Value Evaluation of Quantitative Aspergillus fumigatus-Specific IgG Antibody Test in the Diagnosis of Non-neutropenic Invasive Pulmonary Aspergillosis.

Background: The role of Aspergillus-specific IgG antibody test in the diagnosis of non-neutropenic invasive pulmonary aspergillosis (IPA) is still uncertain, and related studies are also limited. Purpose: This study aims to evaluate the quantitative test value of Aspergillus fumigatus-specific IgG antibody in non-neutropenic IPA, which could provide additional evidence for related clinical diagnosis. Methods: This prospective study collected clinical data of suspected IPA patients from January, 2020 to December, 2022, and patients were divided into two groups, IPA and non-IPA. The study analyzed clinical characteristics and diagnostic value of Aspergillus-specific IgG antibody test, using the receiver operating characteristic (ROC) curve to evaluate diagnostic efficacy. Results: The study enrolled 59 IPA cases and 68 non-IPA cases, the average admission age of IPA group was 63.2±9.6 (33-79), and the gender ratio (male:female) of IPA group was 42:17. The proportion of patients with history of smoking and COPD were higher in IPA group (59.3% vs 39.7%, P=0.027; 33.9% vs 14.7%, P =0.011, respectively). The level of Aspergillus fumigatus-specific IgG antibody in IPA group was significantly higher than non-IPA group (202.1±167.0 vs 62.6±58.0, P<0.001). The area under the ROC curve was 0.799 (95%CI: 0.718, 0.865 P<0.001), and the cut-off with best diagnostic efficacy was 91 AU/mL. Conclusion: Immunological test plays an important role in the diagnosis of pulmonary aspergillosis, and Aspergillus-specific IgG antibody test has the good diagnostic value in non-neutropenic IPA.

Sensitive and rapid identification of pathogens by droplet digital PCR in a cohort of septic patients: a prospective diagnostic study.

BACKGROUND: There is a critical need for a rapid and sensitive pathogen detection method for septic patients. This study aimed to investigate the diagnostic efficacy of Digital droplet polymerase chain reaction (ddPCR) in identifying pathogens among suspected septic patients. METHODS: We conducted a prospective pilot diagnostic study to clinically validate the multiplex ddPCR panel in diagnosing suspected septic patients. A total of 100 sepsis episodes of 89 patients were included in the study. RESULTS: In comparison to blood culture, the ddPCR panel exhibited an overall sensitivity of 75.0% and a specificity of 69.7%, ddPCR yielded an additional detection rate of 17.0% for sepsis cases overall, with a turnaround time of 2.5 h. The sensitivity of ddPCR in the empirical antibiotic treatment and the non-empirical antibiotic treatment group were 78.6% versus 80.0% (p > 0.05). Antimicrobial resistance genes were identified in a total of 13 samples. Whenever ddPCR detected the genes beta-lactamase-Klebsiella pneumoniae carbapenemase (blaKPC) or beta-lactamase-New Delhi metallo (blaNDM), these findings corresponded to the cultivation of carbapenem-resistant gram-negative bacteria. Dynamic ddPCR monitoring revealed a consistent alignment between the quantitative ddPCR results and the trends observed in C-reactive protein and procalcitonin levels. CONCLUSIONS: Compared to blood culture, ddPCR exhibited higher sensitivity for pathogen diagnosis in suspected septic patients, and it provided pathogen and drug resistance information in a shorter time. The quantitative results of ddPCR generally aligned with the trends seen in C-reactive protein and procalcitonin levels, indicating that ddPCR can serve as a dynamic monitoring tool for pathogen load in septic patients.

An externally validated clinical-laboratory nomogram for myocardial involvement in adult idiopathic-inflammatory-myopathy patients.

