Qn Heintz Lecture Notes Id Touro

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S4BBT4L2 Heintz (Hepatitis virus) HBV PEP: HBIG 0.06 mL/kg IM HbsAg + & HbeAg+ = highest risk of CA, biochem, histologic, virologic Sx Tx in acute but Tx in chronic Chronic: HbsAg+ > 6 mo, HBV DNA ≥ 20000 IU/mL = 105 copies/Ml, ALT > 2x ULN (ALT most specific to liver) Peginterferon a2a (Pegasys) Peginterferon a2b (Peg-Intron) Lamivudine Adefovir Entecavir Telbivudine Tenofovir or Emtricitabine

180 mcg sq qwk x48wk (DOC); CI if severe 10xULN SE: flu-like Sx, fatigue, anorexia, nvd, sleep alteration, inj site rxn, BMS, hair thin/loss, retinopathy, thyroid, worse DM, depress, ↓libido, hepatitis (everything except nephrotoxicity) 1.5 mcg/kg sq qwk x 48 wk (max 100 mcg sq qwk) – not FDA approved 100 qd x ≥ 1 yr need to add adefovir/TDF or switch to ETV b/c ↑resistance so 2nd line 300 if HIV coinfection 10 qd x ≥ 1 yr 0.5 – 1 qd x ≥ 1 yr also as 1st line but expensive, only as monoTx 0.5 for naïve & 1 for LAM refractory 600 qd x ≥ 1 yr; SE similar to LAM 300 qd x ≥ 1 yr not FDA approved if HIV Co-flares: Travada (TDF + (3TC or LAM)) + NNRTI or PI/R

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S4BBT4L2 Heintz (Hepatitis virus) HCV RVR (rapid) better PPV in SVR: undetect HCV RNA (<50-100 IU/mL) @ 4 wk EVR (early) better NPV in SVR: ≥ 2 log decline fr pre Tx level @ 12 wk ETR: undetect HCV @ end of tx (48wk) SVR: sustained @ 6 mo post Tx (72wk)

PegIFN a2a PegIFN a2b PLUS Ribavirin in 2dd

HCV Genotype 1 x 48wks 180 mcg sq qwk 1.5 mcg/kg sq qwk Weight based dosing 1000mg/day (≤75kg) 1200mg/day (≥75kg)

HCV Genotype 2&3 x 24wks (48wk if coinfect) (Hemodialysis: 135mcg) CrCl 30-50: ↓25%, 10-29: ↓50% Regardless of weight 800mg/day

CI = uncontrolled depression (d/c if suicide), solid organ transplant, autoimmune hep, unTx hyperthyroid, preg, severe cardio/pulmon, uncontrolled DM, <3yo, HSR ANC <1.5 (1500 cell/mm3), Plt<80, ALT > 10xULN, CrCl<50(Peg) RBC = anemia, Hgb <13 m, <12 fm SCr>1.5, ClCr<50 Severe CODP, asthma, cardiac

Other Meds (FDA approved): LATE: Lamivudine, Adefovir, Entecavir, Telbivudine Non FDA approved: Tenofovir, Entricitabine: use in HIV-HBV coinfection QUANG BUI

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S4BBT4L7 Tx: CAP Absence of abnorm VS is <1% chance PNA: RR>20, HR>100, T>100.4F(37.8C); CXR is definitive role in Dx; hard to collect sputum DRSP: drug resist Staph P: age >65, abx tx 3mo prior (esp beta-lactam or FQ), EtOH, multiple comorbid, immunosupp meds

PATHOGEN

TX

OUTPATIENT Streptococcus pneumoniae Haemophilus influenzae Mycoplasma pneumoniae Chlamydia pneumoniae RSV, influenza virus A & B, Parainfluenzae, Adenovirus 1. no abx in last 3 mo - macrolide (azithro, clarith) - doxycycline 2. comorbid (HF, DM, EtOH, asplen) - resp FQ (moxi, gemi, levo) - beta-lactam + macrolide

