What is the general mechanism of action for antiinfectives/antimicrobial agents?

Stops microorganism spread by interfering with genetic components and/or replication/reproductive growth:

1. Inhibit cell wall synthesis      

2. Inhibit protein synthesis - necessary for cell walls and other structures  

3. Disrupt cell membranes         

4. Inhibit reproduction - inhibit RNA or DNA synthesis             

5. Inhibit cell metabolism and growth - block necessary components -                                                                                antimetabolite

Goal: kills enough of the organism or slows its growth enough so the antural body defenses can overcome invading agent.

What are the nontoxic adverse effects of antiinfectives/antimicrobial agents in general

and what do you do to check for them?

NONTOXIC ADVERSE EFFECTS       HOW TO CHECK FOR EFFECTS

1.   Hypersensitivity                                       

          - rash/hives/pruritis           - skin -- rash

          - fever, chills                   - temp -- fever

          - anaphylaxis                   - resp/cardic -- distress

2.   superimposed/secondary/       - look for new signs of infection:

      opportunistic infections            check oral mucous membranes,

                                                 skin folds, GI/GU and resp. tracts

3.   GI upset: N/V/A/D  (PO)         - I/O, GI upset

4.   Resistance                    

Incidence of adverse effects increases with renal insufficiency,

liver disease and in older adults

What are the toxic adverse effects of antiinfectives/antimicrobial agents in general

and what do you do to check for them?

TOXIC ADVERSE EFFECTS          CHECKING FOR ADVERSE EFFECTS

1.   Nephrotoxicity                   - BUN, Cr. I/O

2.   Neurotoxicity                     - LOC and hearing

         · D LOC

         · ototoxicity

3.   Hepatotoxicity                   - ALT, AST

4.   BMD – blood dyscrasias       - CBC (anemia, thrombocytopenia,

                                              leukipenia)

Incidence of adverse effects increases with renal insufficiency,

liver disease, and in older adults

What general teaching is involved

with antiinfectives/antimicrobial agents?

TEACHING

1.  Take entire course of meds (don’t share or save).

2.  Take at regular intervals

3.  Report signs of hypersensitivity

4.  Stress good nutrition and personal hygiene.

5.   Take probiotic supplements or cultured dairy products

6.   Use contraception (alternative to BCPs)

What are the general administration

guidelines for antiinfectives/antimicrobials?

ADMINISTRATION

1.  Check MAR for identification of any drug allergies.

2.   Send specimen of probable infection source for culture and sensitivity ( C & S) before starting therapy when possible.

3.  Administer on time and at appropriate intervals to provide optimal blood levels.

3.   Give in deep muscle for IM injections

4.  Be aware of IV incompatibilities when administering > 1 antiinfective agents.

5.  Oral agents are usually given on an empty stomach to enhance absorption.

6.  Contraindications:  pregnancy/lactation (Categories B-X)

What are the general pharmacotherapeutics

for antiinfectives/antimicrobial agents and how

do you check for therapeutic effect?

PHARMACOTHERAPEUTICS

1.   Treat actual infections

2.   Prevent infections (prophylaxis)

    Consider factors that increase a person’s risk of infection:

           immuno compromised, age extremes, neutropenia, malnutrition, impaired

           circulation (DM), invasive procedures, other chronic illnesses

THERAPEUTIC EFFECT:

1.  Monitor systemic indicators of infection:

         ·  WBC

         ·  Temp at least every shift

2.  Monitor actual site of infection – repeat cultures

3.  Monitor peak & trough levels, esp. for agents with narrow spectrum

penicillin G

(Pentids)

A/T/A/T

Antiinfectives - Antibacterial (MC) - Penicillins (SC)

Check for history of allergies; most common for drug-induced anaphylaxis

Take with full glass of water; do NOT drink acidic juice

penicillin G

(Pentids)

A/T/A/T

Antiinfectives - Antibacterial (MC) - Penicillins (SC)

observe for allergic responses (focus)

check electrolytes, esp. Na⁺ and K⁺ (more FYI)

Hypersensitivity

Resistance

GI distress (PO agents)

Blood dyscrasias (rare)

penicillin G

(Pentids)

