Table 2.
Clinical Response at Test of Cure Assessment by Risk Factora
| Study Population | ||||||
|---|---|---|---|---|---|---|
| CE | c-mITT | |||||
| Risk Factor | Tigecycline, n (%) | Levofloxacin, n (%) | Tigecycline - Levofloxacin, % Difference (95% CI) | Tigecycline, n (%) | Levofloxacin, n (%) | Tigecycline - Levofloxacin, % Difference (95% CI)b |
| Overall | ||||||
| Cure | 253 (89.7) | 252 (86.3) | 3.4 (-2.2 - 9.1) | 319 (81.0) | 321 (79.7) | 1.3 (-4.5 - 7.1) |
| Failure | 29 (10.3) | 40 (13.7) | 45 (11.4) | 57 (14.1) | ||
| Indeterminate outcome | — | — | 30 (7.6) | 25 (6.2) | ||
| Aged ≥65 Years | ||||||
| Cure | 73 (88.0) | 77 (81.9) | 6.0 (-5.7 - 17.2) | 89 (77.4) | 91 (77.8) | -0.4 (-11.7 - 10.9) |
| Failure | 10 (12.0) | 17 (18.1) | 13 (11.3) | 19 (16.2) | ||
| Indeterminate outcome | — | — | 13 (11.3) | 7 (6.0) | ||
| Prior Antibiotic Failure | ||||||
| Cure | 9 (81.8) | 14 (70.0) | 11.8 (-26.3 - 40.4) | 46 (79.3) | 55 (76.4) | 2.9 (-12.8 - 17.8) |
| Failure | 2 (18.2) | 6 (30.0) | 9 (15.5) | 15 (20.8) | ||
| Indeterminate outcome | — | — | 3 (5.2) | 2 (2.8) | ||
| Bacteremia | ||||||
| Cure | 21 (84.0) | 14 (70.0) | 14.0 (-13.1 - 40.6) | 23 (74.2) | 18 (58.1) | 16.1 (-9.4 - 39.1) |
| Failure | 4 (16.0) | 6 (30.0) | 6 (19.4) | 9 (29.0) | ||
| Indeterminate outcome | — | — | 2 (6.5) | 4 (12.9) | ||
| Multilobar Disease at Baseline | ||||||
| Cure | 66 (82.5) | 58 (80.6) | 1.9 (-11.2 - 15.4) | 89 (74.8) | 74 (73.3) | 1.5 (-10.5 - 13.8) |
| Failure | 14 (17.5) | 14 (19.4) | 19 (16.0) | 18 (17.8) | ||
| Indeterminate outcome | — | — | 11 (9.2) | 9 (8.9) | ||
| COPD | ||||||
| Cure | 26 (81.3) | 23 (76.7) | 4.6 (-17.7 - 26.8) | 29 (65.9) | 28 (68.3) | -2.4 (-23.0 - 18.7) |
| Failure | 6 (18.8) | 7 (23.3) | 8 (18.2) | 9 (22.0) | ||
| Indeterminate outcome | — | — | 7 (15.9) | 4 (9.8) | ||
| Hypoxemia | ||||||
| Cure | 59 (88.1) | 62 (82.7) | 5.4 (-7.7 - 17.9) | 77 (77.8) | 82 (75.9) | 1.9 (-10.4 - 13.8) |
| Failure | 8 (11.9) | 13 (17.3) | 11 (11.1) | 14 (13.0) | ||
| Indeterminate outcome | — | — | 11 (11.1) | 12 (11.1) | ||
| Renal Insufficiency or BUN >19.6 mg/dL or Urea >7 mmol/L | ||||||
| Cure | 85 (86.7) | 79 (78.2) | 8.5 (-2.9 - 19.6) | 102 (81.0) | 97 (75.8) | 5.2 (-5.5 - 15.7) |
| Failure | 13 (13.3) | 22 (21.8) | 15 (11.9) | 24 (18.8) | ||
| Indeterminate outcome | — | — | 9 (7.1) | 7 (5.5) | ||
| Diabetes or Glucose >13.9 mmol/L | ||||||
| Cure | 35 (97.2) | 29 (74.4) | 22.9 (4.8 - 39.9) | 41 (83.7) | 41 (71.9) | 11.7 (-5.8 - 27.9) |
| Failure | 1 (2.8) | 10 (25.6) | 3 (6.1) | 12 (21.1) | ||
| Indeterminate outcome | — | — | 5 (10.2) | 4 (7.0) | ||
| Alcohol Abuse | ||||||
| Cure | 24 (85.7) | 23 (85.2) | 0.5 (-21.2 - 22.5) | 27 (79.4) | 27 (81.8) | -2.4 (-23.1 - 18.7) |
| Failure | 4 (14.3) | 4 (14.8) | 4 (11.8) | 5 (15.2) | ||
| Indeterminate outcome | — | — | 3 (8.8) | 1 (3.0) | ||
| Altered Mental Status | ||||||
| Cure | 5 (71.4) | 7 (87.5) | -16.1 (-58.9 - 31.0) | 6 (66.7) | 8 (88.9) | -22.2 (-59.5 - 23.1) |
