Antimicrobial Review

8/22/2019 Antimicrobial Review

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Antimicrobial ReviewDaryl Norwood, PharmD

Associate Professor

FAMU COPPS


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Objectives Identify different types of bacteria

Determine appropriate antibiotic for empiric treatment

Identify different antibiotics and their respective classes

Understand the pharmacology and spectrum of

different antibiotics

Determine antibiotics of choice for certain infections


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Bacteria

Gram-positive: stain dark blue

or violet

Gram-negative: stain red or

pink

Cocci: spherical shaped

Bacilli (rods): rod shaped

Spirillum: spiral shaped

Gram positive cocci and gram negative bacilli
http://en.wikipedia.org/wiki/File:Gram_stain_01.jpg


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Gram-positive Aerobes Gram-positive cocci

Streptococci: (pneumonococcus, enterococcus,

viridans)

Staphylococci: (S. aureus, S. epidermidis)

Gram-positive rods (bacilli)

Corynebacterium

Listeria


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Gram-negative Aerobes Gram-negative cocci

Neisseria: (N. meningitidis, N. gonorrhea)

M. catarrhalis

Gram-negative rods

Enterobacteriaceae (E. Coli, Klebsiella, Enterobacter,

Citrobacter, Proteus, Serratia, Salmonella, Shigella)

Pseudomonas

Haemophilus influenzae (coccobacilli morphology)Campylobacter


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Anaerobes Gram-positive cocci

Peptococcus and peptostreptococcus

Gram-positive rods (bacilli)

Clostridia (C. perfringens, C. tetani)

Propionibacterium acnes

Gram-negative rods (bacilli)

Bacteriodes (B. fragilis, B. melaninogenicus) Fusobacterium


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Atypical Bacteria

Atypical Bacteria

Chlamydia (C.trachomatis, C. psittaci, C.

pneumoniae (TWAR), LGV, Ureaplasma

Mycoplasma pneumoniae Legionella pneumophilia

Mycobacteria (Myobacterium tuberculosis, M. avium

intracellulare/complex)


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Other Notable Bugs Fungi (Candida sp., Aspergillus, Histoplasma,

Cryptococcus, Coccidioides, Mucor)

Viruses {Influenza, Hepatitis (A,B,C), HIV, Rubella,Herpes simplex virus (HSV), Herpes Zoster (VZV),Cytomegalovirus (CMV), Epstein barr virus,Respiratory Syncytial Virus)}

Rickettsia (Rocky Mountain Spotted Fever, Q fever)

Spirochetes (Treponema pallidum)

Protozoa (Pneumocystis carinii, Toxoplasma gondii)


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Pathogens and their Sites


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Antibiotics Beta-Lactams

Penicillins

Cephalosporins

Carbapenems

Aminoglycosides

Quinolones

Macrolides (and Ketolides)

Monobactam

Carbapenems

Glycopeptides

Tetracyclines

Miscellaneous Agents

Trimethoprim/Sulfamethoxazole(Bactrim)

Clindamycin (Cleocin)

Metronidazole (Flagyl)

Quinupristin/dalfopristin(Synercid)

Linezolid (Zyvox)

Daptomycin (Cubicin)


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Penicillins Natural

Antistaphylococcal

Aminopenicillins Antipseudomonal

Beta-lactamase inhibitor combinations


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Penicillins Mechanism of Action: bactericidal, inhibit bacteria cell wall synthesis,

reducing cell wall stability, thus causing membrane lysis.

Adverse Effects:

Hypersensitivity reactions - maculopapular rash, anaphylaxis, serumsickness (fever, malaise, joint pain 7-10 d post therapy)

Gastrointestinal - diarrhea esp. ampicillin. Pseudomembranous colitisfrom clostridium.

Local reactions - IM-pain, redness at injection site/IV phlebitis, burningand redness

Hepatotoxicity - in LFTs, hepatitis (rare)-most common w/oxacillin.