INPATIENT NONICU

INPATIENT ICU

    Legionella

 

1. β-lactam (CTX or Unasyn) + macrolide 2. resp FQ

 Enterobacteriacea Pseudomonas aerigunosa, Staph aureus 1. DRSP, Enterobact & Leg (DEL) - β-lactam + (macrolide or resp FQ) 2. DEL & Pseudomonas A - Zosyn, cefepime, or mero + cipro or (AG + azithro/cipro) 3. DEL, PA & Staph aureus - (2) + linezolid or vanco

ATYPICAL PNEUMONIA: insidious presentation Common pathogen: Chlamydophila pneumonia, Mycoplasma pneumoniae, Legionella pneumophila, influenza A & B Tx: Double coverage for bact: macrolide, resp FQ, TCN (not Doxycycline); generally beta-lactam + Tx for atypical For influenza: Oseltamivir (Tamiflu) initiate w/in 48 hours of Sx onset QUANG BUI

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S4BBT4L8 Heintz (HAP & VAP) Def: PNA developing ≥ 48 h after admission (HAP) or endotracheal intubation (VAP Risk factors: intubation, >60yo, AMS, major surger (esp neuro), trauma (esp head), acid suppression Immunosupp, pulmon dz (COPD, ARDS), chronic lung dz (CF, bronchiectasis), GN colonization Prolonged hospitalization, broad spectrum abx exposure Criteria for Clinical DX: new or persistent pulmonary infiltrate on Xray AND ≥ 2 of : 36C > T > 38C, 5000 > WBC > 1000 cells/mm3; purulent endotracheal aspirate - accuracy of aspirate sample fr LRT: o endotracheal aspirate TA (least accurate)  bronchoalveolar lavage sample (BAL)  protected specimen brush sample PSB aka Bartlett’s Brush (most accurate) - Clinical Pulmonary Infection Score: CPIS score > 6 associated w/ high likelihood of VAP/HAP CPIS POINTS 0 1 2 Tracheal secretions Rare Abundant Abundant & purulent (esp Bartlett’s) CXR infiltrations None Diffuse Localized T© 36.5-38.4 38.5-38.9 ≥ 39 and ≤ 36 WBC (/mm3) 4-11 K < 4K or > 11K & bands (L shift) PaO2/FiO2 (oxygenation) > 240 or ARDS ≤ 240 and no evidence of ARDS (A = arteriolar, a = alveolar) (ARDS = acute resp distress syndrome) microbio Negative Positive MDR = multiple drug resistant; abx 90d before, hosp ≥ 5d; hi freq of abx resistance in hosp; immunosupp dz &/or tx Presence of RF for HCAP: hosp > 2d 90d before, nursing home, extended-care facility, QUANG BUI

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Home infusion tx (including abx), chronic dialysis w/in 30d, home wound care, family w/ MDR pathogen

S4BBT4L8 Heintz (aspiration pneumonia) Def: inhalation (macroaspiration) of oropharyngeal or gastric contents into larynx & LRT; may cause A pneumonitis Risk factors: anything that compromises ability to swallow: Stroke, neuromuscular dz, sedation, lethargy, etOH, dysphagia, intubation & chronic illness Most cases from normal flora aerobic & anaerobic GPC >> GN Peptostreptococcus, S pneumoniae, viridans Streptococci, S aureus More common in alcoholics, nursing homes & hospital acquired: Kleb, Ecoli, Saureus & anaerobic GNR Empiric Tx (important to know setting ot pt aspirated) * do NOT use Clinda monotx if GN aerobes suspected (etOHic, SNF) AsP (alone) CTX + MTZ preferred Or Clinda* or Moxi or Unasyn CAP (inpt) AsP + CAP (admitted to hospital) CTX + MTZ + Doxycycline Or Moxi/Levo ± MTZ AsP (outpatient) Clinda, Augmentin, Moxi PO AsP (LTC facility, SNA, HAP) Or Zosyn/Meropenem alone Levo or Cefepime ± MTZ (documented aspiration) Sever periodontal dz, Zosyn Or Combo of 2 drugs: Putrid sputum, or etOHism CTX/Cefepime + Clinda or MTZ (admitted to hospital) Or FQ + Clinda or MTZ

