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Gram Positive pathogengs
- Staphylococcus aureus (MSSA, MRSA, GISA)
- S. pyogenes
- Streptococcus pneumoniae (PRSP)
- Enterococcus faecium (VRE, LR-VRE)
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Gram negative pathogens
- Pseudomonas aeruginosa
- Acinetobacter
- Klebseilla
- Enterobacteriacea
- E. Coli, Enterobacter,
- Citrobacter, Serratia,
- Proteus
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Mechanisms of resistance
- •Enzymatic inactivation
- •Efflux pumps : pump drug out of cell
- •Changing in antibiotic binding site
- •Change in permeability : increase thickness of cell wall
- Mutations
- Acquisition of Plasmid
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Mechanisms amoung B lactam
- strep pnuemo: change in PBP
- MSSA: enzymatic inactivation
- MSRA: change in PBP
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Steps to preven antimicrobial resistance
- Vaccinate
- use local data
- Stop treatment when cured
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Penicillin Advantages and Disadvantages
- AD: low cost, easy administration, excellent tissue penetration, favorable therapeutic index
- DIS: b lactamase, allergic reaction
- allergy, dosing
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Penicillin adverse reactions
- hypersensitivity
- neutropenia, thrombocytopenia
- interstitial nephritis
- autoimmune hemolytic anemia
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Penicillin Spectrum
- ABCG strep
- viridans
- syphilis
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Penicillin dosing
cont. infusion--> should be written as infusion over 24hrs not q 24
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Aminopenicillins
- Ampicillin: 3g IV q 6h
- Amoxicillin: 500 mg po q 8 h
- CANNOT BE GIVE BY CONT INFUSION
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Aminopenicillins + B lactamase inhib
- s. aureus
- e coli
- klebsiella
- anerobes
- used in polymicrobial infections (animal, human bits, bowel perforation, intra abdominal abcesses, PID, diabetic foot)
- --> amp/sulbactam
- --> amox. clav (fixed dose of clav)
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pseudomonas aeruginosa
- whore
- minimal nutrient req.
- in tennis shoes
- nosocomial
- presents as UTA, pneumonia, UTI, osteomyelitis, burns, otitis, endocarditis
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anti-pseudomonal penicillins
- extended gram ned spectrum
- Ticarcillin-- high na content: CI in renal failure
- Peperacillin-- 12-16 g per day in 4 divided doses
- stable for cont. infusion
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anti- pseudomal + b lactamase
- MSSA
- h influenza
- klebsiella
- anerobes
- polymicrobial infections
- ticarcillin/ clav
- piperacillin/tazobactam: 4.5 g q 6 hours based on kidney function
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Penicillinase resistant penicillins
- Coagulase positive = S. aureus
- Coagulase negative = S. epidermidis, S. saprophyticus
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Cephalosporins advantages and distadvantages
- Advantages
- Dosed less frequently
- Disadvantages
- select for cephalosporinases and ESBL
- no activity against Enterococcus sp.
- expensive
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1st generation ceph
- cephalexin- 500mg q 6h
- cefazolin- surgical prophylaxis, cellulitis,
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cefepine
- staph aureus
- pseudomans
- BID: 2g q 8h
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Carbapenems
- imipenem/ cilastatin
- peropenem
- doripenem
- MSSA
- b Fragilis
- pseudomonas
for serious nosocomial infections
SE: seizures
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Ertapenem
- once daily
- - does not cover pseudomonas or enterococcus
- - for intra-abdominal and complicaetd ssi
- - T1/2= 4 hours
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Aztreonam
- only gram neg (pseudomonas)
- used when allergic to PCNs but cross reaction with ceftazidime
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b lactam allergy
Type I: Immediate hypersensitivity, IgE mediated, anaphylaxis, minutes
Type II: Cytotoxic antibodies, IgG, IgM bind to renal/blood cells, anemia, leucopenia, thrombocytopenia, nephritis, dose and duration dependant
Type III: Immune Complexes, IgG, IgM bind to antigens and form circulating complexes, serum sickness, 7-14 days after initiation
Type IV : Cell mediated, no antibody involved, T-cell dependant, T-cells recognize the antigen leading to WBC recruitment to the site leading to inflammation, contact dermatitis
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Entercococcus
- - Normal gut flora
- - E. faecalis accounts for 90% of isolates and E.faecium ~10% of isolates
- - Multidrug resistant (including vanco.) strains of E.faecium have increased and referred to as VRE
- - Not intrinsically virulent but may act synergistically with other organisms
- - Contact precautions are critical
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Vanco
- - gram pos for resistant organisms
- - not for MSSA
- - potential for VRE
- - for c. difficile
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Vanco PD
- 1 g q 8-12 h or 15mg/kg q 12-- dose for renal
- -AUC/MIC monitoring
- - maintain 10-20 mcg/ml
- - dont use if MRSA isolate is 2mcg/ml
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Quinupristin/ Dalfospristin
- VRE facium
- Step
- MRSA
- MRSE
- monitor myalgias and LFTS
