tigecycline in the intensive care unit what has clinical experience taught us-

Tigecycline in the ICU
Only a few investigations have been undertaken assessing tigecycline in critically ill patients
These include
early experience with tigecycline for VAP and bacteremia caused by MDR Acinetobacter baumannii
Fraction 1.0
of total patients
0.8
0.6
0.4
0.2
0.0
Survival fraction Cumulative effective antimicrobial initiation
Time from hypotension onset (h)
Adequate antimicrobial therapy should start within 1 hour
Continuous renal replacement therapy, n (%) 23 (20)
Current ICU stay, median (IR) days
16 (8Βιβλιοθήκη Baidu 30)
Patient outcome
ICU mortality n=46 (41%) Hospital mortality n=61 (54%)
Tigecycline inhibits protein synthesis by binding to the 30S-ribosomal subunit and preventing peptide chain elongation
In vitro activity against
Including
Garnacho-Montero et al. Crit Care Med 2019;31:2742–2751; Vallés et al. Chest 2019;123:1615–1624
Insufficient β-lactam concentrations in the early phase of severe sepsis and septic shock
13 Spanish ICUs
113 patients
Baseline characteristics
Patients
Total, n (%) Sex, n (%)
Male Female Median (range) age, years Apache, mean ± SD SOFA points, mean ± SD Diagnostic group, n (%) Medical Surgical Trauma Underlying disease, n (%) Hypertension Cancer COPD Diabetes mellitus
N=80, APACHE II 22, 71% on MV
The blood concentration of Meropenem 1g initial dosage for sepsis and septic shock appear adequate
27% of the patients had AKI, and despite having been prescribed with standard non-AKI initial doses, most of them had suboptimal concentrations after the first dose.
Anthony KB et al. Clin Infect Dis 2019;46:567-70
Spanish clinical experience with tigecycline in critically ill patients
A multicentre retrospective observational study
Zhanel GG et al. Expert Rev Anti Infect Ther 2019;4:9-25; Noskin GA. Clin Infect Dis
2019;41:S303-14; Edelstein PH et al. Antimicrob Agents Chemother 2019;47:533-40
Kumar A et al. Crit Care Med 2019;34:1589-96
Mortality Associated with Appropriate Therapy in Patients with Serious Infections
Rello et al Alvarez-Lerma
Garnacho-Montero et al
Vallé s et al
0
20
40
60
80 100
Mortality (%)
Rello et al. Am J Respir Crit Care Med 2019;156:196–200; Alvarez-Lerma. Intensive Care Med 2019;22:387–394 Ibrahim et al. Chest 2000;118:146–155; Luna et al. Chest 2019;111:676–685
ICU, intensive care unit; MDR, multi-drug resistant
Schafer JJ et al. Pharmacotherapy
2019;27:980-7; Swoboda S et al. J Antimicrob Chemother 2019;61:729-33;
related ecological adverse events
The Goals of Empiric Antibacterial Therapy
Treating the patient - Target Pathogen - Consider PD profile - Tailored spectrum
Outcome of infection: resolved n=37 (32.7%) improved n=34 (30.1%) indeterminate n=13 (11.5%) therapy failure n=27 (23.9%)
Mortality rate attributable to the infection treated with tigecycline other antibiotics was 16.8% (n=19)
Ibrahim et al
Why do we see continued Mortality?
• Continuation of terminal process • Delay in the initiation of therapy
• Inadequate dose / exposure
Luna et al
tigecycline for the treatment of patients with severe sepsis or septic shock in a surgical ICU
serious infections caused by MDR gram-negative pathogens treated with tigecycline
Taccone et al. Insufficient β-lactam concentrations. Critical Care 2019;14(4):126-135
OPTAMA: Northern China
(Shenyang, Beijing, Tianjin and Jinan)
Probability of target attainment (%)
Gram-positive bacteria
MRSA and VRE
Gram-negative bacteria
ESBLs
Anaerobes
Atypical bacteria
MRSA, methicillin-resistant Staphylococcus aureus; VRE, vancomycin-resistant enterococci; ESBL, extended-spectrum beta-lactamase
66.0
44.3
Imipenem 1 g q8h
98.1
99.8
78.8
61.0
Meropenem 0.5 g q8h
99.3
99.7
81.4
67.5
Meropenem 1 g q8h
99.3
100.0
84.9
82.1
EC = E coli; KP = K pneumoniae; AB = A baumannii; PSA = P aeruginosa;; pip/taz = piperacillin/tazobactam
Wang H, et al. International Journal of Antimicrobial Agents 2019;30:452-457.
Tigecycline
Approved by EMEA in May 2019 for complicated intra-abdominal infection (cIAI) and complicated skin and soft tissue infection (cSSTI) 500mg q12h
Tigecycline in the intensive care unit: what has clinical experience taught us?
Jordi Rello Vall d’Hebron University Hospital, Universitat Autonoma Medical School
Regimen
EC (n=113) KP (n=92)
AB (n=67) PSA (n=89)
Cefoperazone/sulbactam 1g q12h 27.8
34.4
15.8
8.5
Cefotaxime 2 g q12h
31.6
40.3
2.4
3.1
Ceftriaxone 2 g q24h
38.0
Risk factors
Risk factor
Prior antibiotics, n (%)
113 (100)
Mechanical ventilation, n (%)
89 (79)
Septic shock, n (%)
52 (46)
Renal dysfunction, n (%)
45 (40)
Barcelona, Spain
新春愉快，恭喜发财
Aim of my talk
Striking the balance between
Successful treatment of critically ill
patients
Tackling the rise of MDR pathogens
Reducing antibiotic-
45.4
10.3
4.5
Ceftazidime 2 g q12h
84.5
78.3
39.4
59.5
Ciprofloxacin 0.4 g q12h
9.8
41.0
6.2
36.8
Ciprofloxacin 0.4 g q8h
11.5
41.0
17.2
47.5
Imipenem 0.5 g q8h
97.1
98.4
Protecting the community - Increase eradication - Minimize resistance - Reduce ABX duration [exposure]
Optimising anti-infective therapy: time to treatment
113 (100)
80 (71) 33 (29) 61 (44-72) 19.6 ± 7.3 7.9 ± 3.8
64 (57) 36 (32) 13 (12)
52 (46) 28 (25) 24 (21) 15 (13)
COPD, chronic obstructive pulmonary disease