Introduction
Materials and methods
Study overview and setting
VAP and CRBSI case definitions
Microbiologic methods
Definition of adequate empiric antibiotic treatment
Data sources
Deriving a weighted-incidence syndromic combined antibiogram (WISCA)
Statistical analysis
Sample size calculation
Results
Receipt of adequate empiric antibiotic therapy
Baseline characteristics of patients receiving or not receiving early adequate antibiotic treatment
Characteristics | Patients receiving early adequate treatment within 24 h (n = 84) | Patients not receiving early adequate treatment within 24 h (n = 79) | P-value |
---|---|---|---|
Age, years, median (IQR) | 56 (36 to 75) | 64.13 (46.25 to 76) | 0.09 |
Male sex, n (%) | 63 (75%) | 57 (72%) | 0.72 |
Admission source, n (%) | |||
Emergency Room | 31 (37%) | 25 (32%) | 0.51 |
Ward | 14 (17%) | 21 (27%) | 0.13 |
Operating Room | 17 (20%) | 11 (14%) | 0.31 |
Step-up | 6 (7%) | 8 (10%) | 0.58 |
Other | 16 (19%) | 14 (18%) | 0.84 |
ICU Type, n (%) | |||
Medical | 28 (33%) | 25 (32%) | 0.87 |
Surgical | 0 (0%) | 1 (1.3%) | 0.48 |
Trauma | 2 (2%) | 5 (6%) | 0.27 |
Burns | 9 (11%) | 7 (8.7%) | 0.79 |
Neurosurgical | 36 (43%) | 30 (38%) | 0.63 |
Cardiac | 9 (11%) | 11 (14%) | 0.64 |
ICU level, n (%) | |||
Level 3 | 84 (100%) | 79 (100%) | 1.00 |
Comorbidities, n (%) | 66 (78.6%) | 62 (78.5%) | 1.00 |
Heart disease | 25 (30%) | 16 (20%) | 0.21 |
Peripheral vascular | 9 (10.8%) | 6 (8%) | 0.59 |
Diabetes | 16 (19%) | 17 (21%) | 0.70 |
Renal disease/dialysis | 13 (15.5%) | 10(13%) | 0.66 |
Hypertension | 27 (32%) | 29 (36%) | 0.62 |
COPD/asthma | 12 (14%) | 6 (8%) | 0.22 |
Lung disease | 7 (8.3%) | 11 (14%) | 0.32 |
Gastrointestinal disease | 10 (12%) | 15 (19%) | 0.28 |
Liver disease | 2 (2.4%) | 6 (8%) | 0.16 |
Neurological disease | 14 (16.7%) | 15 (19%) | 0.84 |
Solid organ cancer | 13(15.5%) | 12 (15%) | 1.00 |
Leukemia/lymphoma | 3 (11.1%) | 3 (4%) | 1.00 |
Chemotherapy/radiation | 4 (15.5%) | 8 (10%) | 0.24 |
Surgery | 10 (12%) | 18 (23%) | 0.10 |
Infection | 2(2.4%) | 7 (9%) | 0.09 |
Multi organ dysfunction score, median (IQR) | 4 (2 to 6.2) | 5 (3 to 6.5) | 0.76 |
Organisms, n (%) | |||
Mono-microbial | 59 (70%) | 58 (73.4%) | 0.73 |
Poly-microbial | 25 (30%) | 21 (26.6%) | 0.73 |
Frequent organisms, n (%) | |||
Streptococcus pneumoniae
| 3 (3.6%) | 8 (10%) | 0.12 |
Staphylococcus aureus
| 19 (23%) | 17 (21.5%) | 1.00 |
Serratia marcescens
| 2 (2.4%) | 3 (4%) | 0.67 |
Pseudomonas aeruginosa
| 22 (27%) | 12 (15%) | 0.12 |
Klebsiella pneumonia
| 5 (6%) | 9 (11.5%) | 0.27 |
Klebsiella oxytoca
| 5 (6%) | 2 (2.5%) | 0.44 |
Haemophilus influenzae
| 10 (12%) | 5 (6.3%) | 0.28 |
Escherichia coli
| 8 (9.5%) | 1 (1.4%) | 0.03 |
Enterococcus faecalis
| 3 (3.6%) | 5 (6.3%) | 0.49 |
Enterobacter cloacae
| 3 (3.6%) | 5 (6.3%) | 0.49 |