A/T/A/T

Antiinfectives - Antibacterial (MC) - Penicillins (SC)

follow-up labs especially if h/o renal or CV disease

Drug-drug interactions:

oral anticoagulants - PCN interferes with platelet aggregation

BCP - PCN decreases efficacy

Diuretics - use with caution

cefotaxime

(Claforan)

A/T/A/T

Antiinfectives - Antibacterials (MC) - Cephalosporins (SC)

Check for history of allergies - cross sensitivity to PCN

cefotaxime

(Claforan)

A/T/A/T

Antiinfectives- Antibacterials (MC)- Cephalosporins (SC)

Hypersensitivity - cross-sensitivity to penicillins

Monitor for allergic responses

GI: Antibiotic-associated pseudomembranous colitis (AAPMC)

Nephrotoxicity if preexisting renal dz -check urine output; BUN & Cr.

observe for frequent loose stools and other GI effects (AAPMC)

cefotaxime

(Claforan)

A/T/A/T

Antiinfectives- Antibacterials (MC)- Cephalosporins (SC)

Follow-up labs especially if h/o renal disease

Report adverse effects, especially diarrhea, changes in urinary output

No ETOH - disulfiram-like effect

Drug-drug interactions:

     oral anticoagulants - decrease prothrombin

     (decrease vit. K metabolism)

cefotaxime

(Claforan)

Mechanism of Action

Antiinfectives- Antibacterial (MC)- Cephalosporins (SC)

High spectrum of gm (-) and gm (+) organisms

Resistant strains

longer duration of action

tetracycline HCL

(Achromysin)

A/T/A/T

Antiinfectives- Antibacterial (MC)- Tetracyclines (SC)

Routes: PO, IM, topical

Frequency: QID - Short T_1/2

Do not give with: milk prodects, iron, Mg⁺⁺ containing laxatives/antacids, antilipiemics (all decrease drug absorption)

            Wait ~2 hours after taking meds to take antacids

Contraindications: 2nd half pregnancy, whildren <8y/o (teeth), severe renal or liver disease

tetracycline HCL

(Achromysin)

A/T/A/T

Antiinfectives- Antibacterial (MC)- Tetracyclines (SC)

Resistance

GI: N/V/D

Photosensitivity - sun burn easily in direct sunlight

Yello-brown discoloration of teeth if given to patients <8y/o

Category D

tetracycline HCL

(Achromysin)

Mechanism of Action

Antiinfectives- Antibacterial (MC)- Tetracyclines (SC)

Broad spectrum - Bacteriostatic

Alternate for PCN resistance

Due to resistance, use limited to: chlamydial infections, Lyme's Disease, Rocky Mountain spotted fever, H. pylori

Long-term treatment of acne vulgaris

tetracycline HCL

(Achromysin)

A/T/A/T

Antiinfectives- Antibacterial (MC)- Tetracyclines (SC)

Take as directed - full glass of water

Avoid sun exposure - use suncreen

Report adverse effects

Other drug-drug interactions: decreases effectiveness of BCPs

Do NOT use expired meds - high risk of nephrotoxicity

Do not give with: milk prodects, iron, Mg⁺⁺ containing laxatives/antacids, antilipiemics (all decrease drug absorption)

            Wait ~2 hours after taking meds to take antacids

erythromycin

(E-Mycin, Erythrocin)

Mechanism of Action

Antiinfectives- Antibacterial (MC)- Macrolides (SC)

Alternative to PCN allergies; broad spectrum

Low doses = bacteriostatic; high doses = bacteriocidal

Most gram (+) and many gram (-)

Variety of strep infections (resp, skin)

Legionnaire's disease

Pertussis prophalaxis

H. influenza

erythromycin

(E-Mycin, Erythrocin)

A/T/A/T

Antiinfectives- Antibacterial (MC)- Macrolides (SC)

Take with full glass of water

shake/mix suspensions thoroughly

Do not give with fruit juices

erythromycin

(E-Mycin, Erythrocin)

A/T/A/T

Antiinfectives- Antibacterial (MC)- Macrolides (SC)

GI: N/V/D/abdominal pain

     monitor PO intake and stools

Check liver enzymes: AST, ALT

Hypersensitivity

Rare: Hepatotoxicity

erythromycin

(E-Mycin, Erythrocin)

A/T/A/T

Antiinfectives- Antibacterial (MC)- Macrolides (SC)

Report adverse effects

Drug-drug interactions:

- Anesthetics & Antiseizure agents - increased risk of drug toxicity

- Cyclosporine - increased risk of nephrotoxicity

- Increased effects of oral anticoagulants

gentamicin

(Garamycin)

Mechanism of Action

Antiinfectives- Antibacterial (MC)- Aminoglycosides (SC)

Narrow Spectrum

Aerobic gram (-) bacteria systemic infections

Some enterococci infections

Sterilize bowel prior to surgery

Parasitic infections

gentamicin

(Garamycin)

A/T/A/T

Antiinfectives- Antibacterial (MC)- Macrolides (SC)

Route: IM/IV/PO (for bowel prep)

Baseline renal function tests and hearing screening (for toxicity)

Contraindications: neuromuscular disease (e.g. myasthenia gravis, Parkinson's) - AMG (aminoglycosides) cause N-M blockage

Memory Aid: HIGH risk of toxicity = gentamicin = Not a gentleman = mean

gentamicin

(Garamycin)

A/T/A/T

Antiinfectives- Antibacterial (MC)- Macrolides (SC)

Nephrotoxicity - check BUN, Cr, UA during treatment

Ototoxicity

Peak and Trough levels *TEST*

Monitor hearing, tinnitus, dizziness, ataxia

Monitor neuro status - LOC

gentamicin

(Garamycin)

A/T/A/T

Antiinfectives- Antibacterial (MC)- Macrolides (SC)

Take as directed - with full glass of water; drink adequate fluids

Report adverse effects - hearing changes/loss; decrease in urinary fn

Follow up labs: BUN, Cr, hearing, peak/trough levels

Drug-drug interactions:

      other drugs causing ototoxicity (i.e. Lasix, ASA, ampho B)

ciprofloxacin

(Cipro)

A/T/A/T

Antiinfectives- Antibacterial (MC)- Fluoroquinolones (SC)

Route: PO/IV

Do not take with antacids or mineral supplements (iron)

Advantage: longer-acting; can take once or twice daily

Contraindications: neuro conditions, alcoholism

ciprofloxacin

(Cipro)

Mechanism of Action

Antiinfectives- Antibacterial (MC)- Fluoroquinolones (SC)

Variety of gm (+) and gm (-) infections (resp, GI and GU tracts, soft tissue & skin)

MDR - TB

anthrax

ciprofloxacin

(Cipro)

A/T/A/T

Antiinfectives- Antibacterial (MC)- Fluoroquinolones (SC)

GI status: N/V/D, hepatotoxicity (ALT, AST tests)

CNS: dizziness, HA, sleep disturbances

Photosensitivity - sunburns

CV: dysrhythmias

M-S: tendonitis; tendon rupture

ciprofloxacin

(Cipro)

A/T/A/T

Antiinfectives- Antibacterial (MC)- Fluoroquinolones (SC)

Avoid antacids/mineral supplements (iron) - take 4 hrs apart

Report adverse effects

Follow-up labs as indicated - liver

function tests, ECG (depends on underlying conditions)

Limit sun exposure; wear sun screen

TMP-SMZ

(Bactrim, Septra)

Mechanism of Action

Antiinfectives- Antibacterial (MC)- Sulfonamides (SC)

Gram (+) & gram (-) - bacteriostatic

UTIs - E. Coli Proteus, Klebsiella (aka urinary antiseptics)

pneumocystis carini pneumonia

topical agent burns

TMP-SMZ

(Bactrim, Septra)

A/T/A/T

Antiinfectives- Antibacterial (MC)- Sulfonamides (SC)

Route: PO/topical

Give with full glass of water

TMP-SMZ

(Bactrim, Septra)

A/T/A/T

Antiinfectives- Antibacterial (MC)- Sulfonamides (SC)

Resistance

Renal insufficiency due to crystaluria - check for changes in UO

GI: N/V/A

Heme: blood dyscrasias - blocks folic acid synthesis

Hypersensitivity (Stevens-Johnson syndrome) - check skin after sun exposure; check skin for rashes

TMP-SMZ

(Bactrim, Septra)

A/T/A/T

Antiinfectives- Antibacterial (MC)- Sulfonamides (SC)

Take with full glass of water; increase PO fluid intake unless contraindicated

Report adverse effects, especially rash, urinary difficulty

Follow-up labs as indicated - renal function tests, CBC

Limit sun exposure - sunscreen

imipenem

(Primaxin)

