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421 Cards in this Set

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Name the Antibacterial agents that act by inhibiting cell wall synthesis?
Penicillins, Cephalosporins, Vancomycin & Nitrofurantoin
Name the antibacterial agents that act by inhibiting protein synthesis at the 50s Ribosome.
50s Ribosome: Macrolides, Ketolides, clindamyacin, oxanolidinones, streptogramins
Name the antibacterial agents that act by inhibiting protein synthesis at the 30s Ribosome.
Tetracyclines, Glycyclcyline, Aminoglycosides
Name the antibacterial agents that act by inhibiting nuclein acid synthesis.
Fluoroquinolones
Name the antibacterial agents that act by inhibiting folic acid synthesis.
Sulfamethoxazole, trimethoprim
what antibiotics at to inhibit cell wall synthesis??
B-lactams, Cephalosporins, Cabapenems, Vancomycin
Where does Metronidazole work?
Inhibits DNA replication
Where do Fluoroquinolones work?
Inhibit Topoisomerases
Where does Rifampin work?
Inhibits RNA transcription
Where do Sulfonamides work?
Inhibit Nucleotide biosynthesis.
Name the four groups of penicillins
1. Natural Penicillins
2. Aminopenicillins
3. Penicillinase-resistant Penicillins
4. Extended spectrum Penicillins
Which NATURAL penicillin is the only one that can be used orally?
Penicillin V potassium a.k.a Pen Vee K
Name the natural penicillins that are used through IV administration.
Penicillin G Sodium or Penicillin G Potassium
Which natural penicillins are used in an extended injextion/ depot form?
Procain Penicillin & Benzathine Penicillin
What is the major use for natural penicillins?
LIMITED to known susceptible organisms, mild infectins and prophylaxis for dental treatments
Natural Penicillins are the drug of choice in treatment of what organism?
Treponema pallidum (Syphillis)
Natural penicillins possess a___________ spectrum of activity.
Limited
Natural penicillins are effective against which gram + cocci?
Gram + aerobic cocci (excep penicillinase producing strains)Streptocci (beta-hemolytic strep, viridans, group D strep, Streptococcus pneumoniae (if susceptible), enterococcus spp. (inhibited but not killed), some Staph aureus spp., Listeria, Bacillus anthracis
Natural penicillins are effective against which gram - cocci?
Neisseria meningitidis, some Neisseria gonorrhoeae, some strains of H. influenzae, and Pasteurella
Natural penicillins work against these anaerobes...
clostridium, fusobacterium, peptostreptococcus
What are some of the unique cautions when using natural penicillins??
*May be culprit of drug fever

*Jarisch-Herxheimer reaction: secondary to release of protein by syphyllis 1-12 hrs after administration (may see HA, chills, sore throat, sweating, mylagias, increase HR and BP, then hypotension. Resolves in 10-24 hrs.

*Electrolyte disturbances: especially HYPERKALEMIA may occur in high doses particularly with renal dysfunction
Which natural penicillin injectible form is given less frequently? Penicillin G Procaine or Penicillin G Benzathine?
Penicilline G Benzathine (Bicillin LA)is given as a 1 time dose and last 1-4 weeks
Penicillin G Procaine (Wycillin) is given every 12-24 hrs. Both are given IM
What is the average adult dose for Pen Vee K?
250-500 mg PO q6h (25k-50k units/kg/d q 6-8h)
Name the Aminopenicillins.
Amoxicillin and Ampicillin
Which aminopenicillin is only available orally?
Amoxicillin
True or False: Ampicillin is available PO and IV
TRUE
What spectrum of activity do aminopenicillins provide?
NARROW-- Do provide broader coverage than Natural PCNs though
What organism are aminopenicillins known to be very effective against?
Streptococcus pneumoniae
What is a benefit seen when using aminopenicillins?
Effective against a few Gram - organism such as E.coli, Proteus mirabilis, Salmonella, Shigella (some resistance reported) compared to Natural Penicillins
what are some major uses for Aminopenicillins??
upper respiratory tract infections (otitis media), urinary tract infections, STDs, other infections with known susceptible organisms. Also used commonly for prophylaxis for dental procedures and in combination with other agents for treatment of H. pylori.
Name two unique cautions when using aminopenicillins.
*Rash is particularly common when give to patients w/ infections mononucleosis
*C.diff. colitis is more common w/ ampicillin that other Penicillins
True or false: Ampicillin has much buch better oral absorption than amoxicillin.
FALSE: Ampicillin should never be given PO Give amoxicillin instead
What are the Penicillinase producing organisms?
HAMS:
Haemophilus influenzae
Anaerobes-- Especially Bacteroides fragilis
Moraxella catarrhalis
Staphylococcus aureus,- epidermidis, saprophyticus
** ALSO Enterobacteriaceae (Proteus, Klebsiella pneumoniae, E. coli & Citrobacer)
What are the Penicillinase-resistant penicillins?? a.k.a. "anti-staphylococcal penicillins"
Methicillin (IV)
Nafcillin (Unipen, Nafcil- IV)
Oxacillin (Protaphlin- IV, PO)
Dicloxacillin (Dynapen- PO)
Cloxacillin (PO)
What spectrum do Penicillinase resistant penicillins have??
NARROW!! Activity is limited to S. aureus & S. epidermidis and some strains of strep
Penicilinase- resistant penicillins spectrum is reduced due to 2 things:
1)No activity against gram negative organisms
2) Not active against MRSA (Methicillin resistant Staph Aureus)
True or False: if staphylococcus aureus is susceptible to oxacillin it will not be suseptible to cefazolin, clindamycin or erythromycin.
False: Susceptibility is seen with all
What are the major uses for Penicillinase-Resistant Penicillins?
Treatment of infections known or suspected to be caused by Staphylococcus (cellulitis, endocarditis)
Which Penicillinase- Resistant PCN has a unique caution for hepatotoxicity?
OXACILLIN
Which Penicillinase- Resistant PCN as a unique caution for phelbitis?
NAFCILLIN-- also can cause sodium overload
Which Penicillinase- resistant PCN can cause transient leukopenia?
All
What are the unique cautions with nafcillin??
Phlebitis & Sodium overload--get 3.1 mEq of Na/gram of Naf.
What is the unique feature of Extended spectrum penicillins? (structural)
Alterations to the side chains results in greater activity against gram - (eg/ Pseudomonas) organisms compared with other agents
What are the two major types of Extended- spectrum penicillins??
1)Ureidopenicillins
2)Carboxypenicillins
Name the Ureidopenicillins.
Piperacilin (PIPRACIL), Mezlocilin (MEZLIN), Azlocillin (Azlin)
what is the spectrum of activity for Ureidopenicillins?
BROAD--
*Wide spectrum of GRAM(-) coverage INCLUDING Pseudomonas!!
*Better gram(-) coverage than animoPCNs (Enterobacters, Klebsiella)
*Maintains activity agains some Gram(+)-- but is less than aminoPCNs
Name the Carboxypenicillins
Carbenicillin (GEOPEN), Ticarcillin (TICAR)
What is the spectrum of activity for Carboxypenicillins?
BROAD- good Gram(-) coverage Not as active agains Pseudomonas as piperacillin
*Little activity agains gram(+) cocci including Staph, Strep & Enterococcus--Ureido works better
What is the disadvantage of Carboxypenicillins?
Only available IV--> can be used in hospitalized patients
Name the cautions that should be monitored w/ Carboxypenicillins
1)Sodium-overload & HYPOkalemia w/ Ticarcillin (5.2 mEq Na/gm
2)Platelet dysfn w/ Ticarcillin
3)Seizures,HYPOmagnesemia & HYPOcalcemia w/ Carbenicillin
4)SJS
5)GI effects (esp w/ carbenicillin oral) also dry mouth, furry tongue, vaginitis
Name the cautions that should be monitored w/ Ureidopenicillins.
1) Hepatitis
2)Have less Na+/g, less hypokaliemia, less platelet inhibition & greater hpatic excretion (vs renal) than Carboxypenicillins
A beta-lactamase inhibitor is sometimes referred to as a ________________?
Suicide inhibitor
How do Beta-lactamase inhibitor work?
Ihibit beta-lactamases produced by bacteria--> preventing destruction of the antibiotic allowing more to bind to PBP
*Increases the spectrum of the abx vs betalactamase producers (HAMS & Enterobacteriacae)
*DOES NOT work as an antibicrobial as itself!!
Name the beta-lactamase inhibitors & what they are effective against
1)Clavulanate/Clavulanic acid--M. catarrhalis, B. fragilis, H. influenzae, Neisseria gonorrhea, Staph aureus
2)Sulbactam--N. meningitidis & gonorrhea, M. catarrhalis, Acinetobacter
3)Tazobactam--little antimicrobial activity of its own
Name the combination products available that combine Beta lactam & Beta Lacatamase Inhibitors
*Amoxicillin/Clavulanic acid--Augmentin (PO
*Ampicillin/Sulbactam--Unasyn (IV)
*Piperacillin/Tazobactam--Zosyn (IV)
*Ticarcillin/Clavulanate--Timentin (IV)
What is Amoxicillin/Clavulanate Potassium (Augmentin) known to NOT be active against?
Is not active against PCN resistant Strep. pneumoniae
By combining amoxicillin w/ clavulanate potassium, greater efficacy is achieved vs which bugs? (8)
1. Staph aureus
2. H. influenzae
3. M. catarrhalis
4. N. gonorrhoeae
5. E. coli
6. Proteus
7. Klebsiella
8. Bacteroides
Does taking Augmentin with food decrease absorption?