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S4BBT4L9 Heintz (tb)

TUBERCULOSIS (Mycobacterim tuberculosis) – world 2nd leading cause of death from single infectious agent (after HIV) DX:

CXR: upper-lobe opacity w/ cavitation TST (tuberculin skin test): wait 48-72 hours to measure first induration*: ≥ 5 mm HIV, close contact w/ tb case, signif immunosupp = organ transplant or ≥ 15 mg prednisone x ≥ 1 mo ≥ 10mm <5yr immigrant, IVDU, resident/employee of hi-risk congregate settings, ModImm**, malnourish ≥15mm No tb risk factors *boost test = 2-step test (3 wks later) if TST all the time **mod immunosupp = DM, CA, ESRD SYSTEMIC SX (sim to MAC): LOCAL SX:

TX:

fever, night sweats, anorexia, weakness, chronic & productive cough pulmonary cough

nonpharm: controlling Tb transmission: ↓bacteria release, personal protection (N95 respirators), ↓environmental exposure Combo [RIPE] req for cure of active dz. Never add single drug to failing regimen LTBI (latent) Single drug is sufficient (INH x 9mo). R + P not recommended b/c risk of hepatic failure/death Active RIPE x 2mo initial phase  check AFB (acid fast)  INH + RIF x 4mo (if -) or x7mo (if +) continuation phase 7mo if cavitation CXR or if no cavitation but HIV +: INH/RIF

Isoniazid Rifampin Rifabutin Pyrazinamide

DOSE

(qd preferred)

ELIM

DDI

5 mg/kg 10 mg/kg [10 mg/kg/wk 20-25 mg/kg

 300 max  600 max  600 max]  2000 max

Hepatic Hepatic

PHT, CBZ 3A4 (lots)

Hepatic/Renal

None

TOXICITIES Hepatitis, not teratogenic but inc hepatitis in preg; peripheral neuropathy (add VitB6 pyridoxine 25-50 mg/d) Hepatitis (ALT 5xULN) Usually use if Rifampin DDI Hepatitis, hyperuricemia QUANG BUI

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Ethambutol

15-20 mg/kg

 1600 max

Renal

None

Retrobulbar neuritis (ocular)

2nd line for tx failure or resistant/tox to 1st line: FQ (moxi hep elim, levo renal elim), streptomycin S4BCT4L3 Heintz (Infective Endocarditis)

Prosthetic Valve IE

Native Valve Endocarditis

Streptococcus viridans & S bovis PCN Susceptible [IA] MIC ≤ 0.125 mcg/mL

PCN susceptible [IB] MIC ≤ 0.125 mcg/mL

Relative PCN Resistant 0.125 < MIC < 0.5 mcg/mL Tx as Enterococci if MIC > 0.5 mcg/mL PCN Susceptible

Rel/Fully PCN Resistant MIC > 0.125 [Tx same as NVIE by fully PCN-resistant Streptococci (MIC >0.5)]

Aq Crystalline Or CTX PLUS Gentamicin Sulfate PCN G Na 12-18 MU/24H IV cont 2 g/d IV or IM or dd Q4-6H x 4wks x 4wks Preferred in most pts>65yo If non-type 1 PCN allergy or pts w/ impairment of 8th May facilitate outpatient cranial nerve fx, or renal therapy w/ QD dosing impair 12-18 MU/24H IV cont 2 g/d IV or IM 3 mg/kg/d IV or IM or dd Q4H x 2wks x 2wks in 1 dose x 2wks 2 wk regiment not indicated for pts w/ known cardiac or extracardiac abscesses or for those w/ CrCl < 20 mL/min, impaired 8th cranial nerve fx, or Abiotrophia Granulicatella or Gemella sp infection (these sp r often PCN-resistant & should be treated as Enterococci IE) 24 MU/24H IV cont 2 g/d IV or IM 3 mg/kg/d IV or IM or dd Q4H x 4wks (CTX preferred) x 4wks in 1 dose x 2wks

