Search Results (59)

Background: Broad-spectrum antibiotics are often used for suspected infections in patients with hematologic malignancies due to the risk of severe infections. Although antibiotic use can lead to antimicrobial resistance and microbiome dysbiosis, the effects of antibiotics on the microbiome and resistome in patients with acute myeloid leukemia (AML) undergoing remission induction chemotherapy (RIC) are not well understood. Methods: Various statistical models were utilized to examine the effects of antibiotic administration on the microbiome and resistome over time, as well as differences in AR-infection (ARI) and colonization (ARC) by important CDC-threats in 119 AML patients. Results: A greater number of unique antibiotic classes administered correlated with a loss of unique antibiotic resistance genes (ARGs) (R = −0.39, p = 0.008). Specifically, although a greater number of oxazolidinone administrations was correlated with a greater loss of diversity (R = −0.58, p < 0.001), each additional day of linezolid reduced the risk of ARC by ~30% (HR: 0.663, p = 0.047) and decreased the odds of acquiring genes predicted to confer macrolide (HR: 0.50, p = 0.026) resistance. Conclusions: The number of antibiotic administrations and the types of antibiotics used can influence the risk of antibiotic resistance gene (ARG) expansion and ARC events in AML patients undergoing RIC. While certain antibiotics may reduce microbial diversity, they are not always linked to an increase in ARGs or ARC events. Full article

Background/Objectives: The clinical forms of coronavirus disease 2019 (COVID-19) vary widely in severity, ranging from asymptomatic or moderate cases to severe pneumonia that can lead to acute respiratory failure, acute respiratory distress syndrome, multiple organ dysfunction syndrome, and death. Our main objective was to determine the prevalence of bacterial and fungal secondary infections in an intensive care unit (ICU). Secondary objectives included analyzing the impact of these infections on mortality and medical resource utilization, as well as assessing antimicrobial resistance in this context. Methods: We conducted a retrospective cohort study that included critically ill severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients treated in an ICU and analyzed the prevalence of co-infections and superinfections. Results: A multivariate analysis of mortality found that the presence of superinfections increased the odds of death by more than 15-fold, while the Sequential Organ Failure Assessment (SOFA) score and C-reactive protein (adjusted for confounders) increased the odds of mortality by 51% and 13%, respectively. The antibiotic resistance profile of microorganisms indicated a high prevalence of resistant strains. Carbapenems, glycopeptides, and oxazolidinones were the most frequently used classes of antibiotics. Among patients, 27.9% received a single antibiotic, 47.5% received two from different classes, and 24.4% were treated with three or more. Conclusions: The incidence and spectrum of bacterial and fungal superinfections are higher in critically ill ICU patients, leading to worse outcomes in COVID-19 cases. Multidrug-resistant pathogens present significant challenges for ICU and public health settings. Early screening, accurate diagnosis, and minimal use of invasive devices are essential to reduce risks and improve patient outcomes. Full article

(1) Background: S. parasuis is a potential opportunistic zoonotic pathogen that can infect pigs, cattle, and humans, composed of former members of S. suis serotypes 20, 22, and 26. In recent years, unclassified serotypes and a serotype 11 S. parasuis have been discovered. (2) Methods: We characterized two S. parasuis strains (FZ1 and FZ2) isolated from brain samples of paralyzed pigs and examined evolutionary divergence among 22 available S. parasuis and 8 serotype 2 S. suis genomes through whole-genome sequencing and comparative genomic analysis. We compared virulence genes (VGs) and antibiotic resistance genes (ARGs) and analyzed mobile genetic elements (MGEs) in FZ1 and FZ2. (3) Results: Comparative genomics revealed that srtC, ctpV, and sugC may represent key virulence determinants in S. parasuis, although their pathogenic potential appears attenuated compared to serotype 2 S. suis. In addition, S. parasuis exhibited primary resistance to aminoglycosides, macrolides, tetracyclines, and oxazolidinones, while demonstrating heightened susceptibility to oxazolidinone-class antibiotics. Moreover, we found an important association between MGEs and antibiotic resistance in S. parasuis FZ1 and FZ2. (4) Conclusions: This study provides new insights into the genomic and evolutionary characteristics of S. parasuis and provides a new basis for the study of bacterial pathogenesis and drug resistance in the future. Full article

