ANTIBIOTICS ANTIVIRALS ANTIFUNGALS ANTI

download report

Transcript ANTIBIOTICS ANTIVIRALS ANTIFUNGALS ANTI

DRUGS FOR BUGS
??
ANTIBIOTICS
ANTIVIRALSA
ANTIFUNGALS
ANTI-TUBERCULAR
ANTIMALARIAL
ANTIHELMINTHIC
ANTIMYCOBACTERIAL
ANTIVIRALS
ANTIBIOTICS
COMMONLY KNOWN AS
ANTIMICROBIALS
Winter 2013
1
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
GET AN INFECTION?





SKIN NOT INTACT
BLOOD SUPPLY
IMPAIRED
NEUTROPENIA
MALNUTRITION
SUPPRESSION OF
NORMAL
BACTERIAL
BALANCE
SUPPRESSION OF
THE IMMUNE
SYSTEM
 DIABETES
 CHRONIC ILLNESS
 ADVANCED AGE

Winter 2013
3
Infections: 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
4
Infections: Sites of Origin (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
5
Healthcare-Associated Infections:
Prevention
Hand washing
 Antiseptics
 Disinfectants

Winter 2013
6
Healthcare-Associated Infections:
Prevention (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
Winter 2013
7
FUNCTIONS OF ANTIBIOTICS
 BACTERICIDAL – Kills or
destroys microorganisms
 BACTERIOSTATIC – Retards
the growth of microorganisms
Winter 2013
8
IDENTIFICATION OF BACTERIA
GRAM TESTING
CULTURE AND
SENSITIVITY TESTING
SEND 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 ABX
 HYPERSENSITIVITY
(allergy)
 Requires at least one exposure to the
drug
◦ Mild –
 Rash, pruritus, urticaria
◦ Severe –
 Anaphylaxis
 Laryngospasms (wheezing)
 Dyspnea
 Decrease in blood pressure
Winter 2013
15
Winter 2013
16
Winter 2013
17
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 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
Winter 2013
19
Winter 2013
20
Winter 2013
21
Winter 2013
22
SUPERINFECTION
◦ A secondary infection that occurs
during antibiotic therapy in which
normal flora are destroyed
Winter 2013
23
Superinfection
 LOCATION OF INFECTION
◦ GROIN
◦ AXILLA
◦ MOUTH
◦ UNDER BREAST TISSUE
◦ ANY WARM MOIST AREA
 OFFENDING
◦ YEAST
◦ BACTERIA
ORGANISM
Winter 2013
24
Candida Yeast / Thrush
Winter 2013
25
NURSING RESPONSIBILITIES

PATIENT’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
ANTIBIOTIC

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 ANTIBIOTIC
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 ACTION
Inhibition of bacterial cell wall synthesis
 Inhibition of protein synthesis
 Disruption of cell membranes
 Inhibits cell reproduction
 Inhibits cell metabolism

Winter 2013
30
Antibiotics: Sulfonamides

One 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
31
Sulfonamides:
Mechanism of Action
Bacteriostatic action
 Prevent 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
32
Sulfonamides: 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
33
Sulfonamides: Indications (cont’d)

Urinary tract infections

Upper respiratory tract infections
Winter 2013
34
Sulfonamides:
Adverse Effects
Body System
Blood
Integumentary
dermatitis,
Adverse Effects
Hemolytic and aplastic
anemia, agranulocytosis,
thrombocytopenia
Photosensitivity, exfoliative
Stevens-Johnson
syndrome, epidermal
necrolysis
Winter 2013
35
Sulfonamides:
Adverse Effects (cont’d)
Body System
GI
Other
Adverse Effects
Nausea, vomiting, diarrhea,
pancreatitis
Convulsions, crystalluria,
toxic nephrosis,
headache, peripheral neuritis,
urticaria
http://www.youtube.com/watch?v=ifQMm2xuyqc&playnext=
1&list=PL27024F7449C9E999&feature=results_main
Winter 2013
36
Beta-Lactam Antibiotics
 Penicillins
 Cephalosporins
 Carbapenems
 Monobactams
Winter 2013
37
Winter 2013
38
Penicillins
First introduced in the 1940s
 Bactericidal: inhibit cell wall synthesis
 Kill a wide variety of bacteria
 Bacteria produce enzymes capable of
destroying penicillins

