Study your flashcards anywhere!

Download the official Cram app for free >

  • Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off
Reading...
Front

How to study your flashcards.

Right/Left arrow keys: Navigate between flashcards.right arrow keyleft arrow key

Up/Down arrow keys: Flip the card between the front and back.down keyup key

H key: Show hint (3rd side).h key

A key: Read text to speech.a key

image

Play button

image

Play button

image

Progress

1/144

Click to flip

144 Cards in this Set

  • Front
  • Back
___________- glycopepetide antibiotic

Mechanism of Action
Inhibits bacterial cell wall synthesis by _____________through binding to portion of cell wall precursor
Vancomycin

blocking glycopeptide polymerization
Vancomycin:Antimicrobial spectrum
________________including methicillin resistant strains of staphylococcus aureus (MRSA) & methicillin sensitive staph. aureus (MSSA)
Coagulase negative __________
Streptococcus (most strains)
Anaerobes -Clostridium species including __________
Staphylococcus aureus & staphylococcus epidermidis

staphylococci

C.difficle
Vancomycin is bactericidal
V_SA  MIC <_mcg/ml
V_SA  MIC _mcg/ml
V_SA  MIC> __mcg/ml

Most strains of staphylococccus sensitive to Vancomycin with MIC <___mcg/ml
VSSA  MIC <4mcg/ml
VISA  MIC 8mcg/ml
VRSA  MIC> 32mcg/ml

1.5
Vancomycin: Pharmacokinetics
_______absorption minimal
30 to 55% _______bound
Diffuses readily into certain tissues
CSF levels range from 4-9% of serum levels without inflamed meninges
Half life = 4 to 6 hours in adults with normal renal function
70%-90% excreted in _____
Oral

protein

urine
Vancomycin: Adverse Effects
__________
Occurs in 2% of patients
Unclear if elevated peaks or troughs responsible
Data suggests trough___mcg/ml
Peaks _____ mcg/ml
ototoxicity

13-32

21-62
Vancomycin :Adverse Effects
___________
Incidence = 5-15%; 22-35% with aminoglycoside
Appears to be concentration related
Increased risk with trough >__mcg/ml
Can be complicated with __________therapy
Pre-existing renal problem
Nephrotoxicity

30

aminoglycoside
Vancomycin :Adverse Effects
“Red man Syndrome”
___________ mediated reaction
Involves rash over upper body, hypotension
Thought to be related to ________

Dermatological-Rash

Stevens-Johnson’s Syndrome-<1%
Histamine

rapid administration
Vancomycin: FDA Indications

Rx of infections by susceptible organisms
_______,________,_______,_____
Endocarditis prophylaxis
Endocarditis treatment
Staphylococcal enterocolitis
Pseudomembraneous colitis
Diphtheroid infections
MRSA,
staph epidermidis,
strept viridans,
enterococus faecalis
CDC Guidelines for Vancomycin
Situations to *DISCOURAGE*

Routine _________prophylaxis
Rx of single (+) culture for ___________
Empiric therapy of _______-no evidence of gram (+) infection
Continued empiric therapy
MRSA Colonization
Primary therapy for ____________
Topical application or irrigation
Treatment of _______or other susceptible infections
Prophylaxis in _______patients
Prophylaxis for indwelling central or local __________
surgical

coagulase (-) staph

febrile neutropenia

pseudo membraneous colitis

MSSA

low birth wt

catheters
Vancomycin Controversy
Studies indicate Vancomycin not effective in killing bacteria quickly & sterilizing blood as rapidly as _________________
Use ________over Vancomycin (except in MRSA) OR
Unless allergy to beta lactam or MRSA
nafcillin & ampicillin

beta lactam
Vancomycin: Pharmacokinetic Dosing guidelines

Step 1A : Calculate Dose
Vancomycin is dosed based on total body weight (TBW) except in ______
Dose= __mg/kg (max 2gm/dose) 
After calculation, round the dose to the nearest ___mg
Dose – may up to dose to __mg/kg in special populations e.g ____ pts      
obese pts
15mg/kg
250mg

19mg/kg in burn pts
Vancomycin:Pharmacokinetic Dosing guidelines
Step 1B: Calculate Dose (Obese Pts)
Use adjusted body weight (ABW) (>20% IBW)
Weight equations:
Ideal Body Weight (IBW)
Male (kg) = __+ (2.3 x inches of ht >60inches)
Female (kg) = ____ + (2.3 x inches Ht >60inches)

Adjusted Body Weight (ABW)
IBW + ___(Total weight - IBW)
50
45.5

0.4
Vancomycin: Pharmacokinetic Dosing guidelines
Step 2: Calculate Crcl

Use Cockcroft Gault

CrCl male = __________
CrCl female = .85 x ________
(140-age) x IBW
_______________
Scr x72
Vancomycin:Pharmacokinetic Dosing guidelines
STEP 3: Determine Dosing Interval
CrCl (ml/min) Dosing(hrs)
>100
70-90
50-69
30-49
<30
CrCl (ml/min) Dosing(hrs)
>100 12
70-90 18
50-69 24
30-49 48
<30 Base on trough
Vancomycin:Pharmacokinetic Dosing guidelines
STEP 4 : Measure levels
Measure Peak & trough with ___ dose following initiation of therapy or dose adjustment
For dosing interval >__hrs, __ dose may be appropriate for measuring serum concentration
Measure Serum creatinine initially & periodically Q ______if stable
3rd

>48hrs, 2nd dose

4-7days
Vancomycin:Pharmacokinetic Dosing guidelines
STEP 4 : Measure levels
No need to measure concentrations for empiric therapy if anticipated duration ________
Peak= ______ after infusion (only in CNS, bone infections etc.)
Trough= within ______ prior to next dose
<72 hrs

1hr

30mins
Vancomycin:Pharmacokinetic Dosing guidelines
Desired Peak
_______ mcg/ml

Peak too high: Decrease dose
Peak too low: Increase dose

Desired Trough
______mcg/ml
Literature 5-15mcg/ml
6-12mcg/ml (BRGMC)
Trough too high:Extend Interval

