IPCS 2 Medicine Study Set: Cardiac Drugs & Bacteremia

what is bacteremia?

bacteria in the blood

what may increase the likelihood of developing bacteremia by at least 50%?

• Discitis + vertebral osteomyelitis

• Epidural abscesses

• Acute, non-truamatic native septic arthritis

• Meningitis

• Septic shock

• Catheter-related bloodstream infections

• Endovascular infections

What are the common pathogens of bacteremia?

Gram pos

- Staphylococcus aureus

- Streptoococcus pneumoniae

- Enterococcus spp.

Gram neg

- E. coli

- Klebsiella spp.

- Pseudomonas aeruginosa

- Salmonella spp.

what are the different manifestations of shock?

• Hypovolemic

• Obstructive

• Distributive

• Cardiogenic

what is the commonality with all diff types of shock?

lack of oxygen

what are the causes of distributive shock?

• Systemic inflammatory response syndrome (SIRS)

• Sepsis

• Anaphylaxis

• Drug/toxin reactions

what is the clinical presentation of distributive shock?

• dyspnea

• chills

• fatigue

• malaise

• tachypnea

• tachycardia

what does SIRS criteria indicate?

bacteremia or systemic infection may be present

what is the SIRS criteria that must be present in order for to indicate sepsis?

in addition to confirmed or suspected infection:

2 or more of the following...

• HR > 90 bpm

• Temp < 36°C or > 38°C

• WBC < 4,000 or > 12,000 cells/mm^3 or > 10% bands

• RR > 20 bpm or PaO2 mmHg

what is the SOFA score?

- Sequential Organ Failure Assessment

- Predictor of outcomes, NOT diagnostic

> 15 maximum SOFA score predicted mortality = ?

90%

what is the qSOFA score?

• predictor of outcomes

• not diagnostic OR prognostic

• ≥ 2 of the following indicates ~10% mortality:

- Hypotension (SBP < 100)

- AMS (GCS <13)

- Tachypnea (RR>22)

Identifies high-risk patients for in-hospital mortality with suspected infection outside the ICU

SIRS vs qSOFA

SIRS

- may not need labs

- required documentation for admission/payment

- diagnostic tool

qSOFA

- no labs needed

- stratifies risk

- outcomes predictor

what are the characteristics of end organ damage?

• Lactate > 2 mmol/L

• SBP < 90 mmHg

• MAP < 65 mmHg

• Kidney dysfunction (creatinine > 2 mg/dL or platelets < 100,000 cells/mm^3)

• Liver dysfunction (INR > 1.5)

how is fluid resuscitation used for bacteremia, sepsis, and septic shock treatment?

• Deliver 30 mL/kg of crystalloid fluid

• administered prior to other treatments

• may consider colloidal fluids (albumin) if crystalloid fails

How much crystalloid fluid should be delivered to patients in end-stage renal disease or heart failure?

Not 30 mL/kg anymore...

decrease to 500 mL (without considering weight)!!

what fluid should be selected for fluid resuscitation?

preferred choice = buffered crystalloid solutions such as Lactated Ringer's solution or Plasma-Lyte

--> 0.9% NaCl not used as much anymore

what is the normal MAP range?

70-90 mmHg

How is cardiac output calculated?

HR x SV

what are the normal cardiac output ranges?

male = 5.6 L/min

females = 4.9 L/min

what should be used after failure of fluid resuscitation?

vasopressors

vasopressors increase...

vascular resistance

inotropes increase....

cardiac output

what is the target of vasopressors?

MAP, titrate to > 65 mmHg

what are the receptor types in blood vessels?

a1, a2, B2, and V1

what are the receptor types in the heart?

B1 and a1

what are the receptor types in the kidney?

DA

what effect do the a1 and a2 in the blood vessels receptors produce?

constriction

what effect do B2 receptors in the blood vessels produce?

dilation

what effect do V1 receptors in the blood vessels produce?

constriction

what effect do B1 receptors in the heart produce?

tachycardia, increased contractility

what effect do a1 receptors in the heart produce?

increased contractility

what effect do DA receptors in the kidney produce?

dilation

what are the different vasopressors?

• norepinephrine

• epinephrine

• vasopressin

• phenylephrine

• dopamine

what are the different inotropes?

