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AntimicrobialsNUR 127
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Prototype approach to teaching pharmacology:
Uses a prototype (a drug that is representative of it’s class) to help students learn by grouping the medications. It is a method of learning and organizing large
amounts of information.
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OBJECTIVES:1.Identify various types of pathogenic organisms 2.Identify and describe pathogenicity and virulence of common bacterial pathogens3.Discuss the development of anti-infective drug resistance and identify the nurse/patient role in preventing development of resistant pathogens4.Discuss the development and common symptoms of superinfections caused by anti-infective therapy5.Identify prototype drugs within the anti-infective drug classes. Discuss mechanism of action, indication for use, contraindications, adverse effects and administration. Identify drugs within each class with specific features differing from the prototype.
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Terminology Pathogenicity—ability of an organism to cause
disease in a humanVirulence—severity of disease that an organism
is able to cause; a highly virulent pathogens causes disease when present in very small numbers
Acquired Resistance—when a microbe is no longer affected by an anti-infective
Nephrotoxicity—an adverse effect on the kidneys
Hepatotoxicity—an adverse effect on the liverOtotoxicity—an adverse effect on hearingSuperinfection—condition caused when a
microorganism grows rapidly as a result of having less competition in its environment
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Terminology
Anti-infective aka antimicrobial—General term referring to drugs active against pathogens
Antibiotic aka antibacterial—Drugs active against bacteria
Bacteriocidal—kill bacteriaBacteriostatic—slow the growth of bacteriaChemoprophylaxis—prophylactic use of a
medication
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Characteristics of Anti-InfectivesIncludes antibacterials, antivirals and
antifungalsAntibacterials (antibiotics) refer to drugs which
treat bacterial infectionsNarrow spectrumBroad spectrumBactericidal (kills) vs. Bacteriostatic (inhibits)
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Common Human PathogensVirusesGram+:
enterococci, streptococci and staphylococci
Gram- organisms: E.coli, Bacteroides, Klebsiella, Proteus,
Pseudomonas
OpportunisticCommunity-acquired vs. nosocomial
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Common Bacterial Pathogens Staphylococci—Common in wounds , URI’s and
pneumonia (MRSA—resistant strain)Streptococci—Common infection in URI’s, ear
infections & pneumonia Enterococci—Common infection in UTI’s &
wounds (VRE—resistant strain)Escherichia coli—UTI’s; GI infection most
commonly related to contaminated ground beefKlebsiella—Causes respiratory tract infections,
UTI’s, bloodstream, burn wound infectionsPneumococci—Most common cause of
pneumonia in children; otitis mediaProteus—Cause UTI’s and wound infectionsPseudomonas—Cause respiratory tract
infections, UTI’s, wound & burn wound infections (high resistance to many antibiotics)
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Disease Process
Pathogens generally cause disease by one of two basic mechanisms1) Rapid growth2) Production of toxins
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Normal Bacterial FloraColonized areas include the skin, upper
respiratory tract, colon and vaginaSkin Flora (eg, staphylococci, streptococci)Upper Respiratory Tract (eg, staphylococci,
streptococci, pneumococci, Haemophilus influenzae)
Colon (eg, escherichia coli, Klebsiella, Enterobacter, Proteus, Pseudomonas, Bacteroids, clostridia, lactobacilli, strep, staph)
Vaginal (eg, Candida, lactobacilli, Bacteroids)
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Infectious DiseasesPresence of a pathogen plus clinical s/sx
of infection
Patient with a compromised immune system may be prone to opportunistic infections caused by endogenous or environmental flora
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Drug ClassificationClassified by their chemical structure or by their
mechanism of actionMechanism of action
Cell-wall synthesis inhibitors, protein synthesis inhibitors, RNA or DNA synthesis inhibitors, antimetabolites (
Bacteriocidal vs. Bacteriostatic Bactericidal drugs kill organisms Bacteriostatic drugs inhibit growth of organisms
Classification by chemical class Share similar mechanisms of action and side effects
(aminoglycoside, fluoroquinolone, sulfonamide)
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AntimicrobialsUsed to prevent or treat infections
caused by pathogenic microorganisms
Broad-spectrum drugs are effective against a wide variety of microorganisms
Narrow-spectrum drugs are effective against one or a restricted group of microorganisms
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Guidelines for use Collect specimens before beginning
therapy
Avoid use of broad-spectrum drugs
Use with other interventions—universal precautions, hand hygeine, isolation techniques, preoperative skin and bowel cleansing
Multidrug therapy should be avoided except in specific circumstances
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Anti-microbial Drug AdministrationDosage should be individualized
Dosages often determined by grams or milligrams per kilogram of body weight
Routes of administrationMost PO or IVIM doses : deep and into a large muscle
(Ventrogluteal preferred for adults)Topical
