Pogue: Clinical Treatments

Question 1

JP is a 31 y/o male with blood cultures positive
for P.aeruginosa. Which of these agents would
not be appropriate empirically?
– A) cefepime
– B) tigecycline
– C) piperacillin
– D) meropenem

Answer 1

B) tigecycline

Will get a question like this

Question 2

LL is started on ampicillin for an urinary tract
infection with e.faecalis which of the following
adverse events is most likely
– A) nephrotoxicity
– B) increased LFT
– C) allergic reaction
– D) Infusion site reaction

Answer 2

C) allergic reaction

Beta Lactams and allergic rxns

Question 3

Linezolid’s therapy limiting side effect is
– A) a high rate of nephrotoxicity
– B) allergic reactions
– C) thrombocytopenia
– D) drug interactions, lots of ‘em!
– E) hepatotoxicity

Answer 3

C) thrombocytopenia

Will get a question like this

Question 4

Which of the following lacks activity against
VRE
– A) tigecycline
– B) doripenem
– C) daptomycin
– D) linezolid

Answer 4

B) doripenem

Question 5

Skin and Soft Tissue Infections

Most common agents

Answer 5

S.aureus

S.pyogenes (Group A Strep)

Question 6

Skin and Soft Tissue Infections

Common disease states (3):

Answer 6

o	Impetigo
o	Erysipelas (Strep)
o	Cellulitis (Staph, Group B Strep)

Question 7

Streptococcus Pyogenes Infections:
DOC:
What type of resistance is increasing?

Answer 7

Penicillin (only if it is strep pyogenes alone!)

Erythromycin resistance increasing

Question 8

Staphylococcus Aureus Infections:

Empiric coverage:
Recently need to cover:

Answer 8

EMPIRIC COVERAGE WILL USUALLY NEED TO COVER STAPH!!

Increase in CA-MRSA over the past few years requires that we routinely cover for MRSA as well

Question 9

Oral MSSA Agents (3):

Answer 9

Amoxicillin/clavulanic acid

Dicloxacillin (Negative- needs to be dosed 4x per day)

Cephalexin (Negative- needs to be dosed 4x per day)

Question 10

Oral MRSA Agents (5):

Answer 10

Doxycyline
TMP/SMX
Linezolid
Clindamycin (remember to do D test if erythromycin resistant and clindamycin susceptible)
Quinolones?

Question 11

Why are Quinolones last line against MRSA?

Answer 11

Quinolones (maybe respiratory quinolones, which have good activity; BUT really last line!!)

Why? One-step, rapid mutation against staphylococcus resulting in resistance

Question 12

Worried about Staph and Strep Together?

TMP/SMX and doxycycline?
All other MSSA/MRSA agents?

Answer 12

TMP/SMX and doxycycline are NOT RELIABLE against GAS

All other oral MSSA/MRSA agents could be used

Question 13

Skin and Soft Tissue Infections

Treatment Basics:

Answer 13

Use agent with most narrow spectrum

Follow-up at 24-48 hours is crucial: assess success of regimen

Question 14

Use agent with most narrow spectrum:

MSSA:
MRSA:

TMP/SMX?

Answer 14

MSSA: beta-lactam

MRSA: doxycycline, clindamycin are good options; ED physicians often use TMP/SMX if they are sure it is MRSA

Remember: TMP/SMX will NOT cover GAS

Question 15

Severe Cellulitis

MSSA:
MRSA:

Answer 15

Severe Cellulitis: IV therapy is indicated

o MSSA: nafcillin is DOC
o MRSA: vancomycin is DOC (Note: empiric coverage often for MRSA due to increasing prevalence)

Question 16

Cellulitis
Duration of Therapy:

Uncomplicated vs. severe

Answer 16

Duration of Therapy:

Tailored to clinical scenario: this is why follow up assessment is necessary

Uncomplicated Cellulitis: 5 days

Severe Cellulitis: up to 14 days (IV therapy; can step down to oral treatment)

Question 17

Necrotizing Faciitis

Causative Agent:
Polymicrobial Infections:

Answer 17

Causative Agent: S.pyogenes (most commonly); can also be Vibrio, aeromonas and MRSA (more recently)

Polymicrobial Infections: can be seen in at risk populations (PVD, DM, decubitis ulcers)

Question 18

Gas Gangrene

Causative Agent:

Answer 18

Clostridium spp. (most commonly C.perfringens)

Question 19

Necrotizing Infections
Treatment:

Group A Strep and Clostridial Infections:

Clindamycin?