• dobutamine

• milrinone

Norepinephrine used as treatment:

- potent agonist of adrenergic receptors, a1 > B1

- first line in septic shock

Epinephrine used as treatment:

- potent agonist of adrenergic receptors, a1 similar to B1 with some action at B2

- more profound influence on HR than NE

- used as additive in sepsis, cardiogenic

- first line for anaphylaxis

Phenylephrine used as treatment:

- potent a1 agonist

- can induce reflex bradycardia

- must monitor peripheral venous return

Vasopressin used as treatment:

• Non-adrenergic MOA, stimulation of V1 receptor

• refractory shock, primarily in sepsis

Dopamine used as treatment:

• activity at numerous adrenergic sites: a1, B1, and DA

• desired effect = increased HR, titrate until B1 effect clinically appreciated

Dobutamine used as treatment:

• primary B agonism (B1>B2)

• positive inotrope, preferred in cardiogenic shock (increase stroke volume)

Milrinone used as treatment:

• non-adrenergic MOA: potent PDE3 inhibitor, mediated cAMP in cardiac muscle

• non-selective vasodilation

• increased CO

• primary role = cardiogenic shock

what are the adverse effects of vasopressors?

- extravasation

- digital necrosis

what type of IV line is preferred for vasopressors?

central line

what drugs can reverse extravasation?

- phentolamine

- terbutaline

- nitroglycerin ointment

what drugs can also cause digital necrosis in addition to vasopressors?

dopamine + phenylephrine

what should be used as initial therapy for hypovolemia?

• Fluid → Crystalloid (NS, D5, etc.)

• Pressor → N/A, consider starting with norepinephrine/epinephrine

what should be used as initial therapy for sepsis?

• Fluid → Crystalloid (LR preferred), 30 mL/kg initial bolus

• Pressor → Norepinephrine

what should be used as initial therapy for cardiogenic shock?

• Fluid → Crystalloid (NS, D5, etc.), ≤500 mL initial bolus

• Pressor → Dobutamine, milrinone

what antibiotic should be used for gram-negative bacilli bacteremia? what if pseudomonas if a concern? what if resistant to Pseudomonas?

• Consider broad spectrum b-lactam

• If pseudomonas is a concern, you can use a single agent of the following:

- Cefepime

- Piperacillin/Tazobactam

- Ceftazidime

--> If resistant can use antipseudomonal carbapenem (meropenem, imipenem, doripenem)

what antibiotic should be used for pseudomonas bacteremia?

Antipseudomonal b-lactam in addition to aminoglycoside (amikacin, gent, tobra) and/or fluoroquinolone (levoflox)

what antibiotic should be used for gram-positive bacteremia?

• MRSA coverage is encouraged → vanco or dapto (do not use dapto if respiratory source)

• MSSA → preferred agents are B-lactams like nafcillin, cefazolin

what antibiotic should be used for streptococcus bacteremia?

• B-lactam first line

• IV clindamycin to suppress toxin production for at least 48 hrs

• If there is a clindamycin shortage, consider linezolid

what antibiotic should be used for Enterococcus spp. bacteremia?

Ampicillin, if pt has anaphylactic allergy to b-lactams use vancomycin

what antibiotic should be used for Enterococcus faecium bacteremia?

• Vanco resistant...

• Dapto or linezolid are alternatives

how long should one be treated with antibiotics for bacteremia, sepsis, and septic shock?

7-14 days, can consider 10 days from last positive blood culture... change to PO when able to

what are adjunctive therapies used for bacteremia, sepsis, and septic shock?

Corticosteroids (hydrocortisone)

--> For refractory septic shock when pt cant achieve MAP > 65 mmHg, despite fluid + vasopressor

Vitamins

--> DONT USE, doesnt work

what is the pathophysiology of endocarditis?

endothelial damage-> platelet-fibrin deposition and formation of nonbacterial thrombotic endocarditis-> bacteria allows bacterial colonization-> colonization allows formation of vegetation as microorganisms adhere to nonbacterial thrombotic endocarditis lesion-> infective endocarditis with structural abnormality in a valve

what is the clinical presentation of endocarditis?

- variable + nonspecific

- fever, chills, weakness, dyspnea, night sweats, weight loss, and/or malaise

- common heart murmur, may have skin manifestations

- WBC may be normal or slightly elevated

- anemia, thrombocytopenia, elevated erythrocyte sedimentation rate or C-reactive protein, and altered urinary analysis

what is the hallmark laboratory finding for endocarditis?

continuous bacteremia, 3 sets of blood cultures should be collected over 24 hrs

what diagnostic test plays a key role in the diagnosis of ineffective endocarditis?

echocardiography... which should be performed in all suspected cases

what is the gold standard for defining infective endocarditis?

