John Ferguson Infectious Diseases Physician and Microbiologist Newcastle NSW

2019 Part 1 M Med UPNG revision weeks

a An infection which leads to death

b An infection with a SIRS response

c Sepsis in an immunosompromised host

d Sepsis leading to acute organ dysfunction

e An infection plus at least 3 SIRS criteria

Definitions amp Pathogenesis Burden and causes of sepsis Identifying septic patients patient

assessment Approach to septic patient

From the Greek word for ldquoputrefactionrdquo

An exaggerated host response to invasive infection

AKA ldquoblood poisoningrdquo ldquosepticaemiardquo

Infection PLUS a systemic inflammatory response syndrome (SIRS)

Research definition (ACCPSCCM 1992)1

Proven or suspected infection plus SIRS

SIRS=2 or more of

Fever (or hypothermia)

Tachycardia (HRgt90)

Tachypnoea (RRgt20 or PaCO2lt32)

Abnormal white blood cell count (lt4 or gt12)

1 ndash Bone (1992) Chest 1011644

ACCPSCCM 1992)1 Severe sepsis= sepsis + organ dysfunction

httpsjamanetworkcomjournalsjamafullarticle2492881

a An infection which leads to death

b An infection with a SIRS response

c Sepsis in an immunosompromised host

d Sepsis leading to acute organ dysfunction

e An infection plus at least 3 SIRS criteria

Definitions amp Pathogenesis Burden and causes of sepsis Identifying septic patients patient

assessment Approach to septic patient

From the Greek word for ldquoputrefactionrdquo

An exaggerated host response to invasive infection

AKA ldquoblood poisoningrdquo ldquosepticaemiardquo

Infection PLUS a systemic inflammatory response syndrome (SIRS)

Research definition (ACCPSCCM 1992)1

Proven or suspected infection plus SIRS

SIRS=2 or more of

Fever (or hypothermia)

Tachycardia (HRgt90)

Tachypnoea (RRgt20 or PaCO2lt32)

Abnormal white blood cell count (lt4 or gt12)

1 ndash Bone (1992) Chest 1011644

ACCPSCCM 1992)1 Severe sepsis= sepsis + organ dysfunction

httpsjamanetworkcomjournalsjamafullarticle2492881

Definitions amp Pathogenesis Burden and causes of sepsis Identifying septic patients patient

assessment Approach to septic patient

From the Greek word for ldquoputrefactionrdquo

An exaggerated host response to invasive infection

AKA ldquoblood poisoningrdquo ldquosepticaemiardquo

Infection PLUS a systemic inflammatory response syndrome (SIRS)

Research definition (ACCPSCCM 1992)1

Proven or suspected infection plus SIRS

SIRS=2 or more of

Fever (or hypothermia)

Tachycardia (HRgt90)

Tachypnoea (RRgt20 or PaCO2lt32)

Abnormal white blood cell count (lt4 or gt12)

1 ndash Bone (1992) Chest 1011644

ACCPSCCM 1992)1 Severe sepsis= sepsis + organ dysfunction

httpsjamanetworkcomjournalsjamafullarticle2492881

From the Greek word for ldquoputrefactionrdquo

An exaggerated host response to invasive infection

AKA ldquoblood poisoningrdquo ldquosepticaemiardquo

Infection PLUS a systemic inflammatory response syndrome (SIRS)

Research definition (ACCPSCCM 1992)1

Proven or suspected infection plus SIRS

SIRS=2 or more of

Fever (or hypothermia)

Tachycardia (HRgt90)

Tachypnoea (RRgt20 or PaCO2lt32)

Abnormal white blood cell count (lt4 or gt12)

1 ndash Bone (1992) Chest 1011644

ACCPSCCM 1992)1 Severe sepsis= sepsis + organ dysfunction

httpsjamanetworkcomjournalsjamafullarticle2492881

Research definition (ACCPSCCM 1992)1

Proven or suspected infection plus SIRS

SIRS=2 or more of

Fever (or hypothermia)

Tachycardia (HRgt90)

