The management and outcome of cryptococcosis in patients with different immune statuses and treatment protocols: A multicenter real-world study in Jiangsu Province - China.

OBJECTIVE: The incidence of cryptococcosis is increasing in non-immunocompromised patients. However, the evidence on proper management is inadequate in this population. We conducted this multi-center real-world study in pulmonary cryptococcosis patients with different immune statuses, so as to provide practical evidence for optimized clinical management of cryptococcosis, especially for mild-to-moderate immunodeficient diseases patients. METHODS: This is a prospective observational study. The clinical data of patients with proven cryptococcosis were collected and analyzed from 7 tertiary teaching hospitals in Jiangsu Province, China from January, 2013 to December, 2018. Proven cases include pulmonary cryptococcosis, cryptococcal meningitis, cryptococcemia and cutaneous cryptococcosis. Patients were followed up over 24 months. According to their immune status, patients with cryptococcosis were divided into three groups, namely immunocompetent group (IC), mild-to-moderate immunodeficient diseases group (MID), severe immunodeficient diseases group (SID). Meanwhile, pulmonary crypotococcosis (PC) and extrapulmonary crypotococcosis (EPC) were also classified and analyzed. RESULTS: 255 proven cases of cryptococcosis were enrolled. Finally, 220 cases completed the follow-up. 143 proven cases (65.0%) were immunocompetent (IC), 41 cases (18.6%) were MID, and 36 cases (16.4%) were SID. 174 cases (79.1%) were PC and 46 cases (20.9%) were EPC. The mortality was significantly higher in SID and MID patients [47.2% (SID) vs. 12.2% (MID) vs. 0.0% (IC), p<0.001]. The mortality was also significantly higher in EPC patients [45.7% vs. 0.6% (PC), p<0.001]. Patients with alternative initial antifungal treatment had higher mortality than patients with guideline recommended initial treatment [23.1% vs. 9.5%, p=0.041]. In MID group, the mortality of receiving alternative initial antifungal treatment was significantly higher than recommended initial treatment [2/3 vs. 3/34(8.8%), p=0.043]. In pulmonary cryptococcosis patients with MID, the mortality was very similar to IC group [0.0% vs. 0.0% (IC)], lower than SID group [0.0% vs. 11.1% (SID), p=0.555]. However, in extrapulmonary cryptococcosis patients with MID, the mortality was significantly higher than that in IC [62.5% vs. 0.0% (IC)], and similar to SID patients [62.5% vs. 59.3% (SID)]. CONCLUSION: The immune status exert a significant influence on the management and prognosis of cryptococcosis patients. The mortality of cryptococcosis patients with MID is higher than that of immunocompetent patients. For MID patients with pure pulmonary cryptococcosis, it is acceptable to take the treatment recommended as IC patients. For the MID patients with extrapulmonary cryptococcosis, the mortality is high and the initial treatment should follow the regimen for SID patients. Following the recommended treatment regimen in the IDSA guideline can reduce mortality in patients with cryptococcosis. Starting on alternative initial antifungal treatment may bring worse outcomes.

Clinical Features, Treatment, and Outcome of Psittacosis Pneumonia: A Multicenter Study.

Background: We aimed to describe psittacosis pneumonia and risk factors for developing severe pneumonia in this multicenter clinical study. Methods: We collected the data of psittacosis pneumonia cases diagnosed with metagenomic next-generation sequencing (mNGS) assay from April 2018 to April 2022 in 15 tertiary hospitals in China. Results: A total of 122 patients were enrolled; 50.0% had a definite history of bird exposure. In 81.2% of cases, onset happened in autumn or winter. The common symptoms were fever (99.2%), cough (63.1%), fatigue (52.5%), shortness of breath (50.0%), chills (37.7%), central nervous system symptoms (36.9%), myalgia (29.5%), and gastrointestinal tract symptoms (15.6%). Laboratory tests showed that >70% of cases had elevated C-reactive protein, procalcitonin, erythrocyte sedimentation rate, D-dimer, lactate dehydrogenase, and aspartate aminotransferase, and >50% had hyponatremia and hypoproteinemia. The most common imaging finding was consolidation (71.3%), and 42.6% of cases met the criteria for severe pneumonia. Age >65 years and male sex were the risk factors for severe pneumonia. The effective proportion of patients treated with tetracyclines was higher than that of fluoroquinolones (66/69 [95.7%] vs 18/58 [31.0%]; P < .001), and the median defervescence time was shorter. After medication adjustment when the diagnosis was clarified, 119 of 122 (97.5%) patients were finally cured and the other 3 (2.5%) died. Conclusions: Psittacosis pneumonia has a high rate of severe disease. Proven diagnosis could be rapidly confirmed by mNGS. Tetracycline therapy had a rapid effect and a high cure rate.