Duration of therapy varies from single dose to years; most acute infections treated for 7 to 10 days
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Anti-microbial Drug Reactions Hypersensitivity reactions
Occur most often with the ____________ administration
S/Sx: Low grade fever, rash, hives and swelling
Anaphylactic reactionsMore likely to occur with IV route Most often occur within 5-30min of injectionS/Sx: ________________________________________
______________________________________________
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Common Adverse Effects Phlebitis at IV sites; pain at IM sitesNausea & Vomiting—Most Common Side Effect
Diarrhea (severe colitis possible with some antimicrobial therapy—s/sx blood stool, pus mucous)
Bone marrow suppression with thrombocytopenia (decreased plt)—most common with penicillins and cephalosporins
Nephrotoxicity—esp aminoglycosides and sulfonamides
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Common Adverse Effects
Neurotoxicity—IV penicillins or cephalosporins Ototoxicity: S/Sx: Tinnitus , vertigo, hearing loss
HepatoxicityMonitor Liver Function Tests: ALT, AST,
BilirubinS/Sx: Jaundice, dark urine, pale stools, abd pain, fever
Photosensitivity
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Age-Related Considerations-Children
Penicillins and Cephalosporins generally safeFewer clinical trials on childrenErythromycin, Zithromax (azithromycin) and
Biaxin (clarithromycin) considered safe
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Antimicrobials and ChildrenAminoglycosides can cause ototoxicity and
nephrotoxicity. Tetracyclines are contraindicated in children
younger than 8 years old, effects on teethCleocin (clindamycin) admin. requires liver
and kidney monitoring in neonates and infants
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Antimicrobials and ChildrenFluoroquinolones contraindicated in
children under 18 yo. May have effects on weight bearing joints.
Bactrim (trimethoprim-sulfamethoxazole) no longer 1st line due to resistance
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Antimicrobials and Older AdultsPenicillins are generally safe, IV admin. can
cause hyperkalemiaCephalosporins are considered sage but can
affect or worsen renal failureMacrolides are generally safeAminoglycosides are contraindicated in
severe renal impairment
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Antimicrobials and Older AdultsAminoglycosides can also cause
ototoxicityCleocin (clindamycin)-diarrhea, colitisBactrim (trimethoprim-sulfamethoxazole)
may be associated with impaired liver or kidney function
Tetracyclines (except doxycycline) and Macrodantin (nitrofurantoin) are contraindicated in impaired renal function
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In GeneralWith most oral antibiotics, liberal fluid intake
is recommendedAlways be aware of pregnancy category
before administering medication
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Lab ID of PathogensCulture and sensitivitySerology-measures antibody levelsPolymerase Chain Reaction (PCR) detects
the specific DNA for a specific organism
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Antibiotic-Resistant Microorganisms
Occurs when:Clinical condition of host is impairedNormal flora have been suppressedinterrupted or inadequate txType of bacteriaWidespread use of broad spectrum abxEnvironmental setting of host
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Host Defense Weakened byBreaks in skin and mucous membranesImpaired blood supplyNeutropeniaMalnutritionPoor personal hygieneSuppression of normal floraDiabetes, advanced age or
immunosuppression
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Mechanisms of ActionInhibit cell wall synthesis Alter membrane permeability (PCNs,
Cephalosporins, Vancomycin_Inhibition of protein synthesis (EES,
tetracyclines, clindamycin, aminoglycosides)
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Mechanisms of Action cont.Disruption of microbial cell membranes (anti-
fungals)Inhibition of organism reproduction by
interfering w/nucleic acid synthesis (fluoroquinolones, HIV anti-retrovirals)
Inhibition of cell metabolism and growth (sulfonamides)
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AdministrationLabs to Monitor
Blood levels of the antibioticCBC (complete blood count)WBC (white blood cell) count
WBC should return to normal if med is effective
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Prophylactic TherapySTD exposureRecurrent UTIsTBPerioperative infections in high risk patients
or high risk surgeries
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Antibiotic Combination Therapy
Used when infection is caused by multiple microorganisms
Nosocomial infectionsSerious infections in which a combination is
synergistic (aminoglycoside and antipseudomonal PCN)
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Antibiotic Combination Therapy cont.Likely emergence of drug resistant organismsIn those who are immunosuppressed
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Antibiotics Affecting the Bacterial Cell WallPenicillins
Penicillin (P)
Cephalosporins Cefotaxime (P)
Vancomycins vancomycin
Carbapenems meropenem
Monobactam Antibiotics
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Beta LactamsContain a beta-lactam ring that is part of their
chemical structure
An intact beta-lactam ring is essential for antibacterial activity
Include: Penicillins, Cephalosporins, CarbapenemsCross-sensitivity
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PenicillinsPrototype is Penicillin G
Most serious complication is hypersensitivity. Can cause seizures and nephropathy.