Tachypnoea (RRgt20 or PaCO2lt32)

Abnormal white blood cell count (lt4 or gt12)

1 ndash Bone (1992) Chest 1011644

ACCPSCCM 1992)1 Severe sepsis= sepsis + organ dysfunction

httpsjamanetworkcomjournalsjamafullarticle2492881

ACCPSCCM 1992)1 Severe sepsis= sepsis + organ dysfunction

httpsjamanetworkcomjournalsjamafullarticle2492881

httpsjamanetworkcomjournalsjamafullarticle2492881

Sepsis = life-threatening organ dysfunction

caused by a dysregulated host response to

infection

Organ dysfunction = an increase in the

Sequential [Sepsis-related] Organ Failure

Assessment (SOFA) score of 2 points or more

Septic shock = subset of sepsis in which hellip

vasopressor requirement to maintain a mean

arterial pressure of 65 mm Hg or greater and

serum lactate level greater than 2 mmolL (gt18 mgdL) in the absence of hypovolemia

httpsjamanetworkcomjournalsjamafullarticle2492881

Martin et al (2003) NEJM 348(16)

Leading cause of death in intensive care Estimated 18 million casesyear

worldwide1

215000 deaths per year in USA 2

Estimated 13000 ICU admissions and 4875 deaths from severe sepsis in ANZ each year 3

1 Slade (2003) Crit Care 71-2

2 Angus (2001) Crit Care Med 291303

3 Finfer (2004) Int Care Med 30589

28-day mortality in AustraliaUSA Sepsis 10-30 Severe sepsis 25-40 Septic shock 30-60

Long-term outcomes are even worse

These high mortality rates continue despite Advanced supportive care Aggressive antibiotic and surgical

management of infection

Community presentation Healthcare associated

bull Urine bull Skinsoft tissue bull Biliary bull Intra-abdominal bull Pneumonia empyaemabull Brain

bull Severe malariabull Severe denguebull Disseminated TB

bull Intravenous linesbull Urinary cathetersbull Post-operative woundsbull Pneumonia (ICU)bull Skin- decubitus ulcers

Between April 1998 and

March 2000 multi-

resistant enteric gram

negative sepsis occurred

in 106 of 5331 paediatric

admissions (2) but

caused 87 (25) of 353

deaths

Oct 2007- Oct 2008 57 neonates with Klebsiella infection 23 died 31 multi-drug resistant including to 3 G

cephalosporins

Severe malaria Dengue shock syndrome

Incidence of MRSA now high from community and hospital sources (38+)

cf 1990 bacteraemia study by Naraqi et al- no MRSA detected

Lab identification and MRSA detection-must use cefoxitin screen

Mediators- cytokines and

other products of the

immune response to

infection Often an

exaggerated immune

response harms the patient

This is a view of the blood

vessels under the tongue of two

patients

Sublingual lsquoOrthogonal

Polarization Spectralrsquo imaging

Sorensen (1988)

Large cohort of adult adoptees (960 families) in Denmark

Examined risk of premature death (before age 50) in biological parents vs adopted children

If one biological parent had premature death risk in child

All cause 171

Cancers 119

Infections 452 N Engl J Med 1988 Mar 24318(12)727-32

Leading cause of death in intensive care Estimated 18 million casesyear

worldwide1

215000 deaths per year in USA 2

Estimated 13000 ICU admissions and 4875 deaths from severe sepsis in ANZ each year 3

1 Slade (2003) Crit Care 71-2

2 Angus (2001) Crit Care Med 291303

3 Finfer (2004) Int Care Med 30589

28-day mortality in AustraliaUSA Sepsis 10-30 Severe sepsis 25-40 Septic shock 30-60

Long-term outcomes are even worse

These high mortality rates continue despite Advanced supportive care Aggressive antibiotic and surgical

management of infection

Community presentation Healthcare associated

bull Urine bull Skinsoft tissue bull Biliary bull Intra-abdominal bull Pneumonia empyaemabull Brain

bull Severe malariabull Severe denguebull Disseminated TB

bull Intravenous linesbull Urinary cathetersbull Post-operative woundsbull Pneumonia (ICU)bull Skin- decubitus ulcers

