Jinyoung Yang

Background: Non-carbapenemase-producing Enterobacterales with isolated ertapenem resistance (ETP-mono-R) may represent an early stage in the evolution toward broader carbapenem resistance, but whether further resistance induction occurs and its underlying mechanisms remain poorly understood. Methods: Resistance induction was assessed in 3 Escherichia coli, 4 Klebsiella pneumoniae, and 2 Enterobacter cloacae isolates through serial exposure to subinhibitory concentrations of meropenem (MEM), imipenem, ceftazidime-avibactam, or colistin (COL), with antibiotic-free passaging for reversion. Resistance induction under MEM + COL was evaluated separately. Whole-genome sequencing, targeted porin-gene Sanger sequencing, and transcriptional analysis were used to characterize resistance mechanisms across induction stages. Results: Subinhibitory MEM exposure rapidly selected for carbapenem resistance through porin-associated alterations in a species-specific manner. E. coli accumulated loop-region mutations in ompC, while K. pneumoniae predominantly developed disruptive mutations in ompK36, both accompanied by marked transcriptional downregulation. In contrast, E. cloacae retained wild-type porins but showed increased MEM MICs, suggesting a non-porin-mediated mechanism. Subinhibitory exposure to COL alone rapidly induced colistin resistance but was associated with decreased carbapenem MICs. Co-exposure to MEM and COL significantly delayed resistance development and reduced MIC increases (all P < .05). Targeted sequencing of 26 non-carbapenemase-producing K. pneumoniae isolates resistant to all carbapenems revealed widespread disruptive ompK36 alterations, including the S337P substitution identified experimentally, consistent with a shared permeability-loss pathway. Conclusions: In ETP-mono-R Enterobacterales, subinhibitory carbapenem exposure promotes carbapenem resistance, with porin-associated mechanisms predominating in E. coli and K. pneumoniae. Co-exposure to COL attenuates this process, suggesting a potential strategy to delay the emergence of carbapenem resistance.

Jinyoung Yang, M.D., Ph.D., Jae-Hoon Ko, M.D., Ph.D., Sanghoon Lee, M.D., Ph.D., Dong Hyun Sinn, M.D., Ph.D., Jongman Kim, M.D., Ph.D., Kyeongman Jeon, M.D., Ph.D., Jae Berm Park, M.D., Ph.D., Jin-Oh Choi, M.D., Ph.D., Wooseong Huh, M.D., Ph.D., Yae-Jean Kim, M.D., Ph.D., Eun-Suk Kang, M.D., Ph.D., Seung Hoo Lee, M.D., Min Seo Kang, M.D., M.S., Kyungmin Huh, M.D., Ph.D., Sun Young Cho, M.D., Ph.D., Cheol-In Kang, M.D., Ph.D., Doo Ryeon Chung, M.D., Ph.D., and Kyong Ran Peck, M.D., Ph.D.. Ann Lab Med -0001;0:. https://doi.org/10.3343/alm.2025.0459

Seung Hoo Lee, M.D., Tae Yeul Kim, M.D., Jinyoung Yang, M.D., Kyungmin Huh, M.D., Sun Young Cho, M.D., Cheol-In Kang, M.D., Doo Ryeon Chung, M.D., Kyong Ran Peck, M.D., Sunghae Park, M.D., Kyo Won Lee, M.D., Jae Berm Park, M.D., Namkee Oh, M.D., Jinsoo Rhu, M.D., Gyu-Seong Choi, M.D., Jongman Kim, M.D., Wooseong Huh, M.D., Hee Jae Huh, M.D., Eun-Suk Kang, M.D., and Jae-Hoon Ko, M.D.. Ann Lab Med -0001;0:. https://doi.org/10.3343/alm.2025.0376

