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  • 2021, 44(06): 493-500.
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    Abstract    In the past two decades, the infectious diseases caused by a variety of new viruses have presented
    severe challenges to the world health system, including the 2003 severe acute respiratory syndrome (SARS), the
    2009 pandemic A (H1N1), the 2014 middle east respiratory syndrome (MERS), the 2014 Ebola virus disease (EVD),
    the 2015 zika virus (ZIKV) disease, and the 2019 coronavirus disease (COVID-19). This review focuses on the
    epidemiological characteristics of the SARS, H1N1 influenza A, MERS, EVD, ZIKV disease, and COVID-19.
    In addition, the implications for treatment, prevention, and control of COVID-19 were discussed, to provide the
    theoretical support for the prevention and control of various infectious diseases in the future.
  • 2021, 46(06): 501-508.
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    Abstract Antibiotics are widely used worldwide. Thus, a large amount of wastewater containing antibiotics
    is produced. At present, biological nitrogen removal process is often used in the wastewater treatment. The
    microorganisms can be inhibited by the antibiotics, which could affect the biological nitrogen removal performance.
    In this paper, the effects of antibiotics on nitrification, denitrification and anaerobic ammonium oxidation process were
    described. The main mechanisms on the resistance to the inhibition by the antibiotics were summarized. In addition,
    the further research in the treatment of wastewater containing antibiotics was prospected.
  • 2021, 46(06): 509-517.
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    Abstract China is a big country of pig and chicken breeding. Salmonellosis and colibacillosis, as the most
    common bacterial diseases in pig and chicken farms, are often mixed infections, and antimicrobial drugs are used
    in clinical treatment. In recent years, due to the large-scale unreasonable use of antibacterial drugs, Salmonella and
    Escherichia coli have developed serious antimicrobial resistance, and the breeding industry, veterinary clinical
    treatment, and public health have been affected. This article mainly investigates the research progress of antimicrobial
    resistance of pig- and chicken-derived Salmonella and Escherichia coli reported in China in the past three years (2017-
    2019), including the resistance mechanism of pig- and chicken-derived Salmonella and E.coli, common resistance
    genes, resistance types and resistance rates of Salmonella and E. coli isolated in some areas of China, in order to
    strengthen the monitoring and control of antimicrobial resistance.

  • 2021, 46(06): 518-528.
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    Abstract Sulfonamide and sulfamate natural products are naturally occurring compounds containing
    nitrogen(-Ⅲ)-sulfur(+Ⅵ) bonds (N-S bonds), of which the chemical formulas can be expressed as RSO2NR'R'' and
    ROSO2NR'R'', respectively. Sulfonamide and sulfamate groups share similar structures and density distribution of
    electronic cloud with that of the phosphate group, so that they can occupy the active sites in some receptor proteins (such
    as carbonic anhydrase, cyclooxygenase-2, and acetylcholinesterase), and thus have an effect on their physiological
    function. Sulfonamide and sulfamate natural products show a wide range of biological activities, including antibacterium,
    antivirus, anti-inflammatory, antitumor, anticoagulation, and so on. Until now, four N-S bond biosynthetic
    pathways of naturally occurring sulfonamides and sulfamates have been characterized, including ① sulfonic group
    transfer reactions catalyzed by sulfotransferases; ② amino group transfer reactions catalyzed by aminotransferases;
    ③ oxidation reaction catalyzed by SbzM; ④ radical copolymerization catalyzed by XiaH. In this review, these four
    nitrogen-sulfur bond formation mechanisms will be summarized.
  • 2021, 46(06): 529-537.
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    Abstract Bacterial SOS DNA damage repair system affects the growth and development of bacteria, and
    involves many other regulations that influence virulence, drug resistance, and drug resistance adaptability of bacteria.
    Most of the genetic variations produced by antibiotics can be attributed to the induction of SOS repair response. Indepth
    study of the bacterial SOS repair response mechanism and development of the corresponding target inhibitors
    have become a hot direction of research. Therefore, this paper summarized the SOS repair mechanism of bacteria, the
    relationship between SOS repair and bacterial virulence and drug resistance development, as well as the development
    of inhibitors targeting SOS, so as to provide a knowledge base for the in-depth research on the mechanism of bacterial
    resistance and the development of inhibitors against drug resistance.