Between April 1998 and

March 2000 multi-

resistant enteric gram

negative sepsis occurred

in 106 of 5331 paediatric

admissions (2) but

caused 87 (25) of 353

deaths

Oct 2007- Oct 2008 57 neonates with Klebsiella infection 23 died 31 multi-drug resistant including to 3 G

cephalosporins

Severe malaria Dengue shock syndrome

Incidence of MRSA now high from community and hospital sources (38+)

cf 1990 bacteraemia study by Naraqi et al- no MRSA detected

Lab identification and MRSA detection-must use cefoxitin screen

Mediators- cytokines and

other products of the

immune response to

infection Often an

exaggerated immune

response harms the patient

This is a view of the blood

vessels under the tongue of two

patients

Sublingual lsquoOrthogonal

Polarization Spectralrsquo imaging

Sorensen (1988)

Large cohort of adult adoptees (960 families) in Denmark

Examined risk of premature death (before age 50) in biological parents vs adopted children

If one biological parent had premature death risk in child

All cause 171

Cancers 119

Infections 452 N Engl J Med 1988 Mar 24318(12)727-32

28-day mortality in AustraliaUSA Sepsis 10-30 Severe sepsis 25-40 Septic shock 30-60

Long-term outcomes are even worse

These high mortality rates continue despite Advanced supportive care Aggressive antibiotic and surgical

management of infection

Community presentation Healthcare associated

bull Urine bull Skinsoft tissue bull Biliary bull Intra-abdominal bull Pneumonia empyaemabull Brain

bull Severe malariabull Severe denguebull Disseminated TB

bull Intravenous linesbull Urinary cathetersbull Post-operative woundsbull Pneumonia (ICU)bull Skin- decubitus ulcers

Between April 1998 and

March 2000 multi-

resistant enteric gram

negative sepsis occurred

in 106 of 5331 paediatric

admissions (2) but

caused 87 (25) of 353

deaths

Oct 2007- Oct 2008 57 neonates with Klebsiella infection 23 died 31 multi-drug resistant including to 3 G

cephalosporins

Severe malaria Dengue shock syndrome

Incidence of MRSA now high from community and hospital sources (38+)

cf 1990 bacteraemia study by Naraqi et al- no MRSA detected

Lab identification and MRSA detection-must use cefoxitin screen

Mediators- cytokines and

other products of the

immune response to

infection Often an

exaggerated immune

response harms the patient

This is a view of the blood

vessels under the tongue of two

patients

Sublingual lsquoOrthogonal

Polarization Spectralrsquo imaging

Sorensen (1988)

Large cohort of adult adoptees (960 families) in Denmark

Examined risk of premature death (before age 50) in biological parents vs adopted children

If one biological parent had premature death risk in child

All cause 171

Cancers 119

Infections 452 N Engl J Med 1988 Mar 24318(12)727-32

Community presentation Healthcare associated

bull Urine bull Skinsoft tissue bull Biliary bull Intra-abdominal bull Pneumonia empyaemabull Brain

bull Severe malariabull Severe denguebull Disseminated TB

bull Intravenous linesbull Urinary cathetersbull Post-operative woundsbull Pneumonia (ICU)bull Skin- decubitus ulcers

Between April 1998 and

March 2000 multi-

resistant enteric gram

negative sepsis occurred

in 106 of 5331 paediatric

admissions (2) but

caused 87 (25) of 353

deaths

Oct 2007- Oct 2008 57 neonates with Klebsiella infection 23 died 31 multi-drug resistant including to 3 G

cephalosporins

Severe malaria Dengue shock syndrome

Incidence of MRSA now high from community and hospital sources (38+)

cf 1990 bacteraemia study by Naraqi et al- no MRSA detected

Lab identification and MRSA detection-must use cefoxitin screen

Mediators- cytokines and

other products of the

immune response to

infection Often an

exaggerated immune

response harms the patient

This is a view of the blood

vessels under the tongue of two

patients

Sublingual lsquoOrthogonal

Polarization Spectralrsquo imaging

Sorensen (1988)