◦ These enzymes are known as betalactamases
◦ As a result, the medication is not effective
Winter 2013
39
Penicillins
 Natural
penicillins
 Penicillinase-resistant penicillins
 Aminopenicillins
 Extended-spectrum penicillins
Winter 2013
40
Penicillins (cont’d)
 Natural
penicillins
◦ penicillin G, penicillin V potassium
 Penicillinase-resistant
drugs
◦ cloxacillin, dicloxacillin, nafcillin,
oxacillin
Winter 2013
41
Penicillins (cont’d)
 Aminopenicillins
◦ amoxicillin, ampicillin
 Extended-spectrum
drugs
◦ piperacillin, ticarcillin, carbenicillin
◦ Usually used with other drugs;
rarely used alone
Winter 2013
42
Penicillins (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
43
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
44
Penicillins: Indications
 Prevention
and treatment of
infections caused by susceptible
bacteria, such as:
◦ Gram-positive bacteria
◦ Streptococcus, Enterococcus,
Staphylococcus
Winter 2013
45
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
46
Penicillins: Adverse Effects
(cont’d)

Common adverse effects
◦ Nausea, vomiting, diarrhea, abdominal
pain

Other adverse effects are less
common
Winter 2013
47
Penicillins: Interactions

MANY interactions!
◦ NSAIDs
◦ Oral contraceptives – Decreases
effectiveness
◦ Warfarin – Enhanced anticoagulant
effect r/t decrease in intestinal flora
producing vitamin K
◦ Others
Winter 2013
48
MRSA

METHICILLIN RESISTANT
STAPHYLOCOCCUS AUREUS
◦ Hand washing and gloving
◦ Goal is to avoid healthcare associated
infections
◦ “Colonized” means harbors the
bacterial infection
Winter 2013
49
NURSING CONSIDERATIONS
FOR PENICILLIN
◦ Take with a full glass of water
◦ Do not skip doses
◦ Take all of the medication as prescribed
◦ Notify MD of adverse reactions
Winter 2013
50
Winter 2013
51
Cephalosporins
First generation
 Second generation
 Third generation
 Fourth generation
 Fifth generation (not yet marketed)

Winter 2013
52
Cephalosporins (cont’d)
Semisynthetic derivatives
 Structurally and pharmacologically related
to penicillins
 Bactericidal action
 Broad spectrum
 Divided into groups according to their
antimicrobial activity

Winter 2013
53
Cephalosporins:
First Generation
Good gram-positive coverage
 Poor gram-negative coverage
 Parenteral and PO forms
 Examples

◦
◦
◦
◦
cefadroxil
cephradine
cefazolin
cephalexin
Winter 2013
54
Cephalosporins:
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
55
Cephalosporins:
Second Generation



Good gram-positive coverage
Better gram-negative coverage than first
generation
Examples:
 cefaclor
 cefprozil
 cefoxitin
 cefuroxime
 loracarbef
 cefotetan
Winter 2013
56
Cephalosporins:
Second Generation (cont’d)

cefoxitin (Mefoxin): IV and IM
◦ Used prophylactically for abdominal or
colorectal surgeries
◦ Also kills anaerobes

cefuroxime
◦ Zinacef is parenteral form; Ceftin is PO
◦ Surgical prophylaxis
◦ Does not kill anaerobes
Winter 2013
57
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
58
Cephalosporins:
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
59
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
60
Cephalosporins:
Fourth Generation
Broader spectrum of antibacterial activity
than third generation, especially against
gram-positive bacteria
 Uncomplicated and complicated UTI
◦ cefepime (Maxipime)

Winter 2013
61
Cephalosporins:
Fifth Generation
Ceftobipriole (not available)
 Broader spectrum of antibacterial activity
 Effective against a wide variety of
organisms

