ANTIBIOTICSANTIVIRALSAANTIFUNGALS

ANTI-TUBERCULARANTIMALARIALANTIMALARIAL

ANTIHELMINTHICANTIHELMINTHICANTIMYCOBACTERIALANTIMYCOBACTERIAL

ANTIVIRALSANTIVIRALSANTIBIOTICSANTIBIOTICS

COMMONLY KNOWN AS COMMONLY KNOWN AS ANTIMICROBIALSANTIMICROBIALS

Winter 2013 1

DRUGS FOR BUGS ??

WHAT IS AN INFECTION?WHAT IS AN INFECTION?A disease or condition caused by a microorganism that releases toxins or invade body tissues◦Localized infection◦Systemic infection

Winter 2013 2

WHO IS MORE LIKELY TO WHO IS MORE LIKELY TO GET AN INFECTION?GET AN INFECTION?

SKIN NOT INTACT

BLOOD SUPPLY IMPAIRED

NEUTROPENIAMALNUTRITIONSUPPRESSION OF

NORMAL BACTERIAL BALANCE

SUPPRESSION OF THE IMMUNE SYSTEM

DIABETESCHRONIC

ILLNESSADVANCED AGE

Winter 2013 3

Winter 2013 4

Infections: Sites of OriginInfections: Sites of Origin

Community-associated infections◦An infection that is acquired by a person who has not been hospitalized or had a medical procedure (such as dialysis, surgery, catheterization) within the past year

Winter 2013 5

Infections: Sites of Origin Infections: Sites of Origin (cont’d)(cont’d)

Healthcare-associated infections◦Contracted in a hospital or institutional

setting◦Were not present or incubating in the patient

on admission to the facility◦More difficult to treat because causative

microorganisms are often drug resistant and the most virulent

◦One of top ten leading causes of death in the U.S.

◦MRSA most common◦Previously known as nosocomial

Winter 2013 6

Healthcare-Associated Healthcare-Associated Infections: PreventionInfections: Prevention

Hand washingAntisepticsDisinfectants

Winter 2013 7

Healthcare-Associated Healthcare-Associated Infections: Prevention Infections: Prevention (cont’d)(cont’d)Disinfectant

◦Kills organisms◦Used only on nonliving objects

Antiseptic◦Generally only inhibits the growth of microorganisms but does not necessarily kill them

◦Applied exclusively to living tissue

FUNCTIONS OF ANTIBIOTICSFUNCTIONS OF ANTIBIOTICS

Winter 2013 8

IDENTIFICATION OF BACTERIAIDENTIFICATION OF BACTERIA

GRAM TESTINGCULTURE AND SENSITIVITY

TESTINGSEND SPECIMEN FIRST !!!!!

START ANTIBIOTIC BEFORE CULTURE RESULTS ARE KNOWN (EMPIRIC THERAPY)

RX MAY CHANGE WHEN CULTURE IS GROWN

Winter 2013 9

Winter 2013 10

BACTERIAL RESISTANCE

Bacterial resistance◦PENICILLINASE USED BY BACTERIA TO DESTROY PCN

◦BETA-LACTAMASE BREAKS DOWN THE STRUCTURE OF THE ABX INACTIVATING THE DRUG

Winter 2013 11

ANTIMICROBIAL RESISTANCE

UNWISE USE OF ANTIBIOTICS◦ANTIBIOTICS ARE NOT EFFECTIVE

AGAINST VIRAL INFECTIONS

◦WHEN VIRAL SYMPTOMS PERSIST, ABX WILL BE USED FOR A SECONDARY BACTERIAL INFECTION

ANTIBIOTICS MAY BE PRESCRIBED AS PROPHYLACTIC TO ANOTHER TREATMENT OR PROCEDURE

Winter 2013 12

ANTIMICROBIAL RESISTANCE

METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS MRSA◦HAND WASHING AND GLOVING

◦GOAL IS TO AVOID HEALTHCARE ASSOCIATED INFECTIONS

◦“COLONIZED” MEANS HARBORS THE BACTERIA

Winter 2013 13

ANTI-INFECTIVES / ANTIBIOTICS

PROPER DOSE AND DURATION OF THERAPY◦ AVERAGE OF 7 – 10 DAYS OF THERAPY

◦ SPECIFY TIME OF DAY TO TAKE THE DRUGS TO MAINTAIN THERAPEUTIC LEVELS

◦ PATIENT MUST COMPLETE ENTIRE RX

◦ NEVER SAVE FOR USE AT ANOTHER TIME

◦ NEVER SHARE WITH ANOTHER PERSON

Winter 2013 14

ADVERSE REACTIONS TO ABXHYPERSENSITIVITY (allergy)

Requires at least one exposure to the drug

◦Mild – Rash, pruritus, urticaria

◦Severe – Anaphylaxis

Laryngospasms (wheezing)DyspneaDecrease in blood pressure

Winter 2013 15

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ADVERSE REACTIONS TO ABX

CROSS-SENSITIVITY REACTIONS◦If allergic to one antibiotic, allergic to antibiotics from same family

◦EXAMPLE – ALLERGY TO PCN, ALSO MAY BE ALLERGIC TO CEPHALOSPORIN

Winter 2013 18

STEVENS-JOHNSON SYNDROMESTEVENS-JOHNSON SYNDROME

◦Severe (can be fatal) hypersensitivity reaction caused by reaction to a medication

◦Typically involves the skin and mucous membranes developing severe inflammation progressing to necrosis of the tissues. Can also progress to the lining of internal organs.

