ANTIMICROBIAL THERAPY

DEFINITION

n    ANTIMICROBIAL- chemical substance which is capable in low concentrations of inhibiting the growth or killing micro-organisms.   Mold is capable of producing penicillins that kill other micro-organisms.

DEFINITION

n    BROAD SPECTRUM

–  Kills or inhibits the growth of many different organisms including infecting and non-infecting organisms

–  Alters natural flora - can lead to super-infection and pseudomembranous colitis

–  Uses:  Unidentified organism, mixed infections, no other alternatives

DEFINITION

n    NARROW SPECTRUM

–  Inhibits the growth or kills a limited number of different organisms

–  Less potential for super-infections

DEFINITION

n    BACTERIOCIDAL

–  At safe serum levels kills sensitive organisms

–  Effective in immuno-compromised individuals

DEFINITION

n    BACTERIOSTATIC

–  At safe serum levels, inhibits the growth of sensitive micro-organisms

–  Allows the body’s immune system to kill the micro-organisms

–  Ineffective in immuno-compromised individuals

MECHANISM OF ACTION

n    Only effective in replicating organisms

 

n    Interrupts cell wall synthesis, protein synthesis, vitamin utilization

RESISTANCE

n    Inherent - organism never has been sensitive to a particular antimicrobial agent

n    Acquired - organism had previously been sensitive but has acquired an insensitivity

–  Associated with over use of antimicrobial agents

ANTIMICROBIAL SELECTION

n    Identify organism and its sensitivity

n    Identify source of infection

n    Select the most narrow spectrum agent possible

n    Avoid hypersensitivity

n    Cost

n    Use synergistic combination in immuno-compromise patients

CAUSES OF ANTIMICROBIAL FAILURE

n    Fever not due to infection

n    Improper dose

n    Improper selection of antimicrobial

n    Improper duration of therapy

n    Failure to utilize ancillary measures

–  incision and drainage of white blood cells

PATIENT VARIABLES

n    Genetic - metabolism of antimicrobial agents

n    Allergies - cross allergies

n    Age

–  Tetracyclines not used in children due to adverse reactions of teeth mottling and effect on bone growth

PENICILLINS

n    BACTERIOCIDAL

 

n    Allergic to one - allergic to all penicillins

 

n    Narrow to Broad Spectrum

 

n    Crosses Blood Brain Barrier

PENICILLINASE RESISTANT PENICILLINS

n    Resistant to penicillinase enzyme produced by Staph Aureus

n    MRSA strains can still destroy this antimicrobial agent

n    Narrow Spectrum

–  Staph Aureus

•   Infections of skin, otitis, respiratory

PENCILLIN G’s

n    Spectrum

–  Strept pneumonia

•   Respiratory, skin, otitis

–  Anaerobic Strept

•   Respiratory

–  Neisseria

•   STD

–  Trepenema pallidum (syphilis)

•   STD

Wider Spectrum Penicillins

n    Examples:  Ampicillin, amoxicillin

n    Spectrum

–  Same as penicillin G’s

–  E. Coli

•   GI, UTI

–  Hemophilus influenza

•   Respiratory, otitis

–  Enterococcus

•   GI, UTI

EXTENDED SPECTRUM PENCILLINS

n    Examples:  Piperacillin, Ticarcillin, Mezlocillin

n    Synergistic with aminoglycosides

n    Spectrum

–  Same as Wider Spectrum

–  Pseudomonas aeruginosa

 

PENCILLIN POTENTIATORS

n    Examples:  clavulanate, tazobactam, sulbactam

n    Overcomes resistant organisms

n    Overcomes enzymes that would destroy the penicillin antimicrobial agent

CEPHALOSPORINS

n    Bacteriocidal

n    10% cross allergenicity with penicillins

n    First generation does not cross blood brain barrier (BBB)

n    Only cefuroxime of second generation crosses BBB

n    All 3rd generation cross BBB

FIRST GENERATION

n    Spectrum

–  E. Coli

–  Staph

–  Hemophilus influenza

–  Klebsiella

•   respiratory

SECOND GENERATION CEPHALOSPORINS

n    May be effective in first generation resistance

n    Spectrum

–  Bacteroides (anaerobe)

•   GI, respiratory, skin

THIRD GENERATION CEPHALOSPORINS

n    May be effective against organisms resistant to 1st and 2nd generation

n    Synergistic with aminoglycosides

n    Spectrum

–  Similar to second generation

–  Pseudomonas

ERYTHROMYCIN

n    Bacteriostatic

n    Forms

–  Base - oral, poorly absorbed, useful for bowel sterilization prior to surgery

–  Stearate - well absorbed, causes GI upset

–  Estolate - well absorbed, little GI upset, but associated with cholestatic hepatitis

–  Gluceptate, Lactobionate - IV use, cannot give IM

ERYTHROMYCIN

n    USE

–  Penicillin allergy to gram positive cocci for treating respiratory, otitis and syphlis

–  Topical use for acne

–  Legionnaire's Disease

n    SIDE EFFECT

–  Significant GI Upset

 

MACROLIDES

n    Azithromycin (Zithromax®) - Respiratory infection, mycobacterium avium

n    Clarithromycin (Biaxin®) - Respiratory infection, mycobacterium avium, helicobacter pylori

