Xiaohong Zhu, Li Cao, Juan Wang, Xuefeng Lu, Zuoyu Huang, Xiaoping Wen, Lihong Bian, Congxia Wu, Meiyin Zou
{"title":"Identification of Pathogens in HIV-Infected Patients Using Metagenomic Next-Generation Sequencing (mNGS) as Compared to Conventional Microbiological Tests (CMTs).","authors":"Xiaohong Zhu, Li Cao, Juan Wang, Xuefeng Lu, Zuoyu Huang, Xiaoping Wen, Lihong Bian, Congxia Wu, Meiyin Zou","doi":"10.2147/IDR.S491946","DOIUrl":"10.2147/IDR.S491946","url":null,"abstract":"<p><strong>Background: </strong>The rapid and accurate identification of infectious pathogens in HIV-infected patients remains a challenge. Metagenomic next-generation sequencing (mNGS) is a panpathogen assay for rapid diagnosis of infectious diseases. Here, the diagnostic value of mNGS was evaluated in HIV-infected patients and compared with conventional microbiological tests (CMTs).</p><p><strong>Methods: </strong>This study was conducted on 216 hIV-infected patients with suspected opportunistic infections. Infectious pathogen detection was done by mNGS and conventional microbiological tests, respectively.</p><p><strong>Results: </strong>A total of 195 patients (90.2%) were positive for microbial pathogens by mNGS, while 135 patients (62.5%) were positive for microbial pathogens by CMTs. Mixed infection was identified in 92 patients by mNGS, and 41 patients were detected with mixed infection by CMTs. Fungi and virus mixed infection was the most frequent pattern detected by mNGS (32, 14.8%) and CMTs (22, 10.2%). The CD4+ T cell count in patients with mixed pathogens was significantly lower than that in patients infected with a single pathogen. Pathogens were quickly identified by mNGS in 151 patients (69.9%), and appropriate treatments were initiated. In 47 patients antibacterial agents were adjusted based on mNGS results, in 39 patients antifungal agents were changed, and 35 patients had antiviral agents added.</p><p><strong>Conclusion: </strong>mNGS is a valuable tool and enhances rapid microbiological identification in HIV-infected patients. Combined with CMTs, mNGS may facilitate personalized antimicrobial treatment strategies and increase survival.</p>","PeriodicalId":13577,"journal":{"name":"Infection and Drug Resistance","volume":"18 ","pages":"929-940"},"PeriodicalIF":2.9,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Predictors for Invasive Pulmonary Aspergillosis in Acute-on-Chronic Liver Failure Patients: A Retrospective Study.","authors":"Chenxi Yuan, Rongqing Zhu, Lifen Hu, Jiabin Li","doi":"10.2147/IDR.S497840","DOIUrl":"10.2147/IDR.S497840","url":null,"abstract":"<p><strong>Introduction: </strong>Acute-on-chronic liver failure (ACLF) is a severe syndrome that manifests as acute liver function deterioration and organ failure. Coinfection with invasive pulmonary aspergillosis (IPA) in ACLF patients is characterized by high mortality and increasing morbidity. The aim of this study was to explore the early warning factors and prognosis of ACLF patients with IPA coinfection.</p><p><strong>Methods: </strong>In this retrospective study, we collected clinical, biochemical, and microbiological data from patients with ACLF and IPA from May 2019 to May 2023. Univariable and multivariate analyses were used to identify independent risk factors for IPA in ACLF patients. Moreover, the area under the curve (AUC) and decision curve analysis (DCA) were used to evaluate the model performance.</p><p><strong>Results: </strong>A total of 438 patients with ACLF were enrolled, 408 (93.2%) non-IPA patients and 30 IPA (6.8%) including 29 probable cases and one proven case. The 28-day case fatality rate (56.7% vs 29.4%) was higher in ACLF patients with IPA than in ACLF patients without IPA, but without statistical difference. Multivariate analysis revealed that early warning factors for IPA coinfection in ACLF patients included nausea (<i>p</i> = 0.010), expectoration (<i>p</i> < 0.001), bacterial and fungal infections (<i>p</i> < 0.001), corticosteroid use (<i>p</i> = 0.037), surgery (<i>p</i> = 0.081), haemoptysis (<i>p</i> = 0.015) and increased leukocyte counts (<i>p</i> = 0.010). The AUC was 0.934 (<i>p</i> < 0.001), and DCA verified the validity and clinical effectiveness of our model.