Canadian Journal of Infectious Diseases & Medical Microbiology最新文献

Exploring drug susceptibility is a critical endeavor in the scientific community, setting the stage for advancements in understanding and combating various pathogens. Candida kefyr has emerged as a significant pathogen, particularly affecting immunocompromised individuals with hematologic malignancies and HIV/AIDS conditions. This study aimed to assess the antifungal susceptibility profile of Candida kefyr isolates obtained from clinical samples and dairy products. A total of 134 Candida kefyr yeast isolates were retrieved from three distinct groups: (1) healthy individuals (n = 41), (2) patients (n = 24) including hematologic malignancy (n = 9), HIV/AIDS (n = 7), and diabetes (n = 8), (3) dairy products (milk, yogurt, and cheese, n = 69) stored at -70°C in the Shiraz University of Medical Science. All Candida kefyr isolates were previously identified using conventional and molecular methods. Susceptibility to antifungal drugs, including caspofungin, fluconazole, itraconazole, voriconazole, and amphotericin B, was determined using the microdilution method following CLSI-M27-A3 protocols, with results interpreted according to CLSI-M27-S4 guidelines. The study emphasizes the clear variation in antifungal susceptibility testing of Candida kefyr strains when compared across different groups, including patients, healthy people, and dairy products. According to the results, across all groups, a high minimum inhibitory concentration of fluconazole is evident, and healthy individuals show the highest minimum inhibitory concentration geometric means (4.0681). Also, 79.1% of the isolates were wild type to amphotericin B, with the lowest minimum inhibitory concentration compared to other antifungals tested. This suggests that amphotericin B was more effective against Candida kefyr. These findings showed fewer susceptibilities of Candida kefyr to both triazole and echinocandin classes of antifungal agents. Additionally, it is noteworthy that individuals without medical conditions exhibited higher minimum inhibitory concentration rates to these antifungal agents in comparison to those with underlying health conditions. Consequently, timely diagnosis and appropriate therapeutic interventions emerge as imperative in the effective management of candidiasis cases.

Salmonella is the main bacterial pathogen that causes foodborne disease, particularly in developing countries. Nontyphoidal Salmonella (NTS) include Enteritidis and Typhimurium as the most prevalent strains which are one of the significant causes of acute gastroenteritis in children. Therefore, identifying the most predominant serovars, types of common contaminated food, and paying attention to their antibiotic resistance are the main factors in the prevention and control strategy of salmonellosis. This study was undertaken to evaluate the prevalence rate of serovars, the biofilm formation, antimicrobial resistance (AMR) status, and phenotypic virulence factors of Salmonella strains isolated from diarrhea samples in some cities of Iran. A total of 40 (10.41%) Salmonella isolates were recovered from 384 diarrhea samples processed and the most common serovar was Salmonella serovar Typhimurium (82.5). Also, all isolates belonging to serovar Typhimurium showed more virulence factors compared to other serovars. The isolates showed a high resistance rate to ampicillin (95%) and nalidixic acid (87.5%), while a low resistance rate was found for chloramphenicol (2.5%). Moreover, significant variances in the capacity of biofilm formation were found between different Salmonella serotypes. The resistance of NTS to extant choice drugs is a potential public health problem. Constant monitoring of AMR pattern and virulence profile of NTS serovars is suggested for the prevention of salmonellosis in humans.