Backgrounds: Rifabutin is often used instead of rifampin to treat tuberculosis (TB) in solid organ transplant recipients (SOTRs) due to fewer drug interactions with immunosuppressants. However, data on its efficacy are limited. Methods: A retrospective, case-control study was conducted at a tertiary care center in Korea. SOTRs aged ≥18 years with culture-positive pulmonary TB treated with isoniazid and rifabutin for >80% of the treatment duration were included. Those with rifampin-resistant TB or who discontinued immunosuppressants prior to TB diagnosis were excluded. Each SOTR was matched to three non-SOTR controls treated with rifampin-based regimens. The primary outcome was treatment completion without early relapse. Logistic regression with and without overlap weighting was used for analysis. Results: Forty SOTRs and 120 non-SOTRs were analyzed. Baseline TB severity markers (cavitary lesions, smear/culture-positivity) were comparable, but extrapulmonary TB and isoniazid resistance were more common in SOTRs. Treatment duration was longer in SOTRs (median 272 vs 187 days, P < .001). The primary outcome occurred in 90% of SOTRs and 96.7% of controls (P = .108). Treatment completion was lower in SOTRs (92.5% vs 100%, P = .015). No significant differences were observed in TB recurrence or 1-year mortality. TB-attributable deaths were absent in both groups. After overlap weighting, no significant difference was found in the primary outcome (aOR 0.36; 95% confidence interval, 0.01–10.41). Allograft rejection and failure occurred in 10% and 12.5% of SOTRs, respectively. Conclusions: Rifabutin-based therapy in SOTRs achieved treatment outcomes comparable to rifampin-based regimens in non-SOTRs, supporting its use in this population.

Microbiological diagnosis of pleural infection is often hindered by the low sensitivity of conventional culture. The automated blood culture system (ABCS) has been shown to improve diagnostic sensitivity for the culture of non-blood specimens. This study examined the additional diagnostic benefit of ABCS against conventional bacterial culture in patients who underwent thoracentesis or percutaneous drainage. Non-duplicate patients whose pleural fluid samples were tested using both conventional culture and ABCS (BACT/ALERT 3D and VIRTUO, bioMerieux) from 2001 through 2021 were included. Cases were excluded if only contaminants such as coagulase-negative staphylococci, Corynebacterium species, and Bacillus species were identified. Data on culture results, demographics, and laboratory tests were collected. Of the 9,020 patients, 632 patients had positive results in ABCS after excluding those considered contaminants ( n = 180) or those positive only in conventional culture ( n = 5). Conventional culture was positive in 302 (47.8%) patients, whereas 330 (52.2%) patients had isolates only from ABCS. Patients with positive results from ABCS alone had lower pleural fluid lactate dehydrogenase and serum C-reactive protein (CRP) and higher pleural fluid glucose and protein. Among organisms isolated from ABCS alone, viridans group streptococci , Staphylococcus aureus, and Klebsiella spp. were the most common organisms identified. Higher pleural fluid glucose and blood white blood cells and lower CRP were significant factors associated with exclusive ABCS positivity. More than half of the patients whose pleural fluid cultures were positive using ABCS had a negative result on conventional culture. Our results suggest that ABCS might enhance the microbiologic diagnosis of pleural infection. IMPORTANCE: This study demonstrated that an automated blood culture system (ABCS) has superior sensitivity in pleural infections compared with conventional culture. By comparing both methods in over 9,000 patients, researchers found that ABCS detected bacteria in approximately twice as many cases as conventional culture, especially in patients with a high probability of pleural infection. The findings suggest that ABCS can be a valuable tool in improving the accuracy of diagnosing pleural infections, which could lead to better treatment decisions and patient outcomes.

