1.Antibiotics

AntibioticsAntibiotics

Learning ObjectivesLearning Objectives

Identify the Identify the major types of antibioticsmajor types of antibiotics by drug class.by drug class.

Know which Know which auxiliary labelsauxiliary labels to use when to use when dispensing major types of antibiotics.dispensing major types of antibiotics.

Define Define therapeutic effects, side effects, therapeutic effects, side effects, andand administration routesadministration routes of major of major antibiotics.antibiotics.

Use Use antibioticantibiotic and general and general drug drug terminologyterminology correctly in written and oral correctly in written and oral communications.communications.

Anti-Infective Anti-Infective AgentsAgents

Antibiotics:Antibiotics:

SulfonamidesSulfonamides

PenicillinsPenicillins

CephalosporinsCephalosporins

TetracyclinesTetracyclines

AminoglycosidesAminoglycosides

QuinolonesQuinolones

MacrolidesMacrolides


Medications used to treat Medications used to treat bacterial infectionsbacterial infections

Ideally, before beginning Ideally, before beginning antibiotic therapy, the suspected antibiotic therapy, the suspected areas of infection should be areas of infection should be cultured to identify the causative cultured to identify the causative organism and potential antibiotic organism and potential antibiotic susceptibilities.susceptibilities.


Empiric therapy: treatment of an Empiric therapy: treatment of an infection before specific culture infection before specific culture information has been reported or information has been reported or obtainedobtained

Prophylactic therapy: treatment Prophylactic therapy: treatment with antibiotics to prevent an with antibiotics to prevent an infection, as in intra-abdominal infection, as in intra-abdominal surgerysurgery


Bactericidal: kill bacteriaBactericidal: kill bacteriaBacteriostatic: inhibit growth of Bacteriostatic: inhibit growth of susceptible bacteria, rather than susceptible bacteria, rather than killing them immediately; will killing them immediately; will eventually lead to bacterial deatheventually lead to bacterial death

Types of BacteriaTypes of Bacteria

Aerobic bacteria Aerobic bacteria needs oxygen to surviveneeds oxygen to survive

Anaerobic bacteriaAnaerobic bacteriasurvives in the absence of survives in the absence of oxygenoxygen

Bacteria ShapesBacteria Shapes

(a) Round cocci(a) Round cocci

(b) Rod-like bacilli(b) Rod-like bacilli

(c) Spiral-shaped spirochetes (c) Spiral-shaped spirochetes

Gram’s Stain Results and Gram’s Stain Results and Related DiseasesRelated Diseases

ShapShapee

Gram’s Gram’s StainStain

BacteriaBacteria Related Related DiseaseDisease

rodsrods gram-gram-positivepositive

CorynebacteriaCorynebacteria endocarditisendocarditis

gram-gram-negative negative

E. ColiE. Coli UTIUTI


ShapeShape Gram’s Gram’s StainStain


coccicocci gram-gram-positivepositive

StaphylococcusStaphylococcus toxic shock toxic shock syndromesyndrome


NeisseriaNeisseria gonorrheagonorrhea


ShapeShape Gram’s Gram’s StainStain


curved or curved or spiral spiral rodsrods

gram-gram-negativenegative

CampylobacterCampylobacter septicemiasepticemia

spirochetspirocheteses


Treponema Treponema palladiumpalladium

syphilissyphilis

How Antibiotics WorkHow Antibiotics Work

Block protein formationBlock protein formation


Block protein formationBlock protein formation– MacrolidesMacrolides– TetracyclinesTetracyclines– Aminoglycosides Aminoglycosides


Block protein formationBlock protein formation Inhibit cell wall formationInhibit cell wall formation Interfere with DNA formationInterfere with DNA formation


Block protein formationBlock protein formation Inhibit cell wall formationInhibit cell wall formation Interfere with DNA formationInterfere with DNA formation

– Nalidixic acid Nalidixic acid


Block protein formationBlock protein formation Inhibit cell wall formationInhibit cell wall formation Interfere with DNA formationInterfere with DNA formation Prevent folic acid synthesisPrevent folic acid synthesis


Block protein formationBlock protein formation Inhibit cell wall formationInhibit cell wall formation Interfere with DNA formationInterfere with DNA formation Prevent folic acid synthesisPrevent folic acid synthesis

– Sulfonamides Sulfonamides

SulfonamidesSulfonamides

One of the first groups of One of the first groups of antibantibасасterial agentsterial agents

sulfadiazinesulfadiazine sulfamethizolesulfamethizole sulfamethoxazolesulfamethoxazole sulfisoxazolesulfisoxazole

Sulfonamides: Sulfonamides: Mechanism of ActionMechanism of Action Bacteriostatic actionBacteriostatic action Prevent synthesis of folic acid Prevent synthesis of folic acid

required for synthesis of purines required for synthesis of purines and nucleic acidand nucleic acid

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

Structure of Structure of sulfonamidessulfonamides

para-Aminobenzoic acid sulfonamide

Classification of sulfonamidesClassification of sulfonamides(according(accordinglyly to duration to duration of of action) action)

Short aShort acction:tion: streptocid, sulfadimezine, streptocid, sulfadimezine, aethazole, norsulfazole, urosulfan, aethazole, norsulfazole, urosulfan, sulfizoxazole, sulfacyl-sodiumsulfizoxazole, sulfacyl-sodium

Medium duration of action:Medium duration of action: sulfamethoxazole (is a part of co-sulfamethoxazole (is a part of co-trimoxazole)trimoxazole)

Longlasting action:Longlasting action: sulfadimethoxyn, sulfadimethoxyn, sulfapirydazin, sulfamonomethoxynsulfapirydazin, sulfamonomethoxyn

Super longlasting action:Super longlasting action: sulfalen, sulfalen, sulfadoxyn (is a part of fansidar)sulfadoxyn (is a part of fansidar)

Sulfonamides: Sulfonamides: sulfamethoxazole Therapeutic sulfamethoxazole Therapeutic UsesUsesAzo-GantanolAzo-Gantanol Combined with phenazopyridine Combined with phenazopyridine

(an analgesic-anesthetic that affects the (an analgesic-anesthetic that affects the mucosa mucosa of the urinary tract).of the urinary tract).