</p><p><strong>Conclusion: </strong>These findings provide valuable insights for clinicians in the early diagnosis of IPA in ACLF patients and may facilitate timely intervention and treatment.</p>","PeriodicalId":13577,"journal":{"name":"Infection and Drug Resistance","volume":"18 ","pages":"909-918"},"PeriodicalIF":2.9,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effectiveness of Omadacycline in a Patient with <i>Chlamydia psittaci</i> and KPC-Producing Gram-Negative Bacteria Infection.","authors":"Yong Yang, Cheng Li, Xianshuang Fan, Wenming Long, Yuwei Hu, Yiming Wang, Jian Qu","doi":"10.2147/IDR.S505311","DOIUrl":"10.2147/IDR.S505311","url":null,"abstract":"<p><p><i>Chlamydia psittaci</i> is one of the primary pathogens responsible for community-acquired atypical pneumonia. If not treated promptly, it can progress to severe pneumonia and may lead to multiple organ dysfunction as well as secondary infections with multi-drug-resistant (MDR) bacteria. Omadacycline, a novel aminomethylcycline antibiotic derived from tetracycline, exhibits high activity against various bacterial strains. This case report describes a patient who developed severe pneumonia caused by <i>Chlamydia psittaci</i> in conjunction with a MDR bacterial infection. Despite initial treatment with moxifloxacin and doxycycline, the patient experienced treatment failure. The patient's condition deteriorated, presenting complications such as progressive infection, leukopenia, liver dysfunction, electrolyte imbalances, and respiratory alkalosis. Following the adjustment to omadacycline therapy for 48 hours, all complications were rapidly alleviated, leading to successful treatment of the patient.</p>","PeriodicalId":13577,"journal":{"name":"Infection and Drug Resistance","volume":"18 ","pages":"903-908"},"PeriodicalIF":2.9,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Steward Mudenda, Adriano Focus Lubanga, Shazia Jamshed, Bibian Biemba, Racheal Sakala, Mervis Chiyabi, Lorraine Kavubya, Linda Twaambo Milambo, Flavien Nsoni Bumbangi, Joseph Yamweka Chizimu, Kaunda Yamba, Evelyn Wesangula, Audrey Chigome, Aubrey Chichonyi Kalungia, Israel Abebrese Sefah, Zia U I Mustafa, Amos Yared Massele, Zikria Saleem, Richard Mutemwa, Eustarckio Kazonga, Massimo Sartelli, Johanna Catharina Meyer, John Bwalya Muma, Roma Chilengi, Brian Godman
{"title":"Point Prevalence Survey of Antibiotic Use in Level 1 hospitals in Zambia: Future Prospects for Antimicrobial Stewardship Programs.","authors":"Steward Mudenda, Adriano Focus Lubanga, Shazia Jamshed, Bibian Biemba, Racheal Sakala, Mervis Chiyabi, Lorraine Kavubya, Linda Twaambo Milambo, Flavien Nsoni Bumbangi, Joseph Yamweka Chizimu, Kaunda Yamba, Evelyn Wesangula, Audrey Chigome, Aubrey Chichonyi Kalungia, Israel Abebrese Sefah, Zia U I Mustafa, Amos Yared Massele, Zikria Saleem, Richard Mutemwa, Eustarckio Kazonga, Massimo Sartelli, Johanna Catharina Meyer, John Bwalya Muma, Roma Chilengi, Brian Godman","doi":"10.2147/IDR.S509522","DOIUrl":"10.2147/IDR.S509522","url":null,"abstract":"<p><strong>Introduction: </strong>The inappropriate prescribing and use of antibiotics have contributed to the emergence and spread of antimicrobial resistance (AMR). In Zambia, there is a paucity of information on the prescribing patterns and use of antibiotics among hospitalized patients in level 1 hospitals. This study investigated antibiotic use in five level 1 hospitals in Lusaka, Zambia.</p><p><strong>Methods: </strong>This cross-sectional study utilized the World Health Organization (WHO) Point Prevalence Survey (PPS) methodology among in-patients admitted in level 1 hospitals before 08:00 a.m. on the survey day in August 2024. Data were analysed using IBM SPSS version 23.0.</p><p><strong>Results: </strong>The prevalence of antibiotic use among inpatients was 59.0%, with ceftriaxone being the most prescribed. Antibiotics were prescribed mainly for paediatrics and male inpatients. This study found that 53.0% of prescribed antibiotics were from the Access group while 38.2% were from the Watch group of the World Health Organization Access, Watch, and Reserve (AWaRe) classification. Adherence to national treatment guidelines was 36.0%, with most antibiotics prescribed empirically without evidence of culture and sensitivity tests.