the abc of icu – the a is for antibiotics - steve mcgloughlin
TRANSCRIPT
A is for Antibiotics After that we are STUCK
Steve McGloughlin The Alfred
SEPSIS
Sepsis is
Severe Infection (sepsis)………
Age GCS Temp
HR MAP
pH P/F Ratio Creatinine
51 13 39 125 55
7.14 180 140
ARISE
PROCESS
PROMISE
APACHE 25
Age GCS Temp
HR MAP
pH P/F Ratio Creatinine
55 13 39 125 55
7.14 150 140
ARISE
PROCESS
PROMISE APACHE 25
MORTALITY 45%
In Intensive Care………
SevereInfection
?SevereInfection
ED and ICU
Intensivists
Intensivists
Intensivists
SevereInfection ?
Support Fluids
Dialysis
Goal Directed Therapy?
SevereInfection ?
Definitive Antibiotics
Source Control
SevereInfection ?
Support
Antibiotics
Source Control
We need something else!
Sepsis is
What do we have….
Treatment Effect of Antibacterials for CAP • CID 2008:47 (Suppl 3) • S219
Figure 2. Mortality rates among patients with pneumococcal pneumonia in different age groups, in relation to treatment with serum or sulfonamidesand to bacteremia status, as summarized by Finland [5, 18]. Published with permission from the Connecticut State Medical Society [18].
the observed treatment difference greatest among patients con-sidered to have poor condition at baseline. This study remainsvaluable because of its suggestion that baseline condition in-fluences outcome and treatment effect, an important consid-eration for the design of current studies.
Treatment of pneumococcal pneumonia with antibacterialdrugs: observational studies. Finland [5, 18] summarizedmortality among patients with pneumococcal pneumonia whowere seen at Boston City Hospital from 1929 to 1941. Thiscohort included patients who received no specific therapy from1929 to 1940 ( ), patients who received treatment withn p 2832serum from 1929 to 1938 ( ), and patients who re-n p 1029ceived treatment with sulfonamides from 1939 to 1941 (n p
).1220As shown in figure 2, the overall difference in mortality rate
between patients who received no specific therapy and patientswho received a sulfonamide derivative was 24% ( ).41% ! 17%A greater treatment difference was observed for bacteremic pa-tients (all ages combined) than for nonbacteremic patients (allages combined): 48% ( ) versus 17% ( ).78% ! 30% 28% ! 11%Mortality increased substantially with age among both bacter-emic and nonbacteremic patients. These data are summarizedin table 2.
Dowling and Lepper [19] compared case-fatality rates amongpatients who received no specific treatment ( ) withn p 1087those among patients given treatment with pneumococcal an-tiserum ( ), sulfonamides ( ), or penicillin orn p 889 n p 1274other antibiotics, such as tetracyclines ( ). The anti-n p 920bacterial treatment groups were studied from 1938 to 1950,
whereas the group receiving no specific treatment and the se-rum treatment group were historical control patients studiedat Boston City Hospital from 1939 to 1940 and described inearlier publications [21–24]. Overall case-fatality rates (regard-less of bacteremia status or age) were 30.5% among patientswho received no specific treatment, 16.9% among patients whoreceived serum treatment, 12.3% among patients who receivedsulfonamide treatment, and 5.1% among patients who receivedantibiotic therapy (penicillin or tetracyclines), as summarizedin table 2. In this report, mortality was again shown to increasewith age and with the presence of bacteremia, regardless oftreatment.
Austrian and Gold [20] reported survival according to dayof illness for patients with bacteremic pneumococcal pneu-monia given treatment with penicillin from 1952 to 1962( ), those given treatment with pneumococcal antise-n p 298rum ( ), and those given no specific therapy ( ).n p 93 n p 384The last 2 groups were historical control patients described byTilghman and Finland [4]. As shown in figure 3, at day 21 ofillness, the survival rate was 85% among patients given treat-ment with penicillin, 50% among patients given treatment withpneumococcal antiserum, and 17% among patients who re-ceived no specific antipneumococcal therapy. The difference insurvival between the groups given treatment with penicillin andthe historical control group receiving no specific treatment was68% at day 21, 60% at day 14, and 22% at day 7. No differencewas observed in the first 5 days of illness.
In the same publication, Austrian and Gold [20] also re-ported mortality rates according to treatment for a different by guest on June 10, 2016
http://cid.oxfordjournals.org/D
ownloaded from
NNT
Feature Articles
Critical Care Medicine www.ccmjournal.org 1753
regression model uses the same seven time periods as shown in Table 1. Figure 2 illustrates the trend in hospital mortality over timing to first antibiotic, relative to suspicion of sepsis. Table 2 shows that the adjusted hospital mortality odds ratios steadily
increase from 1.00 to 1.52 as time to antibiotic administration increases from 0 to greater than 6 hours where 0–1 hour is the referent group. The probability of mortality increases from 24.6% to 33.1% and is based on a subject having the following characteristics: from the United States, admission source is the ED, and the SSS is 52 (median of all observations).
