Outer membrane vesicles from X-ray-irradiated Pseudomonas aeruginosa alleviate lung injury caused by P. aeruginosa infection-mediated sepsis.

Pseudomonas aeruginosa infection causes pneumonia and sepsis. Previous research found that X-ray radiation can induce P. aeruginosa to release outer membrane vesicles (OMVs) of relatively consistent sizes. This study found that OMVs derived from X-ray-irradiated P. aeruginosa can significantly inhibit lung leakage, inflammatory cell infiltrating into lung, and the production of pro-inflammatory cytokines, IL-1ß and TNFα caused by P. aeruginosa infection under preventive and therapeutic administration conditions. Under the same conditions, OMVs also significantly alleviated pathological characteristics of lung injury, including pulmonary edema, pulmonary hemorrhage, and alveolar wall thickening. OMVs also significantly reduced bacterial burdens in peritoneal cavity, accompanied by a reduction in the number of viable bacteria capable of forming bacterial colonies. Pretreating macrophages and neutrophils with OMVs enhances their bactericidal ability. When bacteria were cocultured with treated cells, the number of viable bacteria capable of forming bacterial colonies was significantly reduced. OMVs themselves have not been shown to cause any lung injury or affect bacterial viability. Therefore, OMVs derived from X-ray-irradiated P. aeruginosa may not only be applied in prevention and treatment of diseases associated with P. aeruginosa infection, but also served as an excellent vaccine development platform.

Case report: Uncommon presentation of Salmonella Dublin infection as a large paravertebral abscess.

Background: Salmonella Dublin is a zoonotic pathogen that is associated with invasive infections and high morbidity and mortality rates. Here we present the case of a 78-year-old man with a rare manifestation of a paravertebral abscess in the thoracolumbar spine caused by Salmonella Dublin. Case presentation: The patient had a history of spinal tuberculosis and poorly controlled diabetes. The abscess was successfully managed by drainage, and a 12-week course of moxifloxacin resulted in complete recovery. Salmonella Dublin was identified using culture-based serotyping. The patient resided in an environment where cattle farming is common; he consumed raw beef and unpasteurized milk, suggesting a potential source of infection. Discussion: Increasing the awareness of Salmonella Dublin as a potential cause of spinal abscesses is important, particularly in patients with structural spinal abnormalities. The timely initiation of appropriate antimicrobial therapy based on susceptibility testing is recommended. This case highlights the pathogenic potential of Salmonella Dublin and emphasizes the importance of effectively managing invasive Salmonella infections.

Real-world effectiveness of ceftazidime/avibactam versus polymyxin B in treating patients with carbapenem-resistant Gram-negative bacterial infections.

OBJECTIVES: To compare the effectiveness of ceftazidime/avibactam (CAZ/AVI) and polymyxin B against carbapenem-resistant Gram-negative bacteria (CRGNB) infections in western China. METHODS: The medical records of patients with CRGNB infections in this hospital from 2018-2022 were retrospectively reviewed. The data included demographic characteristics, laboratory results, antibiotic strategies and clinical outcomes. RESULTS: A total of 378 patients with CRGNB infections were enrolled, including 112 patients in the CAZ/AVI group and 266 patients in the polymyxin B group. The most common pathogen was carbapenem-resistant Klebsiella pneumoniae (44.44%). The rates of treatment failure at 28 days (65.04% vs. 45.54%; P = 0.000) and 28-day in-hospital mortality (20.30% vs. 9.82%; P = 0.014) in the polymyxin B group were higher than those in the CAZ/AVI group. Multivariable analysis revealed that multiple organ dysfunction syndrome (OR 2.730; P = 0.017), acute renal failure (OR 2.595; P = 0.020), higher Charlson comorbidity index (CCI) (OR 1.184; P = 0.011) and Acute Physiology And Chronic Health Evaluation (APACHE) Ⅱ scores (OR 1.149; P = 0.000) were independent risk factors for treatment failure, whereas CAZ/AVI therapy (OR 0.333; P = 0.002) had a protective effect. Multivariate Cox regression analysis revealed that CCI ≥ 5 and APACHE II score ≥ 15 were associated with a higher 28-day in-hospital mortality rate (P < 0.001). CONCLUSION: CAZ/AVI therapy was associated with treatment success among patients with CRGNB infection. However, CAZ/AVI therapy did not improve 28-day in-hospital survival compared with polymyxin B. The CCI ≥ 5 and APACHE II score ≥ 15 affected 28-day in-hospital mortality of CRGNB-infected patients.