Enterobacter aerogenes
| 4 (4.8%) | 5 (6.3%) | 0.74 |
Coagualse-negative staphylococci | 7 (8.3%) | 14 (17.7%) | 0.10 |
Citrobacter koseri
| 5 (6%) | 0 (0%) | 0.06 |
Other | 13 (15.5%) | 18 (22.8%) | 0.32 |
Average duration of hospital admission prior to infection, days, median (IQR) | 10 (5–16) Days | 12 (7 to 46.5) | 0.03 |
Previous antibiotic use in the past 90 days before hospital admission, n (%) | 7 (8.4%) | 8 (10%) | 0.79 |
Previous hospital visit in the past 90 days before hospital admission, n (%) | 13 (15.5%) | 13 (16.5%) | 1.00 |
Outcomes associated with receipt of early adequate treatment among patients with critical care infections
Outcomes | Patients receiving early adequate treatment within 24 h (n = 84) | Patients not receiving early adequate treatment within 24 h (n = 79) | P-Value |
---|---|---|---|
Hospital survival, n (%) | 60 (71%) | 55 (70%) | 0.86 |
ICU survival, n (%) | 66 (79%) | 63 (80%) | 1.00 |
Hospital length of stay, days, median (IQR) | 57 (31 to 92) | 55 (34.25 to 128.75) | 0.25 |
ICU length of stay, days, median (IQR) | 23 (15 to 46) | 28.5 (16.25 to 47.75) | 0.62 |
Post infection hospital, days, median (IQR) | 36 (18 to 69) | 39 (17.5 to 80) | 0.99 |
Length of mechanical ventilation, days, median (IQR) | 18 (10 to 37) | 17 (11 to 38.25) | 0.78 |
Length of pressor use, days, median (IQR) | 5 (0 to 20) | 5 (0 to 27) | 0.96 |
Potential improvement in time to adequate empiric antibiotic coverage for critical care infections with the use of WISCAs
WISCA empiric regimens | Percentage of VAP or CRBSI with documented adequate coverage by this regimen (n = 163) | Excess percentage of adequate coverage compared to retrospective cohort | ||
---|---|---|---|---|
12 h | 24 h | 48 h | ||
Monotherapy
| ||||
Ciprofloxacin | 110 (67%) | +30% | +16% | -8% |
Tobramycin | 75 (46%) | +9% | -5% | -29% |
Ceftriaxone | 77 (47%) | +10% | -4% | -28% |
Ceftazidime | 77 (47%) | +10% | -4% | -28% |
Pip.-Tazo. | 103 (63%) | +26% | +12% | -12% |
Ertapenem | 93 (57%) | +20% | +6% | -18% |
Meropenem | 121 (74%) | +37% | +23% | -3% |
Cloxacillin | 30 (18%) | -19% | -33% | -57% |
Vancomycin | 67 (41%) | +5% | -10% | -34% |
Linezolid | 68 (42%) | +6% | -9% | -33% |
Dual combination therapy
| ||||
Meropenem + Vancomycin | 152 (93%) | +56% | +42% | +18% |
Ertapenem + Vancomycin | 127 (78%) | +41% | +27% | +3% |
Pip.-Tazo. + Vancomycin | 144 (88%) | +51% | +37% | +13% |
Ceftazidime + Vancomycin | 141 (87%) | +50% | +36% | +12% |
Ceftriaxone + Vancomycin | 117 (72%) | +35% | +21% | -3% |
Ciprofloxacin + Vancomycin | 151 (93%) | +56% | +42% | +18% |
Tobramycin + Vancomycin | 151 (93%) | +56% | +42% | +18% |
Ciprofloxacin + Cloxacillin | 134 (82%) | +45% | +31% | +7% |
Tobramycin + Cloxacillin | 116 (71%) | +34% | +20% | -4% |