Used to treat urinary tract infections (UTIs) Used to treat urinary tract infections (UTIs) and to reduce the pain associated with UTIsand to reduce the pain associated with UTIs..

BactrimBactrim Combined with trimethoprim.Combined with trimethoprim. Used to treat UTIs, Pneumocystis carinii Used to treat UTIs, Pneumocystis carinii

pneumonia, ear infections, bronchitis, pneumonia, ear infections, bronchitis, gonorrhea, etc.gonorrhea, etc.

Co-trimoxazole (Bactrim)Co-trimoxazole (Bactrim)

480 - for adults480 - for adults 960 - for adults960 - for adults 120 – for children120 – for children 240 – for children240 – for children

Orally 2 times dailyOrally 2 times daily

Co-trimoxazole = Bactrim Co-trimoxazole = Bactrim (trimeth(trimethooprim + prim + sulfamethoxazole)sulfamethoxazole)

Sulfonamides: Sulfonamides: sulfisoxazole sulfisoxazole Therapeutic UsesTherapeutic UsesAzo-GantrisinAzo-Gantrisin Combined with phenazopyridine Combined with phenazopyridine Used for UTIsUsed for UTIs

PediazolePediazole Combined with erythromycinCombined with erythromycin Used to treat otitis media Used to treat otitis media

Sulfonamides: Side Sulfonamides: Side EffectsEffects

Body SystemBody System EffectEffectBloodBlood Hemolytic and Hemolytic and

aplastic aplastic anemia, anemia, thrombocytopeniathrombocytopenia

IntegumentaryIntegumentary Photosensitivity, Photosensitivity, exfoliative exfoliative dermatitis, dermatitis, Stevens-Johnson Stevens-Johnson syndrome, syndrome, epidermal epidermal necrolysisnecrolysis

Sulfonamides: Side Sulfonamides: Side EffectsEffects

Body SystemBody System EffectEffectGIGI Nausea, Nausea,

vomiting, diarrhea,vomiting, diarrhea, pancreatitispancreatitis

OtherOther Convulsions, Convulsions, crystalluria,crystalluria,

toxic nephrosis, toxic nephrosis, headache, headache, peripheral peripheral neuritis, urticarianeuritis, urticaria

Sulfonamides’ Sulfonamides’ Dispensing IssuesDispensing Issues Avoid the sunAvoid the sun Maintain adequate fluid intakeMaintain adequate fluid intake

Classes of AntibioticsClasses of Antibiotics

Sulfonamides Penicillins Cephalosporins Tetracyclines Macrolides

Ketolides Quinolones Streptogramins Aminoglycosid

es Cyclic Lipopeti

des

Antibiotics: PenicillinsAntibiotics: Penicillins

Natural penicillinsNatural penicillins Penicillinase-resistant penicillinsPenicillinase-resistant penicillins AminopenicillinsAminopenicillins Extended-spectrum penicillinsExtended-spectrum penicillins


Natural penicillinsNatural penicillins penicillin G, penicillin V potassiumpenicillin G, penicillin V potassium

Penicillinase-resistant penicillinsPenicillinase-resistant penicillins cloxacillin, dicloxacillin, methicillin, cloxacillin, dicloxacillin, methicillin,

nafcillin, oxacillinnafcillin, oxacillin


AminopenicillinsAminopenicillins amoxicillin, ampicillin, bacampicillinamoxicillin, ampicillin, bacampicillin

Extended-spectrum penicillinsExtended-spectrum penicillins piperacillin, ticarcillin, carbenicillin, piperacillin, ticarcillin, carbenicillin,

mezlocillinmezlocillin


First introduced in the 1940sFirst introduced in the 1940s Bactericidal: inhibit cell wall Bactericidal: inhibit cell wall

synthesissynthesis Kill a wide variety of bacteriaKill a wide variety of bacteria Also called “beta-lactams”Also called “beta-lactams”

Nucleus of penicillin moleculeL – beta-lactame ring, T – thiazoline ring

N

TL

S

CO

OH

CH3

CH3

O

H2N


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

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

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


Chemicals have been developed to Chemicals have been developed to inhibit these enzymes:inhibit these enzymes:– clavulanic acidclavulanic acid– tazobactamtazobactam– sulbactamsulbactam

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


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

– ampicillin + sulbactam = Unasynampicillin + sulbactam = Unasyn

– amoxicillin + clavulanic acid = amoxicillin + clavulanic acid = AugmentinAugmentin

– ticarcillin + clavulanic acid = Timentinticarcillin + clavulanic acid = Timentin

– piperacillin + tazobactam = Zosynpiperacillin + tazobactam = Zosyn

Unasyn (ampicillin/sulbactam)

Penicillins: Mechanism of Penicillins: Mechanism of ActionAction

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

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

Once bound, normal cell wall synthesis is Once bound, normal cell wall synthesis is disrupted.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: Penicillins: Therapeutic UsesTherapeutic Uses Prevention and treatment of Prevention and treatment of

infections caused by susceptible infections caused by susceptible bacteria, such as:bacteria, such as:– gram-positive bacteriagram-positive bacteria– Streptococcus, Enterococcus, Streptococcus, Enterococcus,

Staphylococcus speciesStaphylococcus species

Penicillins: Adverse Penicillins: Adverse EffectsEffects Allergic reactions occur in 0.7% – Allergic reactions occur in 0.7% –

8% of treatments 8% of treatments – urticaria, pruritus, angioedemaurticaria, pruritus, angioedema

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

and and 10% of these are fatal10% of these are fatal

Penicillins: Side Penicillins: Side EffectsEffects Common side effects:Common side effects:

– nausea, vomiting, diarrhea, nausea, vomiting, diarrhea, abdominal painabdominal pain

Other side effects are less Other side effects are less commoncommon

Penicillins’ Dispensing Penicillins’ Dispensing IssuesIssues Take on an empty stomachTake on an empty stomach

– Food slows absorptionFood slows absorption– Acids in fruit juices or colas Acids in fruit juices or colas

could deactivate the drugcould deactivate the drug

Penicillin ResistancePenicillin Resistance

Penicillinase-resistant Penicillinase-resistant penicillins work against penicillins work against gram-positive aerobes gram-positive aerobes

Extended-spectrum Extended-spectrum penicillins are more resistant penicillins are more resistant to gram-negative bacteriato gram-negative bacteria

Penicillin combinations Penicillin combinations improve effectimprove effect

Antibiotics: Antibiotics: CephalosporinsCephalosporins First GenerationFirst Generation Second GenerationSecond Generation Third GenerationThird Generation Fourth GenerationFourth Generation

Structure of cephalosporinsL – beta-lactame ring, D – dihydrothiazine ring

CH2 O CO CH3

C

O

H2N

O

OH

S

L D

N

Antibiotics: Antibiotics: CephalosporinsCephalosporins

Semisynthetic derivatives from a fungusSemisynthetic derivatives from a fungus Structurally and pharmacologically Structurally and pharmacologically

related 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 Cephalosporins: First GenerationGeneration

cefadroxilcefadroxil cephalexincephalexin cephradinecephradine cefazolincefazolin cephalothincephalothin cephapirincephapirin

– Good gram-positive coverageGood gram-positive coverage– Poor gram-negative coveragePoor gram-negative coverage


First-generationFirst-generation– Similar to penicillinase-resistant Similar to penicillinase-resistant

penicillins with greater gram-penicillins with greater gram-negative coveragenegative coverage

– Used for Used for community-acquired infectionscommunity-acquired infections mild to moderate infectionsmild to moderate infections

Cephalosporins: First Cephalosporins: First GenerationGeneration

cefazolincefazolin cephalexincephalexin

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

IV and POIV and PO POPO

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

Cephalosporins: Cephalosporins: Second GenerationSecond Generation

cefaclorcefaclor •• cefonicidcefonicid

cefprozilcefprozil •• ceforanide ceforanide

cefamandolecefamandole •• cefmetazolecefmetazole

cefoxitincefoxitin •• cefotetancefotetan cefuroximecefuroxime

– Good gram-positive coverageGood gram-positive coverage

– Better gram-negative coverage than first Better gram-negative coverage than first generationgeneration


Second-generationSecond-generation– Increased activity, especially against Increased activity, especially against

Haemophilus influenzaeHaemophilus influenzae– Used for Used for

Otitis media in childrenOtitis media in children Respiratory infectionsRespiratory infections UTIsUTIs

Cephalosporins: Cephalosporins: Second GenerationSecond Generation

CefoxitinCefoxitin cefuroximecefuroxime

(Mefoxin)(Mefoxin) (Kefurox and Ceftin)(Kefurox and Ceftin)

IV and IMIV and IM POPO

Used prophylactically forUsed prophylactically for Surgical Surgical prophylaxisprophylaxisabdominal or colorectalabdominal or colorectalsurgeriessurgeries Does not killDoes not killAlso kills anaerobesAlso kills anaerobes anaerobesanaerobes

Cephalosporins: Third Cephalosporins: Third GenerationGeneration

cefiximecefixime •• ceftizoxime ceftizoxime cefpodoxime proxetilcefpodoxime proxetil •• ceftriaxone ceftriaxone cefoperazonecefoperazone •• ceftazidime ceftazidime cefotaximecefotaxime •• moxalactam moxalactam

– Most potent group against gram-negativeMost potent group against gram-negative– Less active against gram-positiveLess active against gram-positive


Third-generationThird-generation– Active against a wide spectrum of Active against a wide spectrum of

gram-negative organismsgram-negative organisms– Long half-life, so once-a-day dosing Long half-life, so once-a-day dosing

for somefor some– Used forUsed for

Ambulatory patientsAmbulatory patients Children (dosing before or after school)Children (dosing before or after school)


cefixime (Suprax)cefixime (Suprax) Only oral third-generation agentOnly oral third-generation agent Best of available oral cephalosporins Best of available oral cephalosporins

against against gram-negativegram-negative

Tablet and suspensionTablet and suspension

ceftriaxone (Rocephin)ceftriaxone (Rocephin) IV and IM, long half-life, once-a-day dosingIV and IM, long half-life, once-a-day dosing Easily passes meninges and diffused into Easily passes meninges and diffused into

CSF CSF to treat CNS infectionsto treat CNS infections


ceftazidime (Ceptaz, Fortaz, Tazidime, Tazicef)ceftazidime (Ceptaz, Fortaz, Tazidime, Tazicef)

IV and IMIV and IM

Excellent gram-negative coverageExcellent gram-negative coverage

Used for difficult-to-treat organisms such as Pseudomonas spp.Used for difficult-to-treat organisms such as Pseudomonas spp.

Eliminated renally instead of biliary routeEliminated renally instead of biliary route

Excellent spectrum of coverageExcellent spectrum of coverage

Cephalosporins: Cephalosporins: Fourth GenerationFourth Generation

cefepime (Maxipime)cefepime (Maxipime) Newest cephalosporin agents.Newest cephalosporin agents. Broader spectrum of antibacterial Broader spectrum of antibacterial

activity than activity than third generation, especially against third generation, especially against gram-positive bacteria.gram-positive bacteria.