Large cohort of adult adoptees (960 families) in Denmark

Examined risk of premature death (before age 50) in biological parents vs adopted children

If one biological parent had premature death risk in child

All cause 171

Cancers 119

Infections 452 N Engl J Med 1988 Mar 24318(12)727-32

Between April 1998 and

March 2000 multi-

resistant enteric gram

negative sepsis occurred

in 106 of 5331 paediatric

admissions (2) but

caused 87 (25) of 353

deaths

Oct 2007- Oct 2008 57 neonates with Klebsiella infection 23 died 31 multi-drug resistant including to 3 G

cephalosporins

Severe malaria Dengue shock syndrome

Incidence of MRSA now high from community and hospital sources (38+)

cf 1990 bacteraemia study by Naraqi et al- no MRSA detected

Lab identification and MRSA detection-must use cefoxitin screen

Mediators- cytokines and

other products of the

immune response to

infection Often an

exaggerated immune

response harms the patient

This is a view of the blood

vessels under the tongue of two

patients

Sublingual lsquoOrthogonal

Polarization Spectralrsquo imaging

Sorensen (1988)

Large cohort of adult adoptees (960 families) in Denmark

Examined risk of premature death (before age 50) in biological parents vs adopted children

If one biological parent had premature death risk in child

All cause 171

Cancers 119

Infections 452 N Engl J Med 1988 Mar 24318(12)727-32

Oct 2007- Oct 2008 57 neonates with Klebsiella infection 23 died 31 multi-drug resistant including to 3 G

cephalosporins

Severe malaria Dengue shock syndrome

Incidence of MRSA now high from community and hospital sources (38+)

cf 1990 bacteraemia study by Naraqi et al- no MRSA detected

Lab identification and MRSA detection-must use cefoxitin screen

Mediators- cytokines and

other products of the

immune response to

infection Often an

exaggerated immune

response harms the patient

This is a view of the blood

vessels under the tongue of two

patients

Sublingual lsquoOrthogonal

Polarization Spectralrsquo imaging

Sorensen (1988)

Large cohort of adult adoptees (960 families) in Denmark

Examined risk of premature death (before age 50) in biological parents vs adopted children

If one biological parent had premature death risk in child

All cause 171

Cancers 119

Infections 452 N Engl J Med 1988 Mar 24318(12)727-32

Severe malaria Dengue shock syndrome

Incidence of MRSA now high from community and hospital sources (38+)

cf 1990 bacteraemia study by Naraqi et al- no MRSA detected

Lab identification and MRSA detection-must use cefoxitin screen

Mediators- cytokines and

other products of the

immune response to

infection Often an

exaggerated immune

response harms the patient

This is a view of the blood

vessels under the tongue of two

patients

Sublingual lsquoOrthogonal

Polarization Spectralrsquo imaging

Sorensen (1988)

Large cohort of adult adoptees (960 families) in Denmark

Examined risk of premature death (before age 50) in biological parents vs adopted children

If one biological parent had premature death risk in child

All cause 171

Cancers 119

Infections 452 N Engl J Med 1988 Mar 24318(12)727-32

Incidence of MRSA now high from community and hospital sources (38+)

cf 1990 bacteraemia study by Naraqi et al- no MRSA detected

Lab identification and MRSA detection-must use cefoxitin screen

Mediators- cytokines and

other products of the

immune response to

infection Often an

exaggerated immune

response harms the patient

This is a view of the blood

vessels under the tongue of two

patients

Sublingual lsquoOrthogonal

Polarization Spectralrsquo imaging

Sorensen (1988)

Large cohort of adult adoptees (960 families) in Denmark

Examined risk of premature death (before age 50) in biological parents vs adopted children

If one biological parent had premature death risk in child

All cause 171

Cancers 119

Infections 452 N Engl J Med 1988 Mar 24318(12)727-32

Mediators- cytokines and

other products of the

immune response to

infection Often an

exaggerated immune

response harms the patient

This is a view of the blood

vessels under the tongue of two

patients

Sublingual lsquoOrthogonal

Polarization Spectralrsquo imaging

Sorensen (1988)