| Failure | 2 (28.6) | 1 (12.5) | 2 (22.2) | 1 (11.1) | ||
| Indeterminate outcome | — | — | 1 (11.1) | 0 (0) | ||
| WBC Count >30 x 109/L or <4 x 109/L | ||||||
| Cure | 10 (76.9) | 11 (73.3) | 3.6 (-32.1 - 36.7) | 13 (65.0) | 13 (68.4) | -3.4 (-33.5 - 27.7) |
| Failure | 3 (23.1) | 4 (26.7) | 3 (15.0) | 4 (21.1) | ||
| Indeterminate outcome | — | — | 4 (20.0) | 2 (10.5) | ||
| CURB-65 Score ≥2 | ||||||
| Cure | 72 (85.7) | 82 (82.8) | 2.9 (-8.9 - 14.1) | 88 (76.5) | 96 (79.3) | -2.8 (-14.0 - 8.3) |
| Failure | 12 (14.3) | 17 (17.2) | 14 (12.2) | 19 (15.7) | ||
| Indeterminate outcome | — | — | 13 (11.3) | 6 (5.0) | ||
| Fine Score Category III-V | ||||||
| Cure | 125 (89.3) | 115 (80.4) | 8.9 (-0.1 - 17.7) | 149 (80.1) | 144 (76.6) | 3.5 (-5.2 - 12.2) |
| Failure | 15 (10.7) | 28 (19.6) | 22 (11.8) | 33 (17.6) | ||
| Indeterminate outcome | — | — | 15 (8.1) | 11 (5.9) | ||
| At Least 2 Clinical Instability Criteria | ||||||
| Cure | 207 (90.0) | 198 (86.1) | 3.9 (-2.4 - 10.2) | 252 (80.5) | 247 (77.9) | 2.6 (-4.0 - 9.1) |
| Failure | 23 (10.0) | 32 (13.9) | 36 (11.5) | 46 (14.5) | ||
| Indeterminate outcome | — | — | 25 (8.0) | 24 (7.6) | ||
| Higher Risk of Mortality | ||||||
| Cure | 188 (89.5) | 152 (81.3) | 8.2 (0.9 - 15.7) | 223 (80.8) | 193 (76.0) | 4.8 (-2.5 - 12.1) |
| Failure | 22 (10.5) | 35 (18.7) | 34 (12.3) | 44 (17.3) | ||
| Indeterminate outcome | — | — | 19 (6.9) | 17 (6.7) | ||
CE: clinically evaluable; c-mITT: clinical modified intention to treat; COPD: chronic obstructive pulmonary disease; BUN: blood urea nitrogen; WBC: white blood cell.
Clinical cure was defined as all signs and symptoms of pneumonia improved or resolved, chest radiographs improved or not worse, no further antibiotic therapy necessary for treatment of pneumonia and no appearance of new signs and symptoms of pneumonia. Clinical failure was defined as persistence or worsening in signs and symptoms of the acute process, failure to show improvement in clinical findings, initial improvement in signs and symptoms followed by clinically significant worsening before test of cure assessment, additional necessary antimicrobial therapy for pneumonia, progression of chest radiograph abnormalities, death after study day 2 due to pneumonia or death due to a treatment-related adverse event.
Indeterminate outcome (clinically modified intention to treat population only) was defined as the patient was lost to follow-up, or died within 2 days after the first dose of study drug for any reason other than a treatment-related adverse event or died after 2 days because of non-infection-related reasons or infection other than pneumonia (as judged by the investigator).
95% confidence intervals (CIs) for overall differences were calculated using the normal approximation method with continuity correction. 95% CIs by risk factor differences were calculated using the Wilson score method with continuity correction. Unadjusted risk differences and CIs are presented.