all P < 0.05), and the separation rate of Candida spp. was higher, with statistical significance in airway secretion and urine samples (both P < 0.05), but the separation rate of Staphylococcus aureus among the three groups was not affected by antibiotics. In addition, the isolation rate of Streptococcus spp. in blood and urine samples decreased significantly (both P < 0.05) after antibiotics exposure. Interestingly, no statistical difference was found for microbes isolated from body fluid specimens between the two groups. CONCLUSIONS: The outcome revealed that antibiotic-insensitive organisms such as non-fermentative bacteria and fungi were more frequently isolated after antibiotics exposure. However, this trend might be specimen dependent and was not obvious in body fluid specimens.

The prognostic value of total T3 after acute cerebral infarction is age-dependent: a retrospective study on 768 patients.

BACKGROUND: Serum triiodothyronine (T3) concentration was reported to be associated with the prognosis after acute ischemic stroke. The aim of this study was to evaluate the effect of age on the prognostic value of thyroid-related hormones after an acute ischemic stroke. METHODS: This was a retrospective study involving the review of 1072 ischemic stroke patients who had been consecutively admitted to the hospital within 72 h of symptom onset. Total triiodothyronine (T3), total thyroxine (T4), free T3, free T4, and thyroid-stimulating hormone (TSH) were assessed to determine their values for predicting functional outcome at the first follow-up clinic visits, which usually occurred 2 to 4 weeks after discharge from the hospital. RESULTS: A total of 768 patients were finally included in the study and divided into two age groups: a younger group (age < 65 years) and an older group (age ≥ 65 years). On univariate analysis, four factors-lower total T3, free T3 concentrations, higher scores on the National Institute of Health Stroke Scale (NIHSS) and the presence of atrial fibrillation-were associated with poor functional outcomes in both groups. In addition, older age, female gender, higher free T4, and lower TSH levels were also associated with poor function in the older group. On multiple logistic regression analysis, higher NIHSS scores (odds ratio [OR] =1.95; 95% confidence interval [CI], 1.66-2.30; P ≤ .001) and lower total T3 concentrations (OR = 0.06; 95% CI, 0.01-0.68; P = .024) remained independently associated with poor functional outcome in the older group. However, the independent association with poor function of lower total T3 was not confirmed in the younger group. CONCLUSIONS: The prognostic value of low total T3 is age-associated and more meaningful in an older population.

Regulation of recombinant Trichinella spiralis 53-kDa protein (rTsP53) on alternatively activated macrophages via STAT6 but not IL-4Rα in vitro.

Classically activated macrophages (M1) or alternatively activated macrophages (M2) have different functions during helminth infections including Trichinella spiralis (T. spiralis). The excretory/secretory antigens (ESA) of T. spiralis can inhibit macrophage pro-inflammatory cytokines production. However, the specific molecules of ESA that regulate macrophages have not been identified. We previously reported that recombinant T. spiralis derived molecule 53-kDa protein (rTsP53) had protected mice from colitis. Furthermore, in the present study in vitro, we investigated rTsP53 showed anti-inflammatory function by inducing peritoneal macrophages to M2 with expressing M2 molecules of mannose receptor (MR), a novel mammalian lectin (Ym1), arginase-1 (Arg1), and interleukin (IL)-10. Next, we found the effect of rTsP53 on M2 independently of IL-4Rα. But rTsP53 can act dependently on signal transducers and activators of transcription 6 (STAT6). These results further imply that rTsP53 has potential as prospective immuno-therapeutics for inflammatory disorders.

Gene therapy with HSV1-sr39TK/GCV exhibits a stronger therapeutic efficacy than HSV1-TK/GCV in rat C6 glioma cells.

Although the combination of herpes simplex virus type 1 (HSV-1) thymidine kinase (TK) with ganciclovir (GCV) has been shown as a promising suicide gene treatment strategy for glioma, the almost immunodepressive dose of GCV required for its adequate in vivo efficacy has hampered its further clinical application. Therefore, In order to reduce the GCV dose required, we aim to compare the therapeutic efficacy of HSV1-sr39TK, an HSV1-TK mutant with increased GCV prodrug catalytic activity, with wildtype TK in C6 glioma cells. Accordingly, rat C6 glioma cells were first transfected with pCDNA-TK and pCDNA-sr39TK, respectively, and the gene transfection efficacy was verified by immunocytochemistry and western blot analysis. Then the in vivo sensitivity of these transfected C6-TK and C6-sr39TK cells to GCV was determined by 3-(4,5)-dimethylthiahiazo-(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) colorimetric assay and Hoechst-propidium iodide (PI) staining. Finally, a subcutaneously C6 xenograft tumor model was established in the nude mice to test the in vitro efficacy of TK/GCV gene therapy. Our results showed that, as compared with wildtype TK, HSV1-sr39TK/GCV demonstrated a stronger therapeutic efficacy against C6 glioma both in vitro and in vivo, which, by reducing the required GCV dose, might warrant its future use in the treatment of glioma under clinical setting.

