Successful management of Mycobacterium abscessus pneumonia in a 53-day-old immunocompetent infant.

Pulmonary infection due to Mycobacterium abscessus complex (MABC) usually occurs in children with underlying risk factors including cystic fibrosis (CF), chronic lung disease, and immunocompromised status, but rarely in immunocompetent children without underlying lung disease, especially in infants. We present a case of MABC pulmonary disease (MABC-PD) in an otherwise healthy 53-day-old male infant with one week of cough and respiratory distress. Computed tomography showed multiple masses across both lungs. Isolated mycobacteria from his bronchoalveolar lavage fluid were identified as MABC. We describe our complete evaluation, including immunodeficiency evaluation incorporating whole exome sequencing and our therapeutic process given complicated susceptibility pattern of the M. abscessus isolate, and review literature for MABC-PD in immunocompetent children. The infant was successfully treated through prolonged treatment with parenteral Amikacin, Cefoxitin, Linezolid, and Clarithromycin, combined with inhaled Amikacin.

Association Between Promoter Methylation of Vitamin D Metabolic Pathway Genes and Tuberculosis and Diabetes Comorbidity in a Chinese Han Population: A Case-Control Study.

Background: Deficiency vitamin D and hyperglycemia could be related to weakened innate immune response and aggravate the progression of tuberculosis (TB). This study hypothesized that DNA promoter methylation of the pivotal genes in the vitamin D metabolic pathway might be related to diabetes and tuberculosis co-morbidity (TB-DM) susceptibility. Methods: A total of 50 TB-DM and 50 healthy subjects (HS) were included in the present study. Targeted bisulfite sequencing was applied to detect the methylation of the promoter regions of candidate genes in the vitamin D metabolic pathway (CYP24A1, CYP27B1, CYP2R1, DHCR7, and VDR) in whole blood. Results: The overall methylation level of candidate genes in this study was lower in patients with TB-DM than HS, except for CYP2R1. The results of the ROC demonstrated the potential of CYP24A1, CYP27B1, DHCR7, and VDR promoter methylation as a biomarker for diagnosing TB-DM, with all the AUC above 0.7. In subgroup analysis, we found that lower circulating vitamin D is related to a low level of CYP24A1, CYP27B1, and DHCR7 promoter methylation in patients with TB-DM. With decreasing methylation level, risk of TB-DM was significantly increased (odds ratio, 95% CI 0.343, 0.144-0.821 for CYP24A1; 0.461, 0.275-0.773 for CYP27B1; 0.09, 0.015-0.530 for DHCR7; 0.006, 0.0003-0.115 for VDR). Besides, our results revealed that there was a significant correlation between DNA promoter methylation of selected genes in the vitamin D metabolic pathway and platelet indices in TB-DM. However, there was no correlation between DNA methylation of the four genes and fasting glucose and HbA1c. Conclusion: Our results could suggest that the selected genes in the vitamin D metabolic pathway may be involved in the pathological process of TB-DM, but independent of the process of hyperglycemia to impaired immune responses to Mtb.

The correlation of temporal changes of neutrophil-lymphocyte ratio with seizure severity and the following seizure tendency in patients with epilepsy.

