We describe pulmonary cryptococcosis in a 28-year-old previously healthy man. Exhaustive immunological investigations revealed a primary NK cell deficiency associated with a secondary impaired anti-Cryptococcus CD8 lymphocyte response and the expansion of a CD8Vβ14 + T cell clone. This case illustrates the potential role of NK cells in immunity against Cryptococcus.
Objective: To examine the characteristics and spatiotemporal changes in the phenotypes and genotypes of extended-spectrum β-lactamases (ESBLs) in Escherichia coli strains isolated from bloodstream infections (BSIs) across China between 2014 and 2021.
Methods: 983 ESBL-positive E. coli strains were collected from BSIs in 66 hospitals across different geographic regions in China from 2014 to 2021. The phenotypic confirmation of ESBL was performed through the double-disc diffusion method. The genetic type was determined using polymerase chain reaction (PCR) followed by DNA sequencing.
Results: Between 2014 and 2021, the prevalence of ESBL-positive E. coli steadily decreased from 61.2 to 49.6%. Among 983 phenotypically confirmed ESBL-positive E. coli, 763 (77.6%) were confirmed to carry ESBL genes, with the majority being of the CTX-M type, which is further divided into 23 subtypes and dominated by the CTX-M-9 and CTX-M-1 groups, with 457/763 and 333/763, respectively. Other ESBLs and ampC genes, such as blaOXA-1, blaCMY, and blaDHA-1, often coexisted with either the CTX-M-9 or CTX-M-1 groups. blaCTX-M-14 (34.3%, 157/457) and blaCTX-M-55 (45.9%, 153/333) were the dominant subtypes in the CTX-M-9 and CTX-M-1 groups, respectively. A notable increase in blaCTX-M-27 was observed, particularly from 2019 to 2021, with 26.4%, 23.1%, and 25.8% in all genotypes. Regarding the geographical distribution of the ESBLs, the highest rate of ESBL genetic positivity was observed in Southwest China, accounting for 84.9% (45/53), and the lowest was observed in Northeast China, with 73.2% (30/41). The abundance of the blaCTX-M-27 genotype, in particular, exhibited a notable increase in Southwest China, with 31.4% (14/45) of the strains exhibiting this genotype, followed by the CTX-M-55 genotype, with 13.6% (6/45) of the strains exhibiting this genotype.
Conclusions: This study demonstrated a steadily decreasing trend in the incidence of ESBLs and predominant CTX-M type ESBLs, particularly the CTX-M-9 and CTX-M-1 groups, in E. coli strains across China, a notable increase in the blaCTX-M-27 genotype and regional variations in the ESBL gene distribution were detected.
Background: Nemonoxacin is a new quinolone with an antibacterial efficacy against methicillin-resistant Staphylococcus aureus (MRSA). Certain sequence types (STs) have been emerging in Taiwan, including fluoroquinolone-resistant ST8/USA300. It's an urgent need to determine nemonoxacin susceptibility against ST8/USA300 and other emerging lineages, if any. Additionally, molecular characterization of nemonoxacin resistance among different lineages has yet to be defined.
Methods: Non-duplicated MRSA blood isolates from five hospitals during 2019-2020 were collected and genotyped by pulsed-field gel electrophoresis, and further correlated to their STs. Antimicrobial susceptibility testing for all antibiotics was performing by using Sensititre standard panel, except nemonoxacin by using agar dilution method. Selected isolates with nemonoxacin MICs ≥ 0.5 mg/mL were sequenced for quinolone resistance-determining regions (QRDRs).
Results: Overall, 915 MRSA isolates belonged to four major lineages, ST8 (34.2%), ST59 (23.5%), ST239 (13.9%), and clonal complex 45 (13.7%). Two-thirds of tested isolates were non-susceptible to moxifloxacin, especially ST8/USA300 and ST239. Of them, proportions of nemonoxacin non-susceptibility by a tentative clinical breakpoint (tCBP) of 1 µg/mL among four major lineages appeared to be different (P = 0.06) and highest in ST239 (22.2%), followed by ST8/USA300 (13.5%). Among 89 isolates sequenced, 44.1% of ST8 and all ST239 isolates had ≥ 3 amino acid substitutions (AAS) in gyrA/parC (group A) or 2 AAS in gyrA/parC with additional AAS in gyrB/parE (group B). Compared to other AAS patterns, isolates in group A had the greatest non-susceptible proportions to nemonoxacin (86.9%; overall/pair-wised comparisons, P < 0.05).
