Rattibha

➡️ Antimicrobial therapy has been used for millennia
➡️ Treating severe infections can be lifesaving
➡️ However, the widespread use of antimicrobials also has downsides
A 🧵
1/16

➡️ 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
2/16

➡️ 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”"
3/16

➡️ 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
4/16

➡️ 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
5/16

➡️ 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
6/20

➡️ 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➡️ Infections, previously the most common cause of death, had been replaced by non-infectious causes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
7/16

➡️ 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
8/16

➡️ 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
9/16

➡️ 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?
10/16

➡️ 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
11/16

➡️ 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
12/16

➡️ 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
13/16

➡️ 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
14/16