Antibiotic Use In DentistryAntibiotic Use In Dentistry

Pharmacology of the Pharmacology of the AntibioticsAntibiotics

The anti-infective drugsThe anti-infective drugs

Anti-infective agents are Anti-infective agents are drugs that are drugs that are designed to act selectively on foreign designed to act selectively on foreign organismsorganisms that have invaded and that have invaded and infected the bodyinfected the body

The anti-infective drugsThe anti-infective drugs

Anti-infective drugs - range from Anti-infective drugs - range from AntiAntibacterialsbacterials AntiAntifungalsfungals AntiAntiprotozoalsprotozoals AntiAntihelminthicshelminthics AntiAntivirals virals AntiAntimycobacterialmycobacterial

General Mechanisms of Action of General Mechanisms of Action of anti-infective agentsanti-infective agents

The mechanisms are: The mechanisms are: Inhibition the Inhibition the biosynthesis of biosynthesis of

bacterial cell WALLbacterial cell WALL Inhibition of protein synthesis Inhibition of protein synthesis Some change Some change the cell membrane the cell membrane

permeabilitypermeability Some inhibit DNA synthesisSome inhibit DNA synthesis

ExamplesExamples

CELL WALL CELL WALL INHIBITORSINHIBITORS

penicillin, penicillin, cephalosporin, cephalosporin, vancomycinvancomycin

PROTEIN PROTEIN SYNTHESIS SYNTHESIS INHIBITORSINHIBITORS

Macrolides, Macrolides, aminogylcosidesaminogylcosides

CELL WALL CELL WALL PermeabilityPermeability

KetoconazoleKetoconazole

DNA SYNTHESIS DNA SYNTHESIS INHIBITORSINHIBITORS

QuinolonesQuinolones

Spectrum of Activity of Anti-infectivesSpectrum of Activity of Anti-infectives

Narrow spectrumNarrow spectrum

Broad-spectrumBroad-spectrum

Spectrum of Activity of Anti-infectivesSpectrum of Activity of Anti-infectives

Narrow spectrum anti-infectives affect Narrow spectrum anti-infectives affect only a few bacterial typesonly a few bacterial types

The early penicillin drugs are examples.The early penicillin drugs are examples.

Spectrum of Activity of Anti-infectivesSpectrum of Activity of Anti-infectives

Broad-spectrum anti-infectives affect Broad-spectrum anti-infectives affect many bacteria.many bacteria.

Meropenem is an example. Meropenem is an example. Because narrow spectrum antibiotics Because narrow spectrum antibiotics

are selective, are selective, they are more active they are more active against single organismsagainst single organisms than the than the broad spectrum antibiotics. broad spectrum antibiotics.

Spectrum of Activity of Anti-Spectrum of Activity of Anti-infectivesinfectives

Anti-infectives that interfere with the Anti-infectives that interfere with the ability of the cell to reproduce/replicate ability of the cell to reproduce/replicate without killing them are called without killing them are called BACTERIOSTATIC drugs. BACTERIOSTATIC drugs.

Tetracycline is an example. Tetracycline is an example.

Spectrum of Activity of Anti-Spectrum of Activity of Anti-infectivesinfectives

Antibiotics that can aggressively cause Antibiotics that can aggressively cause bacterial death are called bacterial death are called BACTERICIDAL. BACTERICIDAL.

These properties (-cidal and –static) can These properties (-cidal and –static) can also depend on the antibiotic also depend on the antibiotic concentration in the blood.concentration in the blood.

(e.g. Erythromycin and Clindamycin may (e.g. Erythromycin and Clindamycin may be bactericidal at higher blood levels)be bactericidal at higher blood levels)

Spectrum of Activity of Anti-infectivesSpectrum of Activity of Anti-infectives

BacteriostaticBacteriostatic

Erythromycin, tetracyclines, Erythromycin, tetracyclines,

clindamycin, chloramphenicol, clindamycin, chloramphenicol,

spectinomycin, sulfonamidesspectinomycin, sulfonamides

BactericidalBactericidal

- Penicillins, Cephalosphorins, - Penicillins, Cephalosphorins,

Metronidazole, Aminoglycosides, Metronidazole, Aminoglycosides,

Vancomycin, PolymyxinVancomycin, Polymyxin

Factors That Determine the Likehood Of a Factors That Determine the Likehood Of a microorganism Causing an Infection:microorganism Causing an Infection:

1.1. Virulence of the microorganismVirulence of the microorganism

2.2. Number of the microorganism presentNumber of the microorganism present

3.3. Resistance of the hostResistance of the host

Common Adverse Reactions to Common Adverse Reactions to Anti-infective TherapyAnti-infective Therapy

The most common adverse effects are due The most common adverse effects are due to the direct action of the drugs in the to the direct action of the drugs in the following organ system- Neuro, nephro following organ system- Neuro, nephro and GI systemand GI system

Common Adverse Reactions to Common Adverse Reactions to Anti-infective TherapyAnti-infective Therapy

1.1. NephrotoxicityNephrotoxicity– Antibiotics that are metabolized and Antibiotics that are metabolized and

excreted in the kidney most excreted in the kidney most frequently cause kidney damage.frequently cause kidney damage.

Common Adverse Reactions to Common Adverse Reactions to Anti-infective TherapyAnti-infective Therapy

2. Gastro-intestinal toxicity2. Gastro-intestinal toxicity Direct toxic effect to the cells of the GI Direct toxic effect to the cells of the GI

tract can cause nausea, vomiting, tract can cause nausea, vomiting, stomach pain and diarrhea. stomach pain and diarrhea.

Some drugs are toxic to liver cells and Some drugs are toxic to liver cells and can cause hepatitis or liver failure. can cause hepatitis or liver failure.

Common Adverse Reactions to Common Adverse Reactions to Anti-infective TherapyAnti-infective Therapy

3. CNS toxicity3. CNS toxicity When drugs can pass through the brain When drugs can pass through the brain

barrier and accumulate in the nervous barrier and accumulate in the nervous tissues, they can interfere with neuronal tissues, they can interfere with neuronal function.function.

Common Adverse Reactions to Common Adverse Reactions to Anti-infective TherapyAnti-infective Therapy

4. Hypersensitivity4. Hypersensitivity Most protein antibiotics can induce the Most protein antibiotics can induce the

body’s immune system to produce body’s immune system to produce allergic responses.allergic responses.

Drugs are considered foreign Drugs are considered foreign substances and when taken by the substances and when taken by the individual, it encounters the body’s individual, it encounters the body’s immune cells.immune cells.

Common Adverse Reactions to Common Adverse Reactions to Anti-infective TherapyAnti-infective Therapy

5. Super-infections5. Super-infections Opportunistic infections that develop Opportunistic infections that develop

during the course of antibiotic therapy during the course of antibiotic therapy are called are called SUPERINFECTIONSSUPERINFECTIONS. .

Beta-lactam antibioticsBeta-lactam antibiotics

Antibiotics containingAntibiotics containing beta-lactam ringbeta-lactam ring Classification (based on structure)Classification (based on structure)

– PenicillinsPenicillins– CephalosporinsCephalosporins– CarbapenemsCarbapenems– MonobactamsMonobactams

และและ– Beta-lactamase inhibitorsBeta-lactamase inhibitors

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The PENICILLINSThe PENICILLINSNarrow spectrum penicillinsNarrow spectrum penicillins

– Penicillin GPenicillin G– Penicillin VPenicillin V

Broad Spectrum Penicillins (aminopenicillin)Broad Spectrum Penicillins (aminopenicillin)– AmoxicillinAmoxicillin– AmpicillinAmpicillin– BacampicillinBacampicillin

Penicillinase-resistant Penicillin (anti-staphyloccocal penicillins)Penicillinase-resistant Penicillin (anti-staphyloccocal penicillins)– CloxacillinCloxacillin– NafcillinNafcillin– MethicillinMethicillin– DicloxacillinDicloxacillin– Oxacillin Oxacillin

Extended-Spectrum penicillins (Anti-pseudomonal penicillins)Extended-Spectrum penicillins (Anti-pseudomonal penicillins)– CarbenicillinCarbenicillin– MezlocillinMezlocillin– PiperacillinPiperacillin– TicacillinTicacillin

Beta-lactamase inhibitorsBeta-lactamase inhibitors– Clavulanic acidClavulanic acid– SulbactamSulbactam– TazobactamTazobactam

Penicillins : ClassificationPenicillins : ClassificationGroup 1:Group 1: Benzyl penicillinBenzyl penicillin

Pen GPen GGroup 2:Group 2: Orally absorbed penicillinOrally absorbed penicillin

Pen VPen VGroup 3:Group 3: Staphylococcal penicillinase-Staphylococcal penicillinase-

resistant penicillinsresistant penicillinsCloxacillinCloxacillin

Group 4:Group 4: Extended or broad-spectrum Extended or broad-spectrum penicillinspenicillinsAminopenicillinsAminopenicillinsAmidopenicillinsAmidopenicillins

Group 5:Group 5: Antipseudomonal penicillinsAntipseudomonal penicillinsCarboxypenicillinsCarboxypenicillinsUreidopenicillinsUreidopenicillins

Group 6:Group 6: Beta-lactamase resistant penicillinsBeta-lactamase resistant penicillins2727

Penicillin : Spectrum of Penicillin : Spectrum of ActivityActivity

Gram-positi

ve

Gram-negativ

e

Beta-lactam

ase

Pseudomonas

Group 1 + 2 Pen G, Pen V

++++ + Sensitive

-

Group 3 Antistaph Pen

+++ + ResistantS.

aureus

-

Group 4Aminopenicillins

++++ ++ Sensitive

-

Group 4Amidopenicillins

++ +++ Sensitive

-

Group 5Antipseudomonas

++++ ++ Sensitive

+

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PenicillinPenicillinThe action of PenicillinsThe action of Penicillins The penicillin and penicillinase-resistant The penicillin and penicillinase-resistant

penicillins produce BACTERICIDAL penicillins produce BACTERICIDAL effects by effects by interfering with the ability of interfering with the ability of susceptible bacteria to biosynthesize susceptible bacteria to biosynthesize the framework of the cell wall. the framework of the cell wall.

