Outbreak of High-Risk Clone ST323 Klebsiella pneumoniae Resistant to Ceftazidime–Avibactam Due to Acquisition of blaVEB-25 and to Cefiderocol Due to Mutated fiu Gene
Abstract
:1. Introduction
2. Results
2.1. Antibiotic Susceptibility Testing and Molecular Investigation of the Isolates
2.2. Epidemiologic Investigation of the Outbreak
3. Discussion
4. Materials and Methods
4.1. Detection of the Outbreak
4.2. Bacterial Isolates
4.3. Susceptibility Testing
4.4. DNA Extraction, Genome Sequencing, and Data Analysis
4.5. Transferability of blaVEB-25 Genes
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Patient (No., Sex, Age) | 1 | 2 | 3 | 4 | 5 | Laboratory Strain | ||||
---|---|---|---|---|---|---|---|---|---|---|
Male | Female | Male | Male | Male | ||||||
75 | 71 | 46 | 79 | 77 | ||||||
Isolate | 1-R.2 | 1-S.7 | 2-R.1 | 3-R.5 | 3-BL.6 | 4-R.8 | 4-BS.3 | 5-R.4 | TOP10/pl-VEB-25 * | TOP10 |
Source | Rectal | Sputum | Rectal | Rectal | Blood | Rectal | Bronchial secretions | Rectal | Transformant | Laboratory strain |
Day of isolation | 27 December 2023 | 9 January 2024 | 2 January 2024 | 2 January 2024 | 22 January 2024 | 22 January 2024 | 10 January 2024 | 22 January 2024 | - | - |
MLST-type | ST323 | ST323 | ST323 | ST323 | ST323 | ST323 | ST323 | ST323 | ND | ND |
KPC-type | KPC-2 | KPC-2 | KPC-2 | KPC-2 | KPC-2 | KPC-2 | KPC-2 | KPC-2 | None | None |
VEB-type | VEB-25 | VEB-25 | VEB-25 | VEB-25 | VEB-25 | VEB-25 | VEB-25 | VEB-25 | VEB-25 | None |
Antibiotics tested | in mg/L | |||||||||
Penicillins | ||||||||||
Amoxicillin/ Clavulanate | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | ≤4 |
Ampicillin/ Sulbactam | >16 | >16 | >16 | >16 | >16 | >16 | >16 | >16 | >16 | 4 |
Piperacillin/ Tazobactam | >64 | >64 | >64 | >64 | >64 | >64 | >64 | >64 | 64 | ≤4 |
Cephalosporins | ||||||||||
Cefuroxime | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | 4 |
Cefoxitin | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | 8 | 8 |
Cefotaxime | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | 32 | ≤0.25 |
Ceftazidime | >256 | >256 | >256 | >256 | >256 | >256 | >256 | >256 | >256 | 0.25 |
Ceft/avi | >256 | >256 | >256 | >256 | >256 | >256 | >256 | >256 | >256 | 0.25 |
Ceftriaxone | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | ≤0.25 |
Ceft/taz | >16 | >16 | >16 | >16 | >16 | >16 | >16 | >16 | >16 | ≤0.25 |
Cefepime | >16 | >16 | >16 | >16 | >16 | >16 | >16 | >16 | 8 | ≤0.12 |
Cefiderocol | 32 | 32 | 32 | 32 | 32 | 32 | 32 | 32 | 2 | 0.016 |
Monobactams | ||||||||||
Aztreonam | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | ≤1 |
Aztreonam/Avibactam ** | R | R | R | R | R | R | R | R | R | S |
Carbapenems | ||||||||||
Ertapenem | >4 | >4 | >4 | >4 | >4 | >4 | >4 | >4 | ≤0.12 | ≤0.12 |
Imipenem | >8 | >8 | >8 | >8 | >8 | >8 | >8 | >8 | ≤0.25 | ≤0.25 |
Imipenem/ Relebactam | 0.5 | 0.5 | 0.5 | 0.5 | 1 | 0.5 | 1 | 0.5 | 0.5 | 0.25 |
Meropenem | >8 | >8 | >8 | 16 | 16 | >32 | >32 | >8 | 0.032 | 0.032 |
Meropenem/ Vaborbactam | 0.25 | 0.25 | 0.25 | 0.125 | 0.125 | 0.25 | 0.25 | 0.25 | 0.032 | 0.032 |
Aminoglycosides | ||||||||||
Amikacin | >256 | >256 | >256 | >256 | >256 | >256 | >256 | >256 | >256 | 2 |
Gentamicin | >256 | >256 | >256 | >256 | >256 | >256 | >256 | >256 | >256 | 0.5 |
Tobramycin | >8 | >8 | >8 | >8 | >8 | >8 | >8 | >8 | >8 | ≤1 |
Tetracyclines | ||||||||||
Tigecycline | >4 | >4 | >4 | >4 | >4 | >4 | >4 | >4 | 0.25 | 0.25 |
Miscellaneous agents | ||||||||||
Fosfomycin | 64 | 64 | 64 | 64 | 64 | 64 | 64 | 64 | 16 | 0.25 |
Colistin | 0.5 | 0.5 | 0.5 | 0.5 | 0.5 | >4/2 | >4/2 | 0.5 | ≤0.25 | ≤0.25 |
Trimethoprim/ Sulphamethoxazole | >160 | >160 | >160 | >160 | >160 | >160 | >160 | >160 | >160 | ≤20 |
Chloramphenicol | 128 | 128 | 64 | 128 | 128 | 64 | 64 | 64 | 16 | 2 |
Isolate | 4-BS.3 | TOP10/pl3 | 3-BL.6 | TOP10/pl6 |
---|---|---|---|---|
Source | Bronchial secretions | Transformant | Blood | Transformant |
Day of isolation | 10 January 2024 | - | 22 January 2024 | - |
