AntimicrobialsNUR 127

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.

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.

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

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

Characteristics of Anti-InfectivesIncludes antibacterials, antivirals and

antifungalsAntibacterials (antibiotics) refer to drugs which

treat bacterial infectionsNarrow spectrumBroad spectrumBactericidal (kills) vs. Bacteriostatic (inhibits)

Common Human PathogensVirusesGram+:

enterococci, streptococci and staphylococci

Gram- organisms: E.coli, Bacteroides, Klebsiella, Proteus,

Pseudomonas

OpportunisticCommunity-acquired vs. nosocomial

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)

Disease Process

Pathogens generally cause disease by one of two basic mechanisms1) Rapid growth2) Production of toxins

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)

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

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)

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

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

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

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: ________________________________________

______________________________________________

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

-

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

Age-Related Considerations-Children

Penicillins and Cephalosporins generally safeFewer clinical trials on childrenErythromycin, Zithromax (azithromycin) and

Biaxin (clarithromycin) considered safe

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

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

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

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

In GeneralWith most oral antibiotics, liberal fluid intake

is recommendedAlways be aware of pregnancy category

before administering medication

Lab ID of PathogensCulture and sensitivitySerology-measures antibody levelsPolymerase Chain Reaction (PCR) detects

the specific DNA for a specific organism

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

Host Defense Weakened byBreaks in skin and mucous membranesImpaired blood supplyNeutropeniaMalnutritionPoor personal hygieneSuppression of normal floraDiabetes, advanced age or

immunosuppression

Mechanisms of ActionInhibit cell wall synthesis Alter membrane permeability (PCNs,

Cephalosporins, Vancomycin_Inhibition of protein synthesis (EES,

tetracyclines, clindamycin, aminoglycosides)

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)

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

Prophylactic TherapySTD exposureRecurrent UTIsTBPerioperative infections in high risk patients

or high risk surgeries

Antibiotic Combination Therapy

Used when infection is caused by multiple microorganisms

Nosocomial infectionsSerious infections in which a combination is

synergistic (aminoglycoside and antipseudomonal PCN)

Antibiotic Combination Therapy cont.Likely emergence of drug resistant organismsIn those who are immunosuppressed

Antibiotics Affecting the Bacterial Cell WallPenicillins

Penicillin (P)

Cephalosporins Cefotaxime (P)

Vancomycins vancomycin

Carbapenems meropenem

Monobactam Antibiotics

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

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.

Indications for Penicillins

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)

Cephalosporins

Also derived from a mold

Broad spectrum with activity against both gram positive and gram negative bacteria

Cefotamine (P)- 3rd generation

Cephalosporins

Indications-surgical prophy, tx infections of the respiratory tract, skin, bone and joints, urinary tract, brain and spinal cord and in septicemia

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

ExamplesOral—Keflex (cephalexin); Ceclor (cefaclor),

Lorabid (lorcarbef); Omnicef (cefdinir)Parenteral—Ancef (kefzol); Mefoxin

(cefoxitin); Claforan (cefotaxime), Fortaz (ceftazidime), Rocephin (ceftriaxone); Maxipime (cefepime)

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)

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

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

Antibiotics affecting Protein SynthesisAminoglycosides

Gentamicin (P)Tetracyclines

Tetracycline (P)Macrolide Antibiotics

Erythromycin (P)

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)

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

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

TetracyclinesBroad spectrum bacteriostaticMicrobial resistance emerging

Effective against Chlamydia, Mycoplasma, protozoa (e.g. Malaria, Giardia, Leishmaniasis)

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

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

MacrolidesInclude: Zithromax (azithromycin), Biaxin

(clarithromycin), (erythromycin) (P) and Dynabac (dirithromycin)

Effective against gram positive cocci, Neisseria, Treponema, Mycoplasma,Bacteroides, Clostridia and Corynebacterium

Macrolide Management Considerations & Contraindications

Interacting drugs include: Coumadin, Theophylline, Prednisone, Norpace, Lanoxin, Tegretol, Alfenta and Parlodel (dopamine agonist)

Contraindicated in liver diseaseContraindicated in hypersensitivity

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

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

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

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

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

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

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

SulfonamidesContraindicated in renal failureCan cause bone marrow depression,

especially in elderlyWith Bactrim, can cause folic acid deficiencyCan cause cholestatic jaundice in rare cases

Sulfonamide preparaionsAzulfidine (sulfasalazine) is used in tx of

ulcerative colitis and in RAMay cause crystalluria. Liberal fluids needed.

Sulfonamides cont.Sulfamylon used in burns—especially

w/Pseudomonas—can cause metabolic acidosis, is painful w/application

Silver sulfadiazine—useful in burns

Treating Viral & Fungal Infections

Viral and Fungal Diseases

HepatitsHerpes Simplex Herpes ZosterInfluenzaHIV

candidiasis

Antifungals: 2 types

1. Systemic antifungal

2. Superficial antifungal

AntifungalsFluconazole (Diflucan)Nystatin (P), (Mycostatin)

May be used orally, topically, or vaginallyGenerally well tolerated

Viral Replication

Anti-Viral AgentsAcycolvir (P)

Indications: HSV, Herpes zosterA/E: lightheadedness, anorexia, n/v,

HA.Confusion, tremors, szIV may be nephrotoxic