To be maximally effective, inhibitors of To be maximally effective, inhibitors of cell wall synthesis require actively cell wall synthesis require actively proliferating microorganisms; they have proliferating microorganisms; they have little or no effect on bacteria that are not little or no effect on bacteria that are not growing and dividing.growing and dividing.

PenicillinPenicillin

The bacterium will have The bacterium will have weakened cell wall, will swell weakened cell wall, will swell and then burst from the osmotic and then burst from the osmotic pressure within the cell. pressure within the cell.

The penicillins are among the most widely The penicillins are among the most widely effective antibiotics and also the least toxic effective antibiotics and also the least toxic drugs known, but increased resistance has drugs known, but increased resistance has limited their uselimited their use

Penicillins : drug Penicillins : drug resistanceresistance

Major mechanism –Major mechanism – production of production of Beta-lactamasesBeta-lactamases– PenicillinasesPenicillinases– CephalosporinasesCephalosporinases– Carbapenem-hydrolyzing enzymesCarbapenem-hydrolyzing enzymes

MRSA – Methicillin resistance MRSA – Methicillin resistance S. aureusS. aureus– MRSA – important health problemMRSA – important health problem– Order of resistance development of StaphylococciOrder of resistance development of Staphylococci

Non-resistant StaphNon-resistant Staph sensitive to Pen Gsensitive to Pen G Resistant StaphResistant Staph resistant toresistant to Pen GPen G sensitive to sensitive to

MethicillinMethicillin MRSAMRSA resistant to Pen Gresistant to Pen G resistant to resistant to MethicillinMethicillin

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Penicillins : Penicillins : PharmocokineticsPharmocokinetics

Penicillins – Organic acidPenicillins – Organic acid Penicillins 2 formsPenicillins 2 forms

– Acid-labile Acid-labile - Pen G- Pen G parenteral routeparenteral route– Acid-stableAcid-stable - Pen V- Pen V oral routeoral route

PK parameters in generalPK parameters in general– Low VdLow Vd– Short Half-lifeShort Half-life– Distribute mostly in extracellular waterDistribute mostly in extracellular water– Move hardly across biological membranesMove hardly across biological membranes

Excreted mostly via kidneysExcreted mostly via kidneys

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Penicillin Penicillin

Therapeutic Indications of Therapeutic Indications of penicillin:penicillin:

The penicillins are indicated for The penicillins are indicated for the treatment of streptococcal the treatment of streptococcal infectionsinfections

SyphilisSyphilis TetanusTetanus

Adverse Effects of PenicillinsAdverse Effects of Penicillins

GI system effects- GI system effects- the major adverse the major adverse effects of penicillin therapy involve the effects of penicillin therapy involve the GITGIT. .

Nausea, vomiting, diarrhea, abdominal Nausea, vomiting, diarrhea, abdominal pain, glossitis, stomatitis, gastritis, sore pain, glossitis, stomatitis, gastritis, sore mouth and furry tongue. mouth and furry tongue.

The reason for some of these effects The reason for some of these effects (superinfection) is associated with the (superinfection) is associated with the loss of bacterial flora.loss of bacterial flora.

Adverse Effects of PenicillinsAdverse Effects of Penicillins

Hypersensitivity reactions- rashes, Hypersensitivity reactions- rashes, pruritus, fever and urticaria pruritus, fever and urticaria

These indicate mild allergic reaction. These indicate mild allergic reaction. Wheezing and diarrhea may also occur. Wheezing and diarrhea may also occur.

Anaphylaxis can also happen leading to Anaphylaxis can also happen leading to shock or death. It occurs in 5-10% of shock or death. It occurs in 5-10% of those receiving penicillins. those receiving penicillins.

Pain and inflammation on injection sitesPain and inflammation on injection sites

Adverse reactions of penicillinAdverse reactions of penicillin

Nephritis:Nephritis: Neurotoxicity: Neurotoxicity: The penicillins are irritating The penicillins are irritating

to neuronal tissue, and they can provoke 4. to neuronal tissue, and they can provoke 4. seizures if injected intrathecally or if very seizures if injected intrathecally or if very high blood levels are reached. Epileptic high blood levels are reached. Epileptic patients are particularly at risk.patients are particularly at risk.

Penicillins : Clinical UsesPenicillins : Clinical Uses

Commonly used PenicillinsCommonly used Penicillins– Benzyl PenicillinBenzyl Penicillin

Pen G, Pen VPen G, Pen V

– Extended-spectrum PenicillinsExtended-spectrum Penicillins Ampicillin, AmoxicillinAmpicillin, Amoxicillin

– Penicillins + Beta-lactamase inhibitorsPenicillins + Beta-lactamase inhibitors Group 3 andGroup 3 and Group 5Group 5

– Used for specific case of infectionUsed for specific case of infection– Group 3 Anti-StaphGroup 3 Anti-Staph– Group 5 Anti-PseudomonasGroup 5 Anti-Pseudomonas

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Penicillins and aminoglycosides: The antibacterial effects of Penicillins and aminoglycosides: The antibacterial effects of all the all the ββ-lactam antibiotics are synergistic with the -lactam antibiotics are synergistic with the aminoglycosides. aminoglycosides.

Because cell wall synthesis inhibitors alter the permeability of Because cell wall synthesis inhibitors alter the permeability of bacterial cells, these drugs can facilitate the entry of other bacterial cells, these drugs can facilitate the entry of other antibiotics (such as aminoglycosides) that might not ordinarily antibiotics (such as aminoglycosides) that might not ordinarily gain access to intracellular target sites. gain access to intracellular target sites.

This can result in enhanced antimicrobial activity. This can result in enhanced antimicrobial activity. [Note: Although the combination of a penicillin plus an [Note: Although the combination of a penicillin plus an

aminoglycoside is used clinically, these drug types should aminoglycoside is used clinically, these drug types should never be placed in the same infusion fluid, because on never be placed in the same infusion fluid, because on prolonged contact, the positively charged aminoglycosides prolonged contact, the positively charged aminoglycosides form an inactive complex with the negatively charged form an inactive complex with the negatively charged

penicillinspenicillins.].]

Routes of administration: Routes of administration: Ticarcillin, carbenicillin, piperacillin, and the Ticarcillin, carbenicillin, piperacillin, and the combinations of ampicillin with sulbactam, ticarcillin with combinations of ampicillin with sulbactam, ticarcillin with clavulanic acid must be administered intravenously (IV) clavulanic acid must be administered intravenously (IV) or intramuscularly (IM). or intramuscularly (IM). Penicillin V, amoxicillin, amoxicillin combined with Penicillin V, amoxicillin, amoxicillin combined with clavulanic acid, and the indanyl ester of carbenicillin (for clavulanic acid, and the indanyl ester of carbenicillin (for treatment of urinary tract infections) are available only as treatment of urinary tract infections) are available only as oral preparations. oral preparations. Others are effective by the oral, IV, or IM routes .Others are effective by the oral, IV, or IM routes .Depot forms: Procaine penicillin G and benzathine Depot forms: Procaine penicillin G and benzathine penicillin G are administered IM and serve as depot penicillin G are administered IM and serve as depot forms. They are slowly absorbed into the circulation and forms. They are slowly absorbed into the circulation and persist at low levels over a long time period.persist at low levels over a long time period.

absorptionabsorption Absorption of all the penicillinase-resistant Absorption of all the penicillinase-resistant

penicillins is decreased by food in the penicillins is decreased by food in the stomach, because gastric emptying time is stomach, because gastric emptying time is lengthened, and the drugs are destroyed in lengthened, and the drugs are destroyed in the acidic environment. Therefore, they the acidic environment. Therefore, they must be administered 30 to 60 minutes must be administered 30 to 60 minutes before meals or 2 to 3 hours postprandially. before meals or 2 to 3 hours postprandially.

Other penicillins are less affected by food.Other penicillins are less affected by food.

DistributionDistribution

The The ββ-lactam antibiotics distribute well -lactam antibiotics distribute well throughout the body. throughout the body.

All the penicillins cross the placental barrier, All the penicillins cross the placental barrier, but none has been shown to be teratogenic.but none has been shown to be teratogenic.

However, penetration into certain sites, such However, penetration into certain sites, such as bone or cerebrospinal fluid (CSF), is as bone or cerebrospinal fluid (CSF), is insufficient for therapy unless these sites insufficient for therapy unless these sites are inflamedare inflamed

ExcretionExcretion

The primary route of excretion is through the The primary route of excretion is through the organic acid (tubular) secretory system of organic acid (tubular) secretory system of the kidney as well as by glomerular filtration. the kidney as well as by glomerular filtration.

Patients with impaired renal function must Patients with impaired renal function must have dosage regimens adjusted.have dosage regimens adjusted.

The penicillins are also excreted into breast The penicillins are also excreted into breast milk.milk.