OBJECTIVES: This study aimed at identifying clinical and laboratory risk factors for myocardial involvement (MI) in idiopathic inflammatory myopathies (IIMs) patients as well as constructing a risk-predicted nomogram for prediction and early identification of MI. METHODS: An IIMs cohort in southeastern China was constructed, including 504 adult IIMs patients who met the inclusion and exclusion criteria, and were hospitalized at four divisions of the First Affiliated Hospital, Zhejiang University School of Medicine from January 1st 2018 to April 30st 2022. After dividing patients into the training cohort and the validation cohort, risk factors for MI were identified through least absolute shrinkage and selection operator regression and multivariate logistic regression. A risk-predicted nomogram was established and validated internally and externally for discrimination, calibration and practicability. RESULTS: In this cohort, 17.7% of patients developed MI and the survival was significantly inferior to that of IIMs patients without MI (P < 0.001). In the training cohort, age > 55 years old (P < 0.001), disease activity > 10 points (P < 0.001), interleukin-17A (IL-17A) > 7.5 pg/ml (P < 0.001), lactic dehydrogenase (LDH) > 425 U/L (P < 0.001), anti-mitochondrial antibodies (AMAs, P = 0.017), and anti-MDA5 antibody (P = 0.037) were significantly correlated with development of MI. A nomogram was established by including the above values to predict MI and was found efficient in discrimination, calibration, and practicability through internal and external validation. CONCLUSION: This study developed and validated a nomogram model to predict the risk of MI in adult IIMs patients, which can benefit the prediction and early identification of MI as well as timely intervention in these patients.

Clinical impact of metagenomic next-generation sequencing of peripheral blood for the diagnosis of invasive mucormycosis: a single-center retrospective study.

IMPORTANCE: Given the high fatality rates, prompt and accurate identification of the fungal culprit is crucial, emphasizing the need for invasive mucormycosis. Unfortunately, mucormycosis lacks definitive biomarkers, depending primarily on smears, cultures, or pathology, all necessitating invasive specimen collection from the infection site. However, obtaining valid specimens early in critically ill patients poses substantial risks and challenges. Whether peripheral blood metagenomic next-generation sequencing (mNGS) can enhance early mucormycosis diagnosis, especially when direct specimen collection from the infection site is challenging, is warranted. This is a large-scale clinical study conducted to evaluate the utility and clinical impact of mNGS of peripheral blood for the diagnosis of invasive mucormycosis. We believe our study provided both novelty in translational medicine and a great value for the medical community to understand the strengths and limitations of mNGS of peripheral blood as a new diagnostic tool for the diagnosis and management of invasive mucormycosis.

The application of nanopore targeted sequencing for pathogen diagnosis in bronchoalveolar lavage fluid of patients with pneumonia: a prospective multicenter study.

OBJECTIVE: To evaluate the value of nanopore targeted sequencing in diagnosing pneumonia pathogens. METHODS: This large-scale multicentre prospective study performed in 8 hospitals across China from April to October 2022. Hospitalised patients with a diagnosis of pneumonia at admission were included. Complete clinical data were collected, and bronchoalveolar lavage fluid were obtained from each patient. These samples underwent simultaneous testing using conventional microbial testing, metagenomic next-generation sequencing, and nanopore targeted sequencing. RESULTS: A total of 218 patients were included. Among the 168 cases of pulmonary infection, 246 strains of pathogens were confirmed. Nanopore targeted sequencing outperformed conventional microbial testing, identifying more pathogens with a sensitivity increase of 47.9% (77.2% vs. 29.3%). Metagenomic next-generation sequencing had a sensitivity of 82.9%. Total of 70.1% patients had consistent results in both metagenomic next-generation sequencing and nanopore targeted sequencing. Nanopore targeted sequencing exhibited significantly higher sensitivity in detecting Pneumocystis jiroveci, cytomegalovirus, Mycobacterium tuberculosis, Nontuberculous mycobacteria, Streptococcus pneumoniae, and Mycoplasma pneumoniae compared to conventional microbial testing. However, metagenomic next-generation sequencing demonstrated higher sensitivity than nanopore targeted sequencing for Aspergillus (88.5% vs. 53.8%). Regarding the detection of co-infections, nanopore targeted sequencing displayed significantly higher sensitivity than conventional microbial testing (76.7% vs. 28.7%) and was on par with metagenomic next-generation sequencing (76.7% vs. 82.9%). CONCLUSION: Nanopore targeted sequencing performs equally well as metagenomic next-generation sequencing in bronchoalveolar lavage fluid for pathogen diagnosis in pneumonia, both methods showing higher sensitivity than conventional microbial testing. Nanopore targeted sequencing can be considered a reliable method for diagnosing pathogens in pneumonia.