DISCUSSIONThe results of this study confirm, in the largest population of patients with severe sepsis and septic shock reported to date, that delay in antibiotic administration was associated with increased in-hospital mortality. In addition, we confirm the increasing risk associated with delay—there was a linear increase in the risk of mortality for each hour delay in anti-biotic administration from the first through the sixth hour after patient identification This relationship between delay in antibiotic administration and mortality has been demon-strated before by Kumar et al (5). However, the population in that study was patients with septic shock, and the delay was from the onset of hypotension. Our study findings are distinct and unique in the population studied and the location of these patients in the hospital: similar results were found in patients with either severe sepsis or septic shock, and consistent results were also seen when patients were stratified by severity (num-ber of organ failure) and whether sepsis was identified in the ED, on the wards, or in the ICU. This study demonstrates, for
Number of acute organ dysfunction
1 1,898 (40.1) 2,078 (45.2) 1,363 (45.1) 777 (44.8) 458 (44.2) 275 (43.0) 942 (42.1)
< 0.001
2 1,653 (35.0) 1,587 (34.5) 1,060 (35.1) 608 (35.1) 358 (34.5) 227 (35.5) 732 (32.7)
3 847 (17.9) 681 (14.8) 436 (14.4) 268 (15.5) 154 (14.9) 99 (15.5) 387 (17.3)
4 265 (5.6) 207 (4.5) 131 (4.3) 68 (3.9) 51 (4.9) 31 (4.8) 134 (6.0)
5 65 (1.4) 42 (0.9) 30 (1.0) 13 (0.8) 16 (1.5) 8 (1.3) 41 (1.8)
Cardiovascular
No cardiovascular dysfunction
376 (7.9) 379 (8.3) 265 (8.8) 168 (9.7) 115 (11.1) 57 (8.9) 349 (15.6)
< 0.001
Cardiovascular dysfunction no hypertension
803 (17.0) 1,004 (21.8) 659 (21.8) 402 (23.2) 174 (16.8) 116 (18.1) 403 (18.0)
Total shock 3,549 (75.1) 3,212 (69.9) 2,096 (69.4) 1,164 (67.2) 748 (72.1) 467 (73.0) 1,484 (66.4)
Lactate > 4 260 (5.5) 332 (7.2) 249 (8.3) 117 (6.8) 64 (6.2) 26 (4.1) 114 (5.1)
Vasopressors only
2,273 (48.1) 1,938 (42.2) 1,309 (43.3) 769 (44.4) 522 (50.3) 346 (54.1) 1,126 (50.4)
Lactate > 4 and vasopressors
1,016 (21.5) 942 (20.5) 538 (17.8) 278 (16.0) 162 (15.6) 95 (14.8) 244 (10.9)
IQR = interquartile range, LOS = length of stay, ED = emergency department.ap value based on Pearson chi-square test for categorical variables and Wilcox rank-sum test for continuous variables.
TABLE 1. (Continued). Patient Characteristics by Timing in Hours to the First Antibiotic
Patient Characteristic, n (%)
Antibiotic Timing (Hr)
pa0.0–1.0 1.0–2.0 2.0–3.0 3.0–4.0 4.0–5.0 5.0–6.0 > 6.0
Figure 2. Predicted hospital mortality and the associated 95% CIs for time to first antibiotic administration. The results are adjusted by the sepsis severity score (SSS), ICU admission source (emergency department [ED], ward, vs ICU), and geographic region (Europe, United States, and South America). Probability of hospital mortality is based on the subject having the following specific characteristics: the patient is from the United States, admission source is the ED, and the SSS is 52 (median of all observations).
Why Not?
Sick Very Sick
Which Antibiotic? I want you to be honest?
The thoughtless person playing with penicillin treatment is morally responsible for the death of the
person who succumbs to infection with the penicillin resistant organism.
Pandrug resistant
214000 neonatal sepsis deaths attributable to
resistant pathogens
Series
170 www.thelancet.com Vol 387 January 9, 2016
have been documented by various studies from Asia: a multi-country analysis estimated the average prevalence of MRSA in Asian hospitals at 67·4%, with the lowest rate of 22·6% in India and the highest rate of 86·5% in Sri Lanka.27 Community-acquired MRSA averaged 25·5% across the eight countries in the study, with the lowest rate of 2·5% in Thailand and the highest rate of 38·8% in Sri Lanka.
