Raoultella terrigena is a bacterium commonly isolated from environmental sources, with rare reports of isolation from clinical samples. Multidrug resistance is also rare. In this study, R. terrigena was obtained from the uterine lavage of a thoroughbred mare. Broth microdilution and disc diffusion methods were used to determine susceptibility to antimicrobials. Whole genome sequencing was performed to identify and characterise the presence of mobile genetic elements, antimicrobial resistance and virulence genes. Pan-genome analysis allowed comparison of the genome of this isolate with other R. terrigena isolates. Phenotypic resistance was detected to cefazolin, ceftiofur, cefotaxime, ticarcillin/clavulanic acid, tetracycline, doxycycline, gentamicin, sulfamethoxazole/trimethoprim and chloramphenicol. The genome included two plasmids (IncQ1/IncU and IncFII/rep_cluster_2078 types). Also identified in the IncQ1/IncU plasmid were genes conferring resistance to aminoglycosides, fluoroquinolones, rifamycin, phenicols, cephalosporins, diaminopyrimidines, sulfonamides and tetracycline. Except for enrofloxacin susceptibility, the presence of resistance genes was consistent with observed phenotypes. Genes conferring resistance to antiseptics, biocides and metals were also detected. Phylogenetic analysis of the combined dataset, including the isolate in this study and publicly available genomes, revealed two distinct clades, with equine isolates clustering together with other animal-derived isolates. The emergence of antimicrobial resistance in rare opportunistic pathogens underlines the importance of continuous monitoring of such bacteria and emphasizing the need for developing antimicrobial stewardship programs in veterinary settings.

Corticosteroid-antibiotic combinations are commonly used in veterinary ophthalmic practice, yet the potential for corticosteroids to modulate antimicrobial susceptibility remains incompletely characterized. This study evaluated the in vitro effects of fluorometholone (FML) on the antimicrobial susceptibility of three major canine ocular pathogens-Staphylococcus pseudintermedius, Streptococcus canis, and Pseudomonas aeruginosa-and compared its interaction profile with that of dexamethasone.

Antibiotic-associated encephalopathy (AAE) is a serious adverse drug reaction that can cause significant neurological complications. This study aimed to identify the antibiotics associated with AAE by mining data from the US Food and Drug Administration Adverse Event Reporting System (FAERS), thereby providing insights into antibiotic-related neurotoxicity risks. Disproportionality analysis was performed using the reporting odds ratio method based on FAERS data from Q1 2004 to Q4 2024. A total of 87 preferred terms potentially related to AAE were identified. Antibiotics classified under Anatomical Therapeutic Chemical codes J01 to J07 and other antimicrobial agents were included. All identified antibiotics were grouped into 3 categories according to their clinical neurotoxic profiles. In total, 13,698 patients with AAE were identified over the 21-year period. The 5 most frequently reported antibiotics were metronidazole (1464 cases), levofloxacin (1447), ciprofloxacin (1290), ertapenem (825), and imipenem/cilastatin (788). The incidence of AAE increased with age. Among the 121 antibiotics analyzed, 52 showed positive reporting odds ratio signals: 28 were classified as type 1, 6 as type 2, and 18 as type 3. Most AAE cases occurred within 10 days of antibiotic exposure, except for several agents, including meropenem/vaborbactam and ticarcillin/clavulanic acid (type 1), and isoniazid, pyrazinamide, rifampicin, and paromomycin (type 3), which exhibited delayed onset. This study represents the first large-scale pharmacovigilance analysis of AAE using FAERS data and identifies 52 antibiotics with significant neurotoxicity signals. Most antibiotics trigger early-onset AAE, and older patients demonstrate greater susceptibility. These findings expand our understanding of AAE and inform safer antibiotic use.