Virulence Factors and Pathogenicity Mechanisms of Acinetobacter baumannii in Respiratory Infectious Diseases.

Acinetobacter baumannii (A. baumannii) has become a notorious pathogen causing nosocomial and community-acquired infections, especially ventilator-associated pneumonia. This opportunistic pathogen is found to possess powerful genomic plasticity and numerous virulence factors that facilitate its success in the infectious process. Although the interactions between A. baumannii and the pulmonary epitheliums have been extensively studied, a complete and specific description of its overall pathogenic process is lacking. In this review, we summarize the current knowledge of the antibiotic resistance and virulence factors of A. baumannii, specifically focusing on the pathogenic mechanisms of this detrimental pathogen in respiratory infectious diseases. An expansion of the knowledge regarding A. baumannii pathogenesis will contribute to the development of effective therapies based on immunopathology or intracellular signaling pathways to eliminate this harmful pathogen during infections.

The combined use of parasternal intercostal muscle thickening fraction and P0.1 for prediction of weaning outcomes.

BACKGROUND: A variety of parameters and diaphragmatic ultrasound in ventilator weaning has been studied extensively, and the findings yield inconsistent conclusions. The parasternal intercostal muscle holds important substantial respiratory reserve capacity when the central drive is enhanced, the predictive value of combining parasternal intercostal muscle ultrasound parameters with P0.1(airway occlusion pressure at 100 msec) in assessing ventilator weaning outcomes is still unknown. OBJECTIVES: Our study aimed to evaluate the predictive efficacy of parasternal intercostal muscle ultrasound in conjunction with P0.1 in determining weaning failure. METHODS: We recruited patients who had been admitted to ICU and had been receiving mechanical ventilation for over two days. All patients underwent a half-hour spontaneous breathing trial (SBT) with low-level pressure support ventilation (PSV). They were positioned semi-upright for parasternal intercostal muscle ultrasound evaluations, including parasternal intercostal muscle thickness (PIMT), and parasternal intercostal muscle thickening fraction (PIMTF); P0.1 was obtained from the ventilator. Weaning failure was defined as the need for non-invasive positive pressure ventilation or re-intubation within 48 h post-weaning. RESULTS: Of the 56 enrolled patients with a mean age of 63.04 ± 15.80 years, 13 (23.2%) experienced weaning failure. There were differences in P0.1 (P = .001) and PIMTF (P = .017) between the two groups, but also in patients with a diaphragm thickness ≥ 2 mm. The predictive threshold values were PIMTF ≥ 13.15% and P0.1 ≥ 3.9 cmH2O for weaning failure. The AUROC for predicting weaning failure was 0.721 for PIMTF, 0.792 for P0.1, and 0.869 for the combination of PIMTF and P0.1. CONCLUSIONS: The parasternal intercostal muscle thickening fraction and P0.1 are independently linked to weaning failure, especially in patients with normal diaphragm thickness. The combination of parasternal intercostal muscle thickening fraction and P0.1 can serve as a valuable tool for the precise clinical prediction of weaning outcomes. TRIAL REGISTRATION: Chinese Clinical Trial Registry website (ChiCTR2200065422).

Zoonotic fungus Arthroderma multifidum causing chronic pulmonary infection.

A rare case of fungus Arthroderma multifidum infection occurred in a 63-year-old man. The patient had some risk factors, including occupational exposure, immunosuppressive state, and structural basis following pulmonary tuberculosis and pneumothorax surgery. The pathogen was repeatedly isolated from bronchoalveolar lavage fluid and identified by gene sequencing. It is the first report of human infection caused by A. multifidum. Whole genome sequencing and analysis of its genomic characterization are completed. The findings provide us with a key clinical insight that the combination of immune suppression and environmental exposure could create an ideal condition for zoonotic fungal infections.

Clinical outcomes and risk factor of immune checkpoint inhibitors-related pneumonitis in non-small cell lung cancer patients with chronic obstructive pulmonary disease.

