TABLE 1.
Characteristics of cases treated with ceftolozane-tazobactam and controls
| Characteristica | Total | Cases | Controls | P value |
|---|---|---|---|---|
| No. of cases | 57 | 19 | 38 | |
| Male (n [%]) | 43 | 16 (84.2) | 27 (71.1) | 0.343 |
| Age (years) (mean [SD]) | 53.6 (17.2) | 45.6 (14.6) | 57.6 (17.2) | 0.012 |
| Hematologic malignancy (n [%]) | 0.125 | |||
| AML | 17 (29.8) | 10 (52.6) | 7 (18.4) | |
| ALL | 8 (14) | 2 (10.5) | 6 (15.8) | |
| NHL | 17 (29.8) | 5 (26.3) | 12 (31.6) | |
| HL | 1 (1.8) | 0 (0) | 1 (2.6) | |
| MDS | 5 (8.8) | 0 (0) | 5 (13.2) | |
| MM | 5 (8.8) | 0 (0) | 5 (13.2) | |
| AA | 1 (1.8) | 1 (5.3) | 1 (2.6) | |
| Other | 1 (1.8) | 1 (5.3) | 1 (2.6) | |
| Stage (n [%]) | 0.118 | |||
| Induction | 11 (19.3) | 3 (15.8) | 8 (21.1) | |
| Consolidation | 10 (17.5) | 6 (31.6) | 4 (10.5) | |
| Reinduction | 12 (21.1) | 5 (26.3) | 7 (18.4) | |
| Allo-HSCT | 14 (24.6) | 5 (26.3) | 9 (23.7) | |
| Auto-HSCT | 5 (8.8) | 0 (0.0) | 5 (13.2) | |
| Progression | 5 (8.8) | 0 (0) | 5 (13.2) | |
| MASCC score (mean [SD]) | 14.1 (6.2) | 10.2 (2.7) | 16.1 (6.6) | 0.0001 |
| MASCC score <21 (n [%]) | 42 (75.0) | 19 (100.0) | 23 (62.2) | 0.002 |
| Charlson (mean [SD]) | 3.18 (2.1) | 3 (1.96) | 3.26 (2.20) | 0.659 |
| Age-adjusted Charlson (mean [SD]) | 4.26 (2.63) | 3.63 (2.14) | 4.58 (2.83) | 0.204 |
| Comorbidities(n [%]) | 0.461 | |||
| Liver disease | 1 (1.8) | 0 (0.0) | 1 (2.6) | |
| COPD | 7 (12.3) | 0 (0.0) | 7 (18.4) | |
| Heart disease | 6 (10.5) | 3 (15.8) | 3 (7.9) | |
| HIV | 2 (3.5) | 1 (5.3) | 1 (2.6) | |
| Diabetes | 4 (7.0) | 2 (10.5) | 2 (5.3) | |
| CKD | 3 (5.3) | 1 (5.3) | 2 (5.3) | |
| Other | 6 (10.5) | 1 (5.3) | 5 (13.2) | |
| Place of acquisition (n [%]) | 0.013 | |||
| Hospital acquired | 33 (57.9) | 15 (78.9) | 18 (47.4) | |
| Healthcare associated | 11 (19.3) | 4 (21.1) | 7 (18.4) | |
| Community acquired | 13 (34.2) | 0 (0.0) | 13 (34.2) | |
| Source of infection (n [%]) | 0.738 | |||
| CVC/PICC | 12 (21.1) | 4 (21.1) | 8 (21.1) | |
| Respiratory | 14 (24.6) | 5 (26.3) | 9 (23.7) | |
| Urinary | 12 (21.1) | 2 (10.5) | 10 (26.3) | |
| Skin and soft tissue | 4 (7.0) | 1 (5.3) | 3 (7.9) | |
| Genital | 5 (8.8) | 2 (10.5) | 3 (7.9) | |
| Perianal | 3 (5.3) | 1 (5.3) | 3 (5.3) | |
| Primary | 7 (12.3) | 4 (21.1) | 3 (7.9) | |
| Length of stay prior to infection (days) (mean [SD]) | 23.6 (34.9) | 30.4 (39.4) | 20.2 (32.6) | 0.302 |
| Leucocytes (cells/mm3) (mean [SD]) | 3,219 (7,617) | 3,478 (10,511) | 3,089 (5,831) | |
| Neutropenia <500 cells/mm3 (n [%]) | 32 (56.1) | 12 (63.2) | 20 (52.6) | 0.574 |
| Duration of neutropenia prior to infection (days) (mean [SD]) | 19.8 (37.7) | 24.9 (45.3) | 17 (33.5) | 0.540 |
| New renal failure (n [%]) | 16 (31.4) | 7 (41.2) | 9 (26.5) | 0.345 |
| SOFA (mean [SD]) | 4.84 (3.57) | 5.42 (3.0) | 4.5 (3.9) | 0.379 |
| Sepsis according to qSOFA (n [%]) | 10 (17.9) | 3 (15.8) | 7 (18.9) | NSb |
| ICU admission (n [%]) | 12 (21.1) | 5 (26.3) | 7 (18.4) | 0.509 |
