Expected resistant phenotypes (formerly intrinsic resistance) from EUCAST 2023

1. Enterobacterales, Aeromonas 2. Gram negative non-fermenters

Antibiotic-associated encephalopathy (AAE) 💊🧠



1/6 doi.org/10.1212/wnl.00…
Type I AAE (seizure/myoclonus)

⭐Excitotoxicity due to disruption of inhibitory signals mediated by GABA (esp class A receptor)
⭐Typically caused by β-lactams
⭐Imipenem: more basic amino acid side chain at C2➡️stronger inhibition of GABA➡️more epileptogenic

2/6

Review article on melioidosis @NatureRevMicro



1. Global epidemiology

🦠Endemic in South and SE Asia, as well as Australia doi.org/10.1038/s41579…
2. Virulence factors and host immune response

⚔️B.pseudomallei can persist and reproduce within macrophages for extended durations. They can also escape from endocytic vacuoles by secretion systems

🧵Some non-antibacterial indications of antibiotics 💊

1. TMPSMX
➡️ Antifungal: Pneumocystis jiroveci
➡️ Antiprotozoal: Cystoisospora belli, Cyclospora cayetanensis, Toxoplasma gondii

It can be used both for treatment and prophylaxis 2. Clindamycin

➡️ Antifungal: alternative option for pneumocystis jiroveci (+ primaquine)
➡️ Antiprotozoal: alternative option for toxoplasmosis (+ pyrimethamine), babesiosis and malaria (+ quinine for both)

🧵Some combinations of antibiotics and non-antibiotics that should be avoided💊🚫 1. Flucloxacillin

β-lactams are considered to be less prone to drug interactions. Flucloxacillin, however, may ⬇️ tacrolimus concentration presumably through enzyme induction

The same can occur with flucloxacillin and broad spectrum azoles (vori/posa)

link.springer.com/article/10.100…

🧵Signs named with food in infectious diseases😋

1. Donut

Granuloma consisting of dense fibrin ring and epithelioid macrophages surrounding a central lipid vacuole on H&E staining, typically associated with Q fever (Coxiella burnetii infection) 2. Cheese pizza

Yellow white retinal lesions with retinal haemorrhages seen on fundoscopic exam of cytomegalovirus (CMV) retinitis

Infections associated with freshwater exposure

1/8 1. Swimming pools

➡️Gastrointestinal infections are common
➡️Giardia, cryptosporidium and norovirus are chlorine resistant
➡️Outbreak of shigellosis associated with splash pads occurred in Kansas in 2022

2/8

Infections associated with marine exposure

1/9 1. Vibrio vulnificus

➡️3 types of infections: acute GE, septicemia, necrotizing SSTI
➡️Highly concentrated within oysters 🦪
➡️Risk factors: DM, liver disease, iron overload
➡️💊: Ceftazidime + Doxycycline
➡️Early surgical debridement for necrotizing SSTI

2/9

How Staph aureus manipulates our immune system to cause invasive infections🦠🤒

⭐Inhibits neutrophil extravasation and chemotaxis
⭐Inhibits complement activation and phagocytosis
⭐Inhibits neutrophil-mediated killing
⭐Kills host immune cells

nature.com/articles/nrmic…

1/4 ⭐Secretes coagulase (remember it's coagulase +ve) and Staph aureus superantigen-like 10 (SSL-10)
➡️Promotes agglutination with fibrin
➡️Protects it from phagocytes

2/4

Ceftriaxone is obviously not a popular choice for MSSA bacteremia among #IDtwitter

There is no prospective data showing it's inferior to other options so far

So why? First of all, why ceftriaxone?

Most common reason: once daily dosing which makes it good for OPAT

There are 2 flaws here...

Management of enterococcal bacteremia

1. Workup and treatment principles for different types of enterococcal bacteremia 2. Mechanism of antibiotic resistance

Double beta-lactam therapy may not sound appealing, but it might be more widely applicable than you think

A 🧵 1. Enterococcus faecalis endocarditis

•Ampicillin + ceftriaxone has comparable efficacy but less toxicity versus ampicillin + aminoglycoside
•Works by complementary PBP binding of the 2 agents
•May not be applicable to Enterococcus faecium

pubmed.ncbi.nlm.nih.gov/31050740/

A few things about cefazolin

1.General
•1st generation parenteral cephalosporin
•Active against MSSA, Streptococci (A,B,C,G,viridans) and aerobic GNB (E.coli, Klebsiella, Proteus)
•2 most common indications: MSSA BSI, pre-op prophylaxis 2.MSSA BSI
•Both cefazolin and anti-staphylococcal penicillins (ASP) are recommended treatment options for MSSA BSI
•Synergism when combined with ertapenem (complementary PBP binding, action on biofilm, ?effect on immune response)
pubmed.ncbi.nlm.nih.gov/31773134/

A few things about Amoxicillin-clavulanate

1. Spectrum
•Broad (Yes it is) aerobic and anaerobic coverage (MSSA, Enterococcus, Bacteroides, common Gram -ve e.g. E.coli, even ESBL if for UTI)
•Also potentially useful for melioidosis, capnocytophaga, certain nocardia, etc 2. WHO Group D3 anti-TB
•Regarded as possessing anti-TB activity, either by itself or in combination with meropenem/imipenem (mainly for the clavulanate component)
•Should only be considered in MDR setting when there are no better alternatives

Something to share about piperacillin/tazobactam

1. Broad spectrum BLBLI

• Covers Gram +ve incl MSSA, Gram -ve incl Pseudomonas, and anaerobes incl Bacteroides
• Good for empiric treatment of neutropenic fever, intra-abdominal infection, nosocomial sepsis 2. Important caveats

• Does not cover MRSA
• Not recommended for CNS infection, due to poor BBB penetration esp for tazobactam
• ESBL/AmpC producers ➡️ meropenem is preferred (MERINO and MERINO-2)

Infectious diseases in a few maps

From someone yearning for travel 1. Meningitis belt

Areas in Sub-Saharan African with high incidence of meningococcal meningitis

Be careful with what you eat...

What you eat What you get What you eat What you get