Infection and Drug Resistance最新文献

Background: 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).

Methods: 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.

Results: 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.

Conclusion: 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.

Background: Linezolid resistance in methicillin-resistant Staphylococcus aureus (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.

Methods: 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 optrA and cfr, mutations of 23S rRNA gene and ribosomal protein (L3, L4, L22) encoding genes (rplC, rplD, rplV).

Results: 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 23S rRNA gene (C2404T) and one mutation in amino acid sequences of ribosomal protein (Met208Thr) were firstly identified among linezolid-resistant strains. Except G2576T mutations in 23S rRNA 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 23S rRNA gene increased correspondingly.

Conclusion: 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.

Introduction: Treating infections caused by azole-resistant Candida spp. 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 Candida auris and other Candida spp.

Materials and methods: A total of 21 clinical Candida spp. 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. Galleria mellonella larvae were employed to evaluate the antifungal efficacy of PP and/or azoles in the treatment of C. auris infections in vivo.

Results: 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 C. albicans and C. auris isolates. To extend these results in vivo, G. mellonella was infected with C. auris 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.

Conclusion: Combining PP with azoles represents a promising approach to effectively disrupting the growth of azole-resistant C. auris and other Candida spp. such that it may be a promising anti-Candida therapeutic option.

Background: Zygomycosis, also termed mucormycosis, is a rare yet highly fatal fungal infection caused by Mucorales species, notably Rhizopus spp.

Case presentation: This case study details a 72-year-old man with diabetes, pulmonary tuberculosis, and nephrotic syndrome who developed acute necrotizing fasciitis attributable to R. oryzae. Despite initial empirical antibiotic therapy, the infection progressed rapidly. Metagenomic next-generation sequencing (mNGS) facilitated a swift diagnosis, identifying R. oryzae in blood and drainage samples. The treatment included amphotericin B and isavuconazole, along with aggressive surgical debridement. The patient exhibited substantial improvement, and he was discharged after stabilization.

Conclusion: This case highlights the critical role of early diagnosis through mNGS and the need for a multidisciplinary approach to manage severe mucormycosis in immunocompromised patients.

Purpose: The National Action Plan on antimicrobial resistance (NAP-AMR) in Tanzania is focused on blood stream infections and urinary tract infections despite skin and soft tissue infections (SSTIs) being common. This study assessed the proportion of laboratory-confirmed SSTIs, identify bacterial species involved, analyze AMR phenotypes, and investigate the risk factors associated with multidrug-resistant (MDR) SSTIs.

Patients and methods: Analytical cross-sectional study was conducted between January and June 2023, involving 614 patients with SSTIs. Patients' information was collected using standard AMR surveillance tools, and either pus swabs or pus aspirate or necrotic tissues were collected and analyzed using standard microbiological procedures, WHONET and STATA software programs.

Results: The median age (interquartile range) of patients was 34 (14-54) years with males accounting for 54.4%. Laboratory-confirmed SSTIs was 72.5% (445/614), yielding 586 bacterial isolates. The most frequent SSTIs types were surgical site infections (30.0%), chronic wounds (27.9%), and traumatic wounds (19.7%). The commonest pathogens were Staphylococcus aureus (17.1%), Escherichia coli (17.1%), and K. pneumoniae (16.0%). The AMR phenotypes identified were methicillin resistant Staphylococcus aureus, 29.0%; Extended-spectrum beta lactamase producing Gram-negative bacteria, 47.3%; and carbapenem resistant Gram-negative bacteria, 12.9%. The overall MDR SSTIs was 40.9% (251/614) and was significantly higher among inpatients compared to outpatients [OR (95% CI); p-value: 1.86 (1.33-2.59); p-value<0.001].

Conclusion: Approximately three-quarter of patients have laboratory-confirmed SSTIs caused predominantly by MDR pathogens. Revisiting SSTIs treatment guidelines at BMC and inclusion of SSTIs in the on-going AMR surveillance in Tanzania are recommended.

Purpose: Klebsiella pneumoniae is a globally prevalent pathogen responsible for severe hospital- and community-acquired infections, and presents significant challenges for clinical management. Current therapeutic strategies are no longer able to meet the clinical needs; therefore, there is an urgent need to develop novel therapeutic strategies. This study aimed to evaluate the efficacy of phage therapy in treating bacterial infections.

Methods: Isolated phage vB_Kpn_HF0522 and phage morphology were observed using transmission electron microscopy. Analysis of vB_Kpn_HF0522 characteristics, including optimal multiplicity of infection (MOI), one-step growth curve, host range, stability in different environments, and adsorption capacity. The phage genomic sequence was analyzed to explore evolutionary relationships. The effect of phage vB_Kpn_HF0522 on biofilms was assessed using crystal violet staining assay. The Galleria mellonella (G. mellonella) infection model and mouse infection models were established to evaluate the practical application potential of the phage and the fitness cost of phage-resistant bacteria.

Results: Phage was isolated from hospital sewage for experimental studies. Genome analysis revealed that vB_Kpn_HF0522 is a double-stranded linear DNA virus. Biological characterization demonstrated that this phage specifically targets serotype K1 K. pneumoniae with an optimal multiplicity of infection (MOI) of 0.01, effectively disrupting biofilms and inhibiting bacterial growth. The bacterial growth rate remained largely unchanged after the phage resistance mutation, but mice infected with the mutant strain showed significantly higher survival rates than those infected with the wild-type strain. vB_Kpn_HF0522 increased the survival rate of infected G. mellonella from 12.5% to 75%, inhibited incisional surgical site infections and alleviated inflammatory response in mice.