Large cohort of adult adoptees (960 families) in Denmark

Examined risk of premature death (before age 50) in biological parents vs adopted children

If one biological parent had premature death risk in child

All cause 171

Cancers 119

Infections 452 N Engl J Med 1988 Mar 24318(12)727-32

This is a view of the blood

vessels under the tongue of two

patients

Sublingual lsquoOrthogonal

Polarization Spectralrsquo imaging

Sorensen (1988)

Large cohort of adult adoptees (960 families) in Denmark

Examined risk of premature death (before age 50) in biological parents vs adopted children

If one biological parent had premature death risk in child

All cause 171

Cancers 119

Infections 452 N Engl J Med 1988 Mar 24318(12)727-32

Sorensen (1988)

Large cohort of adult adoptees (960 families) in Denmark

Examined risk of premature death (before age 50) in biological parents vs adopted children

If one biological parent had premature death risk in child

All cause 171

Cancers 119

Infections 452 N Engl J Med 1988 Mar 24318(12)727-32

N Engl J Med 1988 Mar 24318(12)727-32Genetic and environmental influences on premature death in adult adopteesSoslashrensen TI1 Nielsen GG Andersen PK Teasdale TWAuthor informationAbstractTo assess genetic and environmental influences on adult mortality we followed 960 families that included children born during the period 1924 through 1926 who were placed early in life with adoptive parents unrelated to them We evaluated the risks of dying from all causes or from specific groups of causes between the ages of 16 and 58 years for adoptees with a biologic or adoptive parent who died of the same cause before the age of either 50 or 70 We compared these risks with the adoptees risk of dying from the same causes between the ages of 16 and 58 when either the biologic or adoptive parents were still alive at the ages of 50 and 70 The death of a biologic parent before the age of 50 resulted in relative risks of death in the adoptees of 171 (95 percent confidence interval 114 to 257) for all causes 198 (125 to 312) for natural causes 581 (247 to 137) for infections 452 (132 to 154) for cardiovascular and cerebrovascular causes and 119 (016 to 899) for cancers The death of an adoptive parent resulted in relative risks of death in the adoptees that were close to unity for all causes natural causes and infections 302 (072 to 128) for vascular causes and 516 (120 to 222) for cancers A similar but weaker pattern was observed when either a biologic or adoptive parent died before the age of 70 We conclude that premature death in adults has a strong genetic background--especially death due to infections and vascular causes

Definitions amp Pathogenesis Burden and causes of sepsis Identifying septic patients patient

assessment Approach to septic patient

1 Clinical assessment- origin of patient HIV past medical history including diabetes immunosuppressive medication

2 Laboratory diagnostic testing3 Antibiotics after cultures- as early as possible4 Administer oxygen5 Resuscitation ndash Fluids 6 Source identification and control7 Adequate glycaemic control (keep blood glucose

near normal )8 Consider corticosteroids ndash patients unresponsive to

fluid challenge vasopressors

Early appropriate RECOGNITION is the key NSW health Sepsis Pathway

Automated system ndash BACTEC- better media for growing bacteria accommodates larger volume of patientrsquos blood- increases sensitivity

Aseptic collection procedure important to avoid contamination with skin flora

Quicker to become positive ndash usually within 12 hours

Broth is Gram stained and then subcultured

httpsaimednetau20150918maximising-the-value-of-blood-cultures

1 Clinical assessment- origin of patient HIV past medical history including diabetes immunosuppressive medication

2 Laboratory diagnostic testing3 Antibiotics after cultures- as early as possible4 Administer oxygen5 Resuscitation ndash Fluids 6 Source identification and control7 Adequate glycaemic control (keep blood glucose

near normal )8 Consider corticosteroids ndash patients unresponsive to

fluid challenge vasopressors

Early appropriate RECOGNITION is the key NSW health Sepsis Pathway

Automated system ndash BACTEC- better media for growing bacteria accommodates larger volume of patientrsquos blood- increases sensitivity