Gram-negative organisms are by far the biggest threat because of growing resistance to carbapenems, which until recently were eff ective against multidrug-resistant strains. Carbapenem-resistant Enterobacteriaceae (CRE) have now been detected worldwide. New Delhi metallo-β-lactamase (NDM) enzymes, fi rst reported in 2008, are now reported worldwide.28 In the USA in 2012, 4·6% of acute-care hospitals reported at least one CRE healthcare-associated infection. Carbapenem resistance in common Enterobacteriaceae has increased sharply over the past decade: the proportion of Enterobacteriaceae that were CRE increased from 0% in 2001 to 1·4% in 2010, with most of the increase observed in Klebsiella spp.29 The rapid international spread of resistance genes, such as extended-spectrum β-lactamase (ESBL), NDM-1, and Klebsiella pneumoniae carbapenemase (KPC), suggests the nature of the serious threat of antimicrobial resistance. The sharp increase in resistance is clear in the case of β-lactamase antibiotics. Nearly 1000 resistance-related β-lactamases, including novel classes of genes, have been identifi ed, a ten-fold increase since 1990.30
Hospital data from developing countries suggest that pathogens causing neonatal infections (in the fi rst 28 days of life) are frequently resistant to the WHO-recommended regimen of ampicillin and gentamicin: 71% of Klebsiella spp and 50% of Escherichia coli were resistant to gentamicin.17 Resistance has also been reported as high in early-onset, presumably maternally acquired neonatal infections reported from hospital series in developing countries; 60–70% of E coli and nearly 100% of Klebsiella spp are ampicillin-resistant, and 40–60% of Klebsiella spp are resistant to gentamicin (appendix).31 High rates of ESBL production in E coli have restricted use of second-line therapy with extended-spectrum cephalosporins.32 Many newborns in hospitals in South Asia are now treated with carbapenems as fi rst-line therapy for sepsis or presumed sepsis. The emergence of pan-resistant untreatable CRE and Acinetobacter spp infections associated with high mortality in neonatal nurseries is of most concern.33
Figure 2 shows the estimated number of neonatal deaths attributable to resistant sepsis infections in the fi ve countries with the highest numbers of neonatal deaths in the world. Resistance-attributable neonatal sepsis deaths are greatest in India, where 56 524 neonates (33 683 LHS minimum, 89 620 LHS maximum) die each year owing to neonatal sepsis caused by bacteria resistant to fi rst-line antibiotics. These deaths are also high in Pakistan (25 692 deaths; 16 486 LHS minimum, 39 660 LHS maximum), Nigeria (19 405 deaths; 6797 LHS minimum, 35 490 LHS maximum),
Figure 1: Estimated pneumonia deaths avertable in under-5 populations with improved antibiotic access Countries with less than 100 deaths averted are not labelled. Data on under-5 population with suspected pneumonia receiving antibiotics are from 1990 to 2013; data from the most recent year reported is used, when available.
0 20 40 60 80
Trendline weighted bythe under-5 populationof each country
100
0
1
2
3
4
5
6
Pneu
mon
ia d
eath
s (du
e to
Stre
ptoc
occu
s pne
umon
iae a
nd H
aem
ophi
lus
influ
enza
e typ
e b) p
er 10
00 ch
ildre
n ag
ed yo
unge
r tha
n 5 y
ears
Under-5 population with suspected pneumonia receiving antibiotics (%)
IndiaNigeria
DR Congo
Pakistan
China
Ethiopia
Afghanistan
Sudan
Indonesia
Somalia
Mali
Niger
Uganda
Chad
Tanzania
Burkina Faso
Kenya
Yemen
MozambiqueCameroon
Myanmar
Philippines
Côte d’Ivoire
Bangladesh
Guinea
IraqMadagascar
Nepal
Malawi
Ghana
Burundi
Benin
Sierra Leone
UzbekistanZambia
Egypt
Haiti
SenegalIran
Central African Republic
Togo
VietnamMorocco
BrazilRwanda Zimbabwe
Mauritania
Cambodia
Tajikistan
Algeria
Congo (Brazzaville)
Guinea−Bissau
Bolivia
ColombiaTurkey
Thailand
North KoreaLaos
ArgentinaKazakhstanPeru
Timor−Leste
Dominican Republic
Equatorial Guinea
Kyrgyzstan Syria
Gambia
Comoros Swaziland
Honduras
ParaguayUkraine
India (169 760)
Nigeria (49 407)
Nepal (2 434)
Hypothetical under-5 pneumonia deaths averted with universal antibiotic access
1 million Avoidable deaths in 2013 in under 5’s from pneumonia
170 000 deaths in India
avoidable with Antibiotics
We need more than
antibiotics?
A disease caused by an uncontrolled division of abnormal cells in a part of the body.
