There are a four major types of gram-negative resistance mechanisms:
1.Enzymatic degradation
2.Change in binding site (e.g. MecA)
3.Loss of porin channels
4.Efflux pumps.
We will review here 1 and 3.
The most widely used classification of β-lactamases is the Ambler classification.
- Serine β-L vs. Metallo β-L
- A, B, C, D
See this brief commentary on the classification academic.oup.com/jac/article/55…
However, to help identify phenotypes in clinical practice, maybe this table can be more helpful. Hope it helps #IDfellows learn and recognize them.
Please provide feedback and suggestions for future versions.
Shoutout to @sukritibanthiya for creating this amazing infographic.
AmpC β-lactamases (Class C); Case 1
- “SPACE organisms”: Serratia, Pseudomonas, Acinetobacter, Citrobacter, and Enterobacter
Or
- Recently found AMPCHES (Credit to Dr. Arias @SuperBugDoc). May be easier to remember to some
Add A: Aeromonas/Acinetobacter
AmpC β-lactamases (Class C)
Key identifiers:
•Reliably R to Cephamycins (cefoxitin).
•Cefepime can overcome inactivation and activity is retained.
•Phenotype: Derepressed (low vs. high level production) vs. inducible production (repressed)
Continues...
...
•Basal–minimal production irrespective of βL presence (<3%🦠)
•Inducible–production at baseline, transiently & reversibly⬆️in presence of βL, reversible, most 🦠
•Constitutive–mutant🦠that always produce ⬆️quantities irrespective of presence of βL;AKA “stably derepressed”
ESBL-producing; Case 2
Key identifiers:
•Ceftriaxone/PCN resistant.
•Cephamycins (cefoxitin) susceptible.
•Cefepime often tests susceptible. Some institutions won’t report Cefepime because of possible worsening outcomes
Molecular dx: CTX-M (most frequent US), TEM, SHV
Serine carbapenemases: KPC (class-A), OXA-48 (class-D); Case 3
Key identifiers:
•Resistant to all traditional β-lactams, including carbapenems.
•Inhibited by avibactam (Avycaz), vaborbactam (Vabomere), relebactam (Recabrio).
Molecular diagnosis: KPC, OXA-48
Metallo-β-lactamases: (NDM, VIM, IMP); Case 4
Key identifiers:
•Resistant to all β-lactams.
•MBL dont hydrolyze Aztreonam, but organisms usually co-carry other β -lactamases (i.e. AmpC). Thus, combination Aztreonam–Avibactam can have activity.
Molecular dx: NDM, VIM, IMP
OprD-mediated; Case 5
Organisms: Pseudomonas aeruginosa
OprD is porin that facilitates diffusion of carbapenems into the cell. Decreased expression results in resistance.
Key identifiers:
• Resistant to carbapenems, especially imipenem
That is it! Hope you enjoy it. Thanks for the feedback and for sharing!
We will post new polls on resistant gram-negative treatment followed by tweetorials on the management very soon. Stay tuned!
Hi #IDFellows and #IDTwitter, back with another case: 63F h/o ESRD on HD p/w fever. Blood cx positive for MSSA x 4 days. Blood cx clear on day 5 with Rx Cefazolin. TTE on HD2 without vegetations. What is the best next step?
1/ Let’s talk about when to get a TEE for Staph aureus bacteremia (SAB) to identify infective endocarditis (IE)!
We welcome Rookies (Anyone Pre-ID fellowship), Legends (those post-ID fellowship), and everything in between!
Participation includes the full game experience with questions, badges, and individual leaderboard.
Because this is a Fellows competition, you cannot join an individual team for the cup competition. But you can play as a large group (aka the bleachers).
We know is subjective & expect feedback/future improvements 👇
1. Clinical management of Staphylococcus aureus bacteremia: a review. pubmed.ncbi.nlm.nih.gov/25268440/
👉 A must read written by Holland et al. where they review the evidence of the management of SAB.
2. Impact of Infectious Disease Consultation on Quality of Care, Mortality, and Length of Stay in Staphylococcus aureus Bacteremia: Results From a Large Multicenter Cohort Study. pubmed.ncbi.nlm.nih.gov/25701854/
👉ID consult associated with reduced inpatient mortality.
1/ #IDTwitter and #IDFellows, here is another #IDboardreview question: 20F p/w pharyngitis w/fever. There is no cough. Exam: Cervical adenopathy; tonsillar exudate. Rapid Strep antigen test pos. You start to prescribe her Amoxicillin but there is an allergy alert.
2/ She reports an allergic reaction to penicillin around age 8 or 9. She had a rash but no other symptoms. It resolved following discontinuation of med. She did not receive any treatment. Which of the following would you do next?
3/ Today we are going to talk about everyone’s favorite – #penicillin#allergy!
1/ Follow up for our #IDFellows and #IDTwitter on an #IDCase - 25 year old female with behcet's disease and chronic pain who presents for positive T Spot done for screening. Started on Rifampin for latent TB Infection. She calls 3 days later with diffuse pain.
2/ Great job, #IDTwitter, honing in on the issue! This was intentionally vague to stimulate discussion. As you alluded to, the key lies in what else she was taking. But first, what might we worry about as adverse effects Rifampin?
3/ Allergic reactions to rifampin are relatively rare though they have been described. However, patients may experience flushing, rash and itching that is unrelated to hypersensitivity. Rifampin can often be continued in these patients. PMID: 10575418