CephalosporinsCephalosporinsIntroductionIntroduction

Effective in the treatment of all strains of bacteria Effective in the treatment of all strains of bacteria affected by penicillins and some strains resistant to affected by penicillins and some strains resistant to penicillins penicillins

Classification: Classification: Divided into first-, second-, third-, Divided into first-, second-, third-, and fourth-generation drugsand fourth-generation drugs

CephalosporinsCephalosporins

First generation CephalosporinsFirst generation Cephalosporins– Cefazolin (Ancef) – Cefazolin (Ancef) – MSSA, Surgical ProphylaxisMSSA, Surgical Prophylaxis– Cephalexin Cephalexin

Second generation CephalosporinsSecond generation Cephalosporins– CefoxitinCefoxitin– CefotetanCefotetan

CephalosporinsCephalosporins

Third generation CephalosporinsThird generation Cephalosporins– Ceftriaxone – Ceftriaxone – meningitis, pneumonnia, meningitis, pneumonnia,

gonorrhaegonorrhae– Ceftazidime – Ceftazidime – Pseudomonas, Pyelonephritis Pseudomonas, Pyelonephritis

Fourth generation CephalosporinsFourth generation Cephalosporins– Cefepime – Similar to the 3rdgen. compounds, Cefepime – Similar to the 3rdgen. compounds,

but more resistant to hydrolysis by some but more resistant to hydrolysis by some ββ-- lactamases.lactamases.

zz

Cephalosporins: Cephalosporins: ActionsActions

Exert bactericidal effectExert bactericidal effect– Have a beta-lactam ringHave a beta-lactam ring

Targets the bacterial cell wall, making it Targets the bacterial cell wall, making it defective and unstabledefective and unstable

Cephalosporins:Cephalosporins: Uses Uses

Used to treat infections caused by bacteriaUsed to treat infections caused by bacteria– Respiratory Respiratory – Ear Ear – Bone/jointBone/joint– Genitourinary tract infections Genitourinary tract infections

Used during peri-operative periodUsed during peri-operative period

PHARMACOKINETICSPHARMACOKINETICS

Excretion is via the kidney and dose Excretion is via the kidney and dose adjustments must be made for impaired adjustments must be made for impaired renal function.renal function.

CephalosporinsCephalosporins: Adverse Reactions: Adverse Reactions

Gastrointestinal reactionsGastrointestinal reactions– Nausea; vomiting; diarrhea Nausea; vomiting; diarrhea

Administration route reactionsAdministration route reactions– Intramuscularly; intravenouslyIntramuscularly; intravenously

Other body system reactionsOther body system reactions– Headache; dizziness; malaise; heartburn; fever; Headache; dizziness; malaise; heartburn; fever;

nephrotoxicity; hypersensitivity; aplastic anemia; nephrotoxicity; hypersensitivity; aplastic anemia; toxic epidermal necrolysistoxic epidermal necrolysis

Allergy: Approximately 10% of people allergic Allergy: Approximately 10% of people allergic to penicillin are also allergic to cephalosporinsto penicillin are also allergic to cephalosporins

In contrast, the incidence of allergic reactions to cephalosporins is one to two percent in patients not allergic to penicillin

Cephalosporins:Cephalosporins: Adverse Reactions Adverse Reactions (continue)(continue)

CephalosporinsCephalosporins: Contraindications and : Contraindications and PrecautionsPrecautions

Contraindicated in patients allergic to Contraindicated in patients allergic to cephalosporins or penicillinscephalosporins or penicillins

Used cautiously in patients with:Used cautiously in patients with: – Renal disease; hepatic impairment; bleeding Renal disease; hepatic impairment; bleeding

disorder disorder

Cephalosporins: Interactions Cephalosporins: Interactions

Drug Common use Effect of interaction

Aminoglycosides

(Gentamicin)

Anti-infective Increased risk for nephrotoxicity

Oral anticoagulants

(Coumadin)

Blood thinner Increased risk for bleeding

Promoting an optimal response to therapyPromoting an optimal response to therapy– Oral administration: Question patient regarding Oral administration: Question patient regarding

allergy to cephalosporins or penicillinsallergy to cephalosporins or penicillins– shake oral suspensionsshake oral suspensions– Administer around the clockAdminister around the clock– Administer orally at least 1 hour before or 2 Administer orally at least 1 hour before or 2

hours after meals hours after meals – If patient experiences GI upset: Administer with If patient experiences GI upset: Administer with

food food

Promoting an optimal response to therapy (cont’d)Promoting an optimal response to therapy (cont’d) People with phenylketonuria need to be People with phenylketonuria need to be

aware that the oral suspension cefprozil aware that the oral suspension cefprozil contains phenylalaninecontains phenylalanine

Interferes with urine test results – diabetic Interferes with urine test results – diabetic patientspatients

CARBAPENEMSCARBAPENEMS

IMIPENEMIMIPENEM

MeropenemMeropenem

ErtapenemErtapenem

ANTIBACTERIAL SPECTRUMANTIBACTERIAL SPECTRUM

Broadest antimicrobial spectrum of any Broadest antimicrobial spectrum of any lactam antibiotic.lactam antibiotic.

Organisms resistant to other types of Organisms resistant to other types of antibiotics. antibiotics.

MECHANISM OF ACTIONMECHANISM OF ACTION

Similar to other Similar to other lactams.lactams.

Resistant to hydrolysis by Resistant to hydrolysis by lactamases.lactamases.

PHARMACOKINETICSPHARMACOKINETICS

Not absorbed orally; usually given IV.Not absorbed orally; usually given IV.Predominantly excreted by the kidneys.Predominantly excreted by the kidneys.Hydrolyzed by a renal tubular enzyme Hydrolyzed by a renal tubular enzyme (dehydropeptidase(dehydropeptidase) ) so given combined with so given combined with cilastatin. cilastatin. This enzyme forms an inactive metabolite This enzyme forms an inactive metabolite that is potentially nephrotoxic. Compounding the that is potentially nephrotoxic. Compounding the imipenem imipenem with with cilastatin cilastatin protects the parent drug and, protects the parent drug and, thus, prevents the formation of the toxic metabolite. thus, prevents the formation of the toxic metabolite. This allows the drug to be used in the treatment of This allows the drug to be used in the treatment of urinary tract infections.urinary tract infections.

Lactamase inhibitorsLactamase inhibitors ββ-Lactamase inhibitors, such as -Lactamase inhibitors, such as clavulanic acid, clavulanic acid,

sulbactamsulbactam, and , and tazobactamtazobactam, contain a , contain a ββ-lactam ring -lactam ring but, by themselves, do not have significant but, by themselves, do not have significant antibacterial activity. antibacterial activity.

Instead, they bind to and inactivate Instead, they bind to and inactivate ββ--lactamases, --lactamases, thereby protecting the antibiotics that are normally thereby protecting the antibiotics that are normally substrates for these enzymes. The substrates for these enzymes. The ββ--lactamase --lactamase inhibitors are therefore formulated in combination inhibitors are therefore formulated in combination with with ββ--lactamase sensitive antibiotics.--lactamase sensitive antibiotics.

VancomycinVancomycin has become increasingly important because of its has become increasingly important because of its

effectiveness against multiple drug-resistant effectiveness against multiple drug-resistant organisms, such as MRSA and enterococciorganisms, such as MRSA and enterococci

Vancomycin Vancomycin inhibits synthesis of bacterial cell wallinhibits synthesis of bacterial cell wall Vancomycin Vancomycin is used in individuals with prosthetic is used in individuals with prosthetic

heart valvesheart valves Vancomycin Vancomycin acts synergistically with the acts synergistically with the

aminoglycosides, and this combination can be aminoglycosides, and this combination can be used in the treatment of enterococcal endocarditisused in the treatment of enterococcal endocarditis

vancomycinvancomycin Side effects are a serious problem with Side effects are a serious problem with

vancomycin vancomycin and include fever, chills, and/or and include fever, chills, and/or phlebitis at the infusion site.phlebitis at the infusion site.

Flushing and shock results from histamine Flushing and shock results from histamine release associated with a rapid infusion. release associated with a rapid infusion.

If an infusion-related reaction occurs, slow the If an infusion-related reaction occurs, slow the infusion rate to administer vancomycin over 2 infusion rate to administer vancomycin over 2 hours, increase the dilution volume, or pretreat hours, increase the dilution volume, or pretreat with an antihistamine 1 hour prior to with an antihistamine 1 hour prior to administration. Additionally, reactions can be administration. Additionally, reactions can be treated with antihistamines and steroids. treated with antihistamines and steroids.

Dose-related hearing loss has occurred in Dose-related hearing loss has occurred in patients with renal failure who accumulate the patients with renal failure who accumulate the drug. drug.

Ototoxicity and nephrotoxicity are more Ototoxicity and nephrotoxicity are more common when common when vancomycin vancomycin is administered is administered with another drug (for example, an with another drug (for example, an aminoglycoside) that can also produce these aminoglycoside) that can also produce these effects.effects.

It is not absorbed orallyIt is not absorbed orally

Protein synthesis inhibitorsProtein synthesis inhibitors A number of antibiotics exert their antimicrobial effects by A number of antibiotics exert their antimicrobial effects by

targeting the bacterial ribosome, which has components targeting the bacterial ribosome, which has components that differ structurally from those of the mammalian that differ structurally from those of the mammalian cytoplasmic ribosome.cytoplasmic ribosome.

the bacterial ribosome is smaller (70S) than the mammalian the bacterial ribosome is smaller (70S) than the mammalian ribosome (80S) and is composed of 50S and 30S subunits ribosome (80S) and is composed of 50S and 30S subunits (as compared to 60S and 40S subunits).(as compared to 60S and 40S subunits).