Trough too low:Decrease Interval
25-40mcg/ml

5-10mcg/ml
Vancomycin:Pharmacokinetic Dosing guidelines
Step 5: Renal Failure Patients
Dose __ mg/kg of TBW or ABW x 1
Check random level in hemodialysis patient in__days
If level 16-17 can redose in 24hrs i.e. Q96hrs
Recheck in __ days after subsequent doses
Note:
Hemodialysis does not appreciably remove Vancomycin
_________ remove Vancomycin
Monitor concentrations more frequently
15mg/kg

3 days

5 days

CAVH & CAVHD
VANC DOSING

WT --------DOSE--------INFUSION
>120kg
100-120kg
60-100kg
40-60kg
25-40kg
>120kg 1.75gm 90mins
100-120kg 1.5gm 90min
60-100kg 1-1.5gm 60-90mins
40-60kg 750mg 60mins
25-40kg 500mg 60min
Vancomycin:Pharmacokinetic Dosing Guidelines
Strong correlation between Vancomycin clearance &______

Recent data- prolonged therapy (>10days) result in _________in drug clearance despite stable renal function

Close monitoring required
creatinine clearance

decline
Vancomycin:Summary
Vancomycin- treatment of _____________

Misuse & concern for resistance- CDC guidelines

Use ___________for Methicillin susceptible organism

Use lower doses in _________to prevent toxicity

adult dose:__________based on:
Young healthy adult with:
Adequate Weight
Creatinine Clearance
g (+) infections

beta latam

elderly

1 gm q 12 hrs
Mr CJ, a 65 yr old male pt has just been admitted to the medical unit. Pt’s blood cultures 3 days later are positive for MRSA. Pt’s data is as follows Scr =1.4,Wt= 160lbs,Ht = 5ft 10 ins. Pt’s IBW is:
A) 73kg
B) 60kg
C) 80kg
A) 73kg**
B) 60kg
C) 80kg
Vancomycin Case Study
2. Mr CJ. a 65 yr old male pt has just been admitted to the medical unit. Pt’s blood cultures 3 days later are positive for MRSA. Pt’s data is as follows Scr =1.4,Wt= 160lbs,Ht = 5ft 10 ins. Pt.’s CrCl is
A) 54ml
B) 46ml
C) 80ml
A) 54ml**
B) 46ml
C) 80ml
Vancomycin Case Study
3. Mr CJ., a 65 yr old male pt has just been admitted to the medical unit. Pt’s blood cultures 3 days later are positive for MRSA. Pt’s data is as follows Scr =1.4, Wt= 160lbs,Ht = 5ft 10 ins. Determine Pt’s Vancomycin Dose & Interval
A) 1gm IVPB Q24hrs
B) 1gm IVPB Q12hrs
C) 2gm IVPB Q24hrs
A) 1gm IVPB Q24hrs**
B) 1gm IVPB Q12hrs
C) 2gm IVPB Q24hrs
Vancomycin Case Study
4. Mr CJ.’s trough should be measured
A) With the 3rd dose
B) With the 5th dose
C) No need to measure trough
A) With the 3rd dose**
B) With the 5th dose
C) No need to measure trough
Vancomycin Case Study
5. Ms CJ,s measure trough is 16mcg/ml
You would adjust the therapy as follows:
A) Hold dose, & extend interval to achieve trough <12
B) Increase the dose & extend interval
C) Do nothing about it
A) Hold dose, & extend interval to achieve trough <12 **
B) Increase the dose & extend interval
C) Do nothing about it
Large family of broad spectrum B- lactam antimicrobials
Introduced in the 1960’s- widely used
Demonstrate low rates of ________
Have a favorable pharmacokinetic profile
Used as first line agents for ______,________,_________.
Most recent generation -1997
Some offer unique spectrum of activity; some “me- too agents”
Cephalosporins

toxicity

pneumonia, meningitis, gonorrhea
Cephalosporins- Mechanism of Action
Exert antimicrobial effect by interfering with bacterial cell wall synthesis (peptidoglycan)
Peptidoglycan surrounds bacterial cell wall thereby providing strength & rigidity
Bactericidal against organisms that produce autolytic enzymes e.g. __________________
Generally bacteriostatic against others e.g.P __________
Streptococcus pneumoniae

aeuruginosa
Cephalosporin Pharmacokinetics
Important differences include:
amount of absorption after oral ingestion
Serum half life
Concentration in CSF
Most cephalosporins eliminated __________
Exceptions include _______,_________,________
No oral formulation achieves _____________
renally

cefixime, cefoperazone, ceftriaxone

therapeutic concentrations in CSF
Cephalosporin Kinetics (CSF)
No 1st generation agent provides _________
2nd Generation-only _________achieves therapeutic CSF levels

Comparative studies find cefuroxime less efficacious than _________,__________
sufficient CSF penetration

Cefuroxime

cefotaxime, ceftriaxone
Cephalosporin Kinetics (CSF)
Cephalosporins with proven effectiveness for Rx of meningitis-
__________- 3rd generation
__________- 3rd generation
__________- 3rd generation
__________- 4th generation
Cefotaxime
ceftriaxone
ceftazidime
cefepime
Cephalosporin – Adverse Effects
Have a favorable efficacy to toxicity profile
GI Effects- N/V or diarrhea (oral agents)
____________– IV agents (1-2%)
Pain –for IM injections _____________
Hypersensitivity or allergic reactions-1-3%
Dermatological- _________ -common
Serum sickness –children on _____________
Anaphylaxis – rare – 0.02%
Cross reactive _________allergy in pts with PCN allergy –poorly defined 5.4 -16.5%
Hematologic toxicity-thrombocytopenia or leukopenia
Thrombophlebitis

(Ceftriaxone-lidocaine)

maculopapular rash

cefaclor,cefprozil

cephalosporin
Cephalosporins
1st Generation More gram___& < gram ____ coverage

Most active against aerobic gram (+) ______

Includes MSSA
gram (+)

gram (-)

cocci
Cephalosporins Classification
2nd generation = _____gram (+) coverage &
___gram (-) coverage

Variable activity against staphylococcus

More active against selected ____________

Some active against anaerobes- _____________
Less

More

gram (-) organisms

cefoxitin, cefotetan (given for abdominal surgeries)
Cephalosporins- Classification

