1,721,027 research outputs found
Ralstonia mannitolilytica bacteraemia: a case report and literature review
No full textRalstonia mannitolilytica is a difficult-to-diagnose, aerobic, Gram-negative bacillus, mainly causing healthcare infections in immunocompromised hosts. We report the first case of R. mannitolilytica bacteraemia in a kidney transplant recipient. Identification of R. mannitolilytica was finally performed by 16S rRNA gene sequencing. All cases of R. mannitolilytica bacteraemia reported in the English language literature over the past 20 years are reviewed to alert clinicians to the epidemiological, clinical, diagnostic, prognostic and microbiologic features of this emerging pathogen
Parvimonas micra bacteremia following endoscopic retrograde cholangiopancreatography: A new route of infection
Full text linkIn vivo emergence of ceftazidime/avibactam, cefiderocol and aztreonam/avibactam cross-resistance in a patient with KPC-producing Klebsiella pneumoniae infection after Cefiderocol-based treatment
No full textNo abstract availabl
Exposure to the agricultural fungicide tebuconazole promotes Aspergillus fumigatus cross-resistance to clinical azoles. [Comini S. is the co-first author; Banche G. is the corresponding author; Cuffini A.M. is the co-corresponding author]
No full textResistance to clinical triazoles in Aspergillus fumigatus is a growing concern for individuals at high risk of Aspergillus infection. Two triazole resistance selection routes are currently being investigated: one occurring in triazole-treated patients in healthcare settings, and the second taking place in the environment due to the widespread use of agricultural triazoles. This study aimed to assess the ability of agricultural azoles to promote cross-resistance to clinical azoles in A. fumigatus. Five A. fumigatus isolates susceptible to clinical azoles were exposed to the triazole 14α-demethylase inhibitor, tebuconazole (TBC), and then antifungal susceptibility tests for voriconazole, itraconazole, posaconazole and isavuconazole were performed. Under TBC selection pressure, all A. fumigatus isolates exhibited resistance to clinical triazoles. However, only two displayed a multiresistant phenotype to clinical azoles. TBC exposure was also associated with delayed conidia formation and progressive absence of conidiation. Noteworthy, no TBC-exposed clones harbored TR34/L98H mutation, as judged by real-time PCR assays. The observation that TBC exposure promotes cross-resistance to clinical triazoles warrants careful and thorough assessment of the human health risk associated with agricultural azoles. The absence of TR34/L98H mutation in cross-resistant A. fumigatus isolates suggests that other cyp51A mutations may be involved in clinical azole cross-resistance
In vivo development of resistance to novel β-lactam/β-lactamase inhibitor combinations in KPC-producing Klebsiella pneumoniae infections: a case series
Full text linkIntroduction: Understanding the dynamics that may characterize the emergence of KPC variants with resistance to novel β-lactam/β-lactamase inhibitor combinations (βL/βLICs) represents a challenge to be overcome in the appropriate use of recently introduced antibiotics. Methods: Retrospective case series describing development of multiple resistance to novel βL/βLICs in patients with KPC-producing Klebsiella pneumoniae (KPC-Kp) infections treated with these drugs. Clinical-microbiological investigation and characterization of longitudinal strains by Whole-Genome Sequencing were performed. Results: Four patients with KPC-Kp bloodstream infections were included. Most frequent clinical features were kidney disease, obesity, cardiac surgery as reason for admission, ICU stay, treatment with ceftazidime/avibactam, and pneumonia and/or acute kidney injury needing renal replacement therapy as KPC-Kp sepsis-associated complications. The development of resistance to ceftazidime/avibactam was observed in four longitudinal strains (three of which were co-resistant to aztreonam/avibactam and cefiderocol) following treatments with ceftazidime/avibactam (n = 3) or cefiderocol (n = 1). Resistance to meropenem/vaborbactam and imipenem/cilastatin/relebactam was observed in one case after exposure to ceftazidime/avibactam and imipenem/cilastatin/relebactam. Resistome analysis showed that resistance to novel βL/βLICs was related to specific mutations within blaKPC carbapenemase gene (D179Y mutation [KPC-33]; deletion Δ242-GT-243 [KPC-14]) in three longitudinal strains, while porin loss (truncated OmpK35 and OmpK36 porins) was observed in one case. Conclusion: Therapy with novel βL/βLICs or cefiderocol may lead to the selection of resistant mutants in the presence of factors influencing the achievement of PK/PD targets. KPC variants are mainly associated with resistance to ceftazidime/avibactam, and some of them (e.g. KPC-14) may also be associated with reduced susceptibility to aztreonam/avibactam and/or cefiderocol. Loss of function of the OmpK35 and OmpK36 porins appears to play a role in the development of resistance to meropenem/vaborbactam and/or imipenem/relebactam, but other mechanisms may also be involved
Increased bla(KPC) Copy Number and OmpK35 and OmpK36 Porins Disruption Mediated Resistance to Imipenem/Relebactam and Meropenem/Vaborbactam in a KPC-Producing Klebsiella pneumoniae Clinical Isolate