Aseptic collection procedure important to avoid contamination with skin flora

Quicker to become positive ndash usually within 12 hours

Broth is Gram stained and then subcultured

httpsaimednetau20150918maximising-the-value-of-blood-cultures

Early appropriate RECOGNITION is the key NSW health Sepsis Pathway

Automated system ndash BACTEC- better media for growing bacteria accommodates larger volume of patientrsquos blood- increases sensitivity

Aseptic collection procedure important to avoid contamination with skin flora

Quicker to become positive ndash usually within 12 hours

Broth is Gram stained and then subcultured

httpsaimednetau20150918maximising-the-value-of-blood-cultures

Automated system ndash BACTEC- better media for growing bacteria accommodates larger volume of patientrsquos blood- increases sensitivity

Aseptic collection procedure important to avoid contamination with skin flora

Quicker to become positive ndash usually within 12 hours

Broth is Gram stained and then subcultured

httpsaimednetau20150918maximising-the-value-of-blood-cultures

Cocci in clumps ndashStaph aureus coagulase negative staph (contaminants usually)

Cocci in chains-streptococci or enterococci

Gram positive rods -clostridia bacillus listeria

Rods- plump- E coli Klebsiella and similar anaerobic species

Slender rods-pseudomonas

Cocci ndash Neisseria meningitidis (the meningococcus)

Cocco-bacilli -Acinetobacter

Candida (left) Cryptococcus (right with capsule ndashindia ink preparation) predominantly filamentous moulds very rare

IV line infections (candida)

Skinsoft tissuebone infection High rates of methicillin-resistant Staphylococcus aureus (MRSA)

PMGH 2016 - 39 to 60 isolate testing as MRSA across adult and paediatric groups inpatient and non-inpatient locations

Implication ndash MRSA resistant to all available betalactam agents ndash eg flucloxacillin amoxycillin+clavulanate ceftriaxone

Pneumonia Streptococcus pneumoniae- benzylpenicillin remains

the mainstay Meningitis

Streptococcus pneumoniae- ceftriaxone (also covers Haemophilus influenzae and Neisseria meningitidis)

Options

Vancomycin iv ndash given as loading dose 25mgkg (actual body weight) slow infusion (red man syndrome) then twice daily dosage

[Chloramphenicol ivoral

[doxycycline or co-trimoxazole- oral options

High mortality- correlated with age of patient higher for MRSA

Define lsquouncomplicatedrsquo and lsquocomplicatedrsquo cases

Risk of relapse up to 3 months later Echocardiogram in the second week of

treatment Minimum 2 weeks IV treatment at

endocarditis doses 4 weeks minimum for complicated cases httpsaimednetau20151015essential-

clinical-care-of-staphylococcus-aureus-bloodstream-infection-sab

Rods- plump- E coli Klebsiella and similar anaerobic species

Slender rods-pseudomonas

Cocci ndash Neisseria meningitidis (the meningococcus)

Cocco-bacilli -Acinetobacter

Candida (left) Cryptococcus (right with capsule ndashindia ink preparation) predominantly filamentous moulds very rare

IV line infections (candida)

Skinsoft tissuebone infection High rates of methicillin-resistant Staphylococcus aureus (MRSA)

PMGH 2016 - 39 to 60 isolate testing as MRSA across adult and paediatric groups inpatient and non-inpatient locations

Implication ndash MRSA resistant to all available betalactam agents ndash eg flucloxacillin amoxycillin+clavulanate ceftriaxone

Pneumonia Streptococcus pneumoniae- benzylpenicillin remains

the mainstay Meningitis

Streptococcus pneumoniae- ceftriaxone (also covers Haemophilus influenzae and Neisseria meningitidis)

Options

Vancomycin iv ndash given as loading dose 25mgkg (actual body weight) slow infusion (red man syndrome) then twice daily dosage