3rd Generation = _______gram (+) activity & _____gram(-)

Most active against gram (-) organisms

Some active against __________- __________, to a lesser extent cefoperazone
Lesser
>>>

pseudomonas aeruginosa
Ceftazidime
Cephalosporins- Classification
4th generation =
gram (+) __ gram(-)

Active against ___________

_________only agent in this class
=

pseudomonas

cefepime
1st GEN Ceph
Generic /Brand/ Route of Adm.
Cefadroxil _______ Oral
Cephalexin _______ Oral
Cephradine _______ po,IV,IM*
Cefazolin _______ IM,IV
Cephalothin _______ IM,IV
Cephapirin _______ IM,IV
Cefadroxil-Duricef
Cephalexin-Keflex
Cephradine-Velosef
Cefazolin-Ancef,Kefzol
Cephalothin-Keflin
Cephapirin-Cefadyl
Cephalosporins 2nd Generation
Generic /Brand /Route of Adm.
Loracarbef _________ Oral
Cefprozil __________ Oral
Cefuroxime Axe _______ Oral
Cefonicid________IM, IV
Cefamandol ________IM, IV
Cefotetan_______ IM,IV
Cefoxitin________IM, IV
Cefuroxime_______IM, IV
Cefaclor_________ Oral
Loracarbef Lorabid 3-400mgBID
Cefprozil Cefzil 500mg BID
Cefuroxime Axe Ceftin500mgBID
Cefonicid Monocid
Cefamandol Mandol
Cefotetan Cefotan **1-2gm BID
Cefoxitin Mefoxin 1gm q 8hrs
Cefuroxime Zinacef .75-1.5gm q 8 hrs
Cefaclor Ceclor
3rd Generation Cephalosporins
Generic /Brand/ Route of Adm.
Cefixime _____ Oral
Cefpodoxime _____ Oral
Ceftibuten _____ Oral
Cefdinir _____ Oral
Cefoperazone _____ IM,IV
Cefotaxime _____ IM,IV
Ceftazidime _____ IM,IV
Ceftizoxime _____ IM,IV
Ceftriaxone _____ IM,IV
Generic Brand Route of Adm.
Cefixime Suprax
Cefpodoxime Vantin
Ceftibuten Cedax
Cefdinir Omnicef
Cefoperazone Cefobid
Cefotaxime Claforan
Ceftazidime Fortaz,Tazicef
Ceftizoxime Cefizox
Ceftriaxone Rocephin
4th Generation Cephalosporins
Generic/ Brand /Route of Adm.
Cefepime _______ IM,IV
Cefpirome†

† = Investigational agent
Generic Name Brand Name
Cefepime Maxipime
Cephalosporin Usage
Excellent choices for initial _________- broad spectrum of activity & low toxicity
Choice depends on clinical setting, patient factors, local susceptibility
Obtain _________prior to empiric therapy
Cultures available- change to most active, least costly, preferably with narrow spectrum of activity
empiric Rx

cultures
Spectrum of Inactivity
Some organisms including enterococci, Listeria , atypical organisms- ________,________,________always resistant to cephalosporins

Little activity (except ________,_________) against bacteroides fragilis
Legionella, Mycoplasma, chlamydia

cefoxitin, cefotetan
3rd (?2nd) Generation cephalosporins used for Rx of ____
Rationale:
emergence & increase in PCN- resistant S. pneumoniae
Beta-lactamase producing Haemophilus species
CAP
Community Acquired Pneumonia (CAP) Agents
Hospitalized patient
__________(Claforan) 1gm IVPB Q8 –12 hours OR
Ceftriaxone (Rocephin ___gm IVPB Q24 hours
Above (2) agents most active against S. Pneumoniae isolates with dec susceptibility to PCN

Add __________ when atypical organisms suspected or Doxycyline
??Cefuroxime 750mg-1.5gm Q8hrs- resistance
Cefotaxime

1gm IVPB Q24 hours

macrolide (Zithromax, Biaxin)
Indications- Community Acquired Pneumonia (CAP)
For Aspiration Pneumonia
Add agent active against anaerobic bacteria

Use ____________
Alternatively can use _______1.5-3gm IVPB Q 6hrs as monotherapy
Clindamycin or Metronidazole

Unasyn
Indications- Nosocomial Pneumonia
Caused by highly resistant gram (-) bacilli
Use ___________1-2gm IVPB Q8 hrs OR
________1-2gm IVPB Q12hrs Plus
An __________– Tobramycin, Gentamicin etc
Can do once daily dosing Aminoglycoside (5mg/kg Q24hrs) if good renal function
Cefepime preferred for ________
Ceftazidime

Cefepime + aminoglycoside

E. cloacae
Indications- Meningitis
3rd Generation cephalosporins- drug of choice for may types of bacterial meningitis
__________2gm IVPB Q6hrs OR
__________2gm IVPB Q 12hrs

Achieve therapeutic CSF levels against most etiologic agents- community acquired
Add __________if high rates of B-lactam resistant pneumococci
***Cefotaxime
***Ceftriaxone

Vancomycin
Indications- Meningitis
Add __________to regimen for infants, elderly, or immunocompromised pts. for possible coverage of ___________
Meningitis in post neurological setting
Caused by staphylococci or Gram (-) like P. aeruginosa

Use _________2gm IVPB Q 8hrs OR
Use ________1-2gm Q 8 - 12hrs
***Ampicillin ***
L. monocytogenes

Ceftazidime
Cefepime
Indications- Febrile Neutropenia
For patients with fever & neutropenia, initial Rx can be:

_________1-2gm IVPB Q 8hrs OR
_________1-2gm IVPB Q8-12hrs

Add _________ for documented gram (-) infection or severe illness
Ceftazidime
Cefepime
Aminoglycoside
Indication- Sexually Transmitted Diseases
Isolates of Neisseria gonorrhea resistant to PCN increasingly common
Treatment of uncomplicated GC
__________125mg to 250mg IM x 1dose or
__________400mg PO x 1 dose OR
__________200mg PO x 1 dose OR
_________1000mg PO x 1 dose
Longer courses of therapy necessary for complicated disease or disseminated infection
Ceftriaxone
Cefixime
Cefpodoxime
Cefuroxime Axetil
Indications- Surgical Prophylaxis
Ideal agent for peri-operative antimicrobial prophylaxis
Active against most common infecting isolate – staphylococci
Safe
Inexpensive
___________is preferred prophylactic antimicrobial agent for most purposes
Cefazolin
Indications- Bacterial Endocarditis
Often due to highly susceptible organisms such as __________________
Traditionally treated with ___, with or without an ________
Recent studies confirm efficacy of ___________
Dose = 2gm IVPB Q24hrs
Simplified regimen attractive for outpatient therapy
Strep. viridans, Strep. Bovis
**PCN**, w or w/o aminoglycoside

ceftriaxone
1) ____________– surgical prophylaxis, Rx of uncomplicated skin infections
2) _____________- CAP, bacterial meningitis,infections due to susceptible organism
Cefazolin

Cefotaxime or Ceftriaxone
A 45yr w/male undergoing Rx for lung cancer has just been admitted with CC of fever, cough, malaise. Temp=102.5F, P=96
Lab Data WBC= 2.5, ANC=300,H/H= 8/24
Pt should be started on:
1) Cefepime 2gm IVPB Q8hrs+ Gentamicin
2)Ceftriaxone 2gm Q12hrs + Tobramycin
3)Ceftazidime 2gm Q8hrs + Cipro
1) Cefepime 2gm IVPB Q8hrs+ Gentamicin
Cephalosporin – Review
A 50yr old male patient comes to the ER with a hx of fever, neck stiffness etc. ER MD suspects meningitis. Pt should be started on this empiric ATB regimen
1) Primaxin 500mg IVPB Q6hours
2) Ceftriaxone 2gm IVPB Q 12hours
3)Cefotaxime 2gm IVPB Q 8hours
2) Ceftriaxone 2gm IVPB Q 12hours
Cephalosporin – Review
Which of these cephalosporins is commonly used for antimicrobial prophylaxis prior to surgery ?
1) Cefuroxime Axetil
2) Ceftizoxime
3) Cefoperazone
4) Cefazolin
4) Cefazolin
A bactericidal antibiotics from streptomyces

Share chemical antibacterial , antimicrobial, pharmacologic & toxic characteristics

Used widely against gram negative (-) enteric bacteria e.g. in bacteremia sepsis, in combination with PCN or other antimicrobials

MOA: Irreversible___________
aminoglycosides

inhibitors of protein synthesis
Aminoglycosides: Overview
- most widely used
- limited to topical & oral use
- limited to topical use
-oldest in the market; limited
-similar to gent.& tobramycin
Gentamicin ,Tobramycin,Amikacin

Neomycin
Kanamycin
Streptomycin
Neltimicin
Aminoglycosides: General Properties
Have a _________to which various amino sugars are attached by glycoside linkage

Frequently exhibit _________ activity with Beta lactams or Vancomycin

Synergistic activity- in combination, eradicate organisms more rapidly than when used alone

Aminoglycosides may ________ drugs resulting in loss of activity-do not mix together for administration
hexone ring

synergistic

complex with Beta lactam
Aminoglycosides: Pharmacokinetics
Absorbed poorly from the ______-Entire oral dose excreted in feces

IM absorption good- peak _______
IV administration given over _______

Serum conc. Similar for both IV & IM adm.
Are cleared by the _________
GI tract

60-90mins

30-60mins

kidneys
Aminoglycosides: Dosing
Half life = ______hrs, increasing to ______hrs in pts with significant renal impairment
Only partially & irregularly removed by ________= 40-60%

Renal insufficiency-either dose is kept constant & interval between doses increased OR interval is kept constant & dose is reduced
2-3 , 24-48

hemodialysis
aminoglycosides
_________dependent killing

_________________- antibacterial activity persist beyond time which measurable drug present- hours;
Single Lg. dose = better efficacy
concentration

post antibiotic effect (PAE)
Aminoglycosides: Toxicity
Toxicity _________dependent
Toxicity unlikely to occur until certain _________is achieved

Once conc, achieved, time above threshold concentration critical.
Trough above ________ predictive of toxicity

Time above this threshold greater with multiple doses of drug than with single large dose
time and concentration

threshold concentration

2mcg/ml
Aminoglycosides: Dosing
______________for pts with good renal function
OR
________dosing is less toxic
2-3divided doses/day

Once daily
Aminoglycosides: Once Daily Dosing Exceptions

____________- streptococcal staphylococcal, enterococcal - in combination therapy

__________

__________ patients

Efficacy not defined in above conditions
Endocarditis
Pregnancy
Pediatric
Aminoglycosides: Once Daily Dosing Advantages
Determination of serum conc. Unnecessary unless aminoglycosides given for more than ___ days


Less nursing time required

Lends itself to ___________

Requires dose or interval adjustment with __________ insufficiency e.g. in septic shock
3
outpatient therapy

renal
Aminoglycosides: Once Daily Dosing
CrCl-Gent/Tobramycin-Amikacin
=/>100ml/mn __ q24h __ q24h
80ml/min __ q24h __ q24h
50ml/min 3 q24h 9 q24h
<50ml/min 2 q24h 6 q24h
Use Cockcroft Gault formula for CrCl
5 15
4 12

**Amikacin = 3(Gent or Tobra)
Aminoglycosides: Traditional Dosing
Use loading dose of _mg/kg/dose followed by

Maintenance dose of ___mg/kg/dose

If CrCl 100ml/min & > use q8hr dosing

If CrCl 50-100ml/min use q12hr dosing

renal impairment give 2mg/kg/dose, check trough with _____ maintenance dose
LD = 2mg/kg
MD = 1.5mg/kg/dose

2nd
Aminoglycosides: Traditional Dosing
Trough < _ mcg/ml
Peak ___mcg/ml
Check Peak or trough with ___________dose

Checking peaks now unnecessary
Check trough ________ before next dose
Check peak ________ after dose
Trough concentrations >2mcg/ml indicate _________- extend interval
2mcg/ml
5-10mcg/ml