Background: Changes in the neutrophil-lymphocyte ratio (NLR) has been reported to be associated with epilepsy. Here we aim to investigate the correlation of temporal changes of NLR level with seizure severity and the follow-up seizure attacks in patients with epilepsy (PWE). Methods: We performed a retrospective analysis of the laboratory data including leukocyte count and NLR within 24 h of acute seizure and during the follow-up period of 5-14 days after acute seizure (NLR1, NLR2, respectively) in 115 PWE, and 98 healthy individuals were included as controls in this study. The correlation of laboratory data with seizure types, etiology of epilepsy, anti-seizure drugs (ASDs), seizure severity, and the follow-up seizure attacks in PWE was studied. Results: Leukocyte count (P < 0.001) and NLR level (P < 0.001) were found significantly different between PWE and controls. On the other hand, a multivariable logistic regression analysis showed that NLR1 level (OR = 2.992, P = 0.001) and admission leukocyte (OR = 2.307, P = 0.002) were both independently associated with acute epileptic seizures. Especially, higher NLR1 level was significantly associated with status epileptics (P = 0.013) and recurrent seizures after admission (P < 0.001). Furthermore, the multivariable logistic regression analysis indicated that higher NLR1 was a predictor for the tendency of the following recurrent seizure attacks (OR = 1.144, P = 0.002). NLR2 was inversely correlated with ASDs taken (P = 0.011). Levels of NLR1 (r = 0.441, P < 0.001) and NLR2 (r = 0.241, P = 0.009) were both positively correlated with seizure severity. Conclusions: Seizures were correlated with the alterations of systemic inflammation reflected by leukocyte and NLR. NLR1 and admission leukocyte were both independently associated with acute epileptic seizures. Higher NLR1 was associated with status epilepticus and independently predicted the tendency of the following epileptic seizures. NLR2 was significantly associated with ASDs taken. Besides, NLR may be used as a biomarker for seizure severity.

Lack of Association Between Helicobacter pylori Infection and the Risk of Thyroid Nodule Types: A Multicenter Case-Control Study in China.

The prevalence of Helicobacter pylori infection is high worldwide, while numerous research has focused on unraveling the relationship between H. pylori infection and extragastric diseases. Although H. pylori infection has been associated with thyroid diseases, including thyroid nodule (TN), the relationship has mainly focused on potential physiological mechanisms and has not been validated by large population epidemiological investigations. Therefore, we thus designed a case-control study comprising participants who received regular health examination between 2017 and 2019. The cases and controls were diagnosed via ultrasound, while TN types were classified according to the guidelines of the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS). Moreover, H. pylori infection was determined by C14 urea breath test, while its relationship with TN type risk and severity was analyzed using binary and ordinal logistic regression analyses. A total of 43,411 participants, including 13,036 TN patients and 30,375 controls, were finally recruited in the study. The crude odds ratio (OR) was 1.07 in Model 1 (95% CI = 1.03-1.14) without adjustment compared to the H. pylori non-infection group. However, it was negative in Model 2 (OR = 1.02, 95% CI = 0.97-1.06) after being adjusted for gender, age, body mass index (BMI), and blood pressure and in Model 3 (OR = 1.01, 95% CI = 0.97-1.06) after being adjusted for total cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein on the basis of Model 2. Control variables, including gender, age, BMI, and diastolic pressure, were significantly correlated with the risk of TN types. Additionally, ordinal logistic regression results revealed that H. pylori infection was positively correlated with malignant differentiation of TN (Model 1: OR = 1.06, 95% CI = 1.02-1.11), while Model 2 and Model 3 showed negative results (Model 2: OR = 1.01, 95% CI = 0.96-1.06; Model 3: OR = 1.01, 95% CI = 0.96-1.05). In conclusion, H. pylori infection was not significantly associated with both TN type risk and severity of its malignant differentiation. These findings provide relevant insights for correcting possible misconceptions regarding TN type pathogenesis and will help guide optimization of therapeutic strategies for thyroid diseases.

Clinical efficacy of low-dose emetine for patients with COVID-19: a real-world study.