This study investigates the occurrence, antimicrobial resistance (AMR) profiles, virulence factors, and plasmid composition of Enterococcus species isolated from salad ingredients in the United Arab Emirates (UAE). Four hundred salad vegetable items collected from local markets, over ten months through 2023, were screened, yielding an Enterococcus detection rate of 85.5% (342/400). E. casseliflavus was the most commonly identified species (50%), followed by E. faecium (20%) and E. faecalis (16%). Among 85 Enterococcus isolates tested for antimicrobial susceptibility, 55.3% displayed resistance to at least one agent, with 18.8% classified as multidrug-resistant (MDR). All isolates were not resistant to ampicillin, linezolid, teicoplanin, tigecycline, and high-level gentamicin. Intrinsic phenotypic resistance to vancomycin was found in E. gallinarum and E. casseliflavus, while low-level (<5%) ciprofloxacin and erythromycin resistance was sporadically detected in E. faecium and E. faecalis. Whole-genome sequencing (WGS) of 14 isolates (nine E. faecium, four E. faecalis, and one E. casseliflavus) unveiled a complex resistome. We report the first detection in salad vegetables of vancomycin resistance genes (vanC, vanXY-C2) in a vancomycin-susceptible E. faecalis isolate. Identifying tetM, ermB, and optrA genes in the studied isolates further underscored emerging resistance to tetracyclines, macrolides, and oxazolidinones. Concurrently, virulence gene analysis revealed 74 putative virulence factors, with E. faecalis harboring a higher diversity of biofilm-related and exoenzyme-encoding genes. One E. faecalis strain carried the cytolysin cluster (cylI, cylS, cylM), highlighting its pathogenic potential. Plasmid profiling identified 19 distinct plasmids, ranging from 3845 bp to 133,159 bp. Among the genome-sequenced isolates, mobilizable plasmids (47.3%) commonly carried AMR genes, especially tet(L) and tet(M), whereas conjugative plasmids (10.5%) did not harbor resistance determinants. These findings highlight that salad vegetables can still harbor and potentially transmit Enterococcus strains with clinically relevant resistance determinants and virulence traits. Enhancing foodborne AMR surveillance with WGS and targeted interventions is key to controlling its spread in the food. Full article

Background/Objectives: Oxazolidinones are novel antimicrobial agents used to combat bacterial infections, particularly multidrug-resistant strains. However, the synthesis of oxazolidinone derivatives, such as linezolid, often involves the use of 3,4-difluoronitrobenzene (DFNB) as an initiator. Despite its effectiveness, residual DFNB in drug products raises significant health concerns due to its structural similarity to toxic and carcinogenic nitrobenzenes. This contamination is particularly concerning in pharmaceutical formulations, where it poses potential patient safety hazards. Therefore, strict concentration limits for this impurity are necessary. Methods: To ensure tight control of DFNB concentrations, this study established an 8.3 µg/g target limit. An advanced high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to overcome current limitations in detecting trace DFNB. Under negative atmospheric pressure chemical ionization (APCI) conditions, DFNB exhibited characteristic ion formations, including [M]^•− through electron capture and [M − F + O]⁻ via substitution reactions. The quantitative method utilizes MS/MS ion transitions of the substitution product while optimizing chromatographic and spectrometric parameters to enhance both sensitivity and specificity. Conclusions: Validation tests confirm the efficiency, precision, and accuracy of this method, with a low limit of quantification (LOQ) of 5 ng/mL (0.83 µg/g). This technique enables accurate detection and quantification of DFNB in linezolid active pharmaceutical ingredient (API) and various formulations, providing a reliable tool for quality control. This method ensures the safe use of linezolid by effectively monitoring and minimizing the risks associated with DFNB contamination. Full article

