Table I
Demographic data and characteristics of the fourteen patients with K. pneumoniae co-producing KPC-2, OXA-48, VIM-1 and CTX-M-15 during the outbreak.
| Patient ID/Isolate no. | Age (years)/sex | Hospital ward(s) | Date of isolation | Type of specimen | Status (type) of colonization/infection | Duration of hospitalization (days) | Underlying conditions | Antimicrobial used prior to isolation of carbapenemase producer(s) | Antimicrobial used as treatment for infections | Outcome Alive/Dead |
|---|---|---|---|---|---|---|---|---|---|---|
| 3 | 74/M | OAIT | 08/03/2018 | Rectal swab | Colonization | 03/01-14/04/2018 (102 days) | Abdominal Aortic Aneurysm (AAA) | Ciprofloxacin + Gentamycin + Itraconazole | Metronidazole | Dead |
| 6965 | 60/F | OAIT | 28/02/2018 | Rectal swab | Colonization | 08/02-01/04/2018 (53 days) | Tuberculosis, Chronic Obstructive Pulmonary Disease (COPD) | Colistin + Voriconazole | – | Dead |
| 6976/1 6976/2 | 45/M | OAIT | 01/03/2018 12/03/2018 | Rectal swab Blood | Colonization Bacteremia | 21/02-29/03/2018 (37 days) | Guillain-Barré Syndrome (GBS) | Colistin + Linezolid | Ampicillin/sulbactam + Amikacin | Alive |
| 1 | 67/F | OAIT | 07/03/2018 | Rectal swab | Colonization | 02/03-29/06/2018 (112 days) | COPD, diabetes, hypertension | Ceftriaxone + Levofloxacin | – | Dead |
| 6968 (index case) | 63/M | NR | 28/02/2018 | Rectal swab | Colonization | 16/02-31/03/2018 (44 days) | Hypertension, atherosclerosis | Ceftriaxone + Metronidazole | – | Alive |
| 2 | 69/M | NR | 07/03/2018 | Rectal swab | Colonization | 23/02-28/03/2018 (34 days) | Post-stroke conditions | – | – | Alive |
| 4 | 43/M | NR | 08/03/2018 | Rectal swab | Colonization | 26/02-12/03/2018 (15 days) | Hypertension | Ceftriaxone + Metronidazole | – | Dead |
| 154/25428 | 61/M | NR | 30/07/2018 | Rectal swab | Colonization | 04/07-06/08/2018 (34 days) | Stroke | – | – | Dead |
| 7/25804 | 70/M | NR | 04/08/2018 | Rectal swab | Colonization | 25/07-02/08/2018 (9 days) | Stroke | Amoxicillin/clavulanic acid | – | Alive |
| 11/25808 | 50/F | NR | 04/08/2018 | Rectal swab | Colonization | 23/07-03/08/2018 (12 days) | Stroke | – | – | Alive |
| 13/25810 | 77/M | NR | 04/08/2018 | Rectal swab | Colonization | 22/07-09/08/2018 (19 days) | Hypertension, ischemic heart disease | Amoxicillin/clavulanic acid | – | Alive |
| 6 | 70/F | REU | 09/03/2018 | Rectal swab | Colonization | 26/02-14/03/2018 (17 days) | Diabetes, metastatic lung cancer | – | – | Alive |
| 7 | 78/F | REU | 09/03/2018 | Rectal swab | Colonization | 27/02-16/03/2018(18 days) | Rheumatoid Arthritis (RA), hemorrhagic diathesis, coronary disease, peptic ulcer disease, hypertension, atherosclerosis, gout | Imipenem | Vancomycin | Alive |
| 5 | 90/F | REU | 08/03/2018 | Rectal swab | Colonization | 03.03-17.03.2018 (14 days) | Atherosclerosis, acute arterial thrombosis of the lower extremity | Meropenem + Amikacin | – | Alive |

Fig. 1.
Gantt diagram depicting a timeline of patients’ admissions in relationship with the three wards and the length of stay in each ward. Epidemic curve based on the number of K. pneumoniae isolated in the time frame of the study.
Abbreviations: OAIT-Department of Anaesthesia and Intensive Care, NR-Department of Neurology with the Stroke Subdepartment, REU-Department of Internal Medicine and Rheumatology.