The drug binds reversibly to the 30S subunit of the bacterial The drug binds reversibly to the 30S subunit of the bacterial ribosome, thereby blocking access of the amino acyl-tRNA ribosome, thereby blocking access of the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor siteto the mRNA-ribosome complex at the acceptor site

Thus, bacterial protein synthesis is inhibited ( Thus, bacterial protein synthesis is inhibited (

The mammalian mitochondrial ribosome, The mammalian mitochondrial ribosome, however, more closely resembles the however, more closely resembles the bacterial ribosome. bacterial ribosome.

Thus, although drugs that interact with the Thus, although drugs that interact with the bacterial target usually spare the host cells, bacterial target usually spare the host cells, high levels of drugs such as high levels of drugs such as chloramphenicol or the tetracyclines may chloramphenicol or the tetracyclines may cause toxic effects as a result of interaction cause toxic effects as a result of interaction with the host mitochondrial ribosomes.with the host mitochondrial ribosomes.

tetracyclinestetracyclines

As broad-spectrum, bacteriostatic As broad-spectrum, bacteriostatic antibiotics, the tetracyclines are effective antibiotics, the tetracyclines are effective against gram-positive and gram-negative against gram-positive and gram-negative

bacteria as well as against organisms other bacteria as well as against organisms other than bacteria.than bacteria.

Widespread resistance to the tetracyclines Widespread resistance to the tetracyclines limits their clinical use.limits their clinical use.

Absorption: All tetracyclines are adequately but Absorption: All tetracyclines are adequately but incompletely absorbed after oral ingestion .incompletely absorbed after oral ingestion .

However, taking these drugs concomitantly with However, taking these drugs concomitantly with dairy foods in the diet decreases absorption due to dairy foods in the diet decreases absorption due to the formation of nonabsorbable chelates of the the formation of nonabsorbable chelates of the tetracyclines with calcium ions. tetracyclines with calcium ions.

Nonabsorbable chelates are als oformed with other Nonabsorbable chelates are als oformed with other divalent and trivalent cations (for example, those divalent and trivalent cations (for example, those found in magnesium and aluminum antacids and in found in magnesium and aluminum antacids and in iron preparations).iron preparations).

Fate: All the tetracyclines concentrate in the liver, Fate: All the tetracyclines concentrate in the liver, where they are, in part, metabolized and conjugated to where they are, in part, metabolized and conjugated to form soluble glucuronides. form soluble glucuronides.

The parent drug and/or its metabolites are secreted The parent drug and/or its metabolites are secreted into the bile. into the bile.

Most tetracyclines are reabsorbed in the intestine via Most tetracyclines are reabsorbed in the intestine via the enterohepatic circulation and enter the urine by the enterohepatic circulation and enter the urine by glomerular filtration.glomerular filtration.

Obstruction of the bile duct and hepatic or renal Obstruction of the bile duct and hepatic or renal dysfunction can increase their half-lives.dysfunction can increase their half-lives.

[Note: Tetracyclines are also excreted in breast milk.][Note: Tetracyclines are also excreted in breast milk.]

tetracyclinestetracyclines

Gastric discomfort:Gastric discomfort: Effects on calcified tissues: Effects on calcified tissues: Deposition in the Deposition in the

bone and primary dentition occurs during bone and primary dentition occurs during calcification in growing children. This causes calcification in growing children. This causes discoloration and hypoplasia of the teeth and a discoloration and hypoplasia of the teeth and a temporary stunting of growth.temporary stunting of growth.

Fatal hepatotoxicity:Fatal hepatotoxicity: PhototoxicityPhototoxicity Pseudotumor cerebri: Pseudotumor cerebri: Benign, intracranial Benign, intracranial

hypertension characterized by headache and hypertension characterized by headache and blurred vision may occur rarely in adults.blurred vision may occur rarely in adults.

SuperinfectionsSuperinfections

AminoglycosidesAminoglycosides Aminoglycoside antibiotics had been the mainstays for Aminoglycoside antibiotics had been the mainstays for

treatment of serious infections due to aerobic gram-treatment of serious infections due to aerobic gram-negative bacilli. negative bacilli.

However, because their use is associated with serious However, because their use is associated with serious toxicities, they have been replaced to some extent by toxicities, they have been replaced to some extent by safer antibiotics, such as the third- and fourth-generation safer antibiotics, such as the third- and fourth-generation cephalosporins, the fluoroquinolones, and the cephalosporins, the fluoroquinolones, and the carbapenems.carbapenems.

All aminoglycosides are bactericidal. The exact All aminoglycosides are bactericidal. The exact mechanism of their lethality is unknown because other mechanism of their lethality is unknown because other antibiotics that affect protein synthesis are generally antibiotics that affect protein synthesis are generally bacteriostatic.bacteriostatic.

Administration:Administration: The highly polar, polycationic structure of The highly polar, polycationic structure of the aminoglycosides prevents adequate absorption after the aminoglycosides prevents adequate absorption after oral administration. Therefore, all aminoglycosides (except oral administration. Therefore, all aminoglycosides (except neomycin must be given parenterally to achieve adequate neomycin must be given parenterally to achieve adequate serum levels. [Note: The severe nephrotoxicity associated serum levels. [Note: The severe nephrotoxicity associated with neomycin precludes parenteral administration.with neomycin precludes parenteral administration.

once-daily dosing with the aminoglycosides can be once-daily dosing with the aminoglycosides can be employed; this results in fewer toxicities. employed; this results in fewer toxicities.

The exceptions are pregnancy, neonatal infections, and The exceptions are pregnancy, neonatal infections, and bacterial endocarditis, in which these agents are bacterial endocarditis, in which these agents are administered in divided doses every 8 hours. administered in divided doses every 8 hours.

The dose that is administered is calculated based on lean The dose that is administered is calculated based on lean body mass, because these drugs do not distribute into fat.]body mass, because these drugs do not distribute into fat.]

Fate:Fate: Metabolism of the aminoglycosides Metabolism of the aminoglycosides does not occur in the host. All are rapidly does not occur in the host. All are rapidly excreted into the urine, predominantly by excreted into the urine, predominantly by glomerular filtration.glomerular filtration.

Accumulation occurs in patients with renal Accumulation occurs in patients with renal failure and require dose modification.failure and require dose modification.

It is important to monitor plasma levels of It is important to monitor plasma levels of gentamicin, tobramycingentamicin, tobramycin, and , and amikacin amikacin to to avoid concentrations that cause dose-avoid concentrations that cause dose-related toxicitiesrelated toxicities

Patient factors, such as old age, previous Patient factors, such as old age, previous exposure to aminoglycosides, and liver exposure to aminoglycosides, and liver disease, tend to predispose patients to disease, tend to predispose patients to adverse reactions.adverse reactions.

Adverse effectsAdverse effects

OtotoxicityOtotoxicityDeafness may be irreversible and has been known to Deafness may be irreversible and has been known to affect fetuses in utero. affect fetuses in utero. Patients simultaneously receiving another ototoxic Patients simultaneously receiving another ototoxic drug, such as drug, such as cisplatin cisplatin or the loop diuretics, or the loop diuretics, furosemide, furosemide, bumetanidebumetanide, or , or ethacrynic acid, ethacrynic acid, are particularly at risk. are particularly at risk. Vertigo and loss of balance may also occur, because Vertigo and loss of balance may also occur, because

these drugs affect the vestibular apparatusthese drugs affect the vestibular apparatus ..

NephrotoxicityNephrotoxicityranging from mild, reversible renal impairment ranging from mild, reversible renal impairment to severe, acute tubular necrosis, which can be to severe, acute tubular necrosis, which can be irreversible.irreversible.

MacrolidesMacrolides Erythromycin Erythromycin was the first of these drugs to find clinical was the first of these drugs to find clinical

application, both as aapplication, both as a drug of first choice and as an drug of first choice and as an alternative to alternative to penicillin penicillin in individuals who are allergic to in individuals who are allergic to ββ--lactam antibiotics. lactam antibiotics.

TheThe newer members of this family, newer members of this family, clarithromycin clarithromycin andand azithromycinazithromycin, have some features in common with, and , have some features in common with, and othersothers that improve on, that improve on, erythromycinerythromycin. .

TelithromycinTelithromycin isis the first ketolide antimicrobial agent that has the first ketolide antimicrobial agent that has been approved and is now in clinical use. been approved and is now in clinical use.

Ketolides andKetolides and macrolides have very similar antimicrobial macrolides have very similar antimicrobial coverage. However, the ketolides are active against many coverage. However, the ketolides are active against many macrolidemacrolide resistantresistant gram-positive strainsgram-positive strains

Mechanism of actionMechanism of action

The macrolides bind irreversibly to a site on the The macrolides bind irreversibly to a site on the 50S subunit of the bacterial ribosome, thus 50S subunit of the bacterial ribosome, thus inhibiting theinhibiting the translocation steps of protein translocation steps of protein synthesissynthesis

Generally considered to be bacteriostatic, they Generally considered to be bacteriostatic, they may be bactericidal at higher dosemay be bactericidal at higher dose

Erythromycin: Erythromycin: This drug is effective against This drug is effective against many of the same organisms as many of the same organisms as penicillin G. penicillin G. therefore, it is used in patients who are allergic to therefore, it is used in patients who are allergic to the penicillins.the penicillins.