Antimicrobial spectrum of cephalosporins

Generation Generation of of

cephalosporicephalosporinsns

Active towards Active towards Stability Stability towards beta-towards beta-

lactamaselactamase

GramGram--positive positive bacteriabacteria

Gram-Gram-negativnegative e bacteribacteriaa

StaphylStaphylo coccio cocci

Gram-Gram-negative negative bacteriabacteria

ІІ ++++++ +/-+/- ++++ -- ІІІІ ++++ ++ ++++ +/-+/-

ІІІІІІ ++ ++++++ ++ ++

ІІVV ++++ ++++++ ++++ ++++


Alert the Pharmacist if a Alert the Pharmacist if a patient allergic to patient allergic to penicillins is receiving a penicillins is receiving a cephalosporin prescription.cephalosporin prescription.

Warning!

Cephalosporins Side Cephalosporins Side EffectsEffects Share side effects of penicillinShare side effects of penicillin Few may initiate unique toxic Few may initiate unique toxic

reactionsreactions Lower frequency of toxicity than Lower frequency of toxicity than

many other antibioticsmany other antibiotics

Complications, caused by cephalosporins

Irritation of mucous membrane of digestive tract, Irritation of mucous membrane of digestive tract, infiltrates after intromuscular introduction , phlebitis infiltrates after intromuscular introduction , phlebitis after inrtavenous introduction after inrtavenous introduction

Disbacteriosis, superinfectionDisbacteriosis, superinfection Allergic reactions, including cross allergy with Allergic reactions, including cross allergy with

penicillinspenicillins Granulocytopenia (in case of treatment during more Granulocytopenia (in case of treatment during more

than 2 weeks)than 2 weeks) Hemorrhages (inhibition of synthesis of factors of Hemorrhages (inhibition of synthesis of factors of

blood coagulation in liver) – cephalosporins ІІІblood coagulation in liver) – cephalosporins ІІІ Nephrotoxicity (accumulation in epithilial cells of Nephrotoxicity (accumulation in epithilial cells of

kidney canalicules)kidney canalicules) Encephalopathy (hyperreflexia, судоми, coma) Encephalopathy (hyperreflexia, судоми, coma)


All of the cephalosporins look All of the cephalosporins look alike when written in the alike when written in the generic form. Watch for generic form. Watch for dosing and indications for use.dosing and indications for use.

Warning!

Antibiotics: Antibiotics: TetracyclinesTetracyclines demeclocycline (Declomycin)demeclocycline (Declomycin) oxytetracyclineoxytetracycline tetracyclinetetracycline doxycycline (Doryx, Doxy-Caps, doxycycline (Doryx, Doxy-Caps,

Vibramycin)Vibramycin) minocyclineminocycline

Antibiotics: Antibiotics: TetracyclinesTetracyclines Natural and semi-syntheticNatural and semi-synthetic Obtained from cultures of Obtained from cultures of

StreptomycesStreptomyces Bacteriostatic—inhibit bacterial Bacteriostatic—inhibit bacterial

growthgrowth Inhibit protein synthesisInhibit protein synthesis Stop many essential functions of Stop many essential functions of

the bacteriathe bacteria

Antibiotics: Antibiotics: TetracyclinesTetracyclines 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, Thus, dairy products, antacids, and iron and iron salts reduce absorption of salts reduce absorption of tetracyclinestetracyclines

Tetracyclines: Tetracyclines: Therapeutic UsesTherapeutic Uses Wide spectrum:Wide spectrum:

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

Demeclocycline is also used to Demeclocycline is also used to treat SIADH, and pleural and treat SIADH, and pleural and pericardial effusionspericardial effusions

Therapeutic Uses of Therapeutic Uses of TetracyclinesTetracyclines AcneAcne Chronic bronchitisChronic bronchitis Lyme diseaseLyme disease MycoplasmaMycoplasma pneumoniaepneumoniae

infectioninfection RickettsiaRickettsia infection infection Some venereal diseases, such as Some venereal diseases, such as

ChlamydiaChlamydia infection infection Traveler’s diarrheaTraveler’s diarrhea

Tetracyclines: Side Tetracyclines: Side EffectsEffects

Strong affinity for calcium Strong affinity for calcium Discoloration of permanent teeth Discoloration of permanent teeth

and tooth and tooth enamel in fetuses and childrenenamel in fetuses and children

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


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

Superinfection (overgrowth of Superinfection (overgrowth of nonsusceptible organisms such as nonsusceptible 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

Tetracyclines’ Tetracyclines’ Dispensing IssuesDispensing Issues Avoid antacids to avoid chelation Avoid antacids to avoid chelation

with mineralswith minerals PhotosensitizationPhotosensitization To be avoided by pregnant To be avoided by pregnant

women and childrenwomen and children Expired drugs are dangerousExpired drugs are dangerous

Antibiotics: Antibiotics: AminoglycosidesAminoglycosides

gentamicin (Garamycin)gentamicin (Garamycin) kanamycinkanamycin neomycinneomycin streptomycinstreptomycin tobramycintobramycin amikacin (Amikin)amikacin (Amikin) netilmicin netilmicin


Natural and semi-syntheticNatural and semi-synthetic Produced from StreptomycesProduced from Streptomyces Poor oral absorption; no PO formsPoor oral absorption; no PO forms Very potent antibiotics with Very potent antibiotics with

serious toxicitiesserious toxicities BactericidalBactericidal Kill mostly gram-negative; some Kill mostly gram-negative; some

gram-positive alsogram-positive also


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

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


Three most common (systemic): gentamicin, Three most common (systemic): gentamicin, tobramycin, amikacintobramycin, amikacin

Cause serious toxicities:Cause serious toxicities:

– Nephrotoxicity (renal failure)Nephrotoxicity (renal failure)

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

Must monitor drug levels to prevent toxicitiesMust monitor drug levels to prevent toxicities

Aminoglycosides: Side Aminoglycosides: Side EffectsEffects

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

HeadacheHeadache ParesthesiaParesthesia Neuromuscular blockadeNeuromuscular blockade DizzinessDizziness VertigoVertigo Skin rashSkin rash FeverFever SuperinfectionsSuperinfections