The clinical value of Aspergillus-specific IgG antibody test in the diagnosis of nonneutropenic invasive pulmonary aspergillosis.

OBJECTIVES: Aspergillus-specific IgG antibody (Asp IgG) has been successfully applied in the diagnosis of chronic pulmonary aspergillosis. We explored its value in nonneutropenic invasive pulmonary aspergillosis (IPA) by a multicenter, prospective, and controlled study. METHODS: We enrolled 372 clinically suspected nonneutropenic patients with IPA from February 2015 to August 2022. After excluding 4 cases with Aspergillus colonization, the remaining 368 cases were finally confirmed as patients with IPA (n = 99), or non-IPA patients (n = 269) consisting of community-acquired pneumonia (n = 206), tuberculosis (n = 22), nontuberculous mycobacteria (n = 5), lung abscess (n = 6), or noninfectious diseases (n = 30). Asp IgG in plasma samples was tested by enzyme-linked immunosorbent assay. RESULTS: At cut-off value of ≥80 AU/mL, Asp IgG had much higher sensitivity (59.6% vs. 19.2%, p < 0.0001), but lower specificity (77.0% vs. 96.3%, p < 0.0001) than serum galactomannan (GM) (cut-off value of ≥1.0), and similar sensitivity (59.6% vs. 55.6%, p = 0.611) but lower specificity (77.0% vs. 91.2%, p = 0.001) than bronchoalveolar lavage fluid (BALF) GM (cut-off value of ≥1.0), respectively. Combination diagnosis of either positive for Asp IgG or BALF GM had higher sensitivity (81.0% vs. 55.6%, p = 0.002), but lower specificity (75.2% vs. 91.2%, p = 0.001) than BALF GM alone. The receiver operating characteristic curve showed that Asp IgG had an optimal diagnostic value when the cut-off value was 56.6 AU/ml, and the sensitivity and specificity were 77.8% and 63.9%, respectively. DISCUSSIONS: The diagnostic value of Asp IgG for IPA is superior to serum GM, and a little inferior to BALF GM in nonneutropenic patients with IPA. Considering the convenience of taking blood samples, it is a good screening and diagnostic method for nonneutropenic patients with IPA, especially for those who cannot bear invasive procedures.

Therapeutic drug monitoring and safety evaluation of voriconazole in the treatment of pulmonary fungal diseases.