OBJECTIVE: Emetine, an isoquinoline alkaloid that is enriched at high concentrations in the lung, has shown potent in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The aim of this study was to better understand the effectiveness of low-dose emetine for patients with coronavirus disease 2019 (COVID-19). METHODS: In this real-world study, 63 patients with mild or common COVID-19 were recruited from Wuhan Fangcang Shelter Hospital and five COVID-19-designated hospitals in Anhui Province, China from February to March 2020. Thirty-nine patients from Wuhan Fangcang Shelter Hospital were assigned to a pragmatic randomized controlled clinical trial, and 24 patients from the 5 COVID-19-designated hospitals in Anhui Province underwent a real-world study. The medication course of emetine was less than 10 days. The main symptoms and adverse reactions of all patients were observed and recorded. The primary outcome measure was the time required for a negative SARS-CoV-2 RNA result or the negative result rate on day 10. Secondary outcomes included axillary temperature, transcutaneous oxygen saturation, and respiratory frequency recovery. The study was approved by the Ethics Committee of The First Affiliated Hospital of Anhui Medical University on February 20, 2019 (approval No. PJ2020-03-19) and was registered with the Chinese Clinical Trial Registry on February 20, 2019 (registration number: ChiCTR2000030022). RESULTS: The oxygen saturation values were higher in the treatment group than in the control group on the first day after enrollment for patients treated at Fangcang Shelter Hospital. The axillary body temperature, respiratory rate, and oxygen saturation among patients in Fangcang Shelter Hospital were related to the time effect but not to the intervention measures. The respiratory rate and oxygen saturation of patients in the Anhui designated hospitals were related to the intervention measures but not to the time effect. The axillary body temperature of patients in Anhui designated hospitals was related to the time effect but not to the intervention measures. CONCLUSION: Our preliminary study shows that low-dose emetine combined with basic conventional antiviral drugs improves clinical symptoms in patients with mild and common COVID-19 without apparent adverse effects, suggesting that moderately increased doses of emetine may have good potential for treatment and prevention of COVID-19.

Early-Warning Immune Predictors for Invasive Pulmonary Aspergillosis in Severe Patients With Severe Fever With Thrombocytopenia Syndrome.

Aspergillus-related disease was confirmed to be associated with immune disorders in patients, severe patients with severe fever with thrombocytopenia syndrome (SFTS) infected by novel phlebovirus were confirmed to have severe immune damage including cellular immunosuppression and cytokine storms. Secondary invasive pulmonary aspergillosis (IPA) in severe SFTS patients can increase fatality rate. This study investigated early-warning predictive factors of secondary IPA in severe SFTS patients. Receiver operating characteristic analysis was used to assess the value of immune parameters to predict IPA in SFTS patients. The cut-off values of CD4+ and CD8+ T-cell counts to predict IPA were 68 and 111 cells/mm3, with sensitivities of 82.6% and 72%, and specificities of 56.7% and 83.3%, respectively. Cut-off values of IL-6, TNF-α, IL-8, and IL-10 to predict IPA incidence in critically ill SFTS patients were 99 pg/mL, 63 pg/mL, 120 pg/mL, and 111 pg/mL, with sensitivities of 90.0%, 86.7%, 83.3% and 90.0% and specificities of 80.4%, 71.7%, 82.6% and 65.2%, respectively. Lower CD4+ and CD8+ T-cells counts, higher levels of IL-6, TNF-α, IL-8 and IL-10, higher incidence of pancreatic and renal damage, early antibacterial therapy of carbapenems, and intensive care unit admission were risk factors of IPA in SFTS patients. Multivariate logistic regression analysis indicated counts of CD4+ T-cells <68 cells/mm3 combined with CD8+ T-cells <111 cells/mm3 (odds ratio [OR] 0.218, 95% confidence interval [CI] 0.059-0.803, p=0.022), IL-6 >99 pg/ml combined with IL-10 >111 pg/ml (OR 17.614, 95% CI 2.319-133.769, p=0.006), and brain natriuretic peptide level >500 pg/ml (OR 13.681, 95% CI 1.994-93.871, p=0.008) were independent risk factors for IPA in SFTS patients. The mortality in the IPA group was significantly higher than in the non-IPA group (p=0.001). Early antifungal treatment of IPA patients was significantly associated with improved survival (log-rank, p=0.022). Early diagnosis of IPA and antifungal treatment can improve the prognosis of SFTS patients. Besides, we speculate SFTS may be as a host factor for IPA.

Prevalence of Plasmid-Mediated Determinants With Decreased Susceptibility to Azithromycin Among Shigella Isolates in Anhui, China.