Oxazolidinones, novel synthetic antibacterials, inhibit protein biosynthesis and show potent activity against Gram-positive bacteria, including Mycobacterium tuberculosis (MTB). In this study, we aimed to compare the in vitro activity of linezolid (LZD) and four oxazolidinones, including tedizolid (TZD), contezolid (CZD), sutezolid (SZD), and delpazolid (DZD), against multidrug-resistant tuberculosis (MDR-TB) and pre-extensively drug-resistant tuberculosis (pre-XDR-TB) isolates from Hainan. We established their epidemiological cut-off values (ECOFFs) using ECOFFinder software and analyzed mutations in rrl (23S rRNA), rplC, rplD, mce3R, tsnR, Rv0545c, Rv0930, Rv3331, and Rv0890c genes to uncover potential mechanisms of oxazolidinone resistance. This study included 177 MTB isolates, comprising 67 MDR and 110 pre-XDR-TB isolates. Overall, SZD exhibited the strongest antibacterial activity against clinical MTB isolates, followed by TZD and LZD, with CZD and DZD showing equivalent but weaker activity (SZD_MIC50 = TZD_MIC50 < LZD_MIC50 < CZD_MIC50 = DZD_MIC50; SZD_MIC90 < TZD_MIC90 = LZD_MIC90 < CZD_MIC90 = DZD_MIC90). Significant differences in MIC distribution were observed for TZD (p < 0.0001), CZD (p < 0.01), SZD (p < 0.0001), and DZD (p < 0.0001) compared to LZD but not between MDR-TB and pre-XDR-TB isolates. We propose the following ECOFFs: SZD, 0.5 µg/mL; LZD, TZD, and CZD, 1.0 µg/mL; DZD, 2.0 µg/mL. No statistically significant differences in resistance rates were observed among these five drugs (p > 0.05). We found that eight MTB isolates (4.52% [8/177]) resisted these five oxazolidinones. Among these, only one isolate, M26, showed an amino acid substitution (Arg79His) in the protein encoded by the rplD gene, which conferred cross-resistance to TZD and CZD. Three distinct mutations were identified in the mce3R gene; notably, isolate P604 displayed two insertions that contributed to resistance against all five oxazolidinones. However, no significant correlation was observed between mutations in the rrl, rplC, rplD, mce3R, tsnR, Rv0545c, Rv0930, Rv3331, and Rv0890c genes with oxazolidinone resistance in the clinical MTB isolates tested. In summary, this study provides the first report on the resistance of MTB in Hainan to the five oxazolidinones (LZD, TZD, CZD, SZD, and DZD). In vitro susceptibility testing indicated that SZD exhibited the strongest antibacterial activity, followed by TZD and LZD, while CZD and DZD demonstrated comparable but weaker effectiveness. Mutations in rplD and mce3R were discovered, but further research is needed to clarify their role in conferring oxazolidinone resistance in MTB. Full article

Streptococcus pyogenes (Group A Streptococcus, GAS) is a Gram-positive pathogen responsible for both superficial and invasive infections (iGAS), with increasing global incidence in recent years. This study aims to characterize the molecular and clinical features of iGAS cases in Bologna and Imola (Italy) between 2022 and 2024. Thirty-five invasive isolates were analyzed through whole-genome sequencing (WGS) to investigate the distribution of emm types, antimicrobial resistance (AMR) genes, and virulence factors. Clinical and epidemiological data were retrospectively collected and analyzed. The majority of cases (80%) were recorded in 2023, predominantly among patients aged over 65 (60%). Bloodstream infections were present in 97.1% of cases, and comorbidities such as diabetes and immunosuppression were common. Empirical antibiotic therapy often involved penicillin/β-lactam inhibitors, while oxazolidinones were the most frequently used in targeted regimens. The in-hospital mortality rate was 20%. Genomic analysis identified emm1, emm12, and emm89 as the most prevalent types, associated with specific virulence profiles and resistance determinants. This study highlights the critical role of emm typing and genomic characterization in understanding the pathogenicity of GAS. These findings contribute to the identification of risk factors for severe outcomes and underscore the need for targeted prevention and treatment strategies in vulnerable populations. Full article

Linezolid is an oxazolidinone antibiotic and is considered a last-resort treatment option for serious infections caused by problematic Gram-positive pathogens, including vancomycin-resistant enterococci. The present study aimed to explore the linezolid resistance mechanisms and genomic characteristics of two vancomycin-susceptible Enterococcus faecalis isolates from Bulgaria. The strains designated Efs2503-bg (inpatient from Pleven) and Efs966-bg (outpatient from Varna) were recovered from wounds in 2018 and 2023, respectively. Antimicrobial susceptibility testing, whole-genome sequencing, multilocus sequence typing, and phylogenomic analysis based on 332 linezolid-resistant E. faecalis genomes were performed. Efs2503-bg was high-level resistant to linezolid (MIC > 256 mg/L) and displayed the G2576T mutation affecting three of the four 23S rDNA loci. Efs966-bg (MIC = 8 mg/L) carried a plasmid-located optrA determinant surrounded by fexA and ermA. No mutations in the genes encoding for ribosomal proteins L3, L4, and L22 were detected. The isolates belonged to the sequence types ST6 (Efs2503-bg) and ST1102 (Efs966-bg). Phylogenomic analysis revealed that Efs2503-bg and Efs966-bg are genetically distinct, with a difference of 12,051 single-nucleotide polymorphisms. To our knowledge, this is the first report of linezolid-resistant enterococci in Bulgaria. Although the global incidence of linezolid-resistant enterococci is still low, their emergence is alarming and poses a growing clinical threat to public health. Full article