  • 2021, 46(06): 538-544.
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    Abstract Objective In this study, the structure and function of tylosin reductase from Streptomyces fradiae
    was explored. Methods The protein sequence and gene sequence of tylosin reductase were obtained by searches
    and comparisons in NCBI database, and the three-dimensional model and phylogenetic tree of tylosin reductase were
    established. In addition, prokaryotic expression and purification of the enzyme was performed and the activity of
    enzyme was determined. Results The sequence length of tylosin reductase gene from Streptomyces fradiae ATCC
    19609 was 996bp, which encoded a polypeptide of 331 amino acids. The tertiary structure of the enzyme included ten
    barrel-shaped α helices, eight β folds and a NADPH binding site. Phylogenetic analysis showed that tylosin reductase
    belonged to the AKR12 family of aldo-keto reductase superfamily. The results of determination of enzyme activity
    demonstrated tylosin reductase had a wide range of substrates, and its specific activity to tylosin was 0.128U/mg.
    Conclusion It is confirmed that tylosin reductase from Streptomyces fradiae could catalyze the reduction of tylosin.
    This experiment can provide basic theoretical support for inhibiting the activity of tylosin reductase and improving the
    purity of tylosin fermentation products.
    Key words Tylosin reductase; Protei
  • 2021, 46(06): 545-551.
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    Abstract Objective Using Pseudomonas aeruginosa model strain PAO1 as the model to evaluate the effect
    of the classic anti-tuberculosis drug D-cycloserine on inhibition of bacterial virulence by targeting the quorumsensing
    (QS) system. Methods Virulence phenotyping experiments combined with fluorescence quantitative
    PCR were used to investigate the effect of D-cycloserine on the expression of virulence factors and QS-encoding
    genes regulated by P. aeruginosa QS system. Caenorhabditis elegans infection model was then used to evaluate
    the protection by D-cycloserine against the challenge of P. aeruginosa. Results D-cycloserine could significantly
    inhibit the production of biofilm, pyocyanin, and extracellular proteases of P. aeruginosa. D-cycloserine also reduced
    the expression levels of a series of QS-controlled genes. Furthermore, the application of D-cycloserine protected C.
    elegans from P. aeruginosa challenge, in both of the fast killing and the slow killing assays. Conclusion This study
    reveals that D-cycloserine can effectively inhibit the QS system and virulent factors of P. aeruginosa which makes
    D-cycloserine a potential anti-virulent drug as an antibiotic substitute.
  • 2021, 46(06): 552-556.
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    Abstract Objective Fungi were isolated from rhizosphere soil of Cynanchum bungei Decne., the excellent
    strains with antibacterial activities were screened, and the active compounds were isolated and identified. Methods
    The fungi were isolated from rhizosphere mud samples by the gradient dilution method. The compounds were
    separated and purified by using positive/reverse phase silica gel and semi-preparative high performance liquid
    chromatography, and the structures of the active compounds were confirmed by MS and NMR spectroscopic method.
    Results 83 strains of fungi were isolated from three samples, among which seven strains were screened to have the
    activity of inhibiting Staphylococcus aureus and Escherichia coli, and two naphthalene pyranones rubrofusarin B
    (1) and fonsecin B (2) were isolated and identified from the secondary metabolites of Aspergillus niger SDFMU-45.
    Conclusion The antimicrobial activity of compounds 1 and 2 was tested, and the results showed that the MIC
    values of compounds 1 and 2 against the standard strains of Staphylococcus aureus were 250μg/mL and 187μg/mL
    respectively, and 2.89μg/mL and 620μg/mL against the standard strains of E. coli.
  • 2021, 46(06): 557-563.