Conclusion: These findings indicate that vB_Kpn_HF0522 has significant potential for treating specific bacterial infections, and may serve as an antimicrobial agent for research and clinical anti-infective therapy.

Purpose: Since the publication of the 2011 Infectious Diseases Society of America (IDSA) guidelines for empirical treatment of febrile neutropenia (FN), there have been significant shifts in pathogen profiles and emerging challenges in treatment. These include increased prevalence of multidrug-resistant (MDR) bacteria and changes in the distribution of Gram-negative or Gram-positive bacteria (GPB). The study aims to update and optimize empirical treatment strategies for hematological malignancy (HM) patients, a population particularly vulnerable to these evolving threats.

Methods: A literature review was conducted on studies published between January 2010 and December 2023 regarding empirical treatment of FN in HM patients, focusing on pathogen characteristics, treatment regimens, and duration of therapy.

Results: Approximately one-third of HM patients with FN experience fever of unknown origin (FUO), while 40-50% have clinically documented infections (CDI), and 10-30% present with microbiologically documented infections (MDI), with a predominance of Gram-negative bacteria (GNB). Factors such as prolonged neutropenia, prior broad-spectrum antibiotic use, and previous infections with drug-resistant bacteria are associated with MDR infections. Cefepime, piperacillin/tazobactam (PTZ), and carbapenem are viable empirical treatments for high-risk HM patients, though cefepime monotherapy's advantage remains uncertain. In cases of pneumonia, shock, or suspected carbapenem-resistant infections, combination therapy, tigecycline, and newer antibiotics like ceftazidime/avibactam (CAZ/AVI) are often used. Empirical broad-spectrum antibiotics can be safely discontinued in FUO patients after 48 hours of clinical stability and apyrexia.

Conclusion: Proper selection of empirical antibiotics and determining optimal treatment duration are essential for reducing antibiotic resistance and improving outcomes in HM patients with FN. These findings underscore the need for updated clinical guidelines that address evolving pathogen profiles and the growing challenge of MDR infections.

Objective: To analyze the influencing factors of postoperative pulmonary infection in patients with severe traumatic brain injury, and establish and validate a column chart prediction model.

Methods: A retrospective study was conducted on 314 patients with severe traumatic brain injury in our hospital from January 2022 to March 2024. They were separated into an internal validation group of 235 cases and an external validation group of 79 cases randomly. The internal validation group was grouped into an infection group of 73 cases and an non-infection group of 162 cases. All patients underwent pathogen detection and identification.

Results: A total of 96 strains of pathogens were isolated from 73 patients with concurrent pulmonary infections. Independent risk factors for postoperative pulmonary infection in patients with severe TBI included age ≥ 60 years, diabetes, tracheotomy, operation time ≥ 4 hours, sputum excretion in the supine position, mechanical ventilation duration ≥ 7 days, and GCS score < 8 points mechanical ventilation duration (P<0.05). The constructed column chart prediction model had high discrimination, calibration, and clinical practical value.

Conclusion: The column chart model, incorporating age, diabetes, tracheotomy, operation time, sputum excretion position, mechanical ventilation duration and GCS score, can effectively predict pulmonary infections in severe traumatic brain injury patients.

Purpose: The purpose of this study was to evaluate the antibacterial activity and mechanism of linalool against Methicillin-resistant Staphylococcus aureus (MRSA).

Methods: The determination of the antibacterial activity of linalool against clinically isolated MRSA strains was based on the minimum inhibitory concentration (MIC) and growth curve analysis. Finally, the inhibition mechanism of linalool was elucidated through metabolomic analysis and molecular docking.

Results: Among the isolated strains, penicillin resistance was found to be the highest, while resistance to daptomycin/quinupristin-dalfopristin, linezolid, vancomycin, tetracycline, telithromycin, and levofloxacin was not observed. The MIC range of linalool was 211.24-1.65 μg/mL, with MIC₅₀ and MIC₉₀ values of 13.2 μg/mL and 105.62 μg/mL, respectively. Metabolomic analysis revealed that linalool interferes with various substance metabolisms and energy metabolism in MRSA, with the glutathione pathway potentially being a key pathway affected by linalool. Molecular docking revealed that linalool exhibited good binding potential to the target glutathione.

Conclusion: This study suggests that linalool could be developed as a drug or preservative to inhibit MRSA growth.

The global dissemination of carbapenem-resistant Enterobacteriaceae poses a significant threat to public health. In this study, we identified two clinical Klebsiella isolates, K. quasipneumoniae ACESH02628 and K. pneumoniae ACESH02857, harboring the bla _NDM-5 gene in China. Both strains exhibited multidrug resistance, including reduced susceptibility to carbapenems, and carried transferable NDM-5-bearing plasmids. Specifically, S1-pulsed-field gel electrophoresis (PFGE), southern blotting, and whole-genome sequencing revealed that ACESH02628 contained an IncHI2/IncHI2A-type plasmid, while ACESH02857 carried an IncX3-type plasmid, both associated with the regional spread of NDM-5. Comparative analyses showed high genetic similarity with previously reported NDM-5 plasmids from Salmonella enterica and Escherichia coli in China, underscoring the ease of horizontal transfer and potential for broader dissemination. Our findings highlight the emergence of NDM-5-producing K. quasipneumoniae of clinical origin and reinforce the need for vigilant surveillance and infection control measures to curb the proliferation of these highly resistant pathogens.