Traditional Vietnamese medicine Kovir capsule in patients with mild COVID-19: A double-blind randomized controlled trial.

Kovir capsule, a polyherbal medicine developed from Ren Shen Bai Du San formulation, has been used in various diseases including respiratory infections. A randomized, placebo-controlled, double-blind study was conducted to evaluate the safety and efficacy of Kovir capsule (TD0069) in the treatment of mild COVID-19 patients. Patients aged from 18 to 65 years who were PCR-confirmed with SARS-CoV-2 and had the mild disease were recruited and randomized to either Kovir capsule (34 patients) or placebo (32 patients) for up to 14 days or until discharge. Efficacy outcomes were time to viral clearance, daily viral load, time to symptom resolution, daily symptom score based on 16 pre-defined symptoms, and progression to severe/critical COVID-19. Safety outcomes were adverse events. Viral load decreased over time similarly in the two groups. Viral clearance time was also similar in both groups (median: 8 days). Kovir group had a more rapid decrease of symptom score and significantly lower time to symptom resolution than placebo (median: 4 vs. 7 days). Two patients in the placebo group developed severe COVID-19. No patient experienced adverse events. Kovir capsule is safe and can improve symptom resolution in mild COVID-19 patients. A large-scale trial is required to confirm these findings.

New eight genes identified at the clinical multidrug-resistant Acinetobacter baumannii DMS06669 strain in a Vietnam hospital.

BACKGROUND: Acinetobacter baumannii is an important nosocomial pathogen that can develop multidrug resistance. In this study, we characterized the genome of the A. baumannii strain DMS06669 (isolated from the sputum of a male patient with hospital-acquired pneumonia) and focused on identification of genes relevant to antibiotic resistance. METHODS: Whole genome analysis of A. baumannii DMS06669 from hospital-acquired pneumonia patients included de novo assembly; gene prediction; functional annotation to public databases; phylogenetics tree construction and antibiotics genes identification. RESULTS: After sequencing the A. baumannii DMS06669 genome and performing quality control, de novo genome assembly was carried out, producing 24 scaffolds. Public databases were used for gene prediction and functional annotation to construct a phylogenetic tree of the DMS06669 strain with 21 other A. baumannii strains. A total of 18 possible antibiotic resistance genes, conferring resistance to eight distinct classes of antibiotics, were identified. Eight of these genes have not previously been reported to occur in A. baumannii. CONCLUSIONS: Our results provide important information regarding mechanisms that may contribute to antibiotic resistance in the DMS06669 strain, and have implications for treatment of patients infected with A. baumannii.

Antifungal susceptibility of invasive Candida bloodstream isolates from the Asia-Pacific region.

Bloodstream infections caused by Candida species are of increasing importance and associated with significant mortality. We performed a multi-centre prospective observational study to identify the species and antifungal susceptibilities of invasive bloodstream isolates of Candida species in the Asia-Pacific region. The study was carried out over a two year period, involving 13 centers from Brunei, Philippines, Singapore, South Korea, Taiwan, Thailand, and Vietnam. Identification of Candida species was performed at each study center, and reconfirmed at a central laboratory. Susceptibility testing was performed using a commercial broth dilution panel (Sensititre YeastOne YST-010, Thermofisher, United Kingdom) with susceptibility categorisation (S = susceptible, S-DD = susceptible dose-dependent) applied using breakpoints from the Clinical Laboratory Standards Institute. Eight hundred and sixty-one Candida isolates were included in the study. The most common species were C. albicans (35.9%), C. tropicalis (30.7%), C. parapsilosis (15.7%), and C. glabrata (13.6%). Non-albicans species exceeded C. albicans species in centers from all countries except Taiwan. Fluconazole susceptibility was almost universal for C. albicans (S = 99.7%) but lower for C. tropicalis (S = 75.8%, S-DD = 6.1%), C. glabrata (S-DD = 94.9%), and C. parapsilosis (S = 94.8%). Echinocandins demonstrated high rates of in vitro susceptibility (S>99%) against C. albicans, C. tropicalis, and C. parapsilosis This study demonstrates that non-albicans species are the most common isolates from bloodstream infections in most countries in the Asia-Pacific region, with C. tropicalis as the predominant species. Because of the prevalence of reduced susceptibility to fluconazole in non-albicans species, the study indicates that echinocandins should be the antifungal of choice in clinically unstable or high-risk patients with documented candidemia.

Spread of methicillin-resistant Staphylococcus aureus between the community and the hospitals in Asian countries: an ANSORP study.

OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) is highly prevalent in hospitals in many Asian countries. Recent emergence of community-associated (CA) MRSA worldwide has added another serious concern to the epidemiology of S. aureus infections. To understand the changing epidemiology of S. aureus infections in Asian countries, we performed a prospective, multinational surveillance study with molecular typing analysis. METHODS: We evaluated the prevalence of methicillin resistance in S. aureus isolates in CA and healthcare-associated (HA) infections, and performed molecular characterization and antimicrobial susceptibility tests of MRSA isolates. RESULTS: MRSA accounted for 25.5% of CA S. aureus infections and 67.4% of HA infections. Predominant clones of CA-MRSA isolates were ST59-MRSA-SCCmec type IV-spa type t437, ST30-MRSA-SCCmec type IV-spa type t019 and ST72-MRSA-SCCmec type IV-spa type t324. Previously established nosocomial MRSA strains including sequence type (ST) 239 and ST5 clones were found among CA-MRSA isolates from patients without any risk factors for HA-MRSA infection. CA-MRSA clones such as ST59, ST30 and ST72 were also isolated from patients with HA infections. CONCLUSIONS: Our findings confirmed that MRSA infections in the community have been increasing in Asian countries. Data also suggest that various MRSA clones have spread between the community and hospitals as well as between countries.

In vitro culture and differentiation of osteoblasts from human umbilical cord blood.

It is well accepted that human umbilical cord blood (UCB) is a source of mesenchymal stem cells (MSCs) which are able to differentiate into different cell phenotypes such as osteoblasts, chondrocytes, adipocytes, myocytes, cardiomyocytes and neurons. The aim of this study was to isolate MSCs from human UCB to determine their osteogenic potential by using different kinds of osteogenic medium. Eventually, only those MSCs cultured in osteogenic media enriched with vitamin D(2) and FGF9, were positive for osteocalcin by RT-PCR. All these cells were positive for alizarin red, alkaline phosphatase and Von Kossa. The results obtained from RT-PCR have confirmed that osteogenesis is complete by expression of the osteocalcin marker. In conclusion, vitamin D(2), at least in vitro, may replace vitamin D(3) as an osteogenic stimulator factor for MSC differentiation.

Epidemiology and clinical outcomes of community-acquired pneumonia in adult patients in Asian countries: a prospective study by the Asian network for surveillance of resistant pathogens.

Appropriate antimicrobial treatment of community-acquired pneumonia (CAP) should be based on the distribution of aetiological pathogens, antimicrobial resistance of major pathogens, clinical characteristics and outcomes. We performed a prospective observational study of 955 cases of adult CAP in 14 hospitals in eight Asian countries. Microbiological evaluation to determine etiological pathogens as well as clinical evaluation was performed. Bronchopulmonary disease (29.9%) was the most frequent underlying disease, followed by cardiovascular diseases (19.9%), malignancy (11.7%) and neurological disorder (8.2%). Streptococcus pneumoniae (29.2%) was the most common isolate, followed by Klebsiella pneumoniae (15.4%) and Haemophilus influenzae (15.1%). Serological tests were positive for Mycoplasma pneumoniae (11.0%) and Chlamydia pneumoniae (13.4%). Only 1.1% was positive for Legionella pneumophila by urinary antigen test. Of the pneumococcal isolates, 56.1% were resistant to erythromycin and 52.6% were not susceptible to penicillin. Seventeen percent of CAP had mixed infection, especially S. pneumoniae with C. pneumoniae. The overall mortality rate was 7.3%, and nursing home residence, mechanical ventilation, malignancy, cardiovascular diseases, respiratory rate>30/min and hyponatraemia were significant independent risk factors for mortality by multivariate analysis (P<0.05). The current data provide relevant information about pathogen distribution and antimicrobial resistance of major pathogens of CAP as well as clinical outcomes of illness in Asian countries.

Antimicrobial susceptibility of Shigella isolates in eight Asian countries, 2001-2004.

BACKGROUND AND PURPOSE: Shigellosis is a major health problem in developing countries, causing 91 million episodes and 414,000 deaths in Asia annually. Because of increasing trends towards drug resistance, this study was undertaken to monitor local resistance patterns of Shigella isolates from 8 Asian countries. METHODS: Ninety eight Shigella isolates collected from 8 centers in 8 Asian countries from July 2001 to July 2004 were analyzed in terms of serogroup distribution and antimicrobial susceptibility. RESULTS: The most common serogroup of Shigella isolates was Shigella flexneri (49/98, 50%), followed by Shigella sonnei (44/98, 45%). The highest resistance rate was found for trimethoprim-sulfamethoxazole (81%), followed by tetracycline (74%) and ampicillin (53%). Overall, 76 Shigella isolates (78%) were multidrug-resistant strains; S. flexneri had a higher multidrug resistance rate than S. sonnei (74% vs 23%). Increasing ciprofloxacin and ceftriaxone resistance was observed; approximately 10% and 5% of isolates were resistant to ciprofloxacin and ceftriaxone, respectively. Five ceftriaxone-non-susceptible strains (from Taiwan [3], Hong Kong [1] and The Philippines [1]) and 10 ciprofloxacin-non-susceptible strains (from Hong Kong [2], The Philippines [1], Korea [2], Vietnam [4] and Sri Lanka [1]) were isolated. CONCLUSIONS: High rates of multidrug resistance and steady increases in ceftriaxone and ciprofloxacin resistance of Shigella are serious pubic health concerns in Asian countries. Continuous monitoring of resistance patterns among Shigella isolates is necessary.