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    Abstract Objective Taxonomic identification and mutagenesis breeding on a self-isolated staurosporineproducing
    strain HY1. Methods The strain HY1 was identified through the homology analysis of 16S rDNA gene
    sequence, combined with its morphological characteristics, culture characteristics, physiological and biochemical
    properties. Ultraviolet-Lithium chloride (UV-LiCl), atmospheric and room temperature plasma (ARTP), and
    nitrosoguanidine (NTG) were used as mutagens in treating the strain HY1, and the plate containing tryptophan and
    methionine was used to screen the strains. Results The taxonomical studies showed that the strain HY1 belonged
    to Streptomyces sp.. The mutant strain, named HY6-S36, was selected. The genetic performance was stable and the
    productivity of staurosporine reached 360mg/L, which was 80% higher than the original strain. Conclusion The new
    high-yield and stable strain can provide excellent strains for the industrialization of staurosporine.
  • 2021, 46(06): 564-568.
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    Abstract Objective To establish a new method for the dissolution curve determination of azithromycin
    Tablet, and evaluate the dissolution profiles of domestic generic tablets and the original tablets in four different
    kinds of pH mediums. Methods The paddle method of dissolution determination method was adopted, the
    rotation speed was 75 r/min, with the dissolution medium volume of 900 mL. UPLC was adopted to determine the
    content of azithromycin in pH 2.0 hydrochloride acid, pH 4.5 phosphoric acid, pH 6.0 phosphoric acid and pH 6.8
    phosphate buffer solution; the cumulative dissolution was calculated, the dissolution profiles were drawn, and the
    similarity of dissolution profiles were evaluated. Results In four different pH dissolution media, the dissolution
    amount of domestic and original azithromycin tablets all reached more than 85% in 15 minutes, which indicated
    that the dissolution behaviors of two batches of domestic imitated products were basically the same with the original
    azithromycin tablets, and the judgment was similar. Conclusion The method is suitable for the dissolution curve
    determination of azithromycin tablets, providing a reference for further quality consistency evaluation.
  • 2021, 46(06): 569-572.
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    Abstract Objective This article reports a novel method called 2D-HPLC-QTOF which was used to identify
    the-ring-opening compound of biapenem. Methods The impurities were separated by 1D-HPLC,The salt was
    desalted by 2D-HPLC and the unknown impurity was danalyzed by QTOF. The impurity was synthesized according
    to the speculated structure and confirmed by NMR. Results This method effectively solved the problem that the
    chromatographic system containing nonvolatile salt in the mobile phase of biapenem was not suitable for rapid
    identification of impurities by liquid chromatography-mass spectrometry, and confirmed that the unknown impurity
    was a-ring-opening compound of biapenem. Conclusion This method can identify the-ring-opening compound of
    biapenem and it has many advantages such as simplicity, accurateness, and sensitivity.
  • 2021, 46(06): 573-583.
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    Abstract Daptomycin is a new anti-resistant antibiotic used in clinic. Due to its structural characteristics, it is
    easy to be degraded in acid or alkaline conditions. In this study, we used UPLC/MS to compare and analyze the acid
    degradation products of daptomycin and its lactone hydrolysate, respectively, and found that the main degradation
    products of daptomycin was aspartyl-alanylamide bond breaking product. The main degradation products of lactone
    hydrolysate were heptapeptides with molecular weight of 974 and nonapeptides with molecular weight of 1160.
    Through comparison, we also determined that the related substances with molecular weight of 974 mainly came from
    acid degradation of lactone hydrolysates. The chemical structure and amino acid sequence of the heptapeptide were
    determined by NMR.
  • 2021, 46(06): 584-588.
