Unit 5: Critical Care

Risk Factors for infective Endocarditis

Previous endocarditis, prosthetic valves, intracardiac devices, congenital HD, other valve issues, HF, males, 50 yo or more, Hx of IVDU, immune comorbidities, poor dental health/recent dental procedure

Primary Pathogens in IE

MSSA/MRSA, Staph epidermidis, Strep viridans and gallolyticus, E. facealis

GNBs that are implicated in IE but less common

Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella (HACEK)

Which ABX are bactericidal

Beta-Lactams (Pens/Cephs), Glycopeptides (Vanc, Vancins, Daptomycin), AGs, FQs

Why are beta-lactams so good against Strep

Bind to PBPs with high affinity, no Beta-lactamase production in strep, avoid efflux

What is important to watch in a patient when giving high doses of Penicillins?

Na and K levels for hypokalemia and hypernatremia due to sodium salts in the ABX

Mechanisms of Aminoglycoside resistance

limited intracellular uptake, bugs can produce ribosomes that don’t bind the AG, enzymatic inactivation of the AG

Which mechanism of AG resistance most affects gentamicin?

enzymes of inactivation

Which mechanism of AG resistance most affects streptomycin?

Target binding site (ribosome) resistance

Describe BL/AG synergy

BLs will open cell wall by inhibiting cell wall creation, which allows the AG to get inside bacteria and prevent protein creation (including PBP) which further allows BL to prevent cell wall synthesis

What limitations are there to 2 week BL/AG therapy?

Children can’t b/c of ADEs, older patients/renal function issues

What major DDI is present with Vancomycin and AGs

higher incidence of nephrotoxicity

Why is Rifampin used in PVE treatment

sterilizes foreign bodies and breaks down “film”

IE treatment caused by GNBs

Ceftriaxone or Amp or Cipro

define sepsis

life-threatening acute organ dysfunction due to infection

define septic shock

subset of septic patients with circulatory dysfunction that provides a higher risk of mortality

True or False: Sepsis can be caused by any pathogen

True

Most common infections that progress to sepsis

Pneumonia, Abdominal infections, UTIs

SIRS criteria in sepsis

2 or more of: Temp >101 or < 96.8, HR more than 90, RR greater than 20 or PCO2 < 32, WBC >12 or <4 or 10% or more bands

SOFA in sepsis

screening for organ failure, acute change in score greater than 2 indicates organ dysfunction

How do we diagnose sepsis?

Blood cultures are mainstay, must get two samples (1 set) from different locations, other cultures if possible infection source is there (ex. urine)

Role of procalcitonin in sepsis

0.05-0.5 mcg/L indicates infection may be present, mainly used to tell us when to stop ABX

Goals of therapy for Sepsis

Don’t die, stop infection, MAP > 65 (60-65 in older pts), Lactate < 2 mmol/L, urine output > 0.5 mL/kg/hr

Principles of antimicrobial therapy in sepsis

Baseline of treatment, use broad-spectrum to cover likely pathogen, must be given asap (within 1 hour of known sepsis), if no shock and suspected sepsis ABX start window opens to 3 hours

Fluid resuscitation needs in sepsis

30 mL/kg ASAP (within 3 hours), use IBW if BMI over 30

Preferred fluids for fluid resuscitation in sepsis

crystalloids (NS, LRs, plasma-lyte), you can use colloids at 1/3 of crystalloid need (albumin)

Alpha-receptor agonist vasopressors

norepinephrine and phenylephrine

Other vasopressors

Vasopressin and Angiotensin II

Vasopressor/Inotropes

Epinephrine and Dopamine

Inotrope only

dobutamine

Corticosteroid of choice in sepsis

hydrocortisone

ADRs of Vasopressor therapy

ischemia, extravasation, HR changes, arrhythmias

Norepinephrine use in sepsis

1st line Vasopressor if you can use, promotes alpha-1 vasoconstriction also has inotropic beta-1 effect but not clinically significant

Dosing of NE in sepsis

continuous infusion that is titrated to keep MAP > 65, can be given in peripheral line if needed for short period

Vasopressin use in sepsis

“2nd line”, Binds to V1 receptor, causing vasoconstriction, added when NE dose reaches 0.2 mcg/kg/min, only agent NOT affected by acidosis, only infusion that is NOT titrated

Vasopressin ADRs/warnings

ischemia, caution in HFrEF, can precipitate angina, MI, or ventricular arrhythmia

Epinephrine use in sepsis

3rd line vasopressor or 1st line VP/inotrope, may be preferred and bradyarrhythmic/cardic patients, B2 activity may cause metabolic ADRs

Dosing of Epinephrine in sepsis

continuous infusion titrated to keep MAP > 65

Phenylephrine use in spesis

peripheral vasoconstriction by alpha-1 agonism, good for tachycardia patients since it does not affect heart, titrated to keep MAP > 65, can be given via peripheral line if no central access