[Chloramphenicol ivoral

[doxycycline or co-trimoxazole- oral options

High mortality- correlated with age of patient higher for MRSA

Define lsquouncomplicatedrsquo and lsquocomplicatedrsquo cases

Risk of relapse up to 3 months later Echocardiogram in the second week of

treatment Minimum 2 weeks IV treatment at

endocarditis doses 4 weeks minimum for complicated cases httpsaimednetau20151015essential-

clinical-care-of-staphylococcus-aureus-bloodstream-infection-sab

Candida (left) Cryptococcus (right with capsule ndashindia ink preparation) predominantly filamentous moulds very rare

IV line infections (candida)

Skinsoft tissuebone infection High rates of methicillin-resistant Staphylococcus aureus (MRSA)

PMGH 2016 - 39 to 60 isolate testing as MRSA across adult and paediatric groups inpatient and non-inpatient locations

Implication ndash MRSA resistant to all available betalactam agents ndash eg flucloxacillin amoxycillin+clavulanate ceftriaxone

Pneumonia Streptococcus pneumoniae- benzylpenicillin remains

the mainstay Meningitis

Streptococcus pneumoniae- ceftriaxone (also covers Haemophilus influenzae and Neisseria meningitidis)

Options

Vancomycin iv ndash given as loading dose 25mgkg (actual body weight) slow infusion (red man syndrome) then twice daily dosage

[Chloramphenicol ivoral

[doxycycline or co-trimoxazole- oral options

High mortality- correlated with age of patient higher for MRSA

Define lsquouncomplicatedrsquo and lsquocomplicatedrsquo cases

Risk of relapse up to 3 months later Echocardiogram in the second week of

treatment Minimum 2 weeks IV treatment at

endocarditis doses 4 weeks minimum for complicated cases httpsaimednetau20151015essential-

clinical-care-of-staphylococcus-aureus-bloodstream-infection-sab

Skinsoft tissuebone infection High rates of methicillin-resistant Staphylococcus aureus (MRSA)

PMGH 2016 - 39 to 60 isolate testing as MRSA across adult and paediatric groups inpatient and non-inpatient locations

Implication ndash MRSA resistant to all available betalactam agents ndash eg flucloxacillin amoxycillin+clavulanate ceftriaxone

Pneumonia Streptococcus pneumoniae- benzylpenicillin remains

the mainstay Meningitis

Streptococcus pneumoniae- ceftriaxone (also covers Haemophilus influenzae and Neisseria meningitidis)

Options

Vancomycin iv ndash given as loading dose 25mgkg (actual body weight) slow infusion (red man syndrome) then twice daily dosage

[Chloramphenicol ivoral

[doxycycline or co-trimoxazole- oral options

High mortality- correlated with age of patient higher for MRSA

Define lsquouncomplicatedrsquo and lsquocomplicatedrsquo cases

Risk of relapse up to 3 months later Echocardiogram in the second week of

treatment Minimum 2 weeks IV treatment at

endocarditis doses 4 weeks minimum for complicated cases httpsaimednetau20151015essential-

clinical-care-of-staphylococcus-aureus-bloodstream-infection-sab

Options

Vancomycin iv ndash given as loading dose 25mgkg (actual body weight) slow infusion (red man syndrome) then twice daily dosage

[Chloramphenicol ivoral

[doxycycline or co-trimoxazole- oral options

High mortality- correlated with age of patient higher for MRSA

Define lsquouncomplicatedrsquo and lsquocomplicatedrsquo cases

Risk of relapse up to 3 months later Echocardiogram in the second week of

treatment Minimum 2 weeks IV treatment at

endocarditis doses 4 weeks minimum for complicated cases httpsaimednetau20151015essential-

clinical-care-of-staphylococcus-aureus-bloodstream-infection-sab

High mortality- correlated with age of patient higher for MRSA

Define lsquouncomplicatedrsquo and lsquocomplicatedrsquo cases

Risk of relapse up to 3 months later Echocardiogram in the second week of

treatment Minimum 2 weeks IV treatment at

endocarditis doses 4 weeks minimum for complicated cases httpsaimednetau20151015essential-

clinical-care-of-staphylococcus-aureus-bloodstream-infection-sab

Intra-abdominal biliary urine source infections high mortality especially if treatment delayed