Vancomycin HCL

24 MU/24H IV cont 2 g/d IV or IM 3 mg/kg/d IV or IM or dd Q4-6H x 6wks x 6wks in 1 dose x 2wks PCN or CTX + Gent has NOT demonstrated superior cure rates when compared to monoTx for pts w/ highly susceptible strains; Gent is not rec for pts w/ CrCl < 30 mL/min 24 MU/24H IV cont 2 g/d IV or IM 3 mg/kg/d IV or IM or dd Q4-6H x 6wks x 6wks in 1 dose x 6wks

20 mg/kg/d IV dd Q8-12H

30 mg/kg/d IV dd Q12H x 4wks Only for pts who can’t tolerate PCN/CTX (allergy/toxicity) Adjust dose for PK = 30-45; Tr = 10-15 mcg/mL (clinically Tr 15-20 mcg/mL ideal) 30 mg/kg/d IV dd Q12H x 4wks Only for pts who can’t tolerate PCN/CTX x 6wks Only for pts who can’t tolerate PCN/CTX 30 mg/kg/d IV dd Q12H x 6wks Only for pts who can’t tolerate PCN/CTX

Native & Prosthetic Valve Endocarditis: HACEK (Haemophilus, Actinobacilus, Cardiobacterium, Eikenella, Kingella) – use 1 agent QUANG BUI

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CTX Unasyn Cipro (FQ)

2 g/d IV or IM 12 g/d IV dd Q6H 1.5 g/d PO or 1200 mg/d IV dd Q8-12H

x 4 wks native But x 6 wks prosthetic

May substitute cefotaxime or another 3rd/4th gen (FQ?) FQ = cipro, levo, moxi Only for pt not tol ceph & ampi or to facilitate PO tx

S4BCT4L3 Heintz (Infective Endocarditis) Infective endocarditis req long tx courses w/ HIGH dose of BacteriCIDAL agents Epidemiology: ♂:♀ 1.7:1, IVDU signif RF, 4th leading cause of life-threatening ID Syndrome, 30-50 yo (uncommon in children) RF: preexisting cardiac valvular, complex (non)cyanotic congenital heart dz, prosthetic valve, prev endocarditis… Native Valve Streptococci (esp viridans) IVDU/Prosthetic Staphylococci (SA esp), GNR (also w/ cirrhosis) Elderly/nosocomial Enterococci

Native Valve

Staphyloccocal (risk factors: IVDU & prosthetics) Oxacillin Susceptible MSSA & MSSE

Nafcillin or Oxacillin ± Gentamicin Sulfate

12 g/d IV dd Q4-6H or 2 g IV Q4H 3 mg/kg/d IV or IM in 2-3 dd

X 6wks X 3-5d

MSSA & MSSE PCN-allergic (consider skin test) Oxacillin Resistant MRSA & MRSE

Cefazolin ± Gentamicin Sulfate

6 g/d IV dd Q8H or 2 g IV Q8H 3 mg/kg/d IV or IM in 2-3 dd

X 6wks X 3-5d

Vancomycin OR Daptomycin (never Linezolid)

30 mg/kg/d dd Q8-12H 6 mg/kg IV daily

X 6wks X 6wks

Nafcillin/Oxacillin for complicated RT-sided & LT-sided AG accelerate Killing in-vitro but clinical benefits of AG has not been established Avoid cephalosporins in pts w/ anaphylactoid rxns to betalactams [AG benefits not established] Adjust Vanco dose to achieve 1 H PK = 30-45 mcg/mL or Tr = 10-15 mcg/mL [Trough = 15-20 mcg/mL if MIC=2] Daptomycin only FDA for Right-sided

