1200 j lipman
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THE ANTIMICROBIAL ARMS RACE
GETTING THE LAUNCH CODES RIGHT
Department of
Intensive Care MedicineRoyal Brisbane Hospital University of Queensland
Professor Jeffrey Lipman
Duration of hypotension prior to effective antimicrobial therapy: impact
on survival in septic shock
Kumar et al. Crit Care Med 2006;34:1589–96
Time of first dose of antibiotics after the onset of shock (hours)
0–30′
100
80
60
40
20
0
Mor
tailt
y (%
)
30′–1h 1–2 2–3 3–4 4–5 5–6 6–9 9–12 12–24 24–36 >36
GETTING THE LAUNCH CODES RIGHT
STRUCTURE The “BAD” effects of antibiotics
ie collateral damageLack of good infection definitions
eg Diagnosis of line related infection (amongst others)
Lack of sensitive biomarker ie how do you know when to start
BOWEL BACTERIAL LOAD
MORE BACTERIA IN/ON OUR BODY THAN CELLS
10 quadrillion cells 100 quadrillion bacterial
cells
ANTIBIOTICS KILL BACTERIA, BUT NOT ALL
The main risk factor for IR-GNB colonization was prior imipenem exposure. The odds ratio for colonization was already as high as 5.9 (95% confidence interval [95% CI], 1.5 to 25.7) after 1 to 3 days of exposure and increased to 7.8 (95% CI, 2.4 to 29.8). In conclusion, even brief exposure to imipenem is a major risk factor for IR-GNB carriage.
after 1 to 3 days of exposure
Kritsotakis et al J Antimicrob Chemother 2011;66:1383-91
DURATION OF THERAPY
CASE STUDY
52 YR OLD FEMALE WITH 60% TBSA BURNSGM-NEG ANTIBIOTICSD7 pre-op piptazD11 pre-op meropenem + gentD12 pre-op meropenem – plus 1 dose post opD14 pre-op meropenem – plus 1 dose post op
plus pre-op gentD14 Cultures taken Stenotrophomonas
CPIS< 6 : “std” vs 3 days cipro
MAIN RESULTS: ICU Mortality – same, BUT: ICU LOS LESS, 30 DAY MORTALITY LESS Resistance 15% vs 35%,
COMMENTS: Small study, low risk pts, a start
Some other OPD trials
AJRCCM 2000:162: 505-11
Basic resistance to disease that a species possesses
First line of defence against infection. The characteristics include the following:
Responses are broad and non-specific No memory or lasting protective immunity There is a limited repertoire of recognition
molecules The responses are phylogenetically ancient
INNATE (NONSPECIFIC) IMMUNITY
IMPORTANT TO REALISE THAT ONLY THIS PART NEEDS (and in fact responds to) ANTIBIOTICS
COMMON ICU INFECTIONS• VAP• LINE RELATED INFECTIONS• INTRA-ABDOMINAL INFECTIONS• NEUROSURGICAL – VENTRICULITIS• BURNS• UTI probably less so
BLOOD STREAM INFECTIONS EASIER TO DIAGNOSE
VAPDefinitions include many subjective components such as chest radiography, respiratory secretion assessment and chest auscultation findings. As a consequence, interobserver discordance for detecting VAP is high
The correlation between VAP defined using NHSN/CDC criteria and histological pneumonia is poor given that clinical signs have low specificity for VAP
VAP
• Despite keeping VAP fixed at 10%, the apparent rate of VAP varied between 6.0% and 31.6%
Variation in the apparent prevalence of VAP, depending on the frequency of other diseases in an ICU population.
Variation in the apparent prevalence of VAP, depending on the frequency of other diseases in an ICU population.
Not surprising then that 1.Attributable mortality varies from paper to paper2.What one person diagnoses and treats as VAP differs from the next consultant3.Therefore outcome of antibiotic therapy and duration thereof is fraught with difficulty
VAP
Published March 22, 2011
VAC was defined as ≥2 days of stable or decreasing daily minimum PEEP or FiO2 followed by a rise in daily minimum PEEP by ≥2.5 cm H2O lasting ≥2 days or a rise in daily minimum FiO2 by ≥15% lasting ≥2 days
“…..Our study shows that VAC is a simple and objectively defined parameter…......VAC's simplicity, objectivity, and consistent association with adverse outcomes make it a promising metric to succeed VAP for measuring quality and safety of care in ventilated patients.”
Critical Care Medicine March 2014
Some hospitals rated 0% of cases as having pneumonia; others
classified 100% as having pneumonia (median, 50%; interquartile range, 33–66%).