Conclusions: Our study confirmed ST8/USA300 MRSA has disseminated in Taiwan. Using a tCBP defined by a higher parenteral daily dosage, nemonoxacin retained potency against moxifloxacin non-susceptible isolates. Patterns of AAS in QRDRs among different lineages may contribute to difference of nemonoxacin susceptibility.
Proteus mirabilis (P. mirabilis) is one of the most important causative pathogens associated with complicated urinary tract infections with a 20% incidence. For epidemiological determinations, several phenotypic and molecular typing methods have been implicated. Sixty P. mirabilis isolated undergo antibiotic susceptibility test by standard Kirby Bauer method. They showed high resistance to nitrofurantoin and trimethoprim/sulfamethoxazole that appear mainly in 3rd age group. The 2nd age group comprised most of the resistant isolates to the tested antibiotics. A total of 73.33% of isolates were classified as multi drug resistance (MDR) and 78.3% of isolates were distributed in several antibiotypes with MAR index over 0.2. Twenty-one isolates were strong biofilm-producers and they were significantly related to MDR. Different virulence factors as protease, urease and hemolysin production are detected. Detection of several virulence genes by PCR; zapA and ureC were harbored by all isolates, followed by rsbA (95%), ureA and flaA (93%), hpmA (91.7%) and mrpA (73.3%). Determination of genetic diversity between isolates was performed by different methods (RAPD, ISSR, ERIC, BOX-AIR and REP-PCR) by using several parameters as typeability and discriminatory power indicating that ERIC-PCR was the best method followed by REP-PCR 1R. Rand's & Wallace coefficients were used for calculating the congruence among typing methods. Conclusions: The results obtained from both conventional and molecular typing methods indicated that molecular methods are superior to conventional methods in the discrimination of isolates. ERIC-PCR and Rep-PCR provide high discrimination ability among P. mirabilis clinical isolates contributing to epidemiological studies.
Purpose: Monotherapy with vancomycin or daptomycin remains guideline-based care for methicillin-resistant Staphylococcus aureus bacteremia (MRSA-B) despite concerns regarding efficacy. Limited data support potential benefit of combination therapy with ceftaroline as initial therapy. We present an assessment of outcomes of patients initiated on early combination therapy for MRSA-B.
Methods: This was a single-center, retrospective study of adult patients admitted with MRSA-B between July 1, 2017 and April 31, 2023. During this period, there was a change in institutional practice from routine administration of monotherapy to initial combination therapy for most patients with MRSA-B. Combination therapy included vancomycin or daptomycin plus ceftaroline within 72 h of index blood culture and monotherapy was vancomycin or daptomycin alone. The primary outcome was a composite of persistent bacteremia, 30-day all-cause mortality, and 30-day bacteremia recurrence. Time to microbiological cure and safety outcomes were assessed. All outcomes were assessed using propensity score-weighted logistic regression.
Results: Of 213 patients included, 118 received monotherapy (115 vancomycin, 3 daptomycin) and 95 received combination therapy with ceftaroline (76 vancomycin, 19 daptomycin). The mean time from MRSA-positive molecular diagnostic blood culture result to combination therapy was 12.1 h. There was no difference between groups for the primary composite outcome (OR 1.58, 95% CI 0.60, 4.18). Time to microbiological cure was longer with combination therapy (mean difference 1.50 days, 95% CI 0.60, 2.41). Adverse event rates were similar in both groups.
Conclusions: Early initiation of ceftaroline-based combination therapy did not improve outcomes for patients with MRSA-B in comparison to monotherapy therapy.
Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) is recognized as a common clinical conditional pathogen with blaOXA-23 gene-mediated multidrug-resistance that is a significant threat to public health safety. Timely and effective infection control measures are needed to prevent their spread.