</p><p><strong>Conclusion: </strong>This study found a high use of antibiotics and low adherence to treatment guidelines in level 1 hospitals in Lusaka, Zambia. The findings of this study demonstrate the need to establish and strengthen antimicrobial stewardship programs and strengthen laboratory capacity to aid clinicians in diagnosing, treating, and managing patients across level 1 hospitals in Zambia.</p>","PeriodicalId":13577,"journal":{"name":"Infection and Drug Resistance","volume":"18 ","pages":"887-902"},"PeriodicalIF":2.9,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11837744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Sub-Therapeutic Concentrations of Hexetidine Induce Virulence Gene Expression in <i>Candida albicans</i>.","authors":"Banu Uygun-Can, Tanju Kadir","doi":"10.2147/IDR.S498943","DOIUrl":"10.2147/IDR.S498943","url":null,"abstract":"<p><strong>Purpose: </strong>Intraoral concentrations of antimicrobial agents such as hexetidine (HEX) using alternative antimycotics fluctuate significantly due to the dynamics in the oral cavity, which can affect both the virulence capacity and the outcome of antimycotic therapy in the management of denture stomatitis-associated oral candidiasis.</p><p><strong>Methods: </strong>This study was carried out to evaluate the impact of different sub-therapeutic HEX concentrations (1/100, 1/200) for different times (0.5, 2, 24, 48 h) on the expression levels of the virulence (<i>hwp1, plb1, plb2, sap4, sap5, sap6</i>) and drug-resistance (<i>cdr1, cdr2, mdr1, erg11</i>) genes of <i>Candida albicans</i> SC5314. Total RNA was extracted immediately after antimicrobial exposure. The qRT-PCR data were performed using the comparative 2<sup>-ΔΔCT</sup> method to calculate the relative expression of the target genes after treatment to HEX concentrations, standardized to the actin housekeeping gene.</p><p><strong>Results: </strong>Expression levels of the <i>hwp1</i> and <i>plb1</i> genes decrease after exposure to HEX to higher concentrations at 0.5 h, while the expression level of the <i>plb2</i> gene increases. Only the expression of the <i>erg11</i> gene showed a significant decrease within the resistance genes at 0.5 h. <i>Sap5, plb2</i>, and <i>mdr1</i> are overexpressed at 48 h. Sub-therapeutic levels of HEX affect the virulence and drug-resistance genes of <i>C. albicans</i>.</p><p><strong>Conclusion: </strong>These results give an idea of future strategies for developing and using HEX as an adjunctive therapy for oral candidiasis. The innovation and clinical relevance of our research lie in its exploration of how low doses of HEX influence gene expression over varying time periods, potentially paving the way for alternative therapeutic strategies.</p>","PeriodicalId":13577,"journal":{"name":"Infection and Drug Resistance","volume":"18 ","pages":"875-885"},"PeriodicalIF":2.9,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thandizo Kapatsa, Adriano Focus Lubanga, Akim N Bwanali, Gracian Harawa, Steward Mudenda, Pascal C Chipewa, Mapeesho Kamayani, Tumaini John Makole, Abdisalam Yusuf Ali, Abdullahi Abdirasak Mohamed, Kim Tae Youn, Lorie Kim, Won D Daniel, Matthew Kim, Tarek Emir Chehab, Thomas Nyirenda
{"title":"Behavioral and Socio-Economic Determinants of Antimicrobial Resistance in Sub-Saharan Africa: A Systematic Review.","authors":"Thandizo Kapatsa, Adriano Focus Lubanga, Akim N Bwanali, Gracian Harawa, Steward Mudenda, Pascal C Chipewa, Mapeesho Kamayani, Tumaini John Makole, Abdisalam Yusuf Ali, Abdullahi Abdirasak Mohamed, Kim Tae Youn, Lorie Kim, Won D Daniel, Matthew Kim, Tarek Emir Chehab, Thomas Nyirenda","doi":"10.2147/IDR.S503730","DOIUrl":"10.2147/IDR.S503730","url":null,"abstract":"<p><strong>Introduction: </strong>Antimicrobial resistance (AMR) is currently one of the twenty-first century's biggest threats to public health. Addressing AMR is often operationalized as requiring 'behavior change' of clinicians and patients and improving the drug development pipeline. Few studies and interventions have approached AMR as a challenge fundamentally embedded within the cultural fabric of modern societies and their varied economic, social and political organizations. This systematic review aimed to gather and review the available data on the behavioral and socio-economic determinants of AMR in sub-Saharan Africa (SSA).