CLINDAMYCIN

n    Bacteriostatic

n    Use

–  Anaerobic Infections - GI, respiratory

n    Adverse Reactions

–  Diarrhea

–  Pseudomembranous colitis - therefore limit therapy to no more than 7 days

METRONIDAZOLE

n    BACTERIOSTATIC/BACTERIOCIDAL

n    USE

–  Trichomonas

–  Anaerobic Infections

–  Helicobacter pylori

n    ADVERSE REACTION

–  Disulfiram like reaction with alcohol

VANCOMYCIN

n    BACTERIOCIDAL

n    No oral absorption, but given orally to treat pseudomembranous colitis

n    Use

–  Penicillin allergy for gram positive cocci

–  MRSA

–  Pseudomembranous colitis

VANCOMYCIN

n    Monitor

–  Peak and Trough Blood Levels

n    Adverse Reactions

–  Ototoxic

–  Nephrotoxic

TETRACYCLINES

n    Bacteriostatic

n    Extremely Broad Spectrum - risk of super-infection

n    FOOD/DRUG INTERACTION

–  Minerals: Mg, Ca, Fe, Al (antacids)

TETRACYCLINES

n    Avoid in Children - affects teeth and long bone

n    Side Effects

–  Photosensitivity, GI upset

n    Do not use expired medication

–  Fanconi Syndrome

n    Use

–  Chlamydia, acne, COPD, cholera

 

CHLORAMPHENICOL

n    Hepatic elimination

n    Poor elimination in infants

n    Crosses Blood Brain Barrier

n    Adverse Reaction - Aplastic anemia

n    Use

–  Meningitis

–  Anaerobic Infections

 

AMINOGLYCOSIDES

n    No oral absorption

n    Nephrotoxic and Ototoxic

n    Monitor therapy with peak and trough levels

n    Good gram negative coverage

n    Synergistic with penicillins

AMINOGLYCOSIDES

n    Tobramycin and amikacin reserved for resistance to gentamicin

n    Neomycin used orally for bowel sterilization

n    USE

–  Intravenous for systemic gram negatives

–  Topical

–  Ophthalmic and otic

QUINOLONES

n    Broad spectrum

n    Minerals block absorption

n    Affects tendon growth in children

n    Increasing rate of resistance

n    Use

–  UTI

–  Respiratory Infection

URINARY TRACT INFECTION

n    Increasing resistance in hospital and community acquired infections

n    Sulfonamides (Sulfa) not very useful any more

SULFONAMIDES

n    High acquired resistance

n    Use in combination with trimethoprim to overcome resistance

n    Trimethoprim/sulfamethoxazole (co-trimoxazole) inhibits bacteria ability to activate folic acid to tetrahydrofolate

CO-TRIMOXAZOLE

n    Use

–  UTI

–  Respiratory Infection

–  Pneumocystis Carinii (high dose therapy)

n    Adverse Reactions

–  Anemia associated with high dose therapy

–  Serious Skin Rashes

–  Diarrhea

METHENAMINE

n    Breaks down to formaldehyde in acidic environment

n    Enteric coated to avoid breakdown in the stomach

n    Cranberry juice and Vitamin C help acidify urine

n    Not useful with indwelling foley catheters

FUNGAL INFECTIONS

n    SYSTEMIC

–  Respiratory (coccidioidomycosis)

–  Urinary

–  Meningitis

n    DERMATOLOGIC

–  Athlete’s Foot

AMPHOTERICIN B

n    Intravenous and Bladder Irrigation

n    Precipitates in Saline, therefore intravenous admixtures in Dextrose and bladder irrigation in water

n    Protect from light

n    Test dose is administered

n    Dose is gradually increased

AMPHOTERICIN B

n    Adverse Reactions

–  Headache, chills, fever

•   premedicate with antipyretic, steroids, and/or antihistamines

–  Thrombophlebitis

•   Premedicate with an anticoagulant

–  Hypokalemia

–  Nephrotoxicity - reversible

FLUCONAZOLE

n    Oral and Intravenous Therapy

n    Less effective than amphotericin

n    Less side effects

n    Advantage:  oral agent for systemic infections

Nystatin

n    Oral and Topical

n    Oral use for candida (thrush)

n    Topical use for skin and vaginal infections

Flucytosine

n    Oral Use

n    Adjunct therapy for meningitis

Miscellaneous

n    Miconazole - topical and vaginal use

n    Griseofulvin - oral for dermatologic and nail infections - duration of therapy can be 6 months to a year

n    Ketoconazole - dermatologic and oral infections

n    Terbinafine - Nail infections

Mycobacterium

n    Slow growing organism

n    Difficult to eradicate

n    Mycobacterium tuberculi can be cured

TUBERCULOSIS THERAPY

n    Non-compliance leads to resistance

n    Minimal to Moderate disease requires two drugs for two years

n    Advanced (disseminated) disease requires three drugs for three years

n    Prophylactic therapy for healthy positive converters for 9 to 12 months

n    Most medications are hepatotoxic

VIRAL THERAPY

n    Some viral infections cannot be cured

–  HIV, Herpes

n    Some agents may stop flare ups

–  Acyclovir

n    Some agents may hasten recovery

–  Amantadine - Influenza type A