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  • ZHOU Li-jin, WANG Yuan, LI Jia, ZHOU Xiang
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    Klebsiella pneumoniae (KP) can be classified into classic Klebsiella pneumoniae (cKP) and hypervirulent Klebsiella pneumoniae (hvKP) according to phenotypic characteristics and genetic markers. Epidemiological data indicate that hvKP infections are more prevalent among healthy community-dwelling adults, and its epidemic region has expanded from the Asia-Pacific region to a global scale. To better characterize hvKP, this article systematically reviews the biological and epidemiological features, virulence factors, drug resistance and related mechanisms of hvKP. This review aims to provide a reference for in-depth understanding of the pathogenic and drug-resistant nature of hvKP, as well as for the development of novel diagnostic and therapeutic strategies.
  • LIU Dai-mei, LI Shi-yu, TAN Hua-bing, YI Hua-wei
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    Scrub typhus is a natural focal disease caused by infection with Orientia tsutsugamushi. In recent years, the incidence of this disease has shown an upward trend in the AsiaPacific region. Delayed therapeutic efficacy and even drug resistance have been observed in clinical practice, which poses a severe challenge to the effective prevention and treatment of scrub typhus. This article systematically reviews the current clinical application and drug resistance trends of antiscrub typhus agents, the molecular basis of drug resistance mechanisms in scrub typhus, as well as the research directions and challenges for the development of novel antiscrub typhus drugs. It aims to provide a reference for the research and development of new antiscrub typhus agents and the subsequent exploration of therapeutic strategies against scrub typhus.
  • NORBU Dhondup, ZHU Chen-qi
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    Objective: To investigate the quantitative value transfer law of flavonoid components during the preparation of the reference sample of Wendan Decoction, a classical famous Chinese formula, and provide a scientific basis for the establishment of its specifications and development of its preparations. Methods: The reference sample of Wendan Decoction was prepared by the traditional water decoction process. A high-performance liquid chromatography (HPLC) method was established for the simultaneous determination of naringin, hesperidin and neohesperidin (the key flavonoid components), and systematic methodological validation was performed. The content changes of the three components (naringin, hesperidin and neohesperidin) and the extract yield in each preparation step were determined, the component transfer rates were calculated, and the quantitative value transfer characteristics were analyzed. Results: Naringin, hesperidin and neohesperidin presented absorption peaks at 30.115, 32.633 and 36.851 min, respectively. The water decoction of complete Wendan Decoction formula showed identical absorption peaks for the three components, with good baseline separation and no interference peaks. Through linear regression processing and standard curve plotting, it was found that the three components exhibited good linearity within their respective concentration ranges (r>0.999). The relative standard deviations (RSDs) of precision, stability and repeatability tests were all less than 2%, and the spiked recoveries met the required criteria. The extract yield of three batches of water decoction ranged from 11.96% to 14.59% (average 13.09%), and that of the three batches of concentrated solution ranged from 9.57% to 11.13% (average 10.31%). The transfer rate experiment showed that, the transfer rates of naringin, hesperidin and neohesperidin from herbal pieces to water decoction were 11.98%-13.00%, 20.00%-27.82% and 13.00%-17.00%, respectively; those from water decoction to concentrated solution were 81.99%-96.84%, 86.93%-100.00% and 82.91%-100.47%, respectively; and those from concentrated solution to lyophilized powder were 85.84%-114.69%, 89.86%-102.66% and 102.94%-104.92%, respectively. Conclusion: The established HPLC method for simultaneous determination of multi-index components of Wendan Decoction is accurate and reliable. Naringin, hesperidin and neohesperidin can be transferred completely through the process of "water decoction-concentrated solution-lyophilized powder", indicating that flavonoid components are effectively preserved without obvious loss during preparation.