3rd or 4th

30mins
30-60mins

toxicity
Aminoglycosides: Once Daily Dosing

Check serum conc _______ of therapy depending on stability of renal function

Trough – < _ mcg/ml between 18-24hrs after dosing

Trough goal allows sufficient time for washout of drug to occur before next dose
2nd or 3rd day

1mcg/ml
Aminoglycosides: Once Daily Dosing Monitoring

Can measure serum conc. 2hrs & 12hrs after dosing, then adjust dose based on clearance OR
Can measure serum conc. 8hrs after dose- if 8hr conc between _______mcg, the target trough will be achieved in 18hrs

______-checking unnecessary –will be high
1.5-6 mcg

Peaks
Aminoglycosides Tissue Penetration
Highly ______& do not enter cells readily
Do not penetrate the ______
In active inflammation CSF levels reach 20% of plasma levels- higher in neonatal meningitis
Concentrations high in the ________, modest in _____(30% serum conc.)
Conc in _________50-90% that of plasma
polar
CNS & eye

renal cortex, bile

synovial & pleural fluid
Aminoglycosides Adverse Effects
_________: mostly Neomycin, Kanamycin, & Amikacin
_________high frequency hearing loss or
________damage manifested as vertigo ; mostly _________
Occur after _ days of therapy esp. using high doses, in elderly & renal insufficiency
Ototoxicity
Tinnitus
vestibular damage: Streptomycin & Gentamicin

5 days
Aminoglycosides Adverse Effects
_________→ increase Scr or decreased CrCl, Increased trough occur after 5days of therapy
Concurrent use with _________or other nephrotoxic antimicrobials- Vanc, Ampho B can potentiate nephrotoxicity

High doses- produce a curare-like effect with neuromuscular blockade →____________reversible with Ca gluconate or neostigmine

Hypersensitivity-occurs rarely
Nephrotoxicity
loop diuretics

respiratory paralysis
Aminoglycosides-Indications
Treatment of__________ enteric bacteria esp. when drug resistant e.g., in sepsis
Used with_________ for synergistic purposes to extend coverage to gram (+) organisms
Used with ____ to treat enterococcal ________ & to shorten duration of therapy for staph & streptococcal endocarditis
gram (-)
β-lactam antibiotics
PCN : endocarditis
Isolated from streptomyces griseus

Resistance has emerged in most species, severely limiting the usefulness of this agent
Streptomycin
Aminoglycosides-Streptomycin Indications
Mycobacterial infections- used as 2nd line agent for Rx of __________
Used only in combination with other agents to prevent resistance
Dose= ________ gm/day
Dose (children)_____mg/kg/day

NonTuberculous Infections- _______,________, & sometimes brucellosis
Dose= _ gm/day; children __mg/kg/day given IM in combination with oral tetracycline
tuberculosis
0.5-1gm/day
child 7.5-15mg/kg/day

plague, tularemia
1gm/day
children 15mg/kg/day IM
Aminoglycosides-Streptomycin Adverse Effects
____________– occurs with prolonged contact with the drug

Pain at injection site- common, but not severe

____________-vertigo, loss of balance

__________to new born if given during pregnancy→contraindicated
Fever, skin rash
Vestibular toxicity
Deafness
Aminoglycosides-Gentamicin Activity
Isolated from Micromonospora purpurea
Effective against G ___org.

Active alone & synergistic with β-lactam antibiotic against _________, proteus, enterobacter, _________, serratia, stenotrophomonas & other gram (-) rods

No activity against _________
GRAM (+) & gram (-)

pseudomonas,klebsiella

anaerobes
Aminoglycosides-gentamicin Resistance
__________relatively resistance to gentamicin due to inability to penetrate the cell
Gent +_________-bactericidal due to enhance uptake of drug & inhibition of cell wall synthesis
Gram (-) bacteria that are gentamicin- resistant are usually susceptible to _________- more resistant to modifying enzyme activity
Streptococci & enterococci

Vanc or PCN

amikacin
Aminoglycosides-Gentamicin Indications
Mainly used as empiric therapy for severe infections caused by gram (-) bacteria likely resistant to other therapies as in pneumonia, sepsis
Pseudomonas
___________
__________,
__________
acinetobacter
klebsiella

dose of ___ mg/kg/day in 3 divvied doses with PCN or cephalosporin

Studies indicate once daily dosing equally effective & less toxic
Enterobacter
serratia
proteus

5-6mg/kg/day
Aminoglycosides-Gentamicin Indications
Given with PCN G for bactericidal activity against __________
Should not be used as a single agent to treat ___________infections as resistance easily develops
Do not use as singe agent for treatment of ___________because penetration of infected lung tissue is poor
strept viridans or enterococcal endocarditis

staphylococcal

pneumonia
Aminoglycosides-Gentamicin(topical Administration)
Creams, ointments or solutions containing 0.1-0.3% gentamicin sulfate used for treatment of __________
Also used to prevent intravenous _________
Also used for _____infection
burns, wounds or skin leisions

catheter infections

ocular
Aminoglycosides-Gentamicin-Intrathecal (IT) Administration
___________caused by gram(-) bacteria
Dose: ______mg given IT daily
IT or IV not beneficial to neonates with meningitis
__________ gentamicin, toxic
3rd generation cephalosporins for gram (-) meningitis have now rendered this therapy obsolete
Meningitis : 1-10mg qd

Itraventricular
Aminoglycosides: Gentamicin-Adverse effects
____________- reversible, & usually mild.
____________- tends to be irreversible- mainly vestibular dysfunction- loss of hearing can occur.
Incidence 1-5%
Occurs following >5 days of therapy
Nephrotoxicity
Ototoxicity
Aminoglycosides: Tobramycin
Has an antibacterial effect similar to __________except:
Gentamicin more active against serratia, &
Tobramycin more active against __________
Gent. & Tobra. Effective against ___________
Enterococcus faecium resistant to Tobramycin
Pharmacokinetics properties similar to Gentamicin
Tobramycin more expensive than Gentamicin
___________ SE can occur
Nephrotoxicity of Tobramycin less than Gent.
~Gentamicin

