Critical Care Reviews Profile picture
May 4, 2023 16 tweets 10 min read Read on X
➡️ Antimicrobial therapy has been used for millennia
➡️ Treating severe infections can be lifesaving
➡️ However, the widespread use of antimicrobials also has downsides

A 🧵

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➡️ Throughout history, honey, herbs & metals were often used
➡️ One of the earliest known antimicrobial therapies was the topical use of mouldy bread
➡️ This intervention has been recorded in many ancient civilisations, including Egypt, China, Serbia, Greece & Rome

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➡️ Mercury was used for epidemic diseases since the 1300s & especially syphilis
➡️ However, the treatment could be worse than the disease, with mercury poisoning possible
➡️ Treatment could last years, leading to the saying “A night with Venus, a lifetime with mercury”"

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➡️ Paul Erhlich discovered how to identify bacteria by staining them
➡️ He noted some stains were toxic for specific bacteria
➡️ In 1909, he discovered the arsenic-based Salvarsan for syphilis
➡️ This was the first modern antibiotic

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➡️ Alexander Fleming famously discovered penicillin in 1928
➡️ However, it had been used long before
➡️ In 1897, Ernest Duchesne noted Arabian stable boys treating saddle sores with mould from their saddles
➡️ He isolated Penicillium notatum from the mould

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➡️ German scientist Gerhard Domagk explored azo dyes, discovering Prontosil's therapeutic effects in 1932
➡️ French researcher Ernest Fourneau found Prontosil converted into sulfanilamide
➡️ This breakthrough launched the sulfonamide class & the Golden Age of Antibiotics

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➡️ At the beginning of the 20th century, life expectancy was 47 years
➡️ By 2019, in the USA, it was 79 years 
➡️ Infections, previously the most common cause of death, had been replaced by non-infectious causes
➡️ Antibiotics, along with other advances, had a huge impact

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➡️ However, it hasn't been plain sailing
➡️ Bacteria naturally develop resistance to toxins
➡️ MRSA was first identified in 1960, a year after methicillin was introduced
➡️ Genes encoding resistance to antibiotics have been identified in 30,000 year old permafrost sediments

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➡️ In 2019, there were an estimated 5 million resistance-associated deaths & 1·3 M attributable deaths
➡️ In the USA, > 2.8 M resistant infections occur yearly, with > 35,000 deaths
➡️ Globally, by 2050, there may be 10M deaths/year, costing the economy $100 trillion

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➡️ There are many drivers of antibiotic resistance
➡️ These include excessive & inappropriate use of broad spectrum antimicrobials
➡️ But, with 50% of critically ill septic patients lacking an identified pathogen, how can use be reduced?
➡️ How do we square the circle?

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➡️ Carbapenems are broad spectrum beta-lactam antibacterials
➡️ Their efficacy is dependent on the duration their serum concentration exceeds the pathogen's MIC
➡️ Continuous infusions can help achieve this
➡️ The aim is ⬆️ antimicrobial efficacy with ⬇️ risk of resistance

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➡️ The BLING II trial compared continuous with intermittent infusions of beta lactams in 432 patients with severe sepsis
➡️ There was no significant difference in
🔴 ICU free days
🔴 90-day survival
🔴 Clinical cure
➡️ However, the trial was not definitive

12/16

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➡️ Enter the MERCY trial!
➡️ An international, multi-center randomised double-blind trial in 600 pts with sepsis
➡️ Meropenem 3g continuous infusion vs 1g 8 hourly bolus
➡️ The primary endpoint is a composite outcome of mortality & emergence of drug-resistant pathogens

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➡️ Join us in @TitanicBelfast to hear results of the MERCY trial at #CCR23
➡️ @GiacomoMonti & @giovannilandoni will present the trial
➡️ Is continuous infusion of meropenem the future?

criticalcarereviews.com/meetings/ccr23

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@TitanicBelfast @GiacomoMonti @giovannilandoni ➡️ #CCR23 is supported by

🔴 @VisitBelfast
🔴 @belfastcc
🔴 @NITouristBoard
🔴 @BelfastTrust

See you in Belfast in June

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More from @CritCareReviews

Apr 20, 2023
➡️ Throughout history, the most mystical substance of all has been blood
➡️ It has been coveted and desired
➡️ Fought for and defended
➡️ Stolen, yet freely given

A 🧵

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➡️ Blood has always been a symbol of power
➡️ In Greek mythology, ichor, the blood of the Gods, was a golden fluid
➡️ It was immortal, pure, & untainted by human weaknesses
➡️ The Gods derived their divine powers & longevity from it