Antibiotics: Antibiotics: QuinolonesQuinolones

ciprofloxacin (Cipro)ciprofloxacin (Cipro) enoxacin (Penetrex)enoxacin (Penetrex) lomefloxacin (Maxaquin)lomefloxacin (Maxaquin) norfloxacin (Noroxin)norfloxacin (Noroxin) ofloxacin (Floxin)ofloxacin (Floxin)

QuinolonesQuinolones

Excellent oral absorptionExcellent oral absorption Absorption reduced by Absorption reduced by

antacidsantacids First oral antibiotics effective First oral antibiotics effective

against against gram-negative bacteriagram-negative bacteria

Quinolones: Quinolones: Mechanism of ActionMechanism of Action

BactericidalBactericidal Effective against gram-Effective against gram-

negative organisms and some negative organisms and some gram-positive organismsgram-positive organisms

Alter DNA of bacteria, causing Alter DNA of bacteria, causing deathdeath

Do not affect human DNADo not affect human DNA

Quinolones: Quinolones: Therapeutic UsesTherapeutic Uses

Lower respiratory tract Lower respiratory tract infectionsinfections

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 Quinolones: Side EffectsEffects

Body SystemBody System EffectsEffectsCNSCNS headache, headache,

dizziness, fatigue, dizziness, fatigue, depression, restlessnessdepression, restlessness

GIGI nausea, nausea, vomiting, diarrhea, vomiting, diarrhea, constipation, thrush, constipation, thrush, increased liver functionincreased liver function studiesstudies

Quinolones: Side Quinolones: Side EffectsEffects

Body SystemBody System EffectsEffectsIntegumentaryIntegumentary rash, pruritus, rash, pruritus,

urticaria, urticaria, flushing, flushing, photosensitivity photosensitivity (with (with lomefloxacin)lomefloxacin)

OtherOther fever, chills, blurred fever, chills, blurred vision, vision, tinnitustinnitus

Quinolones’ Quinolones’ Dispensing IssuesDispensing Issues Not to be given with theophyllineNot to be given with theophylline Antacids interfere with absorptionAntacids interfere with absorption Avoid exposure to sunAvoid exposure to sun

Antibiotics: Antibiotics: MacrolidesMacrolides

erythromycin erythromycin azithromycin (Zithromax)azithromycin (Zithromax) clarithromycin (Biaxin)clarithromycin (Biaxin) dirithromycindirithromycin troleandomycintroleandomycin

– bactericidal actionbactericidal action

Erythromycin Erythromycin FormulationsFormulations

Macrolides: Macrolides: Therapeutic UsesTherapeutic 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 Macrolides: Side EffectsEffects

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

Macrolides’ Dispensing Macrolides’ Dispensing IssuesIssues

Although most antibiotics should be Although most antibiotics should be taken on an empty stomach, taken on an empty stomach, erythromycins usually cause severe erythromycins usually cause severe GI distress, so should be taken with GI distress, so should be taken with foodfood

Antibiotic Dispensing Antibiotic Dispensing IssuesIssues

Mix exactly as directed by manufacturerMix exactly as directed by manufacturer Swab counting tray with alcohol between Swab counting tray with alcohol between

drugs to prevent cross-contaminationdrugs to prevent cross-contamination

Warning!

Antibiotic Side EffectsAntibiotic Side Effects

Most antibiotics should be taken Most antibiotics should be taken on an empty stomach to attain on an empty stomach to attain faster absorptionfaster absorption

Examples of exceptionsExamples of exceptions– nitrofurantoin (Macrobid, nitrofurantoin (Macrobid,

Macrodantin)Macrodantin)– cefuroxime (Ceftin, Zinacef)cefuroxime (Ceftin, Zinacef)

Antibiotics: Nursing Antibiotics: Nursing ImplicationsImplications

Before beginning therapy, assess drug Before beginning therapy, assess drug allergies; hepatic, liver, and cardiac allergies; hepatic, liver, and cardiac function; and other lab studies.function; and other lab studies.

Be sure to obtain thorough patient health Be sure to obtain thorough patient health history, including immune status.history, including immune status.

Assess for conditions that may be Assess for conditions that may be contraindications to antibiotic use, or that contraindications to antibiotic use, or that may indicate cautious use.may indicate cautious use.

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


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


Patients should be instructed to take Patients should be instructed to take antibiotics exactly as prescribed and for antibiotics exactly as prescribed and for the length of time prescribed; they should the length of time prescribed; they should not stop taking the medication early not stop taking the medication early when they feel better.when they feel better.

Assess for signs and symptoms of Assess for signs and symptoms of superinfection: fever, perineal itching, superinfection: fever, perineal itching, cough, lethargy, or any unusual cough, lethargy, or any unusual discharge.discharge.

Antibiotics: Nursing Antibiotics: Nursing ImplicationsImplications For safety reasons, check the For safety reasons, check the

name of the medication carefully name of the medication carefully since there are many agents that since there are many agents that sound alike or have similar sound alike or have similar spellings.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 The most common side effects of antibiotics are nausea, vomiting, and antibiotics are nausea, vomiting, and diarrhea.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 least 2400 Should be taken with at least 2400

mL of fluid mL of fluid per day, unless contraindicated.per day, unless contraindicated.

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

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

Antibiotics: Nursing Antibiotics: Nursing ImplicationsImplicationsPenicillinsPenicillins Any patient taking a penicillin should be Any patient taking a penicillin should be

carefully monitored for an allergic reaction for carefully monitored for an allergic reaction for at least 30 minutes after its administration.at least 30 minutes after its administration.

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



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

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


TetracyclinesTetracyclines Milk products, iron preparations, antacids, Milk products, iron preparations, antacids,

and other dairy products should be avoided and other dairy products should be avoided because of the chelation and drug-binding because of the chelation and drug-binding that occurs.that occurs.