Klebsiella pneumoniae is a pathogen that commonly causes hospital-acquired infections. Bacterial biofilms are structured bacterial communities that adhere to the surface of objects or biological tissues. In this study, we investigated the genome homology and biofilm formation capacity of ESBL-producing K. pneumoniae. Thirty ESBL-producing K. pneumoniae isolates from 25 inpatients at Ruijin Hospital, Shanghai, were subjected to pulsed-field gel electrophoresis (PFGE) to estimate genomic relatedness. Based on the chromosomal DNA patterns we obtained, we identified 21 PFGE profiles from the 30 isolates, eight of which had high homology indicating that they may have genetic relationships and/or potential clonal advantages within the hospital. Approximately 84% (21/25) of the clinical patients had a history of surgery, urinary tract catheterization, and/or arteriovenous intubation, all of which may have increased the risk for nosocomial infections. Biofilms were observed in 73% (22/30) of the isolates and that strains did not express type 3 fimbriae did not have biofilm formation capacity. Above findings indicated that a high percentage of ESBL-producing K. pneumoniae isolates formed biofilms in vitro and even though two strains with cut-off of PFGE reached 100% similarity, they generated biofilms differently. Besides, the variability in biofilm formation ability may be correlated with the expression of type 3 fimbriae. Thus, we next screened four ESBL-producing K. pneumoniae isolates (Kpn5, Kpn7, Kpn11, and Kpn16) with high homology and significant differences in biofilm formation using PFGE molecular typing, colony morphology, and crystal violet tests. Kpn7 and Kpn16 had stronger biofilm formation abilities compared with Kpn5 and Kpn11. The ability of above four ESBL-producing K. pneumoniae isolates to agglutinate in a mannose-resistant manner or in a mannose-sensitive manner, as well as RNA sequencing-based transcriptome results, showed that type 3 fimbriae play a significant role in biofilm formation. In contrast, type 1 fimbriae were downregulated during biofilm formation. Further research is needed to fully understand the regulatory mechanisms which underlie these processes.

The emergence of hypervirulent strains of Acinetobacter baumannii poses a significant threat in intensive care units (ICU). This study aimed to molecularly characterize hypervirulent A. baumannii strains isolated from ICU patients with respiratory infections. Six strains were isolated from ICU patients over one month. Isolates were identified by phenotypic characterization biochemical properties and 16s RNA sequencing. Antibiotic susceptibility testing was conducted followed by resistance genes detection by PCR. MLST, and PFGE were employed to analyse clonal relationships among strains. Plasmid replicon typing and plasmid transmission frequencies were determined. The isolated strains exhibited diverse clinical manifestations, including acute respiratory distress syndrome (ARDS). Antibiotic susceptibility testing revealed multidrug-resistance phenotype. Molecular analysis revealed a complex genetic landscape of antibiotic resistance genes, including ESBLs and carbapenemases, as well as virulence genes such as ompA, csuE, and exoS. The multiple sequence types indicating genetic diversity among the strains as ST1512, ST622, and ST149 (each type two isolates). Plasmid characterization revealed the presence of diverse replicon types associated with multidrug resistance. This study provides comprehensive insights into the phenotypic, molecular, and epidemiological characteristics of hypervirulent A. baumannii outbark in ICU.

Elderly patients with carbapenem-resistant Enterobacteriales (CRE) infections represent considerable mortality rates. But data on the risk factors for the death of elderly patients following such infection remain limited. We aimed to assess the clinical outcomes, identify mortality-associated risk factors, and determine the antibiotic resistance and resistance genes of isolates for these patients. Hospitalized patients aged ≥65 years with CRE infection from January 2020 to December 2020 were retrospectively reviewed. Isolates identification and molecular characterization of CRE were carried out. Logistic regression analysis was applied to assess the potential factors associated with mortality. Of the 123 elderly patients with CRE infection included in our study, the all-cause mortality rate was 39.8% (49/123). The most prevalent pathogen was carbapenem-resistant Klebsiella pneumoniae (CRKP, 116 of 123). The overall rates of multidrug-resistant (MDR) and extensively drug-resistant (XDR) were 100.0% and 66.7%. All CRE isolates exclusively harbored a singular variant of carbapenemase gene, such as bla _KPC-2, bla _IMP-4, bla _NDM-5, or bla _OXA-48, while 98.4% of isolates harbored more than one β-lactamase gene, of which 106 (86.2%) isolates harbored bla _CTX-M, 121 (98.4%) isolates harbored bla _TEM, and 116 (94.3%) isolates harbored bla _SHV. Multivariable logistic regression analysis revealed that mechanical ventilation (adjusted odds ratio (AOR) = 33.607, 95% confidence interval (CI): 4.176-270.463, P < 0.001), use of tigecycline during hospitalization (AOR = 5.868, 95% CI: 1.318-26.130, P = 0.020), and APACHE II score (AOR = 1.305, 95% CI: 1.161-1.468, P < 0.001) were independent factors associated with increasing the mortality of patients with CRE infection, while admission to intensive care unit (ICU) during hospitalization (AOR = 0.046, 95% CI: 0.004-0.496, P = 0.011) was a protective factor. CRE-infected elderly patients with mechanical ventilation, use of tigecycline during hospitalization, and high APACHE II score were related to poor outcomes. The isolates carried various antibiotic genes and presented high antibiotic resistance. These findings provide crucial guidance for clinicians to devise appropriate strategies for treatment.