No, it does not decrease absorption but DOES reduce the GI side effects
What is Augmentin ES indicated for?
Acute Otitis media due to Strep pneumoniae and B-lactamase producing strains of Haemophilus influenzae & Moraxella catarrhalis-- in children
What is the ratio of Amoxicillin to Clavulanate Potassium in Augmentin and Augmentin ES?
Augmentin--4-7:1
Augmentin ES 14:1
Is the incidence of diarrhea with Augmentin ES increased, decreased or similar to regular Augmentin?
Similar to regular Augmentin formulation
What is Augmentin XR indicated for?
Indicated for use in treating community acquired pneumonia, bronchitis or sinusitis in which a higher amount of amoxicilin would be needed to eradicate the causative microorganism.
How much Amoxicillin and Clavulanate do each Augmentin XR tablet have?
Amoxicillin: 1000mg
Clavulanate: 62.5
Regular Augmentin has 125mg of Clavulanate
What is the adult dose of Augmentin XR?
Two tablets q12h (Total 4g/250mg daily)
What would be a key counselling point for patients taking Augmentin XR?
Be advised to take with meal or snack-- enhances absorption of amoxicillin and helps to minimize the possiblitiy of GI upset
The added uses of Ampicillin/Sulbactam (Unasyn)and Augmentin are...? (5)
1)Intra-abdominal infections
2)gynecological infections
3)community acquired pneumonia
4)Animal or human bites
5)Diabetic foot ulcers
When covering against Pseudomonas list the ranking order of Betalactamase inhibitor antibiotics...
PIPERCILLIN (Ureidopcn)
Mexlocillin (Ureidopcn)
Azlocillin (Ureidopcn)
Ticarcillin (Carboxypcn)
Carbenicillin (Carboxypcn)
What are the added uses for Zosyn & Timentin??
Coverage of Piperacillin & Ticarcillin alone PLUS: Beta-lactam producing organism (Mostly gram negatives) and anaerobes
** IS USED FOR SERIOUS INFECTIONS when broad spectrum coverage is required
What serious infections are commonly treated w/ Zosyn or Timentin?
Nosocomial infections, polymicrobial infections & diabetic foot
** Is no advantage for gram (+) infection versus other alternatives or for PSEUDOMONAS as a single pathogen
When considering PCN as a treatment option what are some things to keep in mind?
*Many pcn derivatives are destroyed by gastric acid & must be administered IV
*Generally have short t1/2 & require frequent administration
*Primarily eliminated by the kidney--> good urine concentrations but need to be adjusted in renal dysfunction
what is Probenecid used for?
Is given to decrease renal elimination & increase serum concentrations
What are the common Adverse Effects or reactions seen w/ PCN?
1)Allergic rxn: rash/urticaria, anapylaxis, drug fever or serum sickness
2)GI: n/v/d, pseudomembranous colitis
3)Renal: Interstitial nephritis (after large doses esp PCN or Ampicillin)
4)Neurological (w/ high doses): Irritability, confusion, myoclonic jerk, visual, seizures
5)Hematoligic: thrombocytopenia, hemolytic anemia, granulocytopenia, eosinophilia (after course >7d)
6)Venous irritation at injxn site
What drug group has to be "challenged" if there is a suspected allergic reaction to penicillin?
Cephalosporin
What drug reaction commonly seen w/ Ampicillin when taken in conjunction w/ ALLOPURINOL?
Increased frequency of rash
What is the potential drug reaction seen when oral contraceptives are taken with either ampicillin or oxacillin?
Decreases effect of antibiotic
Is the incidence of diarrhea with Augmentin ES increased, decreased or similar to regular Augmentin?
Similar to regular Augmentin formulation
What is Augmentin XR indicated for?
Indicated for use in treating community acquired pneumonia, bronchitis or sinusitis in which a higher amount of amoxicilin would be needed to eradicate the causative microorganism.
How much Amoxicillin and Clavulanate do each Augmentin XR tablet have?
Amoxicillin: 1000mg
Clavulanate: 62.5
Regular Augmentin have 125mg of Clavulanate
What is the adult dose of Augmentin XR?
Two tablets q12h (Total 4g/250mg daily)
What would be a key counselling point for patients taking Augmentin XR?
Be advised to take with meal or snack-- enhances absorption of amoxicillin and helps to minimize the possiblitiy of GI upset
The added uses of Ampicillin/Sulbactam (Unasyn)and Augmentin are...? (5)
1)Intra-abdominal infections
2)gynecological infections
3)community acquired pneumonia
4)Animal or human bites
5)Diabetic foot ulcers
When covering against Pseudomonas list the ranking order of Betalactamase inhibitor antibiotics...
PIPERCILLIN (Ureidopcn)
Mexlocillin (Ureidopcn)
Azlocillin (Ureidopcn)
Ticarcillin (Carboxypcn)
Carbenicillin (Carboxypcn)
What are the added uses for Zosyn & Timentin??
Coverage of Piperacillin & Ticarcillin alone PLUS: Beta-lactam producing organism (Mostly gram negatives) and anaerobes
** IS USED FOR SERIOUS INFECTIONS when broad spectrum coverage is required
What serious infections are commonly treated w/ Zosyn or Timentin?
Nosocomial infections, polymicrobial infections & diabetic foot
** Is no advantage for gram (+) infection versus other alternatives or for PSEUDOMONAS as a single pathogen
When considering PCN as a treatment option what are some thing to keep in mind?
*Many pcn derivatives are destroyed by gastric acid & must be administered IV
*Generally have short t1/2 & require frequent administration
*Primarily eliminated by the kidney--> good urine concentrations but need to be adjusted in renal dysfunction
what is Probenecid used for?
Is given to decrease renal elimination & increase serum concentrations
What are the common Adverse Effects or reactions seen w/ PCN?
1)Allergic rxn: rash/urticaria, anapylaxis, drug fever or serum sickness
2)GI: n/v/d, pseudomembranous colitis
3)Renal: Interstitial nephritis (after large doses esp PCN or Ampicillin)
4)Neurological (w/ high doses): Irritability, confusion, myoclonic jerk, visual, seizures
5)Hematoligic: thrombocytopenia, hemolytic anemia, granulocytopenia, eosinophilia (after course >7d)
6)Venous irritation at injxn site
What drug group has to be "challenged" if there is a suspected allergic reaction to penicillin?
Cephalosporin
What drug reaction commonly seen w/ Ampicillin when taken in conjunction w/ ALLOPURINOL?
Increased frequency of rash
What is the potential drug reaction seen when oral contraceptives are taken with either ampicillin or oxacillin?
Decreases effect of abx
How do Cephalosporins work?
Work by inhibiting bacterial cell wall synthesis
-- classified at generations 1-4
What is the known absorption/ pharmacokinetic property that makes cephalosporins advantageous?
Excellent absorption from GI tract and penetrate well into tissues-- some even penetrate CSF
Cephalosporins are TIME-DEPENDENT or CONCENTRATION DEPENDENT KILLERS?
Time dependent bactericidal killers; must be administered in frequent intervals to maintain adequate concentrations above the MIC-- same as PCNs
What are the 1st Generation ORAL Cephalosporins??
Cephalexin (KEFLEX)
Cefadroxil (Duricef)
What are the 2nd Generation Oral Cephalosporins?
Cefuroxime (Ceftin)
Cefprozil (Cefzil)
Cefaclor (Ceclor)
Loracarbef (Lorabid)
What are the 3rd Generation ORAL Cephalosporins?
Cefposoxime (Vantin)
Ceftibuten (Cedax)
Cefdinir (Omnicef)
Cefditoren (Spectracef)
What are the 4th Generation ORAL Cephalosporins?
THERE AREN'T ANY!!
What are the 1st Generation IV Cephalosporins?
Cefazolin (Ancef)
What are the 2nd Generation IV Cephalosporins?
Cefuroxime (ZINACEF)
Cefoxitin (MEFOXIN)
What are the 3rd Generation IV Cephalosporins?
Ceftriaxone (Rocephin)
Ceftazinime (Fortaz)
Cefotaxim (Claforan)
What are the 4th Generation IV Cephalosporins?
Cefepime (MAXIPIME)
What is the noticeable difference that is seen between Cephalosporin generations?
As the generations increase, they lose gram (+) coverage except against Strep. pneumo. but they GAIN gram (-) coverage
What coverage do the Cepholosporins have vs Entercoccus?
NONE
What generation of Cephalosporin is effective vs Pseudomonas?
3rd (Ceftazinime) & 4th (Cefepime) generation only
Which generation of Cephalosporin has greater coverage against Staph aureus? 1, 2, 3 or 4?
1st ++++
2nd +++
3rd ++ Ceftriaxone (ROCEPHIN)
4th ++
Which generation of cephalosporin has the best coverage vs Strep. pneumo.?
1st ++
2nd +++
**3rd ++++ Ceftriaxone (ROCEPHIN)**
4th +++
What will 1st Generation Cephalosporins work against?
Mostly Gram(+)-- Staph & Strep
Some Gram(-)-- such as Enterobacters; Proteus, E.coli, Klebsiella
What will 1st generation Cephalosporins NOT work against?
