Table 1.
Characteristics of the matched cohort population
| Variables | Matched population (N = 122) | Cases and controlsa | ||
|---|---|---|---|---|
| Cases (N = 61) | Controls (N = 61) | P value | ||
| Gender male, n (%) | 84 (68.9) | 44 (72.1) | 40 (65.6) | 0.558 |
| Age, years, median (IQR) | 68.0 (57.0–78.0) | 67.0 (56.0–77.5) | 69.0 (58.5–79.0) | 0.603 |
| ICU, n (%) | 36 (29.5) | 18 (29.5) | 18 (29.5) | 1.0 |
| SARS-CoV-2 coinfection, n (%) | 9 (7.4) | 5 (8.2) | 4 (6.6) | 1.0 |
| CCI, median (IQR) | 6 (5–9) | 6 (4–9) | 6 (5–9) | 0.730 |
| CCI ≥ 3, n (%) | 106 (86.9) | 50 (82.0) | 56 (91.8) | 0.179 |
| Diabetes, n (%) | 31 (25.4) | 16 (26.2) | 15 (24.6) | 1.0 |
| Cerebral and/or cardiovascular disease, n (%) | 77 (63.1) | 34 (55.7) | 43 (70.5) | 0.133 |
| COPD, n (%) | 38 (31.1) | 20 (32.8) | 18 (29.5) | 0.845 |
| Chronic kidney disease, n (%) | 31 (25.4) | 15 (24.6) | 16 (26.2) | 1.0 |
| Pre-admission dialysis, n (%) | 4 (3.3) | 2 (3.3) | 2 (3.3) | 1.0 |
| Chronic liver disease, n (%) | 17 (13.9) | 10 (16.4) | 7 (11.5) | 0.602 |
| Cancer, n (%) | 41 (33.6) | 21 (34.4) | 20 (32.8) | 1.0 |
| Immunosuppression,bn (%) | 38 (31.1) | 23 (37.7) | 15 (24.6) | 0.171 |
| Solid organ transplant, n (%) | 13 (10.7) | 9 (14.8) | 4 (6.6) | 0.240 |
| Rectal KPC-Kp colonization, n (%) | 97 (79.5) | 50 (82.0) | 47 (77.0) | 0.654 |
| Serum lactate (mmol/L), median (IQR) | 2.2 (1.5–3.6) | 2.0 (1.4–3.5) | 2.4 (1.7–4.0) | 0.511 |
| C-reactive protein (mg/dL), median (IQR) | 10.2 (5.4–17.4) | 10.2 (5.6–18.1) | 10.5 (4.8–16.3) | 0.415 |
| Procalcitonin (ng/dL), median (IQR) | 4.5 (0.8–28.9) | 3.6 (0.8–28.1) | 4.8 (1.0–30.8) | 0.595 |
| Continuous renal replacement therapy, n (%) | 14 (11.5) | 7 (11.5) | 7 (11.5) | 1.0 |
| Hospital acquired Healthcare acquired |
101 (82.8) 21 (17.2) |
47 (77.0) 14 (23.0) |
54 (88.5) 7 (11.5) |
0.149 |
| Septic shock, n (%) | 25 (20.5) | 14 (23.0) | 11 (18.0) | 0.654 |
| Pitt score, median (IQR) | 2.0 (1.0–4.0) | 3.0 (2.0–4.0) | 2.0 (1.0–4.0) | 0.173 |
| ICS, median (IQR) | 6 (3–8) | 6 (3–8) | 6 (3–8) | 0.682 |
| ICS ≥ 8, n (%) | 39 (32.0) | 20 (32.8) | 19 (31.1) | 1.0 |
| Available FOF MIC | 75 (61.5) | 29 (47.5) | 46 (75.4) | 0.003 |
| Source of infection, n (%) | ||||
| Primary bacteraemia | 34 (27.9) | 17 (27.9) | 17 (27.9) | — |
| CLRBSI | 4 (3.3) | 2 (3.3) | 2 (3.3) | |
| Urinary tract | 36 (29.5) | 18 (29.5) | 18 (29.5) | |
| Intra-abdominal | 26 (21.3) | 13 (21.3) | 13 (21.3) | |
| Lower respiratory tract [including VAP] | 22 (18.0) [14 (63.6)] | 11 (18.0) [7 (63.6)] | 11 (18.0) [7 (63.6)] | |
| CZA MIC, median (IQR) | 2 (2–4) | 2 (2–4) | 2 (2–4) | 0.813 |
| Antimicrobial regimens, n (%) | ||||
| CZA + MEM | 40 (32.8) | — | 40 (65.6) | — |
| CZA + FOF | 61 (50.0) | 61 (100) | — | |
| CZA + otherc | 8 (6.5) | — | 8 (13.1) | |
| CZA monotherapy | 13 (10.7) | — | 13 (21.3) | |
| FOF dose (g/day), median (IQR) | — | 16 (12–24) | — | — |
| FOF dose ≥ 16 g/day, n (%) | — | 43 (70.5) | — | — |
| Early active therapy,dn (%) | 53 (43.4) | 32 (52.5) | 21 (34.4) | 0.067 |
| Appropriate definitive therapy,en (%) | 113 (92.6) | 56 (91.8) | 57 (93.4) | 1.0 |
| CZA prolonged infusion, n (%) | 52 (42.6) | 32 (52.5) | 20 (32.8) | 0.044 |
| Performed source control,fn (%) | 60 (64.8) | 25 (60.7) | 35 (68.9) | 0.168 |
| Duration of definitive treatment, median (IQR) | 14 (11–19) | 14.0 (11.0–17.0) | 15 (11.5–19.5) | 0.348 |
CZA, ceftazidime/avibactam; FOF, fosfomycin; MEM, meropenem. Bold type indicates statistical significance.
Cases were patients with KPC-Kp BSI receiving CZA + FOF; controls were patients with KPC-Kp BSI receiving CZA alone or in combination with in vitro non-active drugs different from FOF (CZA ± other).
Immunosuppression was defined as either steroid therapy with prednisone (or its equivalent) at a dose of >0.5 mg/kg/day for at least 1 month or the receipt of chemotherapy, TNF-α inhibitors, cyclophosphamide, azathioprine, methotrexate or mycophenolate mofetil in the previous 90 days.
‘Other’ includes CZA in association with one antibiotic among gentamicin, tigecycline or colistin.
Early active therapy was classified as appropriate if at least one administered antibiotic exhibited in vitro activity within 24 h.
Definitive antibiotic therapy (defined as the definitive antimicrobial treatment administered after the availability of susceptibility results) was considered appropriate if KPC-Kp was susceptible to CZA, and CZA was administered within 48–72 h from the index BC collection.
The percentage of source control was calculated only on the patients for whom it was considered necessary.