Answer 19

PROMPT SURGICAL DEBRIDEMENT

Group A Strep and Clostridial Infections: penicillin + clindamycin

Clindamycin: although it has decent activity against these agents, really given to suppress toxins (via inhibition of protein synthesis); hypothetically, other ribosomal Abx would work as well

Question 20

Animal Bites

Empirical treatment:
Skin bugs:
Mouth bugs:

Answer 20

Animal Bites:
• Need to cover Pasturella multocida empirically!!
- Also staph and strep (because these are on the skin)
- Also anaerobes (because these are in the mouth)

Question 21

Animal Bites
Treatment:

PO:
IV:

Answer 21

Pasturellla often has a beta-lactamase: therefore, B-lactam/B-lactamase inhibitors are the mainstay of therapy

Amoxicillin/Clavulanic Acid: PO

Ampicillin/Sulbactam: IV

Alternatives: doxycycline, moxifloxacin (especially in penicillin allergies)

Question 22

Treatment of human bites:

Answer 22

Human bites (and fists to the mouth) should be treated the same way (minus the need for Pasturella coverage)

Question 23

Diabetic Foot Ulcers

Causative Agents:

Answer 23

G(+) cocci, predominantly S.aureus; as time goes on, GNR and anaerobes as well

Question 24

Diabetic Foot Ulcers

Treatment of uninfected ulcers:

Answer 24

Treatment: UNINFECTED ULCERS SHOULD NOT BE TREATED; ONLY TREAT UNTIL INFECTION RESOLVES Empiric

Question 25

Diabetic Foot Ulcers | Therapy:

Answer 25

Therapy: o IV therapy initially o Commonly with vanomycin + amp/sulbactam (however, a wide variety of regimens can be used to cover the likely pathogens)