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    Abstract Objective To analyze the distribution and antibiotic resistance profile of Gram-negative bacteria
    of blood stream infection in 11 children’s hospitals. Methods According to the technical program of China
    Antimicrobial Resistance Surveillance System (CARSS), the identification and antimicrobial susceptibility tests of
    those organisms were conducted and the results were interpreted according to CLSI guideline 2018. Results A total
    of 14,078 strains were collected from blood samples in these hospitals between 2016 to 2018, of which gram-negative
    bacteria accounted for 35.1%(4,937/14,078), respectively. The top 5 species were Escherichia coli, Stenotrophomonas maltophilia, Klebsiella pneumoniae, Achromobacter xylosoxidans and Pseudomonas aeruginosa. Less than 10%
    of the Escherichia coli were resistant to piperacillin-tazobactam, cefotetan, meropenem, ertapenem, and imipenem,
    respectively. Meanwhile, less than 10% of the Klebsiella pneumoniae were resistant to tigecycline, tobramycin,
    and amikacin, respectively. 12.5%, 13.0%, 0.4% and 40.8%, 37.7%, 20.0% of the Pseudomonas aeruginosa and
    Acinetobacter baumannii were resistant to levofloxacin, meropenem, and imipenem, respectively. Conclusion The
    resistance of Gram-negative bacteria to commonly used antibiotics occurred in various extents in bloodstream
    infections in children. We should pay great attention to the results of surveillance of bacterial resistance, and use
    antibiotics rationally.
  • 2021, 46(06): 589-595.
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    Abstract Objective To investigate the antibiotic resistance of clinical isolates in the First People’s Hospital
    of Anqing in 2018. Methods The antimicrobial susceptibility testing was carried out according to a unified protocol
    using automated systems or the Kirby-Bauer method. Results were interpreted according to CLSI 2018 breakpoints
    and analyzed by WHONET 5.6 software. Results A total of 962 bacterial isolates were collected in 2018. There
    were 218 strains (22.7%) of Gram-positive bacteria and 744 strains (77.3%) of Gram-negative bacteria. The most
    frequently isolated bacteria were Escherichia coli (24.9%), followed by Klebsiella pneumoniae, and Pseudomonas
    aeruginosa. The strains were mainly isolated from the respiratory tract (38.6%) and secretion (22.6%). The prevalence
    of methicillin-resistant Staphylococcus aureus and methicillin-resistant coagulase-negative Staphylococcus (MRSA
    and MRCNS) was 29.4% and 91.3%, respectively. No Staphylococcus strains were found resistant to linezolid or
    vancomycin. Enterococcus faecalis and Enterococcus faecium accounted for 29.8% and 70.2% of total Enterococcus
    isolates. No Enterococcus strains were found resistant to vancomycin. The prevalence of ESBLs-producing strains was 56.8% in E. coli, 44.2% in Klebsiella spp., and 5.3% in Proteus mirabilis. Enterobacteriaceae strains were still highly
    susceptible to carbapenems. The resistance rates of Klebsiella pneumoniae and Enterobacteriaceae to imipenem were
    lower than 4.8%. The resistance rate of P. aeruginosa to imipenem was 20.9%, but lower than 25% to levofloxacin,
    ciprofloxacin, piperacillin-tazobactam, tobramycin, cefepime, ceftazidime, gentamycin, and amikacin. The resistance
    rate of Acinetobacter baumannii to imipenem was 78.9%, and the resistance rates to all the antibiotics tested except
    amikacin and minocycline were higher than 65%. Conclusion The clinical bacterial isolates show various levels of
    resistance to antibacterial agents. More attention should be paid to infection control measures. The communication
    between laboratorians and clinicians should be further improved in addition to rational use of antimicrobial agents and
    the spread of resistant strains should be prevented.
  • 2021, 46(06): 596-603.