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is the most common co-morbidity associated with non-small cell lung cancer (NSCLC) patients. Immune checkpoint inhibitors related pneumonitis (CIP) is a common immune-related adverse event that can be life-threatening. The study aims to evaluate the association of COPD with the incidence and outcome of CIP in NSCLC patients receiving immune checkpoint inhibitors (ICIs). MATERIALS AND METHODS: We retrospectively collected data from 122 patients diagnosed with NSCLC and treated with ICIs in our department. Baseline pulmonary function was performed in the whole cohort. The incidence, risk factors, treatment and outcome of CIP patients were evaluated. Furthermore, the efficacy of ICIs in patients with COPD was analyzed. RESULTS: Nineteen patients (15.5%, 19/122) developed CIP during ICIs treatment, most patients with CIP were grade 1-2, and the incidence of CIP was comparable in patients with COPD and those without COPD (18.0% vs. 13.1%, P = 0.618). In addition, an increasing trend in the incidence of CIP among patients with pulmonary fibrosis on baseline chest CT scans (27.3% vs. 13.0%, P = 0.093). There is a longer progression-free survival in COPD patients than the non-COPD patients. CONCLUSION: Coexisting COPD did not predict the higher risk of CIP in NSCLC treated with ICIs therapy. Nevertheless, pre-existing pulmonary fibrosis on CT scan may increase the risk of CIP, close monitoring is advised in these patients during ICIs.

Tislelizumab-related enteritis successfully treated with adalimumab: A case report.

BACKGROUND: With programmed death-1 (PD-1) inhibitors becoming the standard treatment for lung cancer, PD-1-related adverse reactions and treatment have gradually become prominent. CASE SUMMARY: First reported case of tislelizumab-related enteritis successfully treated with adalimumab 40mg every 2 wk for 3 times in an advanced lung cancer patient who received first-line tislelizumab/pemetrexed/carboplatin for 4 cycles. The patient continued receiving the treatment of pemetrexed/carboplatin after symptoms, abdominal computed tomography and colonoscopy improved, significant diarrhea was not occurred. CONCLUSION: Adalimumab can be an effective treatment option for patients with PD-1 antibody related enteritis if they do not respond well to glucocorticoid treatment.

Nosocomial Infections in Nonsurgical Patients Undergoing Extracorporeal Membrane Oxygenation: A Retrospective Analysis in a Chinese Hospital.

Background: The effect of nosocomial infections (NIs) in adult patients undergoing ECMO has been rarely reported in China. Moreover, the effect of NIs on ECMO patients' mortality is still unclear and inconclusive according to literature data. In this study, we examined the prevalence, risk factors, causative organisms, and effects on outcomes of NIs in ECMO patients. Methods: A total of 79 nonsurgical patients (mean age 53.3±15.2 year (yr); 66% male) who underwent ECMO between January 2011 and September 2020 were enrolled in this retrospective study. Patients' demographic and clinical data and ECMO parameters were collected from all patients. Results: Among 79 patients who underwent ECMO for a total of 1253 ECMO days (mean time 15.9±14.1 d), 42 developed NIs. We observed 30 ventilator-associated pneumonia (VAP), 19 bloodstream infections (BSIs), and 4 urinary tract infections, corresponding to 23.9/1000 ECMO days, 15.2/1000 ECMO days, and 3.2/1000 ECMO days, respectively. ECMO duration (22.0±16.5 VS 8.9±5.3 d, P < 0.001), invasive mechanical ventilation (IMV) duration (27.4±20.5 VS 11.4±10.1 d, P < 0001), and ICU length of stay (35.9±22.9 VS 15.7±9.2 d, P < 0.001) were longer in patients with NIs. The independent risk factors for NIs were ECMO duration (Odds Ratio [OR], 1.414; 95% Confidence Interval [CI], (1.051-1.238); P = 0.002) and viral pneumonia (OR, 5.788; 95% CI, (1.551-21.596); P = 0.009). Gram-negative bacteria were the most common causative organisms of NIs; Acinetobacter baumannii (A. baumannii), Klebsiella pneumoniae (K. pneumoniae), and Pseudomonas aeruginosa (P. aeruginosa) were the most common bacteria. BSI (OR, 8.106; 95% CI, (1.384-47.474); P = 0.02) was an independent predictor for mortality. Conclusion: NIs are common complications in patients during ECMO treatment, especially VAP, followed by BSI. Also, BSI can negatively affect the survival rate.

