Measuring antibiotics in exhaled air in critically ill, non-ventilated patients: A feasibility and proof of concept study

This article by Herregodts and colleagues was published online during January 2019 in the Journal of Critical Care.
Purpose:  Measurement of antibiotic concentrations is increasingly used to optimize antibiotic therapy. Plasma samples are typically used for this, but other matrices such as exhaled air could be an alternative.
Materials and methods:  We studied 11 spontaneously breathing intensive care unit patients receiving either piperacillin/tazobactam or meropenem. Patients exhaled in the ExaBreath® device, from which the antibiotic was extracted. The presence of antibiotics was also determined in the condensate found in the device and in the plasma.
Results:  Piperacillin or meropenem could be detected in the filter in 9 patients and in the condensate in 10. Seven patients completed the procedure as prescribed. In these patients the median quantity of piperacillin in the filter was 3083 pg/filter (range 988–203,895 pg/filter), and 45 pg (range 6–126 pg) in the condensate; meropenem quantity was 21,168 pg/filter, but the quantity in the condensate was below the lower limit of quantification. There was no correlation between the concentrations in the plasma and quantities detected in the filter or condensate.
Conclusions:  Piperacillin and meropenem can be detected and quantified in exhaled air of non-ventilated intensive care unit patients; these quantities did not correlate with plasma concentrations of these drugs.
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A complete and multifaceted overview of antibiotic use and infection diagnosis in the intensive care unit: results from a prospective four-year registration

This article in Critical Care September 2018 issue was produced by De Bus and colleagues.
Background:  Preparing an antibiotic stewardship program requires detailed information on overall antibiotic use, prescription indication and ecology. However, longitudinal data of this kind are scarce. Computerization of the patient chart has offered the potential to collect complete data of high resolution. To gain insight in our global antibiotic use, we aimed to explore antibiotic prescription in our intensive care unit (ICU) from various angles over a prolonged time period.
Methods:  We studied all adult patients admitted to Ghent University Hospital ICU from 1 January 2013 until 31 December 2016. Antibiotic prescription data were prospectively merged with diagnostic (suspected focus, severity and probability of infection at the time of prescription, or prophylaxis) and microbiology data by ICU physicians during daily workflow through dedicated software. Definite focus of infection and probability of infection (classified as high/moderate/low) were reassessed by dedicated ICU physicians at patient discharge.
Results:  During the study period, 8763 patients were admitted and overall antibiotic consumption amounted to 1232 days of therapy (DOT)/1000 patient days. Antibacterial DOT (84% of total DOT) were linked with infection in 80%; the predominant foci were the respiratory tract (49%) and the abdomen (19%). A microbial cause was identified in 56% (3169/5686). Moderate/low probability infections accounted for 42% of antibacterial DOT prescribed for respiratory tract infections; for abdominal infections, this figure was 15%. The median treatment duration of moderate/low probability respiratory infections was 4 days (IQR 3-7). Antifungal DOT (16% of total DOT) were linked with infection in 47% of total antifungal DOT. Antifungal prophylaxis was primarily administered in the surgical ICU (76%), with a median duration of 4 DOT (IQR 2-9).
Conclusions:  By prospectively combining antibiotic, microbiology and clinical data we were able to construct a longitudinal, multifaceted data set on antibiotic use and infection diagnosis. A complete overview of this kind may allow the identification of antibiotic prescription patterns that require future antibiotic stewardship attention.
The full text of the article is available via this link.

Effect of procalcitonin-guided antibiotic treatment on clinical outcomes in intensive care unit patients with infection and sepsis patients: a patient-level meta-analysis of randomized trials

The secondary research was published in the journal Critical Care in August 2018 by Wirz and others.
Background:  The clinical utility of serum procalcitonin levels in guiding antibiotic treatment decisions in patients with sepsis remains unclear. This patient-level meta-analysis based on 11 randomized trials investigates the impact of procalcitonin-guided antibiotic therapy on mortality in intensive care unit (ICU) patients with infection, both overall and stratified according to sepsis definition, severity, and type of infection.
Methods:  For this meta-analysis focusing on procalcitonin-guided antibiotic management in critically ill patients with sepsis of any type, in February 2018 we updated the database of a previous individual patient data meta-analysis which was limited to patients with respiratory infections only. We used individual patient data from 11 trials that randomly assigned patients to receive antibiotics based on procalcitonin levels (the “procalcitonin-guided” group) or the current standard of care (the “controls”). The primary endpoint was mortality within 30 days. Secondary endpoints were duration of antibiotic treatment and length of stay.
Results:  Mortality in the 2252 procalcitonin-guided patients was significantly lower compared with the 2230 control group patients (21.1% vs 23.7%; adjusted odds ratio 0.89, 95% confidence interval (CI) 0.8 to 0.99; p = 0.03). These effects on mortality persisted in a subgroup of patients meeting the sepsis 3 definition and based on the severity of sepsis (assessed on the basis of the Sequential Organ Failure Assessment (SOFA) score, occurrence of septic shock or renal failure, and need for vasopressor or ventilatory support) and on the type of infection (respiratory, urinary tract, abdominal, skin, or central nervous system), with interaction for each analysis being > 0.05. Procalcitonin guidance also facilitated earlier discontinuation of antibiotics, with a reduction in treatment duration (9.3 vs 10.4 days; adjusted coefficient -1.19 days, 95% CI -1.73 to -0.66; p < 0.001).
Conclusion:  Procalcitonin-guided antibiotic treatment in ICU patients with infection and sepsis patients results in improved survival and lower antibiotic treatment duration.
The full text of this article is freely available via this link.