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    Abstract Objective The clinical distribution and drug resistance of methicillin-resistant Staphylococcus
    aureus (MRSA) was studied from 2015 to 2019 to provide suggestions for clinical rational drug use and infection
    control. Methods 461 strains of MRSA isolated from the People's Hospital of Inner Mongolia Autonomous Region
    from January 2015 to December 2019 were retrospectively analyzed in the aspects of the source of specimens, the
    distribution of departments, the changing trend of detection rate and drug resistance rate. The drug resistance of 461 strains of MRSA and 1007 strains of methicillin sensitive Staphylococcus aureus (MSSA) were compared and
    analyzed. The data were analyzed by Whonet 5.6 software and SPSS 22.0 software. Results The detection rates of
    MRSA from 2015 to 2019 were 40.70%, 24.75%, 26.83%, 34.33%, and 30.72%, with an average of 31.34%. MRSA
    was mainly distributed in the ICU ward, the cadre health care ward, neurosurgery, neurology, and pediatrics, with the
    constituent ratios of 17.35%,16.70%,15.84%,12.80%, and 7.81%, respectively. The Department of Neurology had the
    highest detection rate of MRSA (74.68%). The detection rate of MRSA in ICU (64%) was significantly higher than
    that in non-ICU wards (28.31%,P<0.05). MRSA was mainly isolated from sputum, secretion, blood, pus, and urine,
    with the constituent ratios of 52.28%, 20.61%, 9.76%, 5.42%, and 4.34%, respectively. The detection rate of MRSA
    in sputum was 60.40%, which was the highest detection rate and was significantly higher than that in non-sputum
    samples (20.52%, P<0.05). From 2015 to 2019, the drug resistance rates of MRSA to erythromycin, nitrofurantoin,
    linezolid, vancomycin, and quinuptin/dafurtin had little change (P>0.05); the drug resistance rates to gentamicin,
    rifampicin, ciprofloxacin, levofloxacin, moxifloxacin, clindamycin, and tetracycline showed a downward trend
    (P<0.05). The 5-year average drug resistance rate was 50%~100%; the resistance rate to cotrimoxazole showed an
    upward trend (P<0.05). Compared with MSSA, MRSA had higher resistance rates to penicillin, gentamicin, rifampicin,
    ciprofloxacin, levofloxacin, moxifloxacin, clindamycin, erythromycin, nitrofurantoin, and tetracycline(P<0.05),
    except linezolid, vancomycin, and quinuputin/dapfoptin. However, the resistance rate of MSSA to cotrimoxazole was
    significantly higher than that of MRSA(P<0.05). Conclusion MRSA is mainly distributed in ICU, mainly from
    sputum. MRSA infection has decreased slightly in the past five years, but the detection rate of MRSA is still around
    30%, showing multiple drug resistance. Therefore, the hospital should strengthen the management of antimicrobial
    agents, bacterial resistance monitoring, hand hygiene, disinfection and isolation, and other measures to effectively
    control the infection and drug resistance of MRSA.
  • 2021, 46(06): 604-610.
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    Abstract Objective To understand the distribution and drug resistance of pathogenic bacteria in patients
    with pneumonia in neurosurgery, and to analyze the risk factors for MDRO infection. Methods The clinical data of
    159 patients with neurosurgical pneumonia were retrospectively analyzed to investigate the distribution of pathogenic
    bacteria in sputum culture and resistance. Risk factors for infection with MDRO were analyzed using single factor
    and multiple factor analyses. Results A total of 174 strains of pathogenic bacteria were isolated from 159 patients.
    Among the 135 Gram-negative bacteria (77.6%), 43 were Acinetobacter baumannii (24.7%), 39 were Klebsiella
    pneumoniae (22.4%), and 28 were Pseudomonas aeruginosa (16.1%). Among the Gram-positive bacteria (19.0%),
    there were 24 strains of Staphylococcus aureus (13.8%), including 103 MDRO (59.2%) and 71 non-MDRO (40.8%).
    The MDRO composition ratio was from high to low, followed by 37 strains of Acinetobacter baumannii (35.9%),
    19 strains of Klebsiella pneumoniae (18.4%), 17 strains of Pseudomonas aeruginosa (16.5%), and 16 strains of
    Staphylococcus aureus (15.5%). The results of the single-factor analysis showed that nine factors, including time of stay in the NICU, number of days of antibiotics, type of antibiotics, combination of antibiotics, antimicrobial strategy,
    use of glucocorticoids, type of pneumonia, endotracheal intubation, and Ventilator-associated pneumonia (VAP),
    were statistically significant for the occurrence of MDRO infection (P<0.05). Multivariate logistic regression analysis
    showed that antibiotic "ladder up" (OR: 4.824, 95%CI: 1.439~16.169, P=0.011), combination of antimicrobial
    agents (OR=4.615, 95%CI :1.338~15.922, P=0.016), and endotracheal intubation (OR: 2.627, 95%CI: 1.166~5.918,
    P=0.020) were risk factors for MDRO infection in patients with neurosurgical pneumonia. Conclusion In high-risk
    patients with neurosurgical pneumonia caused by MDRO infection, active prevention and control and intervention
    measures should be taken to reduce the incidence and mortality of MDRO nosocomial infection.
