Category Archives: Infection

ICM Experimental 1: Concepts of Critical Illness


Inflammatory balance and imbalance

(Peter Pickkers)


Originally thought that pro-inflammatory phase occurs first, followed by anti-inflammatory phase

Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy


Initial inflammatory response NOT predictive of which patients become immunoparalysed later


Broad defects in the energy metabolism of leukocytes underlie immunoparalysis in sepsis.

Acute phase of infection- Warburg effect is seen in immune cells

This is absent in immunoparalysis, but can be reversed by IFN-gamma –> pharmacological intervention possibilities

Mounting overwhelming pro-inflammatory and anti-inflammatory responses early on = poorer outcome (refractory shock, immunoparalysis, late secondary infections and death)


To Attack or Tolerate: Novel concepts in host response

(Michael Bauer)


Innate immune system has memory, related to Warburg metabolism

Tiny doses of beta-glucan / LPS induce state of trained immunity; higher doses can cause immunoparalysis

Central role of Haem / Fe:

  • in the presence of free haem, a benign response turns into profound infection independent of pathogen dose
  • Hemopexin / haem oxygenase binds / removes extracellular free haem, uncontrolled sepsis can be controlled


Potential to manipulate haem response in addition to antimicrobials and anti-inflammatory drugs


Host Stress and Strain

(Mervyn Singer)

Critical illness strain on body analogous to that seen in Hooke’s Law of elasticity

  • within reversible zone –> acute illness and organ dysfunction –> recovery
  • beyond a ‘point of no return’, enters irreversible zone –> death


Less resilient pt: ‘point of no return’ shifts to left à tolerate less strain

Hardy pt: ‘point of no return’ shifts to right à more resistant to death


Intervention strategy to target specific phase of illness



Cardiac Troponin T (NOT as a marker of cardiac event) as an independent predictor of in-hospital mortality in emergency dept pts with suspected infection (de Groot et al., Emerg Med J 2014; 31:882-8)


Pathophysiological responses shouldn’t be simply viewed as disturbances of physiology, but as factors that accommodate the body to the insult

Is ‘shutting down’ an evolutionary mechanism?

–> Permissive hypercapnoea, hypoxaemia, hypotension, oliguria, anaemia etc could be beneficially targeted to help organs reach recovery phase, e.g.

  • ? avoid stressors (catecholamines, pain, severe cardioresp upset)
  • ? avoid arterial hyperoxia or even normoxia
  • ? induce hibernation or suspended animation
  • ? vagal stimulation of anti-inflammatory cholinergic pathway
  • ? beta-blockade +/- alpha-2-agonism
  • ? chill out psychologically
  • Acceptable patient-specific ranges need to be identified; timing, dosing and duration of intervention are Critical

Further reading:

The stress response and critical illness: A review (Cuesta et al., Crit Care Med 2012; 40:3283-9)


Stressing the obvious? An allostatic look at critical illness (Brame et al., Crit Care Med 2010; 38[Suppl.]: S600-7)


Changing the paradigm: Personalised antibiotics dosing for critically ill


(Prof Jeffery Lipman)

Interesting and thought provoking talk about how we might be inappropriately dosing antibiotics in our critically ill patients.

pK changes in ICU patients (also changes during the course of their ICU admission). Hence dosing is complex and studies confirm that it is very variable across ICUs.


IMG_0084 IMG_0087 IMG_0088



pD properties of antibacterials and hence kill characteristics different across the various classes of antibiotics.

IMG_0091 IMG_0093 IMG_0095



Proposed solutions:



The problem is that trials which had looked at continuous vs intermittent dosing of antibiotics e.g. BLINGs and BLISS, have focussed on clinical cure rather than mortality. Watch out for BLING3

Strategies in antibiotic therapy #EuAsia18

Nebulised antibiotics (J Oto)

IMG_3106 IMG_3108

Choice of antibiotics for nebulisation

  • not all antibiotics can be nebulised
  • produce high local concentrations with rapid clearance (poor systematic exposure)

Efficiency of abx nebulisation

  • Particle size
  • Nebuliser type
  • Nebuliser position
  • Circuit humidification management
  • Ventilator settings to avoid turbulence

Nebulization of Antiinfective Agents in Invasively Mechanically Ventilated Adults: A Systematic Review and Meta-analysis.

