Introduction
Materials and methods
Study design and patients
Cost impact prediction
Parameter | Description | Unit | Value | Source | Used in equation |
---|---|---|---|---|---|
Cost
t
| Full cost per PCR test | € | 300 | Additional file 1 | 1, 4, 5, |
DG
| Days gainable on adequate treatment when utilizing PCR+ information | day | 2.78 = 80.5/29 | [17]a |
2,3,4
|
Mean total duration of inadequate treatment (as observed in PCR+ episodes with 0.5 ≤Du
IA
≤ 7.5) | day | 3.28 = 0.5 + DG | [17]a | 2, 5, | |
Factor which translates days on earlier adequate treatment into outcome in terms of mean days reduced length of stay (deltaLOS = LOS
Inad
- LOS
Ad
) | - | 1.15 = 3.763 day/3.276 day |
3, 4
| ||
Incidence of inadequate treatment in the PCR+ group | - | 0.397 = 29/73 | Figure 1 |
4, 5
| |
LY
gained
| Mean # years survival of survivors of ICU sepsis, age cohort >60 c | yr | 5.43 b = 12.3 * 488/1105 | [26] |
6
|
Mortality rate of inadequately treated PCR+ patients | - | 0.414 = 12/29 | Figure 1 |
5
| |
RR
†
| Relative risk of non-survival (@ inadequate/adequate treatment) | - | 2.315 |
5
| |
Sh
PCR+
| Share of episodes with at least 1 PCR+ microorganism | - | 0.330 = 73/221 | Table 2 |
4, 5
|
TAT
PCR
| Time between PCR sampling and result reported (hours) | hr | 12 | [17] |
2
|
Utility
health.state
| Health state utility after ICU sepsis | QALY/yr | 0.68 | [26] |
6
|
Mortality prediction
Statistical analysis
Results
Prediction of impact on morbidity, length of ICU stay and cost
Totals | PCR + episodes | Share of PCR+ epsiodesbSh
PCR+
| BC+ episodes | Share of BC+ epsiodesb
Sh
BC+
| |
---|---|---|---|---|---|
Total a | 221 | 73 | 0.33 | 44 | 0.20 |
Underlying diagnoses
a
| |||||
- Intra-abdominal sepsis | 87 | 31 | 0.36 | 22 | 0.25 |
- Nosocomial pneumonia | 80 | 28 | 0.35 | 21 | 0.26 |
- Community acquired pneumonia | 6 | 1 | 0.17 | 0 | 0 |
- Multi-organ dysfunction syndrome | 7 | 4 | 0.57 | 4 | 0.57 |
- Catheter related sepsis; post cardiac surgery | 45 | 18 | 0.40 | 9 | 0.20 |
- Neutropenic fever | 15 | 5 | 0.33 | 2 | 0.13 |
- Bone/joint infection | 9 | 4 | 0.44 | 0 | 0 |
Other | 46 | 11 | 0.24 | 3 | 0.07 |
Prediction of impact on mortality
Age | Co-morbidity | Infectious focus | PCR+ pathogen a | # days gainable b | Evidence for PCR+ relevance c | |
---|---|---|---|---|---|---|
BC+ | Other test | |||||
74 | Pleural lesion | Peritonitis |
Aspergillus, Candida
| 4 |
Candida
| Aspergillus antigen+ |
79 | Decompensated heart (right side) | Cholangitis |
Pseudomonas, (Escherichia coli)
| 7 |
Pseudomonas
| Bile- duct cul+ |
66 | Liver transplantation | Peritonitis |
Stenotropho-monas
| 4 | Stenotropho-monas, | Tracheal swab cul+ |
77 | Hemodialysis | Catheter-related | CoNS d | 2 | CoNS (2×) | Pos. tracheal swab cul+ |
47 | Trauma | Pneumonia | CoNS d | 2 | CoNS, Pseudomonas | Catheter-tip CoNS+ |
55 | Poly-trauma | Abdominal (late detected) |
Enterobacter
| 7 |
Enterobacter
| Enterobacter in cul+ |
62 | Cardiothoracic surgery | Pneumonia; unclear: 2nd focus | Staph.aureus: MRSA | 2 | MRSA+ (3×) | Thorax, sternum cul+ |
58 | Artherosklerosis | Pneumonia |
Aspergillus
| 2.5 | - | Bronchial aspirate cul+ |
78 | Rectal neo-plasm; perforat-ed abscess | Intra-abdominal |
Enterococcus faecium
| 1.5 |
Enterococcus faecium
(post mortem) | Enterococcus faecalis in drainage cul+ |
85 | Cardiac surgery | Pneumonia |
Klebsiella
| 3 | Enterobacter (equivalent the- rapy change ) | |
71 | Bypass surgery | Pneumonia |
Enterococcus faecalis; (Pseudomonas)
| 3 |
Enterococcus faecalis
| Pseudomonas in cul+ |
77 | Cardiac surgery | Pneumonia |
Klebsiella
| 5 |
Klebsiella
| Klebsiella in cul+ |
Potential risk of false-positive PCR results
Discussion
Conclusions
Key messages
-
Multiplex PCR pathogen detection is useful as an adjunct to blood cultures to support early adjustment of empiric antimicrobial therapy.
-
The incremental cost is justified for patients with over 25% inadequate initial treatment, especially in the presence of high daily treatment cost and risk of severe complications from inadequate treatment.
-
The prediction model provides guidance when designing and evaluating interventional trials that incorporate PCR into managing antimicrobial treatment in sepsis. It can also be used to explore relative utility and price-worthiness of alternative molecular assays, or of how to best implement them into laboratory routines.