All medications should be taken with 6 to 8 All medications should be taken with 6 to 8 ounces of fluid, preferably water.ounces of fluid, preferably water.

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


AminoglycosidesAminoglycosides Monitor peak and trough blood levels of Monitor peak and trough blood levels of

these agents to prevent nephrotoxicity these agents to prevent nephrotoxicity and ototoxicity.and ototoxicity.

Symptoms of ototoxicity include Symptoms of ototoxicity include dizziness, tinnitus, and hearing loss.dizziness, tinnitus, and hearing loss.

Symptoms of nephrotoxicity include Symptoms of nephrotoxicity include urinary casts, proteinuria, and increased urinary casts, proteinuria, and increased BUN and serum creatinine levels.BUN and serum creatinine levels.


QuinolonesQuinolones Should be taken with at least 3 L of Should be taken with at least 3 L of

fluid per day, unless otherwise fluid per day, unless otherwise specifiedspecified

Antibiotics: Nursing Antibiotics: Nursing ImplicationsImplicationsMacrolidesMacrolides These agents are highly protein-bound These agents are highly protein-bound

and will cause severe interactions with and will cause severe interactions with other protein-bound drugs.other protein-bound drugs.

The absorption of oral erythromycin is The absorption of oral erythromycin is enhanced when taken on an empty enhanced when taken on an empty stomach, but because stomach, but because of the high incidence of GI upset, of the high incidence of GI upset, many agents many agents are taken after a meal or snack.are taken after a meal or snack.


Monitor for therapeutic effects:Monitor for therapeutic effects: Disappearance of fever, lethargy, Disappearance of fever, lethargy,

drainage, and rednessdrainage, and redness

The ABC’s of The ABC’s of AntibioticsAntibiotics

Lourdes Irizarry, MDLourdes Irizarry, MD

Associate Professor of MedicineAssociate Professor of Medicine

Albuquerque VAMC & UNM SOMAlbuquerque VAMC & UNM SOM

Principles of Antimicrobial Principles of Antimicrobial TherapyTherapy

Site of actionSite of action Individual patientIndividual patient Ecology of the institutionEcology of the institution EfficacyEfficacy ToxicityToxicity CostCost

Classes of AntibioticsClasses of Antibiotics

Beta lactamsBeta lactams MonobactamsMonobactams CarbapenemsCarbapenems Macrolides/Azalides/LincosamidesMacrolides/Azalides/Lincosamides AminoglycosidesAminoglycosides FluoroquinolonesFluoroquinolones OxazolidinonesOxazolidinones

Antibiotic brandsAntibiotic brands

50 penicillins50 penicillins 71 71

cephalosporinscephalosporins 12 tetracyclines12 tetracyclines 8 8

aminoglycosidesaminoglycosides 1 monobactam1 monobactam 3 carbapenems3 carbapenems

9 macrolides9 macrolides 2 2

streptograminsstreptogramins 3 dihydrofolate 3 dihydrofolate

reductase reductase inhibitorsinhibitors

1 oxazolidinone1 oxazolidinone 5.5 quinolones5.5 quinolones

Inhibition of Cell Cell Wall Inhibition of Cell Cell Wall SynthesisSynthesis

Vancomycin, teicoplaninVancomycin, teicoplanin Beta-lactamsBeta-lactams MonobactamsMonobactams CarbapenemsCarbapenems

Inhibition of Protein Inhibition of Protein SynthesisSynthesis

50 S inhibitors50 S inhibitors– macrolidesmacrolides

– chloramphenicochloramphenicoll

– clindamycinclindamycin

30 S inhibitors30 S inhibitors– tetracyclinetetracycline

– aminoglycosideaminoglycosidess

– oxazolidinonesoxazolidinones

Interference with basic Interference with basic cell functionscell functions

– quinolonesquinolones DNA gyraseDNA gyrase

Folic acid Folic acid metabolismmetabolism

– trimethopritrimethoprimm

– sulfonamidesulfonamidess

Antibiotic InactivationAntibiotic Inactivation

Destruction or modificationDestruction or modification– Ex: Beta-lactamase productionEx: Beta-lactamase production

Alteration of the antibiotic Alteration of the antibiotic target site(s)target site(s)– Ex: Abnormal PBPsEx: Abnormal PBPs

Prevention of access to targetPrevention of access to target– Ex: Efflux pump & Deletions of Ex: Efflux pump & Deletions of

porinsporins

Antibiotic Essentials’Antibiotic Essentials’

Antibiotic Gram(+)

Gram.(-)

Anaerobes CNS

PCN +Strep. A,Listeria,

Enterococcus(Not Staph.Not PRSTP)

-N.meingitidis

EikenellaPasteurella

+/ - +Neurosyphilis

N.meningitidis

Nafcillin MSSA - - +

Ampicillin +Enterococcus(Not S. pyogenes,

Not Sthaph.)

+/ -E.coli,

ProteusB-lactamase neg.H.flu, Moraxella

+/ - +Listeria

Antibiotic Essentials’ Antibiotic Essentials’ (2)(2)

Antibiotic Gram.(+)

Gram.(-)

Anaerobes CNS

Ticarcillin +i.e. PCN

NotEnterococcus

+++P.aeruginosa

(NotAcitenobacter)

+ +/ -

Piperacillin +i.e. PCN

E. faecalis

+++ + +/ -

Mezlocillin +i.e. PCN

Enterococcus

+++ + +/ -


Antibiotic Gram.(+)

Gram.(-)

Anaerobes CNS

Ampicillin/Sulbactam

+++MSSA, MSSE

Not PRSTP

+i.e.