BACKGROUND: Beta-lactams are among the most successful antibiotics for treating bacterial infections, but its use is impeded by increasing resistance. The contribution of BlrAB and CreBC two-component regulatory systems (TCSs) to β-lactam resistance is reported in Aeromonas spp. and Pseudomonas aeruginosa, respectively. Stenotrophomonas maltophilia, an opportunistic pathogen, is resistant to most β-lactams due to the chromosomally encoded β-lactamases L1 and L2. The role of CreBC TCS in the β-lactam resistance of S. maltophilia is still unclear. In this article, we aimed to address this issue. RESULTS: The susceptibility of KJΔBC, a creBC mutant of S. maltophilia KJ, to ceftazidime (CAZ) and ticarcillin-clavulanate increased compared to that of the wild-type KJ. Consistently, the CAZ-induced β-lactamase activity of KJΔBC was lower than that of the wild-type KJ. To find out the candidate responsible for the ΔcreBC-mediated β-lactam susceptibility increase and β-lactamase activity decrease, transcriptome results of wild-type KJ and KJΔBC were analyzed, focusing on the genes whose encoding proteins are involved in peptidoglycan (PG) homeostasis. Among the genes surveyed, anmK was the highest upregulated in KJΔBC. anmK encodes an anhydro-N-acetylmuramic acid kinase, which converts anhMurNAc to MurNAc-6P in the PG recycling pathway. The anmK gene and its upstream gene Smlt0416 (annotated as anmH) formed a two-member operon. Promoter activity of anmHK operon was upregulated in KJΔBC. However, the CAZ challenge hardly altered creBC and anmHK operons expression. anmK, but not anmH, deletion from the KJΔBC chromosome reverted CAZ resistance and CAZ-induced β-lactamase activity to the wild-type level. CONCLUSIONS: In unstressed S. maltophilia, CreBC TCS is activated and partially represses anmHK operon, favoring PG recycling toward the NagK-dependent pathway. In the CAZ-treated creBC mutant, anmHK operon is derepressed and the elevated AnmK activity may enhance the AnmK–MupP–AmgK–MurU–MurCDEF pathway, thereby increasing UDP-MurNAc-pentapeptide levels and decreasing β-lactam-induced β-lactamase activity. A creBC–anmK–L1/L2 regulatory circuit responsible for CAZ resistance has been established in S. maltophilia.

The aim of this study was to determine the antimicrobial susceptibility, virulence genotypes, presence of extended spectrum β-lactamase (ESBL) and carbapenemase genes, and clonality of Pseudomonas aeruginosa isolates responsible for lower respiratory tract infections in patients admitted to the National Bone Marrow Transplant Center (NBMTC) of Tunisia. During the 11-year study period, a total of 50 P. aeruginosa isolates were responsible for lower respiratory tract infections. Isolates were studied by determining their serotypes, antimicrobial susceptibility, genes encoding ESBL/carbapenemases and virulence factors, and genetic relatedness by ERIC-PCR. High to moderate resistance rates were observed for ticarcillin, ticarcillin-clavulanic acid, piperacillin-tazobactam, ceftazidime, cefepime, imipenem, meropenem, ciprofloxacin, amikacin, and fosfomycin. One isolate showed an ESBL phenotype encoded by the blaSHV-2a gene. Of 13 isolates resistant to both imipenem and meropenem, the blaGES gene was amplified in nine isolates. Isolates exhibited 19 virulence genotypes, of which five were prevalent: V1 (14 genes; n=14), V2 (14 genes, n=6), V3 (all genes, n=6), V4 (13 genes, n=5), and V5 (13 genes, n=5). ERIC-PCR showed high genetic heterogeneity. These findings highlight the high genetic heterogeneity of P. aeruginosa isolates in these neutropenic patients, as well as their remarkable pathogenic power, raising significant concern.

