Transcript Antibiotics09

Antibiotics
Antiviral
Antifungal
Antimalarial
Antiseptic & Disinfectant Agents
Antiinflammatory &
Antirheumatic
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Medications used to treat bacterial
infections
Ideally, before beginning antibiotic
therapy, the suspected areas of
infection should be cultured to
identify the causative organism and
potential antibiotic susceptibilities
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Empiric therapy: treatment of an infection
before specific culture information has
been reported or obtained
Prophylactic therapy: treatment with
antibiotics to prevent an infection, as in
intra-abdominal surgery or after trauma
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Therapeutic response
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Decrease in specific signs and symptoms of
infection are noted (fever, elevated WBC, redness,
inflammation, drainage, pain)
Subtherapeutic response
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Signs and symptoms of infection do not improve
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Superinfection
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Antibiotic resistance
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Host factors
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Genetic host factors
G6PD deficiency
 Slow acetylation
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Allergic reactions
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Sulfonamides
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Penicillins
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Cephalosporins
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Tetracyclines
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Aminoglycosides
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Quinolones
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Macrolides
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clindamycin (Cleocin)
dapsone
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linezolid (Zyvox)
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metronidazole (Flagyl)
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nitrofurantoin (Macrodantin)
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quinupristin and dalfopristin (Synercid)
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daptomycin (Cubicin)
Four common mechanisms of action
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Interference with cell wall synthesis
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Interference with protein synthesis
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Interference with DNA replication
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Acting as a metabolite to disrupt critical
metabolic reactions inside the bacterial cell
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Bactericidal: kill bacteria
Bacteriostatic: inhibit growth of susceptible
bacteria, rather than killing them immediately;
will eventually lead to bacterial death
One of the first groups of antibiotics
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Sulfadiazine (Coptin)
Sulfamethoxazole
Sulfisoxazole (Gantrisin)
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Used to treat otitis media, UTIs, other conditions
Often combined with another antibiotic
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Sulfamethoxazole-trimethoprim (Bactrim)
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Bacteriostatic action
Prevent synthesis of folic acid required
for synthesis of purines and nucleic acid
Do not affect human cells or certain
bacteria—they can use preformed folic acid
Only affect organisms that synthesize their
own folic acid
 Treatment
of UTIs caused by susceptible strains
of:
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Enterobacter spp., Escherichia coli, Klebsiella spp.,
Proteus mirabilis, Proteus vulgaris, Staphylococcus
aureus
 Nocardiosis
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Pneumocystis jiroveci pneumonia (PJP)
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(caused by Nocardia - pneumonia)
co-trimoxazole (Bactrim, Septra)
Upper respiratory tract infections
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trimethoprim/sulfamethoxazole (co-trimoxazole,
Bactrim, Septra)
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Used to treat UTIs, PJP, otitis media, other conditions
erythromycin/sulfisoxazole (Pediazole)
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Used to treat otitis media
Body System
Adverse Effects
Blood
Hemolytic and aplastic anemia,
agranulocytosis, thrombocytopenia
Integumentary
Photosensitivity, exfoliative dermatitis,
Stevens-Johnson syndrome, epidermal
necrolysis
GI
Nausea, vomiting, diarrhea,
pancreatitis
Other
Convulsions, crystalluria, toxic
nephrosis, headache,
peripheral neuritis, urticaria
Sulfonamides
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Should be taken with at least 2000 mL
of fluid per day, unless contraindicated
Oral forms should be taken with food or
milk to reduce GI upset
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Natural penicillins
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Penicillinase-resistant penicillins
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Aminopenicillins
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Extended-spectrum penicillins
Natural penicillins
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penicillin G, penicillin V potassium
Penicillinase-resistant drugs
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cloxacillin, dicloxacillin, nafcillin, oxacillin
Aminopenicillins
 amoxicillin, ampicillin, bacampicillin
Extended-spectrum drugs
 piperacillin, ticarcillin, carbenicillin
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First introduced in the 1940s
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Bactericidal: inhibit cell wall synthesis
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Kill a wide variety of bacteria
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Also called “β-lactams”