◦TABER’S – TOXIC EPIDERMAL NECROLYSIS

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SUPERINFECTION

◦A secondary infection that occurs during antibiotic therapy in which normal flora are destroyed

Winter 2013 23

SuperinfectionLOCATION OF INFECTION

◦GROIN◦AXILLA◦MOUTH◦UNDER BREAST TISSUE◦ANY WARM MOIST AREA

OFFENDING ORGANISM◦YEAST◦BACTERIA

Winter 2013 24

Candida Yeast / Thrush

Winter 2013 25

NURSING RESPONSIBILITIESPATIENT’S RESPONSE TO THERAPY

◦ EVALUATE TEMPERATURE, APPETITE AND GENERAL LEVEL OF WELLNESS

FLUID INTAKE ◦ DRUGS ARE NEPHROTOXIC◦ ADVISE PATIENT TO INCREASE PO INTAKE◦ FULL GLASS OF WATER WITH MED◦ WATER WILL DECREASE GI SYMPTOMS

OTHER MEDS◦ LOOK FOR CONTRAINDICATED MEDS◦ LOOK FOR HERBAL INTERACTIONS

Winter 2013 26

CHARACTERISTICS OF ANTIBACTERIALS

BROAD SPECTRUM

NARROW SPECTRUM

MECHANISM OF ACTION

Winter 2013 27

BROAD SPECTRUM BROAD SPECTRUM ANTIBIOTICANTIBIOTIC

AN ANTIBIOTIC THAT IS EFFECTIVE AGAINST BOTH GRAM-NEGATIVE AND GRAM-POSITIVE BACTERIAL SPECIES

BROAD-SPECTRUM AGENTS INCLUDE ◦CARBAPENEMS ◦EXTENDED-SPECTRUM CEPHALOSPORINS◦BETA-LACTAM/BETA-LACTAMASE

INHIBITOR COMBINATIONS◦FLUOROQUINOLONES

Winter 2013 28

NARROW SPECTRUM NARROW SPECTRUM ANTIBIOTICANTIBIOTIC

AN ANTIBIOTIC EFFECTIVE AGAINST A LIMITED NUMBER OF MICROORGANISMS.

EXAMPLES OF NARROW-SPECTRUM AGENTS INCLUDE

PENICILLIN G MACROLIDES NITROFURANTOIN METRONIDAZOLE AZTREONAM NALIDIXIC ACID

Winter 2013 29

MECHANISMS OF ACTIONMECHANISMS OF ACTIONInhibition of bacterial cell wall

synthesisInhibition of protein synthesisDisruption of cell membranesInhibits cell reproductionInhibits cell metabolism

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Winter 2013 31

Antibiotics: SulfonamidesAntibiotics: SulfonamidesOne of the first groups of antibiotics

◦Sulfadiazine◦Sulfamethoxazole◦Sulfisoxazole

Often combined with another antibiotic◦Sulfamethoxazole combined with

trimethoprim (a nonsulfonamide antibiotic), known as Bactrim, Septra, or co-trimoxazole (SMX-TMP)

◦This combination is used commonly

Winter 2013 32

Sulfonamides: Sulfonamides: Mechanism of ActionMechanism of Action

Bacteriostatic actionPrevent synthesis of folic

acid required for synthesis of purines and nucleic acid

Do not affect human cells or certain bacteria

Only affect organisms that synthesize their own folic acid

Winter 2013 33

Sulfonamides: IndicationsSulfonamides: Indications

Effective against both gram-positive and

gram-negative bacteria Treatment of UTIs caused by susceptible

strains of:◦Enterobacter , Escherichia coli, Klebsiella ,

Proteus mirabilis, Proteus vulgaris, Staphylococcus aureus

Winter 2013 34

Sulfonamides: Indications Sulfonamides: Indications (cont’d)(cont’d)

Urinary tract infectionsUpper respiratory tract infections

Winter 2013 35

Sulfonamides: Sulfonamides: Adverse EffectsAdverse Effects

Body System Adverse EffectsBlood Hemolytic and aplastic

anemia, agranulocytosis, thrombocytopenia

Integumentary Photosensitivity, exfoliative dermatitis, Stevens-Johnson syndrome, epidermal necrolysis

Winter 2013 36

Sulfonamides: Sulfonamides: Adverse Effects (cont’d)Adverse Effects (cont’d)

Body System Adverse EffectsGI Nausea, vomiting,

diarrhea, pancreatitisOther Convulsions,

crystalluria,toxic nephrosis,

headache, peripheral neuritis, urticaria

http://www.youtube.com/watch?v=ifQMm2xuyqc&playnext=1&list=PL27024F7449C9E999&feature=results_main

Winter 2013 37

Beta-Lactam Antibiotics AntibioticsPenicillinsCephalosporinsCarbapenemsMonobactams

Winter 2013 38

Winter 2013 39

Penicillins Penicillins First introduced in the 1940sBactericidal: inhibit cell wall

synthesisKill a wide variety of bacteriaBacteria produce enzymes

capable of destroying penicillins◦These enzymes are known as beta-

lactamases◦As a result, the medication is not

effective

Winter 2013 40

Penicillins

Natural penicillinsPenicillinase-resistant penicillins

AminopenicillinsExtended-spectrum penicillins

Winter 2013 41

Penicillins (cont’d) (cont’d)

Natural penicillins◦penicillin G, penicillin V potassium

Penicillinase-resistant drugs◦cloxacillin, dicloxacillin, nafcillin, oxacillin

Winter 2013 42

Penicillins (cont’d) (cont’d)