AmpicillinH. flu,

MoraxellaFew Klebsiella

+++ -

Ticarcillin/Clavulanic

acid

+++MSSA, MSSENot Enterococcus

+++No increasedactivity for

Pseudomonas

+++ -

Piperacillin/Tazobactam

+++MSSA, MSSE,Enterococcus

+++No increasedactivity for

Pseudomonas

+++ -


Antibiotic Gram.(+)

Gram.(-)

Anaerobes CNS

1st gen.Cephalosporins

+MSSA,MSSENot STP

NotEnterococcus

+/ -Not B-

lactamaseproducers

- -


3rd GenCephalosporin

Gram.(+)

Gram.(-)

Anaerobes CNS

Ceftazidime - +++Anti-

pseudomonal

- +++

Ceftriaxone +++MSSA, MSSE,

PRSTPNot Enterococcus

++Not anti-

pseudomonal

- +++

Cefotaxime +++Not ideal for

Staph.Not Enterococcus

++Not anti-

pseudomonal

++ +++

Ceftizoxime ++Not ideal for

Staph.Not Enterococcus

++Not anti-

pseudomonal

++ +++


4th GenerationCephalosporin

Gram.(+)

Gram.(-)

Anaerobes CNS

Cefepeme +++MSSA, MSSE

NotEnterococcus

+++Anti-

pseudomonal

- +++

Antibiotic Essentials: Antibiotic Essentials: (7)(7)

Antibiotic Gram.(+)

Gram.(-)

Anaerobes CNS

MeropenemImipenem

+++Not MRSA, NotEnterococcus

+++Not.

Sternothrophomonas

+++ +

Aztreonam - +++ - +/ -

Antibiotic Essentials’: Antibiotic Essentials’: (9)(9)

Antibiotic Gram.(+)

Gram.(-)

Anaerobes CNS

AzithromycinClarithromy

+Not

Enterococcus+/- SAU

H. FluMoraxella

- -

Erythromycin +Not

Enterococcus+/-SAU

+/- H. flu &Moraxella

- -


Erythromycin and Clarithromycin Erythromycin and Clarithromycin have hepatic metabolism via have hepatic metabolism via cytochrome p-450 cytochrome p-450 (Increase levels of (Increase levels of theophylline, warfarin, triazolam, theophylline, warfarin, triazolam, bromocriptine, carbamazepine and bromocriptine, carbamazepine and cyclosporin)cyclosporin)

Erythromycin iv from causes Erythromycin iv from causes phlebitis, not Azithromycin, no IV phlebitis, not Azithromycin, no IV Clarithromycin (too venous toxic)Clarithromycin (too venous toxic)

Classification of Classification of FuoroquinolonesFuoroquinolones

First generationFirst generation– nalidixic acidnalidixic acid

Second Second generationgeneration– norfloxacinnorfloxacin– ciprofloxacin*ciprofloxacin*– ofloxacinofloxacin– levofloxacinlevofloxacin

Third generation**Third generation**

– gatifloxacingatifloxacin (sparfloxacin, (sparfloxacin,

grepafloxacin)grepafloxacin)

Fourth Fourth generation***generation***– moxifloxacinmoxifloxacin– trovafloxacin, trovafloxacin,

(clinafloxacin)(clinafloxacin)

Activity of Fluoroquinolones Activity of Fluoroquinolones Against Gram Positive BacteriaAgainst Gram Positive Bacteria

Species Cipro. Gati. Levo. Moxi. Trova Oflox

MSSA 0.5-.078 0.1-0.13 0.25 0.06 0.06 0.125-1

MRSA 3.13-32 0.2-16 16 4 4

S. epi 0.39-1 0.2-0.25 0.5-1 0.13 0.015-4 0.125-1

E.faecalis

1.56-4 0.78-2 1-3.13 1 0.12-2 1-8

E.faecium

3.13-16 1.56-4 3.13-8 1-4 0.25-8 1-4

S.pneumo

1.56-4 0.5 1-3.13 0.12-0.25

0.12-0.5

1-2

Activity of Fluoroquinolones for Activity of Fluoroquinolones for Gram Negative BacteriaGram Negative Bacteria

Species

E.cloac

E.coli

Amp.-R

Kleb.

Cefz.-R

Pseudo.

Cipro

0.03-0.1

0.016-0.516

0.06-0.398

0.78-8

Gati

0.06-0.2

0.016-0.18

0.1-0.39

4

3.13-32

Levo

0.06

0.03

16

0.13

16

32

Moxi

0.06

0.008

8

0.13

8

32

Trova

0.06

0.03-0.5

32

0.13-0.5

16

2-32

Oflox

0.03-0.12

0.25-32

Activity of Fluoroquinolones Activity of Fluoroquinolones Against AnaerobesAgainst Anaerobes

Species Cipro Gati Levo Moxi Trova

B. frag 2-128 0.25-1 2 0.12 0.25-2

C.difficile 16-32 1-2 8 - 1-2-16

Peptostre 0.5-8 1 3.13>4 2 0.25-0.5

Susceptibility of S.pneumoniae

to Fluoroquinolones

Year

Pn

eu

mococci W

ith

R

ed

uced

S

uscep

tib

ilit

y t

o

Flu

oro

qu

inolo

nes (

%)

No.

of

Pre

scri

pti

ons

per

100

Pers

ons

0

1

2

3

4

5

88 89 90 91 92 93 94 95 96 97 98

0

1

2

3

4

5

6

Ages 15-64Age 65 and older

Chen DK, et al. N Engl J Med. 1999;341:233-239.

Activity of New Activity of New Fluoroquinolones Against Fluoroquinolones Against MRSA, VRE and PRSPMRSA, VRE and PRSP

MRSA VRE PRSP QTc change

Levofloxacin +/- +/- ++ 4.6 msc

Gatifloxacin +/- +/- ++++ 2.9 msc

Moxifloxacin +/- +/- ++++ 6 msc

Gemifloxacin +/- +/- ++++ 5 msc

Ciprofloxacin +/--- +/--- +/--- ?

