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 Vancomycin in MRSA treatment?

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

Do we use clindamycin for skin MRSA?

No

Where does Strep Pneumoniae mainly colonize?

The respiratory tract

What are some common infectious syndromes caused by strep pneumoniae?

Upper and lower respiratory tract infections, otitis media, meningitis

T/F: Getting the pneumococcal vaccines will remove the strep pneumoniae as a causative pathogen in disease states.

False, it does decrease the incidence and severity but does not remove it as a causative pathogen.

What are the mainstay of treatment for strep pneumoniae?

beta lactams

What are good drugs of choice for non-CNS strep pneumoniae infections?

penicillin, ampicillin, amoxicillin

What is a good treatment option for CNS infections of strep pneumoniae?

Ceftriaxone

What are good (respiratory) alternatives for treating strep pneumoniae?

Moxifloxacin and Levofloxacin

Can we use ciprofloxacin for strep pneumoniae? why?

No because it is not a respiratory fluoroquinolone because of lack of activity against the pathogen.

Despite being highly effective, why don’t we use fluoroquinolones as a first line treatment for Strep pneumoniae?

AE profile; tendon rupture, CNS adverse events, QT prolongation (moxifloxacin), C. diff infections, chelation DDIs

Can we consider macrolides and doxycycline for strep pneumoniae infections?

Yes but they are highly limited by increased resistance.

Which antibiotic is strep pneumoniae more resistant to: doxycycline or azithromycin?

Azithromycin (50% resistance)(doxy is only ~20%)

Can we use vancomycin in strep pneumoniae infections? when?

Yes and for some CNS infections

Where does strep pyogenes (group A strep) mainly colonize?

The skin

What are common directed therapies for strep pyogenes?

Penicillin and Amoxicillin

What is the caveat for directed therapies with strep pyogenes?

We often need to cover for staph as well, so all of the staph options come into play.

What is the exception drugs that we DO NOT use for strep pyogenes?

Doxycycline and Clindamycin (due to resistance and AE profile)

Is TMP-SMX necessarily inactive against GAS?

No, historically we were concerned but it was related to testing issues. It may still have activity and can be considered when clinically appropriate.

Where do enterococcus species mainly colonize?

The GI and genitourinary tracts

What kinds of infections can enterococcus species cause?

Intra-abdominal, UTI, Bacteremia, Infective Endocarditis, Wound infections

T/F: Enterococcal infections are often polymicrobial

True, which is why knowing all clinically available treatments is important

What is the most common enterococcus?

E. faecalis

Which enterococcus is most susceptible to penicillins?

E. faecalis

Which enterococcus is more resistant to both penicillins and vancomycin?

E. faecium

What is the initial approach when dealing with most E. faecalis infections?

Ampicillin or Penicillin

What is the initial approach when dealing with most E. faecium infections?

Assume VRE until proven otherwise; Linezolid, Dapto or Tigecycline/Eravacycline/Omadacycline or Oritavancin

What is the mutation in VRE encoded by?

A shift from D-alaD-ala to D-ala D-lac encoded by VanA genes

T/F: Rapid diagnostic testing can confirm VanA/VanB presence

True

When would we use combination therapy for enterococcus treatment?

In infective endocarditis

What is the combination therapy for enterococcal infective endocarditis?

Ampicillin + Ceftriaxone

When can we use penicillin and beta lactamase inhibitor combinations in enterococcal treatment?

With polymicrobial infections

What are some penicillin / BLI combinations?

Amoxicillin/Clavulanate, Ampicillin/Sulbactam, Piperacillin/Tazobactam

What are the treatment options we use in VRE?

Linezolid, Daptomycin, Tigecycline, Eravacycline, Omadacycline and Oritavancin

What are the biggest cons of using Tigecycline and Eravacycline?

Super high volume of distribution, so not really good for bloodstream infections.

What are the shared AE of Tigecycline and Eravacycline?

N/V

What is a unique caution to Tigecycline?

May cause pancreatitis

What is a unique AE to Eravacycline?

Hypofibrinogenemia

What is unique about Omadacycline as a VRE drug (hint: route of admin)

Only oral option aside from Linezolid

What is the main AE of Omadacycline?

N/V and you should separate from food by 2-4 hours

What is the unique MOA of Oritavancin?

It binds to peptidoglycan precursors, inhibiting cell wall synthesis and anchors into inner cell membrane, causing disruption.

What are the pros of Oritavancin?

It has a long t1/2 meaning it is dosed only once a week

Do we ever want to use Cephalosporins as monotherapy for enterococcal infections? Why?

No, because they lack reliable activity.