Mechanism of Action

Antiinfectives-Antibacterial (MC)-Misc. Antibacterials(SC)

Carbapenems (Sub SC)

PCN-resistant organisms

broad-spectrum - bacteriocidal

mixed with cilastatin - to maintain drug levels

(decreased inactivation before excretion)

imipenem

(Primaxin)

A/T/A/T

Antiinfectives- Antibacterial (MC)- Misc. Antibacterials (SC)

Carbapenems (Sub SC)

Check for allergies

Route: IV

imipenem

(Primaxin)

A/T/A/T

Antiinfectives-Antibacterial (MC)-Misc. Antibacterials(SC)

Carbapenems (Sub SC)

(Similar to PCN. but only given IV and can be used for more serious infections)

observe for allergic responses (focus)

check electrolytes, esp. Na⁺ and K⁺ (more FYI)

Hypersensitivity

Resistance

GI distress (PO agents)

Blood dyscrasias (rare)

imipenem

(Primaxin)

A/T/A/T

Antiinfectives-Antibacterial (MC)-Misc. Antibacterials(SC)

Carbapenems (Sub SC)

(Similar to PCN. but only given IV and can be used for more serious infections)

follow-up labs especially if h/o renal or CV disease

Drug-drug interactions:

oral anticoagulants - PCN interferes with platelet aggregation

BCP - PCN decreases efficacy

Diuretics - use with caution

nitrofurantoin

(Macrodantin)

Mechanism of Action

Antiinfectives- Antibacterials (MC)- Misc. Antibaterials(SC)

Treat or prevent lower UTIs

Low doses = bacteriostatic

high doses = bacteriocidal

nitrofurantoin

(Macrodantin)

A/T/A/T

Antiinfectives- Antibacterials (MC)- Misc. Antibaterials(SC)

Route: PS

Contraindications: hematologic disorders, renal dysfunction

nitrofurantoin

(Macrodantin)

A/T/A/T

Antiinfectives- Antibacterials (MC)- Misc. Antibaterials(SC)

GI: N/V/A/D

hypersensitivity

blood dyscrasias

neurotoxicity - peripheral neuritis - muscle weakness, tingling/numbness

allergies - monitor for pulmonary sx

check urinary status - change in UO

CBC - watch for other infections, bleeding

nitrofurantoin

(Macrodantin)

A/T/A/T

Antiinfectives- Antibacterials (MC)- Misc. Antibaterials(SC)

Maintain adequate PO fluid intake unless contraindicated

Report adverse effects, especially rash, urinary difficulty, bleeding

Report neuro changes - safety precautions

Follow-up labs as indicated - renal function tests, CBC

vancomycin

(Vancocin)

Mechanism of Action

Antiinfectives- Antibacterials (MC)- Misc. Antibaterials(SC)

Monocactams (Sub SC)

alternative to PCN allergies

gram (+) - MRSA

pseudomembraneous colitis (oral)

vancomycin

(Vancocin)

A/T/A/T

Antiinfectives- Antibacterials (MC)- Misc. Antibaterials(SC)

Monobactams (Sub SC)

Route: IV/PO

Baseline tests: hearing, renal function tests

CDC 'limits' use due to VRA (Vanco resistant entercocci)

vancomycin

(Vancocin)

A/T/A/T

Antiinfectives-Antibacterials (MC)-Misc. Antibaterials(SC)

Monobactams (Sub SC)

Nephrotoxicity - BUN, Cr, UA

Ototoxicity - check for hearing changes, tinnitus, dizziness, ataxia

Peak/Tough levels

"Red-man" syndrome - run IV slowly - observe skin for slushing, hypotension, muscle pain

(Memory Aid: similar to aminogly - mean; vanco - vicious!)

vancomycin

(Vancocin)

A/T/A/T

Antiinfectives- Antibacterials (MC)- Misc. Antibaterials(SC)

Drink adequate fluids

Report adverse effects - hearing changes/loss; decrease in urinary fn

Follow-up labs: BUN, Cr, hearing, peak/trough levels

Drug-drug interactions: other drugs causing ototoxicity

isoniazid

(INH)

Principles of Drug Therapy

Antiinfectives-Antituberculars (MC)-1st-line agents (SC)