Meropenem + Tobramycin | 126 (77%) | +40% | +26% | +2% |
Ertapenem + Tobramycin | 126 (77%) | +40% | +26% | +2% |
Pip.-Tazo. + Tobramycin | 128 (79%) | +42% | +28% | +4% |
Ceftazidime + Tobramycin | 102 (63%) | +26% | +12% | -12% |
Ceftriaxone + Tobramycin | 115 (71%) | +34% | +20% | -4% |
Meropenem + Ciprofloxacin | 143 (88%) | +51% | +37% | +13% |
Ertapenem + Ciprofloxacin | 143 (88%) | +51% | +37% | +13% |
Pip.-Tazo. + Ciprofloxacin | 144 (88%) | +51% | +37% | +13% |
Ceftazidime + Ciprofloxacin | 137 (84%) | +47% | +33% | +9% |
Ceftriaxone + Ciprofloxacin | 136 (83%) | +46% | +32% | +8% |
Ciprofloxacin + Tobramycin | 135 (82%) | +45% | +31% | +7% |
WISCA empiric regimens | Percentage of VAP with documented adequate coverage by this regimen (n = 107) | Excess percentage of adequate coverage compared to retrospective cohort | ||
---|---|---|---|---|
12 h | 24 h | 48 h | ||
Monotherapy
| ||||
Ciprofloxacin | 82 (77%) | +37% | +24% | 0% |
Tobramycin | 55 (51%) | +11% | -3% | -26% |
Ceftriaxone | 59 (55%) | +15% | +2% | -22% |
Ceftazidime | 58 (54%) | +14% | +1% | -23% |
Pip.-Tazo. | 74 (69%) | +29% | +16% | -8% |
Ertapenem | 70 (65%) | +25% | +12% | -12% |
Meropenem | 91 (85%) | +45% | +32% | +8% |
Cloxacillin | 29 (27%) | -13% | -26% | -50% |
Vancomycin | 36 (34%) | -6% | -19% | -43% |
Linezolid | 36 (34%) | -6% | -19% | -43% |
Dual combination therapy
| ||||
Meropenem + Vancomycin | 99 (93%) | +53% | +40% | +15% |
Ertapenem + Vancomycin | 77 (72%) | +32% | +19% | -5% |
Pip.-Tazo. + Vancomycin | 92 (86%) | +46% | +33% | +9% |
Ceftazidime + Vancomycin | 89 (83%) | +43% | +30% | +6% |
Ceftriaxone + Vancomycin | 68 (64%) | +24% | +11% | -13% |
Ciprofloxacin + Vancomycin | 101 (94%) | +54% | +41% | +17% |
Tobramycin + Vancomycin | 99 (93%) | +53% | +40% | +16% |
Ciprofloxacin + Cloxacillin | 99 (93%) | +53% | +40% | +16% |
Tobramycin + Cloxacillin | 93 (87%) | +47% | +34% | +10% |
Meropenem + Tobramycin* | 94 (88%) | +48% | +35% | +11% |
Ertapenem + Tobramycin | 93(87%) | +47% | +34% | +10% |
Pip.-Tazo. + Tobramycin* | 96 (90%) | +50% | +37% | +13% |
Ceftazidime + Tobramycin* | 79 (74%) | +14% | +21% | -3% |
Ceftriaxone + Tobramycin | 92 (86%) | +46% | +33% | +9% |
Meropenem + Ciprofloxacin* | 101 (94%) | +54% | +41% | +17% |
Ertapenem + Ciprofloxacin | 100 (93%) | +53% | +40% | +16% |
Pip.-Tazo. + Ciprofloxacin* | 102 (95%) | +55% | +42% | +18% |
Ceftazidime + Ciprofloxacin* | 100 (93%) | +53% | +40% | +16% |
Ceftriaxone + Ciprofloxacin | 99 (93%) | +53% | +40% | +16% |
Ciprofloxacin + Tobramycin | 99 (93%) | +53% | +40% | +16% |
WISCA empiric regimens | Percentage of CRBSI with documented adequate coverage by this regimen (n = 56) | Excess percentage of adequate coverage compared to retrospective cohort | ||
---|---|---|---|---|
12 h | 24 h | 48 h | ||
Monotherapy
