Category Archives: Infection

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

Antimicrobial resistance – a global challenge

This was a great session looking at the emerging and now obvious problem of antibiotic resistance.  Melvyn Mer opened with an overview of the problem:

Health professionals are afraid NOT to prescribe antibiotics and this is a major (but not the only) factor driving resistance across the world.  Despite international and national initiatives (such as the Anti Microbial Resistance review from the UK prime minister ) the problem is growing…

The organisms that are involved have changed over the last few years, with the pattern moving from gram positives to gram negatives – that being said MRSA and VRE are still a problem.  However the emergence of extended-spectrum Beta-lactamases (ESBLs) in Klebsiella, E Coli and Proteus along with beta-lactamase resistance among Enterobacters and Citrobacters, AND multi drug resistance in Pseudomonas aeruginosa, Acinetobacter spp., and Stenotrophomonas maltophilia becoming more common sets a scene where we ALL have a responsibility to think about antibiotics.  ICU of course tends to gather a lot of these together – the EPIC studies tell us that half the pts on ICU are infected at any one time.

This (open access) paper from the Annals of Intensive Care is worth a read to get a good overview.

Another takeaway from Melvyn Mers talk (apart from his inspirational quotes and singing!) was the spread of resistant fungals around the world.  An azole resistant candida, previously confined to the southern hemisphere, has now been isolated in the UK and an ICU somewhere in England has been fighting an outbreak of it over the last year (This alert from Public Health England from July this year is worth a read as are their guidelines on treating it).

How can we do anything about this? Well there a number of things.  Mer thought we (as a speciality) need to have clear guidelines to support health professionals NOT giving antibiotics, that there needs to be a push to address the agricultural sector (60% of worldwide antibiotics are used in animals) and, perhaps most relevant, was his plea to “get your own house in order”.  Start small…

There followed a talk from Matteo Bassetti showing the link between MDR infection with mortality – and unsurprisingly perhaps, there is a link.

Also the DALI study was mentioned – a really important ESICM study from Jason Roberts et al which not only said that ICU patients more often than not have inappropriate dosing regimens and antibiotic levels, but linked that with a poor outcome.  Worth a look: open access PDF of DALI trial

One of the solutions may well be tailoring / personalising antibiotics to the individual, including combination therapy, e.g.:

Otherwise, Dr Bassettis summary was this:

Finally in this session we heard about an initially French but now global initiative to help combat antibiotic resistance the – the world alliance against antimicrobial resistance (you can read about it here).  Overall it is one important part of the fightback that aims to bring in professionals from across the animal and human medicine spectrum and take action on antibiotic resistance.

Antibiotic stewardship in ICU

An important topic as antibiotic resistance is a growing problem across the world.

Dr Escoresa-Ortega presented her study looking at antibiotic de-escalation, and showed that antibiotics are often not de-escalated when they should be (about 70% of the time).  She identified risk factors for “no de-escalation” as a high SOFA score, previous antibiotic use, and abdominal or respiratory source of infection.  An interesting point made during the session is why exactly we dont de-escalate, and this study helps point to patient factors – but maybe there are more physician factors at play.

Next an interesting paper trying to think about what we ought to do with patients on antibiotics and renal replacement therapy.  The paper presented by Dr Muller looked at drug levels in 16 patients and showed the “best” strategy for amikacin was to use extended high dose therapy (25 mg/kg 48-hourly).  Again an interesting discussion ensued.  In general the principles of using antibiotics when on renal replacement are

  1. Start with a high dose first and then back off
  2. Use continuous (not intermittent) methods of renal replacement
  3. Use CVVHDF preferentially
  4. Interestingly continue RRT for 48hrs – should this be even in the face of no OTHER clinical indication? Im not sure, but if high dose has been given it could be a risk to stop.
  5. Drug monitoring – some in the room are great advocates for this, but it is a scarce resource in most ICU environments.  Apart from for amoniglycosides and glycopeptides routine access to therapeutic drug monitoring is rare (at least in a show of hands in the lecture here…)

Then we discussed Linezolid – a paper presented by Dr Munoz-Bermudez showed that only about a quarter of patients were in range when treated with the drug for gram positive infection at a dose of 600mg BD (most were subtherapueetic).  Renal failure seemed to be associated with both over and under treatment.  This is an odd but interesting finding if one considers that the manufacturers do not recommend drug dose alteration in linezolid treatment, but illustrates the problem with using these drugs in the ICU – many of the antibiotics are licensed following trials that dont have lots of critically ill patients.  Another plug for drug monitoring from the enthusiasts and they have a point.

Finally we heard about the Spanish zero resistance programme – an attempt to deal with the problem of antibiotic resistance via various measures.  One of these is use of a checklist – and Dr  Carvalho Brugger did a neat study looking at using a checklist.  It didn’t perform particularly well, missing several patients with resistant bugs – it only picked up 36% of them. Better than nothing? Or another form to get in the way…

The chair of the session Jeffrey Lipman finished with a caution; taking too many lessons on dealing with antibiotic resistance from one country to another might not work – we need to adapt to our own unit/region/country.