Impact of antibiotic therapy in severe community-acquired pneumonia:

Antibiotic therapy (AT) is the cornerstone of the management of severe community-acquired pneumonia (CAP). However, the best treatment strategy is far from being established | Journal of Critical Care



  • In SCAP patients, the use of combination of antibiotics that includes a macrolide is associated a better hospital and long term (6 months) survival.
  • Courses of antibiotic therapy longer than 7 days are not associated with survival benefit but lead to longer ICU and hospital LOS.
  • Serum lactate showed to be a good prognostic marker of hospital mortality in SCAP patients.

Full reference: Pereira, J.M. et al. (2017) Impact of antibiotic therapy in severe community-acquired pneumonia: Data from the Infauci study. Journal of Critical Care. Published online: 4 September 2017

Early Antibiotics & Fluids Key in Sepsis Management

Sepsis and septic shock are medical emergencies that require immediate action | Anesthesiology News

Early resuscitation should begin with early antibiotics and fluids, as well as the identification of the source of infection, according to new guidelines that were released at the Society of Critical Care Medicine’s (SCCM) 2017 Critical Care Congress.

In addition, the new guidelines say a health care provider who is trained and skilled in the management of sepsis should reassess the patient frequently at the bedside. “It is not the initial assessment, but the frequent reassessment that will make a difference,” said Andrew Rhodes, MD, FRCP, FRCA, FFICM, the co-chair of the guidelines committee.

Read the full news story here

Antibiotic therapy in critically ill patients

Martin-Loeches, I. et al. European Journal of Anaesthesiology. Published online: 30  January 2017

Antimicrobial treatment is the cornerstone of infection treatment, and the selection of appropriate antibiotic treatment for critically ill patients is challenging. Clinicians working with critically ill patients usually feel a greater obligation towards their patient than towards maintenance of the delicate ecological balance of prevalent microbiological threats and their resistance patterns. Although antibiotic overtreatment is a frequent phenomenon, patient outcomes need not be compromised when antibiotic treatment is driven by informed decision-making.

At the 2016 Euro Anaesthesia Conference (London, UK), the European Society of Anaesthesia Intensive Care Scientific Subcommittee convened an expert panel on antibiotic therapy. This article summarises the main conclusions of the panel, namely the principles of antibiotic therapy that all physicians working with critically ill patients must know.

Read the abstract here

Healthcare-Associated Pneumonia in the ICU: Guideline-Concordant Antibiotics and Outcome

Attridge, R.T. et al. Journal of Critical Care | Published online: August 11, 2016

L0075034 An intensive care unit in a hospital.
Image source: Robert Priseman – Wellcome Library // CC BY-NC-ND 4.0

Purpose: Recent data have not demonstrated improved outcomes when guideline-concordant (GC) antibiotics are given to patients with healthcare-associated pneumonia (HCAP). This study was designed to evaluate the relationship between health outcomes and GC therapy in patients admitted to an ICU with HCAP.

Materials and Methods: We performed a population-based cohort study of patients admitted to >150 hospitals in the U.S. Veterans Health Administration system to compare baseline characteristics, bacterial pathogens, and health outcomes in ICU patients with HCAP receiving either GC-HCAP therapy, GC community-acquired pneumonia (GC-CAP) therapy, or non-GC therapy. The primary outcome was 30-day patient mortality. Risk factors for the primary outcome were assessed in a multivariable logistic regression model.

Results: A total of 3593 patients met inclusion criteria and received GC-HCAP therapy (26%), GC-CAP therapy (23%), or non-GC therapy (51%). GC-HCAP patients had higher 30-day patient mortality compared to GC-CAP patients (34% vs. 22%, P < .0001). After controlling for confounders, risk factors for 30-day patient mortality were vasopressor use (OR, 95% CI; 1.67, 1.30–2.13), recent hospital admission (1.53, 1.15–2.02), and receipt of GC-HCAP therapy (1.51, 1.20–1.90).

Conclusions: Our data do not demonstrate improved outcomes among ICU patients with HCAP who received GC-HCAP therapy.

Read the abstract here

Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial

The Lancet Infectious Diseases

Median consumption of antibiotics was 7.5 daily defined doses (DDD) in the procalcitonin-guided group v 9.3 DDD in the standard-of-care group (absolute difference 2.69, p<0.0001), and median duration of treatment was 5 v 7 days respectively (absolute difference 1.22, p<0.0001).

Antibiotic resistance: World on cusp of ‘post-antibiotic era’

The world is on the cusp of a “post-antibiotic era”, scientists have warned after finding bacteria resistant to drugs used when all other treatments have failed.
They identified bacteria able to shrug off the drug of last resort – colistin – in patients and livestock in China.
They said that resistance would spread around the world and raised the spectre of untreatable infections.
It is likely resistance emerged after colistin was overused in farm animals.
Bacteria becoming completely resistant to treatment – also known as the antibiotic apocalypse – could plunge medicine back into the dark ages.