  • 2021, 46(06): 611-615.
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    Abstract Objective To investigate the clinical features and risk factors of Pseudomonas aeruginosa in our
    hospital in order to provide references for the control of hospital infections and the application of antibacterial drugs.
    Methods The clinical distribution and drug resistance of Pseudomonas aeruginosa isolated from our hospital in
    2018—2019 were analyzed. Single factor and Logistic regression were used to analyze risk factors of carbapenemresistant
    Pseudomonas aeruginosa (CRPA). Results CRPA accounted for 21.34% of Pseudomonas aeruginosa
    (150/703). Pseudomonas aeruginosa and CRPA were mainly isolated from sputum specimens (61.02%, 60.67%)
    and distributed in ICU wards (47.82%, 52.00%). Pseudomonas aeruginosa had a high resistance rate to various
    antibacterial drugs and the sensitivity rates to polymyxin B and amikacin were up to 100% and 98.44%. Multivariate
    regression analysis showed that the OR values of basic disease, invasive treatment, co-infection with other pathogens,
    and ICU were 14.470, 12.677, 9.216, and 6.381, respectively, with P values all <0.05. Conclusion Pseudomonas
    aeruginosa was mainly isolated from sputum specimens and distributed in ICU wards. The drug resistance was serious.
    Basic diseases, invasive treatment, co-infection with other pathogens and ICU were major risk factors for CRPA infection.
  • 2021, 46(06): 616-620.
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    Abstract Objective To investigate the inhibitory function and mechanism of tannic acid (TA) combined
    with fluconazole on Staphylococcus aureus and Candida albicans polymicrobial biofilms. Methods Three clinical
    methicillin-resistant S. aureus (MRSA) strains were collected in 2019 and named as SA1, SA2, and SA3, respectively.
    The influence of growth ability of S. aureus and C. albicans DAY185 mixed strains after the action of tannic acid
    or combined with fluconazole were measured using the spectrophotometer method, and their effects against the
    polymicrobial biofilm formation ability were further analyzed using the crystal violet staining method. Scanning
    Electron Microscope (SEM) was used to assess the impact of tannic acid combined with fluconazole on polymicrobial
    biofilms structure. Real-time quantitative PCR (qRT-PCR) was conducted to detect the expression of biofilm-related genes ALS1, ALS3, and RBT1 of C. albicans DAY185 and icaA, sarA, and cidA of SA1. Results Tannic acid could
    reduce the growth ability and biofilm formation ability of S. aureus and C. albicans mixed strains. Its inhibitory effect
    was more significant when combined with fluconazole. SEM showed the attachment of S. aureus on hyphae of C.
    albicans was reduced significantly after tannic acid and fluconazole treatment. qRT-PCR revealed that tannic acid
    combined with fluconazole could mainly reduce the expression levels of adhesion related genes ALS3 of C. albicans
    and icaA and sarA of S. aureus. Conclusion Tannic acid combined with fluconazole could reduce the polymicrobial
    biofilms formation by S. aureus and C. albicans, and its mechanism was mainly by diminishing the genes expression
    (ALS3) involved in the formation of C. albicans hyphae and adhesion related genes icaA and sarA of S. aureus.
  • 2021, 46(06): 621-627.
