Dr Patrick N A Harris, Prof David L. Paterson, University of Queensland Centre for ... QLD, 4029, Email: p.harris@uq.edu.au Tel: +61 423785006 Fax: +61 7 3346 5509. Prof Paul A. Tambyah, Dr Mo Yin, National University Hospital, Singapore, ...
Meropenem and Piperacillin-tazobactam have Comparable Outcomes in Treatment of Bloodstream Infections Caused by Extended Spectrum Beta-lactamase Producing E.coli and Klebsiellae Patrick N A Harris1, Paul A. Tambyah2, Mo Yin2, Roland Jureen2, Stuart Paynter1, Jonathan Chew3, Jaminah Ali2, & David L. Paterson1 Centre for Clinical Research at The University of Queensland 2 National University Hospital, Singapore Results
Widespread use of carbapenems for treatment of infections caused by extended-spectrum β-lactamase (ESBL) producing Gram-negative bacilli has contributed to increasing carbapenem resistance. Despite some studies suggesting that β-lactam/β-lactamase inhibitor (BLBLI) combination antibiotics are non-inferior to carbapenems, their use has been limited by concerns of clinical efficacy. We compared outcomes between patients treated with BLBLIs and carbapenems for bloodstream infection (BSI) caused by ceftriaxone nonsusceptible E coli and Klebsiella spp., in an institution with a relative high incidence of ESBL-producing isolates.
Table 2: Baseline characteristics of patients given definitive monotherapy with a BLBLI or carbapenem Definitive treatment cohort
Definitive cohort (n=47)
BLBLI (n=25)
Empirical Carbapenem (n=8)
Definitive BLBLI (n=24)
* Empirical and definitive groups are non-mutually exclusive
Definitive Carbapenem (n=23)
CAZ
TZP
CXM
IPM
MEM
AMC
NIT
LVX
CTX
FOX
FEP
ETP
R (%)
100
100
59
71
0
35
96
0
100
0
0
60
1
71
100
11
0
0
I (%)
0
0
0
3
3
0
4
0
0
0
0
0
0
0
0
20
4
0
S (%)
0
0
41
27
97
65
0
100
0
100
100
40
99
29
0
68
96
100
Total tested
79
79
79
79
79
79
79
79
79
79
79
73
79
79
79
79
79
79
0
Female
13 (54%)
12 (52%)
49 (54%)
R (%)
100
100
85
30
0
31
100
0
100
0
0
45
38
15
100
0
92
Hospital acquired
7 (29%)
4 (17%)
20 (22%)
I (%)
0
0
0
40
0
0
0
0
0
0
0
0
8
0
0
8
8
0
Community acquired
7 (29%)
9 (39%)
42 (46%)
S (%)
0
0
15
30
100
69
0
100
0
100
100
55
54
85
0
92
0
100
Healthcare associated
10 (42%)
10 (43%)
29 (32%)
Total tested
13
13
13
10
13
13
13
13
13
13
13
11
13
13
13
13
13
13
2 [1-4]
2 [1-5]
2 [1-4]
26
20
24 [15-28]
2 (8%)
5 (22%)
11 (12.1)
22 (92%)
17 (74%)
79 (87%)
K. pneumoniae
R = resistant, I = intermediate, S = susceptible; CRO = ceftriaxone, AMP = ampicillin, SXT = trimethoprim-sulphamethoxazole, AMK = amikacin, GEN = gentamicin, CAZ = ceftazidime, TZP = piperacillin-tazobactam, CXM = cefuroxime, IMP = imipenem, MEM = meropenem, AMC = amoxicillin-clavulanate, NIT = nitrofurantoin, LVX = levofloxacin, CTX = cefotaxime, FOX = cefoxitin, FEP = cefepime, ETP = ertapenem Figure 3: 30-day mortality for patients treated with BLBLI or carbapenem as definitive monotherapy
4 (4%)
12 (50%)
8 (34%)
32 (35%)
Moderate to severe liver disease
3 (13%)
1 (4%)
7 (8%)
Diabetes without end organ damage
6 (25%)
5 (22%)
21 (23%)
0.50
.
4 (17%)
Metastatic solid tumour
2 3 4 Days following positive blood culture
5
6
Carbapenem
7 (31%)
19 (21%)
HR 1.00 (95%CI 0.37 to 2.74; p=0.999) (controlled for age, acquisition status, CCI, ICU, organism, and appropriate empirical therapy)
1 (4%)
1 (4%)
4 (4%)
Leukaemia or lymphoma
1 (4%)
2 (9%)
7 (8%)
Urinary device
5 (21%)
3 (13%)
15 (17%)
Immunosuppressive treatments
2 (8%)
4 (17%)
12 (13%)
3GC
7 (29%)
6 (26%)
33 (36%)
BLBLI
11 (46%)
5 (22%)
25 (28%)
0 (0%)
2 (9%)
8 (9%)
6 (25%)
10 (43%)
25 (27%)
15 (63%)
15 (65%)
50 (55%)
Other*
*Including combinations of carbapenem / BLBLI / 3CG CCI = Charlson Co-morbidity index, IQR = Inter-quartile range, ICU = intensive care unit, 3GC = third-generation cephalosporins
5
10 15 20 Days following positive blood culture
25
30
Definitive treatment
15 (17%)
Appropriate empirical therapy
0
Definitive treatment
Carbapenem
BLBLI
Figure 4: Length of hospital admission for patients treated with BLBLI or carbapenem as definitive monotherapy 1.00
Moderate to severe renal disease
5 (22%)
1
0.75
4 (17%)
0
BLBLI
HR 0.77, 95%CI 0.12 to 4.85; p=0.779(controlled for age, acquisition status, CCI, ICU, organism, and appropriate empirical therapy)
There were no significant differences in subsequent isolation of a carbapenem resistant organism (4.3% vs. 4.2%, p=1.0), C. difficile infection (13.0% vs. 8.3%, p=0.67) or relapsed bloodstream infection (0% vs. 2%, p=0.23).
0.50
Diabetes with organ damage
0.75
0.00
Co-morbidity / devices:
0.25
Other / unknown source
0.95
0 (0%)
0.90
1 (4%)
0.85
43 (47%)
Neutropenic sepsis
0.80
12 (13%)
13 (57%)
Survival
2 (9%)
9 (38%)
0.75
2 (8%)
Urinary tract
Proportion not recovered
Hepato-biliary
1.00
1.00
Figure 2: Days to recovery from SIRS (
