Anti-Infective Agents

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

Anti-Infective AgentsAnti-Infective AgentsAntibiotics:Antibiotics:

SulfonamidesSulfonamides

PenicillinsPenicillins

CephalosporinsCephalosporins

TetracyclinesTetracyclines

AminoglycosidesAminoglycosides

MacrolidesMacrolides

QuinolonesQuinolones


AntibioticsAntibiotics

• Medications used to Medications used to treat bacterial treat bacterial infectionsinfections

• Culture and sensitivity Culture and sensitivity before therapybefore therapy


Antibiotics DefinitionsAntibiotics Definitions

• Empiric therapy: treatment of an infection Empiric therapy: treatment of an infection before culturebefore culture

• Prophylactic therapy: treatment with Prophylactic therapy: treatment with antibiotics to prevent an infectionantibiotics to prevent an infection

• Broad spectrum- effective against several Broad spectrum- effective against several groups of microorganismsgroups of microorganisms

• Narrow spectrum- effective against a few Narrow spectrum- effective against a few groupsgroups


Antibiotics DefinitionsAntibiotics Definitions

• Bactericidal: kill bacteriaBactericidal: kill bacteria

• Bacteriostatic: inhibit growth of susceptible Bacteriostatic: inhibit growth of susceptible bacteria, rather than killing them immediately; bacteria, rather than killing them immediately; will eventually lead to bacterial deathwill eventually lead to bacterial death

• Superinfection: elimination of normal bacteria Superinfection: elimination of normal bacteria and other bacteria take overand other bacteria take over


NosocomialNosocomial

• Hospital Acquired InfectionsHospital Acquired Infections

• Patients with decreased resistancePatients with decreased resistance

• Often drug resistant strainsOften drug resistant strains

– Staph (Skin, Lungs)Staph (Skin, Lungs)

– Psuedomonas (Lungs, Wounds)Psuedomonas (Lungs, Wounds)

– Proteus (Wound, UTI)Proteus (Wound, UTI)


http://www.fda.gov/fdac/features/http://www.fda.gov/fdac/features/2002/402_bugs.html2002/402_bugs.html


Antibiotic Resistant MicroorganismsAntibiotic Resistant Microorganisms

Methicillin Resistant Staphylococcus Aureus (MRSA)Methicillin Resistant Staphylococcus Aureus (MRSA)

Penicillin Resistant StreptococcusPenicillin Resistant Streptococcus

Vancomycin Resistant EnterococciVancomycin Resistant Enterococci


Antibiotics: SulfonamidesAntibiotics: Sulfonamides

One of the first groups of antibioticsOne of the first groups of antibiotics

• sulfadiazinesulfadiazine

• sulfamethizolesulfamethizole

• SulfamethoxazoleSulfamethoxazole

• sulfisoxazolesulfisoxazole


Sulfonamides: Mechanism of ActionSulfonamides: Mechanism of Action

• Bacteriostatic actionBacteriostatic action

• Prevent synthesis of folic acid required for Prevent synthesis of folic acid required for synthesis of purines and nucleic acidsynthesis of purines and nucleic acid

• Does not affect human cells or certain Does not affect human cells or certain bacteria—they can use preformed folic acidbacteria—they can use preformed folic acid


Sulfonamides: sulfamethoxazole Sulfonamides: sulfamethoxazole Therapeutic UsesTherapeutic Uses

BactrimBactrim• Combined with trimethoprim.Combined with trimethoprim.

• Used to treat UTIs, Pneumocystis carinii pneumonia, Used to treat UTIs, Pneumocystis carinii pneumonia, ear infections, bronchitis, gonorrhea, etc.ear infections, bronchitis, gonorrhea, etc.