Methods: We conducted a retrospective study of CRAB patients at three teaching hospitals from 2019 to 2022. We identified bacterial isolates, collected clinical data, and performed antimicrobial susceptibility testing. Genome characteristics of isolates were investigated by whole genome sequencing. Multilocus sequence typing and phylogenetic trees were used to assess the genetic similarity of isolates. Acquired antimicrobial resistance genes and virulence factors carried in the isolated group genome were analyzed by ResFinder, PubMLST and VFDB. Sequence alignment was used to analyze genetic environment around blaOXA-23. Phylogenetic tree was constructed to analyze the genetic relationship of isolates.
Results: A total of 92 non-repetitive CRAB isolates were collected, with sputum samples accounting for the majority (94.57%, n = 87) of samples. These were distributed into ST2, with ST2 identified to have the highest prevalence of infection, accounting for 99.99% (n = 91) of all isolates. The major resistance genes identified were blaOXA-23, blaOXA-66, blaOXA-51, and blaADC. Also, 92 CRAB strains showed high levels of resistance to common clinical antibiotics, but not minocycline. Meanwhile, most of the isolates carried virulence genes such as various ompA, csuA, csuB, csuC, csuD, abaI, abaR, lpxC, lpxA, and bmfRS. Single nucleotide polymorphism (SNP) analyses further indicated that the bacterial genome was progressively polymorphic with time. We analyzed the environment of the blaOXA-23 gene and found that CRAB accumulated in the context of prominent environmental antibiotic exposure and had longer survival times in the antibiotic environment, resulting in the tendency of bacteria to develop greater antibiotic resistance.
Conclusions: We find that CRAB is prevalent within the ICU and is progressively resistant to antibiotics over time. Enhanced clinical understanding and timely management of CRAB infections will be crucial to minimize or even eliminate the spread of CRAB within the ICU setting.
Background: The emergence of colistin resistance in carbapenem-resistant Klebsiella pneumoniae (CRKP) is a significant public health concern, as colistin has been the last resort for treating such infections. This study aimed to investigate the prevalence and molecular characteristics of colistin-resistant CRKP isolates in Central South China.
Methods: CRKP isolates from twelve hospitals in Central South China were screened for colistin resistance using broth microdilution. The epidemiological characteristics, virulome, resistome, plasmid replicons and two-component systems associated with colistin resistance of colistin-resistant isolates were explored by whole-genome sequencing. The mgrB gene and the relative expression of the pmrC and pmrK genes were analyzed by polymerase chain reaction (PCR) and real-time quantitative PCR, respectively. The bacterial virulence was evaluated through a Galleria mellonella larvae infection model.
Results: Of the 429 nonduplicate CRKP isolates, 26 (6.1%) were colistin-resistant and they included eight clonal clusters. Six distinct sequence type (ST)-capsule loci (KL) types were identified: ST11-KL64, ST11-KL47, ST963-KL16, ST307-KL102, ST751-KL64 and ST5254-KL47. 88.5% (23/26) of them were found to carry at least one carbapenemase gene, including blaKPC-2 (65.4%, 17/26) and blaNDM-1 (7.7%, 2/26), as well as coharbouring blaKPC-2 and blaNDM-1 (15.4%, 4/26). Diverse mutations of colistin resistance-related genes were observed, with mgrB inactivation by insertions and the T157P deleterious mutation in pmrB being detected in 57.7% and 42.3% of the colistin-resistant isolates, respectively. In addition, a novel deleterious mutation, R248P, in the crrB gene was found in two ST11 isolates. 88.5% of the 26 isolates presented an increase in pmrK transcription, and 69.2% of them had an overexpression of the pmrC gene. All the 16 ST11-KL64 isolates and one ST751-KL64 isolate (65.4%, 17/26) carried at least two hypervirulence biomarkers and showed high virulence in vivo.
Conclusions: This study highlights the presence of different colistin resistance mechanisms in isolates belonging to the same clone and identified multiple clonal transmission clusters in colistin resistant isolates, including the globally high-risk ST11 and ST307 clones, of which a significant proportion exhibited high virulence. Consequently, it is crucial to enforce measures to prevent the ongoing spread of colistin resistance.