◦ MRSA
◦ Pseudomonas
Winter 2013
62
Cephalosporins:
Adverse Effects

Similar to penicillins
◦ Mild diarrhea, abdominal cramps, rash,
pruritus, redness, edema

Potential cross-sensitivity with
penicillins if allergies exist
Winter 2013
63
Carbapenems
Very broad-spectrum antibacterial
action
 Reserved for complicated body cavity
and connective tissue infections
 May cause drug-induced seizure
activity

◦ This risk can be reduced with proper
dosage

All given parenterally
Winter 2013
64
Carbapenems

imipenem/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)

Winter 2013
65
Monobactams
Aztreonem (Azactam) Only drug in this
catagory
 Beta-lactam antibiotic
 Gram negative bacteria
◦ Inhibits cell wall synthesis

Common adverse effects
Winter 2013
66
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
67
Macrolides:
Mechanism of Action
Prevent protein synthesis within
bacterial cells
 Considered bacteriostatic
 Bacteria will eventually die
 In high enough concentrations, may
also be bactericidal

Winter 2013
68
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
69
Macrolides: Indications (cont’d)
 azithromycin
and clarithromycin
◦ Recently approved for mycobacterium aviumintracellular 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
Winter 2013
70
Macrolides: Indications (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.
Winter 2013
71
Macrolides: Adverse Effects

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
72
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
73
Tetracyclines
demeclocycline (Declomycin)
 oxytetracycline
 tetracycline
 doxycycline (Doryx, Vibramycin)
 minocycline
 tigecycline (Tygacil)

Winter 2013
74
Tetracyclines (cont’d)
Natural and semisynthetic
 Obtained from cultures of Streptomyces
 Bacteriostatic—inhibit bacterial growth
 Inhibit protein synthesis
 Stop many essential functions of the
bacteria

Winter 2013
75
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
76
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
77
Tetracyclines: Adverse Effects
 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
78
Tetracyclines: Adverse Effects
(cont’d)

Alteration in intestinal flora may
result in:
◦ Superinfection (overgrowth of
nonsusceptible organisms such as
Candida)
◦ Diarrhea
◦ Pseudomembranous colitis
Winter 2013
79
Tetracyclines: Adverse Effects
(cont’d)
 May
also cause:
◦ Vaginal candidiasis
◦ Gastric upset
◦ Enterocolitis
◦ Maculopapular rash
◦ Other effects
Winter 2013
80
Winter 2013
81
Antibiotic Therapy: Toxicities

Ototoxicity
◦ Temporary or permanent hearing loss, balance
problems

Nephrotoxicity
◦ Varying degrees of reduced renal function
◦ Rising serum creatinine may indicate reduced
creatinine clearance
Monitor trough levels every 5 to 7 days while
on therapy or as ordered
 Monitor serum creatinine levels at least every 3
days as an index of renal function

Winter 2013
82
Aminoglycosides
gentamicin (Garamycin)
 neomycin (Neo-fradin)
 tobramycin (Nebcin)
 amikacin (Amikin)
 kanamycin
 streptomycin

Winter 2013
83
Aminoglycosides (cont’d)
Natural and semisynthetic
 Produced from Streptomyces
 Poor oral absorption; no PO forms
 Very potent antibiotics with serious
toxicities
 Bactericidal; prevent protein synthesis
 Kill mostly gram-negative bacteria;
some gram-positive also

Winter 2013
84
Aminoglycosides: Indications
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

Winter 2013
85
Aminoglycosides:
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
Winter 2013
86
Aminoglycosides:
Adverse Effects

Cause serious toxicities
◦ Nephrotoxicity (renal damage)
◦ Ototoxicity (auditory impairment and
vestibular impairment [eighth cranial
nerve])

Must monitor drug levels to prevent
toxicities
Winter 2013
87
Winter 2013
88
Aminoglycosides:
Adverse Effects (cont’d)

Ototoxicity and nephrotoxicity are
the most significant
◦
◦
◦
◦
◦
◦
◦
Headache
Paresthesia
Fever
Superinfections
Vertigo
Skin rash
Dizziness
Winter 2013
89
Quinolones
ciprofloxacin (Cipro)
 norfloxacin (Noroxin)
 levofloxacin (Levaquin)
 moxifloxacin (Avelox)