Pseudomonas

Enterococcus *FAECALIS*

Ototoxicity & Nephrotoxicity
Aminoglycosides: Amikacin
Is a derivative of ________- les toxic than parent molecule
Resistant to enzymes that inactivate Gent. & Tobra.
Used against more resistant organisms
Active against gram (-) org like _____________
Dose ___ mg/kg/day in 2-3 divided doses
Typical dose maybe ____ mg IV/IM Q12hrs
Kanamycin
Pseudomonas, Enterobacter & Serratia

15mg/kg/day

500mg IV/IM Q12hrs
Aminoglycosides: Amikacin
Peak levels ____ mcg/ml
Troughs < _ mcg/ml
Also nephrotoxic & ototoxic
PEAK 20-40 mcg/ml
Troughs <5mcg/ml
Aminoglycosides: Neomycin
Neomycin too toxic for parental use
dose __ gm PO q6-8hrs x 24-48hrs in preparation for _________ surgery
Given with erythromycin 1 gm base
_______ = 1gm q6-8hr with protein intake to reduce ammonia intoxication- replace by use of lactulose
Also ___________ SE
1gm PO q6-8hrs x 24-48hrs: bowel surgery

hepatic coma

nephrotoxic & ototoxic
Aminoglycosides: Kanamycin
Can be instilled in _________ during surgery

Absorption from peritoneal cavity has resulted in curare-like neuromuscular blockade

__________can be used as antidotes
peritoneal cavity

Calcium gluconate & neostigmine
Aminoglycosides: Conclusion
Good agents against _______
Use limited by ototoxicity & nephrotoxicity
Used for _________ purposes to treat some gram (+) infections
gram (-) infections


synergistic
unique 4 membered lactam ring

Within each group compounds stable to gastric acid, suitable for oral administration: (3)
Penicillin V, Dicloxacillin,
Amoxicillin
Penicillins e.g.
Antistaphylococcal PCN
e.g ____________
Extended spectrum PCN
______________
antipseudomonal Penicillins
PCN G

Nafcillin

Ampicillin
Classification
Penicillins e.g. Penicillin G
Have greater activity against:
gram (+) organisms,
gram ______________,
non beta lactamase producing anaerobes
Have little activity against G _________
Are susceptible to hydrolysis by beta lactamases
G(-) cocci

gram (-) rods
Penicillins: Classification
Antistaphylococcal Penicillins:
Active against ___________
Inactive against __________
& gram (-)____________
Are resistant to ____________
staphylococci & streptococci

enterococci, anaerobic bacteria, & gram (-)cocci & rods

staphylococcal β lactamases
Penicillins: Classification
Extended spectrum Penicillins
Retain the antibacterial spectrum of PCN,
Have improved activity against __________
Are destroyed by____________
gram (-) organisms

beta lactamases
Penicillins: Formulation
Pen. G- defined in units
Crystalline Na Pen G –has _________units/mg
1million units = 0.6gm
1unit = 0.6 µg
Semi synthetic PCNs, prescribed by weight, not mg
1600 units/mg
MIC of PCN or other ATB given in µg/ml or mcg/ml
Most PCNs- as _______ salts
__________has 1.7meq K per million units or
__________has 2.8meq/gm
Sodium (Na) or Potassium (K)

Pen G Potassium

Nafcillin
PCNs like all β-lactam antibiotics inhibits bacterial growth thru inhibition of ____________
bacterial cell wall synthesis
Penicillins: Pharmacokinetics
Absorption of oral PCNs dependent on their acid stability & protein binding
__________– acid labile
__________- GI absorption erratic
__________(3)- acid stable, well absorbed PO
Absorption of oral PCNs (except Amoxicillin) impaired by food-give 1-2hrs ac or pc
__________- highly protein bound- produces lower level of free drug in serum
__________(2)– less protein bound
__________(2)- formulated to delay absorption → prolonged blood &tissue concentration
Benzathine PCN (1.2m units)- level maintained x 10days-3wks
Procaine PCN 600,000 units IM- levels 12-24hrs
Methicillin

Nafcillin

Ampicillin, Amoxicillin, & dicloxacillin

Nafcillin

Pen G, Ampicillin

Benzathine & Procaine PCN
PCN- poor penetration into: 3

PCN – in bacterial meningitis, conc. achieved with daily dose 0f 18-24million units(kill strains of neumococci,meningococcal)
eye, prostrate, CNS
Penicillins: Pharmacokinetics
PCN- ________elimination

Half life PCN G -__mins, 10hrs in renal failure

Half life of __________& extended PCNs – 1 hr, excreted more slowly

Adjust dose for renally eliminated PCNs
_________- excreted by biliary excretion

_____________(3)-eliminated by kidney & biliary excretion
Renal

30 min

Ampicillin

Nafcillin

Oxacillin, dicloxacillin, cloxacillin
Blood levels of all PCN raised by adm. of __________0.5mg Po q6hrs

Probenecid- impairs tubular secretion of weak acids e.g. Β lactam compounds
Probenecid
Penicllin G. – drug of choice for infections caused by:
_____________
meningococci,
__________ (18-24 mil/day; plus aminoglycoside for endocariditis)
PCN susceptible pneumococci,
non beta lactamase producing ______________
treponema pallidum & other spirochetes,
actinomeyces & other gram (+) rods
streptococci,
enterococci
staphylococci
Penicllin G.

Dose= -______ million units/day given IV in ____ divided doses depending on org. site & severity of infection

Can be given by continuous infusion


__________ – oral form of PCN
Indicated for minor infections – poor bioavailability & qid dosing & narrow spectrum
4- 24million units/day given IV in 4 to 6 divided doses

Penicillin V
Benzathine PCN. & Procaine PCN G.