Critical Care Medicine March 2014
Conclusions: “In this nationally representative study of hospitals, assignment of VAP is extremely variable, enough to render comparisons between hospitals worthless, even when standardized cases eliminate variability in clinical data abstraction………
VAP IS DYINGIn its place will be
IVAC (Infection associated Ventilator Associated Complications)
HAP • Pipes in patient • Temperature• WCC• Atelectasis
I put it to you we over treat here tooI put it to you we over treat here too
Basic resistance to disease that a species possesses
First line of defence against infection. The characteristics include the following: Responses are broad and non-specific No memory or lasting protective immunity There is a limited repertoire of recognition
molecules The responses are phylogenetically ancient
INNATE (NONSPECIFIC) IMMUNITY
OTHER DEFINITIONS
Line related sepsisVentriculitis
Infections associated with conditions such as •Pancreatitis•Burns
CASE STUDY
52 YR OLD FEMALE WITH 60% TBSA BURNSGM-NEG ANTIBIOTICSD7 pre-op piptazD11 pre-op meropenem + gentD12 pre-op meropenem – plus 1 dose post opD14 pre-op meropenem – plus 1 dose post op
plus pre-op gentD14 Cultures taken Stenotrophomonas
CASE STUDY 52 YR OLD FEMALE WITH 60% TBSA BURNS
D14 Cultures taken StenotrophomonasNo clinical alteration in vital signs but given Bactrim 3 weeks later Ps. grown from burn wounds, sputum and blood cultures No clinical alteration in vital signs but given cefepimeArbitrarily 7 days and stopped with no alteration
before cefepime and after cefepime
OTHER DEFINITIONS
Line related sepsisVentriculitis
Infections associated with conditions such as •Pancreatitis•Burns
BIOMARKERS?
“An ideal biomarker should distinguish between various stages of bacterial infection, inform further diagnostic tests, help to time treatment, and provide information about prognosis…….”
Lancet Infect Dis. 2013 May;13(5):382-4
Crit Care Med 2012; 40: 2304–2309
Conclusions: Procalcitonin measuring for the initiation of antimicrobials did not appear to be helpful in a strategy aiming at decreasing the antibiotic consumption in intensive care unit patients.
Our analysis found a significant association between the presence of shock and elevation in PCT which was evident in the infected and noninfected cohort. This finding is particularly relevant in understanding the role of PCT in the critically ill where shock is common.
Crit Care Med 2012;40:2781-7
Prevalent infections demonstrated a trend toward a higher PCT peak than did incident infections.…….. the capacity to produce a PCT response in the face of a new infection may be blunted in those who are already critical ill
Crit Care Med 2012;40:2781-7
Conclusions: …..Shock had an association with higher procalcitonin values independent of the presence of infection. Trends in differences in procalcitonin values were seen in patients who had incident vs. prevalent infections.
Crit Care Med 2012;40:2781-7
SEPTICYTE
BIOMARKERS Certainly they haven’t been shown to help us in burns and pancreatitis.
BNP goes up in SEPSIS
Early work from us Anesth Analgesia Case reports Nov 2013Crit Care Med Accepted Feb 2014
0
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7
12 24 36 48 72 96 120 144 168
CIl/
m2
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3500
SV
RI
Cardiac index
Systemic vascular resistance index
* * *
* * *
*=p<0.01
Myocardial function in burns
Sepsis
Normal burn
55yo M TBSA 22% Sepsis Day 3
0
1
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12 24 36 48 72 96 120 144 168
CIl/
m2
0
500
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3500
SV
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BNP 1,347ng/L at this point
55yo M TBSA 22% Sepsis Day 3
Cardiac index
BNP 30pg/L0-48 hours Systemic vascular
resistance index
MeasureMeasure
BNPBNP PCTPCT SISI SVRISVRI
SensitivitySensitivity 88%88% 47 %47 % 63 %63 % 82%82%
SpecificitySpecificity 100%100% 47 %47 % 74 %74 % 86%86%
PPVPPV 100%100% 55 %55 % 78 %78 % 88 %88 %
NPVNPV 86%86% 39 %39 % 59 %59 % 77 %77 %
Sensitivity & Specificity
BNP 97%
SVRI 85%
SI 80%
PCT 56%
GETTING THE LAUNCH CODES RIGHT
STRUCTURE The “BAD” effects of antibiotics
ie collateral damageLack of good infection definitions
eg Diagnosis of line related infection (amongst others)
Lack of sensitive biomarker ie how do you know when to start
Kritsotakis et al J Antimicrob Chemother 2011;66:1383-91
DURATION OF THERAPY
IMPORTANT TO REALISE THAT ONLY THIS PART NEEDS (and in fact responds to) ANTIBIOTICS
“An ideal biomarker should distinguish between various stages of bacterial infection, inform further diagnostic tests, help to time treatment, and provide information about prognosis. Procalcitonin is not a perfect biomarker but it is the best available means for making individualised treatment decisions to reduce duration of antibiotic treatment or withhold antibiotics for non-life-threatening respiratory tract infections”
Lancet Infect Dis. 2013 May;13(5):382-4
Duration of hypotension prior to effective antimicrobial therapy: impact
on survival in septic shock
Kumar et al. Crit Care Med 2006;34:1589–96
Time of first dose of antibiotics after the onset of shock (hours)
0–30′
100
80
60
40
20
0
Mor
tailt
y (%
)
30′–1h 1–2 2–3 3–4 4–5 5–6 6–9 9–12 12–24 24–36 >36
GET YOUR LAUNCH CODES CORRECT
Kumar et al. Crit Care Med 2006;34:1589–96