Pseudomonas aeruginosa is a major cause of health care-associated infections, particularly in intensive care units (ICUs). To the best of our knowledge, this is one of the rare studies reporting the prevalence and antimicrobial resistance patterns of P. aeruginosa in a Tunisian ICU. This retrospective study included all P. aeruginosa strains isolated from ICU patients in Sfax, Tunisia, between 2017 and 2024. A total of 1,126 nonredundant P. aeruginosa strains were obtained from 767 patients. P. aeruginosa strains accounted for 21.1% of all clinical isolates in the ICU. The majority of strains were isolated from respiratory samples (54.6%) and blood cultures (14.3%). The prevalence of resistance rates was highest for ticarcillin (48.3%) and ticarcillin-clavulanic acid (48.6%). The resistance to both ceftazidime and imipenem was observed in 33.6% of P. aeruginosa strains. The prevalence of resistance of P. aeruginosa was 29.8% and 26.2% to ceftazidime-avibactam (CAV) and ceftolozane-tazobactam (C/T), respectively. The prevalence of resistance to amikacin and ciprofloxacin was 36.2% and 37.9%, respectively. Of the 1,126 isolates, 346 (30.7%) were multidrug-resistant P. aeruginosa (MDR-PA) strains, presenting resistance to ceftazidime, ciprofloxacin, and amikacin simultaneously. Since 2022, a significant increase in the MDR rate was observed, reaching 46.3% in 2024 (P <0.001). The resistance rates of MDR-PA were 52.5% and 56.8% to C/T and CAV, respectively. None of the tested MDR-PA strains showed resistance to colistin. This study highlights a high prevalence of MDR strains of P. aeruginosa in our ICU, with increasing resistance over recent years. Prevention is highly warranted.

Secondary pulmonary infections are crucial and pivotal contributing factors to clinical deterioration in patients with pulmonary tuberculosis. Research remains limited regarding the specific population and regional epidemiology of these secondary infections, despite its clinical importance. This study provides an in-depth analysis of the primary bacterial pathogens and their antimicrobial resistance rates among hospitalized pulmonary tuberculosis patients with concurrent pulmonary infections in Yangzhou, China, from 2021 to 2024. Suitable sputum samples and leftover bronchoalveolar lavage fluid samples were collected for bacterial culture identification and drug sensitivity testing. The annual and regional distributions of strains and the evolution of resistance rates were analyzed using the chi-square test and the Cochran-Armitage trend test. A total of 514 strains of pathogenic bacteria were cultured from 410 samples, with 499 strains (97.08 %) being Gram-negative bacteria. Klebsiella pneumoniae was the most common Gram-negative bacterium (40.27 %), followed by Pseudomonas aeruginosa (15.18 %), while Staphylococcus aureus was the primary Gram-positive bacterium (1.75 %). The drug sensitivity tests results over different years showed that K. pneumoniae exhibited significant resistance rates against doxycycline, ceftazidime, cefepime, cefuroxime, cefazolin, cefotaxime, levofloxacin, ticarcillin/clavulanate, amikacin, and norfloxacin (P < 0.05). The resistance rates of P. aeruginosa to cefazolin and ciprofloxacin were also statistically significant (P < 0.05). The drug sensitivity test results across different regions showed that the resistance rate of K. pneumoniae to minocycline in urban patients was statistically significant (P = 0.012), while the resistance rates of P. aeruginosa to tobramycin and ciprofloxacin in rural patients were statistically significant (P < 0.05). Annual statistics of extended-spectrum beta-lactamase ESBL-producing K. pneumoniae resistant strains showed significant annual increases (P < 0.05). Moreover, data on resistant strains in urban and rural areas indicated that the detection rate of ESBL-producing Escherichia coli in rural areas was higher than that in urban areas (P = 0.052), and the detection rate of ESBL-producing K. pneumoniae resistant strains in rural areas was significantly higher than in urban areas (P = 0.005). The rise of new carbapenem-resistant K. pneumoniae strains in 2023 should be monitored. This study provides strong data support to formulate antibiotic treatment plans for patients with tuberculosis and respiratory infections, reduce the risk of resistant strain transmission, and optimize clinical treatment strategies.