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Bacteria produce enzymes capable of
destroying penicillins
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These enzymes are known as β-lactamases
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As a result, the medication is not effect
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Chemicals used to inhibit these enzymes:
Clavulanic acid
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Tazobactam
Sulbactam
Bind with β-lactamase and prevent the enzyme
from breaking down the penicillin -- making the
drug more effective
Penicillin-β-lactamase inhibitor
combination drugs
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ampicillin + sulbactam = Unasyn
amoxicillin + clavulanic acid = Augmentin
ticarcillin + clavulanic acid = Timentin
piperacillin + tazobactam = Zosyn
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Penicillins enter the bacteria via the cell wall
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Inside the cell they bind to penicillin-binding protein
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Once bound, normal cell wall synthesis is
disrupted
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Result: bacteria cells die from cell lysis
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Penicillins do not kill other cells in the body
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Prevention and treatment of infections
caused by susceptible bacteria, such as:
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Gram-positive bacteria
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Streptococcus, Enterococcus, Staphylococcus
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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 β-lactam antibiotics
Cross-reactivity between penicillins and cephalosporins is
between 1% and 18%
Common adverse effects
 Nausea, vomiting, diarrhea, abdominal pain
Other adverse effects are less common
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MANY interactions!
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NSAIDs
Oral contraceptives
warfarin
Others
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Any patient taking a penicillin should be carefully
monitored for an allergic reaction for at least
30 minutes after its administration
The effectiveness of oral penicillins is
decreased when taken with caffeine, citrus
fruit, cola beverages, fruit juices, or tomato
juice
Administer with at least 6 ounces of water
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Four Generations:
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Semisynthetic derivatives from a fungus
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Structurally and pharmacologically related
to penicillins
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Bactericidal action
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Broad spectrum
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Divided into groups according to antimicrobial activity
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Used for surgical prophylaxis, URIs,
otitis media
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cefazolin (Ancef and Kefzol): IV or IM
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cephalexin (Keflex): PO
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Good gram-positive coverage
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Better gram-negative coverage than first
generation
Cefmetazole IV
 Cefoxitin (Mefoxin) IV
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cefoxitin (Mefoxin): IV and IM
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Cefprozil (Cefzil) PO
Cefaclor (Ceclor) PO
Used prophylactically for abdominal or colorectal surgeries
Also kills anaerobes
cefuroxime (Kefurox and Ceftin): PO
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Surgical prophylaxis
Does not kill anaerobes
ceftriaxone (Rocephin)
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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
ceftazidime (Fortaz, Tazidime)
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IV and IM forms
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Excellent gram-negative coverage
Used for difficult-to-treat organisms such as Pseudomonas
Eliminated renally instead of biliary route
Excellent spectrum of coverage
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Newest cephalosporin drugs
Broader spectrum of antibacterial activity than
third generation, especially against grampositive bacteria
Tx: UTI, Skin infections, pneumonia
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cefepime (Maxipime) GM +/cefdinir
cefditoren pivoxil (Spectracef)
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Similar to penicillins
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Mild diarrhea, abdominal cramps, rash, pruritis,
redness, edema
Potential cross-sensitivity with penicillins
if allergies exist
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Orally administered forms should be given
with food to decrease GI upset, even
though this will delay absorption
Some of these drugs may cause a
disulfiram (Antabuse)-like reaction when
taken with alcohol
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Very broad-spectrum antibacterial action
Reserved for complicated body cavity and
connective tissue infections
May cause drug-induced seizure activity
All given parenterally
imipenem-cilastatin (Primaxin)
 Used for treatment of bone, joint, skin, and soft
tissue infections
 Cilastatin inhibits an enzyme that breaks down
imipenem
meropenem (Merrem) – bacterial meningitis
ertapenem (Invanz) - newest
aztreonam (Azactam)
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Synthetic β-lactam antibiotic
Primarily active against aerobic gram-negative
bacteria (E. coli, Klebsiella spp., Pseudomonas spp.)
Bactericidal
Used for moderately severe systemic infections
and UTIs
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Prevent protein synthesis within bacterial cells
Considered bacteriostatic - Bacteria will eventually die
In high enough concentrations, may also be
bactericidal
erythromycin (E-mycin