OBJECTIVE: The aims of this study were to describe azithromycin (AZM) susceptibility patterns among Shigella isolates in Anhui, China and identify predictors of resistance with mobile element-mediated genes. METHODS: A total of 517 non-duplicate Shigella isolates (449 S. flexneri and 68 S. sonnei) were collected in the Anhui Province of China from September 2011-September 2015, and screened for the plasmid-mediated genes of decreased susceptibility to AZM (DSA), using polymerase chain reaction amplification and sequencing. Conjugation experiments and pulsed-field gel electrophoresis were conducted for all mphA-positive DSA isolates. RESULTS: The DSA rate for 449 S. flexneri isolates was 33.6%, compared with 39.7% for 68 S. sonnei isolates. Among 161 DSA S. flexneri isolates, 93 (57.8%) carried the mphA gene. Among 27 DSA S. sonnei isolates, 11 (40.7%) carried the mphA gene. However, other plasmid-mediated DSA genes were not found in these isolates. A total of 89 transconjugants (95.7%) were obtained from 93 mphA-positive S. flexneri isolates through conjugation, and 10 transconjugants (90.9%) were obtained from 11 mphA-positive S. sonnei isolates. Furthermore, the minimum inhibitory concentrations (MICs) of AZM among 89 S. flexneri transconjugants ranged from 4 to 128 µg/mL, with an MIC50 of 8 µg/mL and MIC90 of 32 µg/mL. The MICs of AZM among 10 S. sonnei transconjugants ranged from 4 to 256 µg/mL, with an MIC50 of 8 µg/mL and MIC90 of 64 µg/mL. Thirteen clusters were found for mphA-positive S. flexneri, and five clusters were found for mphA-positive S. sonnei. Furthermore, 10 homologous isolates among 13 mphA-positive S. flexneri isolates with high-level DSA were from Sixian county and were multidrug-resistant strains. Of the 10 homologous S. flexneri isolates, eight were from children (≤5 years old), and two from the elderly (>60 years old). CONCLUSION: Our study demonstrates that the DSA for Shigella isolates was severe, and the plasmid-mediated mphA gene was the most common macrolide resistance gene detected in Shigella isolates collected in Anhui, China. The mphA-positive S. flexneri isolates with high-level DSA facilitated clonal spread in children and the elderly. This finding is noteworthy and warrants further study.

The absence of coronavirus in expressed prostatic secretion in COVID-19 patients in Wuhan city.

Due to the cellular entry of the novel coronavirus (SARS-CoV-2) modulated by angiotensin converting enzyme 2 (ACE2), the ACE2 bearing prostate is therefore hypothesized as a susceptible organ to COVID-19. To delineate whether the pathogenic SARS-CoV-2 of the coronavirus disease (COVID-19) could be detected in the expressed prostatic secretion (EPS), a total of ten male patients with confirmed COVID-19 were recruited. All patients were stratified into two groups: one group with positive nasopharyngeal swabbing SARS-CoV-2 within 3 days of the EPS taken day (PNS group, n = 3) and the other group with previously positive nasopharyngeal swabbing SARS-CoV-2 but turned negative before the taken day (PNNS group, n = 7). The COVID-19 patients showed elevated inflammatory indictors, i.e. C-reaction protein (3.28 (1.14, 33.33) mg/L), erythrocyte sedimentation rate (22.50 (8.00, 78.50) mm/h), and interleukin-6 (6.49 (4.96, 21.09) pg/ml). Serum IgM against SARS-CoV-2 was only positive in the PNS group, whereas serum IgG was positive for all patients. Furthermore, our data showed for the first time that none of the COVID-19 patients had positive SARS-CoV-2 RNA in EPS. To this end, this study found the negativity of SARS-CoV-2 in EPS and possibly exclude the sexual transmission of COVID-19.

Anisotropic source modelling for turbulent jet noise prediction.

An anisotropic component of the jet noise source model for the Reynolds-averaged Navier-Stokes equation-based jet noise prediction method is proposed. The modelling is based on Goldstein's generalized acoustic analogy, and both the fine-scale and large-scale turbulent noise sources are considered. To model the anisotropic characteristics of jet noise source, the Reynolds stress tensor is used in place of the turbulent kinetic energy. The Launder-Reece-Rodi model (LRR), combined with Menter's ω-equation for the length scale, with modified coefficients developed by the present authors, is used to calculate the mean flow velocities and Reynolds stresses accurately. Comparison between predicted results and acoustic data has been carried out to verify the accuracy of the new anisotropic source model. This article is part of the theme issue 'Frontiers of aeroacoustics research: theory, computation and experiment'.