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Prosthetic Valve

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Nafcillin or Oxacillin + Rifampin + Gentamicin Sulfate

12 g/d IV dd Q4H or 2 g IV Q4H 300 mg/d IV or PO Q8H 3 mg/kg/d IV or IM in 2-3 dd

X ≥ 6wks X ≥ 6wks X 2 wks

Oxacillin Resistant MRSA & MRSE

Vancomycin OR Daptomycin

30 mg/kg/d dd Q12H 6 mg/kg IV daily (Q48H – CrCl<30)

X ≥ 6wks X ≥ 6wks

+ Rifampin + Gentamicin Sulfate

300 mg/d IV or PO Q8H 3 mg/kg/d IV or IM in 2-3 dd

X ≥ 6wks X 2 wks

Cefazolin 2g IV Q8H may be substituted (if allergy); PCN G 24 MU/d can be used if strain is PCN-S (MIC≤0.1) & doesn’t produce beta-lactamase (rare): if T1-HSR then substitute Nafcillin w/ Vanco 15mg/kg IV Q12H or Dapto 6mg/kg IV/d (Rt-sided IE only) Adjust dose to achieve Vanco 1 H Peak = 30-45 mcg/mL & Tr = 10-15 mcg/mL [T=15-20 if MIC =2] If allergic to Vanco or fail on Vanco, then sub w/ Dapto (Rtsided IE only) Gentamicin dosed as synergistic

S4BCT4L3 Heintz (Infective Endocarditis) Enterococcal Species – Native or Prosthetic Valve IE N/PVE Enterococci & Fully PCN-Resist Streptococci, Abiotrophila sp, Granulicatella sp

Suscept to AG & Vanco, Resistant to PCN & Ampi [beta-lactamase producing E faecalis] Resistant to PCN, AG & Vanco [E faecium]

Ampicillin Na Or Aq Cryst PCN G Na

12 g/d IV dd Q4H or 2g IV Q4H 18-30 MU/d IV cont or dd Q4H

X 4-6wks X 4-6wks

+ Gentamicin Sulfate Or CTX Vancomycin + Gentamicin Sulfate Or Strepto Or CTX Unasyn + Gentamicin Vancomycin + Gentamicin Linezolid Or Synercid (Quinupristin-Dalfopristin)

3 mg/kg/d IV or IM dd Q8H 2 g Q12H 30 mg/kg/d IV dd Q12H 3 mg/kg/d IV or IM dd Q8H 15 mg/kg/d IV dd Q12H 2 g IV Q12H 12 g/d IV dd Q6H 3 mg/kg/d IV or IM dd Q8H 30 mg/kg/d IV dd Q12H 3 mg/kg/d IV or IM dd Q8H 600 mg IV or PO Q12H 22.5 mg/kg/d dd IV Q8H

X 4-6wks X 6 wks X 6 wks X 6 wks X 6wks X 6wks X 6wks X ≥ 8 wks X ≥ 8wks

Ampi native valve: 4 wks rec for pts w/ Sx ≤ 3mo 6 wks tx rec for Sx ≥ 3mo PCN min 6 wks prosthetic valve CTX 2g Q12H opt for synergy if not gent Vanco/Gent only for pts who can’t tol PCN/ampi w/ 6 wks rec b/c Vanco has ↓act vs enterococci Use strepto or CTX if resist to gent Unlikely that strain will be susceptible to gent; if strain is gent resistant, >6wks of unasyn is req Vanco only if pt can’t tol Unasyn Should consult ID specialist; cardiac valve replacement may be necessary for bacteriologic cure; cure w/ abx alone QUANG BUI

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<50%; severe usu reversible thrombocytopenia may occur w/ >2wks linezolid tx; Synercid only effective vs E faecium & can cause severe myalgia

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