| ||||
Ciprofloxacin | 28 (50%) | +20% | +2% | -21% |
Tobramycin | 20 (36%) | +6% | -12% | -35% |
Ceftriaxone | 18 (32%) | +2% | -16% | -39% |
Ceftazidime | 19 (34%) | +4% | -13% | -37% |
Pip.-tazo. | 29 (52%) | +22% | +4% | -19% |
Ertapenem | 23 (41%) | +11% | -7% | -30% |
Meropenem | 30 (54%) | +24% | +6% | -17% |
Cloxacillin | 1 (2%) | -28% | -47% | -69% |
Vancomycin | 31 (55%) | +25% | +7% | -16% |
Linezolid | 32 (57%) | +27% | +9% | -14% |
Dual-combination therapy
| ||||
Meropenem + Vancomycin* | 53 (95%) | +65% | +47% | +24% |
Ertapenem + Vancomycin | 50 (89%) | +59% | +42% | +18% |
Pip.-Tazo. + Vancomycin* | 52 (93%) | +63% | +45% | +22% |
Ceftazidime + Vancomycin* | 52 (93%) | +63% | +45% | +22% |
Ceftriaxone + Vancomycin | 49 (88%) | +58% | +40% | +17% |
Ciprofloxacin + Vancomycin | 52 (93%) | +63% | +45% | +22% |
Tobramycin + Vancomycin | 50 (89%) | +59% | +41% | +18% |
Ciprofloxacin + Cloxacillin | 35 (63%) | +33% | +15% | -8% |
Tobramycin + Cloxacillin | 23 (41%) | +11% | -7% | -30% |
Meropenem + Tobramycin | 32 (57%) | +27% | +9% | -14% |
Ertapenem + Tobramycin | 33 (59%) | +29% | +11% | -12% |
Pip.-Tazo. + Tobramycin | 32 (57%) | +27% | +9% | -14% |
Ceftazidime + Tobramycin | 23 (41%) | +11% | -7% | -30% |
Ceftriaxone + Tobramycin | 23 (41%) | +11% | -7% | -30% |
Meropenem + Ciprofloxacin | 42 (75%) | +45% | +27% | +4% |
Ertapenem + Ciprofloxacin | 43 (77%) | +47% | +29% | +6% |
Pip.-Tazo. + Ciprofloxacin | 42 (75%) | +45% | +27% | +4% |
Ceftazidime + Ciprofloxacin | 37 (66%) | +36% | +18% | -5% |
Ceftriaxone + Ciprofloxacin | 37 (66%) | +36% | +18% | -5% |
Ciprofloxacin + Tobramycin | 36 (64%) | +34% | +16% | -7% |
Discussion
Conclusions
Key messages
-
In contrast to traditional antibiograms, WISCAs display the likelihood of coverage for a specific infectious syndrome (rather than individual pathogens), and also take into account the potential for poly-microbial infections and the use of multi-drug regimens
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WISCAs can be constructed based on local ecology data for common ICU infections such as VAP or CRBSI
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In this retrospective cohort study, only 1/3 of patients received adequate coverage by 12 h, 1/2 of patients 24 h and only 3/4 of patients by 48 h from culture collection
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Use of WISCA-guided double antibiotic therapy regimens could potentially have resulted in adequate coverage rates +56%, +42% and +18% higher than current care at 12-h, 24-h and 480 h time points
-
Prospective research is needed to determine whether actual provision of WISCA antimicrobial prescribing-aids to ICU clinicians are associated with improvements in timely and rational antimicrobial treatment