No full textHerein, we report the in vivo evolution of imipenem/relebactam-resistance in KPC-producing K. pneumoniae (KPC-Kp) isolated from a critically-ill patient treated with multiple combination therapies based on ceftazidime-avibactam or meropenem-vaborbactam. Imipenem/relebactam-resistance was associated to meropenem-vaborbactam cross-resistance and was due to truncated OmpK35 and OmpK36 porins and increased copy of bla(KPC) copy number. Genome analysis demonstrated that imipenem/relebactam-resistant KPC-Kp harbored a second copy of bla(KPC)-carrying Tn4401 in a ColRNAI plasmid as a consequence of a transposition event
Resistance to sulbactam/durlobactam in carbapenem-resistant Acinetobacter baumannii in treatment-naive setting: in vitro data and genomic insights from Italian bloodstream isolates
No full textObjectives: This study evaluated the in vitro activity of sulbactam/durlobactam and comparators against carbapenem-resistant Acinetobacter baumannii (CRAB) bloodstream isolates from Italy and investigated genomic mechanisms underlying resistance. Methods: A total of 110 consecutive CRAB isolates (2021-2023) were tested for susceptibility to sulbactam/durlobactam, cefiderocol, colistin, and comparators. Whole-genome sequencing (WGS) was performed on sulbactam/durlobactam-resistant isolates to characterize β-lactamase genes, outbreak dynamics, and mutations in penicillin-binding proteins (PBPs). Results: Sulbactam/durlobactam inhibited 88.7% of isolates (MIC50 = 2 mg/L; MIC90 > 64 mg/L), while 12.7% were resistant. Cefiderocol and colistin showed 91.8% and 96.4% susceptibility rates, respectively. All resistant isolates carried blaOXA-23, and three also harbored blaNDM-1. WGS revealed close clonal relationships (average nucleotide identity > 99%) among blaNDM-1 positive isolates (ST231) and among OXA-23-only isolates (ST837/ST369), indicating local outbreak dynamics. Comparative PBP analysis identified recurrent substitutions P112S and G137R (PBP1b), N392T and A515V (PBP3), and S329N (PBP5). Structural correlation suggests these mutations reduce β-lactam binding and may contribute to resistance, particularly when combined with NDM-1. Conclusions: This study provides early evidence of sulbactam/durlobactam resistance in treatment-naïve CRAB from Italy, driven by NDM-1 co-production and PBP alterations. The coexistence of epidemic ST231 and ST837/ST369 clones highlights the need for continuous genomic surveillance and prudent antibiotic stewardship to prevent dissemination of resistant A. baumannii lineages
Assessment of rapid direct E-test on positive blood culture for same-day antimicrobial susceptibility
No full textIntroduction: Early and appropriated antimicrobial therapy showed to positively impact on the clinical improvement of septic patients. The aim of this study was to evaluate E-test methodology to obtain rapid results of antimicrobial susceptibility, starting directly from blood culture bottles positive to Gram-negative monomicrobial flora.
Materials and methods: One hundred and five blood culture samples positive to Gram-negative rods at the microscopic examination were collected. Bacterial identification from early subculture on blood agar after 4 h incubation and rapid direct E-test from blood culture broth were performed on every sample. Antibiotics MIC were achieved after 5-6 h of incubation. Resulting MIC values were compared with those obtained with reference E-test from the overnight subculture. Categorical agreement (CA) and essential agreement (EA) were evaluated.
Results: Comparison between rapid direct E-test and reference E-test showed CA ranging from 95.1 to 100 % and 88.2 to 100 % for Enterobacteriaceae (EB) and for non-fermenting Gram-negative bacilli, respectively. Rapid direct E-test showed an overall EA of 80.1 %, revealing different EA rates for the tested antibiotics. Among carbapenemase-producing EB, CA of 87.5 % and EA of 75.5 % for MP were achieved.
Discussion: The same-day communication of the antimicrobial susceptibility represents an important challenge in the multidrug-resistance era. Despite not being able to anticipate actual MIC values, the rapid direct E-test may be useful to obtain preliminary AST results in 5-6 h, especially if used in association with phenotypic or genotypic tests to identify the main resistance mechanisms
Detection of antibiotic resistance genes from blood cultures: performance assessment and potential impact on antibiotic therapy management
No full textMolecular assays may constitute a valid method for timely prediction of antimicrobial resistance and optimization of empirical antibiotic therapies. This study assessed ELITe MGB assays of blood cultures to detect the main carbapenemase and extended-spectrum beta-lactamase (ESBL) genes, Staphylococcus aureus and mec genes in less than 3 h. Excellent agreement was found between the results of genotypic and conventional phenotypic approaches. Retrospective analysis of medical records revealed that approximately 50% of bloodstream infections caused by ESBL-producing Enterobacteriaceae, carbapenemase-producing Enterobacteriaceae or meticillin-resistant S. aureus were initially treated with inactive drugs. Overall, 36.3% of patients could have been treated with appropriate therapy at least 24 h earlier if molecular data had been used
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