Sulfonamides: Side EffectsSulfonamides: Side Effects

• PhotosensitivityPhotosensitivity

• CrystalluriaCrystalluria

• Delayed skin reactionsDelayed skin reactions


Antibiotics: PenicillinsAntibiotics: Penicillins

• Natural penicillinsNatural penicillins

• Penicillinase-resistant penicillinsPenicillinase-resistant penicillins

• AminopenicillinsAminopenicillins

• Extended-spectrum penicillinsExtended-spectrum penicillins



• Inhibit the synthesis of Inhibit the synthesis of bacterial cell wallbacterial cell wall

• BactericidalBactericidal

• Therapeutic levels are Therapeutic levels are not usually obtained in not usually obtained in intraocular and intraocular and cerbrospinal fluidcerbrospinal fluid

• Rapidly excreted in Rapidly excreted in through the kidneysthrough the kidneys



• First introduced in the 1940sFirst introduced in the 1940s

• Bactericidal: inhibit cell wall synthesisBactericidal: inhibit cell wall synthesis

• Kill a wide variety of bacteriaKill a wide variety of bacteria

• Also called “beta-lactams”Also called “beta-lactams”



• Bacteria produce enzymes capable of Bacteria produce enzymes capable of destroying penicillins.destroying penicillins.

• These enzymes are known as These enzymes are known as beta-lactamases.beta-lactamases.

• As a result, the medication is not effective.As a result, the medication is not effective.



• Chemicals have been developed to inhibit Chemicals have been developed to inhibit these enzymes:these enzymes:

– clavulanic acidclavulanic acid

• These chemicals bind with beta-lactamase These chemicals bind with beta-lactamase and prevent the enzyme from breaking down and prevent the enzyme from breaking down the penicillinthe penicillin


Prototype: Penicillin GPrototype: Penicillin G

• Widely usedWidely used

• Effectiveness and Effectiveness and minimal toxicityminimal toxicity

• Available IV & IMAvailable IV & IM

• Natural PCNNatural PCN


Antibiotics: Penicillins: AugmentinAntibiotics: Penicillins: Augmentin

• Penicillin-beta-Penicillin-beta-lactamase inhibitor lactamase inhibitor combination drugs:combination drugs:

– amoxicillin + clavulanic amoxicillin + clavulanic acid = Augmentinacid = Augmentin

• Inactivate beta-Inactivate beta-lactamase enzymes lactamase enzymes

• Protects PCN and Protects PCN and extends spectrumextends spectrum

• Available POAvailable PO


Penicillins: Mechanism of ActionPenicillins: Mechanism of Action

• Penicillins enter the bacteria via the cell wall.Penicillins enter the bacteria via the cell wall.

• Inside the cell, they bind to penicillin-binding protein.Inside the cell, they bind to penicillin-binding protein.

• Once bound, normal cell wall synthesis is disrupted.Once bound, normal cell wall synthesis is disrupted.

• Result: bacteria cells die from cell lysis.Result: bacteria cells die from cell lysis.

• Penicillins do not kill other cells in the body.Penicillins do not kill other cells in the body.


Penicillins: Therapeutic UsesPenicillins: Therapeutic Uses

• Prevention and treatment of infections Prevention and treatment of infections caused by susceptible bacteriacaused by susceptible bacteria


Penicillins: Adverse EffectsPenicillins: Adverse Effects

• Allergic reactions occur Allergic reactions occur in 0.7% – 8% of in 0.7% – 8% of treatments treatments

– urticaria, pruritus, urticaria, pruritus, angioedemaangioedema

• 10% of allergic 10% of allergic reactions are life-reactions are life-threateningthreatening

and and

• 10% of these are fatal10% of these are fatal


Penicillins: Side EffectsPenicillins: Side Effects

• Common side effects:Common side effects:

– nausea, vomiting, diarrhea, abdominal painnausea, vomiting, diarrhea, abdominal pain