Nephrotoxicity - interstitial nephritis (rare), most common with methicillin

Platelet dysfunction-most common with carbenicillin and ticarcillin Neurologic - encephalopathy, seizures (rare) - with high doses & renal

insufficiency

"procaine reactions" - anxiety, psychosis, feeling of impending doom

Electrolyte abnormalities- K+ with ticarcillin and carbenicillin; Na withticarcillin and carbenicillin


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Natural Penicillins Penicillin G (IV, IM) Procaine Penicillin G (IM) Benzathine

Penicillin G (IM), Penicillin V (PO)

Good coverage: narrow spectrum = some Gm + and - cocci(streptococci, pneumococci, enterococci, meningococci), gram-positive rods (corynebacteria, L.monocytogenes), spirochetes

(Leptospira sp., Treponema sp., Borrelia sp.), and most of anaerobes(peptostreptococci, clostridial species, Actinomyces, not B. fragilis).

Poor Coverage: Staph, Gm (-), GI anaerobes

Uses: low-dose = pseudomembranous tonsillitis, strept throat,streptococcal skin infections (impetigo), or animal bite and scratches.High-dose = endocarditis (caused by viridans streptococci orenterococci), streptococcal, pneumococcal or meningococcal sepsis,clostridial wound infection.


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Antistaphylococcal

Nafcillin (IV), Oxacillin (IV),Dicloxacillin (PO), Methicillin (nolonger used to treat infections)

Methicillin (used for sensitivity/resistance testing): MRSA and ORSA

Good coverage: narrow spectrum, active against beta lactamase

producing Staph aureus (MSSA)

Poor coverage: enterococci, Staph epi (many strands are resistant),

Gm (-), anaerobes. No MRSA coverage.

Uses: skin/soft tissue (cellulitis), endocarditis, osteomyleitis


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Aminopenicillins Ampicillin (IV, PO), Amoxicillin (PO)

Expanded gram (-) activity

Good coverage: H. infl, enterococcus (non-VRE),

Listeria, Proteus, Streptococci(HELPS) Neisseria spp& E. coli

Poor coverage: Staph, Pseudomonas, GI anaerobes

Uses:Amp = UTIs,Amox = URIs (sinusitis, bronchitis & otitis media)


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Antipseudomonals

(extended-spectrum) Mezlocillin, Piperacillin, Carbenicillin,Azlocillin, Ticarcillin (MPCAT)

Piperacillin and Ticarcillin (IV) only agents available in U.S

Good coverage: Pseudomonas (pip>azlo>mezlo=ticar>carben),

Klebsiella, Ecoli, Proteus, Enterobacter spp.,enterococcus(piperacillin) and anaerobes

Poor coverage: Serratia spp (may be resistant)

Uses: Nosocomial infections, usually used in combo with -

lactamase inhibitors


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Mezlocillin

Piperacillin

Carbenicillin

Azlocillin

Ticarcillin


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Beta-lactamase inhibitor

combinations Enhanced coverage against -lactamase producing organisms,

MSSA, anaerobes

Amoxicillin-clavulanic acid (Augmentin)

Otitis media, uti's, upper rti's, skin/soft tissue infections, sinusitis,

Ampicillin-sulbactam (Unasyn)

Polymicrobial infection (no pseudo.) intra-abdominal, utis,anaerobes

Ticarcillin-clavulanic acid (Timentin)

Polymicrobial infections, nosocomial infections, pseudomonas,anaerobes, diabetic foot ulcers

Piperacillin-tazobactam (Zosyn)

Polymicrobial infections, nosocomial infections, anaerobes -

pseudomonas, intra-abdominal (enterococcus)


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Cephalosporins

Mechanism of Action - similar to penicillins

Adverse effect:

Hypersensitivity reactions (~ 0.5 - 2% cross reactivity between

cephalosporins and penicillins) rash, fever, eosinophilia-most

common, hives and anaphylaxis rare

Gastrointestinal - Bile stasis (ceftriaxone), avoid in neonates w/

hyperbilirubinemia

Interfere w/ urine glucose test (cefixime,ceftazidime, cefepime)

Hematologic reactions - hypoprothrombinemia & increase riskof bleeding, with drugs which have NMTT side chain (cefotetan,

cefoperazone) disulfiram reaction (flushing, hypotension,

palpitations, chest pain, HA, weakness) when alcohol is

ingested


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Cephalosporins 1st Generation

ORAL AGENTS

Cephalexin (Keflex)

Cephradine (Velosef)

Cefadroxil (Duricef)