Meningococcal disease and control in China: Findings and updates from the Global Meningococcal Initiative (GMI).

The Global Meningococcal Initiative (GMI) is a global expert group, including scientists, clinicians and public health officials from a wide range of specialities. The goal of the GMI is to prevent meningococcal disease worldwide through education, research, and co-operation. The Chinese GMI roundtable meeting was held in June 2017. The GMI met with local experts to gain insight into the meningococcal disease burden in China and current prevention and vaccination strategies in place. China experienced five epidemics of serogroup A meningococcal disease (MenA) between 1938 and 1977, with peak incidence of 403/100,000 recorded in 1967. MenA incidence rates have significantly declined following the universal introduction of the MenA polysaccharide vaccine in China in the 1980s. Further, surveillance data indicates changing meningococcal epidemiology in China with the emergence of new clones of serogroup B from serogroup C clonal complex (cc) 4821 due to capsular switching, and the international spread of serogroup W cc11. The importance of carriage and herd protection for controlling meningococcal disease was highlighted with the view to introduce conjugate vaccines and serogroup B vaccines into the national immunization schedule. Improved disease surveillance and standardized laboratory techniques across and within provinces will ensure optimal epidemiological monitoring.

Surveillance of antimicrobial susceptibility patterns among Stenotrophomonas maltophilia isolated in China during the 10-year period of 2005-2014.

The antimicrobial resistance pattern was studied among 300 Stenotrophomonas maltophilia isolates collected from 300 nonduplicated inpatients. The average age of the patients was 73.5 ± 14.6 years old. Isolates nonsusceptible to levofloxacin, chloramphenicol, minocycline or trimethoprim/sulfamethoxazole (SXT) were more prevalent in the 99 patients aged over 81 years than in the other patients (p < 0.05). Multidrug resistance was found to be significantly associated with isolates recovered from the blood (72.7%, p = 0.000) and elderly patients (31.3%, p = 0.003). A trend of increased resistance to antimicrobials and higher and higher frequencies of multidrug-resistant isolates were observed through the 10-year period, wherein the percentage of isolates resistant to SXT was significantly changed from 29.7% in 2005-2009 to 47.1% in 2010-2014 (p = 0.02). Clinicians are recommended to pay special attention to the possibility of multidrug-resistant S. maltophilia infection in elderly inpatients.

[The profile of antibiotic resistantpathogens isolated from ascites fluid patients in intensive care unit during past 12 years.

Objective: To investigate the profile and antibiotic resistance of bacteria in patients with ascites infection in intensive care unit (ICU) patients in order to provide a reference for rational clinical use of antibiotics. Methods: A retrospective analysis was conducted. The bacteria isolated from ascetic fluid patients admitted from January 1st, 2004 to October 31st, 2015 to ICU of the First Affiliated Hospital of Anhui Medical University were identified, and their susceptibility to antibiotics was analyzed. Patients, who were admitted from January 1st, 2004 to December 31st, 2009 were assigned to group A, and patients admitted afterwards were assigned to group B. Results: A total of 637 specimens of ascetic fluid were examined, with 185 positive culture (29.0%) during the 12 years, and 203 strains of bacteria were found. Among them 126 strains (62.1%) of gram-negative bacteria (G-), 54 (26.6%) of gram-positive bacteria (G+) and 23 (11.3%) strains of fungi were found. Compared the result of group B with that of group A, the proportion of G- bacteria was increased [71.2% (99/139) vs. 44.2% (27/64)], and that of G+ decreased [17.3% (24/139) vs. 46.9% (30/64)] in group B. The difference was statistically significant (χ2 = 20.34, P = 0.001). The main pathogenic bacteria were G-, and Enterobacteriaceae was the most common pathogenic bacteria in intra-abdominal infection of ICU patients. The isolation rate of Escherichia coli and Klebsiella pneumoniae(35.7%, 10.3%) ranked in the first and third in G- bacteria, respectively. The resistant rate of Escherichia coli against penicillin and third generation cephalosporin were > 95.0% and > 73.3%, and it showed a sensitive rate of 70% to ß-lactam/inhibitor, amikacin and minocycline, and a higher sensitivity to carbapenems and tigecycline (11.1%, 0). Forty-eight strains of non-fermentation bacteria were found with a rate of 23.7%. The positive rates of Acinetobacter baumannii in groups A and B were 7.8% (5/64) and 23.7% (33/139), respectively, and they ranked first among non-fermentation bacteria. Twenty strains (62.5%) multidrug-resistant Acinetobacter baumannii were found. Acinetobacter baumannii showed a resistance rate of 84.6% to cefoperazone/sulbactam, 35.3% to minocycline, and 53.3% to tigecycline. Candida albicans was the most commonly isolated fungus in intra-abdominal infections (87.5%). No strains resistant to common antifungal drugs were isolated. Conclusions: G- bacteria was the main pathogen in intra-abdominal infection in patients with ascites. Non-fermenters showed an increasing trend of producing infection, and the proportion of multidrug-resistant Acinetobacter baumannii infection increased year by year, and more attention should be taken by attending doctors.

