Infectious Diseases Bootcamp 2: Gram Positive Organisms

P702

If a cocci is catalase (-) what is it?

Streptococcus

If a cocci is catalase (+) what is it?

Staphylococcus

What is the coagulase (+) staphylococcus?

S. aureus

Why is S. aureus such a large clinical concern?

It causes a wide variety of infections, and when it gets into the blood, it is notorious for metastasizing to distal sites.

What are coagulase-negative staphylococci associated with?

CLABSI and Infective endocarditis

What is the caveat with coagulase negative cocci?

They are often a contaminant in clinical cultures and may not always be pathogenic.

When coagulase-negative staphylococci are indeed pathogenic, what do we always need to know?

They are (essentially) always methicillin-resistant, so treating them parallels MRSA treatment.

How does penicillin-sensitive Staphylococcus aureus (PSSA) evolve into methicillin-sensitive Staphylococcus aureus(MSSA)?

Using a penicillinase

How does methicillin-sensitive Staphylococcus aureus(MSSA) evolve into methicillin-resistant Staphylococcus aureus (MRSA)?

Acquisition of a new PBP, specifically PBP2a

What agents interfere with cell wall synthesis in gram positive organisms?

B-lactams, Vancomycin

What agents are folic acid inhibitors?

Trimethoprim, Sulfonamides

Which agent interferes with the cell membrane?

Daptomycin

Which agents interfere with DNA replication?

Fluoroquinolones

Which agents are protein synthesis inhibitors?

Macrolides, Lincosamides, Linezolid, Streptogramins, Aminoglycosides, Tetracyclines

Where do we see S. aureus infections?

Skin and soft tissue (cellulitis, bone and joint), pneumonia (HAP, VAP and can sometimes be in CAP), and bloodstream infections (including metastizing to infective endocarditis, osteomyelitis, CNS infections, and septic emboli)

How do we treat PSSA?

The same way as MSSA — we typically wont use a penicillin because of resistance and also hypersensitivity concern.

How do we treat MSSA?

Cefazolin IV is the drug of choice.

What is the key ADE associated with Cefazolin?

hypersensitivity

Why don’t we treat MSSA with methicillin, nafcillin, oxacillin, anymore?

Increased toxicity compared to 1st gen cephalosporins

T/F: Cefazolin is safe to use in penicillin allergy

True

What are the key AE associated with nafcillin, methicillin, oxacillin, etc?

AKI and possible hepatotoxicity

What is another acceptable drug to use in MSSA treatment (hint: same class)

Oral cephalexin

What is a con of using PO cephalexin?

Dosed 4x a day —> inconvenient

T/F: PO Cephalexin is safe to use in penicillin allergy

False because of similar side chains

What else should you do if you choose to use a penicillin in MSSA treatment?

Can add a beta-lactamase inhibitor; i.e sulbactam, tazobactam, clavulanic acid

What is the key ADE associated with amp/sulbactam and pip/tazo and amox/clav?

hypersensitivity

What other key ADE is also present with amox/clav?

GI distress

What is MRSA encoded by and why do we care?

the mecA gene, because rapid diagnostics can detect this and show us if a strain is MRSA.

What is the historic drug of choice for MRSA?

Vancomycin

What are the pharmacologic “headaches” associated with MRSA?

multiple daily doses, IV only for systemic use, ~10% rate of AKI, needs TDM, infusion site reaction AE

What are alternatives for bloodstream infections MRSA within definitive therapy (i.e when we know its MRSA)

Daptomycin (IV), Linezolid (IV and PO), Ceftaroline and Ceftobiprole (IV)

What are oral options for skin infections (MRSA)?

TMP-SMX, Doxycycline

Do we use Clindamycin for MRSA?

NO because of the AE profile and CDAD especially

What is good about daptomycin as an alternative for MRSA?

Once daily dosing and no TDM needed

What AE of concern is there with daptomycin?

CPK elevations and a subsequent DDI with statins

Can we use daptomycin for MRSA pneumonia? Why?

No, because it irreversibly binds to pulmonary surfactant and becomes inactivated.

Can we use Linezolid in MRSA pneumonia?

Yes!

What AE(s) of concern is there with Linezolid?

THROMBOCYTOPENIA and also optic neuritis with prolonged use

What is a DDI we still may be concerned with regarding Linezolid?

SSRIs due to weak MAO inhibition

When would we use ceftaroline and ceftobiprole for bloodstream MRSA?

occassionally for refractory disease

What are the AE we are concerned about with TMP-SMX?

Hypersensitivity and hyperkalemia

What significant DDIs does TMP-SMX have?

ACE-I/ARB/potassium sparing diuretics, and Warfarin

What AE are we concerned about with doxycycline?

Photosensitivity

What DDI is significant with doxycycline?

Chelation with ions/multivitamins