With the introduction of ceftazidime-avibactam worldwide, the antimicrobial activity of new β-lactam/β-lactamase inhibitors (BL/BLIs) needs to be investigated. From January 2020 to June 2023, Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales were collected. With a broth microdilution test of new BL/BLIs, cross-activity test with nine combinations of BLs and new BLIs and dose-escalation titration test for non-susceptible isolates were conducted to investigate inhibitory activities of new BLIs. A total of 188 isolates was collected and most isolates (186/188, 98.9%) carried the KPC-2 gene exclusively, while two isolates (1.1%) co-harbored NDM-1. Among the 186 KPC-2-producing isolates, 184 (98.9%) were susceptible to ceftazidime-avibactam, 173 (93.0%) to imipenem-relebactam, and 184 (98.9%) to meropenem-vaborbactam. All isolates non-susceptible to imipenem-relebactam or meropenem-vaborbactam became susceptible when avibactam replaced relebactam or vaborbactam, with 7 of 11 (63.6%) imipenem-relebactam non-susceptible isolates and both (100.0%) of the meropenem-vaborbactam non-susceptible isolates. When the minimum inhibitory concentrations (MICs) of BLs were compared using log ₂ scales, combinations with avibactam showed statistically significant efficacy in lowering MICs compared to relebactam and vaborbactam (all P < 0.05). In the dose-escalation test of new BLIs, increasing dose of all new BLIs corresponded to increased susceptibility to BLs. Ceftazidime-avibactam exhibited excellent susceptibility against KPC-2-producing Enterobacterales unless co-harboring metallo-β-lactamase. The cross-combination test against non-susceptible isolates suggests that the inhibitory activity of avibactam was superior to those of relebactam or vaborbactam. Increasing the dose of new BLIs produced increased susceptibility to BLs, suggesting that high-concentration regimen need to be developed. IMPORTANCE: This study investigated 188 Klebsiella pneumoniae carbapenemase (KPC)-2-producing Enterobacterales collected from January 2020 to June 2023 in a tertiary care hospital of Korea. Most isolates were susceptible to ceftazidime-avibactam (98.9%) and meropenem-vaborbactam (98.9%), while susceptibility to imipenem-relebactam was lower (93.0%). The cross-combination test using nine combinations of the individual β-lactams (BLs) and new β-lactamase inhibitors (BLIs) showed that the inhibitory activity of avibactam was significantly superior to relebactam or vaborbactam when the Log ₂ MIC of BLs were compared for each combination with BLIs (all P < 0.05). The dose-escalation test of new BLIs demonstrated that increasing doses of new BLIs corresponded to increased susceptibility to BLs. Taken together, this study illustrates the excellent activity of ceftazidime-avibactam against KPC-2-producing Enterobacterales and suggests further investigation into high-concentration regimens for potentially non-susceptible clinical isolates.

Tixagevimab/cilgavimab is a monoclonal antibody used to prevent coronavirus disease 2019 among immunocompromised hosts and maintained neutralizing activity against early omicron variants. Omicron BN.1 became a dominant circulating strain in Korea early 2023, but its susceptibility to tixagevimab/cilgavimab is unclear. We conducted plaque reduction neutralization test (PRNT) against BN.1 in a prospective cohort (14 patients and 30 specimens). BN.1 PRNT was conducted for one- and three-months after tixagevimab/cilgavimab administration and the average PRNT ND₅₀ of each point was lower than the positive cut-off value of 20 (12.9 ± 4.5 and 13.2 ± 4.2, respectively, P = 0.825). In the paired analyses, tixagevimab/cilgavimab-administered sera could not actively neutralize BN.1 (PRNT ND₅₀ 11.5 ± 2.9, P = 0.001), compared with the reserved activity against BA.5 (ND₅₀ 310.5 ± 180.4). Unlike virus-like particle assay, tixagevimab/cilgavimab was not active against BN.1 in neutralizing assay, and would not be effective in the present predominance of BA.2.75 sublineages.

Jeong IO, et al. J Korean Surg Soc. 2009 Dec;77(6):423-428. http://dx.doi.org/10.4174/jkss.2009.77.6.423

Hypervirulent Klebsiella pneumoniae (hvKp) was initially reported predominantly in East Asia and has emerged as a major community-acquired pathogen. In recent years, hvKp has also been recognized a...

Background: Hypervirulent Klebsiella pneumoniae (hvKP) bloodstream infections (BSIs) have traditionally been associated with favorable outcomes. However, with increasing emergence of antimicrobial resistance, clinical impact of hvKP is evolving. We aimed to identify clinical and microbiological factors, including virulence factors, associated with 30-day mortality in hvKP BSIs. Methods: We retrospectively analyzed 575 patients with Klebsiella pneumoniae (KP) BSIs at Keimyung University Dongsan Hospital from January 2014 to December 2023. hvKP was defined by the presence of both rmpA and iutA genes. Clinical characteristics, antimicrobial resistance, virulence factors were compared between the survivors and non-survivors based on 30-day mortality outcomes. Multivariate logistic regression was used to identify independent risk factors for 30-day mortality. Results: Among 575 KP BSIs, 236 (41.0%) were identified as hvKP. In hvKP BSIs, while liver abscess was the predominant source, a notable proportion arose from urinary tract and respiratory infections (30.1% vs. 19.5%, 16.1%). Among hvKP patients, respiratory infection was strongly associated with poor outcomes, with a 30-day mortality of approximately 57.8%. Antimicrobial resistance rates, including carbapenem resistance, did not significantly differ between survivors and non-survivors, though carbapenem-resistant hvKP (3.0%) was noted. K1 serotype and magA gene were associated with survival, whereas K57 serotype was linked to higher mortality. In multivariate analysis, respiratory infection, septic shock, corticosteroid use, and higher Pitt bacteremia score were identified as independent risk factors for 30-day mortality. Conclusion: hvKP BSIs do not necessarily result in better outcomes compared to classical KP. Respiratory infection emerged as a key risk factor for mortality, emphasizing the need for aggressive early management. While antimicrobial resistance was not directly associated with mortality, the emergence of carbapenem-resistant hvKP warrants attention. Capsular serotype analysis revealed that K1 correlated with better outcomes, while K57 was linked to worse prognosis. hvKP BSIs require vigilant management due to their severe clinical presentations and emerging antimicrobial resistance. Disclosures: All Authors: No reported disclosures