• Other side effects are less commonOther side effects are less common


Antibiotics: CephalosporinsAntibiotics: Cephalosporins

• First GenerationFirst Generation

• Second GenerationSecond Generation

• Third GenerationThird Generation

• Fourth GenerationFourth Generation


Antibiotics: CephalosporinsAntibiotics: Cephalosporins

• Semisynthetic derivatives from a fungusSemisynthetic derivatives from a fungus

• Structurally and pharmacologically related Structurally and pharmacologically related to penicillinsto penicillins

• Bactericidal actionBactericidal action

• Broad spectrumBroad spectrum

• Divided into groups according to their Divided into groups according to their antimicrobial activityantimicrobial activity


Cephalosporins: First GenerationCephalosporins: First Generation

cefazolincefazolin cephalexincephalexin

(Ancef and Kefzol)(Ancef and Kefzol) (Keflex and Keftab)(Keflex and Keftab)

IV and POIV and PO POPO

used for surgical prophylaxis, URIs, otitis mediaused for surgical prophylaxis, URIs, otitis media


CephalosporinsCephalosporinsPrototype: Cephalexin (Keflex)Prototype: Cephalexin (Keflex)

• Broad spectrumBroad spectrum

• First generation First generation

• Respiratory, soft tissue, Respiratory, soft tissue, bones, urinary tract, and bones, urinary tract, and bloodstream infectionsbloodstream infections

• Tx pcn resistant GCTx pcn resistant GC

• Contraindicated with prior Contraindicated with prior

severe severe anaphylactic anaphylactic reaction to PCNreaction to PCN


Cephalosporins: Side EffectsCephalosporins: Side Effects

• similar to penicillins similar to penicillins


Antibiotics: TetracyclinesAntibiotics: Tetracyclines

• doxycycline (Doryx, Doxy-Caps, Vibramycin)doxycycline (Doryx, Doxy-Caps, Vibramycin)



• Natural and semi-syntheticNatural and semi-synthetic

• Bacteriostatic—inhibit bacterial growthBacteriostatic—inhibit bacterial growth

• Inhibit protein synthesisInhibit protein synthesis

• Stop many essential functions of the bacteriaStop many essential functions of the bacteria


Tetracyclines: Therapeutic UsesTetracyclines: Therapeutic Uses

• Wide spectrum:Wide spectrum:

– gram-negative, gram-positive, protozoa, gram-negative, gram-positive, protozoa, Mycoplasma, Rickettsia, Chlamydia, syphilis, Mycoplasma, Rickettsia, Chlamydia, syphilis, Lyme diseaseLyme disease



• Bind to CaBind to Ca2+2+ and Mg and Mg2+2+ and Al and Al3+3+ ions to ions to form insoluble complexesform insoluble complexes

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


Tetracyclines: Side EffectsTetracyclines: Side Effects

Strong affinity for calcium Strong affinity for calcium

• Discoloration of permanent Discoloration of permanent teeth and tooth teeth and tooth enamel in fetuses and enamel in fetuses and childrenchildren

• May retard fetal skeletal May retard fetal skeletal development if taken development if taken during pregnancyduring pregnancy



Alteration in intestinal Alteration in intestinal flora may result in:flora may result in:

• Superinfection (overgrowth Superinfection (overgrowth of nonsusceptible of nonsusceptible organisms such as organisms such as Candida)Candida)

• DiarrheaDiarrhea

• Pseudomembranous colitisPseudomembranous colitis



May also cause:May also cause:

• Vaginal moniliasisVaginal moniliasis

• Gastric upsetGastric upset

• EnterocolitisEnterocolitis

• Maculopapular rashMaculopapular rash


Antibiotics: AminoglycosidesAntibiotics: Aminoglycosides

• gentamicin (Garamycin)gentamicin (Garamycin)



• Natural and semi-syntheticNatural and semi-synthetic

• Poor oral absorption; no PO formsPoor oral absorption; no PO forms

• Very potent antibiotics with serious toxicitiesVery potent antibiotics with serious toxicities


• Kill mostly gram-negative; some Kill mostly gram-negative; some gram-positive alsogram-positive also



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

• Often used in combination with other Often used in combination with other antibiotics for synergistic effect.antibiotics for synergistic effect.