DUKE criteria

what does the DUKE criteria define infective endocarditis as?

definite, possible, or rejected

what is the pathological criteria or endocardititis?

vegetation or intracardiac abscess

what is the clinical criteria for defining definite ineffective endocarditis?

2 major criteria -OR- 1 major and 3 minor criteria -OR- 5 minor criteria

what is the clinical criteria for defining possible ineffective endocarditis?

1 major + 1 minor criteria -OR- 3 minor criteria

what is the clinical criteria for defining rejected ineffective endocarditis?

• alternative diagnosis more likely

• symptoms resolved with <4 days of antibiotics

• no pathological evidence on surgery or autopsy

what is the major criteria for ineffective endocarditis?

• positive blood cultures (2 separate cultures)

• evidence of endocardial involvement

• echocardiogram positive (TEE preferred)

what are the bacteria that will result in a positive blood culture for ineffective endocarditis?

• Viridans streptococci

• S. bovis

• HACEK group

• S. aureus

• enterococci

• Single positive culture for Coxiella burnetti or anti-phase IgG titer

what is the minor criteria for ineffective endocarditis?

• predisposition (including structural heart conditions) or IVDA

• Temp > 30°C

• Vascular hemorrhaging or emboli

• Glomerularnephritis, Osler nodes, Roth spots, or rheumatoid factor

• Microbiological evidence present but not meeting major criteria

what antibiotics are used for native valve PCN-sensitive staph and strep?

• Aqueous crystalline penicillin G sodium --> 4 weeks (IIaB)

• Ceftriaxone --> 4 weeks (IIaB)

• Aqueous crystalline penicillin G sodium plus gentamicin --> 2 weeks (IIaB)

• Ceftriaxone plus gentamicin --> 2 weeks (IIaB)

• Vancomycin --> 4 weeks (IIaB)

when is vancomycin recommended for native valve PCN-sensitive staph and strep?

only for patients unable to tolerate penicillin or ceftriaxone

2 week regimens of antibiotic treatment of native valve PCN-sensitive staph and strep are NOT intended for who?

• most patients > 65 yo

• children

• impairment of the eighth cranial nerve function

• renal function with a creatinine clearance < 20mL/min

• known cardiac or extracardiac abscess

• infection with Abiotrophia, Granulicatella, or Gemalla species

what antibiotics are used for native valve PCN-resistant staph and strep?

• Nafcillin or oxacillin --> 6 weeks (IC)

• Cefazolin --> 6 weeks (IB)

• Vancomycin --> 6 weeks (IB)

• Daptomycin --> 6 weeks (IIaB)

when is cefazolin used for native valve PCN-resistant staph and strep?

patients w/ non-anaphylactoid-type penicillin allergies

when is vancomycin used for native valve PCN-resistant staph and strep?

patients with anaphylactoid-type hypersensitivity to penicillin and/or cephalosporins

when is daptomycin used for native valve PCN-resistant staph and strep?

patients w/ immediate-type hypersensitivity reactions to penicillin

what antibiotics are used for native valve methicillin-resistant staph and strep?

• vancomycin --> 6 weeks (IC)

• daptomycin --> 6 weeks (IIbB)

what antibiotics are sensitive strains for enterococci infections?

• ampicillin plus gentamicin --> 4-6 weeks (IIaB)

• Aqueous crystalline penicillin G sodium plus gentamicin --> 4-6 weeks (IIaB)

• Ampicillin plus ceftriaxone --> 6 weeks (IIaB)

• Vancomycin plus gentamicin --> 6 weeks (IIaB)

what is the clinical pearl regarding ampicillin plus gentamicin when used as a sensitive strain for enterococci infections?

native valve plus symptoms present for < 3 months, use 4-week regimen

what is the clinical pearl regarding aqueous crystalline penicillin G sodium plus gentamicin when used as a sensitive strain for enterococci infections?

prosthetic valve or native valve plus symptoms present >3 months, use 6-week regimen

what is the clinical pearl regarding ampicillin plus ceftriaxone when used as a sensitive strain for enterococci infections?

recommended regimen if creatinine clearance is < 50 mL/min at baseline or due to therapy with a gentamicin-containing regimen

what is the clinical pearl regarding vancomycin plus gentamicin when used as a sensitive strain for enterococci infections?

recommended only for patients unable to tolerate penicillin or ampicillin

what antibiotic should be used for gentamicin-resistant strains of enterococci infections?

if susceptible, use streptomycin in the place of gent. in the regimens listed earlier in the quizlet if creatinine clearance is > 50 mL/min

what antibiotic should be used for penicillin-resistant strains of enterococci infections?