Drug interaction:Drug interaction: Erythromycin and telithromycin are Erythromycin and telithromycin are extensively metabolized and are known to extensively metabolized and are known to inhibit the oxidation of a number of drugs inhibit the oxidation of a number of drugs through their interaction with the cytochrome through their interaction with the cytochrome P450 system .P450 system .Interference with the metabolism of drugs such Interference with the metabolism of drugs such as as theophylline theophylline and and carbamazepine carbamazepine has been has been reported for reported for clarithromycinclarithromycinNo interactions have been reported for No interactions have been reported for azithromycinazithromycin..

excretionexcretionErythromycin and azithromycin are primarily Erythromycin and azithromycin are primarily concentrated and excreted in an active form in the bileconcentrated and excreted in an active form in the bilePartial reabsorption occurs through the enterohepatic Partial reabsorption occurs through the enterohepatic circulation. circulation. Inactive metabolites are excreted into the urine. Inactive metabolites are excreted into the urine. In contrast, In contrast, clarithromycin clarithromycin and its metabolites are and its metabolites are eliminated by the kidney as well as the liver, and it is eliminated by the kidney as well as the liver, and it is recommended that the dosage of this drug be adjusted recommended that the dosage of this drug be adjusted in patients with compromised renal function.in patients with compromised renal function.

MacrolidesMacrolides Epigastric distress: Epigastric distress: This side effect is This side effect is

common and can lead to poor patient common and can lead to poor patient compliance for compliance for erythromycinerythromycin..

Cholestatic jaundice:Cholestatic jaundice: Ototoxicity: Ototoxicity: Transient deafness has been Transient deafness has been

associated with associated with erythromycinerythromycin, especially at high , especially at high dosages.dosages.

Patients with hepatic dysfunction should be Patients with hepatic dysfunction should be treated cautiously with treated cautiously with erythromycin, erythromycin, elithromycinelithromycin, or , or azithromycinazithromycin, because these , because these drugs accumulate in the liver. drugs accumulate in the liver.

ClindamycinClindamycin has a has a mechanism of action that is the same as that of mechanism of action that is the same as that of

erythromycin. erythromycin. Clindamycin is employed primarily in the treatment of infections Clindamycin is employed primarily in the treatment of infections

caused by anaerobic bacteria, such as Bacteroides fragilis.caused by anaerobic bacteria, such as Bacteroides fragilis. However, it is also significantly active against However, it is also significantly active against

nonenterococcalnonenterococcal, , gram-positive cocci.gram-positive cocci. Clindamycin is well absorbed by the oral route.Clindamycin is well absorbed by the oral route. Penetration into bone occurs even in the absence of Penetration into bone occurs even in the absence of

inflammationinflammation.. Clindamycin undergoes extensive oxidative metabolism to Clindamycin undergoes extensive oxidative metabolism to

inactive products. The drug is excreted into the bile or urine by inactive products. The drug is excreted into the bile or urine by glomerular filtrationglomerular filtration

Adverse effectsAdverse effectsIn addition to skin rashes, the most serious In addition to skin rashes, the most serious adverse effect is potentially fatal adverse effect is potentially fatal pseudomembranous colitis caused by overgrowth pseudomembranous colitis caused by overgrowth of C. difficile, which elaborates necrotizing toxins. of C. difficile, which elaborates necrotizing toxins. Oral administration of either metronidazole or Oral administration of either metronidazole or vancomycin is usually effective in controlling this vancomycin is usually effective in controlling this serious problem.serious problem.[Note: Vancomycin should be reserved for a [Note: Vancomycin should be reserved for a condition that does not respond to metronidazolecondition that does not respond to metronidazole

QuinolonesQuinolones they inhibit the replication of bacterial DNA by interfering they inhibit the replication of bacterial DNA by interfering

with the action of DNA gyrase (topoisomerase II) and with the action of DNA gyrase (topoisomerase II) and topoisomerase IV during bacterial growth and topoisomerase IV during bacterial growth and reproduction.reproduction.

[Note: Topoisomerases are enzymes that change the [Note: Topoisomerases are enzymes that change the configuration or topology of DNA by a nicking, pass-configuration or topology of DNA by a nicking, pass-through, and resealing mechanism. They do not change through, and resealing mechanism. They do not change the DNA's primary sequence1 the DNA's primary sequence1

Binding of the quinolone to both the enzyme and the DNA Binding of the quinolone to both the enzyme and the DNA forms a ternary complex that inhibits the resealing step, forms a ternary complex that inhibits the resealing step, and can cause cell death by inducing cleavage of the DNA.and can cause cell death by inducing cleavage of the DNA.

All the fluoroquinolones are bactericidal.All the fluoroquinolones are bactericidal. In general, they are effective against gram-In general, they are effective against gram-

negative organisms such as the negative organisms such as the Enterobacteriaceae, Pseudomonas species, Enterobacteriaceae, Pseudomonas species, Haemophilus influenzae, Moraxella catarrhalisHaemophilus influenzae, Moraxella catarrhalis

The newer agents (for example, The newer agents (for example, levofloxacin levofloxacin and and moxifloxacinmoxifloxacin) also have good activity ) also have good activity against some gram-positive organisms .against some gram-positive organisms .

Moxifloxacin Moxifloxacin has activity against many has activity against many anaerobes.anaerobes.

Ingestion of the fluoroquinolones with Ingestion of the fluoroquinolones with sucralfate, antacids containing aluminum or sucralfate, antacids containing aluminum or magnesium, or dietary supplements magnesium, or dietary supplements containing iron or zinc can interfere with the containing iron or zinc can interfere with the absorption of these antibacterial drugs. absorption of these antibacterial drugs.

Calcium and other divalent cations have also Calcium and other divalent cations have also been shown to interfere with the absorption of been shown to interfere with the absorption of these agents. these agents.

The fluoroquinolones with the longest half-The fluoroquinolones with the longest half-lives (levofloxacin and moxifloxacin) permit lives (levofloxacin and moxifloxacin) permit once-daily dosing.once-daily dosing.

All the fluoroquinolones distribute well into All the fluoroquinolones distribute well into all tissues and body fluids. all tissues and body fluids.

Levels are high in boneLevels are high in bone They are excreted by the renal route.They are excreted by the renal route.

quinolonesquinolones GastrointestinalGastrointestinal Central nervous system problems: Central nervous system problems: headache and headache and

dizziness Thus, patients with CNS disorders, such as dizziness Thus, patients with CNS disorders, such as epilepsy, should be treated cautiously with these drugs. epilepsy, should be treated cautiously with these drugs. [Note: [Note: Ciprofloxacin Ciprofloxacin interferes in the metabolism of interferes in the metabolism of theophylline theophylline and may evoke seizures.]and may evoke seizures.]

Phototoxicity: Phototoxicity: Patients taking fluoroquinolones are Patients taking fluoroquinolones are advised to avoid excessive sunlight and to apply advised to avoid excessive sunlight and to apply sunscreens.sunscreens.

However, the latter may not protect completely. Thus, it However, the latter may not protect completely. Thus, it is advisable that the drug should be discontinued at the is advisable that the drug should be discontinued at the first sign of phototoxicity.first sign of phototoxicity.

33

Connective tissue problems: Connective tissue problems: Fluoroquinolones should be avoided in Fluoroquinolones should be avoided in pregnancy, in nursing mothers, and in children pregnancy, in nursing mothers, and in children under 18 years of age, because articular under 18 years of age, because articular cartilage erosion (arthropathy) occurs in cartilage erosion (arthropathy) occurs in immature experimental animals.immature experimental animals.

In adults, fluoroquinolones can infrequently cause In adults, fluoroquinolones can infrequently cause ruptured tendons.ruptured tendons.

Moxifloxacin Moxifloxacin may prolong the QTc interval and, may prolong the QTc interval and, thus, should not be used in patients who are thus, should not be used in patients who are predisposed to arrhythmias or are taking predisposed to arrhythmias or are taking antiarrhythmic medications.antiarrhythmic medications.

CONTRAINDICATIONSCONTRAINDICATIONS AMINOGLYCOSIDES AMINOGLYCOSIDES contraindicated in contraindicated in

1.1. allergies to aminoglycosidesallergies to aminoglycosides2.2. renal failurerenal failure3.3. hepatic diseasehepatic disease4.4. pre-existing hearing losspre-existing hearing loss5.5. myasthenia gravismyasthenia gravis6.6. Parkinson’s Parkinson’s 7.7. pregnancy and lactation.pregnancy and lactation.

MacrolidesMacrolides contraindicated in contraindicated in1.1. the presence of known allergy to any the presence of known allergy to any

macrolide, because cross-sensitivity macrolide, because cross-sensitivity occursoccurs

2.2. Caution should be used in patients with Caution should be used in patients with hepatic dysfunction that could alter the hepatic dysfunction that could alter the metabolism of the drugmetabolism of the drug

3.3. in lactating women because of drug in lactating women because of drug excretion in breast milk excretion in breast milk

4.4. in pregnant women because potential in pregnant women because potential adverse effects on the developing fetusadverse effects on the developing fetus

tetracyclinestetracyclines

1.1. not recommended for use in pregnancy not recommended for use in pregnancy and lactation because the drug can affect and lactation because the drug can affect the bones and teeth, causing permanent the bones and teeth, causing permanent discoloration and sometimes arrest of discoloration and sometimes arrest of growth.growth.

2.2. Tetracyclines are also avoided in children Tetracyclines are also avoided in children less than 8 (eight) years of age because of less than 8 (eight) years of age because of the potential damage to the bones and the potential damage to the bones and permanent discoloration of the teeth.permanent discoloration of the teeth.

3.3. AvoidedAvoided in renal failure only doxycycline. in renal failure only doxycycline.

Quinonlones Quinonlones Contraindicated inContraindicated in1.1. Pregnancy and lactation Pregnancy and lactation

2.2. These agents are found to cause These agents are found to cause significant damage to the cartilages such significant damage to the cartilages such that they are given cautiously to growing that they are given cautiously to growing children and adolescents less than 18 children and adolescents less than 18 years of ageyears of age

Sulfonamides Sulfonamides These agents are contraindicated toThese agents are contraindicated to1.1. patients with known allergy to sulfa drugs, patients with known allergy to sulfa drugs,

sulfonylureas and thiazide diuretics because they sulfonylureas and thiazide diuretics because they share similar structures. share similar structures.