• BIG GUN!!!!BIG GUN!!!!



Cause serious toxicities:Cause serious toxicities:

– Nephrotoxicity (renal Nephrotoxicity (renal failure)failure)

– Ototoxicity (auditory Ototoxicity (auditory impairment and impairment and vestibular [eighth cranial vestibular [eighth cranial nerve])nerve])

• Must monitor drug Must monitor drug levels, pg 581levels, pg 581


Adverse Effects Aminoglycosides Page Adverse Effects Aminoglycosides Page 583583

• NephrotoxicityNephrotoxicity

• OtotoxicityOtotoxicity

• NeurotoxicityNeurotoxicity

• HypersensitivityHypersensitivity


Aminoglycosides: Side EffectsAminoglycosides: Side Effects

Ototoxicity and nephrotoxicity are Ototoxicity and nephrotoxicity are the most significantthe most significant


Antibiotics: QuinolonesAntibiotics: Quinolones

• ciprofloxacin (Cipro)ciprofloxacin (Cipro)



• Excellent oral absorptionExcellent oral absorption

• Absorption reduced by antacidsAbsorption reduced by antacids

• First oral antibiotics effective against First oral antibiotics effective against gram-negative bacteriagram-negative bacteria


Quinolones: Mechanism of ActionQuinolones: Mechanism of Action


• Effective against gram-negative organisms Effective against gram-negative organisms and some gram-positive organismsand some gram-positive organisms

• Alter DNA of bacteria, causing deathAlter DNA of bacteria, causing death

• Do not affect human DNADo not affect human DNA


Quinolones: Therapeutic UsesQuinolones: Therapeutic Uses

• Lower respiratory tract infectionsLower respiratory tract infections

• Bone and joint infectionsBone and joint infections

• Infectious diarrheaInfectious diarrhea

• Urinary tract infectionsUrinary tract infections

• Skin infectionsSkin infections

• Sexually transmitted diseasesSexually transmitted diseases


Quinolones: Side EffectsQuinolones: Side Effects

• DizzinessDizziness

• PhotosensitivityPhotosensitivity

• ConstipationConstipation

• Rash, pruritisRash, pruritis

• FlushingFlushing


Drug InteractionsDrug Interactions

• CimetidineCimetidine

• ProbenicidProbenicid

• AntacidsAntacids

• IronIron


Antibiotics: MacrolidesAntibiotics: Macrolides

• erythromycin erythromycin

• azithromycin (Zithromax)azithromycin (Zithromax)


Macrolides: Therapeutic UsesMacrolides: Therapeutic Uses

Strep infectionsStrep infections

• Streptococcus pyogenes Streptococcus pyogenes (group A beta-hemolytic streptococci)(group A beta-hemolytic streptococci)

Mild to moderate URIMild to moderate URI

• Haemophilus influenzaeHaemophilus influenzae

Spirochetal infectionsSpirochetal infections

• Syphilis and Lyme diseaseSyphilis and Lyme disease

Gonorrhea, Chlamydia, MycoplasmaGonorrhea, Chlamydia, Mycoplasma


Macrolides: Side EffectsMacrolides: Side Effects

GI effects, primarily with erythromycin:GI effects, primarily with erythromycin:

• nausea, vomiting, diarrhea, hepatotoxicity, nausea, vomiting, diarrhea, hepatotoxicity, flatulence, jaundice, anorexiaflatulence, jaundice, anorexia

• Newer agents, azithromycin and clarithromycin: Newer agents, azithromycin and clarithromycin: fewer side effects, longer duration of action, fewer side effects, longer duration of action, better efficacy, better tissue penetrationbetter efficacy, better tissue penetration


Antibiotics: Nursing ImplicationsAntibiotics: Nursing Implications

• Before beginning therapy, Before beginning therapy, assess drug allergies; other assess drug allergies; other labslabs

• Be sure to obtain thorough Be sure to obtain thorough patient health history,.patient health history,.