Allergic Bronchopulmonary Mycosis Caused by Mucor Overlapping With Invasive Pulmonary Mucormycosis: A Case Report.

Mucormycosis is a rare and invasive fungal infection with high mortality. Cases of invasive pulmonary mucormycosis that involve allergic reactions such as allergic bronchopulmonary mycosis are rarely reported. Herein, we describe a case of invasive pulmonary mucormycosis overlapping with allergic diseases in a patient who presented with eosinophilia and high total plasma immunoglobulin E (IgE). The patient was successfully treated with systemic corticosteroids (initial dose of prednisolone approximately 0.5 mg/kg per day, total duration less than 3 months) combined with posaconazole antifungal therapy. The treatment resulted in recovery of peripheral-blood eosinophil count and total plasma IgE, and significant reduction in lung lesions. A subsequent lobectomy was performed. The findings in this case indicate that systemic corticosteroid therapy may contribute to the treatment of pulmonary mucormycosis combined with allergic factors.

Clinical Features of Pulmonary Nocardiosis in Patients with Different Underlying Diseases: A Case Series Study.

Objective: To investigate the clinical features of pulmonary nocardiosis (PN) in patients with different underlying diseases. Methods: Clinical, imaging, treatment and prognosis data from patients diagnosed with PN from July 2011 to June 2021 at the First Affiliated Hospital, Zhejiang University School of Medicine were collected and analyzed. According to different underlying diseases, patients were grouped into immunocompromised host (ICH) group and immunocompetent host (ICO) group, and clinical characteristics were compared between the two groups. Results: There were 64 patients with PN, including 42 males, aged from 21 to 86 (57.1 ± 15.7) years. The most common clinical manifestations were cough, expectoration, fever. There were 41 cases in the ICH group and 23 cases in the ICO group. There were 11 cases with underlying pulmonary diseases in the ICH group, including 2 cases of bronchiectasis, 4 cases of chronic obstructive pulmonary disease (COPD), etc. There were 11 cases of underlying pulmonary basic diseases in ICO group, including 7 cases of bronchiectasis and COPD, 1 case of bronchiectasis, 1 case of COPD, etc. The proportion of patients with bronchiectasis and COPD in the ICO group was significantly higher (P < 0.05). Extrapulmonary nocardiosis infection occurred in 6 patients of the ICH group. During the period of hospitalization, 87.0% patients in ICO group received SMZ/TMP therapy, 73.2% of patients in ICH group received two drug combination therapy. In the ICH group, mortality at 28 days was 14.6% and 8.7% in the ICO group. Conclusion: PN mainly occurred in ICH patients, but also occurred in the ICO cases to a lesser extent, especially in patients with bronchiectasis and/or COPD. Complicated with extrapulmonary infections mainly occurred in ICH population and combination of two antibiotics was often used in ICH group. The case fatality rates were 14.6% in ICH and 8.7% in ICO cases, respectively.

The gigA/gigB Genes Regulate the Growth, Stress Response, and Virulence of Acinetobacter baumannii ATCC 17978 Strain.

