Infections caused by gram-negative organisms are a global concern [1,2]. Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas aeruginosa are major pathogens that can cause healthcare-associated infections, especially if the organisms are carbapenem resistant [3,4]. P. aeruginosa is an opportunistic pathogen that can cause severe infections, such as respiratory tract infections, sepsis, and urinary tract infections, particularly in immunocompromised patients. Moreover, it is an important nosocomial pathogen [5]. In Korea, there have been several reports of metallo-β-lactamase (MBL)-producing P. aeruginosa, including those that produce Verona integron-encoded metallo-β-lactamase (VIM) and active-on-imipenem (IMP) [6], but reports on New Delhi metallo-β-lactamase 1 (NDM-1) are rare. It is important to detect MBL-producing organisms early because these organisms have high mortality rates once they cause infection. Here, we report a case of NDM-1-carrying P. aeruginosa isolated from a clinical specimen in Korea.

An 82-year-old man was transferred from a long-term care facility in November after 1 day of dyspnea. He was discharged from our hospital 8 days ago after 8 months of admission. He presented with dyspnea and low blood pressure. Upon arrival, the blood pressure was 103/71 mmHg, and pulse rate was 119 beats/min. Initial laboratory investigations showed a leukocyte count of 11,960 cells/µL with a dominant neutrophil count and normal platelet count of 37×10⁴/µL. Serum blood urea nitrogen and creatinine levels were elevated to 29.3 and 1.30 mg/dL, respectively, and the estimated glomerular filtration rate was 52.8 mL/min/1.73 m². Moreover, lactic acid and C-reactive protein (CRP) levels were elevated to 8.8 and 17.4 mg/dL, respectively. Chest radiography and computed tomography revealed multifocal peribronchial mixed consolidations in both lungs, suggestive of pneumonia.

The patient was tested for carbapenemase genes before admission according to the infection control guidelines of our hospital. The Xpert Carba-R assay (Cepheid, Sunnyvale, CA, USA), which detects bla _KPC, bla _NDM, bla _VIM, bla _OXA-48, and bla _IMP-1 using real-time polymerase chain reaction (PCR), was performed to test the patient’s rectal swab. Since the test resulted in bla _NDM positivity, culture for carbapenem-resistant Enterobacteriaceae was performed as a follow-up test. After 24 h of incubation, no Enterobacteriaceae were found, and only non-fermentative gram-negative organisms were grown on MacConkey agar. P. aeruginosa was identified by Vitek MS (bioMérieux, Marcy-l’Étoile, France) and tested for antimicrobial susceptibility by Vitek 2 (bioMérieux, Marcy-l’Étoile, France). This isolate was resistant to carbapenems, cephalosporins, aminoglycosides, and quinolones. The modified Hodge test results were weakly positive. Sequencing for detecting bla _NDM was conducted using the primers and PCR conditions used in a previous study [7]. It yielded a 100.0% match with bla _NDM-1 (GenBank accession number HQ652608.1).

Pneumonia was treated with meropenem for 8 days. On the eighth day of hospitalization, laboratory tests showed that leukocyte and creatinine levels normalized to 7930 cells/µL and 1.0 mg/dL, respectively, and the serum CRP level decreased to 1.0 mg/dL. The patient was discharged from our hospital to a long-term care facility.

Since the first discovery of NDM-1-producing P. aeruginosa from Serbia in 2011 [8], it has been isolated mostly in Asia, Europe, and Africa [9-28] (Table 1). ST235 was the only sequence type identified in all previously isolated NDM-1-producing P. aeruginosa strains. A significant number of NDM-1-producing Pseudomonas species have been isolated in West Asian countries, which are known as NDM-1 endemic regions. One study in India investigated 290 clinically isolated carbapenem-resistant P. aeruginosa (CRPA), and 16 (6.6%) were NDM- 1 positive [17]. In Iran, one study in 2020 reported that 12.3% (29/236) of CRPA were found to be positive for bla _NDM-1, which highlights the importance of bla _NDM-1 screening in endemic areas, including Iran [12].

Korean studies on MBL-producing P. aeruginosa reported that VIM and IMP were the main MBL types contained in CRPA [6,9,29]. In 2015, one study reported that 17% (17/100) and 4% (4/100) of CRPA carried bla _IMP-6 and bla _VIM-2, respectively [9]. In 2019, among 345 carbapenem-resistant Pseudomonas species isolated from clinical specimens, 28 carried bla _VIM-2 and 23 carried bla _IMP-6, and there were no bla _NDM-1-positive isolates [6]. Furthermore, Hong et al. analyzed 183 CRPA isolates and found that 8.74% (16/184) harbored the bla _NDM-1 gene and exhibited high-level resistance to many antibiotics [30].

The current Korean antimicrobial resistance surveillance system covers the mandatory reporting of carbapenem-resistant Enterobacteriaceae [31]. The remaining gram-negative organisms, such as A. baumannii and P. aeruginosa, are not included in the mandatory reporting list; therefore, it is difficult to accurately track and manage infections caused by these organisms with antimicrobial resistance genes. However, it should be considered that bla _NDM can be transferred to different species within hospitals through horizontal spread, including plasmid-mediated spread [16,32]. This indicates that bla _NDM in P. aeruginosa can be transferred to Enterobacteriaceae that can spread in the absence of infection control practice. The World Health Organization listed CRPA on the “critical” groups among priority pathogens for antibiotics [33]. We have to monitor and manage gram-negative organisms more actively, not only Enterobacteriaceae but also A. baumannii and P. aeruginosa, which are highly ranked antibiotic-resistant bacteria [33]. Although NDM-producing organisms are mainly endemic in Middle Eastern countries, NDM-1-producing Pseudomonas species were first reported in China in 2020 [34]. Similar to the East Asian region, it is necessary to strengthen the surveillance of carbapenemase genes, including bla _NDM, in Korea.

Experts working in clinical microbiology departments should monitor multidrug resistance in other gram-negative bacteria, not only in Enterobacteriaceae. Although the risks and benefits should be considered, it is necessary to pay attention when CRPA is isolated, and it will also be necessary to consider periodic monitoring, even if not all samples.

The study was approved by the Institutional Review Board of Inje University Ilsan Paik Hospital (IRB number: ISPAIK 2021-05-025), and the requirement for written informed consent was waived.