Do probiotics help prevent ventilator-associated pneumonia in critically ill patients? A systematic review with meta-analysis.

BACKGROUND: Probiotic treatments might contribute to the prevention of ventilator-associated pneumonia (VAP). Due to its unclear clinical effects, here we intend to assess the preventive effect and safety of probiotics on intensive care unit (ICU) patients. METHODS: Eligible randomised controlled trials were selected in databases until 30 September 2019. The characteristics of the studies were extracted, including study design, definition of VAP, probiotics intervention, category of included patients, incidence of VAP, mortality, duration of mechanical ventilation (MV) and ICU stay. Heterogeneity was evaluated by Chi-squared and I2 tests. RESULTS: 15 studies involving 2039 patients were identified for analysis. The pooled analysis suggests significant reduction on VAP (risk ratio, 0.68; 95% Cl, 0.60 to 0.77; p<0.00001) in a fixed-effects model. Subgroup analyses performed on the category of clinical and microbiological criteria both support the above conclusion; however, there were no significant differences in duration of MV or length of ICU stay in a random-effects model. Also, no significant differences in total mortality, overall mortality, 28-day mortality or 90-day mortality were found in the fixed-effects model. CONCLUSIONS: The probiotics helped to prevent VAP without impacting the duration of MV, length of ICU stay or mortality.

Microbiology and Outcomes of Institutionalized Patients With Stroke-Associated Pneumonia: An Observational Cohort Study.

Background: The attributable mortality and microbial etiology of stroke-associated pneumonia (SAP) vary among different studies and were inconsistent. Purpose: To determine the microbiology and outcomes of SAP in the lower respiratory tract (LRT) for patients with invasive mechanical ventilation (MV). Methods: In this observational study, included patients were divided into SAP and non-SAP based on a comprehensive analysis of symptom, imaging, and laboratory results. Baseline characteristics, clinical characteristics, microbiology, and outcomes were recorded and evaluated. Results: Of 200 patients, 42.5% developed SAP after the onset of stroke, and they had a lower proportion of non-smokers (p = 0.002), lower GCS score (p < 0.001), higher serum CRP (p < 0.001) at ICU admission, and a higher proportion of males (p < 0.001) and hypertension (p = 0.039) than patients with non-SAP. Gram-negative aerobic bacilli were the predominant organisms isolated (78.8%), followed by Gram-positive aerobic cocci (29.4%). The main pathogens included K. pneumoniae, S. aureus, H. influenzae, A. baumannii, P. aeruginosa, E. aerogenes, Serratia marcescens, and Burkholderia cepacia. SAP prolonged length of MV (p < 0.001), duration of ICU stay (p < 0.001) and hospital stay (p = 0.027), shortened MV-free days by 28 (p < 0.001), and caused elevated vasopressor application (p = 0.001) and 60-day mortality (p = 0.001). Logistic regression analysis suggested that patients with coma (p < 0.001) have a higher risk of developing SAP. Conclusion: The microbiology of SAP is similar to early phase of HAP and VAP. SAP prolongs the duration of MV and length of ICU and hospital stays, but also markedly increases 60-day mortality.

Ticagrelor-induced thrombotic thrombocytopenic purpura: A case report and review of the literature.

RATIONALE: Ticagrelor, a new type of P2Y12 receptor antagonist, has been highly recommended to be used in acute coronary syndrome by the latest guideline, but its side effects are not well-known. We seek to illustrate a potential fatal condition, thrombotic thrombocytopenic purpura (TTP), caused by ticagrelor. PATIENT CONCERNS: An 87-year-old man who had been prescribed with ticagrelor for 2 months after ST-elevation myocardial infarction (STEMI), presented with severe thrombocytopenia, anemia, renal and liver dysfunction, heart failure and fever. DIAGNOSES: Peripheral blood smear showed schistocytosis, and a disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS13) activity is low, with normal initial coagulation tests, which were compatible with a diagnosis of TTP. INTERVENTIONS: After cessation of ticagrelor and initiation of therapeutic plasma exchange, our patient recovered. OUTCOMES: Re-administration of ticagrelor aggravated TTP and led the patient to death. LESSONS: Clinicians should be aware of the possibility of ticagrelor-induced TTP in patients with a history of recent myocardial infarction; It is of crucial significance to discontinue and never reuse ticagrelor as long as it is suspected to be implicated in TTP.