Long term tx: avg 6-12 mo; up to 24 mo for immunocompromised pts or resistant strains; tuberculocidal

Multi-drug tx: at least 2, sometimes 3-4 agents given concurrently

Due to resistance, slowly-growing nature of organism

Prophylactic use - new (+) TB test; Not used alone unless prophylacticly *Test*

First-line drugs - safer, more effective

Second-line drugs - more toxic, less effective; used when resistance occurs with first-line agents

isoniazid

(INH)

A/T/A/T

Antiinfectives-Antituberculars (MC)-1st-line agents (SC)

Route: PO/IM; qD

Direct observation therapy (DOT) - to ensure compliance

Give Vit B₆ pyridoxine concomitantly (combo with INH)

Duration

-prophylaxis: daily for 6 mo.

-active infection: ex) for non-HIV: 4 first-line drugs for 4 mo. (IR); longer for resistant strains

Contraindications: liver disease

isoniazid

(INH)

A/T/A/T

Antiinfectives-Antituberculars (MC)-1st-line agents (SC)

Hepatotoxicity - AST, ALT

GI: N/V

Blood Dyscrasias: CBC - note RBC, H&H for anemia

check neuro status - muscle weakness, peripheral neuropathy

+ red-orange discoloration of body fluids

isoniazid

(INH)

A/T/A/T

Antiinfectives-Antituberculars (MC)-1st-line agents (SC)

--Non-pharmacologic to increase host resistance: balanced diet, rest, sunshine,

   fresh air

--Decrease spread - cover mouth, dispose of tissues; maintain respiratory isolation  

  (FYI - neg. pressure room), handwashing

--Follow strict drug regimen for full duration - Compliance is Key!

--Follow-up tests: liver enzymes, CBC, CXR, sputum specimen

--Report adverse effects, esp GI

--Avoid: ETOH

--If taking rifampin combo will have red tears, urine, sweat, saliva

--Drug-Drug interactions: phenytoin

amphotericin B

(Funfizone)

A/T/A/T

Antiinfectives - Antifungals (MC) - no subclasses

Route: IV

Baseline labs: BUN, Cr, AST, ALT, electrolytes

Often premedication is needed to offset s/sx with onset of tx (fever, chills, N/V) --> Antipyretic, antiemetic

Influse IV very slowly - monitor vitals during infusion

amphotericin B

(Funfizone)

A/T/A/T

Antiinfectives - Antifungals (MC) - no subclasses

Can be VERY toxic

Hypersensitivity

Onset of tx: N/V, chills, fever, HA (transient)

Nephrotoxicity - BUN, Cr

Hepatotoxicity - AST, ALT

Electrolyte imbalances - hypokalemia

CV: cardiac arrest, hypotension, dysrhythmias

BMD: Blood Dyscrasias - CBC - thrombocytopenia, anemia, leukopenia - develop other infections, bleeding tendencies

amphotericin B

(Funfizone)

A/T/A/T

Antiinfectives - Antifungals (MC) - no subclasses

Take premeds to decrease initial N/V, fever, chills
Follow-up labs as indicated to ID toxicities

Report: decreased UO & increased FV, increased GI sx

Maintain good fluid intake

AVOID: ETOH

Report infusion problems - IV site pain

Multiple drug-drug interactions - speak to MD re: any OTC, herbal tx

         --(too many to mention)

amphotericin B

(Funfizone)

Mechanism of Action

Antiinfectives - Antifungals (MC) - no subclasses

Fungicidal - increase permeability of fungal cell membrane --> allows intracellular contents to leak out

nystatin

(Mycostatin)

Mechanism of Action

Antiinfectives - Antifungals (MC) - no subclasses

Fungicidal - increase permeability of fungal cell membrane --> allows intracellular contents to leak out

nystatin

(Mycostatin)

A/T/A/T

Antiinfectives - Antifungals (MC) - no subclasses

Topical - creams, ointment, powder - clean affected area first

P0 - swish and swallow liquid for oral thrush (2 min) and apply via oral swabs - usual dose is 4 ml

Avoid eating/drinking for 30 min after

nystatin

(Mycostatin)

A/T/A/T

Antiinfectives - Antifungals (MC) - no subclasses

Topical: Skin irritation or rash (contact dermatitis)