Background: Antimicrobial resistance (AMR) poses a significant threat to pediatric health; therefore, precise identification of pathogens as well as AMR is imperative. This study aimed at comprehending antibiotic resistance patterns among critically ill children with infectious diseases admitted to pediatric intensive care unit (PICU) and to clarify the impact of drug-resistant bacteria on the prognosis of children.
Methods: This study retrospectively collected clinical data, identified pathogens and AMR from 113 children's who performed metagenomic next-generation sequencing for pathogen and antibiotic resistance genes identification, and compared the clinical characteristic difference and prognostic effects between children with and without AMR detected.
Results: Based on the presence or absence of AMR test results, the 113 patients were divided into Antimicrobial resistance test positive group (AMRT+, n = 44) and Antimicrobial resistance test negative group (AMRT-, n = 69). Immunocompromised patients (50% vs. 28.99%, P = 0.0242) and patients with underlying diseases (70.45% vs. 40.58%, P = 0.0019) were more likely to develop resistance to antibiotics. Children in the AMRT + group showed significantly increased C-reaction protein, score of pediatric sequential organ failure assessment and pediatric risk of mortality of children and longer hospital stay and ICU stay in the AMRT + group compared to the AMRT+- group (P < 0.05). Detection rate of Gram-negative bacteria was significantly higher in the AMRT + group rather than Gram-positive bacteria (n = 45 vs. 31), in contrast to the AMRT- group (n = 10 vs. 36). Cephalosporins, β-lactams/β-Lactamase inhibitors, carbapenems and sulfonamides emerged as the most common types of drug resistance in children. Resistance rates to these antibiotics exhibited considerable variation across common pathogens, including Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii.
Conclusions: The development of drug resistance in bacteria will significantly affect the prognosis of patients. The significant differences in drug resistance of common pathogenic bacteria indicate that identification of drug resistance is important for the rational use of antibiotics and patient prognosis.
Introduction: Colonisation and infection with Carbapenem-resistant Enterobacterales (CRE) in healthcare settings poses significant risks, especially for vulnerable patients. Genomic analysis can be used to trace transmission routes, supporting antimicrobial stewardship and informing infection control strategies. Here we used genomic analysis to track the movement and transmission of CREs within clinical and environmental samples.
Methods: 25 isolates were cultured from clinical patient samples or swabs, that tested positive for OXA-48-like variants using the NG-Test® CARBA-5 test and whole genome sequenced (WGS) using Oxford Nanopore Technologies (ONT). 158 swabs and 52 wastewater samples were collected from the ward environment. 60 isolates (matching clinical isolate genera; Klebsiella, Enterobacter, Citrobacter and Escherichia) were isolated from the environmental samples using selective agar. Metagenomic sequencing was undertaken on 36 environmental wastewater and swab samples.
Results: 21/25 (84%) clinical isolates had > 1 blaOXA gene and 19/25 (76%) harboured > 1 blaNDM gene. Enterobacterales were most commonly isolated from environmental wastewater samples 27/52 (51.9%), then stick swabs 5/43 (11.6%) and sponge swabs 5/115 (4.3%). 11/60 (18%) environmental isolates harboured > 1 blaOXA gene and 1.9% (1/60) harboured blaNDM-1. blaOXA genes were found in 2/36 (5.5%) metagenomic environmental samples.
Conclusions: Potential for putative patient-patient and patient-ward transmission was shown. Metagenomic sampling needs optimization to improve sensitivity.
Non-O1/non-O139 Vibrio cholerae (NOVC) strains are a distinct group of Vibrio cholerae that do not cause epidemic cholera. NOVC infections usually cause mild forms of gastroenteritis, and rarely severe (extra)intestinal infections, mostly affecting immunocompromised patients. Here, we describe the clinical course of a patient with NOVC bacteremia causing multiple liver abscesses, after drinking from a freshwater well in a non-coastal area. This case highlights the potential of a V. cholerae strain, that is phylogenetically distinct from the current pandemic cholera strain, to cause severe extra-intestinal infections, including liver abscesses.
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：