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    Abstract Objective To optimize fluconazole administration in low-weight premature infants by Monte-
    Carlo models and to provide a reference for individualized administration of fluconazole in low-weight preterm
    infants. Methods According to gestational age, weight, and serum creatinine combined with the distribution of
    minimum inhibitory concentration (MIC) of fluconazole against C. albicans, C. parapsilosis, and C. tropicalis, and
    the population pharmacokinetic parameters of fluconazole in low-weight preterm infants, Crystal Ball 11.1.2.2 was
    applied. We performed Monte Carlo simulation (MCS) on different dosage regimens of different groups, using the
    probability of target attainment (PTA) and cumulative fraction of response (CFR) as evaluation indicators. Results
    When the MIC value of the infected fungus was lower than 2μg/mL and the dose of fluconazole was 6mg/(kg·d), PTA
    could reach above 90%. When the MIC value was higher than 4μg/mL, it was necessary to appropriately increase the dose to obtain treatment effects. The dose of 3mg/(kg·d) could only meet the therapeutic effect when the MIC
    value was≤1μg/mL. When MIC≤1μg/mL, 3mg/(kg·d) could satisfy the therapeutic effect. For extremely preterm
    infants, fluconazole dose of 6mg/(kg·d) could meet the therapeutic effect of MIC≤4μg/mL. For preterm infants after
    28 weeks, the MIC of 4μg/mL was satisfied with fluconazole dose of 6mg/(kg·d) only when the serum creatinine was
    normal or higher than normal. If the serum creatinine was lower than the normal value, the dosage of this medicine
    should be increased appropriately. For the treatment of C. albicans, 3mg/(kg·d) fluconazole could meet the criterion
    of CFR>90%, while for the treatment of C. tropicalis, 6mg/(kg·d) fluconazole could meet the criterion of CFR>90%.
    But for the treatment of C. parapsilosis, when serum creatinine was lower than normal, it was necessary to increase
    the dose of fluconazole. For preterm infants with normal or higher serum creatinine, 6mg/(kg·d) fluconazole could
    meet the criterion of CFR>90%, while for preterm infants with normal serum creatinine after 28 weeks, 9mg/(kg·d) or
    could meet the criterion of CFR>90%, and for preterm infants with higher serum creatinine, 6mg/(kg·d) fluconazole is
    sufficient to meet the criterion of CFR>90%. Concusion The 6mg/(kg·d) dose of fluconazole could basically meet
    the treatment needs of low weight premature infants with normal or higher serum creatinine. However, PTA value was
    affected by gestational age, body weight, and serum creatinine, and the CFR value was related to the MIC distribution
    of pathogenic bacteria. Therefore, to achieve the ideal therapeutic effect of individuals, population pharmacokinetics
    and Monte Carlo models should be combined to realize individual drug delivery scheme.
  • 2021, 46(06): 628-632,S1.
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    Abstract Objective To systematically assess risk factors for antituberculosis drug-induced liver injury
    (ADILI) in Chinese patients. Methods Literatures were retrieved from PubMed,Embase, Cochrane Library,
    CNKI,CBM,Wanfang and VIP database from the establishment of database to May of 2019, and the data about
    the risk factors for ADILI in Chinese patients were collected.Literatures were screened,extracted,and evaluated
    according to inclusion and exclusion criteria by two reviewers. Meta-analysis was conducted using RevMan 5.3
    software.Results A total of 12 literatures were included, all of which were Chinese literatures, including 8216
    patients. A total of 13 exposure factors were screened. Meta-analysis showed that alcoholism (OR=2.54, 95% CI:
    1.97~3.27), history of liver disease (OR=2.60, 95%CI: 2.19~3.08), carrier of hepatitis B antigen (OR=3.15, 95% CI:
    2.66~3.73), diabetes (OR=1.41, 95%CI: 1.18~1.70), cardiac insufficiency (OR=1.72, 95%CI: 1.28~2.30), anemia (OR=4.61, 95%CI: 2.43~7.90), malnutrition (OR=2.48, 95%CI: 1.63~3.77), and tuberculosis retreatment (OR=1.93,
    95%CI: 1.43~2.60) were risk factors for ADILI in Chinese patients(P<0.05). Prophylactic hepatoprotective drugs
    could significantly reduce the incidence of liver damage caused by anti-tuberculosis drugs (OR=0.36, 95%CI: 0.25
    ~0.50, P<0.001). Conclusion Anemia, hepatitis B original antigen carrier, combined with other liver disease history,
    alcoholism, malnutrition, tuberculosis retreatment, cardiac insufficiency, diabetes are risk factors for ADILI in Chinese
    patients. Hepato protective drugs for patients with high risk factors can significantly reduce the incidence of liver
    damage caused by anti-tuberculosis drugs.