• Assess for conditions that Assess for conditions that may be contraindications to may be contraindications to antibiotic useantibiotic use

• Assess for potential drug Assess for potential drug interactions.interactions.



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



• Patients should be instructed to take antibiotics Patients should be instructed to take antibiotics exactly as prescribed exactly as prescribed

• Assess for signs and symptoms of superinfection: Assess for signs and symptoms of superinfection:

– FeverFever

– Cough Cough

– Perineal itchingPerineal itching

– Sore throatSore throat



• Check the name of the medication carefully Check the name of the medication carefully since there are many agents that sound alike since there are many agents that sound alike or have similar spellings.or have similar spellings.



• Each class of antibiotics has specific side Each class of antibiotics has specific side effects and drug interactions that must be effects and drug interactions that must be carefully assessed and monitored.carefully assessed and monitored.

• The most common side effects of antibiotics The most common side effects of antibiotics are nausea, vomiting, and diarrhea.are nausea, vomiting, and diarrhea.

• All oral antibiotics are absorbed better if All oral antibiotics are absorbed better if taken with at least 6 to 8 ounces of water.taken with at least 6 to 8 ounces of water.



SulfonamidesSulfonamides

• Should be taken with at Should be taken with at least 2400 mL of fluid least 2400 mL of fluid per day, unless per day, unless contraindicated.contraindicated.

• Due to photosensitivity, Due to photosensitivity, avoid sunlight and avoid sunlight and tanning beds.tanning beds.

• These agents reduce the These agents reduce the effectiveness of effectiveness of oral contraceptives.oral contraceptives.




• Monitor for 30 minutes.Monitor for 30 minutes.

• The effectiveness of oral The effectiveness of oral penicillins is decreased penicillins is decreased when taken with when taken with caffeine, citrus fruit, cola caffeine, citrus fruit, cola beverages, fruit juices, beverages, fruit juices, or tomato juice.or tomato juice.



CephalosporinsCephalosporins

• Orally administered forms Orally administered forms should be given with food to should be given with food to decrease GI upset, even decrease GI upset, even though this will delay though this will delay absorption.absorption.

• Some of these agents may Some of these agents may cause an Antabuse-like cause an Antabuse-like reaction when taken with reaction when taken with alcohol.alcohol.



TetracyclinesTetracyclines

• AvoidAvoid

– MilkMilk

– IronIron

– antacidsantacids

• 6 to 8 ounces of fluid, 6 to 8 ounces of fluid, preferably water.preferably water.

• Due to photosensitivity, Due to photosensitivity, avoid sunlight and avoid sunlight and tanning beds.tanning beds.




• Monitor peak and trough blood levels Monitor peak and trough blood levels

• Symptoms of ototoxicity Symptoms of ototoxicity

– dizziness, tinnitus, and hearing loss.dizziness, tinnitus, and hearing loss.

• Symptoms of nephrotoxicitySymptoms of nephrotoxicity

– urinary casts, proteinuria, and increased BUN urinary casts, proteinuria, and increased BUN and serum creatinine levels.and serum creatinine levels.




• Should be taken with at Should be taken with at least 3 L of fluid per day, least 3 L of fluid per day, unless otherwise specifiedunless otherwise specified



MacrolidesMacrolides

• These agents are highly protein-bound and These agents are highly protein-bound and will cause severe interactions with other will cause severe interactions with other protein-bound drugs.protein-bound drugs.



Monitor for therapeutic effects:Monitor for therapeutic effects:

• Disappearance of Disappearance of

• FeverFever

• LethargyLethargy

• DrainageDrainage

• RednessRedness

Anti-Infective Agents

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