WILL NOT WORK vs MRSA or Entercoccus, Listeria or atypical pneumonia pathogens such as Chlamydai pneumoniae, Mycoplasma pneumoniae and Legionella pneumopila
What are oral cephalosporin agents commonly used for?
Skin and soft tissue infections, UTI, respiratory tract infections (KEFLEX)
What will 2nd Generation Cephalosporins be affective against?
Improves Gram(-) coverage including H. influenzae and Enterobacters; Proteus, E.coli, Klebiella
What are important features of Cefuroxime, Cefaclor and Cefprozil?
Cefuroxime (CEFTIN), Cefaclor (Ceclor) & Cefprozil (Cefzil)-- 2nd Generation ORAL-->Retain the best coverage of Staph aureus while covering most Gram(-)'s
What is Cefoxitin notably used for??
Has increased activity against anaerobic bacteria (bacteroides) and is used in prophylaxis &/or treatment of intraabdominal infections
What is notable about the 3rd Generation Cephalosporins vs Gram(+) bacteria?
Cefotaxime and Ceftriaxone have best & similar coverage-- are active vs Methicillin susceptible staph & strep-- Including Strep. pneumo. and have good CSF penetration
What is notable about the 3rd Generation Cephalosporins vs Gram(-) bacteria?
Ceftazidime (Fortaz) covers Pseudomonas!! NO ORAL 3rd Generation has activity vs Pseudomonas
Oral 3rd generation have better Gram(-) coverage (Cefpodoxime (VANTIN) & Ceftibuten (CEDAX) are best) than oral 2nd Generations
What is the DOC for Meningitis?
Ceftriaxone (Rocephin) 3rd Generation IV Cephalosporin
What are major uses for Ceftriazone (ROCEPHIN)?
3rd Generation IV Cephalosporin:
Respiratory tract, UTI, Intra-abdominal infection in combo w/ abx w/ anaerobic coverage,MENINGITIS, STDs
What are 4th Generation Cephalosporins known to cover?
Most gram(-) coverage of cephalosporins including PSEUDOMONAS AERUGINOSA and certain Enterobacteraceae that may be resistant to 3rd Generation Cephalosporins
Are broad spectrum-- maintain some gram(+) coverage similar to Cefotaxime and Ceftriaxone
What are some of the class adverse side effects seen with Cephalosporins?
NMTT rxn w/ Cefamandole & Cefoperazone--Prolonged PT, aPTT &/or hyperprothrombinemia; disulfuram type rxn if combine w/ Etoh
Similar SE profile as PCNs (decreases as generations increase especially w/ Ceftazidime)
What affect will be see with food and Cephalosporin administration?
Most are unaffected. Oral Cefuroxime (CEFTIN) absorption is enhanced.
What effect can Cephalosporins have when taken w/ oral contraceptives?
Potientially decrease effect of contraceptive agent.
What is the Monobactam?
Aztreonam (AZACTAM)
What is the mechanism of action for Aztreonam?
Mono-cyclic beta-lactam derivative-- slightly different structure than Cephs & PCNs
What is the spectrum for Aztreonam?
NARROW!! Active only vs GRAM(-) organisms including Pseudomonas
What is Aztreonam considered and alternative for?
AMINOGLYCOSIDES
What is the major use for Aztreonam (AZACTAM)?
Reserved for INPATIENT use (IV ONLY) against resistant gram negative organisms
What are the Adverse effects seen w/ Aztreonam (AZACTAM)?
Relatively safe-- may cause local reactions, increased AST, ALT. Low risk of x-allergenicity w/ PCNs.
Which abx is Aztreonam (AZACTAM) most closely related to structurally?
CEFTAZIDIME (FORTAZ)
Name the Carbepenems.(3)
Imipenem/ cilastatin (PRIMAXIM)
Meropenem (MERREM)
Ertapenem (INVANZ)
What is the mechanism of action for carbepenems?
Beta-lactam derivatives similar PCNs and Cepharlosporins
What spectrum of activity do Carbepenems have?
VERY BROAD-- most broad spectrum available
Cover gram(+), gram(-) including multi-drug resistant strains & anaerobes
Which carbepenem has better gram(+) coverage against things like Enterococcus?
Imipenem/Cilastatin (PRIMAXIN)
Which carbepenem has better gram(-) coverage against things like Pseudomonas?
Meropenem (MERREM)
Which Carbepenem has Pseudomonal and Enterococcal coverage similar to Ampicillin/sulbactam (UNASYN)?
Ertapenem (INVANZ)
What function does Cilastatin serve (Imipenem/Cilastatin= PRIMAXIN)
Has no antibacterial activity
Is a DIHYDROPEPTIDASE given to decrease the nephrotoxic potential of Imipenem
IS NOT a beta-lactamase inhibitor
What are the major uses of Carbepenems?
*Often used for tx of polymicrobial infxns
*Are only available IV and are used for SERIOUS infections, suspected or known resistant organisms or critically ill.
Is there a need to worry about cross reactivity with Carbepenems and PCN?
Is possible
What kind of adjustment is necessary for Carbepenems?
Renal adjustment
What are the Adverse effects witnessed w/ Carbepenems?
1)Nephrotoxicity
2)Seizures
3)GI: N/V/D
4)Rash
5)Drug fever
What is the first Quinolone agent?
Nalidixic acid-- No longer used
What is the first generation Fluoroquinolone agent & what is it typically used for?
Norfloxacin (Noroxin) typically used for UTI
What are the 2nd generation Fluoroquinolone agents?
Ofloxacin (FLOXIN) & Ciprofloxacin (CIPRO)
What are the 3rd generation Fluoroquinolone agents?
Levofloxacin (Levaquin)
Trovafloxacin (Trovan)
What are the 4th generation Fluoroquinolone agents?
Moxifloxacin (AVELOX)
Which fluoroquinolone has restricted use due to its hepatotoxicity?
Trovafloxacin (TROVAN)
What is the mechanism of action for fluoroquinolones?
Inhibits Topoisomerase II (DNA gyrase) and Topoisomerase IV; these enzymes are required for DNA replication and transcription--> bacteria cannot replicate
What type of killing do Fluoroquinolones produce-- TIME DEPENDENT or CONCENTRATION DEPENEDENT?
CONCENTRATION DEPENDENT bactericidal activity is seen w/ fluoroquinolones
What spectrum of activity is seen w/ Fluoroquinolones?
BROAD-- very active against gram(-) bacteria
Which fluoroquinolones have activity against Pseudomonas aerginosa?
Ciprofloxacin & Levofloxacin
CIPRO is only ORAL for Pseudomonas!!
Strep pneumo and other streptococcal spp are covered by...?
Newer fluoroquinolones-- Levofloxacin (LEVAQUIN) Gatifloxacin (removed from market) & Moxifloxacin (AVELOX)
Which fluoroquinolones are considered to be the most "potent" against Strep pneumo?
Moxifloxacin (AVELOX) & Gemifloxacin (FACTIVE)
What are the major uses of Fluoroquinolones?
UTI, abdominal infections, respiratory tract infections, skin & skin structure infections (secondary to gram (-) organisms), STD (GONORRHEA) and infections diarrhea
How are fluoroquinolones most excreted?
Renally-- need to adjust w/ renal dysfn
Which fluoroquinolone doesn't need to be adjusted for renal dysfunction?
Moxifloxacin- is excreted in the feces; have to adjust for hepatic dysfunction instead
What are the adverse side effects seen with Fluoroquinolones?
*CNS
*Taste Perversion
*GI: N/V
*Liver toxicity/ glucose intolerance
*Prolonge QT interval
*Phototoxicity
*Arthritis/Tendonitis
When taking metal-cation containing medications in conjunction with Fluoroquinolones how should they be dosed?
2 hours either side of fluoroquinolone dose.
CYTOCROME P450 RXN:
Ciprofloxacin is a substrate of which CYP?? What will it interact with?
CYP1A2-- Interacts with Theophylline & Warfarin!!
Levo-, Gati- & Moxifloxacin should be monitored with which medications and why?
Wafarin, Digoxin and Theophylline-- can decrease absorption by as much as 50%
Which fluoroquinolones can be dosed once a day?
Levo-, Gemi & Moxifloxacin
Cipro-, Moxi- & Levofloxacin are all available as _________ administrations.
Both IV & PO
Which fluoroquinolones need to be monitored with renal dysfunction?
ALL except Moxifloxacin (AVELOX)
What two constituents form BACTRIM or SEPTRA?
Sulfamethoxazole and Trimethoprim
Sulfanilamide is structurally similar to...?
PABA-- Para amino benzoic acid-- required for folic acid synthesis in bacteria
What is the mechanism of action for Trimethoprim?
Inhibits dihyrofolate reductase which is an enzyme responsible for bacerial folic acid formation
What is the mechanism of action for Sulfamethoxazole?
Is a PABA analog-- competitively interferes with folic acid synthesis--> prevents bacterial growth
What spectrum of activity is seen w/ Sulfamethoxazole/Trimethoprim?
LIMITED: is Bacteriostatic only
Bactrim is known to be effective against what organisms? Gram(-), Gram(+), Pseudomonas?
Gram(-): including H. influenzae, M. catarrhalis, L. monocytogenes and many Enterobacters
Gram(+): Staph. aureus & Strep pneumo.
Effective vs Pneumocystis jiroveci (PCP) & Toxoplasma gondii
NO COVERAGE against Pseudomonas or Gp A Strep
What are the major uses for Sulfmethoxazole/ Trimethoprim (BACTRIM)?