2.2. It is not recommended for use in pregnancy It is not recommended for use in pregnancy because it can cross the placenta and cause birth because it can cross the placenta and cause birth defects and kernicterus.defects and kernicterus.

3.3. Lactating women who take these drugs will Lactating women who take these drugs will excrete them in the breast milk potentially excrete them in the breast milk potentially causing kernicterus, diarrhea and rash in the causing kernicterus, diarrhea and rash in the newborn.newborn.

In Summary….In Summary….

Antibiotic ChoiceAntibiotic Choice

Narrow Spectrum?Narrow Spectrum? Extended/Broad Spectrum?Extended/Broad Spectrum? Gram positiveGram positive Gram negativeGram negative mixedmixed Anaerobes? Consider if the infection is Anaerobes? Consider if the infection is

present > 3days or if no improvement.present > 3days or if no improvement.

Broad Spectrum AntibioticsBroad Spectrum Antibiotics

Affects both Gram + and Gram – bacteria, Affects both Gram + and Gram – bacteria, better for mixed infections.better for mixed infections.

Examples: Amoxicillin, AmpicillinExamples: Amoxicillin, Ampicillin

Narrow Spectrum AntibioticsNarrow Spectrum Antibiotics

Specific for the pathogen.Specific for the pathogen. Fewer disturbances of non-pathogenic Fewer disturbances of non-pathogenic

bacteria.bacteria. Fewer side effects.Fewer side effects. Rapid response for sensitive organisms.Rapid response for sensitive organisms. Ex: Pen VK, Pen G, ErythromycinEx: Pen VK, Pen G, Erythromycin

Principles of Antibiotic Therapy

Therapeutic effectiveness– Clinical indications

Pharmcodynamics, pharmacokinetics

– Age and extent of infection

Patient factors

Age, allergies, compliance, pregnancy risk Patient function

– Renal, hepatic, immunosuppresion, route applicability

Cost– Brand name, length of course, alternatives?

Penicillin G administered parenterally or Penicillin G administered parenterally or penicillin V administered orally are currently penicillin V administered orally are currently the antibiotics of choice for treatment of dental the antibiotics of choice for treatment of dental infections of usual etiology. infections of usual etiology.

Infections caused by penicillinase-producing Infections caused by penicillinase-producing staphylococci or those involving gram-staphylococci or those involving gram-negative bacteria should be treated with a negative bacteria should be treated with a penicillinase-resistant penicillin or an penicillinase-resistant penicillin or an ampicillin-like derivative, respectively. ampicillin-like derivative, respectively.

Erythromycin is a second-choice bacteriostatic Erythromycin is a second-choice bacteriostatic antibiotic, becoming first choice for treating antibiotic, becoming first choice for treating dental infections in patients allergic to penicillin. dental infections in patients allergic to penicillin.

The cephalosporins, similar in action to The cephalosporins, similar in action to ampicillin-like penicillin derivatives, may be ampicillin-like penicillin derivatives, may be used with caution in patients who have used with caution in patients who have exhibited delayed-type allergic reactions to exhibited delayed-type allergic reactions to penicillin and when erythromycin cannot be penicillin and when erythromycin cannot be used. Their lack of advantage over other used. Their lack of advantage over other agents, and their cost, precludes routine use agents, and their cost, precludes routine use for usual dental infections. for usual dental infections.

Clindamycin indicated for treatment of bone Clindamycin indicated for treatment of bone infections and/or anaerobic infections refractory to infections and/or anaerobic infections refractory to commonly used antibiotics. commonly used antibiotics.

Tetracyclines are, at best, third-choice agents for Tetracyclines are, at best, third-choice agents for usual dental infections. However, they are useful usual dental infections. However, they are useful for cases of acute necrotizing ulcerative gingivitis for cases of acute necrotizing ulcerative gingivitis requiring systemic antibiotic therapy when requiring systemic antibiotic therapy when penicillin is precluded. penicillin is precluded.

Vancomycin and streptomycin are used Vancomycin and streptomycin are used prophylactically for prevention of infective prophylactically for prevention of infective endocarditis in patients with prosthetic heart endocarditis in patients with prosthetic heart valves. valves.

Nystatin remains a first-choice agent for Nystatin remains a first-choice agent for treatment of oral candidal infections. treatment of oral candidal infections.

Ketoconazole, an orally active systemic Ketoconazole, an orally active systemic antifungal agent, may be used for monilial antifungal agent, may be used for monilial infections of the oral cavity refractory to infections of the oral cavity refractory to nystatin. nystatin.

Chemotherapy of viral infections is difficult Chemotherapy of viral infections is difficult because lack of effective agents with because lack of effective agents with selective toxicity. selective toxicity.

Herpes infections of the oral cavity have Herpes infections of the oral cavity have been treated--with limited success--with been treated--with limited success--with idoxuridine.idoxuridine.

Acyclovir offers little clinical benefit for Acyclovir offers little clinical benefit for herpes infections in usually healthy patients herpes infections in usually healthy patients but may be of value for treating such but may be of value for treating such infections in immunocompromised patients. infections in immunocompromised patients.

All antimicrobial agents may cause adverse All antimicrobial agents may cause adverse reactions of varying degrees of severity. reactions of varying degrees of severity.

Most orally administered antibiotics may cause Most orally administered antibiotics may cause gastrointestinal disturbances. Superinfections gastrointestinal disturbances. Superinfections occur with broad-spectrum antibiotics and a occur with broad-spectrum antibiotics and a severe form of superinfection, antibiotic-severe form of superinfection, antibiotic-associated colitis, has occurred with almost all associated colitis, has occurred with almost all antibiotics. antibiotics.

Allergic reactions of all degrees of severity can Allergic reactions of all degrees of severity can occur with most antibiotics. The penicillins, occur with most antibiotics. The penicillins, followed by the cephalosporins and tetracyclines, followed by the cephalosporins and tetracyclines, are most frequently implicated in these reactions.are most frequently implicated in these reactions.

Dental Infection

Acute—Rapid growth< 3 days

Chronic > 3 days

Pen VK 500mg q6h orAmox 500mg q8h or

Cephalosporin

Allergic to PCN

Clindamycin 300mg q8h orCephalosporin (check allergic Rxn) or

Azith or Clarithromycin

Think AnaerobesAdd Metronidazole 250-500mg

To PCN, Amox, or Ceph

Clindamycin 300mg q8h

The association amoxicillin-clavulanate was The association amoxicillin-clavulanate was the drug most frequently prescribed by the drug most frequently prescribed by dentists during 2005.dentists during 2005.

The use of antibiotics in dental practice is The use of antibiotics in dental practice is characterized by empirical prescription characterized by empirical prescription based on clinical and bacteriological based on clinical and bacteriological epidemiological factors, with the use of epidemiological factors, with the use of broad spectrum antibiotics for short periods broad spectrum antibiotics for short periods of time, and the application of a very narrow of time, and the application of a very narrow range of antibiotics. range of antibiotics.

The simultaneous prescription of NSAIDs The simultaneous prescription of NSAIDs can modify the bioavailability of the can modify the bioavailability of the antibiotic. antibiotic.

In turn, an increased number of bacterial In turn, an increased number of bacterial strains resistant to conventional antibiotics strains resistant to conventional antibiotics are found in the oral cavity.are found in the oral cavity.

Pregnancy, kidney failure and liver failure Pregnancy, kidney failure and liver failure are situations requiring special caution on are situations requiring special caution on the part of the clinician when indicating the part of the clinician when indicating antibiotic treatment.antibiotic treatment.

Antibiotic StrategiesAntibiotic StrategiesCardinal Rules: Cardinal Rules:

1) Use the right drug. 1) Use the right drug.

2) Use the right dose. 2) Use the right dose.

3) Use the correct dosing schedule. 3) Use the correct dosing schedule.

4) Correct duration.4) Correct duration. Hard and Fast Hard and Fast Use a loading dose to rapidly achieve therapeutic Use a loading dose to rapidly achieve therapeutic

blood levels.blood levels. Avoid combinations of bacteriostatic and Avoid combinations of bacteriostatic and

bacteriocidal drugsbacteriocidal drugs..

BacteriostaticBacteriostatic

Erythromycin, tetracyclines, Erythromycin, tetracyclines,

clindamycin, chloramphenicol, clindamycin, chloramphenicol,

spectinomycin, sulfonamidesspectinomycin, sulfonamides

Erythromycin and Clindamycin may be Erythromycin and Clindamycin may be bactericidal at higher blood levelsbactericidal at higher blood levels

Common pathogens in oral cavityCommon pathogens in oral cavitythe list of bacteria related with oral infections is the list of bacteria related with oral infections is relatively long (cocci, bacilli, gram positive and gram relatively long (cocci, bacilli, gram positive and gram negative organisms, aerobes and anaerobes). negative organisms, aerobes and anaerobes). Necrotic pulp and apical abscesses

Obligate anaerobic bacteriaGram negative rods

Prevotella & porphyomonas spp. (resistance)Fusobacterium spp.Campylobacter rectus

Gram positive rodsEubacterium spp.Actinomycetes spp.

Gram positive cocciPeptostreptococcus spp.

Facultative anaerobic bacteriaGram positive cocci

Strep and Entercoccus spp.