2/16 Image
➡️ Blood has been revered for its restorative properties
➡️ Elizabeth Báthory, a 16th-century Hungarian noblewoman, allegedly killed hundreds of young girls & women
➡️ She bathed in their blood to maintain her youth & beauty

3/16 Image
Read 16 tweets
Apr 6, 2023
➡️ There are ~ 5.8 million trauma deaths per year globally
➡️ Trauma is the largest cause of death below the age of 50
➡️ One-third of severely injured trauma patients are coagulopathic at hospital arrival
➡️ Fibrinogen is often used, but is it effective?

a short 🧵

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➡️ Trauma-induced coagulopathy is due to inflammation & shock
➡️ It is worsened by hypothermia, acidosis, and hemodilution
➡️ Coagulopathy due to hemorrhage is strongly associated with mortality
➡️ 1/3 of early trauma deaths are due to uncontrolled haemorrhage

2/10 Image
➡️ Fibrinogen is depleted early during major bleeding
➡️ It can be replaced with fresh frozen plasma, cryoprecipitate or fibrinogen concentrate
➡️ Cryoprecipitate includes fibrinogen, factor VIII coagulant, von Willebrand factor, fibronectin & factor XIII

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Read 10 tweets
Apr 4, 2023
➡️ Death has always fascinated human civilisations
➡️ Not just the ending of a life, but either preparation for the afterlife or attempts to restore an existing life

A 🧵

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➡️ Ancient Egyptians preserved corpses via mummification for an afterlife
➡️ They removed internal organs, used embalming fluids, linen bandages, & intricate coffins
➡️ The wealthy had pyramids
➡️ Relatives, staff & pets were buried alive for the journey to the afterlife

2/28 Image
➡️ In Greek Mythology, the River Styx separated the worlds of the living & dead
➡️ Charon, the Ferryman, required payment from the deceased for passage
➡️ The dead were buried with a coin
➡️ Those unable to pay were left to wander the river bank for 100 years

3/28 Image
Read 28 tweets
Mar 23, 2023
🚩 Tranexamic Acid - it's complicated....

➡️It's widely used for treatment & prevention of haemorrhage
➡️It's in the WHO's List of Essential Medicines & recommended in the European Traumatic Haemorrhage guideline (2023)
➡️But is it as efficacious as we think?

🧵 1/17
🚩 History

➡️Drs. Utako & Shosuke Okamoto invented TXA in 1962
➡️They identified that the amino acid lysine inhibited the degradation of plasmin, a profibrinolytic enzyme
➡️Lysine was modified to first produce Epsilon- Amino-Caproic Acid and later TXA, x 27 more potent

2/17
🚩 Pharmacology

➡️TXA is a molecular analog of lysine
➡️It inhibits fibrinolysis by preventing the binding of plasminogen to fibrin
➡️This inhibits plasmin formation & displaces plasminogen from the fibrin surface
➡️It also has effects on the immune system & inflammation

3/17
Read 18 tweets
Mar 21, 2023
The Annual Update in Intensive Care and Emergency Medicine 2023 articles have been released to coincide with the Brussels Meeting @ISICEM

10 great papers to enjoy

A thread.....

CCR Journal Watch
criticalcarereviews.com/latest-evidenc…
@ISICEM 1/10

Pelaia. The Role of Transcriptomics in Redefining Critical Illness. Crit Care 2023;27:89

CCR Journal Watch
criticalcarereviews.com/latest-evidenc…
@ISICEM 2/10

Neyton. Metagenomic Sequencing in the ICU for Precision Diagnosis of Critical Infectious Illnesses. Crit Care 2023;27:90

CCR Journal Watch
criticalcarereviews.com/latest-evidenc…
Read 11 tweets
Mar 20, 2023
1/13

➡️ REBOA is an exciting "new" therapy for non-compressible torso haemorrhage
➡️ It's used across the world, but without robust evidence
➡️ Does it work? Is it beneficial?
➡️ A thread...
2/13

🚩 Uncontrollable haemorrhage accounts for
 ➡️ > 80% of combat deaths
  ➡️ ~ 40% of civilian trauma-related deaths
🚩 Many have been determined to be preventable deaths
🚩 ~ 67% of fatal bleeding occurs in the torso region
3/13

Emergency thoracotomy (ET) has a long history in resuscitation

🚩 1880 - Paul Niehans first documented ET in human cardiac arrest
🚩 1901 - Kristian Ingelsrud performed the first successful resuscitation
🚩 1953 - Stephenson had 28% survival in 1200 cardiac arrests
Read 13 tweets

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