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Linezolid
- Oxazolidinone
- VRE
- MRSA
- s. pneumo
- t>mic and auc.mic
- SE: serotonin syndrome, thrombocytopenia
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Daptomycin
- MRSA
- VRE
- cSSTI and bacterema
- skeletal muscle toxicity
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Tigecycline
- MRSA
- VRE
- enterobacteriacea
- Acinebacter
- not active agains pseudo bc of efflux pumps
- SE: NV
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Ceftaroline
the new miracle cephalosporin
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Aminoglycosides
- gentamicin
- tobramycin
- amikacin
- streptomycin
- MSSA
- enterococcus
- pseudomonas (amikacin>tobramycin>gentamycin)
- NOT anerobes
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Amindoglycosides dose
gentamicin and tobramycin
- 1-2mg/kg q 8-12 h-- for enterococcal
- 5-7 mg/ kg q 24h -- for gram neg
adjust for crcl < 60ml/min
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Aminoglycosides Tox
Nephrotoxicity- elderly, renal insuff. dehydration, cirrhosis, long duration
ototoxicity- exposure dependent
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Fluoroquinolones
cipro, levo, mox, gemi
- gram + = pnuemo
- mycoplasma
- chlamycia
- ricketssia
- legionela
peak/mic auc/mic
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Cipro
- staph (not first line bc of resistance)
- mycobacteria
- UTS
- BID
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Moxifloxacin
- CAP
- cSSI
- qd
- not removed by kidney (no UTI)
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Flurorquinolone SE
- dizziness, ha, insomnia
- nvd
- drug interactions: caffiene, metal
- tendinitis
- hypersensitivity
- QT prolongation
- dysglycemia
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Macrolides
- Erythromycin
- -Potent P-450 inhibitor which results in multiple potential drug interactions
- -Dosed q6h, frequent GI distress associated with erythro
- Clarithromycin (Biaxin®)
- -Moderate P-450 inhibitor with significant profile for drug interactions
- -Dosed q12h
- Azithromycin (Zithromax®)
- -No interaction with cytochrome P-450
- -High drug concentration achieved intracellularly
- -Dosed QD
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Azithromycin
- 60 hr t1/2
- gram pos (strep)
- respt tract gram neg
- atypicals and mycobacteria
- not UTIs
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Tetracyclines
- Doxycycline: CAP caused mycoplasma and chlamydia
- Minocycline: p. acnes
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Metronidazole
- B fragilis
- c dificile
- metallic taste
- peripheral neuropathy
- inhibits alc dehydrogenase
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Clindamycin
- b fragilis
- MRSA
- bone penetration
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nitrofurantion
- UTI- VRE, urthritis
- precautions: peripheral neuropathy, lung, g6pd def.
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colistin
- pseudo
- cystic fibrosis pts
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Fosphomycin
preggers resistant UTI
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Limitations of MIC
- Time course
- rate of bacterial kill
- dose-kill relationshipPA
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cmax:mic
- aminoglycosides
- fluroquinolones
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t> MIC
- carbapenems
- cephalosporins
- penicillins
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Strategies to increase t>MIC
- increase dose frequency
- increase duration of infusion
- select agent with lower MIC
- want it between 8 and 16
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Aminoglycosides HDODA
want cmax ratio to be 8-10 to get a peak of 16-20mcg/ml for gentamicinand tobramicin
first dose: 4-7 mg/kg then adjust
aim for undetectable trough
Peak occurs 2 hours after end of infusion
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aminoglycoside traditional dosing
get peak concentration of 4-10 mcg/ml with a ratio of 2-5
for gram positive organisms
- give 1-2 mg/kg q 8 hours then adjust
- - peak concentrations range between 4-8 ug/ml and trough is 1-2 ug/ml
Peak occurs 1 hour after infusion
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Exclusion criteria for HDODS of aminoglycosides
- crcl of <40ml/min
- entercoccus infection
- spinal chord injury
- burn pts
- meningitis
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A patient has renal def. and is getting once daily aminoglycoside
this is traditional dosing not hdoda
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distribution of vanco
- t1/2a = 30 mins
- variable protein binding
- cl relates to crcl
- t1/2 = 3-9 hours
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target trough for vanco
15-20mg
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infusion rate for vanco
<15mg/min
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Vanco TDM
peak: 2 hours after 1 hour infusion
Trough: within 1 hour of next dose
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Loading dose
- <50kg= 1g
- 50-100kg = 2g
- >100kg = 3g
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Vanco dose
- 50-79kg = 1g
- 80- 100kg = 1.5g
- >100 = 2g
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Vanco dose interval
- q8h (CrCl> 100 ml/min)
- q12h (CrCl> 50-100 ml/min)
- 24h (CrCl< 50 mL/min)
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what side are teh aortic and mitral valve on?