  • XIA Wen, ZHANG Han-yuan, SHI Yu
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    Objective: To analyze the virulence characteristics of clinical Klebsiella pneumoniae (KP) isolates and their correlation with drug resistance, and provide a reference for the clinical prevention and treatment of KP infections. Methods: A total of 121 KP strains isolated from specimens of inpatients in various clinical departments of Zhenjiang Hospital of Integrated Traditional Chinese and Western Medicine from January to October 2024 were selected as the research materials. The mucoid phenotype, capsular serotypes (K1, K2, K5, K20, K54 and K57) and virulence genes (rmpA, magA, wcaG, fimH, kfu and Aero) of KP were detected by mucus thread formation test and polymerase chain reaction (PCR). Drug resistance of the KP isolates was determined using the VITEK 2 Compact automatic microbial identification and drug susceptibility analyzer. Finally, the virulence characteristics of clinical KP isolates and their correlation with drug resistance were analyzed. Results: Capsular serotyping of KP showed that all six capsular serotypes were detected, among which K2 was the most prevalent (29 strains, 23.97%), followed by K1 (19 strains, 15.70%) and K57 (12 strains, 9.92%); 48 strains (39.67%) were untyped. Virulence gene detection revealed that, all six virulence genes were detected, with the highest detection rate for fimH (102 strains, 84.30%), followed by rmpA (77 strains, 63.64%) and Aero (77 strains, 63.64%). The magA gene was exclusively detected in K1 strains (19 strains, 15.70%), and wcaG only in K1 and K54 strains (23 strains, 19.01%). The mucus thread formation test showed that, among the 121 isolates, 71 (58.68%) were hypermucoviscous (HV) phenotype and 50 (41.32%) were non-hypermucoviscous (non-HV). The HV isolates were dominated by K1 (16 strains, 22.54%), K2 (24 strains, 33.80%) and K57 (12 strains, 16.90%), whereas 40 (80.00%) non-HV isolates were untyped, with no K5 or K57 detected. Statistical analysis showed significant differences in capsular serotype distribution between HV and non-HV strains (P<0.05). The detection rates of Aero, rmpA and fimH in 71 HV isolates were all above 70.00%, while only fimH showed a high detection rate (92.00%) in 50 non-HV isolates. Significant differences were found in the detection rates of rmpA, wcaG and Aero between the two phenotypes (P<0.05). Drug susceptibility test showed, both phenotypes exhibited 100.00% resistance to ampicillin. HV isolates showed low resistance (less than 10.00%) to all tested antibacterial drugs other than ampicillin, whereas non-HV isolates had resistance rates of less than 10.00% only to meropenem and minocycline. Statistical analysis revealed significant differences in resistance rates between HV and non-HV strains against cefuroxime, ceftriaxone, ceftazidime, cefepime, cefoxitin, piperacillin-tazobactam sodium, gentamicin, amikacin, compound sulfamethoxazole, ciprofloxacin, levofloxacin and imipenem (all P<0.05). Drug-resistant enzyme detection showed that, among the 121 isolates, 27 produced extended-spectrum β-lactamases (ESBLs) and 5 were carbapenem-resistant Klebsiella pneumoniae (CRKP). ESBL-producing/CRKP isolates showed significantly lower detection rates of HV phenotype and common capsular serotypes than non-ESBL-producing/CRKP isolates (9.38% vs 76.40%, P<0.05; 12.50% vs 77.53%, P<0.05). In terms of virulence genes, the detection rates of Aero, rmpA, wcaG and magA were also significantly lower in ESBL-producing/CRKP strains (P<0.05). Conclusion: Clinical HV KP isolates generally display high expression of virulence genes and specific capsular serotypes, but exhibit lower resistance to most antibacterial drugs than non-HV isolates.
  • LI Sheng-hui, LIANG Zhen-sheng
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    Objective: To investigate the in vitro antibacterial activity and mechanism of ethyl gallate against common clinical pathogenic bacteria, and provide a reference for the development of clinical drugs for bacterial infections. Methods: The broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) of ethyl gallate against Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Shigella flexneri and Salmonella, so as to evaluate its in vitro antibacterial activity against pathogenic bacteria. Biochemical methods were used to measure the contents of extracellular alkaline phosphatase, nucleic acids and proteins in bacteria, so as to explore the antibacterial mechanism of ethyl gallate. Results: Ethyl gallate showed the strongest activity against Staphylococcus aureus, Streptococcus pneumoniae and Shigella flexneri (MIC = 256.0 μg/mL), followed by Escherichia coli and Salmonella enterica (MIC = 512.0 μg/mL), and the weakest activity against Klebsiella pneumoniae and Pseudomonas aeruginosa (MIC = 1 024.0 μg/mL). Compared with the blank group, the extracellular levels of alkaline phosphatase, nucleic acids and proteins in Staphylococcus aureus and Shigella flexneri were significantly increased after 6 h of treatment with 256.0 μg/mL ethyl gallate (P<0.01). Conclusion: Ethyl gallate exhibits favorable broad-spectrum antibacterial activity against common clinical pathogenic bacteria, and its antibacterial mechanism may be related to destroying the integrity of the bacterial cell wall and cell membrane.