Treatment of Central Nervous System Infection Caused by Multidrug-Resistant Klebsiella pneumoniae with Colistin Sulfate Intravenously and Intrathecally: A Case Report.

Background: Due to the blood-brain barrier and limited antibiotic choices, polymyxin is currently the first-line agent for the treatment of central nervous system infections (CNSIs) caused by multidrug-resistant Gram-negative bacteria (MDR-GNB). Colistin sulfate, as a polymyxin E different from CMS, is used in Chinese clinics, and there are limited reports on its use in the treatment of CNSIs. Case Presentation: This case describes a 76-year-old man who underwent complex neurosurgery for cervical spinal stenosis. Postoperatively, the patient developed a fever and a poorly healed surgical wound. Numerous blood routine tests, inflammatory markers, pathogenic tests of cervical secretions, cerebrospinal fluid (CSF), and sputum were sent for diagnosis. After empirical antimicrobial treatments failed, the CSF and wound pus cultured carbapenem-resistant Klebsiella pneumoniae. The regimen was adjusted to colistin sulfate intravenously and intrathecal injection combined with tigecycline. In addition, the management of infection foci, including continuous lumbar pool drain, cervical 3-5 internal fixation removal with cervical 1-6 spine dilation, CSF leak repair, and right thigh broad fasciotomy, were performed. After treatment, the patient was discharged with multiple sets of negative CSF cultures and the infection under control. Conclusions: For CNSIs caused by MDR-GNB, the selection of colistin sulfate for intravenous and topical combination treatment is a viable choice.

Delayed diagnosis of multiple systemic disseminated tuberculosis: A case report.

RATIONALE: The clinical manifestations in patients with disseminated tuberculosis (TB) are nonspecific and may present challenges for early diagnosis. PATIENT CONCERNS AND DIAGNOSES: We describe the case of a 44-year-old man who presented with abdominal pain and discomfort for more than a month. He had undergone surgery for a chest wall abscess 9 months ago. Computed tomography scans showed a miliary pattern in the lung and multiple abscesses in the liver, spleen, left psoas major muscle, skin, and soft tissue, with rim enhancement. Mycobacterium tuberculosis was detected in the drainage fluid of the abscesses and surgical slices, and disseminated TB was diagnosed. INTERVENTIONS AND OUTCOMES: With anti-tuberculosis therapy, the abscesses were gradually absorbed and all cultures were negative. LESSONS: The patient exemplifies the difficulty of the early diagnosis of disseminated TB. Disseminated TB should be considered first in patients with multisystem illness, and then evidence should be pursued relentlessly to establish a diagnosis.

Efficacy and safety of polymyxin E sulfate in the treatment of critically ill patients with carbapenem-resistant organism infections.

Objective: Polymyxins are currently the last line of defense in the treatment of carbapenem-resistant organisms (CRO). As a kind of polymyxin available for clinical use in China, we aim to explore the efficacy and safety of colistin sulfate (Polymyxin E sulfate, PES) in this study. Methods: This real-world retrospective study included 119 patients diagnosed with CRO infection and treated with PES for more than 72 h, from May 2020 to July 2022 at West China Hospital. The primary outcome was clinical efficacy at the end of treatment, and secondary outcomes included microbial response, in-hospital mortality and incidence of nephrotoxicity. Results: The effective clinical and microbiological responses were 53.8% and 49.1%, respectively. And the in-hospital mortality was 27.7%. Only 9.2% of patients occurred with PES-related nephrotoxicity. Multivariate analysis revealed that duration of PES was an independent predictor of effective therapy, while age-adjusted Charlson comorbidity index (aCCI) and post-treatment PCT(p-PCT) were independent risk factors for poor outcome. Conclusions: PES can be a salvage treatment for CRO-induced infections with favorable efficacy and low nephrotoxicity. The treatment duration of PES, aCCI and p-PCT were factors related to the clinical effectiveness of PES.