A retrospective study of risk factors for carbapenem-resistant Klebsiella pneumoniae acquisition among ICU patients.

INTRODUCTION: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is rapidly emerging as a life-threatening nosocomial infection. In this study, we aim to identify risk factors, especially antibiotic use, for CRKP infection among intensive care unit (ICU) patients. METHODOLOGY: This was a matched case-control study of a 67-bed ICU in a tertiary care teaching hospital from 1 January 2011 through 30 June 2013. The control cases were selected among the patients with carbapenem-susceptible Klebsiella pneumoniae (CSKP) and were matched with CRKP cases for year of ICU admission and site of infection. The clinical outcomes and antibiotic treatments were analyzed. RESULTS: One hundred and thirty patients were included in the study (65 cases and 65 controls). Bivariable analysis showed that age of patients (p = 0.044), number of antibiotic groups (p = 0.001), and exposure to carbapenems (p < 0.001) were associated with CRKP infection. Using multivariate analysis adjusted for age, prior hospitalization, number of antibiotic groups, and previous exposure to carbapenems, previous carbapenem exposure (p < 0.001) was identified as an independent risk factor for CRKP infection. CONCLUSIONS: These data suggest that exposure to carbapenems is an independent risk factor for CRKP infection. Patients with this clinical factor should be targeted for interventions to reduce the subsequent risk of infection.

Trichinella spiralis excretory-secretory products protect against polymicrobial sepsis by suppressing MyD88 via mannose receptor.

Trichinella spiralis (T. spiralis) or its excretory-secretory products (TsES) protect hosts from autoimmune diseases, which depend on inducing host T helper (Th) 2 immune response and inhibiting inflammatory factors. Sepsis is a systemic inflammatory response syndrome (SIRS) evoked by infection. Little is known about the effects of helminths or their excretory-secretory products on sepsis. Here, we investigated the effects of TsES in a mice model of polymicrobial sepsis. TsES improved survival, reduced organ injury, and enhanced bacterial clearance in septic mice. To investigate the molecular mechanism, macrophages from septic patients or the control group were incubated with TsES. TsES reduced sepsis-inducing inflammatory cytokines mediated by Toll-like receptors (TLR) in vitro by suppressing TLR adaptor-transducer myeloid differentiation factor 88 (MyD88) and nuclear factor- (NF-)-κB. Furthermore, TsES upregulated mannose receptor (MR) expression during sepsis. MR blocking attenuated the effects of TsES on MyD88 and NF-κB expression. In vivo, MR RNAi reduced the survival rate of septic mice treated with TsES, suggesting that TsES-mediated protection against polymicrobial sepsis is dependent on MR. Thus, TsES administration might be a potential therapeutic strategy for treating sepsis.

Combination antibiotic therapy versus monotherapy for Pseudomonas aeruginosa bacteraemia: a meta-analysis of retrospective and prospective studies.

The choice of antibiotic monotherapy or combination therapy to treat Pseudomonas aeruginosa bacteraemia is controversial. The aim of this review was to compare both types of therapy to determine which delivers the best outcome for P. aeruginosa bacteraemia. We systematically searched electronic bibliographic databases, including PubMed, Ovid EMBASE and The Cochrane Library, for clinical studies that compared combination therapy with monotherapy in the treatment of P. aeruginosa bacteraemia. Eligible articles were analysed using Stata(®)/SE software v.12.0. Stratification analysis was conducted by study design and treatment type. Publication bias was assessed using Begg's funnel plot and Egger's test. Ten studies (eight retrospective and two prospective) involving 1239 patients were analysed. We found no difference between combination therapy and monotherapy when the data were combined (odds ratio = 0.89, 95% confidence interval 0.57-1.40; P = 0.614) or when data were analysed in subgroups. Neither combination therapy nor monotherapy treatment appears to have a significant effect on mortality rates in patients with P. aeruginosa bacteraemia. Further studies evaluating the effects of combination therapy or monotherapy in more specialised cases, such as when encountering a multidrug-resistant organism, are necessary.