Given IM- yield low prolonged drug levels

__________1.2million units IM-β hemolytic streptococci pharyngitis (3-4wks)

___________2.4million units IM weekly x 1-3wks-RX syphilis

Procaine PCN G –used for uncomplicated _________ in in past, rarely used now –because many strains PCN resistant
Benzathine PCN

PCN G benzathine

pneumonia or GC
Penicillins: Indications
Antistaphylococcal Penicillins
Are PCNs resistant to __________ (methicillin, nafcillin etc)
Are semi synthetic PCNs indicated for infections caused by β lactamases producing staphylococci, PCN susceptible strains of __________,___________
Not effective against __________and methicillin resistant strains of staphylococci (MRSA)
β lactamases

staphylococci, pneumococci

enterococci
Dose- cloxacillin,dicloxacillin ______mg po q_hrs(acid stable; good absorption
Give 1hrs before meals or 2hrs post meals)
Suitable for localized staph infections
Peds= ______mg/kg/day in _ divided doses
250mg-500mg po q6hrs

Peds= 15-25mg/kg/day in 4 divided doses
Penicillins: Indications
Antistaphylococcal Penicillins

Serious systemic staphylococcal infections ___________ 8-12gm/day given as 1-2gm IV q4-6hrs

Peds 50-100mg/kg/day

Methicillin – no longer used due to nephrotoxicity
oxacillin or nafcillin
Penicillins: Indications
Extended Spectrum Peniciilins groups(3)
Retain the spectrum of Pen G, but have greater activity against __________
Like Pen G, inactivated by β lactamases
Aminopenicillins- Ampicillin & amoxicillin
Similar spectrum of activity, but amoxicillin, better absorbed
Dose= 250-500mg 3x/day for _________
250-500mg 4x/day for ________
Aminopenicillins, Carboxypenicillins,Ureidopenicillins

gram (-) bacteria

amoxicillin
ampiciilin
Penicillins: Indications
Extended Spectrum Peniciilins
Aminopenicillins- Ampicillin & amoxicillin
Most active against PCN resistant ___________
Ampicillin, effective for __________, not to be used against uncomplicated salmonella gastroenteritis

Ampicillin at 4-12gm/day IV useful for infections caused by ________, Listeria monocytogenes, __________like E. Coli, H influenza, & salmonella species
pneumococci

shigellosis

enterococci,gram (-) cocci & bacilli
Many strains of gram (-) organisms produce β lactamases and are resistant to ___________
Ampiciliin used empirically for :(3)
Ampicillin, not active against klebsiella, enterobacter, pseudomonas aeruginosa, citrobacter, serratia, proteus, gram (-) anaerobes
Ampicillin

UTI, meningitis & typhoid
Penicillins: Indications
Caboxypenicillin
Carbenicillin- first antipseudomonal PCN; now obsolete due to advent of better agents
____________, similar to Carbenicillin in activity, but effective in lower doses
Ticarcillin- extends the ampicillin spectrum of activity, (but is less active against enterococci) to include ___________ & enterobacter
Ticarcillin

pseudomonas aeruginosa
Penicillins: Indications
____________–pipercacillin, mezlocillin & azocillin
Similar to taicarcillin, but active against select gram (-) bacteria –__________
Antispeudomonal PCN used in combination with __________ to treat pseudomonal infections – due to propensity for organism to develop resistance during single drug therapy
Ureidopenicillins
klebsiella pnuemonae

aminoglycoside
Penicillins: Combinations
Ampicillin, amoxicillin, ticarcillin & piperacillin- available in combination with β lactamase inhibitor

Addition of β lactamase inhibitor extends activity to include activity against
β lactamase producing strains of ___________
β lactamase producing _________
Staph aureus
gram (-) bacteria
Penicillins: Combinations
Ampicillin, amoxicillin, ticarcillin & piperacillin

Ampicillin + sulbactam = _______(1.5-3gm IVPB q6hrs

Amoxicillin + clavulanic acid = ________(250-500mg po tid, 875mg po bid
Ticarcillin + clavulanic acid = _________3.1gm IVPB Q6hrs
Piperacillin + tazobactam = _______3.375gm IVPB q 6hrs or 4.5gm IVPB q8hrs or (4.5gm IVPB q6hr-nosocomial pneumonia)
Unasyn

Augmentin

Timentin

Zosyn -nosocomial pneumonia
Penicillins: Carbapenems
Extended spectrum penicillins with _______ coverage, ________& pseudomonal coverage
3 antibiotics exist in this group
__________(Primaxin)
Dose: 250-500mg IVPB q6hr
__________(Merrem)
1gm IVPB q8hrs
__________(Invanz)
Igm IVPB q24hrs (has no pseudomonal coverage
gram (+), gram (-)
anaerobic

Imipenem/Cilastin
Merropenem
Etrapenem
Penicillins: Adverse Effects
_________________–most serious
All penicillins, cross sensitizing & cross reacting
Allergic reactions include anaphylactic shock (0.05%) serum sickness (now rare)
Urticaria, intense pruritis, skin rashes, fever, joint swelling
______________(autoimmune rxn)
Eosinophilia
Hemolytic anemia
Vasculitis
_________(for pts with renal failure)
Hypersensitivity/Anaphylaxis

Interstitial nephritis

Seizures
Penicillins: Adverse Effects
Neutropenia ( _________)
Hepatitis (__________)
__________(Interstitial nephritis)
GI upset- n/v, diarrhea (oral doses)
Pseudomembranous colitis (___________)
Vaginial candidiasis
Skin Rashes (_____________)
Nafcillin
Oxacillin
Methicillin
ampicillin
Ampicillin/Amoxicillin
Penicillins:
One of most misused ATB
__% of staphylococcal strains, β lactamase producers
____on the rise
β lactamase producing __________, now common
Broad spectrum PCN eliminate normal flora- predisposing pts to colonization & super infection
90%

MRSA

H. influenzae & N gonorrhea
Quinolone adverse effects
FQ generally well tolerated
All can cause erosion of ________, not recommended in child < 18

GI: n/v, anorexia

CNS: dizzy, HA, lightheaded, drowsy, insomnia, seizures (rare)
____________
____________
Disturb of ________in diabetics
___________
cartilage

hypersensitivity
photosensitivity
Blood Glucose
Crystalluria
Quinolone Drug Interactions
_______may be antagonized by nitrofurantoin

may interfere w/ hepatic metabolism of theophylline and caffeine (4)
Norfloxacin

Enoxcin, cipro, norfloxacin, grepafloxacin
Quinolone 1st Gen
(*po only)
Nalidixic acid (NegGram)
Cinoxacin (Cinobac)