Acinetobacter baumannii is an important pathogen of nosocomial infection. Recently, a group of genes, named "gig" (for Growth in Galleria), have been identified in a contemporary multi-drug resistant clinical isolate of A. baumannii-strain AB5075. Among these so-called gig genes, gigA and gigB were found to promote antibiotic resistance, stress survival, and virulence of AB5075 by interacting with the nitrogen phosphotransferase system (PTSNtr). This study aimed to investigate the roles of gigA/gigB, which appear to comprise a stress-signaling pathway (encoding for an atypical two-component system response regulator and a predicted anti-anti-sigma factor, respectively), and the involvement of ptsP (encoding the Enzyme I component of the PTSNtr) in the growth, stress resistance, and virulence of the widely studied A. baumannii strain ATCC 17978. Genetic analyses of strains harboring mutations of gigA and gigB were performed to investigate the roles of these genes in bacterial growth, stress resistance, evading macrophage defense, and killing of Galleria mellonella larva. In contrast with findings from strain AB5075 where gigA and gigB contribute to aminoglycoside resistance, the data presented herein indicate that the loss of gigA/gigB does not impact antibiotic resistance of strain ATCC 17978. Interestingly, however, we found that deletion of gigA/gigB in the ATCC 17978 background imparts a general growth in laboratory medium and also conferred growth and replication defects within murine macrophages and an inability to kill G. mellonella larvae. Importantly, studies as well as the loss of ptsP restored the phenotypes of the gigA/gigB mutant to that of the wild-type. The data presented herein indicate that in A. baumannii ATCC 17978, the gigA/gigB genes play a key role in both growth and virulence traits, but are dispensable for other stress-resistance survival phenotypes, including aminoglycoside resistance. Our findings thus highlight several similarities and also important differences between the gigA/gigB stress-signaling pathway in two commonly studied isolates of this troublesome pathogen.

Clinical Impact of Metagenomic Next-Generation Sequencing of Bronchoalveolar Lavage in the Diagnosis and Management of Pneumonia: A Multicenter Prospective Observational Study.

Rapid and accurate pathogen identification is necessary for appropriate treatment of pneumonia. Here, we describe the use of shotgun metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage for pathogen identification in pneumonia in a large-scale multicenter prospective study with 159 patients enrolled. The results of mNGS were compared with standard methods including culture, staining, and targeted PCR, and the clinical impact of mNGS was evaluated. A positive impact was defined by a definitive diagnosis made using the mNGS results, or change of management because of the mNGS results, leading to a favorable clinical outcome. Overall, mNGS identified more organisms than standard methods (117 versus 72), detected 17 pathogens that consistently were missed in all cases by standard methods, and had an overall positive clinical impact in 40.3% (64 of 159) of cases. mNGS was especially useful in identification of fastidious and atypical organisms causing pneumonia, contributing to detection of definitive pathogens in 45 (28.3%) cases in which standard results were either negative or insufficient. mNGS also helped reassure antibiotic de-escalation in 19 (11.9%) cases. Overall, mNGS led to a change of treatment in 59 (37.1%) cases, including antibiotic de-escalation in 40 (25.2%) cases. This study showed the significant value of mNGS of bronchoalveolar lavage for improving the diagnosis of pneumonia and contributing to better patient care.

Clinical Characteristics of Chronic Lung Abscess Associated with Parvimonas micra Diagnosed Using Metagenomic Next-Generation Sequencing.

PURPOSE: Parvimonas micra (P. micra) is a Gram-positive anaerobic bacterium distributed in the oral cavity, with a potential to become pathogenic causing lung abscess. Due to the lack of specificity of symptoms and the difficulty in culture, the diagnosis of lung abscess associated with P. micra is delayed. It is essential to elucidate the clinical characteristics of lung abscess associated with P. micra. METHODS: From January 2019 to July 2020, five patients with chronic lung abscess associated with P. micra diagnosed by pathological biopsy and metagenomic next-generation sequencing (mNGS) were analyzed in this retrospective study. RESULTS: Among the five patients, four had a history of smoking, three had periodontitis, and two had a history of drinking. The average course of the disease was 6.5 months. High-density flake-like or mass shadows with irregular boundaries were observed in the chest computed tomography (CT) images of the five patients, and liquefactive necrosis was detected in the middle of the lesions; however, no gas-liquid plane or cavity was noted, making it difficult to distinguish a lung cancer. The pathological biopsy of the five patients showed chronic inflammation of lung tissue, and P. micra was detected by mNGS in the biopsy or bronchoalveolar lavage fluid samples. Two patients were treated with amoxicillin-clavulanate, two had metronidazole, and one had moxifloxacin. Among them, four recovered after receiving antibiotic treatment, and the remaining one underwent surgical resection due to poor antibiotic treatment effect. CONCLUSION: Chronic lung abscess associated with P. micra, common in elderly male smokers with poor oral hygiene, is often diagnosed in a delayed manner and misdiagnosed as lung cancer. The mNGS technology is beneficial to the rapid determination of P. micra.