           Check skin folds or wherever you apply

Oral: N/V/D

nystatin

(Mycostatin)

A/T/A/T

Antiinfectives - Antifungals (MC) - no subclasses

Use only as directed

Good skin or oral care

Avoid tight-fitting clothes for skin infections

Report: rash, skin irritations

fluconazole

(Diflucan)

Mechanism of Action

Antiinfectives - Antifungals (MC) - no subclasses

Fungicidal - increase permeability of fungal cell membrane --> allows intracellular contents to leak out

fluconazole

(Diflucan)

A/T/A/T

Antiinfectives - Antifungals (MC) - no subclasses

Route: PO/IV

Baseline labs: BUN, Cr, AST, ALT, electrolytes

Often premedication is needed to offset s/sx with onset of tx (fever, chills, N/V) --> Antipyretic, antiemetic

Influse IV very slowly - monitor vitals during infusion

fluconazole

(Diflucan)

A/T/A/T

Antiinfectives - Antifungals (MC) - no subclasses

GI: N/V/D

Hepatotoxicity

Reproductive: Menstrual abnormalities, gynecomastia, decreased libido

fluconazole

(Diflucan)

A/T/A/T

Antiinfectives - Antifungals (MC) - no subclasses

Take as ordered

AVOID: ETOH, OTC meds

Report: persistent GI s/sx; reproductive disturbances

Maintain good fluid intake

Follow-up labs as indicated

What are the factors that make

drug therapy difficult for malaria?

Requires multi-drug therapy

Prevention of relapse - tx latent forms due to complex life cycle of Plasmodium (it changes forms)

Prevention - before, during, and after treatment

Treatment - start as soon as sx appear

What are the factors that contribute

to parasitic infections?

Overpopulated areas with poor sanitation

Children - poor hygienic practices

Immunocompromised patients

chloroquine

(Aralen)

Mechanism of Action

Antiinfectives- Antiparasitics (MC)- Antiprotozoal (SC)

Malaria - acute stage, prophylaxis

metronidazole

(Flagyl)

Mechanism of Action

Antiinfectives- Antiparasitics (MC)- Antiprotozoal (SC)

Non-malarial parasitic infections

Anaerobic bacterial infections

mebendazole

(Vermox)

Mechanism of Action

Antiinfectives- Antiparasitics (MC)- Antihelminthic (SC)

Parasitic worms: round worm & pinworms

Characteristics of Viruses

Has protein coat (capsid) surrounded by lipid envelope (compromised of glycoprotein & protein spikes) - triggers immune response.

Enters host cell & uses its genetic materials for replication with the help of enzymes - viruses must be inside host cell to cause infection

Difficult to eliminate virus without injuring normal cells

Viral infections & Drug Therapy

(Implications)

Most self-limiting do not require pharmacotherapy e.g.rhinovifus

Some cause serious diseases: HIV, Herpesviruses

Challenges of antiviral therapy:

-rapid mutation

-difficult to avoid injuring normal cells

-each drug virus-specific

zidovudine

(Retrovir, AZT)

Goals of Therapy

Antiinfectives - Antivirals (MC) - Antiretrovirals (SC)

Decrease HIV RNA load - marker of dz progression

Increase lifespan and quality of life

Decrease transmission from mother to baby

Decrease drug resistance (HAART - combos)

Tx initiated with CD4 under 200 or if symptoms appear

nevirapine

(Viramune)

Goals of Therapy

Antiinfectives - Antivirals (MC) - Antiretrovirals (SC)

Decrease HIV RNA load - marker of dz progression

Increase lifespan and quality of life

Decrease transmission from mother to baby

Decrease drug resistance (HAART - combos)

Tx initiated with CD4 under 200 or if symptoms appear

saquinavir mesylate

(Forovase, Invirase)

Goals of Therapy

Antiinfectives - Antivirals (MC) - Antiretrovirals (SC)

Decrease HIV RNA load - marker of dz progression

Increase lifespan and quality of life

Decrease transmission from mother to baby

Decrease drug resistance (HAART - combos)

Tx initiated with CD4 under 200 or if symptoms appear

acyclovir

(Zovirax)

Goals of Therpy

Antiinfectives - Antivirals (MC) - Antiherpesvirals (SC)

Lessens severity and duration of acute herpes simplex symptoms

Prolongs latent period prevent recurrences

Does not cure