Prevalence and characteristics of Streptococcus pneumoniae "putative serotype 6E" isolates from Asian countries.

The prevalence, antimicrobial susceptibility, and genotypes of Streptococcus pneumoniae "putative serotype 6E" isolates from Asian countries were investigated. A total of 244 S. pneumoniae serogroup 6 isolates obtained from 11 Asian countries were included in this study. Of the 244 serogroup 6 isolates, 101 (41.4%) were typed as "putative serotype 6E," followed by serotypes 6A, 6B, 6C, and 6D (27.0, 20.1, 5.7, and 5.7%, respectively). Multilocus sequence typing revealed that clonal complex (CC) 90, including ST90 and its variants, was the most prevalent clonal group of "putative serotype 6E" isolates (n = 63; 62.4%). CC146 and CC315 were also found frequently in some of the countries. Most of the "putative serotype 6E" isolates showed very high resistance rates against cefuroxime, erythromycin, azithromycin, clarithromycin, clindamycin, and trimethoprim/sulfamethoxazole, probably due to their highly resistant to antimicrobials clone, CC90. Our results indicate that "putative serotype 6E" is prevalent in Asian countries. The clonal dissemination of "putative serotype 6E" isolates was also identified.

Risk factors and pathogenic significance of bacteremic pneumonia in adult patients with community-acquired pneumococcal pneumonia.

OBJECTIVE: This study was performed to identify risk factors for the development of bacteremic pneumonia and to evaluate the impact of bacteremia on the outcome of pneumococcal pneumonia. METHODS: Using a database from a surveillance study of community-acquired pneumococcal pneumonia, we compared data of the bacteremic group with that of the non-bacteremic group. RESULTS: Among 981 adult patients with pneumococcal pneumonia, 114 (11.6%) patients who had documented pneumococcal bacteremia were classified into the bacteremic group. In a multivariable analysis, use of immunosuppressant drugs, younger age (<65 years), and DM were independent risk factors associated with the development of bacteremic pneumonia among patients with pneumococcal pneumonia (all P < 0.05). The mortality rate was significantly higher in the bacteremic group than in the non-bacteremic group (28.6% vs. 8.5%; P < 0.001). The multivariable analysis revealed that concomitant bacteremia was one of the significant risk factors associated with mortality (OR, 2.57; 95% CI, 1.24-5.29), along with cerebrovascular disease and presentation with septic shock (all P < 0.05). CONCLUSIONS: Bacteremia was a common finding in pneumococcal pneumonia and was associated with a higher mortality rate. Several clinical variables may be useful for predicting bacteremic pneumonia among patients with pneumococcal pneumonia.

Clinical impact of methicillin resistance on outcome of patients with Staphylococcus aureus infection: a stratified analysis according to underlying diseases and sites of infection in a large prospective cohort.

OBJECTIVE: This study was conducted to identify the predictors of mortality and to evaluate the impact of methicillin resistance on outcome in patients with Staphylococcus aureus infection according to underlying conditions and type of infection. METHODS: An observational cohort study including 4949 patients with S. aureus infection was conducted. We compared data from patients with MRSA infection with those with MSSA infection. RESULTS: The 30-day mortality rate of MRSA group was significantly higher than that of MSSA group (15.6% vs. 6.2%, P < 0.001). However, MRSA infection was not found to be independent risk factor for mortality after adjusting for other variables (OR = 1.03, 95% CI = 0.80-1.32). When we analyzed patients with S. aureus bacteremia (n = 709), MRSA infection was found to be significantly associated with mortality in multivariate analysis (Adjusted OR = 1.69, 95% CI = 1.15-2.49). When the 30-day mortality rates were compared according to underlying diseases, the 30-day mortality rate of MRSA group was significantly higher than that of MSSA group in patients with malignancy or renal diseases. MRSA infection was also found to be one of the independent risk factors for mortality in patients with malignancy (adjusted OR = 1.69, 95% CI = 1.06-2.70) and in those with renal disease (adjusted OR = 1.70, 95% CI = 1.0-2.89), after adjustment for host variables. CONCLUSIONS: Methicillin resistance adversely affected the outcome of patients with S. aureus infection, in patients with cancer or renal disease and in those with S. aureus bacteremia, although MRSA infection was not found to be significantly associated with higher mortality in overall patient population.