Question 26

``` Diabetic Foot Ulcers Duration: Mild Moderate to severe osteomyelitis ```

Answer 26

Duration: only treat until infection is gone (not until ulcer heals) o Mild Infections: 1-2 weeks o Moderate to Severe Infections: 2-4 weeks o Osteomyelitis: 4-6 weeks

Question 27

BONE AND JOINT INFECTIONS Basics: The most common agents:

Answer 27

Most common causative agents: staphylococcus spp. (MSSA, MRSA, coagulase-negative staph); in certain scenarios, anything can play a role.

Question 28

BONE AND JOINT INFECTIONS | Duration of Therapy:

Answer 28

o At least 3 weeks of therapy for joint infections (4+ weeks for S.aureus or pseudomonas) o At least 4-6 weeks of therapy for bone infections (possibly followed by suppressive therapy)

Question 29

BONE AND JOINT INFECTIONS | Therapy Basics:

Answer 29

o Long duration o Maximum doses (IV) o Bactericidal drugs

Question 30

BONE AND JOINT INFECTIONS Staphylococcus Aureus Infections Therapy: IV

Answer 30

IV therapy to start: o MSSA: nafcillin is the DOC o MRSA: vancomycin is the DOC

Question 31

BONE AND JOINT INFECTIONS Staphylococcus Aureus Infections Therapy: Oral

Answer 31

Oral Therapy: Linezolid: option for patients with limited IV access (not first line)

Question 32

BONE AND JOINT INFECTIONS Staphylococcus Aureus Infections Suppressive Therapy: Commonly used drugs:

Answer 32

Often used for staph infections Commonly used drugs: - Doxycycline - TMP/SMX - Clindamycin

Question 33

BONE AND JOINT INFECTIONS Staphylococcus Aureus Infections Note About Rifampin: Monotherapy: However, commonly used when hardware is involved (prosthetic valves, hips etc.) Why? What is used in these scenarios?

Answer 33

Not good as monotherapy (due to easy mutation) Staph aureus produces a biofilm on foreign material Rifampin has excellent biofilm penetration Nafcillin/Vancomycin + Rifampin used in these scenarios

Question 34

BONE AND JOINT INFECTIONS Staphylococcus Aureus Infections What is given to manage pain?

Answer 34

Anti-inflammatory drugs given to relieve pain Standard antibiotic treatment often effective

Question 35

Gram Negative Infections: First line therapy: Oral Step Down:

Answer 35

First line therapy: IV B-lactam against causative agent Oral Step Down: FQ (due to good oral availability; also good for penicillin allergy)

Question 36

JJ is a 32 y/o with uncomplicated cellulitis. He has a history of anaphylaxis with penicillin. Cultures show s.aureus susceptible to all of the following antibiotics. Which treatment should be chosen? Why? – A) cephalexin – B) linezolid – C) vancomycin – D) doxycycline

Answer 36

D) doxycycline It is less expensive. Cephalexin-penicillin linezoild - more narrow

Question 37

Rifampin‐ remember the pearls • Drug interactions‐ Why? • Your patient is crying blood? • Watch alcohol intake‐ why?

Answer 37

CYP inhibitor Colorizes urine and tears Hepatotoxicity

Question 38

PSEUDOMONAS: G+/-? What do some physicians do?

Answer 38

Gram negative that clinicians worry about because it is virulent and develops resistance easily Some physicians try to use 2 agents to double cover pseudomonal infections- there is no clinical evidence that this is effective in vivo

Question 39

Pseudomonal Treatment:

Answer 39

IV B-lactam for 4-6 weeks - Joint: 4 weeks - Bone: 6 weeks Can also add anti-pseudomonal Aminoglycoside (gentamicin, tobramycin, amikacin) or FQ (cipro, levo) for 2 weeks

Question 40

Review: antipseudomonal agents

Answer 40

* Piperacillin, Piperacillin/tazobactam * Cefepime, Ceftazadime * Aztreonam * Imipenem, Meropenem, Doripenem * Gentamicin, Tobramycin, Amikacin * Ciprofloxacin, Levofloxacin * Polymyxins

Question 41

Disseminated Infections Attacking Joints: | DOC:

Answer 41

Neisseria Gonorrhea: Cetriaxone is the DOC.

Question 42

BACTERIEMIAS Basics: Source Control: Skin/bone/joint: Catheter-related: Pulmonary: Urosepsis:

Answer 42

Source Control: the appropriate therapy differs based on the source of the infection; if you can manage the source you can manage the bacteremia o Skin/Bone/Joint: Gram (+) o Catheter-Related: Gram (+), Gram (-), candida spp. o Pulmonary: organisms associated with pneumonia o Urosepsis: urinary pathogens

Question 43

Catheter-Related Bloodstream Infections: Basics: Therapy:

Answer 43

Basics: o The longer the line is in, the higher the chance (don’t leave it in longer than it has to be) o If you can, remove infected catheter (not always possible) Therapy: antibiotic lock therapy (high concentrations of Abx placed directly in the catheter) - Almost never works

Question 44

Catheter-Related Bloodstream Infections Duration: Coagulase-Negative Staph: Most bacteria and fungi: S.aureus (seeding):

Answer 44

Duration: o Coagulase-Negative Staph: 5-7 days o Most bacteria and fungi: 14 days o S.aureus (seeding): at least 14 days

Question 45

Catheter-Related Bloodstream Infections ``` Candida in the Blood: Empiric therapy: depends on: Risks: No/Low-Risk for C.glabrata: C.glabrata: ```

Answer 45

Empiric therapy depends on risk for fluconazole-resistant organisms (C.glabrata) Risks: recent azole exposure, known carrier of C.glabrata No/Low-Risk for C.glabrata: use fluconazole C.glabrata: use an echinocandin

Question 46

ENDOCARDITIS Basics: Causative Agents:

Answer 46

Basics: - Difficult to treat (often needs surgical intervention) ``` Causative Agents: o G (+) organisms: most common o Gram (-), including pseudomonas o Candida spp. o HACEK organisms ```

Question 47

ENDOCARDITIS Duration: Regimen:

Answer 47

o Duration: usually 4-6 weeks o Regimen: IV antibiotics (max dose, bactericidal); occasionally, highly bioavailable oral drugs may be used (as step down therapy)

Question 48

Strep Endocarditis Causative Agents: Duration of Treatment:

Answer 48

Causative Agents: Viridans strep and S.bovis Duration of Treatment: Standard: 4 weeks; Prosthetic Valve: 6 weeks

Question 49

Strep Endocarditis Treatment: What is preferred? Second-line? What can be added? Why for resistant and sensitive strains?

Answer 49

Treatment: depends on susceptibility pattern B-Lactams Preferred: penicillin (if susceptible) or cetriaxone Vancoycin: if penicillin allergy exists Gentamicin can be added: - Resistant strains: for synergy (entire course of treatment) - Sensitive strains: to shorten duration of therapy (only 2 weeks)

Question 50

Staph Endocarditis: Causative Agents: Treatment: MSSA/MSSE: What if they have an allergy to penicillin? Severe? Non-severe?

Answer 50

Causative Agents: S.aureus and coagulase-negative staph (most commonly S.epidermidis) Treatment: MSSA/MSSE: - Nafcillin for 6 weeks - Gentamicin for 3-5 days (synergy; shortens duration of bacteremia) Penicillin Allergy: Cefazolin (non-severe) Vancomycin (severe)

Question 51

Staph Endocarditis: Treatment MRSA: Prosthetic Valve:

Answer 51

MRSA: Vancomycin (high dose) Prosthetic Valve: May require more than 6 weeks of nafcillin therapy Add rifampin (penetration of biofilm) Gentamicin for 2 weeks

Question 52