Clinical characteristics and outcomes of patients with multidrug-resistant Gram-negative bacterial infections treated with ceftazidime/avibactam.

OBJECTIVES: The aim of this study was to investigate the clinical characteristics and outcomes of patients with infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) treated with ceftazidime/avibactam (CAZ/AVI) during the period September 2019 to June 2020 since CAZ/AVI had been marketed in China. METHODS: A total of 20 MDR-GNB-infected patients were retrospectively identified using the electronic medical record system in West China Hospital. RESULTS: The mean age of the 20 patients was 54.5 ± 17.37 years and 14 (70%) were male. Pneumonia (n = 12; 60%), complicated intra-abdominal infection (n = 10; 50%), and bloodstream infection (n = 7; 35%) were the most common infection sources. Klebsiella pneumoniae (55% 18/33) was the predominant pathogen. The 14-day clinical cure rate was 45%. The 14-day and 30-day mortality rates were 25% and 55%, respectively. No significant difference was found in 30-day mortality between treatment with CAZ/AVI monotherapy and combination regimens (P > 0.05). Three patients suffered from adverse drug reactions such as diarrhoea. CONCLUSION: No significant difference was found between the effectiveness of CAZ/AVI in the clinical failure and cure groups as salvage treatment of MDR-GNB infection.

Prevention and treatment system of novel coronavirus infection in medical and health institutions: experience in West China Hospital of Sichuan University.

The novel coronavirus infection broke out in Wuhan, China, in December 2019, and progressed to a global pandemic. We describe the measures taken by West China Hospital of Sichuan University to address the diagnosis, prevention and treatment of the infection.

Retrospective analysis of 1,641 cases of classic fever of unknown origin.

BACKGROUND: Fever of unknown origin (FUO) is commonly defined as fever higher than 38.3 °C on several occasions during at least 3 weeks with uncertain diagnosis after a number of obligatory investigations. It is a special type of fever and a common disease in internal medicine. However, due to its complex etiology, lack of characteristic clinical manifestations, and insufficient laboratory examination indicators, it often baffles clinicians in diagnosis. We herein present a study of the etiological factors and clinical features of classic fever of unknown origin (FUO) to provide help for related clinical diagnosis and treatment. METHODS: A total of 1,641 cases of patients with classic FUO hospitalized in West China Hospital of Sichuan University between January 1, 2011 and December 31, 2017, were collected, and the etiological factors of classic FUO were analyzed. A special effort was made to explore and screen the laboratory indicators related to infectious diseases, and the above data were compared with the clinical features of tuberculosis and lymphoma, which are difficult to diagnose. RESULTS: Among the 1,641 patients, 1,504 were finally diagnosed through various types of examination or diagnostic methods, and the diagnosis rate was 91.65%. Among all the causes of the 1,641 cases of FUO, 48.69% [799] were infectious diseases, of which tuberculosis was the most common, accounting for 19.50% [320]. Connective tissue diseases were responsible for 19.26% [316] of cases, of which adult-onset Still's disease (AOSD) was the most common, comprising 89 (5.42%) of the cases; 16.94% [278] were neoplastic diseases, and lymphoma (143, 8.71%) cases, was the most common malignant tumor; 6.76% [111] were other diseases; and in 8.35% [137] of cases, the cause was unclear. Through comparative analysis of tuberculosis and lymphoma, no significant differences were found between the symptoms, signs, and non-specific routine examination results of the two diseases. The diagnosis of these diseases was more dependent on tuberculosis-related examinations and pathological examinations. CONCLUSIONS: Infectious diseases are the principal cause of classic FUO, in which tuberculosis accounts for a large proportion. Non-infectious diseases that cause FUO are mainly connective tissue diseases and malignant tumors. Of the various causes of classic FUO, tuberculosis and lymphoma are relatively difficult to diagnose. In most cases, the causes of classic FUO can be ascertained.