azithromycin (Zithromax)
clarithromycin (Biaxin)
Adverse Effects: GI effects, primarily with erythromycin
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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
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These drugs are highly protein-bound and will cause
severe interactions with other protein-bound
drugs
The absorption of oral erythromycin is enhanced
when taken on an empty stomach, but because
of the high incidence of GI upset, many drugs
are taken after a meal or snack
telithromycin (Ketek)
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Only drug in this class
Better antibacterial coverage than macrolides
Active against gram-positive bacteria, including
multi-drug resistant strains of S. pneumoniae
Active against selected gram-negative bacteria
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Indications:
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Community-acquired pneumonia, acute bacterial sinusitis,
bacterial exacerbations of chronic bronchitis
Adverse reactions include:
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Headache, dizziness, GI discomfort, altered potassium levels,
prolonged QT intervals
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Natural and semisynthetic
Obtained from cultures of Streptomyces
Bacteriostatic—inhibit bacterial growth
Inhibit protein synthesis
Stop many essential functions of the bacteria
demeclocycline (Declomycin)
oxytetracycline
tetracycline
doxycycline (Doryx, Vibramycin)
Minocycline
Strong affinity for calcium
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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
Alteration in intestinal flora may result in:
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Superinfection (overgrowth of nonsusceptible
organisms such as Candida)
Diarrhea
Pseudomembranous colitis
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Milk products, iron preparations, antacids, and
other dairy products should be avoided because of
the chelation and drug-binding that occurs
All medications should be taken with 6 to 8 ounces
of fluid, preferably water
Due to photosensitivity, avoid sunlight and
tanning beds
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Before beginning therapy, assess drug allergies; renal,
liver, and cardiac function; and other lab studies
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Be sure to obtain patient health history, including
immune status
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Assess for conditions that may be contraindications to
antibiotic use or that may indicate cautious use
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Assess for potential drug interactions
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It is ESSENTIAL to obtain cultures from
appropriate sites BEFORE beginning
antibiotic therapy
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Each class of antibiotics has specific adverse
effects and drug interactions that must be
carefully assessed and monitored
The most common adverse effects of antibiotics
are nausea, vomiting, and diarrhea
All oral antibiotics are absorbed better if taken with
at least 6 to 8 ounces of water
Monitor for therapeutic effects
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Improvement of signs and symptoms of infection
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Return to normal vital signs
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Negative culture and sensitivity tests
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Disappearance of fever, lethargy, drainage, and
redness
Monitor for adverse reactions
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Therapeutic drug monitoring
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Minimum inhibitory concentration (MIC)
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Concentration-dependent killing
 Once-daily dosing vs. multi-daily dosing
 Peak and trough blood levels
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Synergistic effects
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Post-antibiotic effect (PAE)
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Ototoxicity
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Temporary or permanent hearing loss, balance
problems
Nephrotoxicity
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Varying degrees of reduced renal function
Rising serum creatinine may indicate reduced creatinine
clearance
Monitor trough levels every 3 days while on
therapy or as ordered
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gentamicin (Garamycin)
kanamycin
neomycin (Neo-Fradin)
streptomycin
tobramycin (Nebcin)
amikacin (Amikin)
netilmicin
paromomycin
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Natural and semisynthetic
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Produced from Streptomyces
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Poor oral absorption; no PO forms
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Very potent antibiotics with serious toxicities
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Bactericidal; prevents protein synthesis
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Kill mostly gram-negative; some gram-positive
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Used to kill gram-negative bacteria Pseudomonas,
E. coli, Proteus, Klebsiella, Serratia
Often used in combination with other antibiotics for
synergistic effects
Certain gram-positive infections that are resistant to other
antibiotics
Aminoglycosides poorly absorbed through the GI tract - given IV
Exception: neomycin
 Given orally or by enema - decontaminate the GI tract
before surgical procedures
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Ototoxicity and nephrotoxicity are
the most significant
Headache
 Paresthesia
 Fever
 Superinfections
 Vertigo
 Skin rash
 Dizziness
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ciprofloxacin (Cipro)
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norfloxacin (Noroxin)
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levofloxacin (Levaquin)