PARENTERAL AGENTS

Cephalothin (Keflin)

Cefazolin (Ancef ,

Kefzol)

CLINICAL USE

Gm (+) coverage (including

pcnase-producing strains)

and Gm (-) bacilli (P.

mirabilis, E. coli, K.

pneumoniae) PEK

Cephalexin and and

cephradrine are the most

effective for skin infections,

UTIs & surgical

prophylaxis

*all start with ceph- except cefadroxil and cefazolin


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Cephalosporins 2nd Generation

ORAL AGENTS Cefaclor (Ceclor)

Cefuroxime axetil (Ceftin )

Cefprozil (Cefzil)

PARENTERAL AGENTS

Cefoxitin (Mefoxin)

Cefuroxime axetil (Zinacef )

Cefotetan (Cefotan)

CLINICAL USE Most important is activity

against H. influenza and M.catarrhalis (including betalactamase producing strains).RTIs

Cefaclor useful in otitis media

and sinusitis for PCN allergicpts.

Cefotetan, cefoxitin - mixedaerobic-anaerobic infections(intra-abdominal infections)

Cefuroxime for CAP

Extended gram (-) spectrumHENPEK (H. influenza, E.coli, N. gonorrhea , Proteus,Enterobacter, Klebsiella)

*all start with cef- and lack one, en, or ime ending (except

cefuroxime, ceftaroline, cefdinir)


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Cephalosporins 3rd Generation

ORAL AGENTS

Cefixime (Suprax)

Cefpodoxime (Vantin)

Ceftibuten (Cedax)

Cefditoren (Spectracef)

Cefdinir (Omnicef)

PARENTERAL AGENTS

Ceftazidime (Fortaz ,Tazicef)

Ceftriaxone (Rocephin)

Cefotaxime (Claforan)

Ceftizoxime (Ceftizoxime)

CLINICAL USE

Expanded activity against Gm(-) HENPEKS (includeSerratia spp)

Generally used to treat C.A.P

Valuable in the treatment of

meningitis (penetrate CSF),STDs,

Antipseudomonals(nosocomial infections) -ceftazadime > cefoperazone

Ceftriaxone, cefotaxime has

good activity vs streptococciincluding PCN resistance

* all start with cef- end in ime, one, or en except cefuroxime (2nd),

cefepime (4th), ceftibuten,


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Cephalosporins 4th Generation

Cefepime (Maxipime)

Expanded activity against Gm (-) HENPEKS(Enterobacter spp)

Activity against pseudomonas (similar to ceftazidime)

Activity against streptococcus (similar to ceftriaxone)

Indicated for febrile neutropenia and nosocomial infections

Meningitis: comparable cure rate to ceftriaxone and cefotaxime


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Ceftaroline (Teflaro)

Activity against Gm (-) and many resistant Gm (+) bacteria

including MRSA

Indicated for CAP and skin and subcutaneous infections (MSSA

& MRSA)

Does not cover pseudomonas

Cephalosporins 5th Generation


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Maxipime

(cefepime)

Cefotaxime

Cefuroxime

Ceftriaxone

Ceftazidime


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Carbapenems Imipenem/Cilastatin (Primaxin), Meropenem (Merem), Ertapenem

(Invanz), Doripenem (Doribax)

Mechanism of Action: Bactericidal inhibitor of cell wall synthesis.

Beta-lactams with very broad-spectrum.

Clinically used for serious mixed infections: soft tissue & intra-abdominal grampositive, gram negative, aerobic and anaerobic bacteria.

Only Meropenem indicated in bacterial meningitis in children > 3 months

Doripenem, Meropenem and imipenem are active against pseudomonasaeruginosa (Not ertapenem)

Ertapenem has a long half life; hence once daily dosing.

Doripenem is newest agent, similar spectrum to imipenem and meropenem

Adverse Effects:

Hypersensitivity-rash, fever, pruritis approx. 15 - 20% cross sensitivity withpenicillins. Questionable, recent studies suggest most may tolerate

Seizure -


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Aminoglycosides

Gentamicin

Tobramycin

Amikacin

Streptomycin

Netilmicin

Neomycin


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Aminoglycosides Mechanism of Action: bactericidal, inhibit bacterial protein

synthesis by impeding the function of the 30s ribosomal subunit.