Contraindicated in patients with known allergy to PCN, cephalosporins, or imipenem.
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Indications for Penicillins
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Examples of Penicillins
Penicillins G and V (parenteral); dicloxacillin (antistaph);
Ampicillins—Principen, AmoxilAntipseudomonals—Geocillin (carbenicillin),
Ticar (ticaracillin), Pipracil (piperacillin)Combinations for beta lactamase—Unasyn
(ampicillin/sulbactam), Zosyn (piperacillin/taxobactam)
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Cephalosporins
Also derived from a mold
Broad spectrum with activity against both gram positive and gram negative bacteria
Cefotamine (P)- 3rd generation
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Cephalosporins
Indications-surgical prophy, tx infections of the respiratory tract, skin, bone and joints, urinary tract, brain and spinal cord and in septicemia
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CephalosporinsContraindicated in anaphylaxis to a penicillinMay develop a delayed reaction or cross-
sensitivity
A/E: Hypersensitivity Anaphylaxis GI: n/v/d Pain at injection site
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ExamplesOral—Keflex (cephalexin); Ceclor (cefaclor),
Lorabid (lorcarbef); Omnicef (cefdinir)Parenteral—Ancef (kefzol); Mefoxin
(cefoxitin); Claforan (cefotaxime), Fortaz (ceftazidime), Rocephin (ceftriaxone); Maxipime (cefepime)
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CarbapenemsBroad spectrum, bactericidal, beta-lactam
anti-microbials. Inhibit synthesis of cell walls.
All are parenteral
Indicated for organisms resistant to other drugs
Examples: Merrem (meropenem) and Primaxin (imipenem-cilastatin)
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Monobactam AntibioticsAzactam (aztreonam) is active against gram-
negative bacteria and to many resistant strains
Stable in presence of beta lactamase
Preserves normal gram positive and anaerobic flora
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FYIPenicillins may be given with Probenecid or
aminoglycosides for serious infectionsPCN can cause nephropathiesTicaracillin has been linked to hypernatremiaPCN G can cause hyperkalemiaCaution w/Augmentin in hepatic impairmentNeed to adjust dosages of all beta lactams in
the presence of renal impairment whether PCN, cephalosporins, carbapenems and monobactams
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Antibiotics affecting Protein SynthesisAminoglycosides
Gentamicin (P)Tetracyclines
Tetracycline (P)Macrolide Antibiotics
Erythromycin (P)
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AminoglycosidesBactericidal agents to treat gram negative
organisms such as: Proteus, Klebsiella, Enterobacter, Serratia, Escherichia coli, and Pseudomonas
Narrow specturm
Accumulate in kidneys and ears
Gentamycin (P)
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Aminoglycosides cont.MOA: penetrate cell walls of susceptible
bacteria and bind to 30S ribosomes. —prevent protein synthesis and replication.
Most often affect the respiratory, GU, skin, wound, bowel and bloodstream
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Aminoglycoside—Management Considerations cont.
Measurement of peak and trough levels helps to maintain therapeutic serum levels w/o excessive toxicityDaily dosing
With impaired renal function, dosage of aminoglycosides must be reduced. Dosages or intervals may be reduced.