Hyperlipidemia Caused by Voriconazole: A Case Report.

Voriconazole has been widely used in clinical practice for nearly 20 years. The adverse reactions caused by voriconazole have been reported gradually, such as visual impairment, hepatotoxicity, skin rash. At present, there are few reports about triazole antifungal drugs causing the increase of triglyceride and total cholesterol. Thus, the present study reported a case of chronic pulmonary aspergillosis with significantly increased blood lipids after treatment with voriconazole. In this case, the patient's total cholesterol was normal, and triglyceride was 2.64 times of the upper limit of the reference value at the time of admission. On the 30th day after oral administration of voriconazole 200mg q12h, triglyceride and total cholesterol were 4.55 times and 3.31 times of the baseline levels, respectively, with the trough concentration of voriconazole of 6.6 µ g/mL. After 28 days of voriconazole withdrawal and itraconazole administration, triglyceride decreased to 1.45 times of baseline level and total cholesterol decreased to the normal range. After another 24 days of treatment with voriconazole 200mg q12h, triglyceride increased again to 3.25 times of the baseline level and cholesterol was within the normal range. At the same time, the trough concentration of voriconazole was 3.2 µ g/mL. After 14 days of treatment with voriconazole 100mg q12h, the triglyceride level recovered to the baseline level, with the trough concentration of voriconazole of 1.5 µ g/mL. The Naranjo's rating scale was used, the final score was 10 points, indicating that the causal relationship between voriconazole and dyslipidemia was positive, which was likely to be related to the trough concentration of voriconazole.

Bloodstream Infections due to Carbapenem-Resistant Klebsiella pneumoniae: A Single-Center Retrospective Study on Risk Factors and Therapy Options.

We aimed to compare efficacy of different patterns of antibiotics and explore the risk factors related to mortality in patients with bloodstream infections (BSIs) due to carbapenem-resistant Klebsiella pneumoniae (CRKP). This study retrospectively included 89 patients with BSIs due to CRKP with complete data during the year of 2018 in the First Affiliated Hospital of Zhejiang University School of Medicine. Overall, the 28-day mortality was 47.2% (42/89). Multivariate analysis of Cox regression revealed that hematological malignancy (hazard ratio [HR] 5.698; 95% confidence interval [CI], 2.405-13.504; p < 0.001) and Pitt bacteremia score (HR per unit increase, 1.303; 95% CI, 1.109-1.532; p = 0.001) were identified as independent predictors for 28-day mortality. Among 70 patients with appropriate therapy, 35 received tigecycline (TGC)-based therapy, 20 received polymyxin B (PMB)-based therapy, 9 received ceftazidime/avibactam-based therapy, and 6 patients had other kinds of antibiotics, including ciprofloxacin, amikacin, and cotrimoxazole. By adjusting variables selected by crude analysis, it showed that receiving PMB-based therapy provided a survival benefit comparing with TGC-based therapy (HR, 0.068; 95% CI, 0.018-0.260; p < 0.001). Hematological malignancy and Pitt bacteremia score were independent risk factors of death in patients with BSIs due to CRKP and PMB-based therapy improved survival rate compared with TGC-based therapy.

Seawater-Associated Highly Pathogenic Francisella hispaniensis Infections Causing Multiple Organ Failure.

A rare case of Francisella hispaniensis infection associated with seawater exposure occurred in a deep-sea diving fisherman in Zhejiang, China. He had skin and soft tissue infection that progressed to bacteremia and multiple organ failure. Moxifloxacin treatment cleared the infections, but the patient suffered a sequela of heart damage.

Secondary Bacterial Infections in Critical Ill Patients With Coronavirus Disease 2019.

Secondary bacterial infections occurred in 13.9% (5 of 36) of critical ill patients with coronavirus disease 2019. All 5 patients had been admitted to intensive care unit and received mechanical ventilation before developing bacterial infection. Active surveillance of culture should be performed for critically ill patients. Prevention of nosocomial infection should to be taken seriously.