Adverse Effects:

Nephrotoxicity 5-15%, vestibular & cochlear 2-15% (>amikacin)toxicity associated with aminoglycosides

Pharmacokinetics:

Traditional Dosing (2-3mg/kg/day divided over q8-12).Gentamicin / Tobramycin - Peaks (5-10 mcg/ml) Trough (


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Traditional Dose Monitoring Draw levels off the third dose for:

-Patients with normal renal function based on Creatinine/Bun, I/O's,

medical history; concomitant drug therapy, and hydration status.

When to draw levels: Aminoglycoside: Peak/trough: 30 minutes before

and after a 30 minute infusion.

Draw levels off the first dose for:

- Patients with abnormal renal function based on BUN/SCR; I/O's, edema,

history of renal or cardiac disease.

- Patients receiving other nephrotoxic drugs.

- Patient is neutropenic, febrile, and/or unstable.

- Patient has unstable or increasing serum creatinine.When to draw levels: 1st level: aminoglycoside: 30 minutes post

infusion. 2nd level: at least one half-life (depending on drug) after the 1st

level.


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Clinical Use Excellent Gm (-) coverage, including pseudomonas

Gm (+) coverage: only with beta-lactams as a low dose

synergistic addition vs. enterococcus

Amikacin- has the broadest spectrum

Streptomycin - used to treat plague and tularemia

Neomycin - useful for perioperative bowel sterilization


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Once Daily Dosing Alternative dosing method which may be less

nephrotoxic than conventional dosing with similar

efficacy.

Based on the concentration-dependent killcharacteristic of aminoglycosides.

At approximately 10 times the minimum concentration

necessary for inhibition of bacterial growth, maximal

antimicrobial activity is observed

Used for the treatment of gram negative infections


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Exclusion criteria:

Elderly (age 70 years)

Pregnancy or post-partum

Renal insufficiency (CrCL 50% totalbody surface area)

Determine patients dosing


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Determine patient s dosing

weight (DW) Non-Obese patients:

Use ideal body weight (IBW) unless total body weight (TBW) is less.

IBW (males) = 50 kg + (2.3 x height in inches > 60 inches)

IBW (females) = 45 kg + (2.3 x height in inches > 60 inches)

Obese patients:

Use adjusted body weight (ABW) in obese patients (TBW > 30% over

IBW)

ABW (kg) = IBW + 0.4 (TBW IBW)

Determine patients dose

(round to nearest 20 mg for gentamicin/tobramycin and to nearest 100 mgfor amikacin)

Gentamicin / Tobramycin 4 to 7 mg/kg x DW

Amikacin 15 to 20 mg/kg x DW


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Serum concentration monitoring

Aminoglycoside trough monitoring

Nomogram monitoring

Dosing Interval Methods

(once daily dosing)


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Creatinine Clearance Monitoring

Creatinine ClearanceDosing IntervalmL/min

> 60 Q24h

40-59 Q36h (pre-dose level recommended) or conventional

aminoglycoside dosing suggested

< 40 Use conventional aminoglycoside dosing & take two post-levels

to determine appropriate interval

Twice weekly serum creatinine measurements are recommended to

assess renal function.

For patients with a CrCl < 60 mL/min, a pre-dose aminoglycoside level

may be warranted to ensure that levels are negligible (< 1 mg/L) at the

end of the dosing period. Levels can be drawn prior to second or thirddose. Baseline and weekly audiometry and the E-test are recommended

for patients who require greater than 2 weeks of aminoglycoside therapy.


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Serum Concentration Monitoring

Use trough levels (peak levels NOT rout inely mon itored):

Trough concentrations should be checked 30 to 60 minutes prior to the

next (second) dose. Desired levels:

Gentamicin / tobramycin < 0.5 mcg/mL

Amikacin < 2.5 mcg/mL

If level is greater than desired trough, extend dosing interval by 12 hours

and repeat level prior to next dose (or use conventional dosing and

monitoring methods). If the next level continues to be high, then change to

conventional dosing method.

Repeat level weekly AND with any significant changes in renal function.Serum creatinine should be monitored every 1-3 days.


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In some patients, nomograms often do not accurately predict the correct dose

or dosing interval. Therefore, selective pharmacokinetic monitoring may be

required.