Carbapenems currently serve as the last line of defense when treating serious infections caused by multidrug-resistant Enterobacterales species; however, heteroresistance of these species is thought to cause failure in the treatment with these broad-spectrum antibiotics. This study was designed to determine the prevalence of carbapenem heteroresistance and associated genotypic modifications among phenotypically meropenem-susceptible Escherichia coli and Klebsiella pneumoniae isolates. A total of 204 isolates of E. coli (n: 118) and K. pneumoniae (n: 86) from various clinical samples were included in this prospective experimental study. Identification and antimicrobial susceptibility testing of the isolates were performed by VITEK® (bioMérieux, France). Strains that were found susceptible to carbapenem group antibiotics (meropenem, imipenem, and ertapenem) with automated system were further investigated by disk diffusion method. The isolates with discrete colony growth within the clear inhibition zone among phenotypically meropenem-susceptible strains were tested for heteroresistance with the "gold standard" population analysis profile-area under the curve (PAP-AUC) method. In addition, heteroresistant isolates were analyzed for the presence of carbapenemase genes with in-house PCR method. The heteroresistance prevalence rate was 3.5% for E. coli and 18.1% for K. pneumoniae. The presence of heteroresistance in a total of 10 meropenem-susceptible isolates (E. coli, n: 4; K. pneumoniae, n: 6) was confirmed by the PAP-AUC method. The most frequently detected carbapenemase in heteroresistant isolates was OXA-48 (6/10), followed by NDM-1 (2/10). Meropenem is frequently preferred as initial empirical monotherapy in most of Gram-negative infections in adult and pediatric patients. The presence of heteroresistance against meropenem is too important to ignore, and for this reason, it seems beneficial to prefer combined treatment regimens in clinical practice.

Influenza is defined in traditional Chinese medicine (TCM) as an epidemic febrile illness and is usually treated with herbal compound formulas under the guidance of the "Qu Xie and Fu Zheng" theories. Ma Xing Shi Gan Tang (MXSGD) is a prominent remedy for clearing heat and detoxifying toxins in the clinical treatment of influenza in TCM, playing the role of "Qu Xie." Si Jun Zi Tang (SJZD) is recognized as one of the "Fu Zheng" formulas for strengthening the spleen and nourishing the stomach, with immunomodulatory effects. In this study, we followed the principles of "Qu Xie and Fu Zheng" to explore the effects of MXSGD combined with SJZD on viral pneumonia and its mechanism. Results showed that the couse of MXSGD and SJZD was effective in reducing the mortality rates and severity of lung pathology in lethally infected FM1 mice compared to the use of either drug alone. Moreover, further research demonstrated that the combined use suppressed TLRs and NLRP3 inflammatory signaling pathways at 4 dpi while promoting them at 7 dpi. At 10 dpi, there was a significant increase in CD11c⁺ and CD103⁺ DCs in the lungs. Together, SJZD improved the therapeutic effectiveness of MXSGD in treating influenza virus pneumonia than when used alone. MXSGD and SJZD exhibit synergistic effects in the treatment of influenza, as evidenced by the inhibition of TLR7 and NLRP3 inflammatory pathways early in the infection and facilitation of the response later. They also increase CD11c⁺ and CD103⁺ DC levels, as well as balancing Th1/Th2 cytokines.

Background: In this study, attempts were made to evaluate the frequency of high-level gentamicin-resistant (HLGR) and vancomycin-resistant enterococci (VRE) and the prevalence and antibiotic resistance profile of enterococcal species isolated from pediatric patients referred to Children's Medical Center Hospital, Tehran, over five years.