Winter 2013
90
Quinolones (cont’d)
Also called “fluoroquinolones”
 Excellent oral absorption
 Absorption reduced by antacids
 Effective against gram-negative
organisms and some gram-positive
organisms

Winter 2013
91
Quinolones:
Mechanism of Action
Bactericidal
 Alter DNA of bacteria, causing death
 Do not affect human DNA

Winter 2013
92
Quinolones: Indications
Gram-negative bacteria such as
pseudomonas
 Respiratory infections
 Bone and joint infections
 GI infections
 Skin infections
 Sexually transmitted diseases
 Anthrax

Winter 2013
93
Fluoroquinolones:
Adverse Effects
Body System
CNS
GI
Cardiac
Adverse Effects
Headache, dizziness, fatigue,
depression, restlessness,
insomnia
Nausea, vomiting, diarrhea,
constipation, thrush, increased
liver function studies, others
Prolonged QT interval
Winter 2013
94
Fluoroquinolones:
Adverse Effects (cont’d)
Body System
Integumentary
Other
Adverse Effects
Rash, pruritus, urticaria,
flushing, photosensitivity
(with lomefloxacin)
Fever, chills, blurred vision,
tinnitus
Black box warning: increased risk of tendonitis
and tendon rupture
Winter 2013
95
Other Antibiotics
clindamycin (Cleocin)
 linezolid (Zyvox)
 metronidazole (Flagyl)
 nitrofurantoin (Macrodantin)
 quinupristin and Dalfopristin (Synercid)
 daptomycin (Cubicin)
 vancomycin (Vancocin)
 colistimethate (Coly-mycin)

Winter 2013
96
Other Antibiotics (cont’d)

clindamycin (Cleocin)
◦ Used for chronic bone infections, GU
infections, intra-abdominal infections, other
serious infections
◦ May cause pseudomembranous colitis
Winter 2013
97
Other Antibiotics (cont’d)

linezolid (Zyvox)
◦ New class: oxazolidinones
◦ Used to treat vancomycin-resistant
Enterococcus faecium (VREF,VRE), hospitalacquired 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
Winter 2013
98
Other Antibiotics (cont’d)

metronidazole (Flagyl)
◦
◦
◦
◦
Used for anaerobic organisms
Intra-abdominal and gynecologic infections
Protozoal infections
Several drug interactions
Winter 2013
99
Other 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 wellhydrated
Winter 2013
100
Other 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
Winter 2013
101
Other Antibiotics (cont’d)

daptomycin (Cubicin)
◦ New class: lipopeptide
◦ Used to treat complicated skin and
soft-tissue infections
Winter 2013
102
Other 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
Winter 2013
103
Other 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
Winter 2013
104
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

Winter 2013
105
Nursing Implications (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
Winter 2013
106
ANTIVIRAL MEDICATIONS
Winter 2013
107
Understanding Viruses
 Viral
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
Winter 2013
108
Understanding Viruses (cont’d)

Viruses are difficult to kill because
they live inside the cells
◦ Any drug that kills a virus may also
kill cells
Winter 2013
109
Viral Illnesses
Most viral illnesses are bothersome, but
survivable
 Effective vaccines have prevented some
illnesses
 Effective drug therapy is available for a
small number of viral infections

Winter 2013
110
Antiviral Drugs

Antiviral drugs kill or suppress the virus
by destroying virions or inhibiting ability
to replicate viruses controlled by current
antiviral therapy
Winter 2013
111
Antiviral Drugs (cont’d)
Viruses controlled by current antiviral
therapy
 Cytomegalovirus (CMV)
 Hepatitis viruses
 Herpes viruses
 Human immunodeficiency virus (HIV)
 Influenza viruses (the “flu”)
 Respiratory syncytial virus (RSV)
Winter 2013
112
Antiviral Drugs (cont’d)
Key characteristics of antiviral drugs
 Able to enter the cells infected with virus
 Interfere with viral nucleic acid synthesis
and/or regulation
 Some drugs interfere with ability of virus
to bind to cells
 Some drugs stimulate the body’s immune
system
Winter 2013
113
Antiviral Drugs (cont’d)
Opportunistic infections
 Occur in immunocompromised patients
 Would not normally harm an
immunocompetent person
 Require long-term prophylaxis and
antiinfective drug therapy
 Can be other viruses, fungi, bacteria, or
protozoa
Winter 2013
114
Antiviral 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
Winter 2013
115
Virus Infections