Nomogram Monitoring


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1st Generation: Norfloxacin (Noroxin) (PO, OPTH)

2nd Generation: Ciprofloxacin (Cipro) PO, IV),

Ofloxacin (Floxin) (PO, IV, Otic, OPTH)

3rd Generation: Levofloxacin (Levaquin) PO, IV, Top)

4th Generation: Moxifloxacin (Avelox) (PO),

Gemifloxacin (Factive) (PO)

Quinolones


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Quinolones Mechanism of Action: bactericidal, via inhibition of DNA gyrase.

Adverse Effects:

CNS effects-dizziness, headaches etc. < 3%

Gastrointestinal effects - nausea, diarrhea

Photosensitivity < 2-4%, 7.9% Sparfloxacin-sunlight or artificial UV light

QTc interval prolongation, torsades de pointes

Cartilage toxicity in pediatrics/pregnant and lactating women. Probablysafe in children if other alternatives are not available (Cystic fibrosis)

Black Box Warning: Tendonitis/tendon rupture (esp in elderly,corticosteroid use, pts w/ kidney/heart/lung/ transplant)

Drug Interactions:

Multivalent cations (Mg, Al, Zn, Fe etc.) up to ten fold reduction in serumlevel

Cytochrome P450 - Ciprofloxacin > Ofloxacin/Lomefloxacin

Theophylline/caffeine - no interaction with norfloxacin, ofloxacin,

Avoid using w/drugs that may prolong QT interval (i.e. terfenadine,astemizole, erythromycin, quinidine, procainamide, TCA's)


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Clinical Use Gram negative (excellent) Cipro potent vs P.

aeruginosa Excellent activity against

Enterobacteriaceae Used in Gm (-)

osteomyelitis, bacteremia,gastroenteritis & utis Useful in complicated utis

Gm positive (variable) Third and fourth

generation good strept.Pneumoniae activity =respiratory quinolones

Moderate activity againststaphylococci (MSSA)

Poor to moderate activityvs. enterococci

Atypical Chlamydia, M. pneumoniae,

Legionella

Other pathogens

Mycobacteria: M. aviumcomplex (Cipro), M.Tuberculosis MDRT(ofloxacin/levofloxacin)

STD pathogens: C.trachomatis (ofloxacin), N.gonorrhea

Enteric pathogens: E. Coli,Campylobacter, Salmonella,Shigella


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Macrolides Erythromycin (E-Mycin, Eryc) (PO, IV, OPTH)

Clarithromycin (Biaxin) - (PO)

Azithromycin (Zithromycin) (PO, IV)

Telithromycin (Ketek)Ketolide (PO)

Fidaxomycin (Dificid) (PO)


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Macrolides Mechanism of Action: bacteriostatic; they bind to the 50s ribosomal

subunit, inhibiting bacterial protein synthesis.

Adverse Effects:

Gastrointestinal-gastric stimulant, iv or po. (erythro, clarithro,

telithro)

Cholestatic hepatitis-with erythromycin estolate

Ototoxicity with high doses (erythromycin, azithromycin)

Drug Interactions

Cytochrome P450 active agents (theophylline, carbamazepine,

rifabutin, protease inhibitors) primarily erythromycin,

clarithromycin and telithromycin (3A4)


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Clinical Use Gram-positive bacteria Good activity against gram-

positive organisms, includingstreptococci, andcorynebacterium and Neisseria

Some staphylococcus,azithromycin is less active, as a

result these agents aremicrobiologically inferior todicloxacillin, first gencephalosporins and clindamycinin skin and soft tissue infxns.

Clarithromycin is more active thanerythromycin vs. staphylococciand streptococci

Gram-negative bacteria

Erythromycin has poor-moderateactivity vs. H. influenzae

Azithromycin and telithromycinare more active against H.influenzae.

