High dose tigecycline in critically ill patients with severe infections due to multidrug-resistant bacteria

Table 1 Clinical characteristics of the 63 patients with VAP in the standard-dose (SD) and high-dose (HD) tigecycline (TGC) groups

Variable	SD TGC group (n = 30)	HD TGC group (n = 33)	P-value
Age, years, mean ± standard deviation	64.5 ± 16.9	60.7 ± 12.5	0.31
Male, n (%)	17 (56.6)	24 (72.7)	0.18
SAPS II score, mean ± standard deviation	51.3 ± 14.4	48.5 ± 14.9	0.46
SOFA score at infection occurrence, mean ± standard deviation	7.8 ± 3.2	7.4 ± 2.7	0.49
Septic shock at infection occurrence, n (%)	10 (33.3)	18 (54.5)	0.09
ARDS at infection occurrence, n (%)	2 (6.6)	7 (21.2)	0.09
Diagnosis on ICU admission, n (%)
Medical	24 (80)	24 (72.7)	0.49
Non-medical	6 (20)^b	9 (27.3)^c	0.49
Comorbidities, n (%)
CHF	12 (40)	15 (45.4)	0.66
COPD	4 (13.3)	6 (18.1)	0.59
CRF	4 (13.3)	5 (15.1)	0.83
Malignancies	3 (10)	7 (21.2)	0.22
Diabetes	5 (16.6)	8 (24.2)	0.45
Immunosuppressive status	3 (10)	6 (18.1)	0.35
Comorbidities >1	17 (57)	21 (63.6)	0.57
Microbiological and therapeutically aspects
Concomitant use of other active antibiotics, n (%)	24 (80)	29 (87.9)	0.39
Duration of TGC treatment, days, median (IQR)	6.5 (4 to 12)	9 (6 to 12)	0.13
Initial inadequate treatment, n (%)	14 (46.6)	19 (57.5)	0.38
Responsible pathogens, n (%)
Acinetobacter baumannii XDR	13 (43.3)	15 (45.4)	0.86
Klebsiella pneumoniae MDR/XDR	10 (33.3)	20 (60.6)	0.03
Other bacteria	14 (46.6)	6 (18.1)	0.01
MIC value 1 to 2 mcg/mL^a	8 (32)	23 (79.3)	<0.01
Clinical and microbiological outcome, n (%)
ICU mortality	20 (66.6)	16 (48.4)	0.14
Clinical cure	10 (33.3)	19 (57.5)	0.05
Microbiological eradication	7 (30.4)	12 (57.1)	0.07

^aMIC value was analyzed in 56 patients (26 in the SD TGC group and 30 in the HD TGC group); ^btwo surgical and four trauma; ^csix surgical and four trauma. SAPS II, simplified acute physiology score II; SOFA, sequential organ failure assessment; ARDS, acute respiratory distress syndrome; CHF, chronic heart failure; COPD, chronic obstructive pulmonary disease; CRF, chronic renal failure; MDR, multidrug resistant; XDR, extensively drug-resistant; MIC, minimum inhibitory concentration.
Of the 63 patients with VAP, 53 (84.1%) were treated concomitantly with other active antibiotics, without differences between the two groups (87.9% in the HD versus 80% in the SD group; P = 0.39). Colistin was used in 35 cases (6,000,000 to 9,000,000 IU/day divided into two to three daily doses, after the loading dose), gentamycin in 12 cases (5 to 7 mg/kg q 24 h) and amikacin in 6 cases (15 to 20 mg q 24 h). MICs of colistin, gentamicin and amikacin were of < = 1 mg/L, <= 2 mg/L, and < = 2 mg/L, respectively. All dosages were adjusted for creatinine clearance if necessary. Gentamycin and amikacin peak and trough plasmatic levels were routinely checked.

ISSN: 1364-8535