Herpes-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)
Winter 2013
116
Winter 2013
117
Winter 2013
118
Winter 2013
119
Antiviral Drugs (non-HIV)

Mechanism of action
◦ Inhibit viral replication

Used to treat non-HIV viral infections
◦
◦
◦
◦
Influenza viruses
HSV,VZV
CMV
Hepatitis A, B, C (HAV, HBV, HCV)
Winter 2013
120
Antiviral Drugs (non-HIV) (cont’d)
 Adverse
effects
◦ Vary with each drug
◦ Healthy cells are often killed also,
resulting in serious toxicities
Winter 2013
121
Antiviral Drugs (non-HIV) (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
Winter 2013
122
Antiviral Drugs (non-HIV) (cont’d)

rimantadine (Flumadine)
◦ Same spectrum of activity, mechanism of
action, and indications as amantadine
◦ Fewer CNS adverse effects
◦ Causes GI upset
Winter 2013
123
Antiviral Drugs (non-HIV) (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
Winter 2013
124
Antiviral Drugs (non-HIV) (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)
Winter 2013
125
Antiviral Drugs (non-HIV):
Dose-Limiting Toxicities

ganciclovir
◦ Bone marrow toxicity

foscarnet and cidofovir
◦ Renal toxicity
Winter 2013
126
Antiviral Drugs (non-HIV):
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
Winter 2013
127
Antiviral Drugs (non-HIV):
Ribavirin
Synthetic nucleoside analog
 Given orally, or oral or nasal inhalation
 Inhalation form (Virazole) used for
hospitalized infants with RSV infections

Winter 2013
128
HIV and AIDS

Human 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
Winter 2013
129
Four Stages of HIV Infection*
Stage 1: asymptomatic infection
 Stage 2: early, general symptoms of disease
 Stage 3: moderate symptoms
 Stage 4: severe symptoms, often leading to
death

*WHO model
Winter 2013
130
Opportunistic Infections

Protozoal
◦ Toxoplasmosis of the brain, others

Fungal
◦ Candidiasis of the lungs, esophagus,
trachea
◦ Pneumocystis jirovecii pneumonia, others

Viral
◦ CMV disease, HSV infection, others
Winter 2013
131
Opportunistic Infections (cont’d)

Bacterial
◦ Various mycobacterial infections
◦ Extrapulmonary TB

Opportunistic neoplasias
◦ Kaposi’s sarcoma, others

HIV wasting syndrome
◦ Major weight loss, chronic diarrhea, chronic
fever
Winter 2013
132
Antiretroviral Drugs
HAART
 Highly active antiretroviral therapy
 Includes at least three medications
◦ “Cocktails”

These medications work in different ways
to reduce the viral load
Winter 2013
133
Antiretroviral Drugs (cont’d)

Reverse transcriptase inhibitors (RTIs)
◦ Block activity of the enzyme reverse transcriptase,
preventing production of new viral DNA

Protease 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

Winter 2013
134
Antiretroviral Drugs (cont’d)
 Reverse
transcriptase inhibitors (RTIs)
◦ Nucleoside RTIs (NRTIs)
◦ Nonnucleoside RTIs (NNRTIs)
 Examples
◦ abacavir (Ziagen)
◦ delavirdine (Rescriptor)
◦ didanosine (Videx)
◦ lefavirenze (Sustiva)
Winter 2013
135
Antiretroviral Drugs (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
Winter 2013
136
Antiretroviral Drugs (cont’d)
 Protease
inhibitors (PIs)
◦ Inhibit the protease retroviral enzyme,
preventing viral replication
◦ amprenavir (Agenerase)
◦ indinavir (Crixivan)
◦ nelfinavir (Viracept)
◦ ritonavir (Norvir)
Winter 2013
137
Antiretroviral Drugs (cont’d)
 Fusion
inhibitors
◦ Inhibit viral fusion, preventing viral
replication
◦ A newer class of antiretroviral drugs
◦ Example: enfuvirtide (Fuzeon)
Winter 2013
138
Antiretroviral Drugs (cont’d)