Aminopenicillins◦amoxicillin, ampicillin

Extended-spectrum drugs◦piperacillin, ticarcillin, carbenicillin

◦Usually used with other drugs; rarely used alone

Winter 2013 43

Penicillins (cont’d) (cont’d)

Chemicals have been developed to inhibit these enzymes:◦Clavulanic acid◦Tazobactam◦Sulbactam

These chemicals bind with beta-lactamase and prevent the enzyme from breaking down the penicillin, thus making the drug more effective

Winter 2013 44

Penicillins (Penicillins (cont’d))

Penicillin–beta-lactamase inhibitor combination drugs◦ Ampicillin + sulbactam = Unasyn

◦ Amoxicillin + clavulanic acid = Augmentin

◦ Ticarcillin + clavulanic acid = Timentin

◦ Piperacillin + tazobactam = Zosyn

Winter 2013 45

Penicillins: Penicillins: Indications

Prevention and treatment of infections caused by susceptible bacteria, such as:◦Gram-positive bacteria◦Streptococcus, Enterococcus, Staphylococcus

Winter 2013 46

Penicillins: Adverse Penicillins: Adverse Effects

Allergic reactions occur in 0.7% to 4% of cases ◦Urticaria, pruritus, angioedema

Those allergic to penicillins have a fourfold to sixfold increased risk of allergy to other beta-lactam antibiotics

Cross-sensitivity between penicillins and cephalosporins is between 1% and 4%

Winter 2013 47

Penicillins: Penicillins: Adverse Effects (cont’d)Effects (cont’d)

Common adverse effects◦Nausea, vomiting, diarrhea,

abdominal painOther adverse effects are

less common

Winter 2013 48

Penicillins: Interactions

MANY interactions!◦NSAIDs◦Oral contraceptives –

Decreases effectiveness◦Warfarin – Enhanced

anticoagulant effect r/t decrease in intestinal flora producing vitamin K

◦Others

MRSAMRSAMETHICILLIN RESISTANT

STAPHYLOCOCCUS AUREUS◦Hand washing and gloving

◦Goal is to avoid healthcare associated infections

◦“Colonized” means harbors the bacterial infection

Winter 2013 49

NURSING CONSIDERATIONSNURSING CONSIDERATIONSFOR PENICILLINFOR PENICILLIN

◦Take with a full glass of water

◦Do not skip doses

◦Take all of the medication as prescribed

◦Notify MD of adverse reactions

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Cephalosporins

First generationSecond generationThird generationFourth generationFifth generation (not yet

marketed)

Winter 2013 53

Cephalosporins (cont’d)Cephalosporins (cont’d)

Semisynthetic derivatives Structurally and

pharmacologically related to penicillins

Bactericidal actionBroad spectrumDivided into groups according to

their antimicrobial activity

Winter 2013 54

Cephalosporins: Cephalosporins: First First Generation

Good gram-positive coveragePoor gram-negative coverageParenteral and PO formsExamples

◦ cefadroxil◦ cephradine◦ cefazolin◦ cephalexin

Winter 2013 55

Cephalosporins: Cephalosporins: First Generation (cont’d)First Generation (cont’d)

Used for surgical prophylaxis, and for susceptible staphylococcal infections◦cefazolin (Ancef and Kefzol): IV or IM◦cephalexin (Keflex): PO

Winter 2013 56

Cephalosporins: : Second GenerationSecond Generation

Good gram-positive coverage Better gram-negative coverage

than first generation Examples:

cefaclorcefprozilcefoxitincefuroxime loracarbefcefotetan

Winter 2013 57

Cephalosporins: : Second Generation Second Generation

(cont’d)(cont’d)cefoxitin (Mefoxin): IV and IM

◦Used prophylactically for abdominal or colorectal surgeries

◦Also kills anaerobescefuroxime

◦Zinacef is parenteral form; Ceftin is PO◦Surgical prophylaxis◦Does not kill anaerobes

Winter 2013 58

Cephalosporins: Third Generation

Most potent group against gram-negative bacteria Less active against gram-positive bacteria Examples◦ceftibuten◦cefotaxime◦ceftazidime◦cefdinir◦ceftizoxime◦ceftriaxone◦ceftazidime

Winter 2013 59

Cephalosporins: Cephalosporins: Third Generation (cont’d)Third Generation (cont’d)

ceftriaxone (Rocephin)◦IV and IM, long half-life, once-a-day dosing

◦Elimination is primarily hepatic◦Easily passes meninges and diffused into CSF to treat CNS infections

Winter 2013 60

Cephalosporins: Third Generation (cont’d)ceftazidime (Ceptaz)

◦IV and IM forms◦Excellent gram-negative

coverage◦Used for difficult-to-treat

organisms such as Pseudomonas ◦Eliminated by renal instead of

biliary route◦Excellent spectrum of coverage◦Resistance is limiting usefulness

Winter 2013 61

Cephalosporins: Cephalosporins: Fourth Generation Generation

Broader spectrum of antibacterial activity than third generation, especially against gram-positive bacteria

Uncomplicated and complicated UTI◦cefepime (Maxipime)

