Intestinal Infection of Multi-Resistant NDM-Producing K. pneumoniae in a Patient with NK/T Lymphoma – Case Study

Case Description

A 62-year-old man diagnosed with NK/T lymphoma was hospitalized in August 2021 in the hematology department for autologous stem cell transplantation. On the 3rd day post-procedure, he developed fever and diarrhea. Empirical antibiotic therapy with imipenem/cilastatin at a dose of 500 mg IV every 6 hours and teicoplanin at a dose of 400 mg IV every 12 hours was initiated. However, after 2 days of treatment, the patient remained febrile and had watery diarrhea. On the 5th day post-transplant, the initial combination of antibiotics was replaced with tigecycline at a dose of 100 mg IV every 12 hours and cefoperazone/sulbactam at a dose of 2 g every 8 hours. Due to the development of septic shock, the patient was transferred to the ICU on the 6th day post-transplant.

Here, the antibiotic therapy was changed once again. A combination of imipenem/cilastatin 500 mg IV every 4 hours and ceftazidime/avibactam (CAZ/AVI) at a dose of 2.5 g IV every 8 hours was administered. After 3 days of ICU hospitalization, Klebsiella pneumoniae was detected in both blood cultures and stool samples. The use of the CARBA5 immunological qualitative test confirmed the presence of a New Delhi metallo-beta-lactamase (NDM) producing variant of K. pneumoniae resistant to carbapenems. Based on this finding, a combination of CAZ/AVI 2.5 g IV every 8 hours with aztreonam (ATM) at a dose of 2 g IV every 8 hours was initiated. Shortly after starting this targeted antibiotic therapy, the patient's clinical condition significantly improved and the septical state receded.

Discussion

The presence of metallo-dependent beta-lactamase (MBL) NDM-1 enables bacteria to hydrolyze nearly all beta-lactam antibiotics. ATM belongs to a group of beta-lactam antibiotics that are active against MBL-producing microorganisms, but it is subject to hydrolysis by bacteria producing extended-spectrum beta-lactamases (ESBL). Avibactam can protect ATM from hydrolysis by class A and C beta-lactamases.

The bactericidal effect of the combination of CAZ/AVI with ATM was demonstrated by Marshall et al. on 17 of 21 enterobacteria isolates producing MBL. After 24 hours, the colony-forming units (CFUs) decreased by nearly 4log₁₀. In vitro, synergistic action of ATM and CAZ/AVI against 40 multi-resistant MBL and serine beta-lactamase producing strains of K. pneumoniae was demonstrated. The efficacy of this combination was also found using MIC test strips on 15 clinical isolates of NDM-producing K. pneumoniae. Further prospective studies highlighted significantly lower mortality rates in patients treated with a combination of antibiotics compared to those receiving monotherapy alone.

Several other case studies of successful treatment with the combination of ATM and CAZ/AVI have also been published. In one case, it involved a patient with aplastic anemia, agranulocytosis, and hematogenic sepsis following chemotherapy. Another case demonstrated the treatment of sepsis and successful intestinal decolonization in a patient with thrombotic thrombocytopenic purpura (TTP) complicated by a nosocomial SARS-CoV-2 infection.

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Sources: 
1. Liu S., Lin Q., Ouyang L et al. Successful treatment of ceftazidime/avibactam combined with aztreonam in the NDM-producing Klebsiella pneumoniae bloodstream and intestinal infections in an NK/T lymphoma patient with agranulocytopenia during autologous hematopoietic stem cell transplantation: a case report. Eur J Clin Microbiol Infect Dis 2022 Nov 12: 1–4, doi: 10.1007/s10096-022-04523-3.
2. Marshall S., Hujer A. Mm, Rojas L. J. et al. Can ceftazidime-avibactam and aztreonam overcome β-lactam resistance conferred by metallo-β-lactamases in enterobacteriaceae? Antimicrob Agents Chemother 2017; 61 (4): e02243-16, doi: 10.1128/AAC.02243-16.
3. Maraki S., Mavromanolaki V. E., Moraitis P. et al. Ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam in combination with aztreonam against multidrug-resistant, metallo-β-lactamase-producing Klebsiella pneumoniae. Eur J Clin Microbiol Infect Dis 2021; 40 (8): 1755–1759, doi: 10.1007/s10096-021-04197-3.
4. Bocanegra-Ibarias P., Camacho-Ortiz A., Garza-González E. et al. Aztreonam plus ceftazidime-avibactam as treatment of NDM-1-producing Klebsiella pneumoniae bacteraemia in a neutropenic patient: Last resort therapy? J Glob Antimicrob Resist 2020; 23: 417–419, doi: 10.1016/j.jgar.2020.10.019.
5. Perrotta F., Perrini M. P. Successful treatment of Klebsiella pneumoniae NDM sepsis and intestinal decolonization with ceftazidime/avibactam plus aztreonam combination in a patient with TTP complicated by SARS-CoV-2 nosocomial infection. Medicina (Kaunas) 2021; 57 (5): 424, doi: 10.3390/medicina57050424.