</p><p><strong>Methods: </strong>Articles were sourced from PubMed using search terms across five domains: \"Antimicrobial resistance\", \"Sub-Saharan Africa\", \"Behavioral\", \"Socio-economic\", and specific SSA country names. References were also reviewed for relevant data. This systematic review included original studies published in English between 2015 and 2023, focusing on behavioral and socio-economic factors influencing AMR in human populations in SSA, with AMR as a key outcome.</p><p><strong>Results: </strong>This systematic review identified 30 studies, with 83% (n=25) focusing on self-medication and antibiotic use practices, 67% (n=20) on healthcare providers' practices and knowledge, and 60% (n=18) on community knowledge and perceptions of AMR while 50% (n=15) of studies explored various socio-economic factors. The common themes that emerged from these studies included inadequate evidence-based prescription practices (63%, n=19), financial barriers to accessing antibiotics (50%, n=15), poor community awareness of AMR (53%, n=16), regulatory challenges in antibiotic sales and distribution (47%, n=14), and healthcare infrastructure limitations, including deficient diagnostic capabilities and antimicrobial stewardship programs (40%, n=12).</p><p><strong>Conclusion: </strong>This review's findings provide crucial insights into the behavioral and socioeconomic patterns influencing AMR in sub-Saharan African populations. For AMR interventions to be effective, there is a need for a thorough understanding of people's behaviors and practices about AMR knowledge and antimicrobial use which will help in developing more targeted interventions and policies to address inappropriate antimicrobial use and the spread of AMR.</p>","PeriodicalId":13577,"journal":{"name":"Infection and Drug Resistance","volume":"18 ","pages":"855-873"},"PeriodicalIF":2.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zuheer Meeraalam, Shaker O Alreshidi, Hani B ALBalawi, Naif M Alali, Faris Hashem, Omar M Kirat
{"title":"Incidence and Implications of Culture-Positive Corneoscleral Rims in Corneal Transplantation.","authors":"Zuheer Meeraalam, Shaker O Alreshidi, Hani B ALBalawi, Naif M Alali, Faris Hashem, Omar M Kirat","doi":"10.2147/IDR.S485717","DOIUrl":"10.2147/IDR.S485717","url":null,"abstract":"<p><strong>Background: </strong>Corneal transplantation is a critical procedure for restoring vision affected by different corneal pathologies. However, postoperative infections threaten graft survival, particularly microbial keratitis and endophthalmitis.</p><p><strong>Objective: </strong>This study aims to evaluate the incidence of culture-positive corneoscleral rims (CPCR) among transplanted corneas at a tertiary eye hospital and explore its association with death-preservation and preservation-surgery times.</p><p><strong>Methods: </strong>A retrospective analysis of keratoplasty surgeries performed in 2015 was conducted, involving 603 cases meeting the study criteria.</p><p><strong>Results: </strong>The incidence of CPCR was found to be 4.6%, predominantly bacterial (68%), with Methicillin-resistant Staphylococcus epidermidis (MRSE) being the most common isolate, followed by fungal (32%) species, notably Candida. However, none of the cases developed subsequent keratitis or endophthalmitis post-transplantation. Statistical analysis revealed no significant association between CPCR occurrence and death-preservation or preservation-surgery times.</p><p><strong>Conclusion: </strong>The study underscores the reduced impact of contaminated CPCR on graft outcomes, advocating for targeted fungal culturing, intraoperative practices to mitigate post-transplant infections, and maintaining current prophylactic antibiotic regimens, such as optisolGS ™, which contains streptomycin and gentamicin.</p>","PeriodicalId":13577,"journal":{"name":"Infection and Drug Resistance","volume":"18 ","pages":"847-853"},"PeriodicalIF":2.9,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11830929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xuchen Xu, Xiya Chen, Jing He, Lin Su, Xudong Tong, Ying Sun, Shumin Huang, Guannan Bai, Zhimin Chen