Winter 2013 62

Cephalosporins: : Fifth GenerationFifth Generation

Ceftobipriole (not available)Broader spectrum of antibacterial

activityEffective against a wide variety of

organisms◦MRSA◦Pseudomonas

Winter 2013 63

Cephalosporins: : Adverse EffectsAdverse Effects

Similar to penicillins◦Mild diarrhea, abdominal

cramps, rash, pruritus, redness, edema

Potential cross-sensitivity with penicillins if allergies exist

Winter 2013 64

CarbapenemsVery broad-spectrum antibacterial

actionReserved for complicated body

cavity and connective tissue infections

May cause drug-induced seizure activity◦This risk can be reduced with proper

dosageAll given parenterally

Winter 2013 65

Carbapenemsimipenem/cilastatin (Primaxin)

◦Used for treatment of bone, joint, skin, and soft-tissue infections; many other uses

◦Cilastatin inhibits an enzyme that breaks down imipenem

meropenem (Merrem)ertapenem (Invanz)doripenem (Doribax)

MonobactamsMonobactams

Aztreonem (Azactam) Only drug in this catagory

Beta-lactam antibioticGram negative bacteria

◦Inhibits cell wall synthesisCommon adverse effects

Winter 2013 66

Winter 2013 67

Macrolides

erythromycin (E-mycin, E.E.S, others)

azithromycin (Zithromax)◦“Z-Pack” 3 – 5 day dose pack

clarithromycin (Biaxin)dirithromycin

http://www.youtube.com/watch?v=2g-2oLb0IQw&feature=related

Winter 2013 68

Macrolides::Mechanism of ActionMechanism of Action

Prevent protein synthesis within bacterial cells

Considered bacteriostaticBacteria will eventually dieIn high enough concentrations,

may also be bactericidal

Winter 2013 69

Macrolides: Macrolides: Indications Strep infections

◦Streptococcus pyogenes

(group A beta-hemolytic streptococci) Mild to moderate URI and LRI

◦Haemophilus influenzae Spirochetal infections

◦Syphilis and Lyme disease Gonorrhea, Chlamydia, Mycoplasma

Winter 2013 70

Macrolides: Macrolides: Indications (cont’d)(cont’d)azithromycin and clarithromycin

◦Recently approved for mycobacterium avium-

intracellular complex infection (opportunistic

infection associated with HIV/AIDS)clarithromycin

◦Recently approved for use in combination with omeprazole for treatment of active ulcer disease associated with Helicobacter pylori infection

Macrolides: Macrolides: Indications (cont’d)(cont’d)Fidaxomicin (Dificid)

◦Treatment of Clostridium difficile-associated diarrhea in adults ≥18 years of age.

◦Following oral administration, only minimal systemic absorption occurs; remains mainly confined to and acts locally in the GI tract.

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Winter 2013 72

Macrolides: Adverse : Adverse EffectsEffects

GI effects, primarily with erythromycin◦Nausea, vomiting, diarrhea,

hepatotoxicity, flatulence, jaundice, anorexia

◦Newer drugs, azithromycin and clarithromycin: fewer GI adverse effects, longer duration of action, better efficacy, better tissue penetration

Winter 2013 73

Ketolide

telithromycin (Ketek)◦Only drug in this class◦Better antibacterial coverage than

macrolides◦Active against gram-positive bacteria,

including multi–drug-resistant strains of S. pneumoniae

◦Associated with severe liver disease◦Use is limited

Winter 2013 74

Tetracyclines

demeclocycline (Declomycin)

oxytetracyclinetetracyclinedoxycycline (Doryx,

Vibramycin)minocyclinetigecycline (Tygacil)

Winter 2013 75

Tetracyclines (cont’d) (cont’d)

Natural and semisyntheticObtained from cultures of

StreptomycesBacteriostatic—inhibit bacterial

growthInhibit protein synthesisStop many essential functions

of the bacteria

Winter 2013 76

Tetracyclines: Tetracyclines: Indications

Broad spectrum◦Gram-negative and gram-positive

organisms, protozoa, Mycoplasma, Rickettsia, Chlamydia, syphilis, Lyme disease, acne, others

Demeclocycline is also used to treat SIADH by inhibiting the action of ADH

Winter 2013 77

Tetracyclines (cont’d)Tetracyclines (cont’d)

Bind (chelate) to Ca2+ and Mg2+ and Al3+ ions to form insoluble complexes

Thus, dairy products, antacids, and iron salts reduce oral absorption of tetracyclines

Should not be used in children under age 8 or in pregnant/lactating women because tooth discoloration will occur if the drug binds to the calcium in the teeth

Winter 2013 78

Tetracyclines: Adverse : Adverse EffectsEffects

Strong affinity for calcium ◦Discoloration of permanent teeth and tooth enamel in fetuses and children, or nursing infants if taken by the mother

◦May retard fetal skeletal development if taken during pregnancy

◦ http://www.youtube.com/watch?v=AMAqU7MJ_sc

Winter 2013 79

Tetracyclines: Adverse : Adverse Effects (cont’d)Effects (cont’d)

Alteration in intestinal flora may result in:◦Superinfection (overgrowth of

nonsusceptible organisms such as Candida)

◦Diarrhea◦Pseudomembranous colitis

Winter 2013 80

Tetracyclines: Tetracyclines: Adverse Effects (cont’d)Effects (cont’d)

May also cause:◦Vaginal candidiasis◦Gastric upset◦Enterocolitis◦Maculopapular rash◦Other effects

Winter 2013 81

Antibiotic Therapy: Antibiotic Therapy: ToxicitiesToxicities Ototoxicity

◦ Temporary or permanent hearing loss, balance problems

Nephrotoxicity◦ Varying degrees of reduced renal function◦ Rising serum creatinine may indicate

reduced creatinine clearanceMonitor trough levels every 5 to 7 days while on therapy or as orderedMonitor serum creatinine levels at least every 3 days as an index of renal function