Periodontal Diseases Periodontal Diseases GingivitisGingivitis

Fuso, strep, & actinomycetesFuso, strep, & actinomycetesAdult periodontitisAdult periodontitis

Bacteroides, porphyomonas, peptostreptococcus Bacteroides, porphyomonas, peptostreptococcus & prevotella& prevotellaAcute necrotizing ulcerative gingivitisAcute necrotizing ulcerative gingivitisSpirochetes, prevotella, fusoSpirochetes, prevotella, fuso

Localized juvenile periodontitisLocalized juvenile periodontitisActinobacillusActinobacillus

Streptococcus mutansStreptococcus mutans – causing dental caries ( most – causing dental caries ( most common dental infectioncommon dental infection))

treatment of choice: local physical removal of microbial treatment of choice: local physical removal of microbial plaque on a regular basis( good oral hygiene) plaque on a regular basis( good oral hygiene)

Antibiotics are typically prescribed in dental Antibiotics are typically prescribed in dental practice for some of the following purposespractice for some of the following purposes: : (a) as treatment for (a) as treatment for acuteacute odontogenic odontogenic infections; infections;

(b) as treatment for (b) as treatment for non-odontogenicnon-odontogenic infections; infections;

(c) as (c) as prophylaxis against focal infection prophylaxis against focal infection in in patients at risk (endocarditis and joint patients at risk (endocarditis and joint prostheses); and prostheses); and

(d) as (d) as prophylaxis against local infection prophylaxis against local infection and and systemic spread in oral surgery.systemic spread in oral surgery.

TREATMENT OF THE ACUTE TREATMENT OF THE ACUTE ODONTOGENIC INFECTIONODONTOGENIC INFECTION

Despite the high incidence of odontogenic Despite the high incidence of odontogenic infections, infections, there are no uniform criteria there are no uniform criteria regarding the use of antibiotics to treat them. regarding the use of antibiotics to treat them.

It is suggested that treatment should be It is suggested that treatment should be provided in provided in ulcerative necrotizing gingivitis, ulcerative necrotizing gingivitis, in periapical abscesses, in aggressive in periapical abscesses, in aggressive periodontitis, and in severe infections of periodontitis, and in severe infections of the fascial layers and deep tissues of the the fascial layers and deep tissues of the head and neck. head and neck.

They do not recommend antibiotic treatment They do not recommend antibiotic treatment in chronic gingivitis or periodontal in chronic gingivitis or periodontal abscesses (except in the presence of abscesses (except in the presence of dissemination).dissemination).

There is considerable agreement that the There is considerable agreement that the beta-lactam derivatives are the antibiotics of beta-lactam derivatives are the antibiotics of choice for these processes, provided there choice for these processes, provided there are no allergies or intolerances. However, are no allergies or intolerances. However, there is less consensus regarding which there is less consensus regarding which drug belonging this family should be drug belonging this family should be prescribed. prescribed.

While some authors consider the natural and While some authors consider the natural and semisynthetic penicillins (amoxicillin) to be the semisynthetic penicillins (amoxicillin) to be the options of first choice, others prefer the options of first choice, others prefer the association amoxicillin-clavulanate, due to the association amoxicillin-clavulanate, due to the growing number of bacterial resistance, as well as growing number of bacterial resistance, as well as its broad spectrum, pharmacokinetic profile, its broad spectrum, pharmacokinetic profile, tolerance and dosing characteristics.tolerance and dosing characteristics.

As has been commented above, some authors As has been commented above, some authors have proposed clindamycin as the drug of choice, have proposed clindamycin as the drug of choice, in view of its good absorption, low incidence of in view of its good absorption, low incidence of bacterial resistances, and the high antibiotic bacterial resistances, and the high antibiotic concentrations reached in bone. concentrations reached in bone.

TREATMENT OF NON-TREATMENT OF NON-ODONTOGENIC INFECTIONSODONTOGENIC INFECTIONS

Non-odontogenic infections include specific Non-odontogenic infections include specific infections of the oral cavity (tuberculosis, infections of the oral cavity (tuberculosis, syphilis, leprosy), and nonspecific infections syphilis, leprosy), and nonspecific infections of the mucosal membranes, muscles and of the mucosal membranes, muscles and fascias, salivary glands and bone. Bone fascias, salivary glands and bone. Bone infections are included here on the grounds infections are included here on the grounds that many of them may be of dental origin. that many of them may be of dental origin.

These processes require prolonged These processes require prolonged treatments, and drug associations are used treatments, and drug associations are used that usually include that usually include clindamycin,clindamycin, due to its due to its capacity to reach high concentrations in capacity to reach high concentrations in bone, and bone, and fluorquinolones fluorquinolones (ciprofloxacin, (ciprofloxacin, norfloxacin, moxifloxacin) – to extend the norfloxacin, moxifloxacin) – to extend the bacterial spectrum to include gram bacterial spectrum to include gram negative bacilli, gram positive aerobic negative bacilli, gram positive aerobic cocci and, in the case of third generation cocci and, in the case of third generation fluorquinolones (moxifloxacin), anaerobes. fluorquinolones (moxifloxacin), anaerobes.

It is recommended that empirical treatment It is recommended that empirical treatment with betalactams associated to with betalactams associated to fluorquinolones should be limited, since both fluorquinolones should be limited, since both groups of antibiotics activate common groups of antibiotics activate common resistance mechanisms – thus favoring the resistance mechanisms – thus favoring the appearance of resistances in important appearance of resistances in important pathogens such as Pseudomona pathogens such as Pseudomona aeruginosa and Acinetobacter spp aeruginosa and Acinetobacter spp

The treatment of specific infections caused by The treatment of specific infections caused by mycobacteria requires the use of antibiotics mycobacteria requires the use of antibiotics for long periods of time (from 6 months to 2 for long periods of time (from 6 months to 2 years), and includes the administration of years), and includes the administration of dapsonedapsone (a sulfamide analog), (a sulfamide analog), clofazimine clofazimine (a (a dye with bactericidal action) and dye with bactericidal action) and rifampicin rifampicin for for leprosy, and associations of leprosy, and associations of ethambutol, ethambutol, isoniazid, rifampicin, pyrazinamide and isoniazid, rifampicin, pyrazinamide and streptomycin streptomycin for tuberculosis. for tuberculosis.

The treatment of syphilis, caused by The treatment of syphilis, caused by Treponema pallidum, is based on the Treponema pallidum, is based on the use of use of penicillin G benzatine. penicillin G benzatine.

Administration comprises 2.4 million IU in a Administration comprises 2.4 million IU in a single intramuscular dose in the primary single intramuscular dose in the primary period, three doses of 2.4 million IU via the period, three doses of 2.4 million IU via the intramuscular route, spaced one week apart, intramuscular route, spaced one week apart, in the secondary period. In the tertiary in the secondary period. In the tertiary period a first treatment is provided with period a first treatment is provided with intravenous penicillin G, followed by intravenous penicillin G, followed by penicillin G benzatine via the intramuscular penicillin G benzatine via the intramuscular route once a week during 3 weeks, involving route once a week during 3 weeks, involving a dose of 2.4 million IU each.a dose of 2.4 million IU each.

PROPHYLAXIS OF FOCAL PROPHYLAXIS OF FOCAL INFECTIONINFECTION

The use of antibiotics as prophylaxis for The use of antibiotics as prophylaxis for focal infection is common practice, and has focal infection is common practice, and has been widely accepted in the dental been widely accepted in the dental profession. The paradigm of this model of profession. The paradigm of this model of treatment is the prevention of bacterial treatment is the prevention of bacterial endocarditis, indicated in risk patients in the endocarditis, indicated in risk patients in the context of any invasive procedure within the context of any invasive procedure within the oral cavity.oral cavity.

Prophylaxis for Gastrointestinal and Prophylaxis for Gastrointestinal and Genitourinary ProceduresGenitourinary Procedures: (Gram-negative : (Gram-negative procedures)procedures)

ParenteraParenteral: Ampicillin 2 g IV plus Gentamicin: l: Ampicillin 2 g IV plus Gentamicin: 1.5 mg/kg IM or IV (not to exceed 80mg) 30 min 1.5 mg/kg IM or IV (not to exceed 80mg) 30 min before procedure; followed by ampicillin 1 g IV 6 before procedure; followed by ampicillin 1 g IV 6 hr laterhr later

Penicillin AllergyPenicillin Allergy: Vancomycin 1 g IV infused : Vancomycin 1 g IV infused slowly over 1 hr plus Gentamycin 1.5 mg/kg IM slowly over 1 hr plus Gentamycin 1.5 mg/kg IM or IV ( not to exceed 80 mg) 1 hr before or IV ( not to exceed 80 mg) 1 hr before procedureprocedure

Antibiotic prophylaxis is Antibiotic prophylaxis is NOTNOT recommended for dental patients recommended for dental patients with with plates, pins, or screws,plates, pins, or screws, nor is nor is

it routinely recommended for it routinely recommended for MOSTMOST dental patients with dental patients with TOTAL TOTAL

JOINT REPLACEMENTS.JOINT REPLACEMENTS.