Life-threatening organ dysfunction due to a dysregulated host response to infection
Cancer is
Sepsis is
One definition?
arises when the body's response to an infection injures its own tissues and organs. It may lead to shock, multiple organ failure, and death, especially if not recognized early and treated promptly.
Heart
Brain
Lung
Infection
Liver
Kidney
From a local infection to a general inflammation A local infection – e.g. in the lung – over-comes the body’s local defense mechanisms. Pathogenic germs and the toxins they produce leave the original site of the infection and enter the circulatory system.
Organ dysfunction This leads to a general inflammatory response: SIRS (systemic inflammatory response syndrome) The function of individual organs starts to deteriorate and may completely fail. Sepsis starts with the onset of at least one new organ dysfunction.
Septic Shock
Several organs stop functioning sequentially or simultaneously, and cardio-circulatory failure leads to a sudden drop in blood pressure. This is called septic shock.
Stag
e 1
Stag
e 2
Stag
e 3
Sepsis
© world-sepsis-day.org |made by Lindgruen-GmbH
The source changes the risk of death
MULTIDRUG-RESISTANTPSEUDOMONAS AERUGINOSA
Pseudomonas aeruginosa is a common cause of healthcare-associated infections including pneumonia, bloodstream infections, urinary tract infections, and surgical site infections.
RESISTANCE OF CONCERN ■ Some strains of Pseudomonas aeruginosa have been found to be resistant
to nearly all or all antibiotics including aminoglycosides, cephalosporins, fluoroquinolones, and carbapenems.
■ Approximately 8% of all healthcare-associated infections reported to CDC’s National Healthcare Safety Network are caused by Pseudomonas aeruginosa.
■ About 13% of severe healthcare-associated infections caused by Pseudomonas aeruginosa are multidrug resistant, meaning several classes of antibiotics no longer cure these infections.
PUBLIC HEALTH THREATAn estimated 51,000 healthcare-associated Pseudomonas aeruginosa infections occur in the United States each year. More than 6,000 (or 13%) of these are multidrug-resistant, with roughly 400 deaths per year attributed to these infections.
Percentage of all Pseudomonas aeruginosa healthcare-associated infections that are multidrug-resistant
Estimated number of infections
Estimated number of deaths attributed
Multi-drug resistant Pseudomonas aeruginosa 13% 6,700 440
For more information about data methods and references, please see technical appendix.
6,700 440MULTIDRUG-RESISTANT PSEUDOMONASINFECTIONS
DEATHS
THREAT LEVELSERIOUSThis bacteria is a serious concern and requires prompt
and sustained action to ensure the problem does not grow.51,000 PSEUDOMONAS
INFECTIONS PER YEAR
METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS (MRSA)
80,461 11,285SEVERE MRSA INFECTIONS PER YEAR
DEATHS FROM MRSA PER YEAR
STAPH BACTERIA ARE A LEADING CAUSE OF
HEALTHCARE-ASSOCIATED INFECTIONSTHREAT LEVEL
SERIOUSThis bacteria is a serious concern and requires prompt
and sustained action to ensure the problem does not grow.
Methicillin-resistant Staphylococcus aureus (MRSA) causes a range of illnesses, from skin and wound infections to pneumonia and bloodstream infections that can cause sepsis and death. Staph bacteria, including MRSA, are one of the most common causes of healthcare-associated infections.
RESISTANCE OF CONCERNResistance to methicillin and related antibiotics (e.g., nafcillin, oxacillin) and resistance to cephalosporins are of concern.
PUBLIC HEALTH THREAT CDC estimates 80,461 invasive MRSA infections and 11,285 related deaths occurred in 2011. An unknown but much higher number of less severe infections occurred in both the community and in healthcare settings.
Severe MRSA infections
mostly occur during or soon after inpatient
medical care.
Revised Annualized National Estimates, ABCs MRSA 2005–2011 (updated Nov, 2012)
For more information about data methods and references, please see technical appendix.
The bugs are not the same…
Pathology is not the same
The Narrow Spectrum Era…….
1925
1950
1975
2000
2025
Golden EraNature products
Medicinal Chemistry EraSynthetic tweaking
Resistance eraTarget based, broad spectrum
Narrow-Spectrum eraUnconventionalCombination approachesDiagnostic development
1925
1975
2000
2025
1950
The Narrow Spectrum Era…….
1925
1950
1975
2000
2025
Golden EraNature products
Medicinal Chemistry EraSynthetic tweaking
Resistance eraTarget based, broad spectrum
Narrow-Spectrum eraUnconventionalCombination approachesDiagnostic development
1925
1975
2000
2025
1950
Sepsis is
If ICU and ED want to own sepsis…..
In memory of my sister Bec
Most people spend their time and energy going around problems rather than in trying to solve them.
Henry Ford