82Winter 2013

Aminoglycosides

gentamicin (Garamycin)neomycin (Neo-fradin)tobramycin (Nebcin)amikacin (Amikin)kanamycinstreptomycin

83Winter 2013

Aminoglycosides (cont’d) (cont’d)Natural and semisyntheticProduced from StreptomycesPoor oral absorption; no PO formsVery potent antibiotics with

serious toxicitiesBactericidal; prevent protein

synthesisKill mostly gram-negative

bacteria; some gram-positive also

84Winter 2013

Aminoglycosides: : IndicationsIndications

Used to kill gram-negative bacteria such as Pseudomonas, E. coli, Proteus, Klebsiella, Serratia

Often used in combination with other antibiotics for synergistic effects

Used for certain gram-positive infections that are resistant to other antibiotics

85Winter 2013

Aminoglycosides: Aminoglycosides: Indications (cont’d)Indications (cont’d)

Aminoglycosides are poorly absorbed through the GI tract, and given parenterally

Exception: neomycin◦Given orally to decontaminate

the GI tract before surgical procedures

◦Also used as an enema for this purpose

86Winter 2013

Aminoglycosides: Aminoglycosides: Adverse Adverse Effects

Cause serious toxicities◦Nephrotoxicity (renal damage)◦Ototoxicity (auditory impairment

and vestibular impairment [eighth cranial nerve])

Must monitor drug levels to prevent toxicities

87Winter 2013

Winter 2013 88

Aminoglycosides: Aminoglycosides: Adverse Effects (cont’d) Effects (cont’d)Ototoxicity and nephrotoxicity are

the most significant◦Headache◦Paresthesia◦Fever◦Superinfections◦Vertigo◦Skin rash◦Dizziness

89Winter 2013

Quinolones

ciprofloxacin (Cipro)norfloxacin (Noroxin)levofloxacin (Levaquin)moxifloxacin (Avelox)

90Winter 2013

Quinolones (cont’d)(cont’d)

Also called “fluoroquinolones”Excellent oral absorptionAbsorption reduced by

antacidsEffective against gram-

negative organisms and some gram-positive organisms

91Winter 2013

Quinolones: Quinolones: Mechanism of ActionMechanism of Action

BactericidalAlter DNA of bacteria,

causing deathDo not affect human DNA

92Winter 2013

Quinolones: IndicationsQuinolones: Indications

Gram-negative bacteria such as pseudomonas

Respiratory infectionsBone and joint infectionsGI infectionsSkin infectionsSexually transmitted diseasesAnthrax

93Winter 2013

Fluoroquinolones: Fluoroquinolones: Adverse EffectsAdverse Effects

Body System Adverse EffectsCNS Headache, dizziness,

fatigue, depression, restlessness, insomnia

GI Nausea, vomiting, diarrhea, constipation, thrush, increased liver function studies, others

Cardiac Prolonged QT interval

94Winter 2013

Fluoroquinolones: Fluoroquinolones: Adverse Effects (Adverse Effects (cont’d))

Body System Adverse EffectsIntegumentary Rash, pruritus,

urticaria, flushing, photosensitivity (with lomefloxacin)

Other Fever, chills, blurred vision, tinnitus

Black box warning: increased risk of tendonitis and tendon rupture

95Winter 2013

Other Other Antibioticsclindamycin (Cleocin)linezolid (Zyvox)metronidazole (Flagyl)nitrofurantoin (Macrodantin)quinupristin and Dalfopristin

(Synercid)daptomycin (Cubicin)vancomycin (Vancocin)colistimethate (Coly-mycin)

96Winter 2013

Other Antibiotics (cont’d) Antibiotics (cont’d)

clindamycin (Cleocin)◦Used for chronic bone infections, GU

infections, intra-abdominal infections, other serious infections

◦May cause pseudomembranous colitis

97Winter 2013

Other Other Antibiotics (cont’d) (cont’d)linezolid (Zyvox)

◦New class: oxazolidinones◦Used to treat vancomycin-resistant

Enterococcus faecium (VREF, VRE), hospital-acquired skin and skin structure infections, including those with MRSA

◦May cause hypotension, serotonin syndrome if taken with SSRIs, and reactions if taken with tyramine-containing foods

98Winter 2013

Other Antibiotics (cont’d) Antibiotics (cont’d)metronidazole (Flagyl)

◦Used for anaerobic organisms◦Intra-abdominal and gynecologic

infections◦Protozoal infections◦Several drug interactions

99Winter 2013

Other Antibiotics (cont’d) Antibiotics (cont’d)nitrofurantoin (Macrodantin)

◦Primarily used for UTIs (E. coli, S. aureus, Klebsiella , Enterobacter)

◦Use carefully if renal function is impaired

◦Drug concentrates in the urine◦May cause fatal hepatotoxicity◦Usually well-tolerated if patient is

kept well-hydrated

100

Winter 2013

Other Antibiotics (cont’d) Antibiotics (cont’d)quinupristin and dalfopristin

(Synercid)◦30:70 combination, work

synergistically◦Used for bacteremia and infections

caused by vancomycin-resistant Enterococcus (VRE) and other complicated skin infections

◦May cause arthralgias, myalgias

101

Winter 2013

Other Other Antibiotics (cont’d) (cont’d)daptomycin (Cubicin)

◦New class: lipopeptide◦Used to treat complicated skin and

soft-tissue infections

102

Winter 2013

Other Antibiotics (cont’d) Antibiotics (cont’d)vancomycin (Vancocin)