AAOS recommendationsAAOS recommendations

Prophylaxis recommended – Total joint replacement within the last two years

AND: Compromised immune system OR Type 1 DM OR Previous prosthetic joint infections OR Malnourishment OR

Hemophilia

PROPHYLAXIS OF LOCAL INFECTION PROPHYLAXIS OF LOCAL INFECTION AND SYSTEMIC SPREADAND SYSTEMIC SPREAD

Prophylaxis of local infection is taken to Prophylaxis of local infection is taken to comprise the administration of antibiotics on comprise the administration of antibiotics on a pre-, intra- or postoperative basis, to a pre-, intra- or postoperative basis, to prevent bacterial proliferation and prevent bacterial proliferation and dissemination within and from the surgical dissemination within and from the surgical wound. wound.

prophylaxis in oral surgery in a healthy patient prophylaxis in oral surgery in a healthy patient was only recommended in the case of the was only recommended in the case of the removal of impacted teeth, periapical surgery, removal of impacted teeth, periapical surgery, bone surgery, implant surgery, bone grafting and bone surgery, implant surgery, bone grafting and surgery for benign tumors.surgery for benign tumors.

In subjects with risk factors for local or In subjects with risk factors for local or systemic infection - including oncological systemic infection - including oncological patients, immune suppressed individuals, patients, immune suppressed individuals, patients with metabolic disorders such as patients with metabolic disorders such as diabetes, and splenectomized patients, diabetes, and splenectomized patients, prophylactic antibiotic coverage prophylactic antibiotic coverage should be should be provided before attempting any invasive provided before attempting any invasive procedure.procedure.

Antibiotics and pregnancyAntibiotics and pregnancy group Bgroup B (i.e., warranting caution with treatment (i.e., warranting caution with treatment

during pregnancy) contains the following during pregnancy) contains the following antibiotics: antibiotics: azithromycin, cephalosporins, azithromycin, cephalosporins, erythromycin, metronidazole and penicillins with erythromycin, metronidazole and penicillins with or without beta-lactamase inhibitors.or without beta-lactamase inhibitors.

Group CGroup C in turn includes in turn includes clarithromycin, the clarithromycin, the fluorquinolones and the sulfa drugs (including fluorquinolones and the sulfa drugs (including dapsone).dapsone).

group Dgroup D contains the a contains the aminoglycosidesminoglycosides and and tetracyclinestetracyclines

ANTIBIOTIC USE IN RENAL FAILUREANTIBIOTIC USE IN RENAL FAILURE Many antibiotics are actively eliminated Many antibiotics are actively eliminated

through the kidneys. through the kidneys. The presence of impaired renal function The presence of impaired renal function

requires requires reductionreduction of the drug dose in order to of the drug dose in order to avoid excessively elevated plasma drug avoid excessively elevated plasma drug concentrations that could lead to toxicity. concentrations that could lead to toxicity.

dose adjustment can be carried out by dose adjustment can be carried out by reducing the amount administered in each reducing the amount administered in each dose or by increasing the interval between dose or by increasing the interval between doses (without modifying the amount of drug). doses (without modifying the amount of drug).

ANTIBIOTICS AND LIVER DISEASEANTIBIOTICS AND LIVER DISEASE Some antibiotics are metabolized in the Some antibiotics are metabolized in the

liver, followed by elimination in bile.liver, followed by elimination in bile. In patients with liver failure, the use of such In patients with liver failure, the use of such

antibiotics should be restricted in order to antibiotics should be restricted in order to avoid toxicity secondary to overdose.avoid toxicity secondary to overdose.

Erythromycin, clindamycin, metronidazole Erythromycin, clindamycin, metronidazole and anti-tuberculosis drugs are antibiotics and anti-tuberculosis drugs are antibiotics requiring dose adjustments when requiring dose adjustments when administered to patients with liver failure.administered to patients with liver failure.

Regardless of the above considerations, Regardless of the above considerations, some antibiotics are potentially hepatotoxic. some antibiotics are potentially hepatotoxic. As a result, and whenever possible, they As a result, and whenever possible, they should be avoided in patients with some should be avoided in patients with some active liver disorder. Specifically, active liver disorder. Specifically, tetracyclines and anti-tuberculosis drugs tetracyclines and anti-tuberculosis drugs should be avoided should be avoided

Common Adverse Reactions to Common Adverse Reactions to Anti-infective TherapyAnti-infective Therapy

The most common adverse effects are due The most common adverse effects are due to the direct action of the drugs in the to the direct action of the drugs in the following organ system- Neuro, nephro and following organ system- Neuro, nephro and GI systemGI system

1.1.NephrotoxicityNephrotoxicity1.1. Antibiotics that are metabolized and Antibiotics that are metabolized and

excreted in the kidney most frequently excreted in the kidney most frequently cause kidney damage.cause kidney damage.

22. . Gastro-intestinal toxicityGastro-intestinal toxicity Direct toxic effect to the cells of the GI tract Direct toxic effect to the cells of the GI tract

can cause nausea, vomiting, stomach pain can cause nausea, vomiting, stomach pain and diarrhea. and diarrhea.

Some drugs are toxic to liver cells and can Some drugs are toxic to liver cells and can cause hepatitis or liver failure.cause hepatitis or liver failure.

3. CNS toxicity3. CNS toxicity When drugs can pass through the brain When drugs can pass through the brain

barrier and accumulate in the nervous barrier and accumulate in the nervous tissues, they can interfere with neuronal tissues, they can interfere with neuronal function.function.

Potentially Periodontopathic Potentially Periodontopathic Bacteria:Bacteria:

Adult peiodontitisAdult peiodontitis- Bacteriodes gingivalis- Bacteriodes gingivalis

- B. intermedius- B. intermedius

- Fusobacterium nucleatum- Fusobacterium nucleatum

- Veillonella parvula- Veillonella parvula

- Actinomyces (naestundii, israelli, viscosus)- Actinomyces (naestundii, israelli, viscosus)

Localized Juvenile PeriodontitisLocalized Juvenile Periodontitis

- - Actinobacillus actinomycetemcomitansActinobacillus actinomycetemcomitans

- Capnocytophaga sp.- Capnocytophaga sp.

Streptococcus mutansStreptococcus mutans – causing dental – causing dental caries ( most common dental infection)caries ( most common dental infection)

treatment of choice: local physical removal treatment of choice: local physical removal of microbial plaque on a regular basis( good of microbial plaque on a regular basis( good oral hygiene) oral hygiene)

Antimicrobial use in dentistryAntimicrobial use in dentistry

Infection/Situation Drug of Choice Alternative drugs

Periodontal Disease ANUG (Vincent)

Abscess (perio)

Periodontitis Juvenile Adult

Penicillin V

Penicillin V

Tetracycline Tetracycline

MetronidazoleTetracycline

ErythromycinTetracycline

----MetronidazoleClindamycin

Oral Infections Soft tissue (abscess, cellulitis, post surgical pericornitis) Osteomyelitis

Penicillinase-producing staphylococci Mixed infection insensitive to penicillin Aerobes Anaerobes

Penicillin V

Penicillin V

Cloxacillin

AmoxicillinClindamycin

Erythromycin, Cephalosporin, Clindamycin, TetracyclineCephalosporin, Clindamycin, Erythromycin

Cephalosporin, Clindamycin

Cephalosporin, Sulfonamides,TetracyclineCephalosporin, Metronidazole, Erythromycin, Tetracycline

Prophylactic for Infective endocarditis Rheumatic heart Disease prosthetic Heart valve

Penicillin VAmpicillin + gentamicin

Erythromycin, (Cephalosporin)

I. Prophylaxis treatment For Infective Endocarditis:I. Prophylaxis treatment For Infective Endocarditis:

Prophylaxis for dental, oral, upper respiratory tract or esophageal procedures: (Gram –Prophylaxis for dental, oral, upper respiratory tract or esophageal procedures: (Gram –positive organisms)positive organisms)

Oral: Amoxycillin 2 g orally 1 hr before procedure; children 50mg/kg orally 1 hr before Oral: Amoxycillin 2 g orally 1 hr before procedure; children 50mg/kg orally 1 hr before procedureprocedure

  

Penicillin allergy: Clindamycin 600mg orally 1hr before procedure or Cephalexin 2 g Penicillin allergy: Clindamycin 600mg orally 1hr before procedure or Cephalexin 2 g orally 1 hr before procedureorally 1 hr before procedure

Parenteral: Ampicillin 2 g IM or IV 30 min before procedureParenteral: Ampicillin 2 g IM or IV 30 min before procedure

  

II. Prophylaxis for Gastrointestinal and Genitourinary Procedures:(Gram-negative II. Prophylaxis for Gastrointestinal and Genitourinary Procedures:(Gram-negative procedures)procedures)

Parenteral: Ampicillin 2 g IV plus Gentamicin 1.5 mg/kg IM or IV (not to exceed 80mg) Parenteral: Ampicillin 2 g IV plus Gentamicin 1.5 mg/kg IM or IV (not to exceed 80mg) 30 min before procedure; followed by ampicillin 1 g IV 6 hr later30 min before procedure; followed by ampicillin 1 g IV 6 hr later

Penicillin Allergy: Vancomycin 1 g IV infused slowly over 1 hr plus Gentamycin 1.5 Penicillin Allergy: Vancomycin 1 g IV infused slowly over 1 hr plus Gentamycin 1.5 mg/kg IM or IV ( not to exceed 80 mg) 1 hr before mg/kg IM or IV ( not to exceed 80 mg) 1 hr before procedureprocedure

  

4. Hypersensitivity4. Hypersensitivity Most protein antibiotics can induce the Most protein antibiotics can induce the

body’s immune system to produce body’s immune system to produce allergic responses.allergic responses.

Drugs are considered foreign substances Drugs are considered foreign substances and when taken by the individual, it and when taken by the individual, it encounters the body’s immune cells.encounters the body’s immune cells.

5. Super-infections5. Super-infections Opportunistic infections that develop Opportunistic infections that develop

during the course of antibiotic therapy during the course of antibiotic therapy are called SUPERINFECTIONS. are called SUPERINFECTIONS.