Angiotensin II use in sepsis

added to NE if not at goal MAP, very expensive, must add on VTE prophylaxis

Angiotensin II dosing in sepsis

dosed in nanograms (ng), titrated up by 15 ng/kg/min every 5 minutes as needed, max rate in 1st 3 hours is 80 ng/kg/min, 40 ng/kg/min after 3rd hour

Dopamine use in sepsis

dose-dependent, 5-10 mcg/kg/min primarily stimulates Beta-1, >10 mcg/kg/min primarily stimulates alpha-1, only use in patients at low risk for arrhythmias

What drugs can we not infuse with dopamine in same line?

sodium bicarb, oxidizing agents, or iron salts

Dopamine ADRs

tachycardia, arrhythmias, worsening of pulmonary edema

Dobutamine use in sepsis

Primarily beta-1 stimulation (inotropic), used in cases of hypoperfusion despite adequate fluid resuscitation and MAP, MUST NOT be used without a vasopressor in sepsis

Corticosteroid use in sepsis

used in patients with poor response to fluids and vasopressors, added when dose of NE or Epi is 0.2-0.3 mcg/kg/min 2-4 hours after initial admin, patients already on chronic steroids for other diseases should continue them

Vasopressor deescalation

should be stopped as sepsis resolves, NE should be stopped before vasopressin

Stress ulcer prophylaxis in sepsis

PPIs, and H2RAs (can do either IV or oral)

VTE/DVT prophylaxis in sepsis

UFH, Enoxaparin, Dalteparin, Fondaparinux (used in HIT patients), SCDs

Chlorhexidine use in sepsis

used prophylactically for ventilated patients and catheter related blood-stream infections, both mouthwash and body wash used, it kills a lot of bugs

Hyperglycemia treatment in sepsis

insulin with BG goal of <180 mg/dL, must check BG q1-2 hours until 2 readings below goal, then check q4h

Symptoms of post-sepsis syndrome

sadness, difficulty swallowing, fatigue, muscle weakness, difficulty sleeping, poor memory, anxiety

Vasopressors to avoid for those with sulfite allergies

norepinephrine, epinephrine, phenylephrine, dopamine

Pathophysiology of endocarditis (vegetation formation)

Bacteria adheres to cardiac endothelium (usually valves), then inflammatory response happens leading to production of fibronectin which creates the thrombus which can shelter the bacteria

Consequences of vegetation formation

local valve destruction, prosthetic valves can detach, vegetations can embolize and spread infection in blood stream to other sites, peripheral vascular damage can occur b/c of vegetations

General symptoms of endocarditis

fever, chills, night sweats, loss of appetite, tachycardia, cough, pain in chest/back

General Objective signs of endocarditis

heart murmur, splenomegaly, fever, emboli, skin lesions, clubbing, petechiae, splinter hemorrhage, neurologic signs

Objective signs that are specific to endocarditis

Osler’s nodes, Janeway lesions, Roth’s spots (red flags should go up for IE if you see these)

septic emboli characteristics

occur in more than 25% of IE patients, emboli lodge in lungs in right-sided IE, emboli reach brain, kidney and spleen in left-sided IE, can cause lesions in fingers and toes, abscesses/infarction in large organs

Osler’s nodes characteristics

painful tender nodes that are usually found on pads of fingers and toes

janeway lesions

painless, non-tender embolic plaques found mainly on palms of hands or soles of feet, bacteria can be cultured from them

Roth’s Spots

white-centered retinal hemorrhages that are seen with eye exam

Diagnostic Key points for IE

95% of pts have positive blood cultures, 3 sets must be obtained ideally 30 minutes apart from each other, CBC run for abnormal WBC, ESR/CRP elevated, low Hgb (anemia), ECG tells us if vegetations are present

Duke-ISCVID MAJOR Criteria

Positive blood cultures, positive microbiology lab test (PCR), ECG or CT evidence, PET/CT evidence, Evidence of IE on direct inspection of heart during surgery

Duke-ISCVID minor criteria

Predisposing cardiac conditions, Fever > 100.4, valvular phenomena, immunologic phenomena, microbiologic evidence not meeting major criterion, new valvular regurgitation heard on auscultation

Definite IE as defined by Duke-ISCVID

Any one of: Microbes identified alongside S/Sx, Active IE in or on vegetation, 2 MAJOR criteria, 1 MAJOR criterion and 3 minor criteria, 5 minor criteria

Possible IE as defined by Duke-ISCVID

Any one of: 1 MAJOR and 1 minor criteria, 3 minor criteria

Rejected IE as defined by Duke-ISCVID

firm alternate diagnosis, lack of recurrence despite ABX for < 4 days, criteria not met for possible IE

Treatment goals for IE

eradicate causative organism with minimal drug exposure, decrease M&M, relieve S/Sx, prevent recurrence in HR pts with prophylactic ABX

Major ABX treatment principles in IE

High-dose IV ABX started in hospital, patient stays until stable, most can finish at home as outpatient with IV or even oral ABX, treatment is 4-6 weeks

inoculum effect

resistance to ABX develops due to high bacterial density in vegetations as well as stationary growth b/c the bug thinks its protected, most impacts beta-lactams and glycopepetides, FQs and AGs are less impacted