Coverage: enterobacteriaceae
narrow G __ coverage

Indications: _____
Not for systemic infx
gram (-) coverage

prophylaxis and tx of UTIs
Quinolone 1st Gen

first oral quinolone
tx UTI
______________
dose: 1 gm po qid

_____________
250-500 mg po bid (1gm/d)
Nalidixic acid (NegGram)

Cinoxacin (cinobac)
Quinolone 2nd Gen Coverage
____________
atypical pathogens
*_____________
G _____ coverage
enterbacteriaceae
pseudomonas
G(-) and limited G(+)
Quinolone 2nd Gen Indications
Prostatis
_________infx
STDs
uncomplicated/complicated___
Gastroenteritis
nosocomial

UTIs
Quinolone 2nd Gen
Norfloxacin(_______)-po
Ciprofloxacin(______)-po,IV
Lomefloxacin(________)-po
ofloxacin(_______)-po
enoxacin(________)-NA in US
Noroxin
Cipro
Maxaquin
floxin
penetrex
Quinolone 2nd Gen: __________
gastroenteritis
endocervial and uerethral ________
good efficacy vs many G- and ________
Prostatis
UTIs

Dose:400mg bid x ____d, 1 hr AC or 2 hr PC (uncomplicated UTI)
400mg bid x _____d
Adjust when Crcl < __ml/in
Norfloxacin(Noroxin)
gonorrhea
enterococcus

400mg bid x 7-10d - uncomp
10-21d - comp

< 30ml/min
Quinolone 2nd Gen: _______
TX infectious diarrhea, gonorrhea, _________, prostatis, skin and resp infx

good efficacy vs G- enteric bacteria, ______,________

DOC for ___ caused by p aeruginosa

alternative for TB
Ciprofloxacin (Cipro)

osteomyelitis

salmonella, shigella

UTI
Quinolone 2nd Gen: Cipro
IV - alt 3rd gen cephs and AG for serious infx

Adjust for _____ impaired
PO: ____mg q 12 hr
IV: ________ IVPB BID
RENAL PROB _______
OSTEO ________
renal

po 250 mg q 12 hr
IV 400 mg IV PB BID
(200 mg renal prob)

osteomyelitis: 750 mg BID
2ND GEN QUINOLONE:
tx UTI and bronchitis caused by________or _________

Prophylaxis before _______ surgery
Lomefloxacin (Maxaquin)

H.flu or B. catarrhalis

transurethral surgical proced.
Lomefloxacin (Maxaquin)

adjust dose in ______impairment

high _________

Recommend _______ if on warfarin

Dose: _____ mg po qd
renal

photosensitivity

PT

Dose 400 mg po qd
Ofloxacin (floxin)
replaced by 3rd gen*

tx pul infx and STDx
bacterial prostatis and UTI
single dose tx for _____
alt for _____, _______, ______

Reported to potentiate anticoagulant activity of ________
Renal excretion
Dose: 200-400 mg q 12 hr
gonorrhea

TB, M. leprae, chlamydia

warfarin
Enoxacin (Penetrex)
tx UTI and complicated gonorrhea

cleared renal and hepatic

inhib hepatic metab of ______and _______ and leads to toxicity

Increase serum ________

single dose 400 mg-gonorrhea
BID 200-400 mg - UTI
theophylline and caffeine

digoxin
3rd Gen Quinolones
Sparfloxacin (Zagam) - NA
Gatifloxacin (Tequin) po,IV, NA
Grepafloxacin (Raxar) NA
*Levofloxacin(_______) po,IV
*Moxifloxxacin(______) po, IV
Levaquin

Avelox
3rd Gen Quinolones
Coverage: enterobacter, atypical pathogens, _________

Indications: ____, Sinusitis, Skin infx, _______
streptococci

CAP
UTIs
3rd Gen Quinolones
Sparfloxacin (Zagam)

tx atypical pathogens and CAP(chlamydia, H.flu, M. catarrhalis, mycoplasma, S.pneumo)

Active vs some mycobacteria_______

SE: severe __________
M. leprae

phototoxicity
3rd Gen Quinolones
Sparfloxacin (Zagam)

adjust dose for ______impaired

LD 400 mg then ____mg qdx 10d

CI: pts with _______prolongation
renal

200mg

QT interval
3rd Gen Quinolones:
Gatifloxacin (Tequin)

qd tx for CAP, UTI, ________, _______, and gonorrhea

Broad spectrum against _______

Dose: ___mg qd IV/po
acute sinusitis, bronchitis

G+ and G- organisms

400mg
3rd Gen Quinolones:
Gatifloxacin (Tequin)
off market due to ________

atypical pathogens and CAP

STDs (Gonorrhea,c. trachomatis)

CI: ______failure, QT prolong
QT interval prolongation


hepatic
3rd Gen Quinolones
Levofloxacin (Levaquin)

tx for _______(S pneumo)
Acute bacterial exacerbation of ___________
*_____(S Aureus, S pneumo, M catarrhalis, H. flu, Legionella, Klebsiella, Mycoplasma and Chlamydia pneumo)

Skin infx, UTI, acute pyelonephritis
sinusitis

bronchitis

*CAP*
3rd Gen Quinolones
Levofloxacin (Levaquin)

Alt for _________
Dose adjust in ______
________mg qd IV, po
_______mg qd IV,po for complicated skin infx
_______mg qd x5d for CAP
M. TB
renal impairment
250-500
750
750
3rd gen quinolones
Moxifloxacin (_________)
Best _______ coverage among quinolones
CAP
_________
Skin infx
**Does NOT tx UTIs
Dose: ____mg qd po,IV
Avelox

anaerobic

sinusitis

400 mg qd
4th Gen Quinolones
Trovafloxacin (________)
more potent vs. _________
Better activity vs. B fragilis, Chlamydia, Mycoplasma, Mycobacteria
Superior to other FQ for ________, __________
Once daily for respiratory infx, STDs, and skin and soft tissue infx
Dose: ________mg po qd
________ mg IV qd
Trovan

G+

enterococci,anaerobes

200mg po qd
200-300 mg IV qd