Carbapenem-resistant Enterobacter cloacae complex (CR-ECC), which is rapidly increasing as the cause of nosocomial infections, has limited treatment options. The aim of this study is to investigate the microbiological and clinical traits and molecular epidemiology of isolates of CR-ECC and provide guidance for antibiotic selection in clinical practice. Clinical CR-ECC isolates (ertapenem MIC ≥ 2 mg/L) were collected from 2021 to 2022. Species identification was performed using hsp60 gene analysis, and antibiotic susceptibility tests were conducted by broth microdilution. The clinical characteristics of patients with CR-ECC isolates were retrospectively analyzed. Among the 108 CR-ECC isolates, 25 (23.2%) were non-susceptible to colistin, with colistin susceptibility being higher in Enterobacter hormaechei compared to non- E . hormaechei isolates ( P < 0.0001). Of the 108 CR-ECC isolates, 9 (8.3%) produced carbapenemases, and only 6 of the 22 colistin-resistant CR-ECC isolates (27.3%) harbored the mcr gene. A total of 73 sequence types (STs), including 28 newly identified STs, were detected, demonstrating significant clonal diversity. The most common ST was ST74, known for its high prevalence and association with carbapenem resistance, with 77.8% identified as E. hormaechei subsp. hoffmannii. E. hormaechei was more common in the colistin-susceptible group than in the non-susceptible group (88.0% vs 37.5%, P < 0.0001), and E. hormaechei was the only protective factor for colistin resistance (HR 0.089, CI 0.030–0.261, P < 0.001). Although colistin resistance of CR-ECC is high, colistin could be administered safely to E. hormaechei . It is imperative to maintain ongoing surveillance and to further research on CR-ECC. IMPORTANCE: Although new antibiotics are being developed, there are still limited options for treating carbapenem-resistant Enterobacter cloacae complex (CR-ECC) in regions where their use is restricted. The resistance level to one of these options, colistin, was investigated using bacteria isolated from clinical samples. In clinical practice, colistin is frequently administered empirically without susceptibility testing. However, this study suggests that colistin can be safely administered to certain species such as Enterobacter hormaechei within the CR-ECC.

High concentration of mold spores in inhaled air is an important risk factor for invasive mold infections. COVID‐19 (coronavirus disease 2019)‐associated pulmonary aspergillosis (CAPA) is a serious complication of severe COVID‐19. To investigate the mold distribution in negative‐pressure isolation wards and its potential association with CAPA incidence, we conducted microbiological air sampling and retrospectively analyzed CAPA cases in a tertiary care hospital in Korea during the COVID‐19 pandemic. Air sampling was conducted in January 2022 at multiple sites in four negative‐pressure isolation wards designated for managing severe COVID‐19 patients. A portable microbial air sampler (MAS‐100 NT) was used for air sampling, and Tryptic Soy Agar plates were incubated to identify mold isolates at the genus level. CAPA cases (January 2021–June 2023) were defined by antifungal treatment, mycological evidence (serum galactomannan index > 0.5), and radiological findings. Immunomodulator use, including dexamethasone and tocilizumab, was analyzed to identify clinical risk factors influencing CAPA incidence. Among the isolated molds, Aspergillus (86.7%) was the most prevalent, followed by Penicillium (53.3%), Mucorales (20%), and Paecilomyces (13.3%). Mold concentrations were highest in areas adjacent to a construction site. Intervention procedures, including installing air purifiers and reinforcing seals between the adjoining construction site and isolation ward, effectively reduced mold concentrations and paralleled a decline in CAPA incidence. While increased foot traffic after the relaxation of COVID‐19 restriction measures led to a rise in spore concentration, the incidence of CAPA did not increase, likely due to the decreased use of immunomodulators such as corticosteroids and tocilizumab. Construction‐related mold spore increases can be mitigated with appropriate interventions, and pedestrian traffic near isolation wards may need regulation. Monitoring and mitigating environmental mold contamination are crucial to preventing opportunistic respiratory mold infections in negative‐pressure isolation wards and should be interpreted in conjunction with clinical risk factors.

Shin A, et al. J Korean Med Sci. 2024 Nov;40:e29. https://doi.org/10.3346/jkms.2025.40.e29