◦Natural, bactericidal antibiotic◦Destroys cell wall◦Treatment of choice for MRSA and other

gram-positive infections◦Must monitor blood levels to ensure

therapeutic levels and prevent toxicity◦May cause ototoxicity and nephrotoxicity◦Should be infused over 60 minutes◦Rapid infusions may cause hypotension

103

Winter 2013

Other Antibiotics (cont’d) Antibiotics (cont’d)vancomycin (Vancocin) (cont’d)

◦Monitor IV site closely◦Red man syndrome may occur

Flushing/itching of head, neck, face, upper trunk

Antihistamine may be ordered to reduce these effects

◦Ensure adequate hydration (2 L fluids/24 hr) if not contraindicated to prevent nephrotoxicity

◦Monitor trough levels carefully

104

Winter 2013

Nursing Implications Nursing Implications

It is ESSENTIAL to obtain cultures from appropriate sites BEFORE beginning antibiotic therapy

Instruct patients to take antibiotics exactly as prescribed and for the length of time prescribed; they should not stop taking the medication early when they feel better

105

Winter 2013

Nursing Nursing Implications (cont’d)(cont’d)

Aminoglycosides◦Monitor peak and trough blood levels of these drugs to prevent nephrotoxicity and ototoxicity

◦Symptoms of ototoxicity include dizziness, tinnitus, and hearing loss

◦Symptoms of nephrotoxicity include urinary casts, proteinuria, and increased BUN and serum creatinine levels

106

Winter 2013

ANTIVIRAL MEDICATIONS

Winter 2013 107

Understanding Viruses VirusesViral replication

◦A virus cannot replicate on its own

◦It must attach to and enter a host cell

◦It then uses the host cell’s energy to synthesize protein, DNA, and RNA

108

Winter 2013

Understanding Viruses Viruses (cont’d)(cont’d)

Viruses are difficult to kill because they live inside the cells◦ Any drug that kills a virus may also kill cells

109

Winter 2013

Viral Viral IllnessesMost viral illnesses are

bothersome, but survivableEffective vaccines have

prevented some illnessesEffective drug therapy is

available for a small number of viral infections

110

Winter 2013

Antiviral Drugs DrugsAntiviral drugs kill or suppress

the virus by destroying virions or inhibiting ability to replicate viruses controlled by current antiviral therapy

111

Winter 2013

Antiviral Drugs (cont’d) Drugs (cont’d)Viruses controlled by current

antiviral therapyCytomegalovirus (CMV)Hepatitis virusesHerpes virusesHuman immunodeficiency virus

(HIV)Influenza viruses (the “flu”)Respiratory syncytial virus (RSV)

112

Winter 2013

Antiviral Drugs (cont’d) Drugs (cont’d)Key characteristics of antiviral drugsAble to enter the cells infected

with virusInterfere with viral nucleic acid

synthesis and/or regulationSome drugs interfere with ability of

virus to bind to cells

Some drugs stimulate the body’s immune system

113

Winter 2013

Antiviral Drugs (cont’d) Drugs (cont’d)Opportunistic infectionsOccur in immunocompromised

patientsWould not normally harm an

immunocompetent personRequire long-term prophylaxis

and antiinfective drug therapy

Can be other viruses, fungi, bacteria, or protozoa

114

Winter 2013

Antiviral Drugs (cont’d) Drugs (cont’d)Antiviral drugs

◦Used to treat infections caused by viruses other than HIV

Antiretroviral drugs◦Used to treat infections caused by

HIV, the virus that causes AIDS

115

Winter 2013

Virus Infections InfectionsHerpes-simplex viruses

◦HSV-1 (oral herpes)◦HSV-2 (genital herpes)

Human herpesvirus/VZV◦Chickenpox and shingles (HHV-3 or VZV)

Shingles http://www.youtube.com/watch?v=MEvyptIJsuE

◦Epstein-Barr (HHV-4)◦Cytomegalovirus (HHV-5)◦Kaposi’s sarcoma (HHV-8)

116

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Antiviral Drugs (non-HIV) Drugs (non-HIV)Mechanism of action

◦Inhibit viral replicationUsed to treat non-HIV viral

infections◦Influenza viruses◦HSV, VZV◦CMV◦Hepatitis A, B, C (HAV, HBV, HCV)

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Winter 2013

Antiviral Drugs (non-HIV) Drugs (non-HIV) (cont’d) (cont’d)

Adverse effects◦Vary with each drug◦Healthy cells are often killed also, resulting in serious toxicities

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Winter 2013

Antiviral Drugs (non-HIV) Drugs (non-HIV) (cont’d)(cont’d)

amantadine (Symmetrel) ◦ Narrow antiviral spectrum; active

only against influenza A◦ 2008 CDC guidelines do not

recommend use for treatment or prevention of flu

◦ CNS effects: insomnia, nervousness, lightheadedness

◦ GI effects: anorexia, nausea, others

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Winter 2013

Antiviral Drugs (non-HIV) Drugs (non-HIV) (cont’d)(cont’d)

rimantadine (Flumadine) ◦ Same spectrum of activity,

mechanism of action, and indications as amantadine

◦ Fewer CNS adverse effects◦ Causes GI upset

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Winter 2013

Antiviral Drugs (non-HIV) Drugs (non-HIV) (cont’d) (cont’d)

acyclovir (Zovirax) ◦ Synthetic nucleoside analog◦ Used to suppress replication of:

HSV-1, HSV-2, VZV

◦ Drug of choice for treatment of initial and recurrent episodes of these infections

◦ Oral, topical, parenteral forms

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Winter 2013

Antiviral Drugs (non-HIV) Drugs (non-HIV) (cont’d)(cont’d)

ganciclovir (Cytovene)◦ Synthetic nucleoside analog◦ Used to treat infection with

cytomegalovirus (CMV)◦ Oral, parenteral forms◦ CMV retinitis

Ophthalmic form surgically implanted Ocular injection (fomivirsen)

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Winter 2013

Antiviral Drugs (non-HIV): Drugs (non-HIV): Dose-Limiting ToxicitiesDose-Limiting Toxicities

ganciclovir ◦ Bone marrow toxicity

foscarnet and cidofovir◦ Renal toxicity

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Winter 2013

Antiviral Drugs (non-HIV): Antiviral Drugs (non-HIV): Neuraminidase Neuraminidase Inhibitors

oseltamivir (Tamiflu) and zanamivir (Relenza)◦ Active against influenza types A and B◦ Reduce duration of illness◦ Oseltamivir: causes nausea and vomiting◦ Zanamivir: causes diarrhea, nausea,

sinusitis◦ Treatment should begin within 2 days of

influenza symptom onset

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Winter 2013

Antiviral Antiviral Drugs (non-HIV): (non-HIV): RibavirinRibavirin

Synthetic nucleoside analogGiven orally, or oral or nasal

inhalationInhalation form (Virazole) used

for hospitalized infants with RSV infections

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Winter 2013

HIV and AIDSHIV and AIDSHuman immunodeficiency virus

(HIV) infection and acquired immune deficiency syndrome (AIDS)◦ELISA (enzyme-linked immunosorbent

assay) Detects HIV exposure based on presence of

human antibodies to the virus in the blood

◦Retrovirus◦Transmitted by sexual activity,

intravenous drug use, perinatally from mother to child

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Winter 2013

Four Stages of HIV Four Stages of HIV Infection*Infection*

Stage 1: asymptomatic infectionStage 2: early, general symptoms of

diseaseStage 3: moderate symptomsStage 4: severe symptoms, often

leading to death

*WHO model

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Winter 2013

Opportunistic Infections Infections

Protozoal◦Toxoplasmosis of the brain, others

Fungal◦Candidiasis of the lungs,

esophagus, trachea◦Pneumocystis jirovecii pneumonia,

othersViral

◦CMV disease, HSV infection, others

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Winter 2013

Opportunistic Infections Infections (cont’d)(cont’d)

Bacterial◦Various mycobacterial infections◦Extrapulmonary TB

Opportunistic neoplasias◦Kaposi’s sarcoma, others

HIV wasting syndrome◦Major weight loss, chronic diarrhea,

chronic fever

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Winter 2013

Antiretroviral Drugs Drugs

HAARTHighly active antiretroviral

therapyIncludes at least three

medications◦“Cocktails”

These medications work in different ways to reduce the viral load

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Winter 2013

Antiretroviral Drugs Drugs (cont’d)(cont’d)

Reverse transcriptase inhibitors (RTIs)◦ Block activity of the enzyme reverse transcriptase,

preventing production of new viral DNAProtease inhibitors (PIs)

◦ Inhibit the protease retroviral enzyme, preventing viral replication

Fusion inhibitors◦ Inhibit viral fusion, preventing viral replication

Entry inhibitor-CCR5 coreceptor antagonists

HIV integrase strand transfer inhibitors

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Winter 2013

Antiretroviral Drugs Drugs (cont’d)(cont’d)

Reverse transcriptase inhibitors (RTIs)◦Nucleoside RTIs (NRTIs)◦Nonnucleoside RTIs (NNRTIs)

Examples◦abacavir (Ziagen)◦delavirdine (Rescriptor)◦didanosine (Videx)◦lefavirenze (Sustiva)

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Winter 2013

Antiretroviral Drugs Drugs (cont’d)(cont’d)

zidovudine (Retrovir)◦First anti-HIV medication◦Nucleoside reverse transcriptase inhibitor

◦Can be given to pregnant HIV-positive women and newborn babies to prevent maternal transmission of HIV

◦Major dose-limiting adverse effect: bone marrow suppression

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Winter 2013

Antiretroviral Drugs Drugs (cont’d)(cont’d)

Protease inhibitors (PIs)◦Inhibit the protease retroviral enzyme, preventing viral replication

◦amprenavir (Agenerase)◦indinavir (Crixivan)◦nelfinavir (Viracept)◦ritonavir (Norvir)

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Winter 2013

Antiretroviral Drugs Drugs (cont’d)(cont’d)

Fusion inhibitors◦Inhibit viral fusion, preventing viral replication

◦A newer class of antiretroviral drugs

◦Example: enfuvirtide (Fuzeon)

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Winter 2013

Antiretroviral Drugs Drugs (cont’d)(cont’d)

CCR5 antagonist◦maraviroc (Selzentry)

HIV integrase strand transfer inhibitor◦raltegravir (Isentress)

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Winter 2013

Antiretroviral Drugs Drugs (cont’d)(cont’d)

Combinations of multiple antiretroviral medications are common

Adverse effects vary with each drug and may be severe; monitor for dose-limiting toxicities

Monitor for signs of opportunistic diseases

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Winter 2013

Nursing Nursing Implications Be sure to teach proper application

technique for ointments, aerosol powders, and so on

Emphasize hand washing before and after administration of medications to prevent site contamination and spread of infection