Reduced susceptibility of Candida albicans clinical isolates to azoles and detection of mutations in the ERG11 gene.

We investigated the susceptibility of Candida albicans isolated from clinic specimens to azole antifungal agents and estimated the association of the ERG11 mutations with azole resistance during recent 5years in China. In this study, novel mutations G346A, A434V, and L480F in ERG11 may be related to azole resistance in C. albicans.

Emergence of serogroup C meningococcal disease associated with a high mortality rate in Hefei, China.

BACKGROUND: Neisseria meningitidis serogroup C has emerged as a cause of epidemic disease in Hefei. The establishment of serogroup C as the predominant cause of endemic disease has not been described. METHODS: We conducted national laboratory-based surveillance for invasive meningococcal disease during 2000-2010. Isolates were characterized by pulsed-field gel electrophoresis and multilocus sequence typing. RESULTS: A total of 845 cases of invasive meningococcal disease were reported. The incidence increased from 1.25 cases per 100,000 population in 2000 to 3.14 cases per 100,000 in 2003 (p < 0.001), and peaked at 8.43 cases per 100,000 in 2005. The increase was mainly the result of an increase in the incidence of serogroup C disease. Serogroup C disease increased from 2/23 (9%) meningococcal cases and 0.11 cases per 100,000 in 2000 to 33/58 (57%) cases and 1.76 cases per 100,000 in 2003 (p < 0.01). Patients infected with serogroup C had serious complications more frequently than those infected with other serogroups. Specifically, 161/493 (32.7%) cases infected with serogroup C had at least one complication. The case-fatality rate of serogroup C meningitis was 11.4%, significantly higher than for serogroup A meningitis (5.3%, p = 0.021). Among patients with meningococcal disease, factors associated with death in univariate analysis were age of 15-24 years, infection with serogroup C, and meningococcemia. CONCLUSIONS: The incidence of meningococcal disease has substantially increased and serogroup C has become endemic in Hefei. The serogroup C strain has caused more severe disease than the previously predominant serogroup A strain.

Emergence of CTX-M-3, TEM-1 and a new plasmid-mediated MOX-4 AmpC in a multiresistant Aeromonas caviae isolate from a patient with pneumonia.

Aeromonas species rarely cause pulmonary infection. We report, for what is believed to be the first time, a case of severe pneumonia in a cancer patient caused by Aeromonas caviae. Detailed microbiological investigation revealed that this isolate carried three beta-lactamase-encoding genes (encoding MOX-4, CTX-M-3 and TEM-1) conferring resistance to all beta-lactams but imipenem. The beta-lactamase with a pI of 9.0 was transferred by conjugation and associated with a 7.3 kb plasmid, as demonstrated by Southern blot hybridization. Analysis of the nucleotide and amino acid sequences showed a new ampC gene that was closely related to those encoding the MOX-1, MOX-2 and MOX-3 beta-lactamases. This new plasmid-mediated AmpC beta-lactamase from China was named MOX-4. This is believed to be the first report of MOX-4, CTX-M-3 and TEM-1 beta-lactamases in a multiresistant A. caviae.