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gatifloxacin (Tequin)
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moxifloxacin (Avelox)
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gemifloxacin (Factive)
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Also called “quinolones”
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Excellent oral absorption
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Absorption reduced by antacids
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Effective against gram-negative organisms and
some gram-positive organisms
Mechanism of Action:
 Bactericidal
 Alter DNA of bacteria, causing death
 Do not affect human DNA
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Lower respiratory tract infections
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Bone and joint infections
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Infectious diarrhea
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Urinary tract infections
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Skin infections
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Sexually transmitted diseases
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Anthrax
Body System
Adverse Effects
CNS
Headache, dizziness, fatigue,
depression, restlessness, insomnia
Nausea, vomiting, diarrhea,
constipation, thrush, increased LFTs
GI
Integumentary
Rash, pruritus, urticaria, flushing,
photosensitivity (with lomefloxacin)
Other
Fever, chills, blurred vision, tinnitus
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clindamycin (Cleocin)
dapsone
linezolid (Zyvox)
metronidazole (Flagyl)
nitrofurantoin (Macrodantin)
quinupristin and dalfopristin (Synercid)
daptomycin (Cubicin)
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clindamycin (Cleocin)
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Used for chronic bone infections, GU
infections, intraabdominal infections, other
serious infections
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May cause pseudomembranous colitis
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dapsone
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Used for leprosy (Hansen’s disease), PJP
pneumonia associated with HIV/AIDS, other
uses
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linezolid (Zyvox)
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New class: oxazolidinones
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Used to treat vancomycin-resistant Enterococcus
faecium (VREF, VRE), hospital-acquired skin and
skin structure infections, including those with
MRSA
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May cause hypotension, serotonin syndrome if taken
with SSRIs, and reactions if taken with tyraminecontaining foods
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nitrofurantoin (Macrodantin)
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Primarily used for UTIs (E. coli, S. aureus,
Klebsiella spp., Enterobacter spp.)
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Use carefully if renal function is impaired
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Drug concentrates in the urine
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Usually well-tolerated if patient is kept wellhydrated
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quinupristin and dalfopristin (Synercid)
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30:70 combination, work synergistically
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Used for bacteremia and infections caused by
vancomycin-resistant Enterococcus (VRE) and
other complicated skin infections
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May cause arthralgias, myalgias
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daptomycin (Cubicin)
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New class: lipopeptide
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Used to treat complicated skin and soft-tissue
infections
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Natural, bactericidal antibiotic - Destroys cell wall
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Treatment of choice for MRSA, and other gram-positive infections
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Must monitor blood levels to ensure therapeutic levels and prevent toxicity
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May cause ototoxicity and nephrotoxicity
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Should be infused over 60 minutes -- Monitor IV site closely
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Red man syndrome may occur
 Flushing/itching of head, neck, face, upper trunk
 Antihistamine may be ordered to reduce these effects
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Ensure adequate hydration (2 L fluids/24 hr) if not contraindicated to
prevent nephrotoxicity
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Before beginning therapy, assess drug allergies;
hepatic, renal, and cardiac function
Be sure to obtain thorough patient health history,
including immune status
Assess for conditions that may be contraindications
to antibiotic use or that may indicate cautious use
Assess for potential drug interactions
It is ESSENTIAL to obtain cultures
from appropriate sites BEFORE
beginning antibiotic therapy



Patients should be instructed 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
Assess for signs and symptoms of superinfection:
fever, perineal itching, cough, lethargy, or any
unusual discharge
For safety reasons, check the name of the
medication carefully because there are many drugs
that sound alike or have similar spellings

Each class of antibiotics has specific
adverse effects and drug
interactions that must be carefully
assessed and monitored
Aminoglycosides
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
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
Monitor for therapeutic effects

Improvement of signs and symptoms of infection

Return to normal vital signs

Negative culture and sensitivity tests

Disappearance of fever, lethargy, drainage, and
redness
Monitor for adverse reactions