Instruct patients to wear a glove or finger cot when applying ointments or solutions to affected areas

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Winter 2013

Antitubercular Drugs

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Winter 2013

Antitubercular DrugsTuberculosis (TB)

◦Caused by Mycobacterium tuberculosis

Antitubercular drugs treat all forms of Mycobacterium

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Winter 2013

Mycobacterium Infections

Common infection sitesLung (primary site)BrainBoneLiverKidney

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Winter 2013

Mycobacterium Infections (cont’d)

Aerobic bacillusPassed from infected:

◦Humans◦Cows (bovine) and birds (avian)

Much less common

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Winter 2013

Mycobacterium Infections (cont’d)

Tubercle bacilli are conveyed by dropletsDroplets are expelled by coughing or

sneezing, and then gain entry into the body by inhalation

Tubercle bacilli then spread to other body organs via blood and lymphatic systems

Tubercle bacilli may become dormant, or walled off by calcified or fibrous tissue

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Winter 2013

Antitubercular DrugsFirst-line drugs

◦ isoniazid (INH)*◦ethambutol◦rifampin◦rifabutin◦pyrazinamide (PZA)◦Rifapentine◦streptomycin

*Primary drug used

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Winter 2013

Antitubercular Drugs (cont’d)

Second-line drugs◦capreomycin◦amikacin◦cycloserine◦levofloxacin◦ethionamide◦ofloxacin ◦kanamycin◦para-aminosalicyclic acid (PAS)

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Winter 2013

Antitubercular Drug TherapyAntitubercular Drug TherapyConsiderationsConsiderations

Perform drug-susceptibility testing on the first Mycobacterium that is isolated from a patient specimen to prevent the development of MDR-TB

Even before the results of susceptibility tests are known, begin a regimen with multiple antitubercular drugs (to reduce chances of development of resistance)

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Winter 2013

Antitubercular Drug TherapyConsiderations ( (cont’d))

Adjust drug regimen once the results of susceptibility testing are known

Monitor patient compliance closely during therapy

Problems with successful therapy occur because of patient nonadherence to drug therapy and the increased incidence of drug-resistant organisms

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Winter 2013

Antitubercular Therapy

Effectiveness depends upon:◦Type of infection◦Adequate dosing◦Sufficient duration of treatment

◦Adherence to drug regimen◦Selection of an effective drug combination

151

Winter 2013

Antitubercular Therapy (cont’d)

Problems◦Drug-resistant organisms◦Drug toxicity◦Patient nonadherence

Multidrug-resistant TB (MDR-TB)

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Winter 2013

Isoniazid (INH)Drug of choice for TBResistant strains of Mycobacterium

emergingMetabolized in the liver through acetylation

—watch for “slow acetylators”Used alone or in combination with other

drugsContraindicated with liver disease

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Winter 2013

Adverse EffectsINH

◦Peripheral neuropathy, hepatotoxicity

ethambutol◦Retrobulbar neuritis, blindness

rifampin◦Hepatitis; discoloration of urine, stools, and other body fluids

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Winter 2013

Nursing Implications

Perform liver function studies in patients who are to receive isoniazid or rifampin (especially in elderly patients or those who use alcohol daily)

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Winter 2013

Nursing Implications (cont’d)

Patient education is criticalTherapy may last for up to 24

monthsTake medications exactly as

ordered, at the same time every day

Emphasize the importance of strict adherence to regimen for improvement of condition or cure

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Winter 2013

Nursing Implications (cont’d)

Remind patients that they are contagious during the initial period of their illness—instruct in proper hygiene and prevention of the spread of infected droplets

Teach patients to take care of themselves, including adequate nutrition and rest

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Winter 2013

Nursing Implications (cont’d)

Patients should not consume alcohol while on these medications or take other medications, including over-the-counter medications, unless they check with their physician

Rifampin causes oral contraceptives to become ineffective; another form of birth control will be needed

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Winter 2013

Nursing Implications (cont’d)

Patients who are taking rifampin should be told that their urine, stool, saliva, sputum, sweat, or tears may become reddish orange; even contact lenses may be stained

Pyridoxine may be needed to combat neurologic adverse effects associated with INH therapy

Oral preparations may be given with meals to reduce GI upset, even though recommendations are to take them 1 hour before or 2 hours after meals

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Winter 2013

Nursing Implications (cont’d)

COMPLIANCE AND DOT THERAPY◦Because of the length of treatment, it is difficult to be sure patient will comply

◦Family education may improve compliance

◦DOT = DIRECT OBSERVATION THERAPY

Winter 2013 160

Antifungal Drugs

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Winter 2013

Indications

Systemic and topical fungal infections

Drug of choice for the treatment of many severe systemic fungal infections is amphotericin B

Choice of drug depends on type and location of infection

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Winter 2013

Adverse Effects: Amphotericin B

Fever Chills Cardiac dysrhythmias Nausea and GI upset Renal toxicity Headache Malaise Hypotension Tingling, numbness in hands and feet Lowered potassium and magnesium levels

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Winter 2013

Adverse Effects: Amphotericin B

(cont’d) Main concerns:

◦*Renal toxicity◦*Neurotoxicity: seizures and paresthesias

Many other adverse effects

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Winter 2013

Nursing Implications (cont’d)

amphotericin B◦To reduce the severity of the

infusion-related reactions, pretreatment with an antipyretic (acetaminophen), antihistamines, antiemetics, and corticosteroids may be given

◦Use an IV infusion pump

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Winter 2013