Nebulized Versus IV Amikacin as Adjunctive Antibiotic for Hospital and Ventilator-Acquired Pneumonia Postcardiac Surgeries: A Randomized Controlled Trial.


  • Nebulised abx provides high lung concentration
  • VAP caused by resistant gram negatives may be efficiently treated by nebulised abx without nephrotoxicity
  • Optimisation of nebulisation techniques and procedures needed


Optimising Beta Lactam Therapy (A Wong)

PowerPoint Slides

Screen Shot 2018-04-13 at 11.10.57 Screen Shot 2018-04-13 at 11.11.07 Screen Shot 2018-04-13 at 11.11.34

Continuous versus Intermittent β-Lactam Infusion in Severe Sepsis. A Meta-analysis of Individual Patient Data from Randomized Trials.

Continuous Infusion Versus Intermittent Bolus of Beta-Lactams in Critically Ill Patients with Respiratory Infections: A Systematic Review and Meta-analysis.

Continuous infusion of β-lactam antibiotics for all critically ill patients?

Prolonged infusion piperacillin-tazobactam decreases mortality and improves outcomes in severely ill patients: Results of a systematic review and meta-analysis

An international, multicentre survey of β-lactam antibiotic therapeutic drug monitoring practice in intensive care units.

Using Old Antibiotics in 2018 (J De Waele)


Challenges of old antibiotics

  • Lack of clinical evidence
    • Research in that era different
    • No guidance on RCTs
    • No combination therapy
    • Now used for other indications
  • Availability lacking due to manufacturing and logistical issues
  • Dosing
    • Data based on obsolete data
  • Susceptibility data
    • Lacking for many
    • Not standardised
    • Potential for resistance



EuAsia 2017 Day 2: Not only bacteria

Pre-emptive strategies in non bacterial infection (J De Waele @CriticCareDoc)

Invasive candidiasis has a high mortality (>50%) and expensive (>USD 40K), yet difficult to diagnosis

Terminology important – prophylaxis, pre-emptive, empirical vs directed therapy

Cochrane review available

Risk factors – antibiotic exposure, CVC, TPN, surgery, length of stay, etc BUT ICU climate has changed, better antiobiotic stewardship, less TPN etc

How to predict development of invasive candidiasis

  • Colonisation index – number of positive sites/total sites
  • Candida score – surgery, TPN, sepsis
  • Clinical prediction rule

Key messages

  • Antifungal stewardship
  • Untargeted antifungal treatment complex issue
  • Optimal pt population for prophylaxis difficult to identify
  • Recurrent intestinal leakage after surgery most obvious indication
  • Major impact of antifungal strategies remain to be demonstrated
  • Invasive disease incidence lower – changing risk factors?

2017-04-07 14.31.10 2017-04-07 14.20.12


Antifungal agents for preventing fungal infections in critically ill adults and children with a normal number of neutrophils in the blood

Clinical prediction rules for invasive candidiasis in the ICU: ready for prime time?

Empirical Micafungin Treatment and Survival Without Invasive Fungal Infection in Adults With ICU-Acquired Sepsis, Candida Colonization, and Multiple Organ Failure. The EMPIRICUS Randomized Clinical Trial 

Clinical Practice Guidelines for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America 


Invasive candidiasis: current therapy in critical care (H Qiu)

Major difficulty is differentiating colonisation vs infection

Fungal infection is under diagnosed – post-mortem findings

Candida albican is the major species BUT the situation is changing: Development of flucanozole resistance is increasing in countries e.g. China

Prediction scores have high negative predictive value but poor positive predictive value

Take home message

  • Move common that thought
  • High mortality
  • Earlier therapy not easy
  • Get it right first time (echinocandins)
  • De-escalate
  • Resistance if under treated/dosed


ESCMID† guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients


Severe dengue fever: the role of the intensivist (CM Chen)

Global burden – increase population, global warming, rapid urbanisation

Tropical climate

Spread by the female Aedes mosquito

Dengue classification 1997 – undifferentiated, dengue fever, dengue hemorrhagic fever; updated in 2009 into classes A, B and C

Diagnosis – serology

Dengue fever can cause multi-organ failure

Co-current bacterial infection not uncommon


WHO Dengue guidelines 2009

Critical care for dengue in adult patients: an overview of current knowledge and future challenges