UTI's, Respiratory tract infections, PCP & against susceptible organisms. MAY be effective vs MRSA (particularly if isolated in urine)
What are the adverse effects seen with Sulfamethoxazole/Trimethoprim (BACTRIM)?
Rash/urticaria, Photosensitivity, GI:N/V, Methemoglobinemia, Crystalluria, Hematologic abnormalities-- including hemolytic anemia in pts w/ G-6PD deficiency, MAY CAUSE FALSE ELEVATION IN SERUM CREATININE
What drugs might be affected by Bactrim?
*Phenytoin, warfarin, methotrexate-- may be displaced
*May INCREASE effect of drugs such as oral hypoglycemic agents
What drug should be avoided as a cocommitant therapy with Bactrim if at all possible?
Warfarin-- can increase or decrease INR-- hard to tell what will happen
What class of antibiotics does Vancomycin fall into?
Glycopeptide antibiotics
What is the mechanism of action of Vancomycin?
Bactericidal-- binds to bacterial cell wall and cause blockage of glycoprotein polymerization causing damage to the cytoplasmic membrane of the cell wall.
What spectrum of activity does vancomycin have?
BROAD-- active against aerobic & anaerobic gram POSITIVE organisms
**Including staph, strep pyogenes, strep pneumo., enterococci, corynebacterium and clostridium (including c. diff.)
HAS NO ACTIVITY VS GRAM NEGATIVE ORGANISMS
Vanco works vs Gram (+) or Gram (-) bacteria?
Gram(+)-- has no activity vs Gram (-) bacteria
What are the major uses of vancomycin?
*Serious gram(+) infections including MRSA (IV) that cannot be treated with other narrow abx
*PCN allergy when beta-lactam drug is primary option or for surgical prophylaxis
*Available in capsules which are used in treating C. diff. colitis
(Oral form is not absorbed from GI tract--> kills bacteria by direct contact
What is a unique feature of Vancomycin PO when used to treat C. difficile colitis?
No bioavailability in serum w/ PO; used because has DIRECT contact in GI to kill C. diff.
How is vancomycin eliminated?
80-90% unchanged in URINE; watch w/ renal dysfunction
What are the adverse effects seens w/ Vancomycin?
*Red-Man's Syndrome (IV) due to rapid rate of administration-- sudden decrease in BP, flushing, rash on face, neck & arms, wheezing, NEPHROTOXICITY, Thrombocytopenia and reversible neutropenia
What effects are seen with Vancomycin and Aminoglycosides?
Enhanced possibility of nephrotoxicity and ototoxicity.
What effects might been seen when Amphotericin, Cisplatin or Polymixin are given with Vancomycin?
Increased nephrotoxicity
What adverse effects might be seen when furosemide and vancomycin are taken together?
Increased risk of ototoxicity
What side effects might be seen when Vancomycin and neuromuscular blockers are taken together??
Enhanced Neuromuscular blockade
What is the mechanism of action for Linezolid (ZYVOX)?
Inhibits bacterial ribosomal protein synthesis by binding to a site on the 23S ribosomal RNA of the 50S subunit
** DIFFERENT BINDING SITE FROM OTHER ABX
** IS BACTERIOSTATIC
What spectrum of coverage does Linesolid (ZYVOX) have?
BROAD! Use for multi drug resistant gram(+) cocci
*For Vanco Resistant E. faecium (VRE)
*Nosocomial pneumonia caused by MSSA & MRSA
What are the major uses for Linesolid (ZYVOX)??
VRE & MRSA, skin & soft tissue infection, diabetic foot & nosocomial pneumonia
What adverse effects might be seen with Linezolid??
N/V/D, REVERSIBLE thrombocytopenia (if tx >2weeks) CBC should be monitored-- VIT B6 may help prevent, rare cases of lactic acidosis, greatly increased LFTs
What unique cautions should be observed with Linezolid (ZYVOX)??
Reversible MAOinhibitor; caution pts about tyramine intake (risk of serotonin syndrom or hypertensive crisis)
** Caution use w/ meperidine, SSRIs, SNRIs & MAOIs
What group of antibiotics does Linezolid (ZYVOX) belong to??
Oxazolidinone
What type of antibiotic does Cubicin (DAPTOMYCIN) belong to?
Is a lipopeptide antibiotic
What is the mechanism of action for Cubicin (Daptomycin)?
Binds to bacterial membrane & causes rapid depolarization of membrane potential
*Results in inhibition of protein, DNA & RNA synthesis--> cell death
Cubicin is CONCENTRATION or TIME dependent killing?
Concentration dependent-- Bactericidal
What spectrum does Cubicin (DAPTOMYCIN) have?
BROAD-- Used for multidrug reistant aerobic gram (+) cocci and for Vancomycin Resistant E. faecium (VRE)
What are the major uses for Cubicin (DAPTOMYCIN)?
Severe infections when vancomycin or linesolid is not an option or if bactericidal activity desired
What are the adverse effects seen with Cubicin (Daptomycin)?
MAJOR side effects= myalgia and increased creatine phosphokinase (CPK)-- monitor; if >5x's norm d.c daptomycin
What type of antibiotic is CUBICIN?
Lipopeptide antibiotic
What type of antibiotic is Synercid?
Streptogramin antibiotic
What is the mechanism of action for Synercid (DALFOPRISTIN/QUINOPRISTIN)?
*Inhibits bacterial growth by binding to different sites on the 50S subunit of the ribosome
*Interferes w/ bacterial protein (ribosomal) synthesis
What is the spectrum of activity for Synercid (dalfoprisitn/quinopristin)?
BROAD-- Gram(+) cocci such as Staph spp including MRSA (bactericidal) & VRE (Enterococcus faesium only) (bacteriostatic)
What are the major uses of Synercid??
*Severe life-threatening infections VRE when other agents fail or are contraindicated
*Complicated skin & skin structure infections
*Used infrequently due to adverse effects
What are the unique precautions/ adverse effect seen with Synercid?
Infusion related (thrombophlebitis, inflammation, edema)
MUST BE ADMINISTERED VIA CENTRAL LINE
d/c w/ arthralgias and myalgias
What is the mechanism of action of Rifampin (RIFADIN)?
Blocks bacterial RNA transcription by binding to DNA dependent RNA polymerase.
What is the spectrum of activity for Rifampin (RIFADIN)?
NARROW: Active against Mycobacterium tuberculosis, N. meningitidis, Staph aureus
What are the major uses for Rifampin (RIFADIN)?
*Post exposure prophylaxis against N. meningitidis and H. influenzae type B
*Very effective vs. MRSA HOWEVER when used alone resistance develops rapidly
*MUST be used as adjunctive tx w/ Vanco or Minocyclin or Bactrim
When using Rifampin in treating MRSA, what adverse effects might be seen?
Most common= Rash, N/V
*Muscular & joint pain including cramping
*Increase LFTs
*Reddish-orange discoloration of urine, feces, sweat, tears-- may even discolor contact lenses
What drug interactions might be seen with Rifampin?
May possibly decrease medication effects-- Diltiazem, digoxin, amiodarone, diazepam, haloperidol, metoprolol, morphine, prednisone, rofecoxib, warfarin.. etc.
** INDUCES CYP450**
What is the mechanism of action of Metronidazole (FLAGYL)?
Is reduced to toxic metabolites when it enters cells--> damages bacterial DNA and results in cell death
What spectrum of activity does Metronidazole (FLAGYL) have?
NARROW: active vs anaerobic bacteria including Baceroides fragilis and C. dificile, protozoa (Trichomonas, Giardia) H. pylori
What are the major uses of Metronidazole (FLAGYL)?
**DRUG OF CHOICE for treating C. difficile, bacterial vaginosis
*Used topically to treat acne
*Useful in polymicrobial infxns (combined w/ other agents)
*Treatment of peptic ulcer dz (H. pylori)
What unique effects or cautions might be seen with Metronidazole (FLAGYL)?
GI effects are most common, peripheral neuropathy, disulfram-type rxn & avoid in pregnancy or lactation
What drug interactions might be seen with Metronidazole (FLAGYL)?
**Phenobarbitol, phenytoin,carbamazepine, rifampin-- may increase metabolism of metronidazole
**Anticoagulant effect of warfarin might be increased
Name the Gycylcycline antibiotic.
Tigecycline (TYGACIL)
What is the mechanism of action for Tigecycline??
Similar to tetracycline derivatives-- binds to 30S subunit of ribosome
*structurally similar to minocycline
What is the spectrum of activity for Tigecycline (TYGACIL)??
VERY BROAD SPECTRUM-- activity vs GRAM(+)-- including MRSA and VRE and GRAM(-) except Pseudomonas and anaerobic bacteria
What type of activity does Tigecycline (TYGACIL) have? Bacteriostatic or Bactericidal?
Bacteriostatic
What are the major uses of Tigecycline (TYGACIL)?
FDA approved for complicated intra-abdominal & complicated skin and skin structure infxns
Reserved for SEVERE infxns in hospital setting-- IV ONLY
What are the adverse effects seen with Tigecycline?
Major S.E. is N/V
Why is the use of polymixins limited?
Use is limited due to risk of Neurotoxicity Nephrotoxicity-- dose dependent
Polymixins are active against....?
Pseudomonas and Acinetobacter and other GRAM(-) organisms
What is the mechanism of action for Chloramphenicol??