| Bloodstream infections (n [%]) | 43 (75.4) | 10 (52.7) | 33 (86.8) | 0.008 |
| Pitt bacteremia score (mean [SD]) | 1.39 (1.8) | 1.21 (1.3) | 1.46 (1.9) | 0.672 |
| Susceptibility (no. [%] of nonsusceptible strains) | ||||
| Piperacillin-tazobactam | 29 (50.9) | 18 (94.7) | 11 (29.0) | 0.0001 |
| Ceftazidime | 31 (54.4) | 16 (84.2) | 15 (39.5) | 0.0001 |
| Cefepime | 38 (66.7) | 18 (94.7) | 18 (47.4) | 0.0001 |
| Aztreonam | 49 (87.5) | 18 (94.7) | 31 (83.7) | 0.426 |
| Imipenem | 42 (76.4) | 19 (100) | 25 (65.8) | 0.015 |
| Meropenem | 42 (77.8) | 19 (100) | 23 (65.7) | 0.028 |
| Gentamicin | 46 (80.7) | 19 (100) | 27 (71.1) | 0.009 |
| Tobramycin | 46 (80.7) | 19 (100) | 27 (71.1) | 0.009 |
| Amikacin | 7 (12.5) | 2 (10.6) | 5 (13.5) | 0.349 |
| Fosfomycin | 20 (40.0) | 8 (42.1) | 12 (38.7) | 0.308 |
| Ciprofloxacin | 45 (80.4) | 19 (100) | 25 (67.6) | 0.015 |
| Colistin | 0/43 (0) | 0 (0) | 0 (0) | 0.828 |
| Ceftolozane-tazobactam | 0/19 (0) | 0 (0) | 0 (0) | NS |
| Resistance (CDC) (n [%]) | 0.015 | |||
| Non-multidrug resistant | 11 (19.3) | 0 (0.0) | 11 (28.9) | |
| MDR | 29 (50.9) | 10 (52.6) | 9 (50.0) | |
| XDR | 17 (29.8) | 9 (47.4) | 8 (21.1) | |
| ST175 clone | 25 (83.3) | 11 (100) | 14 (73.7) | 0.129 |
| Appropriate empirical treatment (n [%]) | 28 (49.1) | 8 (42.1) | 20 (52.6) | 0.576 |
| Combined therapy (n [%]) | 20 (35.1) | 8 (42.1) | 12 (31.6) | 0.558 |
| Source control (n [%]) or (no./total no.) | 14/19 | 5 (71.4) | 9 (75.0) | NS |
| Toxicity (n [%]) | 10 (17.5) | 5 (26.3)c | 5 (13.2) | 0.119 |
| Clinical cure (n [%]) or (no./total no.) | ||||
| 14 days | 44 (77.2) | 17 (89.5) | 27 (71.1) | 0.183 |
| Monotherapy | 31/37 | 10 (90.9) | 21 (80.8) | 0.646 |
| Combined therapy | 13/20 | 7 (87.5) | 6 (50.0) | 0.158 |
| Recurrence (n [%]) or (no./total no.) | 7 (12.3) | 3 (15.8) | 4 (10.5) | 0.675 |
| Monotherapy | 4/37 | 1 (10) | 3 (11.5) | NS |
| Combined therapy | 3/20 | 2 (22.2) | 1 (8.3) | 0.537 |
| 30-day mortality (n [%]) or (no./total no.) | 12 (5.3) | 1 (5.3) | 11 (28.9) | 0.045 |
| Monotherapy | 6/37 | 1 (10) | 5 (19.2) | NS |
| Combined therapy | 6/20 | 0 (0) | 6 (50.0) | 0.042 |
| Time from infection to death (days) (mean [SD]) | 157.3 (296.7) | 41.7 (30.1) | 175.6 (316.3) | 0.481 |
a
AML, acute myeloblastic leukemia; ALL, acute lymphoblastic leukemia; NHL, non-Hodgkin lymphoma; HL, Hodgkin lymphoma; MDS, myelodysplastic syndrome; MM, multiple myeloma; AA, aplastic anemia; HSCT, hematopoietic stem cell transplant; COPD, chronic obstructive pulmonary disease; CKD, chronic kidney disease; CVC, central venous catheter; PICC, peripherally inserted central catheter; SOFA, sequential organ failure assessment; ICU, intensive care unit; MDR, multidrug resistant; XDR, extremely drug resistant; SD, standard deviation.
b
NS, not significant.
c
Toxicity attributable to empirical therapy administered before ceftolozane-tazobactam or to other drugs administered with ceftolozane-tazobactam as combined therapy.