Acquired resistance genes | ||||
β-lactamase genes | blaSHV-11, blaKPC-2, blaVEB-25, blaOXA-10, blaTEM-1B | blaKPC-2, blaVEB-25, blaOXA-10, blaTEM-1B | blaSHV-11, blaKPC-2, blaVEB-25, blaOXA-10, blaTEM-1B | blaKPC-2, blaVEB-25, blaOXA-10, blaTEM-1B |
Aminoglycoside-modifying enzyme-coding genes | aph(6)-Id, aph(3″)-Ib, aadA1, ant(2″)-Ia, rmtB | aph(6)-Id, aph(3″)-Ib, aadA1, ant(2″)-Ia, rmtB | aph(6)-Id, aph(3″)-Ib, aadA1, ant(2″)-Ia, aph(3′)-Ia, rmtB | aph(6)-Id, aph(3″)-Ib, aadA1, ant(2″)-Ia, aph(3′)-Ia, rmtB |
Quinolones | qnrS1 | qnrS1 | qnrS1 | qnrS1 |
Tetracycline | tet(A), tet(G) | tet(A), tet(G) | tet(A), tet(G) | tet(A), tet(G) |
Fosfomycin | fosA7, fosA6 | fosA7, fosA6 | ||
Trimethoprim | dfrA23 | dfrA23 | dfrA23 | dfrA23 |
Phenicol | cmlA5 | cmlA5 | cmlA5 | cmlA5 |
Sulfonamide | sul1, sul2 | sul1, sul2 | sul1, sul2 | sul1, sul2 |
Plasmid replicons | ||||
Plasmid replicons | Col440II, ColRNAI, IncC, IncFIB(pQil), IncFII(K), IncFII(pKP91), IncR, repB(R1701) | IncC | Col440II, ColRNAI, IncC, IncFIB(pQil), IncFII(K), IncFII(pKP91), IncR, repB(R1701) | IncC |
A/A Patient | Gender, Age | Charlson Comorbidity Index | Cause of ICU Admission | Date of Colonization by CZA-R KPC-KP Isolate | Antibiotics Prescribed Prior to Colonization | Prior Carbapenem Use (Days) | Type/Date of Infection for BLBLI Administration | Antimicrobial Treatment | Previous Treatment with BLBLI | Treatment Outcome | 28-Day Outcome |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | Male, 75 | 9 | Respiratory failure | 27 December 2024 | CRO, TZP, MFX | No | VAP by CZA-R KPC-KP/9 January 2024 | MER/VAB | No | Reduction of ventilation support, transfer to rehabilitation center | Death on 14th day after infection |
2 | Female, 71 | 7 | Brain injury/Subdural hematoma | 2 January 2024 | VAN, TZP, CRO | Yes (7) | CRBSI by KPC-KP/9 January 2024 | MER/VAB | No | Sterile blood cultures, removal of central line | Alive |
3 | Male, 46 | 1 | Ischemic stroke | 2 January 2024 | CRO, TZP, VAN, MEM | Yes (3) | CRBSI by CZA-R KPC-KP/22 January 2024 | IMI/REL | No | Sterile blood cultures, removal of central line | Alive |
4 | Male, 79 | 8 | Respiratory failure | 8 January 2024 | TZP, VAN, MEM | Yes (13) | VAP by CZA-R KPC-KP/10 January 2024 | MER/VAB | No | Complicated with super infection with CRAB | Death on 10th day after infection |
5 | Male, 77 | 9 | Chest injury | 22 January 2024 | LZD, PZT, MEM | Yes (3) | - | - | No | - | Death occurred within 24 h after BSI with KPC-K. pneumoniae susceptible to CZA |
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Galani, I.; Karaiskos, I.; Souli, M.; Papoutsaki, V.; Gkoufa, A.; Antoniadou, A.; Giamarellou, H. Outbreak of High-Risk Clone ST323 Klebsiella pneumoniae Resistant to Ceftazidime–Avibactam Due to Acquisition of blaVEB-25 and to Cefiderocol Due to Mutated fiu Gene. Antibiotics 2025, 14, 223. https://doi.org/10.3390/antibiotics14030223
Galani I, Karaiskos I, Souli M, Papoutsaki V, Gkoufa A, Antoniadou A, Giamarellou H. Outbreak of High-Risk Clone ST323 Klebsiella pneumoniae Resistant to Ceftazidime–Avibactam Due to Acquisition of blaVEB-25 and to Cefiderocol Due to Mutated fiu Gene. Antibiotics. 2025; 14(3):223. https://doi.org/10.3390/antibiotics14030223
Chicago/Turabian StyleGalani, Irene, Ilias Karaiskos, Maria Souli, Vassiliki Papoutsaki, Aikaterini Gkoufa, Anastasia Antoniadou, and Helen Giamarellou. 2025. "Outbreak of High-Risk Clone ST323 Klebsiella pneumoniae Resistant to Ceftazidime–Avibactam Due to Acquisition of blaVEB-25 and to Cefiderocol Due to Mutated fiu Gene" Antibiotics 14, no. 3: 223. https://doi.org/10.3390/antibiotics14030223
APA StyleGalani, I., Karaiskos, I., Souli, M., Papoutsaki, V., Gkoufa, A., Antoniadou, A., & Giamarellou, H. (2025). Outbreak of High-Risk Clone ST323 Klebsiella pneumoniae Resistant to Ceftazidime–Avibactam Due to Acquisition of blaVEB-25 and to Cefiderocol Due to Mutated fiu Gene. Antibiotics, 14(3), 223. https://doi.org/10.3390/antibiotics14030223