CCR5 antagonist
◦ maraviroc (Selzentry)

HIV integrase strand transfer inhibitor
◦ raltegravir (Isentress)
Winter 2013
139
Antiretroviral Drugs (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

Winter 2013
140
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

Winter 2013
141
Antitubercular Drugs
Winter 2013
142
Antitubercular Drugs

Tuberculosis (TB)
◦ Caused by Mycobacterium tuberculosis

Antitubercular drugs treat all forms of
Mycobacterium
Winter 2013
143
Mycobacterium Infections
Common infection sites
 Lung (primary site)
 Brain
 Bone
 Liver
 Kidney
Winter 2013
144
Mycobacterium Infections (cont’d)
Aerobic bacillus
 Passed from infected:

◦ Humans
◦ Cows (bovine) and birds (avian)
 Much less common
Winter 2013
145
Mycobacterium Infections (cont’d)
Tubercle bacilli are conveyed by droplets
 Droplets 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

Winter 2013
146
Antitubercular Drugs
 First-line
◦
◦
◦
◦
◦
◦
◦
drugs
isoniazid (INH)*
ethambutol
rifampin
rifabutin
pyrazinamide (PZA)
Rifapentine
streptomycin
*Primary drug used
Winter 2013
147
Antitubercular Drugs (cont’d)
 Second-line
◦
◦
◦
◦
◦
◦
◦
◦
drugs
capreomycin
amikacin
cycloserine
levofloxacin
ethionamide
ofloxacin
kanamycin
para-aminosalicyclic acid (PAS)
Winter 2013
148
Antitubercular Drug Therapy
Considerations
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)

Winter 2013
149
Antitubercular Drug Therapy
Considerations (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

Winter 2013
150
Antitubercular Therapy
 Effectiveness
depends upon:
◦ Type of infection
◦ Adequate dosing
◦ Sufficient duration of treatment
◦ Adherence to drug regimen
◦ Selection of an effective drug
combination
Winter 2013
151
Antitubercular Therapy (cont’d)
 Problems
◦ Drug-resistant organisms
◦ Drug toxicity
◦ Patient nonadherence
 Multidrug-resistant TB
(MDR-TB)
Winter 2013
152
Isoniazid (INH)
Drug of choice for TB
 Resistant strains of Mycobacterium
emerging
 Metabolized in the liver through
acetylation—watch for “slow acetylators”
 Used alone or in combination with other
drugs
 Contraindicated with liver disease

Winter 2013
153
Adverse Effects
INH
◦ Peripheral neuropathy, hepatotoxicity
 ethambutol
◦ Retrobulbar neuritis, blindness
 rifampin
◦ Hepatitis; discoloration of urine, stools,
and other body fluids

Winter 2013
154
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)
Winter 2013
155
Nursing Implications (cont’d)
Patient education is critical
 Therapy may last for up to 24 months
 Take medications exactly as ordered,
at the same time every day
 Emphasize the importance of strict
adherence to regimen for improvement of
condition or cure
Winter 2013
156
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

Winter 2013
157
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

Winter 2013
158
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

Winter 2013
159
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
Winter 2013
161
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

Winter 2013
162
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

Winter 2013
163
Adverse Effects: Amphotericin B
(cont’d)

Main concerns:
◦ *Renal toxicity
◦ *Neurotoxicity: seizures and
paresthesias

Many other adverse effects
Winter 2013
164
Nursing Implications (cont’d)

amphotericin B
◦ To reduce the severity of the infusionrelated reactions, pretreatment with
an antipyretic (acetaminophen),
antihistamines, antiemetics, and
corticosteroids may be given
◦ Use an IV infusion pump
Winter 2013
165