left side
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risk factors of endocarditis
- -prosthetic valve
- - mitral valve prolapse with regurgitation
- - IV drug abuse
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viridans strep
- common in mouth and gingiva
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streph bovis
found in gi tract
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enterococci
- found in gi tract
- - includes enteroccus faecalis and faecium
- - difficult to treat and needs combination therapy always
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right sided IE
- IVUD
- MRSA
- low mortality
- treated with abs
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left sided IE
- mostly prosthetic valves
- MRSA and MRSE
- surgery + abs
- three drug regimen
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Virdams strep / S bovis that's PCN- S
- 1. penicllin/ ceftriaxone only
- 2. penicillin/ ceftriaxone + gentamicin
- 3. vanco only
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Vidans/ bovis that PCN- R
- 1.penicillin/ ceftriaxone + gentamicin
- 2. vanco only
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EI- Enterococci that's PCN-S
- 1. Penicillin/ Amp + gent/ strep
- 2. vanco + gent/ strep
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EI- enterococci that's PCN- R
- 1. Vanco + gent/ strep
- 2. Gent+ amp/sulbactam
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EI staph - MSSA
- 1. nafcillin/ cefazolin + gent
- 2. vanco only (pen allergy)
- for prostetic
- 1. add gent + rifampin
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EI- MRSA
1. vanco
- for prostetic
- 1. vanco + gent + rif
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Prophylactic treatment
- Amox 2g
- clindamycin 600mg po
- cephalexin
- azith
- clarith
- one hour prior to procedure
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Common pathogens of CNS infections
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–Streptococcus pneumoniae
- –Neisseria meningitidis
- –Haemophilus inflenzae
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s/s of meningitis
- stiff neck
- headache
- photophobia
- irritable
- kernig and brudzinski
- seizures
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opening pressure
- normal is 100
- over 200 is concerning
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bacteria: eat __ and poop ___
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pathogen in minigitis based on age
- 1-2 years: pneumo, h influenzae
- 2-50: s pneumo, maybe flu, neisserria
- >50: pneumo, nesserria, listeria,
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Emperic therapy of meninigits
- 1-2: dex if h.flu or pneumo + ceftriazone + vanco
- 2-50: dex if pneumo + ceftriaxone + vanco
- >50 : dex if pneumo + ceftriaxone + vanco + amp
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dexamthasone dose
- children: .4mg/kg q 12h for 2 days
- adults: .15mg/kg q 6 h for 2-4 days
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emperic dosing for meningitis
- ceftriaxone: 2g q 12 hours
- vanco: 15 mg/kg q 12
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Neisseria Meningitidis
- Behavioral change, seizures, coma
- •Up to 50% , DIC, purpuric lesions
- •Drug of choice (high doses) X 7 days:
- •Penicillin G IV (if Pen MIC= S)
- •Ceftriaxone or cefotaxime (if Pen MIC= I/R)
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prophylaxis of meningitis
Rifampin po for 4 days
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Streptococcus pneumoniae for meningitis
- DOC (x10-14 days)
- –Ceftriaxone or (cefotaxime)
- –Vancomycin (Cephalosporin allergy or resistance)
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H influenzae for meningitis
DOC: ceftriaxone or cefotaxime
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SIRS
- can be infection or non-infectious etiology
- ► 2 or more of the following are clinical insults:
- -Temperature >38°C or <36°C
- -HR >90 beats/min
- -Respirations >20/min
- -WBC count >12,000/mL or <4,000/mL or >10% immature neutrophils
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Sepsis
- clinical insults which are due to infection
- ► 2 or more of the following are clinical insults:
- -Temperature >38°C or <36°C
- -HR >90 beats/min
- -Respirations >20/min
- -WBC count >12,000/mL or <4,000/mL or >10% immature neutrophils
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Severe sepsis
sepsis with >1 organ dysfunction
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septic shock
- severe sepsis thats hypotensive
- perfusion abnormalities
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pathogen of sepsis
- SA
- pneumo
- e coli
- klebisiella
- psuedo
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adjuctive therapies for sepsis
- Hemodynamic- fluid - NS. vasopressor, inotropic
- oxygen
- nutritional support (high protein low carbs)
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fluic support in sepsis
- isotonic cyrstalloids
- 0.9% nal --> may need 10L in 24 hours
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Inotrope therapy
dopamine and dobutamine
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vasopressor therapy
norepinephrine, phenylephrine, epinephrine
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staph aureus
- anti b lactam
- cephalexin
- ceftriaxone/ ceftaxime
- cefepime
- cipro
- aminoglycosides
- nafcillin
-
s. pneumo
- pen
- ceftriaxone/ ceftaxime
- linezolid
- levo
- azith
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pseudo
- anti-pseudo
- ceftazidime
- cefepine
- cipro
- aminoglycosides
- azetreonam
- azith
- carbapenams
- colistin
- fosphamycin
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enterococc
- NOT CEPHS
- aminopens
- tigecycline
- aminoglycosides (Td)
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B lactams inhibitors
- klebsiella
- e coli
- h influenza
- anerobes
- MSSA
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MRSA/VRE
- vanco
- quin.dal
- dapto
- trigecycline
- trim/sul
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anerobes
- carbapename
- ertapenem
- metronazole
- clindamycin
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