In UTIs, may use lower dosage as excreted by kidneys
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TetracyclinesBroad spectrum bacteriostaticMicrobial resistance emerging
Effective against Chlamydia, Mycoplasma, protozoa (e.g. Malaria, Giardia, Leishmaniasis)
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Indications for useTreatment of uncomplicated urethral,
endocervical or rectal infections caused by chlamydia
Long term treatment of acne
May be used as substitute for penicillin
Doxycycline may be used for Traveller’s diarrhea
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Tetracyclines cont.Contraindicated in renal failure except for doxy
and minocycline
Not indicated in children less than 8 years of age because can cause permanent discoloration of teeth and can depress bone growth
Can cause photosensitivity
Avoid taking within 2 hours of dairy products, w/iron or w/antacids
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MacrolidesInclude: Zithromax (azithromycin), Biaxin
(clarithromycin), (erythromycin) (P) and Dynabac (dirithromycin)
Effective against gram positive cocci, Neisseria, Treponema, Mycoplasma,Bacteroides, Clostridia and Corynebacterium
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Macrolide Management Considerations & Contraindications
Interacting drugs include: Coumadin, Theophylline, Prednisone, Norpace, Lanoxin, Tegretol, Alfenta and Parlodel (dopamine agonist)
Contraindicated in liver diseaseContraindicated in hypersensitivity
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Fluoroquinolones
Synthetic bactericidal drugs with activity against gram positive and gram negative organisms
Most are given orallyExcreted via kidneys
Contraindicated in liver diseaseContraindicated in hypersensitivity
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FluoroquinolonesExamples of floroquinolones: Cipro
(ciprofloxacin), Levaquin (levofloxacin), Floxin (ofloxacin)
Monitor renal and liver functionEnsure adequate fluid intake to prevent
crystalluriaAssess current medications for drugs that interact
Avoid exposure to sunlight
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Miscellaneous--VancomycinActive against gram positives onlyFrequently used to treat MRSACan cause hypotension, flushing and skin
rash if given too quicklyResistance is mountingCan cause “red man sydrome” if given too
quickly Caution in patients w/myasthenia gravis
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MiscellaneousCleocin (clindamycin)—similar in actio to
macrolides; is effective against gram positive cocci and pneumococci
Effective in treating mixed infectionsGreat for acne and bacterial vaginosisCan cause pseudomembranous colitis
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MiscellaneousFlagyl (metronidazole)Effective against anaerobic bacteria, gram
positive bacilli such as clostridium and protozoa such as Giardia, amebiasis, trichomoniasis
Useful topically for rosaceaUsed for bacterial vaginosisDisulfiram-like reaction if taken w/alcohol
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Drug interactionsAmphotericin B, vancomycin, cephalosporins,
loop diuretics, neuromuscular blocking agents can increase the effects of aminoglycosides
Tagamet (cimetidine) and Probenecid increase the effects of the fluoroquinolones
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SulfonamidesBacteriostatic against both gram positive and
gram negative bacteriaResistance is mountingCombination of Bactrim (trimethoprim-
sulfamethoxazole) is useful in the treatment of urinary tract infections and in Pneumocystis carinii
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SulfonamidesContraindicated in renal failureCan cause bone marrow depression,
especially in elderlyWith Bactrim, can cause folic acid deficiencyCan cause cholestatic jaundice in rare cases
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Sulfonamide preparaionsAzulfidine (sulfasalazine) is used in tx of
ulcerative colitis and in RAMay cause crystalluria. Liberal fluids needed.
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Sulfonamides cont.Sulfamylon used in burns—especially
w/Pseudomonas—can cause metabolic acidosis, is painful w/application
Silver sulfadiazine—useful in burns
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Treating Viral & Fungal Infections
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Viral and Fungal Diseases
HepatitsHerpes Simplex Herpes ZosterInfluenzaHIV
candidiasis
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Antifungals: 2 types
1. Systemic antifungal
2. Superficial antifungal
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AntifungalsFluconazole (Diflucan)Nystatin (P), (Mycostatin)
May be used orally, topically, or vaginallyGenerally well tolerated
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Viral Replication
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Anti-Viral AgentsAcycolvir (P)
Indications: HSV, Herpes zosterA/E: lightheadedness, anorexia, n/v,
HA.Confusion, tremors, szIV may be nephrotoxic