[Analysis of Pathogens and Clinical Characteristics in 157 Cases with Infective Endocarditis].

OBJECTIVE: To analyze the clinical characteristics of infective endocarditis (IE) in culture-positive patients,so as to provide the evidences for reasonable diagnosis and treatment of IE. METHODS: We performed a retrospective study of 157 culture-positive IE cases,which were diagnosed according to modified Duke criteria for IE from Jan. 2008 to Aug. 2015. RESULTS: The average age of 157 cases of IE was 40.85 years. One hundred and one patients (64.3%) had various underlying cardiac diseases,including congenital cardiovascular diseases in 44 cases and rheumatic heart diseases in 15 cases. The main clinical manifestations were anemia (147 cases,93.6%),fever(137 cases,87.3%) and heart murmur (120 cases,76.4%). Vegetation was found in 12 cases (7.6%) with transesophageal echocardiography (TEE) but not with transthoracic echocardiography (TTE) . Culture results showed the most common causative microorganisms were Streptococci (76 cases,48.4%),with Viridans streptococci dominated in 70 cases,and Staphylococci (33 cases,21.0%) (Staphylococcus aureus dominated in 18 cases). All patients were treated with antimicrobial agents. Eighty-five patients (54.1%) received surgical intervention,of which 72 cases received valve replacement. Twenty-seven patients were cured,88 patients were markedly improved,38 patients discontinued treatment,and 4 patients died. The therapeutic efficacy of operation group was better. CONCLUSION: The clinical characteristics of IE included: the age of onset increased,congenital heart disease was the most underlying disease,and Viridians streptococci was the most popular causative microorganism. Surgical therapy can effectively improve the outcomes of IE patients.

Comparison of clinical features and prognostic factors in HIV-negative adults with cryptococcal meningitis and tuberculous meningitis: a retrospective study.

BACKGROUND: The incidence of cryptococcal meningitis (CM) and tuberculous meningitis (TBM) have gradually increased in recent years. These two types of meningitis are easily misdiagnosed which leads to a poor prognosis. In this study we compared differences of clinical features and prognostic factors in non-HIV adults with CM and TBM. METHODS: We retrospectively reviewed the medical records of CM and TBM patients from January 2008 to December 2015 in our university hospital in China. The data included demographic characteristics, laboratory results, imaging findings, clinical outcomes. RESULTS: A total of 126 CM and 105 TBM patients were included. CM patients were more likely to present with headache, abnormal vision and hearing, and they might be less prone to fever and cough than TBM patients (P < 0.05). Higher percentage of CM patients presented with cerebral ischemia/infarction and demyelination in brain MRI than TBM patients (P < 0.05). CM patients had lower counts of WBC in CSF, lower total protein in CSF and serum CD4/CD8 ratio than TBM patients (P < 0.05). After three months of treatment, CM group have worse outcome than TBM group (P < 0.05). Multivariate analysis showed that age more than 60y (OR = 4.981, 95% CI: 1.955-12.692, P = 0.001), altered mentation (OR = 5.054, 95% CI: 1.592-16.046, P = 0.006), CD4/CD8 ratios < 1 (OR = 8.782, 95% CI: 2.436-31.661, P = 0.001) and CSF CrAg ≥ 1:1024 (OR = 4.853, 95% CI: 1.377-17.098, P = 0.014) were independent risk factors for poor prognosis for CM patients. For TBM patients, hydrocephalus (OR = 7.290, 95% CI: 1.630-32.606, P = 0.009) and no less than three underlying diseases (OR = 6.899, 95% CI: 1.766-26.949, P = 0.005) were independent risk factors, headache was a protective factor of prognosis. CONCLUSIONS: Our study provided some helpful clues in the differential diagnosis of non-HIV patients with CM or TBM and identified some risk factors for the poor prognosis of these two meningitis which could help to improve the treatment outcome. Further studies are worth to be done.