Materials and methods: A total of 404 enterococcal isolates from different patients referred to the Children's Medical Center between March 2016 and March 2021 were included in this cross-sectional study. Antimicrobial susceptibility testing was performed using standard methods according to the guidelines of the Clinical Laboratories Standards Institute (CLSI).

Results: Approximately one-third of the enterococcal strains were isolated from urology and intensive care units. 17.3% of the isolates were obtained from outpatient sources. However, 82.7% of the isolates were sourced from inpatient settings. We found that the rates of resistance to ampicillin, penicillin, and vancomycin were twice as high in inpatients as in outpatients. Of the total isolates, 87.4% and 49.3% were identified as HLGR and VRE, respectively. In addition, we identified 2% of the VRE isolates that were not susceptible to linezolid. Nitrofurantoin showed excellent activity against enterococcal isolates in the urine, with a susceptibility rate of 92.5%.

Conclusion: The present study reports the highest range of VRE isolated from pediatric patients in Iran. Despite the predominance of HLGR enterococci in our region, vancomycin remains effective against such strains. This study is among the few to demonstrate the incidence of linezolid-insensitive VRE in pediatric patients. Therefore, it is important to evaluate effective infection control measures to prevent linezolid and vancomycin resistance in enterococci.

Objective: To identify the most effective dose of filarial rBmALT-2 and rWbGST alone or in combination against B. malayi infection in vitro and in vivo.

Methods: Mastomys (n = 5-7/group) received intramuscular (i.m.) injection with three different doses (25, 50, and 100 μg) of rBmALT-2 or rWbGST, either alone or in combination with alum as the adjuvant. Protective immunity was studied by in vivo and in vitro cytotoxicity assay. To evaluate the cellular immune response, splenocyte proliferation and cytokine profile were assessed.

Results: Serological results revealed a substantial (p < 0.005) induction of IgG1, IgG2a, and IgG3 responses in vaccinated Mastomys. Mastomys immunized with 50 μg rBmALT-2 + alum induced 79-81% killing against the L3 larvae challenge in vivo and in vitro ADCC assay (p < 0.005); whereas rWbGST + alum alone or in combination with rBmALT-2 + alum induced 63-68% killing (p < 0.005) in vivo and in vitro. Antigen-specific cytokine profiles of Mastomys vaccinated with either BmALT-2, WbGST or a combination showed elevated IL-10, IL-4, and IFN-γ levels, signifying both Th1 and Th2 immune response.

Conclusions: These findings suggest that immunization of Mastomys with a 50 μg/dose of rBmALT-2 + alum four times at a 4-week interval demonstrated considerable protection against B. malayi infection.

Methods: In total, 170 chronic HBV patients and 50 healthy controls of comparable age and gender were included in this case-control study. Clinical, laboratory, and imaging evaluations were conducted. ELISA was used to determine serum IL-6 levels, and TLR2 (rs3804099) genotyping allelic discrimination assay was performed using real-time PCR.

Results: IL-6 values were significantly higher in the HCC group, followed by the cirrhotic group, than those in chronic hepatitis and control groups (p < 0.001), with a significant correlation with disease activity and progression parameters. TRL2 homozygous TT was the most frequent in the control group, but the CC genotype was significantly more prevalent in the HCC group than that in the other groups. Furthermore, the CC genetic variant was associated with higher levels of IL-6 and viral load in all HBV patients, whereas the TT genotype was associated with larger tumor size. Multivariate regression analysis demonstrated that in chronic HBV patients, viral load and TRL2 polymorphism are independent risk factors associated with the progression from chronic hepatitis to liver cirrhosis and to HCC. Similarly, the HBV viral load (p=0.03, OR = 2.45, and 95% CI: 1.69-3.65), IL-6 levels (p=0.04, OR = 3.45, and 95% CI: 2.01-6.9), and TRL2 variants (p=0.01, OR = 4.25, and 95% CI: 2.14-13.5) are independent risk factors associated with disease progression from cirrhosis to HCC.

Conclusion: In chronic HBV patients, TRL2 polymorphism and higher IL-6 levels were positively correlated with a higher likelihood of HCC and chronic hepatitis B disease activity and progression.