Quinupristin/Quinupristin/DalfopristinDalfopristin S. pneumoniaeS. pneumoniae

S.aureusS.aureus (MRSA) (MRSA)

E. faeciumE. faecium (VRE) (VRE)– No activity against No activity against E. faecalisE. faecalis

Others’...Others’...

Metronidazole anaerobic drug Metronidazole anaerobic drug with excellent CNS penetrationwith excellent CNS penetration

Clindamycin: good for Gram.(+) Clindamycin: good for Gram.(+) and anaerobes. Always include in and anaerobes. Always include in the treatment of Strep. skin & soft the treatment of Strep. skin & soft tissue infections. Great for lung tissue infections. Great for lung abscesses. (No CNS penetration)abscesses. (No CNS penetration)

Vancomycin: Vancomycin: InferiorInferior to B- to B-lactams against SAUlactams against SAU

Other highlights...Other highlights...

Cross allergic reaction between Cross allergic reaction between Penicillins, Cephalosporins and Penicillins, Cephalosporins and Carbapenems. Not Aztreonam.Carbapenems. Not Aztreonam.

Aztreonam cross allergy with Aztreonam cross allergy with CeftazidimeCeftazidime

Cephalosporins and Cephalosporins and Metronidazole: Disulfiram reactionMetronidazole: Disulfiram reaction

Ticarcillin: bleeding in uremic Ticarcillin: bleeding in uremic patientspatients

Drugs Under Drugs Under DevelopmentDevelopmentPRSP, MRSA,VISA,VREPRSP, MRSA,VISA,VRE

Lipopetides (Daptomycin: narrow Lipopetides (Daptomycin: narrow therapeutic index)therapeutic index)

GlycyclinesGlycyclines Glycopeptides (Vancomycin Glycopeptides (Vancomycin

analogues)analogues) Fluoroquinolones Fluoroquinolones Macrolides/KetolidesMacrolides/Ketolides Evernimicin (trials on hold)Evernimicin (trials on hold)

Antibiotics With Antibiotics With Immunomodulating Immunomodulating EffectsEffects MacrolidesMacrolides

FluoroquinolonesFluoroquinolones

Quinupristin/Quinupristin/dalfopristin dalfopristin

Future Directions on the Future Directions on the Treatment of InfectionsTreatment of Infections

Usage of immunomudalating agentsUsage of immunomudalating agents Usage of non-antibiotics as Usage of non-antibiotics as

adjuvant therapyadjuvant therapy New approaches to rational drug New approaches to rational drug

designdesign– mappingmapping– bindingbinding– genomicsgenomics

““A collection of A collection of anecdotes is anecdotes is not data.”not data.”

AnonymousAnonymous

““You have to run You have to run towards where the towards where the ball is going to be.”ball is going to be.”

Yogi BerraYogi Berra

““Prediction is Prediction is very difficult, very difficult, particularly particularly about the about the future.”future.”

Neils BohrNeils Bohr

ABT-492ABT-492

4th generation fluororoquinolone4th generation fluororoquinolone Trovafloxacin like activityTrovafloxacin like activity Levofloxacin safety profileLevofloxacin safety profile Little CNS or CV activityLittle CNS or CV activity Iv & poIv & po Phase I trials 2,000Phase I trials 2,000

ABT-723ABT-723

KetolideKetolide– ketone added to erythromycinketone added to erythromycin– quinoline ring increases activityquinoline ring increases activity

Phase II trialsPhase II trials Phase III Fall 2,000Phase III Fall 2,000 S. pneumoniaeS. pneumoniae activity 2-3x activity 2-3x

higher than clarithromycinhigher than clarithromycin


Inhibits RNA dependent protein Inhibits RNA dependent protein synthesis, causing dissociation of synthesis, causing dissociation of peptidyl transfer (tRNA) from the peptidyl transfer (tRNA) from the ribosome during elongation phaseribosome during elongation phase

FluoroquinolonesFluoroquinolonesMechanism of ActionMechanism of Action

Inhibit the activities of DNA Inhibit the activities of DNA gyrase (an essential adenosine gyrase (an essential adenosine triphosphate-hydrolizing triphosphate-hydrolizing topoisomerase) which in turn topoisomerase) which in turn inhibits bacterial DNA peplication inhibits bacterial DNA peplication and transcription. Leading to and transcription. Leading to bacterial death.bacterial death.

Mechanism of Action of Mechanism of Action of Quinolones (2)Quinolones (2)

To accommodate within bacterial To accommodate within bacterial cell, organism’s DNA helix is coiled cell, organism’s DNA helix is coiled and twisted in a direction opposite and twisted in a direction opposite to the double helix (negative to the double helix (negative supercoil). DNA gyrase catalyzes supercoil). DNA gyrase catalyzes the entry of these negative the entry of these negative supercoils into circular supercoils into circular chromosomal DNA and plasmid chromosomal DNA and plasmid DNADNA

Mechanism of Action Mechanism of Action Quinolone (3)Quinolone (3)

DNA gyrase consists of 2A and 2B DNA gyrase consists of 2A and 2B subunits. A interrupts supercoiling. subunits. A interrupts supercoiling. After fixing the negative supercoils After fixing the negative supercoils in place, A reseals the break.in place, A reseals the break.

Quinolones trap the complex after Quinolones trap the complex after strand breakage preventing A from strand breakage preventing A from resealing the breaks. DNA sythesis resealing the breaks. DNA sythesis is halted. is halted.

Mechanisms of Mechanisms of ResistanceResistance Spontaneous mutations in Spontaneous mutations in

bacterial chromosomesbacterial chromosomes– Mutations in A subunit of bacterial Mutations in A subunit of bacterial

DNA gyrase that lowers affinity of DNA gyrase that lowers affinity of drug at gyrase complexdrug at gyrase complex

– Mutations of chromosomally Mutations of chromosomally mediated drug influx and efflux mediated drug influx and efflux systemssystems

– Selection for resistance dependent on Selection for resistance dependent on quinolone and organism quinolone and organism

1.Antibiotics

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