  • HUANG Jun-wei, GUO Ting-ting, LIU Jing
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    Objective: To analyze the pharmaceutical care process for a patient with refractory peritoneal dialysis-associated peritonitis, and provide a reference for anti-infective therapy and medication safety in such patients. Methods and Results: The patient was admitted to the hospital due to turbid ascites for 9 days and diagnosed with refractory peritoneal dialysis-associated peritonitis based on the patient's recent examination results and previous anti-infective treatment. Empirical anti-infective therapy with teicoplanin plus levofloxacin was given. On the second day after admission, next-generation sequencing of ascites indicated Acinetobacter baumannii, and the therapeutic regimen was adjusted to cefoperazone-sulbactam sodium plus tigecycline. After 5 days of treatment, abnormal coagulation parameters including prothrombin time, activated partial thromboplastin time and fibrinogen were observed. After evaluation, clinical pharmacists considered that the abnormalities were most likely induced by cefoperazone-sulbactam sodium combined with tigecycline, and recommended switching the anti-infective regimen to colistimethate sodium plus meropenem. However, the patient developed severe dyspnea immediately after the first intravenous administration of colistimethate sodium. Clinical pharmacists attributed it to colistimethate sodium, and suggested immediate drug discontinuation and hemodialysis to promote drug elimination. The patient's dyspnea gradually improved on the next day. On the 5th day of meropenem treatment, the patient's infectious symptoms and inflammatory markers were significantly relieved, and peritoneal dialysis catheter removal was performed. Conclusion: The treatment of refractory peritoneal dialysis-associated peritonitis is complex and prolonged. Clinical pharmacists should timely optimize and individualize the anti-infective regimen according to the patient's condition and laboratory results to ensure effective treatment, and strengthen the monitoring of adverse drug reactions to guarantee medication safety.
  • WU Xiu-feng, ZHANG Jun, LI Jian-qiang, DING Yong-juan
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    Objective: To analyze the diagnosis and anti-infective treatment process of a patient with Cryptococcus gattii pneumonia, and provide a reference for the early identification and standardized treatment of Cryptococcus gattii infection. Methods and Results: The patient was admitted to the hospital due to cough and expectoration for 1 week. Based on the patient's symptoms, laboratory findings and chest CT results, the patient was initially diagnosed with pulmonary infection and received empirical therapy with moxifloxacin, which was later switched to piperacillin-sulbactam sodium. On the 8th day after admission, the patient's fever, cough and expectoration showed no obvious improvement, and Pseudomonas aeruginosa was detected by sputum culture; the antiinfective regimen was then adjusted to biapenem according to the etiological results. On the 11th day after admission, the patient still had fever, and metagenomic nextgeneration sequencing of bronchoalveolar lavage fluid detected Cryptococcus gattii VG Ⅰ with a sequence count of 20. Despite the low sequence count, clinicians identified Cryptococcus gattii as the pathogenic bacterium in combination with the patient's clinical manifestations and response to antiinfective therapy. After thorough evaluation by physicians and pharmacists, antifungal therapy with liposomal amphotericin B plus flucytosine was initiated. The patient's body temperature returned to normal after 3 days of antifungal therapy. After 2 weeks of antifungal therapy, fever and cough were significantly relieved, and chest CT showed resolution of bilateral pulmonary lesions. Conclusion: Different from Cryptococcus neoformans, which mainly infects immunocompromised individuals, Cryptococcus gattii primarily targets immunocompetent people. Moreover, Cryptococcus gattii rarely causes pulmonary infection and mostly presents with atypical clinical manifestations, leading to easy misdiagnosis or neglect. Therefore, high clinical vigilance should be paid to immunocompetent patients with poor response to empirical treatment. Advanced molecular biological detection techniques are recommended for auxiliary diagnosis to achieve early definite diagnosis and targeted therapy, thereby promoting patient recovery.