PenG Clinical Pearls in IE

given continuously or 4-6 divided doses, Na and K must be monitored, needs renal adjustment, currently in shortage

Ampicillin Clinical Pearls in IE

reconstituted with NS, short stability once diluted, needs renal adjustment, has high sodium content

Nafcillin Clinical Pearls in IE

is an ASP, historically is DOC in MS-staph, CYP3A4 inducer, vesicant, high sodium content, no dose adjustments needed

Oxacillin Clinical Pearls in IE

It is an ASP, almost interchangeable with nafcillin, high sodium content, higher risk of hepatotoxicity than nafcillin, neurotoxic reaction may follow large IV doses (risk higher in renal dysfunction)

Cefazolin Clinical Pearls in IE

more effective against Staph than Ceftriaxone, renal and obesity DA required, caution if true PCN allergy, medium sodium content

Ceftriaxone Clinical Pearls in IE

can be ordered in community setting, no DAs, medium sodium content, ADRs of biliary “sludging”, liver fxn abnormalities

Ceftaroline Clinical Pearls in IE

Active against MRSA, given Q8H for IE, can cause neutropenia in prolonged use (monitor CBCs), no sodium in drug, renal adjustment needed

Ceftobiprole Clinical Pearls in IE

FDA approved for RSIE from S. aureus, not in AHA guidelines, given Q6h for the first 8 days, then Q8h, may cause false positive in urine dipstick test, renal adjustment needed

Vancomycin Clinical Pearls in IE

PK dosing, max infusion rate of 1g/hr, Red Man syndrome is NOT an allergy, pretreat with Benadryl and Tylenol 30 minutes before dose or extend infusion time, concerns for ototoxicity and nephrotoxicity

Daptomycin Clinical Pearls in IE

for Staph and Enterococcus only, high doses used (8-12 mg/kg qday), D/C statins due to myopathy risk

Rifampin Clinical Pearls in IE

Never used as mono-therapy, breaks down “film” on vegetation, started 5-7 days after ABX is started and neg blood cultures, Potent CYP inducer, causes many body fluids to turn red-orange and can stain soft contact lenses

Linezolid Clinical Pearls in IE

Bacteriostatic, can cause serotonin syndrome if pt on other MAOIs or antidepressants, monitor for neutropenia, blood concentrations reduced by rifampin

Gentamicin Clinical Pearls in IE

Reserved for combo with Ceftriaxone in Pen-resistant strep, dosed by IBW, ototoxicity can occur (audiology exam needed after use)

Streptomycin Clinical Pearls in IE

Not addressed in 2026 AHA guidelines, causes more ototoxicity than gent (audiology exam needed), not many places keep in stock, light can darken solution but does not effect drug

Dalbavancin Clinical Pearls in IE

long-acting injectable ABX, 2 dose series (second given after 8 days), long half-life (2 doses give 6-week coverage), must be diluted in 5% dextrose, not effective against Vanc-resistant enterococci

Oritavancin Clinical Pearls in IE

long-acting injectable ABX, 2 dose series, long half-life as well, diluted in D5W or NS, CI with UFH use for 120 hours after dosing, not effective against Vanc-resistant enterococci

Dicloxacillin Clinical Pearls in IE

Oral Penicillin, taken on an empty stomach with at least 120 mL of water, QID dosing, do not lie down after taking

Amoxicillin Clinical Pearls in IE

Oral ABX paired with rifampin or moxifloxacin, QID dosing, not used for staph

Moxifloxacin Clinical Pearls in IE

QD dosing, typical FQ ADRs including QT prolongation, tendon rupture, glucose issues

Clindamycin Clinical Pearls in IE

combined with moxifloxacin, taken with 200-250 mL or water, must remain upright for at least 30 min

Duration of continued therapy in PVE (all 3 GP bugs)

6 weeks

Duration of continued therapy in NVE for Staph and Strep

4 weeks

Duration of continued therapy in NVE for Enterococci

6 weeks

At what point does the duration of therapy clock start in IE?

once bacteremia clears as seen on blood cultures

Inclusion criteria for changing from IV to oral ABX in IE

IE caused by Strep, E. faecalis, MSSA or Coag-neg staph; IV ABX for 10 days and 7 days after valve surgery with stability, no fever, inflammatory makers normal, TEE within 2 days of switch to show no progression

Exclusion criteria for changing from IV to oral ABX in IE

BMI > 40, other infection, suspected reduced oral absorption

Inclusion criteria for switch from IV ABX to Dalbavancin or Oritavancin (Long acting ABX)

Same criteria as oral switch plus unable to receive traditional OPAT due to lack of IV access, housing instability, or active/recent IVDU

Empiric ABX therapy for Native valve IE

Vanc or Daptomycin PLUS Ceftriaxone or Cefazolin

Empiric ABX therapy for Prosthetic valve IE

Vanc/Dapto PLUS cefepime/Pip-tazo or Ceftriaxone if < 3 months since replacement, Add Ceftriaxone, Cefazolin, or Amp-Sul as second agent if > 3 months since valve replacement