``` Enterococcal Endocarditis: Treatment: DOC: If VRE (3): What should be added to cell wall agent for synergy? ```

Answer 52

Ampicillin is the DOC (if sensitive); if not, vancomycin is next in line If VRE: - Daptomycin - Quinupristin/Dalfopristin - Linezolid Gentamicin should be added to cell wall agent for synergy

Question 53

Enterococcal Endocarditis: Duration: Ampicillin susceptible Vancomycin VRE

Answer 53

Duration: o Ampicillin susceptible: 4-6 weeks o Vancomycin: 6 weeks o VRE: at least 8 weeks

Question 54

Miscellaneous Endocarditis Bugs G-: Use what if possible: Some use: Candida: What is notable? Use? HACEK: Common in what type of pts? Commonly used drugs (2):

Answer 54

Gram (-): o Use B-lactam if possible (high doses) o Some use 2 drugs for pseudomonas Candida: o HIGH MORTALITY RATE o Therefore, will always use amphotericin B + flucytosine (synergy) ``` HACEK Organisms: o Gram negatives common in patients in the community who are not IV drug users o Commonly Used: - Ceftriaxone (4 weeks) - Ampicillin/Sulbactam (4 weeks) ```

Question 55

What is the duration of each infection: Prosthetic valve strep endocarditis Coag (‐) staph (Catheter-related bloodstream infection) CRBSI Severe cellulitis Candida bacteremia Pseudomonal joint infection

Answer 55

Prosthetic Valve Strep Endocarditis: 6 weeks Coag (‐) Staph CRBSI: 5-7 weeks Severe Cellulitis: 14 days Candida Bacteremia: 14 days Pseudomonal Joint Infection: 4 weeks

Question 56

Major side effects: Doxycycline TMP/SMX Clindamycin

Answer 56

– Doxycycline – photosensitivity and chelation – TMP/SMX – rash/allergic reactions – Clindamycin – diarrhea