[Clinical Analysis of 94 Patients with Neurocysticercosis in Sichuan Province].

Objective: To analyze the clinical features of neurocysticercosis（NCC） to provide evidence for clinical diagnosis and treatment of the disease. Methods: Medical records of NCC patients in the West China Hospital of Sichuan University received between January 2003 and January 2013 were reviewed retrospectively. The epidemiological data, clinical manifestations, therapeutic procedures and outcomes of the patients were analyzed. Results: A total of 94 NCC patients met the recruiting criteria, of whom 67.0%（63/94） were male, 59.6%（56/94） ranged 30-55 years old, 73.4%（69/94） had a living history in endemic regions such as Aba, Ganzi and Liangshan prefectures, 80.9%（76/94） lived in rural areas. NCC was clinically characterized by epilepsy, headache and intracranial hypertension. The positive rate for anti-T. solium antibodies by ELISA was 96.8%（91/94）, and the total positive scan rate of neuroimaging including CT and MRI was 95.7%（90/94）. In addition, 73 patients were suspected to have NCC at the first diagnosis, with a misdiagnosis rate of 22.3%（21/94）. Seventy-nine of the patients received albendazole treatmentï¼»20 mg/（kg·d）, twice per day for 10 days as one treatment course, 1-3 courses as neededï¼½. Eleven patients received praziquantel（total dose of 120-180 mg/kg, 3 times per day for 3 days as one treatment course, 1-3 courses）, and 4 received a combination of albendazole and praziquantel. Symptoms improved in 77 cases（81.9%）, but 12 of them（12/77, 15.6%） relapsed. The improvement rate of the albendazole group（6/11, 84.8%） was significantly higher than that of the praziquantel group（54.6%）（P<0.05）. Conclusion: NCC more commonly occurs in young males and lacks specific clinical manifestations. Neuroimaging combined with serum specific antibody tests is crucial for diagnosis. Albendazole has better therapeutic effects than praziquantel.

[Analysis of clinical characteristics in 122 adult patients with candidemia].

OBJECTIVE: To analyze the clinical characteristics of patients with candidemia for better clinical diagnosis and management of the disease. METHOD: A retrospective study was carried out in 122 patients with confirmed diagnosis of candidemia from January 2010 to June 2014 in West China hospital of Sichuan University. The clinical features, risk factors, laboratory tests, treatments and clinical outcomes were reviewed and analyzed. RESULTS: The clinical symptoms mainly include chill, shivering and fever (moderate fever or high fever). A total of 85 patients (69.7%) complicated with more than or equal to two kinds of underlying diseases, and 108 patients (88.5%) have more than or equal to three risk factors.There were 82.8% patients with increased white blood cell counts, 49.2% patients with elevated aminotransferase levels and 41.0% patients with increased creatinine levels. The isolated strains were albicans (42, 34.6%), tropicalis (32, 26.2%), glabrata (23, 18.9%) and parapsilosis (18, 14.8%). Susceptibility tests indicated some strains were resistant to antifungal drugs. Sixty-seven patients were cured or improved, 55 died or discharged voluntarily. The mortality rate was 45.1%. The multivariate Logistic regression analysis showed the independent correlative factors of mortality were mechanical ventilation (OR=4.9, P=0.02), malignancy (OR=11.39, P=0.01) and diabetes (OR=5.93, P=0.02). Early empiric anti-fungal therapy helped reduce the fatality rate (OR=0.12, P=0.03). CONCLUSION: Actively treating underlying diseases can improve the clinical effect. The key to decrease the mortality is appropriate antifungal chemotherapy.

Analysis of cerebrospinal fluid protein concentrations of patients with cryptococcal meningitis treated with antifungal agents.