Inhibits protein synthesis by reversible binding to 50S subunit of 70S ribosome
The activity of Chloramphenicol is Bactericidal or Bacteriostatic??
BACTERICIDAL
What spectrum of activity does Chloramphenicol have?
BROAD-- 1st Broad spectrum abx discovered.
*Spectrum similar to Tetracycline (Gram(+), Gram(-) and anaerobic coverage
*Does not cover Staph spp but has been used w/ VRE w/ some success.
What are the major uses of Chloramphenicol?
Typhoid fever, Haemophilus meningitis & lots of unique infxn
What are the 3 major toxicities seen with Chloramphenicol?
1)Aplastic anemia-- usually 3 weeks to 12 mos
2)Bone marrow suppression after short term and prolonged tx (may be dose related)
3)Grey baby syndrome-- characterized by circulatory collapse, cyanosis, acidosis, abdominal distention, myocardial depression, coma, death- associated w/ babies w/ severe liver dz who cannot conjugate the drug at high levels
How is Chloramphenicol metabolized?
Conjugated by the liver w/ glucuronic acid-- forms monoglucuronoide (WATER SOLUBLE)
Is then excreted in bile in sm intestine--> hydrolyzed by bacteria to aglycone, reabsorbed and conjugated again
**Results in 80-90% of monoglucuronide is excreted by kidney.
What is the mechanism of action for Nitrofurantoin (MACRODANTIN)??
Poorly understood-- appears to require enzymatic reduction w/in the bacteria and then inhibits bacterial translation
What is the spectrum of activity for Nitrofurantoin (MACRODANTIN)??
NARROW-- Typically susceptible include E.coli, Staph, Strep, Enterococcus including VRE & Citrobacter
What are the major uses of Nitrofurantoin (MACRODANTIN)?
EXCLUSIVELY for UTI tx or prophylaxis
What are the unique precautions/ adverse effects seen w/ Nitrofurantoin (MACRODANTIN)?
*Hemolytic anemia has occured in pts w/ G6PD deficiency
*Avoid w/ CrCl<60ml/min
*DOES NOT reach site of infxn
*May accumulate & cause adverse effects (Ascending polyneuropathy
Antibiotics don't treat diseases...
They kill the bugs that CAUSE diseases.
What are some examples of Gram(+) organisms??
*Staphylococcus spp
*Streptococcus spp
*Enterococcus
*Clostridium
What are some examples of Gram(-) organisms?
*Enterobacteraciae-- E.coli, Proteus, Enterobacter, Pseudomonas
*Neisseria spp
* Helicobactor pylori
What are the Tetracycline antibiotics? (4)
1)Demeclocycline--Declomycin
2)Doxycycline-- Vibramycin, Vibra-tabs ets
3)Minocycline-- Dynacin, Minocin, Myrac, Solodyn
4)Tetracycline
What is the mechanism of action for Tetracyclines?
Inhibit protein synthesis by reversibly binding to 30S ribosomal subunit and inhibit binding to tRNA
What are some of the major uses for Tetracyclines?
Anthrax,Lyme dz, Chlamydia, Mycoplasma & Rickettsia infxn
**Demeclocycline is used to tx SIADH (primarily)
What is the spectrum of activity of Tetracyclines?
Broad/Limited
Are Tetracyclines Bacteriostatic or Bacteriocidal?
BACTERIOSTATIC; b/c of resistance they are not used against common gram (+) & (-) bacteria-- use is very limited
What are some unique cautions w/ tetracyclines?
Don't use in children >8y/o
Don't use in pregnancy
Photosensitivity
Hepatotoxicity
Superinfxn possible
GI: N/V/D or anorexia
Jarisch- Herxheimer rxn when treating brucellosis or spirochetal infxn
OUTDATED drug can cause nephrotoxicity
What interactions can be seen between Tetracyclines and Ca, Mg, Al, Zn, Bismuth, Dairy, Bile acid sequestriants Kaolin or pectin??
Can cause decrease absorption of tetracyclines
What should be done to keep Tetracyclines from reacting w/ Ca, Mg, Al, Zn, Fe or dairy products?
Separate dosing by 1-2 hrs before or after
What effects can tetracycline have on Warfarin or Digoxin?
Can increase effects of Warfarin or Digoxin
Doxycycline and Tetracycline are major substrate of...?
CYP3A4; Decreased doxycycline levels w/ Rifampin, Phenobarbital, Carbamazepine and others
MAY INCREASE levels of other CYP 3A4 substrates
How should Tetracylines be taken?
ON empty stomach (except doxycycline-- can be taken w/o regard)
What cautions in dosing should be observed?
Caution in Hepatic and renal dosing-- Reduce or avoid
EXCEPT doxycycline-- no adjustment necessary
Name the Macrolide antibiotics
1)Azithromycin--Zithromax, Zmax
2)Clrithromycin--Biaxin, Biaxin XL
3)Dirithromycin--Dynobac
4)Erythromyin--Erytab, Eryderm, EryPed, Erythrocin
5)Troleandomycin
What is the mechanism of action for Macrolides?
Inhibits protein synthesis by binding reversibly to 50S ribosomal subunit, blocks peptide elongation
What are the major uses of Macrolide antibiotics?
*Upper & Lower respiratory tract infxns
*Atypical bacterial infxns
*H. pylori, Mycobacterium avium complex (MAC) Mycobacterium avium intracellular (MAI)
*ACNE
What is the spectrum of activity for Macrolide ABX?
NARROW/BROAD--
Bacteriostatic OR Bacteriocidal at higher concentrations
**Broad aerobic gram (+) & actinomycetes, mycobacteria, legionella, mycoplasmas, chlamydia, rickettsiae, treponemes
**IS DRUG OF CHOICE for ATYPICALS**
What are some unique cautions w/ Macrolides??
1)Prolonged QT intervals-- concurrent use w/ cisapride, pimozide or ergot derivatives
2)Risk of Superinfection
3)GI: N/V/D/Gas
4)Cholestatic hepatitis-- esp w/ erythromycin
5)Transient hearing loss-- associated w/ lg IV doses of Erythromycin
Macrolides are known to _______ CYP3A4 and CYP1A2
INHIBITS
Macrolides may _________ levels of digoxin, warfarin, pimozide, cisapride, carbamazepine, phenytoin, VPA, Benzos, ergot derivatives, quinidines rifampin & others...
INCREASES levels-- inhibits CYP3A4 & CYP1A2-- therefore increases levels of medications that are substrates
Which macrolides need to be adjusted for Renal dysfunction?
Azihromycin & Clarithromycin
(Don't change w/ Dirithromycin or Erythromycin)
Which macrolides need to be adjusted for hepatic dysfunction?
Azithromycin, Dirithromycin, Erythromycin-- use caution -- no specific guidelines available
Don't need to adjust Clrithromycin if renal fn is normal
What is the Ketolide antibiotic discussed?
Telithromycin (KETEK)
What is the mechanism of action of Telithromycin (KETEK)?
Blocks protein synthesis by binding to 23S ribosomal RNA of the 50S ribosomal subunit
What are the major uses for Telithromycin (KETEK)??
*Community acquired pneumonia
*Other indications removed by the FDA & manufacturer due to liver toxicity
What is the spectrum of activity of Telithromycin (KETEK)?
NARROW-- Bacteriostatic or Bacteriocidal at higher concentrations
What bugs are Telithromycin (KETEK)?
Aerobic gram (+) resistant Strep pneumoniae & atypicals
What unique cautions should be considered with Telithromycin (KETEK)?
*Acute Hepatic failure
*Prolongation of QT intervals
*Exacerbation of myasthenia gravis
What are the common side effects seen w/ Telithromycin (KETEK)?
Diarrhea/ loose stools, N/V, HA, dizziness, dysgeusia
What effects would Telithromycin have w/ CYP3A4?
Ketek is metabolized and inhibits CYP3A4.
CYP3A4 inducers may cause _____ levels of Telethromycin
SUB-THERAPEUTIC; drugs like Rifampin, Phenytoin, Carbamazepine, Phenobarbital
CYP3A4 inhibitors may ______ levels of Telethromycin
INCREASE; drugs like Itraconazole, Ketoconazole, Ciprofloxacin & Macrolides
Telithromycine may ______ levels of B-blockers, Digoxin, & Warfarin
may INCREASE levels of B-blockers, Digoxin & Warfarin
Renal dosing of Telithromycin calls for...?
adjustment when CrCl <30ml/min calls for reduxn to 600mg PO-- including pt on hemodialysis-- give does afer dialysis session
Hepatic dosin of Telithromycin...
Hepatic impairment w/ CrCl <30ml/min calls for dose reduxn to 400mg PO daily
What are the Lincosamide antibiotics?
Clindamycin-- CLeocin HCl, Clindagel, CLindaMAx
Lincomycin-- Lincocyin
What is the mechanism of action for Lincosamides?
Inhibits protein synthesis by binding reversibly to the 50S ribosomal subunit blocking protein eleongation
The D-test is used to test for....?
Inducible Clindamycin resistance
What are the major uses for Lincosamide abx?
Infxns involving susceptible organisms, Pelvic inflammatory dz & severe acne
What is the spectrum of activity for Lincosamide abx?
NARROW-- Bacteriostatic or bacteriocidal at higher concentrations
** Effective vs Staph & Strep, anaerobes such as baceroides, peptococcus, peptostreptococcus, protozoa
What are some unique cautions to be considered when using Lincosamide antibiotics?