The black garden ant (Lasius niger) is a widely distributed species across Europe, North America, and North Africa, playing a pivotal role in ecological processes within its diverse habitats. However, the microbiome associated with L. niger remains poorly investigated. In the present study, we isolated a novel species, Paenarthrobacter lasiusi, from the soil of the L. niger anthill. The genome of P. lasiusi S21 was sequenced, annotated, and searched for groups of genes of physiological, medical, and biotechnological importance. Subsequently, a series of microbiological, physiological, and biochemical experiments were conducted to characterize P. lasiusi S21 with respect to its sugar metabolism, antibiotic resistance profile, lipidome, and capacity for atmospheric nitrogen fixation, among others. A notable feature of the P. lasiusi S21 genome is the presence of two prophages, which may have horizontally transferred host genes involved in stress responses. P. lasiusi S21 synthesizes a number of lipids, including mono- and digalactosyldiacylglycerol, as well as steroid compounds that are typically found in eukaryotic organisms rather than prokaryotes. P. lasiusi S21 exhibits resistance to penicillins, lincosamides, fusidins, and oxazolidinones, despite the absence of specific genes conferring resistance to these antibiotics. Genomic data and physiological tests indicate that P. lasiusi S21 is nonpathogenic to humans. The genome of P. lasiusi S21 contains multiple operons involved in heavy metal metabolism and organic compound inactivation. Consequently, P. lasiusi represents a novel species with an intriguing evolutionary history, manifesting in distinctive genomic, metabolomic, and physiological characteristics. This species may have potential applications in the bioaugmentation of contaminated soils. Full article

Antibiotics targeting the bacterial ribosome are essential to combating bacterial infections. These antibiotics bind to various sites on the ribosome, inhibiting different stages of protein synthesis. This review provides a comprehensive overview of the mechanisms of action of clinically relevant antibiotics that target the bacterial ribosome, including macrolides, lincosamides, oxazolidinones, aminoglycosides, tetracyclines, and chloramphenicol. The structural and functional details of antibiotic interactions with ribosomal RNA, including specific binding sites, interactions with rRNA nucleotides, and their effects on translation processes, are discussed. Focus is placed on the diversity of these mechanisms and their clinical implications in treating bacterial infections, particularly in the context of emerging resistance. Understanding these mechanisms is crucial for developing novel therapeutic agents capable of overcoming bacterial resistance. Full article

Multidrug-resistant tuberculosis (MDR-TB) is a global health concern. Standard treatment involves the use of linezolid, a repurposed oxazolidinone. It is associated with severe adverse effects, including myelosuppression and mitochondrial toxicity. As such, it is imperative to identify novel alternatives that are better tolerated but equally or more effective. Therefore, this review aims to identify and explore the novel alternative oxazolidinones to potentially replace linezolid in the management of TB. The keywords tuberculosis and oxazolidinones were searched in PubMed to identify eligible compounds. The individual drug compounds were then searched with the term tuberculosis to identify the relevant in vitro, in vivo and clinical studies. The search identified sutezolid, tedizolid, delpazolid, eperezolid, radezolid, contezolid, posizolid and TBI-223, in addition to linezolid. An additional search resulted in 32 preclinical and 21 clinical studies. All novel oxazolidinones except posizolid and eperezolid resulted in positive preclinical outcomes. Sutezolid and delpazolid completed early phase 2 clinical studies with better safety and equal or superior efficacy. Linezolid is expected to continue as the mainstay therapy, with renewed interest in drug monitoring. Sutezolid, tedizolid, delpazolid and TBI-223 displayed promising preliminary results. Further clinical studies would be required to assess the safety profiles and optimize the dosing regimens. Full article

Oxazolidinone resistance, especially transmissible resistance, is a major public health concern, and the origin of this resistance mechanism is not yet resolved. This study aims to delve into the phylogenetic origin of the transmissible oxazolidinone resistance mechanisms conferring cross-resistance to other drugs of human and veterinary importance. The amino acid sequences of the five cfr ribosomal methylases and optrA and poxtA were used as queries in searches against 219,549 bacterial proteomes in the NCBI RefSeq database. Hits with >40% amino acid identity and >80% query coverage were aligned, and phylogenetic trees were reconstructed. All five cfr genes yielded highly similar trees, with rlmN housekeeping ribosomal methylases located basal to the sister groups of S-adenosyl-methionine-dependent methyltransferases from various Deltaproteobacteria and Actinomycetia, including antibiotic-producing Streptomyces species, and the monophyletic group of cfr genes. The basal branches of the latter contained paenibacilli and other soil bacteria; they then could be split into the clades [cfr(C):cfr(E)] and [[cfr:cfr(B)]:cfr(D)], always with different Bacillaceae in their stems. Lachnospiraceae were encountered in the basal branches of both optrA and poxtA trees. The ultimate origin of the cfr genes is the rlmN housekeeping ribosomal methylases, which evolved into a suicide-avoiding methylase in antibiotic producers; a soil organism (Lachnospiraceae, Paenibacilli) probably acted as a transfer organism into pathogenic bacteria. In the case of optrA, the porcine pathogenic Streptococcus suis was present in all branches, while the proteins closest to poxtA originated from Clostridia. Full article