Table II
Antimicrobial resistance profiles of the studied K. pneumoniae isolates.
| Patient ID/Isolate no. | 3 | 6965 | 6976/1 | 6976/2 | 1 | 6968 | 2 | 4 | 154/25428 | 7/25804 | 11/25808 | 13/25810 | 6 | 7 | 5 | ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Antibiotics: | MIC (pg/ml) | R/I/S | MIC (pg/ml) | R/I/S | MIC (pg/ml) | R/I/S | MIC (pg/ml) | R/I/S | MIC (pg/ml) | R/I/S | MIC (pg/ml) | R/I/S | MIC (pg/ml) | R/I/S | MIC (pg/ml) | R/I/S | MIC (pg/ml) | R/I/S | MIC (pg/ml) | R/I/S | MIC (pg/ml) | R/I/S | MIC (pg/ml) | R/I/S | MIC (pg/ml) | R/I/S | MIC (pg/ml) | R/I/S | MIC (pg/ml) | R/I/S | |
| Penicillins | Amoxicillin/Clavulanic acid | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R |
| Ampicillin | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | |
| Cephalosporins | Cefaclor | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R |
| Cefuroxime | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | |
| Cefotaxime | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | |
| Cefotaxime/Cefotaxime + clavulanic acid | >16/>1 | R | >16/>1 | R | >16/>1 | R | >16/>1 | R | >16/>1 | R | >16/>1 | R | >16/>1 | R | >16/>1 | R | >16/>1 | R | >16/>1 | R | >16/>1 | R | >16/>1 | R | >16/>1 | R | >16/>1 | R | >16/>1 | R | |
| Ceftazidime | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | |
| Ceftazidime/Ceftazidime + clavulanic acid | >34/>4 | R | >34/>4 | R | >34/>4 | R | >34/>4 | R | >34/>4 | R | >34/>4 | R | 34/>4 | R | >34/>4 | R | >34/>4 | R | >34/>4 | R | >34/>4 | R | >34/>4 | R | >34/>4 | R | >34/>4 | R | >34/>4 | R | |
| Cefepime | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | |
| Carbapenems | Doripenem | >32 | R | 16 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R |
| Ertapenem | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | |
| Imipenem | >32 | R | >32 | R | 16 | R | 16 | R | >32 | R | >32 | R | >32 | R | >32 | R | >12 | R | 4 | S | 4 | S | 8 | I | >32 | R | >32 | R | >32 | R | |
| Meropenem | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | |
| Quinolone | Ciprofloxacin | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R |
| Aminoglycosides | Amikacin | 4 | S | 8 | S | 32 | R | 32 | R | 8 | S | 12 | R | 6 | S | 4 | S | 8 | S | 8 | S | 8 | S | 8 | S | 12 | R | 6 | S | 6 | S |
| Gentamycin | 64 | R | 64 | R | 64 | R | 64 | R | 64 | R | 64 | R | 64 | R | 64 | R | 64 | R | 64 | R | 64 | R | 64 | R | 64 | R | 64 | R | 64 | R | |
| Netylmycin | 128 | R | 4 | I | 64 | R | 64 | R | 128 | R | 32 | R | 16 | R | 16 | R | 12 | R | 16 | R | 16 | R | 16 | R | 32 | R | 16 | R | 16 | R | |
| Tobramycin | 64 | R | 64 | R | 32 | R | 32 | R | 64 | R | 64 | R | 64 | R | 64 | R | 32 | R | 64 | R | 64 | R | 64 | R | 64 | R | 64 | R | 64 | R | |
| Other | Aztreonam | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R |
| Colistin | 0.50 | S | 0.75 | S | 0.125 | S | 0.125 | S | 0.50 | S | 0.50 | S | 0.50 | S | 0.50 | S | 0.50 | S | 0.50 | S | 0.75 | S | 0.50 | S | 0.50 | S | 0.50 | S | 0.50 | S | |
| Tetracycline | 32 | R | 128 | R | 8 | R | 8 | R | 32 | R | 32 | R | 32 | R | 8 | R | >256 | R | >256 | R | >256 | R | >256 | R | 8 | R | 8 | R | 128 | R | |
| Tigecycline | 2 | R | 8 | R | 4 | R | 4 | R | 2 | R | 2 | R | 2 | R | 4 | R | 0.75 | R | 0.75 | R | 1.0 | R | 2 | R | 4 | R | 4 | R | 8 | R | |
| Trimethoprim/Sulfamethoxazole | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | >32 | R | |
| Fosfomycin | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | >256 | R | R>256 | R | >256 | R | >256 | R | >256 | R | >256 | R | |

Fig. 2.
Dendrogram of XbaI-digested genomic DNA from carbapenemase-co-producing K. pneumoniae isolates, additionally presenting the results of PCRs for genes encoding carbapenemases and other β-lactamase. PFGE settings: similarity coefficient, Dice; optimization, 1%; tolerance, 1%; clustering method, UPGMA.