• ampicillin-sulbactam plus gentamicin --> 6 weeks (IIbC)

• vancomycin plus gentamicin --> 6 weeks (IIbC)

what antibiotic should be used for enterococcus faecium strains resistant to penicillin, aminoglycosides, and vancomycin in enterococci infections?

• Linezolid --> >6 weeks (IIbC)

• Daptomycin --> >6 weeks (IIbC)

what antibiotics are used in gram-negative infections?

• Ceftriaxone --> 4 weeks (IIaB)

• Ampicillin or ampicillin-sulbactam --> 4 weeks (IIaB)

• Ciprofloxacin --> 4 weeks (IIbC)

what are comments with ceftriaxone when used for gram-negative infections?

other 3rd or 4th generation cephalosporins may be used as an alternative

what are comments with ampicillin/ampicillin-sulbactam when used for gram-negative infections?

should only use if growth is adequate for in vitro susceptibility testing; otherwise, consider organism to be resistant

what are comments with ciprofloxacin when used for gram-negative infections?

recommended for patients with known intolerance to cephalosporins or ampicillin; other fluoroquinolones may be used as an alternative

what agents are recommended for prosthetic valve: strep and staph spp. for highly penicillin-susceptible (MIC≤12) patients?

• Aqueous crystalline penicillin G sodium --> 6 weeks (IIaB)

• Aqueous crystalline penicillin G sodium plus gentamicin --> 2 weeks (IIaB)

• Ceftriaxone --> 6 weeks (IIaB)

• Ceftriaxone plus gentamicin --> 2 weeks (IIaB)

• Vancomycin --> 6 weeks (IIaB)

what are comments regarding the use of aqueous crystalline penicillin G sodium/aqueous crystalline penicillin G sodium plus gentamicin when used for prosthetic valve: strep and staph spp. for highly penicillin-susceptible (MIC≤12) patients?

avoid in patients with CrCl < 30 mL/min

what are comments regarding the use of vancomycin when used for prosthetic valve: strep and staph spp. for highly penicillin-susceptible (MIC≤12) patients?

recommended only for patients unable to tolerate penicillin or ceftriaxone

what agents are recommended for prosthetic valve: strep and staph spp. for highly oxacillin-susceptible patients?

• nafcillin or oxacillin --> ≥6 weeks (IB)

• nafcillin or oxacillin plus rifampin --> ≥6 weeks (IB)

• nafcillin or oxacillin plus gentamicin --> 2 weeks (IB)

• vancomycin --> ≥6 weeks (IB)

• vancomycin plus rifampin --> ≥6 weeks (IB)

• vancomycin plus gentamicin --> 2 weeks (IB)

what agents are recommended for prosthetic valve: strep and staph spp. for highly oxacillin-resistant patients?

• vancomycin --> ≥6 weeks (IB)

• vancomycin plus rifampin --> ≥6 weeks (IB)

• vancomycin plus gentamicin --> 2 weeks (IB)

what agents are used for patients with culture-negative endocarditis, native valve?

• vancomycin plus cefapime --> 4-6 weeks (IIaC)

• vancomycin plus ampicillin-sulbactam --> 4-6 weeks (IIaC)

what agents are used for patients with culture-negative endocarditis, early (<1yr) prosthetic valve?

vancomycin plus cefepime plus rifampin plus gentamicin --> 6 weeks (IIaC)

what agents are used for patients with culture-negative endocarditis, late (<1yr) prosthetic valve?

vancomycin plus ceftriaxone --> 6 weeks (IIaC)

what is the clinical presentation of watery GI infections?

1. 90-95% of cases

2. Stool is watery, moderate to large, and < 10/day

3. Dehydration ranges from mild to severe

4. Mechanisms include: toxins, reduced absorption

5. Etiology: V. cholerae, ETEC, Rotaviruses, Noroviruses

what is the clinical presentation of inflammatory GI infections?

1. 5-10% of cases

2. Stool is bloody, small to moderate, and > 10/day

3. Dehydration is generally mild

4. Mechanisms include: toxins, mucosal invasion

5. Etiology: Shigella spp., Salmonella spp., Campulobacter spp., EHEC, C. diff