DXS10011: studies on structure, allele distribution in three populations and genetic linkage to further q-telomeric chromosome X markers.

The hypervariable tetranucleotide STR polymorphism DXS10011 is a powerful marker for forensic purposes. Investigation of this STR led to an allele nomenclature which is in consensus with the ISFG recommendations. DXS10011 is located at Xq28 and genetically closely linked to DXS7423 and DXS8377 but is unlinked to HPRTB and more distant X-chromosomal STRs. DXS10011 is a very complex marker exhibiting some structural variants within alleles of identical length. Two types of repeat structure (regular and inter-alleles) are known and described as types A and B. Two SNPs which are in strong linkage disequilibrium to the different sequence types were found in the repeat flanking region. The type A sequence consists of a long stretch of uninterrupted homogenous repeats which is highly susceptible to slippage mutation during male meiosis.

High prevalence of antimicrobial resistance among clinical Streptococcus pneumoniae isolates in Asia (an ANSORP study).

A total of 685 clinical Streptococcus pneumoniae isolates from patients with pneumococcal diseases were collected from 14 centers in 11 Asian countries from January 2000 to June 2001. The in vitro susceptibilities of the isolates to 14 antimicrobial agents were determined by the broth microdilution test. Among the isolates tested, 483 (52.4%) were not susceptible to penicillin, 23% were intermediate, and 29.4% were penicillin resistant (MICs >/= 2 mg/liter). Isolates from Vietnam showed the highest prevalence of penicillin resistance (71.4%), followed by those from Korea (54.8%), Hong Kong (43.2%), and Taiwan (38.6%). The penicillin MICs at which 90% of isolates are inhibited (MIC(90)s) were 4 mg/liter among isolates from Vietnam, Hong Kong, Korea, and Taiwan. The prevalence of erythromycin resistance was also very high in Vietnam (92.1%), Taiwan (86%), Korea (80.6%), Hong Kong (76.8%), and China (73.9%). The MIC(90)s of erythromycin were >32 mg/liter among isolates from Korea, Vietnam, China, Taiwan, Singapore, Malaysia, and Hong Kong. Isolates from Hong Kong showed the highest rate of ciprofloxacin resistance (11.8%), followed by isolates from Sri Lanka (9.5%), the Philippines (9.1%), and Korea (6.5%). Multilocus sequence typing showed that the spread of the Taiwan(19F) clone and the Spain(23F) clone could be one of the major reasons for the rapid increases in antimicrobial resistance among S. pneumoniae isolates in Asia. Data from the multinational surveillance study clearly documented distinctive increases in the prevalence rates and the levels of antimicrobial resistance among S. pneumoniae isolates in many Asian countries, which are among the highest in the world published to date.

Macrolide resistance and genotypic characterization of Streptococcus pneumoniae in Asian countries: a study of the Asian Network for Surveillance of Resistant Pathogens (ANSORP).

OBJECTIVES: To characterize mechanisms of macrolide resistance among Streptococcus pneumoniae from 10 Asian countries during 1998-2001. METHODS: Phenotypic and genotypic characterization of the isolates and their resistance mechanisms. RESULTS: Of 555 isolates studied, 216 (38.9%) were susceptible, 10 (1.8%) were intermediate and 329 (59.3%) were resistant to erythromycin. Vietnam had the highest prevalence of erythromycin resistance (88.3%), followed by Taiwan (87.2%), Korea (85.1%), Hong Kong (76.5%) and China (75.6%). Ribosomal methylation encoded by erm(B) was the most common mechanism of erythromycin resistance in China, Taiwan, Sri Lanka and Korea. In Hong Kong, Singapore, Thailand and Malaysia, efflux encoded by mef(A) was the more common in erythromycin-resistant isolates. In most Asian countries except Hong Kong, Malaysia and Singapore, erm(B) was found in >50% of pneumococcal isolates either alone or in combination with mef(A). The level of erythromycin resistance among pneumococcal isolates in most Asian countries except Thailand and India was very high with MIC(90)s of >128 mg/L. Molecular epidemiological studies suggest the horizontal transfer of the erm(B) gene and clonal dissemination of resistant strains in the Asian region. CONCLUSION: Data confirm that macrolide resistance in pneumococci is a serious problem in many Asian countries.