Atypical bacteria: Most macrolides haveexcellent activity vs. atypical respiratorypathogens, including Legionella,Mycoplasma and Chlamydia

Other pathogens: Clarithromycin andazithromycin active vs. Helicobacterpylori & M. avium complex. Azithromycinis efficacious in single-dose treatment ofuncomplicated chlamydia cervicitis andurethritis

Fidaxomycin used to treat C. difficileonly (narrow spectrum)

1

st

line - Bartonella henselae (catscratch bacillus), Bordetella pertussis(whooping cough)


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Monobactams Aztreonam (Azactam)- bactericidal, inhibits cell wall synthesis

Aztreonam does not cross react with PCNs or CEPHS

Aerobic gram negatives only

Moderate activity against Pseudomonas aeruginosa andEnterobacter spp.

No gram positive or anaerobic activity

New inhaled formulation approved for cystic fibrosis

Adverse Effects:

Hypersensitivity - rash Usually safe to use in pts w/ PCN

allergy but AVOID in pts w/ ceftazidime allergy (similar sidechain)

Gastrointestinal - Nausea, vomiting and diarrhea

Gl tid


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Glycopeptides Vancomycin and Telavancin (Vibativ) -1st lipoglycopeptide in US

Mechanism of Action: bactericidal; inhibits bacterial cell wallsynthesis. Telavancin has additional MOA that involves disruption ofmembrane potential and changing cell permeability and bactericidalactivity is concentration dependent unlike vancomycin.

Pharmacokinetics

Vancomycin therapeutic peaks (20 - 40 mcg/ml / troughs 5 - 15mcg/ml)

Telavancin no blood level monitoring necessary

Toxicity

"Red Man Syndrome" RMS-seen with rapid infusion (infuse bothover 60 mins). Fever, chills, phlebitis, rash, and reversibleleukopenia. Ototoxicity - rare if levels < 40 mcg/ml, nephrotoxocity~ 5%

Telavancin may prolong QT interval

Black Box Warningwith Telavancin: Prior to use, women ofchildbearing potential should have a serum pregnancy test.Caused fetal malformations in animals.


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Clinical Uses

Gram-positive: All including methicillin sensitive andmethicillin-resistant Staphylococci and enterococcus

(problems with vancomycin resistant enterococcus)

Vancomycin - skin/soft tissue/bone infections and linesepsis, 2nd line forC. difficile colitis (PO)

Televancin - complicated skin/soft tissue infections

Gram-negative: none


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Tetracyclines Demeclocycline (Declomycin) (PO)

Doxycycline (Adoxa, Doryx, Monodox,

Vibramycin, Oracea, Periostat) (PO, IV)

Minocycline (Minocin, Solodyn) (PO)

Tetracycline (Sumycin) (PO)

Tigecycline (Tygacil) - (IV)


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Tetracyclines Mechanism of Action: Bacteriostatic, inhibits bacterial protein

synthesis via binding to the 30S ribosomal subunit

Adverse Effects: Photosensitivity, hepatotoxicity, GI intolerance

(diarrhea, nausea, anorexia), Contraindicated in pregnancy and

children < 8y/o (tooth discoloration and interference with bonegrowth), Fanconi Syndrome with expired tetracycline Abx

Minocycline (Lupus-like symptoms, vertigo, skin

pigmentation)

Drug Interactions: Avoid use with divalent or trivalent cations. Do

not take concomitantly with milk or dairy products


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Clinical Use Broad spectrum, some gram (+), largely gram (-). ricketssial

infections, and atypical bacteria (Chlamydial infections, M.

pneumoniae)

Doxycycline - 1st line for Rickettsia rickettsii (Rocky Mountain

spotted fever) and Borrelia burgdorferi (Lyme Disease), plague

Mainly used PO

MOA: inhibits bacterial protein synthesis (30s subunit)

Tigacycline: Structure (glycylcycline) helps it to be more effectiveagainst bacterial resistance

Tigacycline: IV only, good activity against MRSA, VSE

Trimethoprim/Sulfamethoxazole


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Trimethoprim/Sulfamethoxazole

(Bactrim) Mechanism of Action: usually bactericidal, sulfamethoxazole inhibits the

formation of dihydrofolic acid from PABA. Trimethoprim inhibitsdihydrofolate reductase, thus blocking bacterial synthesis of folic acid.

Active against gram positve organisms: S. aureus, S. epidermidis, S.pneumoniae

Active against gram negative organisms: E. coli, enterobacter, P. mirabilis,Klebsiella spp., Serratia, Shigella, Neisseria spp.

Other organisms: Pneumocystitis carinii, Nocardia asteroides.