1)Previous psedomembranous colitis; regional enteritis, ulcerative colitis
2)Hypersensitivity rxns
3)Cautions inpts w/ renal or hepatic dysfn
4)Rash, urticareia, increased LFTs azotemia, proteinuria, neutropenia, leukopenia
What drug interactions might be seen with Lincosamides?
May enhance the neuromuscular blocking effect of neuromuscular-blocking agents
What considerations should be made in consideration with Lincosamides and food, renal or hepatic impairment?
Food: Clindamycin can be taken w/o regard to food
Renal impairment-- reduce dose of Lincomycin
Hepatic impairment-- dose adjustment recommended for both Clindamycin & Lincomycin
Amikacin, Gentamicin, Kenamycin, Neomycin, Streptomycin and Tobramycin are all examples of________ abx.
AMINOGLYCOSIDE antibiotics
Amikacin--AMICIN
Gentamicin--GENTAK
Kanamycin--KENTRAX
Neomycin--NEO-FRADIN, NEO-RX
Streptomycin
Tobramycin-- AKTOB, TOBI, TOBREX
AMINOGLYCOSIDE ANTIBIOTICS
What is the mechanism of axn of aminoglycosides??
Inhibits protein synthesis by irreversibly binding the 30S ribosomal subunit at MULTIPLE binding sites
**EXHIBITS POST ANTIBIOTIC EFFECT**
Wat is a unique feature of aminoglycosides?
Exhibit post-antibiotic effects
What are the major use for Amikacin, Gentamicin & Tobramicin?
Hospital acquired pneumonia, Ventilator acquired pneumonia, meningitis, intra-abdominal infxn
*synergistic effect w/ B-lactam or vancomycin for pseudomonas infxns*
What are the major uses for Streptomycin?
Tx of TB, Mycobacterium avium complex--> AIDS; opportunistic
What are the major uses for Neomycin?
Topical use for minor skin infxns, oral for preoperative abdominal antisepsis
What is the major indication for Kanamycin??
HAS LIMITED COVERAGE-- intraabdominal infections
What is the spectrum of activity for Aminoglycosides??
NARROW-- Concentration dependent bactericidal activity
Aminoglycosides have TIME-DEPENDENT or CONCENTRATION- DEPENDENT killing?
CONCENTRATION-DEPENDENT killing
Aminoglycoside antibiotics are effective against primarily_________?
AEROBIC GRAM(-) BACILLI
Which Aminoglycoside has the greatest activity vs mycobacterium?
Streptomycin
Which aminoglycoside has the most activity vs Pseudomonas aeruginosa??
Tobramycin
What are some unique cautions with Aminoglycoside antibiotics?
**DO NOT USE IN PREGNANCY
**Nephrotoxicity-- usually reversible
**Ototoxicity-- IRREVERSIBLE; damage to vestibular or cochlear structures or both; increases w/ cumulative doses
*Neomycin should not be used w/ intestinal obstruxn
Aminoglycoside antibiotics are known to increase nephrotoxicity when taken cocomittantly with....?
PCN, Cephalosporins, Amphotericin B, Loop Diuretics or Vancomycin
Increased risk of aminoglycoside potentiated ototoxicity is seen with...?
VANCOMYCIN and LOOP DIURETICS
It is important to separate dosing of Aminoglycoside and B-lactam abx because...?
Beta-lactams can deactivae Aminoglycosides-- should separate doses
Gentamycin and Tobramycin should be dosed by _______ body weight.
IDEAL BODY WEIGHT
Peaks for Aminoglycosides should fall between ____ & ___ mcg/ml and troughs should be ______mcg/ml
Peaks 3-10 mcg/ml
Troughs <2 mcg/ml
Amikacin should be dosed by ____ body weight.
Ideal body weight.
5-7.5 mg/kg/dose q 8hrs IV, IM MONITOR
The typical dosing from Streptomycin is...?
15-30mg/kg/day (IM)MONITOR
Which aminoglycoside can be dosed without regard for renal function?
NEOMYCIN
Which aminoglycosides need to be dosed with regard for hepatic deficiency?
Gentamicin & Tobramycin-- monitor levels
The typical dosing for Neomycin is...?
The typical dosing for Kanamycin is...?
Neomycin- 90mg/kg/day in divided doses q4hrs PO
Kanamycin-- DOSE BY IBW; 5-7.5 mg/kg/day in 2-3 divided doses IV or IM--MONITOR
Which aminoglycoside doesn't have an injectible form?
NEOMYCIN-- Tablet and oral solution available
Which aminoglycosides have opthalmic preparations?
Gentamicin & Tobramycin
What are the 4 key points to remember with Aminoglycosides in general?
1)Work against Gram(-) bacilli
2)Synergy
3)Oto & Nephrotoxicity
4)Monitor
Define Community Acquired Pneumonia
Lower respiratory tract invection in a patient living w/in the community or outpt setting
*Also applicable to ambulatory nursing home
With a suspected case of CAP what would some of the subjective presentations be?
Deep cough, Increased or changed sputum production, SOB, Chills, Night sweats, Fatigue, Malaise, Weakness, Chest pain (pleuritic)
With a suspeted case of CAP waht would some of the objective presentations be?
Fever (>38C), Increased RR, Sputum production, TACHYCARDIA, ELEVATED WBC, BANDEMIA (Left Shift), Decreased breath sounds, Decreased O2 saturation, Infiltrate on Chest X-ray
What are the clinical presentations that are associated with an increased risk of death?
RR>/=30/min, Diastolic BP </= 60mmHg (Hypotension), Confusion, A Fib, Multilobar Involvement, Hypoxemia, Leukopenia, Bacteremia
What are some of the risk factors associated with CAP?
Oropharyngeal colonization, Risk of aspiration, Elderly, Recent ABX use, Immune status, Underlying/preexisting lung dz
What are the five MOST common pathogens in CAP?
1)Strep pneumoniae
2)Respiratory viruses
3)M. pneumoniae
4)C. pneumoniae
5)H. Influenzae
What are the five LESS common pathogens in CAP?
1)Legionella
2)Pseudomonas
3)Enteric Gm Negatives (Gut- aspirated
4)Staph aureus (??CA-MRSA??)
5)Anaerobes
In dx RTI, modifying factors prove to predispose pts to attack from certain bugs--
1)COPD/Smokers
2)Alcoholism
3)Nursing Home
4)Aspiration
1)H. influenzae, Strep. pneumo., Pseudomonas
2)Strep. pneumo., oral anaerobes, gram negatives (Klebsiella pneumonia)
3)Strep. pneumo, G(-) bacilli, H. influenzae, Staph. aureus, anaerobes
4) G(-) enteric pathogens, oral anaerobes
HIV/Aids patients might be predisposed to RTI caused by...?(8)
1-Strep. pneumo
2-H. influenzae
3-M. tuberculosis (late in dz)
4.PCP
5. Cryptococcus
6. Histoplasma
7. Aspergillus
8. atypical Mycobacteria
Which three antibiotics provide EXCELLENT atypical coverage in treatment of CAP?
Fluoroquinolones, Macrolides & Doxycycline
Which two pathogens have the HIGHEST mortality rate in CAP?
Pseudomonas aeuginosa & Klebsiella Pneumoniae
Which pathogens has the lowest rate of mortality in CAP?
Moraxella pneumoniae
PORT & CURB criteria are used to assess?
CAP treatment-- In or Out patient & Mortality risk
A good sputum sample has _____ Polymorphonuclear Leukocytes & _______ Epithelial Cells
>25 PMNL's & < 25 Epithelial cells-- Low #'s WBC= may be colonization NOT infection; High #'s of epithelial cells = spit NOT sputum
What test is used to detect Legionella in Patients with CAP?
Legionella Urinary Antigen
Detets Legionella pneumophilia w/ ~70-90% accuracy w/ a specificity of 99%
Which test is used to detect Influenza in patients with CAP?
Influenza Rapid Antigen Test; tests for Influenza A & B w/ results in 15-30 mins. Has a sensitivity of 50-70% and 100% specificity
What are the goals of therapy for CAP?
1)Treat infection & irradicate bacteria
2)Prevent complications
3) Maintain normal activity
When treating CAP in OUTPATIENT setting w/ no RECENT ABX tx therapy might include Macrolides or Doxycycline-- WHY??
Macrolides-- Azithro-, Erythro- or Clarithromycin cover atypical pathogens eg/ Mycoplasma spp, Chlamydia spp & Legionella spp
Doxycycline covers atypical pathogens but is NOT approved in kids <8y/o
In treating CAP in an OUTPATIENT setting for a person w/ recent ABX tx OR comorbidities such as COPD, Immunosuppressed, DM, CRF, CHF, Asplenia or CA what might be used and why?
Azithro or Clarithromycin + high dose AMOX OR high dose AMOX + 2nd or 3rd generation Cephalosporin b/c Amox will treat most strains of S. pneumoniae
OR
Respiratory fluroquinolones-- Levo-, Moxi- or Gemifloxacin b/c covers atypicals (NOT for kids)
Empiric treatment of patients for CAP w/ suspected aspirations Augmentin or Clindamycin is often suggested-- why?
COVERS ANAEROBIC BACTERIA!
When empirically treating outpt with CAP caused by influenza w/ bacterial superinfection what antibiotics might be suggested?
Beta-lactam (Hi dose Augmentin, Cefpodoxime, cefprozil, cefuroxime)or Respiratory Fluoroquinolones (Levo-,Moxi or Gemifloxacin)
When treating CAP on a general ward floor IDSA/ATS 2007 guidelines suggest which antibiotics?
