-----KING PSEUDOMONAS------(after @DGlaucomflecken)
--A short #tweetorial on why Pseudomonas is so evil—
#medtwitter #IDTwitter
@ThinkingCC @iceman_ex @avkwong @ABsteward
/1 Image
Let's start with why it's green?
/2
Pseudomonads produce pyocyanin and pyoverdine that give it greenish colour on agar. Hence the name "aeruginosa" meaning "copper rust". Frank Pseudomonas pus can also look greenish for the same reason.
/3 Image
So in my hospital about 40% of Pseudmonas is carbapenem resistant and is in the top 10 causing bloodstream infections and VAPs. Why can't we beat this Mad King? I will cover:
1) Where it lives?
2) Why we can't kill him?
.
.
.
3) But the most important: how can it adapt so well?
- It has a large genome with lots of regulator genes and dormant environmental and antibiotic resistance genes.
- Easily increases gene expression 100 to 1000-fold.
- The library of genes mean that mutations easily result in resistance and then selection of resistant organisms. Image
Quorum sensing: in response to chemical stress QS mediates bacterial colony wide gene expression through the production of messenger molecules.

And that means environmental adaptation, antibiotic resistance. On a population level.
/6 Image
Just a complicated pic about QS
frontiersin.org/articles/10.33…
/7 Image
Can also easily acquire plasmids from fellow gram negative organisms.
/8 Image
Where does it live?

It loves moist places and can be naturally found in soil, water and human gut.

/9 Image
It does not adhere well to skin or mucosal epithelium and therefore becomes pathogenic when the immune system is down, the barrier is pierced by plastic tubes and the gut microbiome is disturbed (just like other ESKAPE pathogens).

/10 Image
It's easy to find moist surfaces in hospital (water tubing, sinks, cleaning equipment) and around the patient (groin, axillae, vent tubing, nebulizer, the list goes on).

/11
Not only this, Pseudomonas has minimal nutritional needs and can adapt to any environement: can grow even anaerobically, and survive eg. dry surfaces, food preservatives, and antiseptics.

doi: 10.1128%2Faem.37.3.505-510.1979
jcp.bmj.com/content/jclinp…) Image
Plays dead like leaf litter frog

In adverse environment loses flagella and becomes immobile (already a smaller target to the immune system) and starts producing biofilm physically protecting itself.

/13 Image
Why we can't kill him?

1) It's outer membrane is naturally impermeable and it has various efflux pumps to protect itself.

/14 Image
2) Target modification
Eg. it's 16S methylase modifies the aminoglycoside target: the 16S ribosome. Or it can develop mutation to it’s topoisomerase gene making it more difficult for fluoroquinolones to bind.

/15 Image
"Food" gets into the bacteria via porin channels. Antibiotics use the same porin channels enter. Pseudo can replace these channels precluding antibiotic entry (eg. carbapenem resistance by OprD deficient porin).

/16
3) Can upregulate efflux pumps to get rid of antimicrobials, eg. MexA–MexB–OprM to remove fluoroquinolones.
4) It can neutralize antibiotics, the most well-known examples are beta-lactamases (AmpC, OXA, IMP VIM, MBL, etc.)

But it can also modify aminoglycosides

/18
--------In summary--------
Pseudomonas is naturally resistant to many antimicrobials, produces biofilm and can survive in a multitude of environments.

It is abundant in the moist hospital environment, including the human gut and is only waiting to attack it’s compromised host.
-------The Most important-----
Shows huge genomic plasticity and can easily adapt to many things we throw at him including antimicrobials and cleaning strategies.
So what to do?

/21 Image
First remember that it is everywhere so it will be on your patient, so try to prevent selection of resistant strains by avoiding long broad-spectrum antimicrobial courses if able.

/22
Prevent infection good everyday ICU practices like removing unnecessary lines and waking up/extubating your patient if able.

Pay attention to isolation precautions and decontaminate the patient’s environment regularly

or....Rebuild your ICU

/23 Image
And if you need to treat a patient with difficult to treat PSA
- if sensitive use high dose, extended infusion of pip/taz, ceftaz, cefepime, cipro, levo (if applicable)

/24
If MDR use a novel beta-lactam beta-lactamase inhibitor combination (BLBLI): ceftolozane-tazobactam, ceftazidime-avibactam, imipenem-cilastatin-relebactam
See ESCMID gl
clinicalmicrobiologyandinfection.com/article/S1198-…
or IDSA
idsociety.org/practice-guide…

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