Nosocomial central nervous system (CNS) infections with carbapenem- and colistin-resistant Gram-negative and vancomycin-resistant Gram-positive bacteria are an increasing therapeutic challenge. Here, we review pharmacokinetic and pharmacodynamic data and clinical experiences with new antibiotics administered intravenously for the treatment of CNS infections by multi-resistant bacteria. Cefiderocol, a new siderophore extended-spectrum cephalosporin, pharmacokinetically behaves similar to established cephalosporins and at high doses will probably be a valuable addition in our therapeutic armamentarium for CNS infections. The new glycopeptides dalbavancin, telavancin, and oritavancin are highly bound to plasma proteins. Although effective in animal models of meningitis, it is unlikely that they reach effective cerebrospinal fluid (CSF) concentrations after intravenous administration alone. The β-lactam/β-lactamase inhibitor combinations have the principal problem that both compounds must achieve adequate CSF concentrations. In the commercially available combinations, the dose of the β-lactamase inhibitor tends to be too low to achieve adequate CSF concentrations. The oxazolidinone tedizolid has a broader spectrum but a less suitable pharmacokinetic profile than linezolid. The halogenated tetracycline eravacycline does not reach CSF concentrations sufficient to treat colistin-resistant Gram-negative bacteria with usual intravenous dosing. Generally, treatment of CNS infections should be intravenous, whenever possible, to avoid adverse effects of intraventricular therapy (IVT). An additional IVT can overcome the limited penetration of many new antibiotics into CSF. It should be considered for patients in which the CNS infection responds poorly to systemic antimicrobial therapy alone. Full article

Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are a global health concern. The propensity of MRSA to form biofilms is a significant contributor to its pathogenicity. Strategies to treat biofilms often involve small molecules that disperse the biofilm into planktonic cells. Linezolid and, by extension, theoxazolidinones have been developed to treat infections caused by Gram-positive bacteria such as MRSA. However, the clinical development of these antibiotics has mainly assessed the susceptibility of planktonic cells to the drug. Previous studies evaluating the anti-biofilm activity of theoxazolidinones have mainly focused on the biofilm inhibition of Enterococcus faecalis and methicillin-sensitive Staphylococcus aureus, with only a few studies investigating the activity of oxazolidinones for eradicating established biofilms for these species. Very little is known about the ability of oxazolidinones to eradicate MRSA biofilms. In this work, five oxazolidinones were assessed against MRSA biofilms using a minimum biofilm eradication concentration (MBEC) assay. All oxazolidinones had inherent antibiofilm activity. However, only ranbezolid could completely eradicate MRSA biofilms at clinically relevant concentrations. The susceptibility of the MRSA biofilms to ranbezolid was synergistically enhanced by coadministration with the nitroxide biofilm dispersal agent C-TEMPO. We presume that ranbezolid acts as a dual warhead drug, which combines the mechanism of action of the oxazolidinones with a nitric oxide donor or cytotoxic drug. Full article

Among bacterial foodborne pathogens, Listeria monocytogenes represents one of the most important public health concerns in seafood industries. This study was designed as a retrospective study which aimed to investigate the trend of antibiotic resistance genes (ARGs) circulation in L. monocytogenes isolates identified (in the last 15 years) from Atlantic salmon (Salmo salar) fresh and smoked fillets and environmental samples. For these purposes, biomolecular assays were performed on 120 L. monocytogenes strains collected in certain years and compared to the contemporary scientific literature. A total of 52.50% (95% CI: 43.57–61.43%) of these samples were resistant to at least one antibiotic class, and 20.83% (95% CI: 13.57–28.09%) were classified as multidrug resistant. Concerning ARGs circulation, tetracycline (tetC, tetD, tetK, tetL, tetS), aminoglycoside (aadA, strA, aacC2, aphA1, aphA2), macrolide (cmlA1, catI, catII), and oxazolidinone (cfr, optrA, poxtA) gene determinants were majorly amplified. This study highlights the consistent ARGs circulation from fresh and processed finfish products and environmental samples, discovering resistance to the so-called critical important antimicrobials (CIA) since 2007. The obtained ARGs circulation data highlight the consistent increase in their diffusion when compared to similar contemporary investigations. This scenario emerges as the result of decades of improper antimicrobial administration in human and veterinary medicine. Full article