1)Ceftriaxone plus a macrolide
OR
2)Respiratory Fluoroquinolones (Levo-, Moxi or Gemifloxacin)
When treating CAP in an ICU ward pt what recommendations would the IDSA/ATS 2007 guidelines have?
1)Ceftriaxone + Azithromycin or a fluoroquinolone or for PCN allergy a Resp fluoroquinolone + Aztreonam
When empirically treating CAP why would Macrolides be used? Advantages/ Disadvantages?
Advantages: Works vs most common pathogens including atypicals; Azith & Clarithromicin can be given w/ ODD & better tolerated than Erythromycin
Disadvantages: Strep. pneumo resistance being reported. Erythromycin DOES NOT have activity vs. H. influenzae
When empirically treating CAP why would AMOXICILIN be used? Advantages/ Disadvantages?
Advantages: PREFERRED drug for Strep. pneumo- active vs 90-95% of straing at 3-4g/day
Disadvantages: Lacks activity vs atypical and B-lactamase producing bacteria
When empirically treating CAP why would AUGMENTIN be used? Advantages/ Disadvantages?
Additional coverage vs H. influenzae, M. cattarhallis, Staph aureus & anaerobes (vs AMOX)
Disadvantages:Lacks atypical coverage, more GI problems & $$
When empirically treating CAP why would ORAL CEPHALOSPORINS be used? Advantages/ Disadvantages?
Advantages:Active vs Strep. pneumo and virtually all H. influenza
Disadvantages: Inactive vs Atypicals: amox more effective vs Strep. pneumo.
When empirically treating CAP why would Doxycycline be used? Advantages/ Disadvantages?
Advantages: Active vs 90-95% or Strep pneumo. & H. influenzae
Disadvantages: Limited data w/ severe ill
When empirically treating CAP why would Resp Fluoroquinolones--Levo-, Moxi- or Gemifloxacin) be used? Advantages/ Disadvantages?
Advantage: Active vs >98% of Strep pneumo and all other common org. & ODD
Disadvantages:Expensive risk of abuse
When empirically treating CAP why would Telithromycin be used? Advantages/ Disadvantages?
Advantages: Has activity vs. Strep. pneumo. resistant to PCN & macrolides
Disadvantages: Drug-drug interaction, hepatotoxicity, QT prolongation
With empirical treatment of CAP why would Clindamycin be used? Advantages/ Disadvantages?
Advantages: Active vs 90% of Strep. pneumo., Staph. aureus & ANAEROBES
Disadvantages: Lacks atypical coverage, High rate of diarrhea & C. diff. colitis
When treating CAP in a hospitalized patient, what courses of antibiotics might be used?
A: Ceftriaxone (ROCEPHIN 1g/QD)or Cefotaxime (CLAFORAN 1g IV TID) PLUS Azithromycin (ZITHROMAX 500mg IV/PO QD) or Clarithromycin or Doxycycline
B: Moxifloxacin (AVELOX-400mg IV/PO QD)or Levofloxacin (LEVAQUIN 750 IV/PO QDx5)
What antiviral medications may be initiated if CAP develops secondary to influenza?
Oseltamivir (TAMIFLU)
*Inhibits neuraminidase enzyme and pevents release of new virions from host cell; active vs both Flu A & B ** MUST INITIATE w/in 48hrs!!**
What are the 3 major syndromes associated with pneumonia caused by aspiration?
1)Chemical pneumonitis-- abrupt increase in wbc; acid
2) Bronchial obstruction secondary to aspiration of particulate matter
3) Bacterial aspiration pneumonia
What predisposing conditions are connected to aspiration pneumonia?
*Alterations in Consciousness
Alcoholism, Seizure disorders, general anesthesia, CVA, Drug intoxication, head injury, severe illness w/ obtundation (Lose ability to swallow)
*Imparied swallowing
*NG tube
*Trach/ Endotrach tube
*Periodontal dz
What medications are prescribed for tx of aspiration pneumonia in an OUTPATIENT setting?
1- Clindamycin
2- Augmenting
3- Fluoroquinolones or 2nd/3rd Gen Cephalosporins + Clindamycin or Metronidazole
What medications are prescribed for tx of aspiration pneumonia in an inpatient setting?
1- Ampicillin/ sulbactam (UNASYN)
2) Pipercillin/tazobactam (Zosyn)
3) 3rd/ 4th Gen Ceph IV + Clindamycin IV or Metronidazole IV
4)Fluoroquinolones IV +Clindamycin IV or Metronidazole IV
What criteria are necessary to convert CAP pts from IV to PO antibiotics?
** Hemodynamically stable
** Temp <100 for at LEAST 8 hrs (most use 24h)
** Improving clinically
Unasyn or Zosyn IV treatment therapies are switched to which abx?
Augmentin for Unasyn
Augmenting + CIPRO for Zosyn
What CAP antibiotic regimens are only available PO?
Clarithromycin (BIAXIN), Erythromycin (E-mycin), Telithromycin (KETECK)& Gemifloxacin (FACTIVE)
How many days should afebrile CAP pts be treated?
How many days will most patients w/ CAP be treated?
MINIMUM of 5 days
Most 7-10 days
Newer guidelines suggest when treating Strep. pneumo. abx therapy may be d/c'ed when?
Once pt is afebrile for 72hrs.
When treating CAP caused by Legionella how long with the course of treatment last?
14 days.
Define Hospital acquired Pneumonia.
Pneumonia that occurs 48hrs or more after admission which was not incubating at time of admission.
Define Ventilator acquired pneumonia
Arises 48-72hrs after endotracheal intubation
What does HCAP stand for?
Healthcare- associated Pneumonia
What are the criteria for HCAP
*Hospitalized in acute care for 2 or more days/90days
*received IV abx, chemo or wound care w/in 30days of current infxn
*attended hospital or hemodialysis clinic
In ventilated patients the incidence of risk ______ with the duration of ventilation.
INCREASES
What are some sources of pathogens in VAP/HAP
Healthcare devices, Environment, Staff
What are some non-modifiable risk factors for HAP?
Sex- more likely in males
Underlying dz-state- eg/ COPD
What are some modifiable risk factors for HAP?
Intubation/mechanical ventilation, Body positioning, Enteral feedings, concomitant medication use, Transfusion, HYPERGLYCEMIA
Early HAP/VAP vs Late HAP/VAP
Early= w/in 4 days
Late= w/in more than 5 days
What is the mortality rate for HAP/VAP?
30-70% in studies; many die of underlying disease states; Bacteremia associated w/ INCREASED mortatlity risk
What are the stereotypical GRAM NEGATIVE microorganisms associated w/ HAP/VAP?? (5)HINT SPACE
SPACE
1)Serratia spp
2)Pseudomonas spp
3)Acinetobacter spp
4)Citrobacter spp
5)Enterobacter spp
What GRAM POSITIVE microorganisms associated w/ HAP/VAP?
Staphylococcus aureus, Streptococcus pneumoniae, Oropharyngeal pathogens-- strep viridans, coagulase negative Staph., Corynebacterium
What aypical microorganisms my be associated w/ HAP/VAP?
Legionella, Viruses, Fungus
What are the typical causative agents for EARLY ONSET nosocomial pneumonia?
Strep. pneumo., H. influenzae, Staph. aureus, VIRUSES
What are the typical causative agents for LATE ONSET nosocomial pneumonia?
Pseudomonas aeruginosa, Staph aureus (Both MSSA & MRSA), aerobic GRAM(-) bacilli eg/ ACINETOBACTER spp, Enterobacteriacae spp such as Klebsiella pneumoniae
What are the risk factors for multidrug resistant pathogens associated w/ HAP/VAP?
*Antimicrobial tx w/in 90 days
*Current hospitalization
*ABX-resistance w/in community
*Presence of risk factor for HCAP
*Immunosuppressive dz &/or tx
Diagnosis of HAP/VAP must include:
*Radiographic infiltrate
*Clinical findings of infxn
(Onset of fever, purulent sputum, Leukocytosis, decline in O2)
If clinical findings of infections are present but chest x-ray reveals NO infiltrate the diagnosis is_____?
Tracheobronchitis
Diagnostic strategies for HAP typically include presence of infiltrate on CXR +....?
at least ONE of the following:
FEVER (at least 38C), LEUKOCYTOSIS, PURULENT TRACHEAL SECRETNS
A bronchoscopy will...?
Scope into R or L or BOTH lungs can allow visual or to take culture
What factors should be considered when selecting abx tx in the treatment of HAP?
*Previous ABX tx
*Pt disposition
*Known prevalence of resistance patterns
*Duration of hospitalization
*Patient condition
Initial selection of abx for treatment of HAP might include________?
Piperacillin/Tazobactam (Zosyn) OR Ceftriazone (ROCEPHIN) + Clindamycin (CLEOCIN)
If PCN Intollerant: Cipro- or Levofloxacin + Clindamycin
If MRSA is suspected in HAP/VAP or HCAP-- what drug might be added on to or in place of Clindamycin (CLEOCIN)?
VANCOMYCIN
What abx might be added in HAP/VAP/HCAP regimin if atypical pathogens are suspected?
Azithromycin or Levofloxacin (IV or PO)
When EMPIRICALLY treating HAP what are the ABX choices?