Aims: The gene polymorphism of voriconazole metabolism-related liver enzyme is notable in East Asia population. It casts a significant influence on the rational use of voriconazole. We conducted this study to investigate the relationship between steady-state voriconazole trough concentration (Ctrough) and adverse effects (AEs), especially hepatotoxicity. Methods: We conducted a real-world study in the Jinling Hospital from January 2015 to June 2020. A total of 140 patients receiving voriconazole were enrolled in this study. The determination and scoring of voriconazole-associated hepatotoxicity were performed according to the Roussel Uclaf Causality Assessment Method scoring scale and the severity of hepatotoxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE). Results: Elevated steady-state voriconazole Ctrough with concomitant AEs are the most common reason for dose adjustments during treatment. Compared with the group without any AEs, voriconazole Ctrough was significantly higher in the hepatotoxicity and neurotoxicity groups, and the incidence of both events showed an overall increasing trend with increasing voriconazole Ctrough. Hepatotoxicity occurred in 66.7% of patients within 7 days of the first dose of voriconazole and 94.4% within 15 days of the dose. Steady-state voriconazole Ctrough >3.61 mg/l was associated with an increased incidence of hepatotoxicity (area under the curve = 0.645, p = 0.047). Logistic regression analysis showed that timely voriconazole dose adjustment was a predictor of attenuated hepatotoxicity after adjustment for confounders, but hepatotoxicity was not associated with voriconazole Ctrough measured at a single time point. Conclusion: Hepatotoxicity and neurotoxicity correlate with voriconazole Ctrough, and dose reduction in patients with elevated steady-state voriconazole Ctrough may prevent hepatotoxicity. In patients with early occurrence of hepatotoxicity, initial therapeutic drug monitoring (TDM) might predict the risk of hepatotoxicity. Follow-up TDM may be necessary to predict late onset hepatotoxicity. Plain Language Summary: Safety of voriconazole for the treatment of pulmonary fungal diseases Introduction: Several studies have suggested an association between the concentration of voriconazole in the blood and liver damage, but the evidence is weak. This study aimed to investigate relationships between voriconazole drug concentration and side effects and to analyze the factors affecting liver damage caused by voriconazole.Methods: We conducted a study at the Jinling Hospital from January 2015 to June 2020, in which a total of 140 patients were finally enrolled.Results: Voriconazole doses were adjusted in 44 patients due to abnormal voriconazole drug concentration or side effects, 32 patients reduced the dose and 8 patients increased the dose. An elevated liver enzyme level was the most common cause for dose adjustment. After the first dose adjustment, most patients achieved the target drug concentration. A total of 18 patients were determined as probable or highly probable to have drug-induced liver injury from voriconazole. Voriconazole drug concentration was significantly higher in the liver damage and nervous system damage groups as compared with the group without any side effects, and most liver damage events occurred within 14 days of the first dose. Voriconazole drug concentration >3.61 mg/l was associated with an increased incidence of liver damage.Conclusion: In this study, approximately one-third of patients with pulmonary fungal disease needed to adjust their dose after the standard dose of voriconazole treatment. The incidence of liver damage and nervous system damage showed an overall increasing trend with increasing voriconazole baseline concentrations. Initial therapeutic drug monitoring may be predictive of liver damage. Follow-up monitoring of liver enzymes may be needed.

Clinical Features, Diagnostic Test Performance, and Prognosis in Different Subtypes of Chronic Pulmonary Aspergillosis.

OBJECTIVE: The aim of this study was to describe clinical features in different subtypes of chronic pulmonary aspergillosis (CPA)-simple aspergilloma (SA), chronic cavitary pulmonary aspergillosis (CCPA), chronic fibrosing pulmonary aspergillosis (CFPA), aspergillus nodule (AN), and subacute invasive aspergillosis (SAIA), respectively, and identify long-term prognosis of CPA. METHODS: We reviewed patients diagnosed with different subtypes of CPA from 2002 to 2020 at Nanjing Jinling Hospital, China. We analyzed the clinical and survival information of five different subgroups. A Cox regression model was used to explore proper antifungal duration and long-term survival factors of CCPA and SAIA. RESULTS: A total of 147 patients with CPA were included, consisting of 11 SA, 48 CCPA, 5 CFPA, 12 AN, and 71 SAIA. The most common underlying pulmonary disease was pulmonary tuberculosis (n = 49, 33%), followed by bronchiectasis (n = 46, 31.3%) and chronic obstructive pulmonary disease (COPD) or emphysema (n = 45, 30.6%), while in SAIA and CFPA groups, the most common was COPD or emphysema (45.1 and 100%). Cough (85%), expectoration (70.7%), hemoptysis (54.4%), and fever (29.9%) were common symptoms, especially in CCPA, CFPA, and SAIA groups. The common imaging manifestations included cavitation (n = 94, 63.9%), fungal ball (n = 54, 36.7%), pleural thickening (n = 47, 32.0%), and bronchiectasis (n = 46, 31.3%). SAIA and CFPA groups had a lower value of hemoglobin (HB) and serum albumin (ALB) with higher C-reactive protein and erythrocyte sedimentation rate. The positive rate of sputum culture, serum galactomannan (GM), and bronchoalveolar lavage fluid GM was 32.7% (36/110), 18.4% (18/98), and 48.7% (19/39), respectively. There were 64.6% (31/48) patients with CCPA and 25.4% (18/71) patients with SAIA who received surgery and the 5-year cumulative survival rate was 92.1 and 66.6%, respectively. SAIA, old age, male, low body mass index (BMI), COPD or emphysema, multiple distribution, low serum ALB, and positive sputum culture were adverse prognosis factors for SAIA and CCPA group, and BMI ≤ 20.0 kg/m2 was independently associated with increased mortality (hazard ratio (HR) 5.311, 95% CI 1.405-20.068, p = 0.014). Multivariable Cox regression indicated that surgery (HR 0.093, 95% CI 0.011-0.814, p = 0.032) and antifungal duration >6 months (HR 0.204, 95% CI 0.060-0.696 p = 0.011) were related to improved survival. CONCLUSION: The clinical features and laboratory test performance are different among SA, CCPA, CFPA, AN, and SAIA. Low BMI was an independent risk factor for survival. Selective surgery and antifungal duration over 6 months were associated with improved survival.