NB 15 of Gram negative (E coli and Klebsiella pneumoniae) isolates were susceptible to chloramphenicol in 2016

Ceftriaxone-resistant isolates (ldquoextended spectrum betalactamaserdquo) are usually resistant to gentamicin cotrimoxazole and ciprofloxacin in POM

Multi-resistant Gram negative sepsis antibiotic options Meropenem (last resort betalactam ndash a carbapenem)

[Fosfomycin (old antibiotic with broad Gram negative spectrum ndash really only practical for urine source infections)

Carbapenemase producing Gram negatives lsquoCPErsquo Colistin (old nephrotoxic IV antibiotic also used via nebulised route)

Essential Drainage of collections Repair of GIT perforations and lavage of

peritoneum Removal of infected invasive devices- IV lines

pacemakers prosthetic joints

SAFE

6997 critically ill

09 Saline vs 4 Albumin

No difference in mortality

Trend to benefit of albumin in sepsis subgroup

OR for mortality 087 [074-102]

aOR for mortality 071 [052-097]

1 SAFE investigators NEJM 3502247

Most physicians under-fill Fluid overloadpulmonary oedema is easier to

treat than established septic shock

(If there is access to modern ICUs)

Excess fluids potentially hazardous in children

httpswwwncbinlmnihgovpubmed27062617

Essential Drainage of collections Repair of GIT perforations and lavage of

peritoneum Removal of infected invasive devices- IV lines

pacemakers prosthetic joints

SAFE

6997 critically ill

09 Saline vs 4 Albumin

No difference in mortality

Trend to benefit of albumin in sepsis subgroup

OR for mortality 087 [074-102]

aOR for mortality 071 [052-097]

1 SAFE investigators NEJM 3502247

Most physicians under-fill Fluid overloadpulmonary oedema is easier to

treat than established septic shock

(If there is access to modern ICUs)

Excess fluids potentially hazardous in children

httpswwwncbinlmnihgovpubmed27062617

SAFE

6997 critically ill

09 Saline vs 4 Albumin

No difference in mortality

Trend to benefit of albumin in sepsis subgroup

OR for mortality 087 [074-102]

aOR for mortality 071 [052-097]

1 SAFE investigators NEJM 3502247

Most physicians under-fill Fluid overloadpulmonary oedema is easier to

treat than established septic shock

(If there is access to modern ICUs)

Excess fluids potentially hazardous in children

httpswwwncbinlmnihgovpubmed27062617

Most physicians under-fill Fluid overloadpulmonary oedema is easier to

treat than established septic shock

(If there is access to modern ICUs)

Excess fluids potentially hazardous in children

httpswwwncbinlmnihgovpubmed27062617

httpswwwncbinlmnihgovpubmed27062617

Annane study 300 refractory septic shock within 8 hours of onset Hydrocortisone 50mg q6h + fludrocortisone 28-Day mortality decreased 55 vs 61 Inadequate adrenal reserve group 53 vs 63

CORTICUS 499 septic shock within 72h (not refractory) Hydrocortisone 50mg q6h 28-Day mortality no change 35 vs 32 Faster reversal of shock 33 vs 58 days No difference according to ldquoadrenal reserverdquo

ADRENAL just reported (2018)

httpswwwncbinlmnihgovpubmed29347874

httpswwwncbinlmnihgovpubmed29347874

There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia

httpswwwncbinlmnihgovpubmed29347874

Tight blood sugar control increases mortality Earlier studies suggested benefit1

NICE-SUGAR2

6104 medical and surgical ICU patients

BSL targets 45-6 vs lt10

Mortality 275 vs 249 (plt005)

Severe hypoglycaemia 68 vs 05

1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283

Prevention (infection control reduce unnecessary antibiotic exposure)

Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics

Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)

Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)

Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations

based on site of infection

Prevention (infection control reduce unnecessary antibiotic exposure)

Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics

Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)

Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)

Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations

based on site of infection