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144 Cards in this Set
- Front
- Back
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___________- glycopepetide antibiotic
Mechanism of Action Inhibits bacterial cell wall synthesis by _____________through binding to portion of cell wall precursor |
Vancomycin
blocking glycopeptide polymerization |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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Vancomycin: Pharmacokinetic Dosing guidelines
Step 2: Calculate Crcl Use Cockcroft Gault CrCl male = __________ CrCl female = .85 x ________ |
(140-age) x IBW
_______________ Scr x72 |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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Cephalosporin Kinetics (CSF)
Cephalosporins with proven effectiveness for Rx of meningitis- __________- 3rd generation __________- 3rd generation __________- 3rd generation __________- 4th generation |
Cefotaxime
ceftriaxone ceftazidime cefepime |
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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 |
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Cephalosporins
1st Generation More gram___& < gram ____ coverage Most active against aerobic gram (+) ______ Includes MSSA |
gram (+)
gram (-) cocci |
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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) |
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Cephalosporins- Classification
3rd Generation = _______gram (+) activity & _____gram(-) Most active against gram (-) organisms Some active against __________- __________, to a lesser extent cefoperazone |
Lesser
>>> pseudomonas aeruginosa Ceftazidime |
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Cephalosporins- Classification
4th generation = gram (+) __ gram(-) Active against ___________ _________only agent in this class |
=
pseudomonas cefepime |
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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 |
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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 |
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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 |
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4th Generation Cephalosporins
Generic/ Brand /Route of Adm. Cefepime _______ IM,IV Cefpirome† † = Investigational agent |
Generic Name Brand Name
Cefepime Maxipime |
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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 |
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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 |
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3rd (?2nd) Generation cephalosporins used for Rx of ____
Rationale: emergence & increase in PCN- resistant S. pneumoniae Beta-lactamase producing Haemophilus species |
CAP
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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) |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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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
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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 |
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1) ____________– surgical prophylaxis, Rx of uncomplicated skin infections
2) _____________- CAP, bacterial meningitis,infections due to susceptible organism |
Cefazolin
Cefotaxime or Ceftriaxone |
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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
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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
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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
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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 |
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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 |
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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 |
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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 |
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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 |
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aminoglycosides
_________dependent killing _________________- antibacterial activity persist beyond time which measurable drug present- hours; Single Lg. dose = better efficacy |
concentration
post antibiotic effect (PAE) |
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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 |
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Aminoglycosides: Dosing
______________for pts with good renal function OR ________dosing is less toxic |
2-3divided doses/day
Once daily |
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Aminoglycosides: Once Daily Dosing Exceptions
____________- streptococcal staphylococcal, enterococcal - in combination therapy __________ __________ patients Efficacy not defined in above conditions |
Endocarditis
Pregnancy Pediatric |
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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 |
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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) |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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Isolated from streptomyces griseus
Resistance has emerged in most species, severely limiting the usefulness of this agent |
Streptomycin
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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Aminoglycosides: Amikacin
Peak levels ____ mcg/ml Troughs < _ mcg/ml Also nephrotoxic & ototoxic |
PEAK 20-40 mcg/ml
Troughs <5mcg/ml |
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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 |
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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 |
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Aminoglycosides: Conclusion
Good agents against _______ Use limited by ototoxicity & nephrotoxicity Used for _________ purposes to treat some gram (+) infections |
gram (-) infections
synergistic |
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unique 4 membered lactam ring
Within each group compounds stable to gastric acid, suitable for oral administration: (3) |
Penicillin V, Dicloxacillin,
Amoxicillin |
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Penicillins e.g.
Antistaphylococcal PCN e.g ____________ Extended spectrum PCN ______________ antipseudomonal Penicillins |
PCN G
Nafcillin Ampicillin |
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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 |
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Penicillins: Classification
Antistaphylococcal Penicillins: Active against ___________ Inactive against __________ & gram (-)____________ Are resistant to ____________ |
staphylococci & streptococci
enterococci, anaerobic bacteria, & gram (-)cocci & rods staphylococcal β lactamases |
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Penicillins: Classification
Extended spectrum Penicillins Retain the antibacterial spectrum of PCN, Have improved activity against __________ Are destroyed by____________ |
gram (-) organisms
beta lactamases |
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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
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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 |
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PCNs like all β-lactam antibiotics inhibits bacterial growth thru inhibition of ____________
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bacterial cell wall synthesis
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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 |
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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
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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 |
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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
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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 |
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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 |
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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 |
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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 |
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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 |
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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
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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Quinolone Drug Interactions
_______may be antagonized by nitrofurantoin may interfere w/ hepatic metabolism of theophylline and caffeine (4) |
Norfloxacin
Enoxcin, cipro, norfloxacin, grepafloxacin |
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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 |
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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) |
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Quinolone 2nd Gen Coverage
____________ atypical pathogens *_____________ G _____ coverage |
enterbacteriaceae
pseudomonas G(-) and limited G(+) |
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Quinolone 2nd Gen Indications
Prostatis _________infx STDs uncomplicated/complicated___ Gastroenteritis |
nosocomial
UTIs |
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Quinolone 2nd Gen
Norfloxacin(_______)-po Ciprofloxacin(______)-po,IV Lomefloxacin(________)-po ofloxacin(_______)-po enoxacin(________)-NA in US |
Noroxin
Cipro Maxaquin floxin penetrex |
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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 |
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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 |
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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 |
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2ND GEN QUINOLONE:
tx UTI and bronchitis caused by________or _________ Prophylaxis before _______ surgery |
Lomefloxacin (Maxaquin)
H.flu or B. catarrhalis transurethral surgical proced. |
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Lomefloxacin (Maxaquin)
adjust dose in ______impairment high _________ Recommend _______ if on warfarin Dose: _____ mg po qd |
renal
photosensitivity PT Dose 400 mg po qd |
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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 |
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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 |
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3rd Gen Quinolones
Sparfloxacin (Zagam) - NA Gatifloxacin (Tequin) po,IV, NA Grepafloxacin (Raxar) NA *Levofloxacin(_______) po,IV *Moxifloxxacin(______) po, IV |
Levaquin
Avelox |
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3rd Gen Quinolones
Coverage: enterobacter, atypical pathogens, _________ Indications: ____, Sinusitis, Skin infx, _______ |
streptococci
CAP UTIs |
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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 |
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3rd Gen Quinolones
Sparfloxacin (Zagam) adjust dose for ______impaired LD 400 mg then ____mg qdx 10d CI: pts with _______prolongation |
renal
200mg QT interval |
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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 |
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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 |
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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* |
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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 |
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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 |
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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 |