*Antipseudomonal Cephalosporins: Cefepime & Ceftazidime
*Antipseudomonal carbapenem: Imipenem or Meropenem
*B-Lactamase/B-lactamase inhibitor +Antipseudomonal fluoroquinolone: ZOSYN + Cipro or Levofloxacin
*Aminoglycosides: Tobra-, Gentamycin, Amikacin
When EMPIRICALLY treating HAP with suspected MRSA what abx are chosen?
VANCOMYCIN or LINESOLID (ZYVOX)
When EMPIRICALLY treating HAP w/ Legionella pneumophilia what should be added to the treatment regimine?
Fluoroaquinolones or Azithromycin instead of aminoglycosides
What type of killing is seen in therapeutic vancomycin dosing? Time-dependent or concentration- dependent??
TIME DEPENDENT
What are the reasons for deterioration or non-resolution of pneumonia in response to abx therapy?
*NOT pneumonia; wrong dx
*Etiology-- not bacterial; could be yeast or viral
*Complicated pneumonia; abscess
*RESISTANT pathogen
*Breakthrough infxn (Dose too low)
Narrowing of antibiotics to the targeted pathogen is important to prevent...?
COLLATERAL DAMAGE
Which microorganism is the biggest problem with collateral damage?
C. diff.
What should pseudomonas be double covered with?
Aminoglycosides or Ciprofloxacin typically-- can stop double coverage when patient starts to get better.
Why are children so susceptible to Acute Otitis Media?
Decreased cellular and humoral immunity
What organisms are resposible for nearly 70% or bacterial otitis media cases?
Strep pneumo., H. influenzae, M. catarrhalis
Gram(+): Staph. aureus, GAS
Gram(-): E.coli
Atypicals: Chlamydia & Mycoplasma
Define Middle Ear Effusion
Any fluid in the middle ear space regardless of cause
Define Myringitis
Erythema of tympanic membrane w/out middle ear effusion; can be mimicked by crying
Define Otalgia
Ear Pain
Define Otorrhea
Discharge from the ear
Define Myringotomy
Slit made in the ear drum to allow drainage of fluid
Define Tympanocentesis
Small gauge needle inserted to drain fluid from middle ear
Acute Otitis Media s/sx's include:
Sudden onset of pain, irritability, fever, nasal congestion, coughing, loss of appetite, vomiting, ear drainage, recent URI
On otoscopic exam a patient w/ otitis media will have:
Buldging, poorly mobile, opaque tympanic membrane (red/yellow) w/ pain on insufflation
Otitis media w/ Effusion
*Fluid behind TM
*No pn w/ insufflation
*Often w/ URI
*May be prelude to AOM
*May be present up to 1mo post tx of AOM
*More common than AOM
What timeline deferrentiates Chronic from Recurrent Otitis media?
Chronic lasts >3months
Recurrent 3 episodes of AOM w/in 6mo or 4 episodes w/in 1yr
When diagnosing Otitis media what does COMPT stand for?
C= Color of tympanic membrane:Pearly gray= norm
O=Other: fluid, pus, perforations w/ otorrhea
M=Mobility:4+=normal
P=Position: Neutral vs Full& buldging
T= Translucence:Norm= Translcent
Approximately what percentage of AOM cases resolve spontaneously?
80%
Approximately what percentage of AOM cases are resolves w/ abx treatment?
94%
Pain management for Otitis media consists typically of Acetaminophen or Ibuprofen. What are the suggested dosing regimines?
APAP: 15mg/kg q6
IBU: 10mg/kg q8: not for kids <6mos
What age group of children are ALWAYS treated with abx for AOM?
Children <6mo; benefit outweighs risk
How do penicillins work?
Interfers w/ bacterial cell wall synthesis by binding to penicillin binding proteins
How do Beta-lactamase inhibitors work?
Binds & inhibits beta-lactamase enzyme
How do Cephalosporins work?
Interfers w/ bacterial cell wall synthesis by binding to the penicillin binding proteins
How do Macrolides work?
Inhibits bacterial RNA-dependent protein synthesis by binding to the 50S ribosomal subunit
How are H. influenzae & M. catarrhalis treated when recognized as pathogen for AOM?
Use b-lactamase stable abx: Augmentin, Cefdinir, Cefuroxime & Ceftriaxone
What is the disadvantage when treating AOM w/ Ceftriaxone?
INTRAMUSCULAR INJXN= PAINFUL!!
What are preventable risk factors for AOM?
Lack of breastfeeding
Extended pacifier use
what immunizations are suggested to reduce the risk of AOM?
Influenza vaccine & Pneumococcal conjugate vaccine
What are some clinical exceptions to treatment regimines?
*Anatomical abnormalities:Cleft palate
*Genetic conditions: Down's
*Immunodeficiency
*Cochlear implants
*AOM w/in 30days
*AOM w/ underlying chronic Otitis media w/ effusion
What are the common bacterial organisms seen w/ pediatric pharyngitis?
Group A Strep: Strep pyogenes
Gp C & G Strep:
Neisseria gonorroea
Corynebacterium diptheriae
Haemophilus influenzae
Mycoplasma pneumoniae
Chlamydia pneumoniae
Moraxella caarrhalis
Strep. pneumo
What are some common viruses seen w/ pediatric pharyngitis?
Rhinovirus
Coronavirus
Adenovirus
Herpes simplex type 1 & 2
Parainfluenza
Enteroviruses- Coxsackie A
Epstein Barr virus
GABHS stands for...?
Group A Beta-hemolytic Streptococcus
What is the GOLD STANDARD for testing for GABHS pharyngitis?
Rapid Streptococcal antigen detection tests (RADT): Sensitivity= 80-90% & FAST results
Which Cephalosporins are effective in treatment of pharyngitis?
1st & 2nd generation Cephalosporins: Cephalexin, Cefaclor, Cefixime, Cefprozil, Loracarbef
What are the classifications for Skin and Soft Tissue Infections? (1-4)
Class I: Afebrile, previously healthy. Oral or topical abx
Class II: Febrile, ill looking w/ no comorbid conditns. IV or PO ABX
Class III:Appears toxic, > unstable comorbidities, limb threatening infxn-Need >1abx typically
Class IV: Sepsis, life-threatening infxn or necrotizing fascititis
What are the typical causes of PRIMARY SSTI?
*Community acquired/ Gram (+); typicall Staph. aureus or Strep pyogenes
*Other bugs: Pseudomonas, Acinetobacter, Enterobacteraciae, E.coli, Anaerobes
What are the typical causes of Secondary SSTI?
*Diabetic foot ulcers, pressure sores--S. aureus, Strep., Bacteroides, Peptostreptococcus, Pseudomonas
*Bites- Animal:Pasturella, S. aureus, Strep., Bacteroides. HUMAN: Eikenella, S. aurueus, Strep. BURNS: Pseudomonas, Enterobacteraceae, Staph. aureus, Strep.
What treatment guidelines were provided for folliculitis?
*Warm compress
*Topical agents-Clindamycin, Erythromycin, Mupirocin, Benzoyl peroxide BID-QID X7days
What treatments guidelines were provided for Carbuncles? For Furuncles?
*PCNase Resistant PCN-- Dicloxacillin 250mg/q6 x 7-10d or Clindamycin 150-300 mg/q6
*Furuncles- small;moist heat & prompt drainage. Large; same tx as furuncle.
What is Impetigo and what are the treatment options?
*Superficial skin infxn usually seen in children; strep pyogenes or staph aureus most common- may resolve spontaneously
*TX: PCNas-Resistant PCN; Dicloxacillin(PEDS) 12.5mg/kg divided
Cephalexin, Defadroxil PenG or PenVK or Clindamycin for PCN allergy--150-300mg q6-8 or 10-30mg/kg/day divided
What is CLostridial Myonecrosis?
Necrotizing infxn involving skeletal muscle; gas produxn and necrosis
Advances rapidly secondary to trauma or surgery
*Clostridum perfringens
What is Necrotizing Fasciitis?
Aerobic or anaerobic infxn of superficial fascia or SQ fat
TypeI: Post surgery or trauma; mixed anaerobes & strep or enterobacteraceae
TypeII: Virulent strains of Strep pyogenes; rapid necrosis of SQ tissue, gangrene, pn, toxicity-associated w/ shock & organ failure
What are the 3 types of Diabetic foot ulcers?
Deep abscess-central plantar space
Dorsum cellulitis-fm infxn of toes
Mal perfomas ulcers- Chronic on calluses of metatarsals
What organisms are typically seen with DOG bites?
Pasteurella, Staph, Strep, Moraxella, Neisseria, Fusobacterium, Bacteroides, Prevotella, Porphyramonas
What organisms are typically seen with CAP bites?
Pasteurella multocida, Mixed anaerobes, Tularemia, Rabies
What is Eikenella commononly associated with?
IVDA endocarditis; lick needle to lubricate
Gram(-) fastidious slow grower
**COMMON w/ human bites**
What type of bugs are generally expected to be seen with diabetic foot infxns?
Staph aureus, Strep spp, Pseudomonas, Peptostreptococcus, Bacteroides fragilis
What 3 things are important for treatment of Diabetic foot infections?
1- debridement & cleansing
2- glycemic control
3- ABX tx
What is the typical abx treatment for diabetic foot infections?
*Augmentin for mild/ non limb threatening
*Ampicillin/Sulbactam or Imipenem/Cilistatin for more severe
**Osteomyelitis requires 6-12 weeks of parenteral tx