{"title":"Epidemiological Changes in Hospitalized Bronchiolitis in Children Under 2 Years of Age in Hangzhou Before and After COVID-19 Restriction Easing.","authors":"Xuchen Xu, Xiya Chen, Jing He, Lin Su, Xudong Tong, Ying Sun, Shumin Huang, Guannan Bai, Zhimin Chen","doi":"10.2147/IDR.S496239","DOIUrl":"10.2147/IDR.S496239","url":null,"abstract":"<p><strong>Background: </strong>Bronchiolitis is a common cause of hospitalization in infants under 2 years of age. The epidemiological effects of changes in hygiene and social behaviors during COVID-19 restrictions on the disease is still debated. This study aimed to analyze the changes in the viral etiology of bronchiolitis in Hangzhou during the COVID-19 restriction period (2022) compared to the period following the easing of restrictions(2023).</p><p><strong>Methods: </strong>This study collected data on patients under 2 years of age who were admitted for bronchiolitis to the Department of Pulmonology at the Children's Hospital, Zhejiang University School of Medicine (Hangzhou) from January, 1, 2022, to December 31, 2023. It also investigated seasonal variations in the incidence of bronchiolitis and pathogen distribution across different years.</p><p><strong>Results: </strong>This study included a total of 697 children with bronchiolitis, with a median age of 7.5 (4.2-12.0) months. Of these, 68.9% were boys and 31.1% were girls. Compared to 2022, the number of bronchiolitis cases in 2023 (388 versus 309) and their proportion of lower respiratory tract infections (39.1% versus 28.2%) have significantly increased (p < 0.001). Whether in 2022 or 2023, respiratory syncytial virus (RSV) was the primary pathogen causing bronchiolitis among children under 12 months of age, while human rhinovirus (HRV) was the main pathogen in children aged 12-24 months. There was a shift in the timing of the peak of several viruses including RSV, human metapneumovirus (HMPV) and parainfluenza virus (PIV) infections in 2023. However, the epidemic trend of HRV presented no significant changes between 2022 and 2023.</p><p><strong>Conclusion: </strong>The findings suggest that bronchiolitis hospitalizations increased markedly after COVID-19 restriction easing, particularly among children aged 12-18 months. There was a shift in the timing of the peak of several viruses including RSV, HMPV and PIV infections in 2023, emphasizing the need for hospitals to anticipate potential irregularities in time in the future.</p>","PeriodicalId":13577,"journal":{"name":"Infection and Drug Resistance","volume":"18 ","pages":"835-845"},"PeriodicalIF":2.9,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11830755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Diversity in Adaptive Evolution of Methicillin-Resistant <i>Staphylococcus aureus</i> Clinical Isolates Under Exposure to Continuous Linezolid Stress in vitro.","authors":"Tala Han, Ting Jia, Junrui Wang","doi":"10.2147/IDR.S493139","DOIUrl":"10.2147/IDR.S493139","url":null,"abstract":"<p><strong>Background: </strong>Linezolid resistance in methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) was reported frequently in recent years, but the mechanism underlying this process was less reported, especially for clinical isolates with different genetic background. Thus, this study aims to explore the adaptive evolution characteristics underlying linezolid resistance in MRSA clinical isolates exposed to continuous induction stress of linezolid in vitro.