Clinical features of cryptococcosis in patients with different immune statuses: a multicenter study in Jiangsu Province-China.

BACKGROUND: Current guidelines support different management of cryptococcosis between severely immunodeficient and immunocompetent populations. However, few studies have focused on cryptococcosis patients with mild-to-moderate immunodeficiency. We performed this study to determine the clinical features of pulmonary (PC) and extrapulmonary cryptococcosis (EPC) and compared them among populations with different immune statuses to support appropriate clinical management of this public health threat. METHODS: All cases were reported by 14 tertiary teaching hospitals in Jiangsu Province, China from January 2013 to December 2018. The trends in incidence, demographic data, medical history, clinical symptoms, laboratory test indicators, imaging characteristics and diagnostic method of these patients were then stratified by immune status, namely immunocompetent (IC, patients with no recognized underlying disease or those with an underlying disease that does not influence immunity, such as hypertension), mild-to-moderate immunodeficiency (MID, patients with diabetes mellitus, end-stage liver or kidney disease, autoimmune diseases treated with low-dose glucocorticoid therapy, and cancer treated with chemotherapy) and severe immunodeficiency (SID, patients with acquired immunodeficiency syndrome, haematologic malignancies, solid organ transplantation or haematologic stem cell transplantation, idiopathic CD4 lymphocytosis, agranulocytosis, aggressive glucocorticoid or immunosuppressive therapy and other conditions or treatments that result in severe immunosuppression). RESULTS: The clinical data of 255 cryptococcosis patients were collected. In total, 66.3% of patients (169) were IC, 16.9% (43) had MID, and 16.9% (43) had SID. 10.1% of the patients (17) with IC were EPC, 18.6% of the patients (8) with MID were EPC, and 74.4% of patients (32) were EPC (IC/MID vs. SID, p < 0.001). Fever was more common in the SID group than in the IC and MID groups (69.8% vs. 14.8% vs. 37.2%, p < 0.001). Of chest CT scan, most lesions were distributed under the pleura (72.7%), presenting as nodules/lumps (90.3%) or consolidations (10.7%). Pleural effusion was more common in SID group compared to IC group (33.3% vs. 2.4%, p < 0.001). Positivity rate on the serum capsular polysaccharide antigen detection (CrAg) test was higher in the SID group than in the other two groups [100.0% vs. 84.4% (MID) vs. 78.2% (IC), p = 0.013]. Positivity rate on the serum CrAg test was also higher in cryptococcal meningitis patients than in PC patients (100.0% vs. 79.5%, p = 0.015). CONCLUSIONS: The clinical presentation of MID patients is intermediate between SID and IC patients and is similar to that of IC patients. The serum CrAg test is more sensitive for the identification of SID or EPC patients.

Epidemiological Trends of Coronavirus Disease 2019 in China.

Background: The Coronavirus Disease 2019 (COVID-19) epidemic broke out in Wuhan, China, and it spread rapidly. Since January 23, 2020, China has launched a series of unusual and strict measures, including the lockdown of Wuhan city to contain this highly contagious disease. We collected the epidemiological data to analyze the trend of this epidemic in China. Methods: We closely tracked the Chinese and global official websites to collect the epidemiological information about COVID-19. The number of total and daily new confirmed cases of COVID-19 in China was presented to illustrate the trend of this epidemic. Results: On January 23, 2020, 835 confirmed COVID-19 cases were reported in China. On February 6, 2020, there were 31,211 cases. By February 20, 2020, the number reached as high as 75,993. Most cases were distributed in and around Wuhan, Hubei province. Since January 23, 2020, the number of daily new cases in China except Hubei province reached a peak of 890 on the eleventh day and then it declined to a low level of 34 within two full-length incubation periods (28 days), and the number of daily new cases in Hubei also started to decrease on the twelfth day, from 3,156 on February 4, 2020 to 955 on February 15, 2020. Conclusion: The COVID-19 epidemic has been primarily contained in China. The battle against this epidemic in China has provided valuable experiences for the rest of the world. Strict measures need to be taken as earlier as possible to prevent its spread.