1st line for Stenotrophomonas Maltophilia (formerly Xanthomonas)andTropheryma whippeli (Whipples Disease)

Clinical uses: uncomplicated utis, acute gonococcal urethritis, acuteexacerbation of chronic bronchitis, shigella, and salmonella infections, andPCP prophylaxis.

Adverse effects: Rash, pruritis, thrombocytopenia, nausea and vomiting

Drug interactions: several including clarithromycin, warfarin, phenytoin


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Clindamycin (Cleocin) Mechanism of Action: bacteriostatic, binds to 50s ribosomal

subunit, thereby suppressing bacterial protein synthesis.

Gram positive organisms (Staph & Strept) and anaerobes (bothgm (+) and gm (-) ) also toxoplasma gondii & pneumocyctis cariniipneumoniae (PCP)

NO activity vs gram negative bacteria.

Clinical uses: Staph infections, Intra-abdominal anaerobicinfections, bacterial vaginosis, aspirational pneumonia, and thirdline to PCN allergic patient intolerant of erythromycin, acne(topical)

Adverse effects-GI disturbances - N/V, pseudomembranouscolitis / increase in LFTs


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Metronidazole (Flagyl) Mechanism of Action: amebicidal, bactericdal, and

trichomonicidal. Inhibits bacterial nucleic acid synthesis.

Adverse effects and Drug interaction:

GI disturbances-metallic taste, nausea, abdominalcramping

Mutagenic and carcinogenic - avoid in 3rd trimester of

pregnancy

Discoloration of urine-reddish-brown Drug interactions-alcohol (disulfiram rxn), increase

bleeding w / warfarin.


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Clinical Uses Active against all anaerobic cocci and anaerobic gram-negative

bacilli (Bacteroides spp, & Fusobacterium)

Preferred agent in amebic dysentery, giardiasis, andtrichomoniasis.

D.O.C. for clostridium difficile colitis

Poor vs. gram-positive and gram negative aerobes

Uses

Anaerobic infections Bacterial vaginosis

C. diff colitis

Parisitic infections

H. Pylori - PUD (eradication, some resistance)

Quinupristin/dalfopristin


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Quinupristin/dalfopristin

(Synercid) Mechanism of Action: dalfopristin inhibits early protein synthesis in

the bacterial ribosome while quinupristin inhibits late phase proteinsynthesis

Active against VREF (vancomycin-resistant Enterococcus faeciumonly, not active against E. faecalis), S. aureus, S. pneumoniae,Methicillin-resistant S. aureus (MRSA) and Methicillin-resistant S.epidermidis (MRSE). May also be active against N. meningitidis, M.catarrhalis, Legionella pneumophilia, M. pneumoniae andClostridium perfringens.

IV only

ADRs include pain and inflammation at injection site, edema,thrombophlebitis. Arthralgias and myalgias are common and may besevere.

Watch for drug interactions, is a potent inhibitor of CYP3A4


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Linezolid (Zyvox) Mechanism of Action: inhibits protein synthesis at the bacterial

ribosome.

Active against VRE (vancomycin-resistant Enterococcus faecium

also active against E. faecalis), S. aureus, S. pneumoniae,

Methicillin-resistant S. aureus (MRSA) and Methicillin-resistant S.epidermidis (MRSE)

No activity against gram negative organisms

P.O and I.V formulation available

Generally well-tolerated, most common side effects are diarrhea,

nausea, and vomiting. If therapy last longer than 2 weeks, monitor

platelets.


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Daptomycin (Cubicin)

Mechanism of Action: binds to bacterial cell membranes andcauses cell death by inducing rapid depolarization of themembrane potential, leading to disruption of DNA, RNA, andprotein synthesis

Active against VRE (vancomycin-resistant Enterococcus faecium

also active against E. faecalis), S. aureus, S. pneumoniae,Methicillin-resistant S. aureus (MRSA) and Methicillin-resistant S.epidermidis (MRSE)

No activity against gram negative organisms

Alternative to other agents (eg, linezolid, quinupristin/dalfopristin)

for treating infections caused by MRSA & VRE

Serious ADRs include: Asthmatic eosinophilia, renal failure, andrhabdomyolysis


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Antimicrobial Review

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