BACKGROUND: Many neurological diseases are accompanied by an increase in the cerebrospinal fluid (CSF) protein concentration, which indicates dysfunction of the blood-CSF/blood-brain barrier. However, the significance CSF protein concentration of patients with cryptococcal meningitis (CM) is not fully understood. The aim of the present was to determine whether CSF protein concentrations correlated with the responses of patients to treatment with antifungal drugs. METHODS: We conducted a retrospective study of the analytical data of 623 lumbar punctures of 46 patients with CM who were treated at West China Hospital. We divided the patients into groups with good or poor responses to antifungal treatment. We used a generalized linear mixed model (GLMM) to evaluate the significance of the differences between the two groups. RESULTS: The baseline CSF protein concentrations of the good antifungal response group (GR-group) (median = 0.97 g/L) were higher compared with those of the poor antifungal response group (PR-group) (median = 0.72 g/L). Analysis using the GLMM indicated that the CSF protein concentration of the GR-group decreased at a rate of 1.8 mg/L per day after antifungal treatment started and was 2.1 mg/L higher compared with that of the PR-group. CONCLUSIONS: Compared with poor responders, we found that the baseline CSF protein concentrations of good responders were higher and decreased at faster rate after the initiation of antifungal treatment.

Effect of da-cheng-qi decoction on pancreatitis-associated intestinal dysmotility in patients and in rat models.

The impairment of intestinal motility and related infectious complications are the predominant clinical phenomenon in patients with severe acute pancreatitis (SAP). We aimed to investigate the effects of Da-Cheng-Qi decoction (DCQD) on the gastrointestinal injury in SAP patients and the potential mechanism involved in rats. DCQD was enema administered to 70 patients for 7 days in West China Hospital. Mortality and organ failure during admission were observed and blood samples for laboratory analysis were collected. We also experimentally examined plasma inflammatory cytokines in rat serum and carried the morphometric studies of the gut. Intestinal propulsion index and serum and tissue vasoactive intestinal peptide (VIP) were also detected. Though DCQD did not affect the overall incidence of organ failure, it shortened the average time of paralytic intestinal obstruction and decreased the morbidity of infectious complications in patients with SAP. Compared with untreated rats, the DCQD lowered the levels of proinflammatory cytokine and decreased the mean pathological intestinal lesion scores. The VIP level in intestinal tissue or serum in DCQD group was obviously lowered and intestinal propulsion index was significantly improved. In conclusion, DCQD has good effect on pancreatitis-associated intestinal dysmotility in patients and in rat models.

[Clinical analysis of 137 patients with visceral leishmaniasis].

OBJECTIVE: To analyze the clinical and epidemiological characteristics of visceral leishmaniasis cases in Sichuan. METHODS: The medical records of 137 patients with visceral leishmaniasis were reviewed between January 2000 and April 2012 in West China Hospital. The epidemiological data, clinical manifestations, laboratory features, diagnosis, therapeutic procedures and outcome of the patients were retrospectively analyzed. RESULTS: Eighty-eight (64.2%) out of 137 cases were the residents in the endemic area of Sichuan Province and adjacent areas, and 49 (35.8%) were non-endemic area residents with a history of visiting endemic area. Patients living in rural areas accounted for 84.7% (116/137), in town for 15.3% (21/137). Visceral leishmaniasis should be strongly suspected in a patient with prolonged fever, marked hepatosplenomegaly, lymphadenectasis, cytopenia and hypergammaglobulinemia. All patients showed positive in rk39 dipstick test, and were treated with antimony sodium gluconate. Among these patients, 86.1% (118/137) were cured by drug, 2.9% (4/137) received splenectomy, and 6.6% (9/137) relapsed. The misdiagnosis rate was 23.4% (32/137). CONCLUSION: Bone marrow smear staining and biopsy, combined with rk39 antibody detection and epidemiological history are crucial for early diagnosis and treatment of visceral leishmaniasis. Antimonials is still an effective therapeutic choice.