原田 壮平

Here, we report the draft genome sequence of Stenotrophomonas maltophilia TUM26315, which exhibits resistance to cefiderocol and to aztreonam combined with ceftazidime-avibactam, despite no prior exposure. The isolate belonged to genomic group 6 and carried blaL1B and blaL2B β-lactamase genes. It also had a frameshift mutation in the cirA gene.

Daptomycin is an alternative agent for invasive infections caused by Corynebacterium species in patients with intolerance to vancomycin. Although it has recently been recognized that treatment failure with daptomycin due to the emergence of resistant strains during treatment is not uncommon in Corynebacterium striatum infections, it has been unclear whether there is a similar risk in Corynebacterium jeikeium infections. In the presenting case, daptomycin treatment for C. jeikeium endocarditis in a liver transplant recipient with neutropenia failed due to the rapid emergence of the resistant strain. Whole-genome sequencing analysis of blood culture isolates confirmed that a mutation in the pgsA gene, which is also involved in the development of daptomycin resistance in C. striatum, emerged after daptomycin exposure. This case demonstrated that there is a risk of treatment failure due to the emergence of daptomycin-resistant strains even in C. jeikeium infections caused by daptomycin-susceptible strains, particularly in immunocompromised patients and in biofilm infections with high bacterial burden.

UNLABELLED: Among Corynebacterium species, Corynebacterium striatum is relatively frequently involved in invasive human infections. In this study, we collected clinical information from patients diagnosed with C. striatum infection at a single cancer center and performed antimicrobial susceptibility testing and whole-genome sequencing of the causative strains. Of the 51 patients with C. striatum infections, 15 (29.4%) had postoperative intra-abdominal infections, eight (15.7%) had postoperative skin and soft tissue infections of the neck, and eight (15.7%) had osteoarticular infections. In 15 patients, C. striatum was detected concomitantly with other bacteria. The median duration of antimicrobial therapy was 25 days, with 43 patients (84.3%) showing clinical improvement by day 14. The crude mortality up to 90 days post-diagnosis was 15.7%. Vancomycin was the most commonly used definitive therapy, and 40 patients (78.4%) received multiple antimicrobial agents. Oral minocycline was often administered in patients requiring long-term treatment. Antimicrobial susceptibility testing of 53 strains, including two strains from follow-up cultures from the same patient, showed that most strains were susceptible to daptomycin and tetracyclines. However, non-susceptibility was noted in two strains (3.8%) for daptomycin and four strains (7.5%) for tetracyclines, each associated with psgA2 mutation and tet(W) carriage. Core-genome single-nucleotide polymorphism analysis of the strains and epidemiological reviews of the source patients identified three suspected clusters of nosocomial transmission involving seven patients. This study demonstrated that C. striatum can cause a range of infections in patients with underlying diseases, such as malignancy, and that nosocomial spread of this pathogen may also occur. IMPORTANCE: The use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, employed for bacterial species identification in this study, has enhanced the recognition of Corynebacterium striatum as an important human pathogen in clinical microbiology laboratories. Our study demonstrated that C. striatum is associated with various healthcare-associated infections, including those requiring prolonged antimicrobial therapy, and that nosocomial transmission of this pathogen can result in the development of infections. In addition, several agents other than vancomycin, such as teicoplanin, tetracyclines, and trimethoprim/sulfamethoxazole, have demonstrated favorable activities. The results of this study indicate the need for further research on the mechanisms and modes of nosocomial transmission of C. striatum, as well as the clinical efficacy of alternative agents to vancomycin, particularly those suitable for prolonged treatment, given the potential side effects associated with vancomycin use.

OBJECTIVE: Guidelines recommend redosing with intravenous prophylactic antibiotics when excessive bleeding exceeds 1500 mL during surgery based on the pharmacokinetics data of cefazolin. However, the necessity for redosing of other antibiotics and the threshold volume of blood loss necessitating such supplementation remain undefined. We investigated plasma antibiotic concentrations during liver transplant surgery in patients with frequent excessive bleeding. METHODS: A single-centre, prospective, observational pharmacokinetic study was conducted. Adult liver transplant recipients who received 2 g of ampicillin and 1 g of sulbactam every 3 h during surgery were included. Blood samples were collected hourly during surgery, and intraoperative bleeding amounts were reviewed from anaesthesia records. Plasma concentrations of ampicillin and sulbactam were determined using validated liquid chromatography-tandem mass spectrometry. The probability of target attainment was set at 80% free time above the MIC (fT > MIC). RESULTS: Twenty participants were included. Of these, 11 participants (55%) were female. The median age, body weight, and bleeding volume were 52 years, 62.1 kg, and 11 158 mL, respectively. The intraoperative clearance of ampicillin was 80.28 mL/min, and sulbactam was 77.23 mL/min. The fT > MIC for both ampicillin and sulbactam tended to be lower with bleeding > 20 000 mL than with less bleeding. Plasma concentrations of ampicillin and sulbactam were maintained during surgery without redosing, even after bleeding exceeded 1500 mL. CONCLUSIONS: Even with excessive bleeding, administering 3 g of ampicillin/sulbactam every 3 h maintained sufficient plasma concentration. Redosing may be unnecessary unless total bleeding exceeds 20 000 mL.

OBJECTIVES: The objective of this study was to determine the pharmacokinetic/pharmacodynamic parameters of teicoplanin associated with optimal outcomes in glycopeptide-susceptible Enterococcus faecium (GSEF) bacteraemia. PATIENTS AND METHODS: We conducted a retrospective review of GSEF bacteraemia cases treated with teicoplanin between 1 April 2009 and 30 May 2023. Total area under the concentration-time curve over 24 h (AUC24) was calculated using a Bayesian approach. The free AUC24 (fAUC24) was estimated based on patient serum albumin levels. MICs were determined using the gradient diffusion method (Etest), and the fAUC24/MICEtest ratio was calculated. The primary outcome was treatment failure, defined as a composite of (i) 30-day all-cause mortality and (ii) microbiological failure, defined as persistent bacteraemia (a positive follow-up blood culture obtained >72 h after initiation of appropriate therapy). Classification and regression tree analysis (CART) was employed to identify the optimal teicoplanin fAUC24/MICEtest value associated with treatment failure. RESULTS: A total of 76 patients were included. Treatment failure occurred in 18 patients (23.7%). A CART-derived teicoplanin fAUC24/MICEtest ≥ 462 was significantly associated with reduced treatment failure (P = 0.002). Multivariable regression analysis revealed that achievement of an fAUC24/MICEtest ≥ 462 was an independent predictor significantly associated with reduced treatment failure (OR, 0.099; 95% CI, 0.005-0.562; P = 0.032). CONCLUSIONS: An fAUC24/MICEtest ≥ 462 was associated with a reduction in treatment failure in GSEF bacteraemia. Further studies are necessary to establish optimal pharmacokinetic/pharmacodynamic targets for GSEF bacteraemia.