</p><p><strong>Methods: </strong>The in vitro susceptibility of 1032 MRSA clinical isolates to linezolid was detected using commercial VITEK-2 equipment via broth microdilution. MRSA isolates with different minimum inhibitory concentration (MIC) values for linezolid were randomly selected to perform the assay of adaptive laboratory evolution with sub-inhibitory concentrations of linezolid. Polymerase chain reaction assays and sequencing techniques were performed to detect well-known molecular determinants related to linezolid resistance, including the expression of <i>optrA</i> and <i>cfr</i>, mutations of 23S rRNA gene and ribosomal protein (L3, L4, L22) encoding genes (<i>rplC, rplD, rplV</i>).</p><p><strong>Results: </strong>After induction with sequentially increasing concentrations of linezolid, all four MRSA strains (L914, L860, L1096, and L2875) evolved into linezolid-resistant strains over various induction times (480, 384, 288, and 240 h) and universally formed small colony variants. A new mutation in the domain V region of <i>23S rRNA</i> gene (C2404T) and one mutation in amino acid sequences of ribosomal protein (Met208Thr) were firstly identified among linezolid-resistant strains. Except G2576T mutations in <i>23S rRNA</i> gene, the distribution of other mutations (A2451T, T2504A, C2404T, T2500A, G2447T) exhibited obvious strain heterogeneity. Furthermore, as the MIC to linezolid increased, the copy numbers of point mutations in the V region of <i>23S rRNA</i> gene increased correspondingly.</p><p><strong>Conclusion: </strong>Strain-specific evolution of resistance to linezolid among MRSA clinical isolates was firstly identified in this study. MRSA isolates with higher MICs for linezolid evolved more easily into resistant ones, which calls for precise monitoring of linezolid resistance levels in patients receiving treatment for MRSA infections with linezolid.</p>","PeriodicalId":13577,"journal":{"name":"Infection and Drug Resistance","volume":"18 ","pages":"819-834"},"PeriodicalIF":2.9,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Pyrvinium Pamoate Synergizes with Azoles in vitro and in vivo to Exert Antifungal Efficacy Against <i>Candida auris</i> and Other <i>Candida</i> Species.","authors":"Jinqing Zhang, Gaolian Li, Jing Hu, Jingwen Tan, Heng Zhang, Yizheng Zhou","doi":"10.2147/IDR.S497929","DOIUrl":"10.2147/IDR.S497929","url":null,"abstract":"<p><strong>Introduction: </strong>Treating infections caused by azole-resistant <i>Candida spp</i>. poses a significant challenge. Previous research has indicated that pyrvinium pamoate (PP) has the potential to augment the antifungal efficacy of azole antifungals against filamentous fungi. The objective of this study was to investigate the antifungal properties of PP, both independently and in conjunction with azoles, against <i>Candida auris</i> and other <i>Candida spp.</i></p><p><strong>Materials and methods: </strong>A total of 21 clinical <i>Candida spp</i>. strains and five azoles were assessed. The antifungal efficacy of PP, either alone or in combination with azoles, was tested according to the reference method. <i>Galleria mellonella</i> larvae were employed to evaluate the antifungal efficacy of PP and/or azoles in the treatment of <i>C. auris</i> infections in vivo.</p><p><strong>Results: </strong>When used to treat these different fungal isolates in vitro, the single-agent efficacy of PP was relatively poor, with minimum inhibitory concentration values ranging from 2 μg/mL - >32 μg/mL. However, PP and azoles exhibited synergistic activity against the majority of analyzed <i>C. albicans</i> and <i>C. auris</i> isolates. To extend these results in vivo,<i> G. mellonella</i> was infected with <i>C. auris</i> strain AR385 and both survival and fungal burden were assessed for treated larvae. The inclusion of PP in combination with itraconazole, voriconazole, or posaconazole resulted in varying degrees of improvement in the survival rates of these larvae.</p><p><strong>Conclusion: </strong>Combining PP with azoles represents a promising approach to effectively disrupting the growth of azole-resistant <i>C. auris</i> and other <i>Candida spp</i>. such that it may be a promising anti-<i>Candida</i> therapeutic option.</p>","PeriodicalId":13577,"journal":{"name":"Infection and Drug Resistance","volume":"18 ","pages":"783-789"},"PeriodicalIF":2.9,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11827495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}