Antibiotics and Otolaryngologists

8/3/2019 Antibiotics and Otolaryngologists

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4/28/2012 Abou-Elhamd 1


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Antibiotics and Otolaryngologists

Dr. Kamal Abou-Elhamd MD

Professor in ENT

College of Medicine

King Faisal UniversitySohag University

Email: [email protected]

http://www.kfu.edu.sa/ar/Spaces/kaboalhamd/Pages/Courses.aspx
http://www.kfu.edu.sa/ar/Spaces/kaboalhamd/Pages/Courses.aspxmailto:[email protected]://www.kfu.edu.sa/ar/Spaces/kaboalhamd/Pages/Courses.aspxhttp://www.kfu.edu.sa/ar/Spaces/kaboalhamd/Pages/Courses.aspxmailto:[email protected]


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Overview of antibiotics

They act as:

Cell wall

inhibitors.

Protein

synthesis

inhibitors.Miscellaneous


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Cell wall inhibitors

Beta Lactams

o Penicillins (PCN)

o Cephalosporins

Vancomycin

Bacitracin

Polymyxin


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Beta Lactams

B-lactams inhibittranspeptidase.

Only effectiveagainst rapidlygrowing organismsthat synthesizepeptidoglycan.(Ineffective againstmycobacteria.)


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Penicillins

5% of patients willdevelop a hypersensitivity

reaction (penicilloic acid).Rashes - most commonreaction. 50% do not havea recurrent rash.Ampicillin - rash in 50-100% of patients withmononucleosis.


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Penicillins

Anaphylaxis 1/10000 patientsAngioedema, rhinitis, asthma, and

anaphylaxis.10% mortality rate.Anaphylaxis possible after negative skin

testing.Avoid all other B-lactamsUsed for common oral infections


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Anti-StaphylococcalPenicillins

Methicillin, nafcillin, oxacillin, cloxacillin (ampiclox)

and dicloxacillin (cloxapen).Resist degradation by penicillinase.

Methicillin is rarely used due to toxicity.

Dicloxacillin - highest serum levels orally.

Nafcillin - preferred parenteral drug.


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Aminopenicillins

Ampicillin (IV) & Amoxicillin (Amoxil:Oral)Ampicillin/sulbactam (Unasyn, IV)Amoxicillin/clavulanate (Augmentin)

Sulbactam and clavulanic acid increase activityagainst B-lactamase producing organisms.Extended antimicrobial spectrum.

Gram negatives: E. coli, Proteus, Salmonella,

Haemophilus, M. catarrhalis, Klebsiella,Neisseria, Enterobacter, Bactoroides.

Used as first line therapy for acute otitis media andsinusitis.


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Antipseudomonal

Penicillins

Ticarcillin, Piperacillin (Pipracil IM/IV), Mezlocillin.Piperacillin/tazobactam (Zosyn; IV)

Tazobactam (B-lactamase inhibitor)

Ticarcillin/clavulanate (Timentin; IV)Active against Pseudomonas, E. coli, klebsiella,enterobacter, serratia and B. fragilis.Lower activity against gram positives

Piperacillin (Avocin) has greater activity than anyother penicillin against Pseudomonas aeruginosaOften used with aminoglycosides when treatingpseudomonal infections


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Summary of penicillins

Penicillin G remains the drug of choice for allinfections caused by sensitive organisms

Crystalline penicillin G is given intravenously.Delayed absorption forms (procaine andbenzathine) are given intramuscularly.

Penicillin V has has better absorption afteroral administration. It usually is substituted forpenicillin G when oral therapy is indicated


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Cephalosporins

Generally more resistant to B-

lactamases.5-10% cross-sensitivity with pcn

allergic pts.1-2% hypersensitivity reactions in

non-pcn allergic pts.Broader spectrum leads toopportunistic infections (candidiasis,

C. difficile colitis).


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First Generation

Cefazolin (Ancef; IV), Cephalexin (Keflex;Oral), Cefadroxil (Duricef: oral)

Spectrum: Most gram positive cocci (Strep,S. aureus), E. coli, Proteus, KlebsiellaThey have primarily gram-positive and limited

gram-negative activity.Use: S. aureusinfection, surgicalprophylaxis.


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Second Generation

Cefuroxime (Zinacef: IV)Cefprozil (Cefzil: oral)Increased activity against H. flu, enterobacter, Neisseria,proteus, E. coli, klebsiella, M. catarrhalis, anaerobesand B.

fragilis.Not as effective against S. aureus as the 1st generation.They have more extensive gram-negative as well asanaerobic bacterial coverageThey are useful in the treatment ofHemophilus influenzaeinfections (acute otitis media, sinusitis, epiglottitis).Cefpodoxime and Cefuroxime active against intermediatelevel resistant strep pneumo.Cefprozil is best absorbed when taken with meals, followed

by yogurt to prevent diarrhea.


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Third Generation

Spectrum: gram negative > gram positive.Ceftriaxone (Rocephin; IM/IV best formeningitis), Cefotaxime (cefotax: IV),Cefixime (Suprax: oral).

Useful for meningitis.Ceftriaxone used for highly resistant andmulti drug resistant strep pneumo along

with vancomycin.Ceftazidime (cefzim:IV) active againstpseudomonas.They are active against some strains of

Pseudomonas


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Fourth Generation

Cefepime (maxipime: IV)Active against Strep, Staph(mssa), aerobic gramnegatives (enterobacter, e. coli, klebsiella, proteusand pseudomonas).


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Cephalosporins Notes

Cephalexin (Keflex)Cephalexin is absorbed orallyIt is less active against many staphylococci andsome anaerobes.It should not be used to treat serious deep tissueinfections.This drug is not as effective as penicillin for most

oral-pharyngeal bacteria

Cephradine (Velosef)Cephradine is similar to cephalexin, but with both

oral and parenteral administration


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Cephalosporins Notes

Cefaclor (Ceclor)This is an oral cephalosporin with some activityagainst Haemophilus influenzae. Itshould not be used for serious deep tissueinfections

Cefotaxime (Claforan)

This is a third-generation cephalosporin with abroad range of activity for gram negativeorganisms including some strains of Pseudomonasand B. fragilis


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Vancomycin

Vancocin IV (The drug is not absorbed orally)Tricyclic glucopeptide - Streptomyces orientalis.Inhibits synthesis of cell wall phospholipids and preventscross-linking of peptidoglycans at an earlier step than B-

lactams.Active against gram positive bacteria, highly resistant Strep.pneumo, Clostridia, Enterococcus, Staph. epiand MRSA.Synergy with aminoglycosides.Therapeutic levels are achieved in most body tissues except

the CSFDrug of choice in treatment of MRSA and highly resistantStrep. SpeciesIt also is used orally to suppress bowel flora and to treat

antibiotic-induced pseudomembranous colitis


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Bacitracin

Polypeptide produced by Bacillus subtillis.Inhibits regeneration of phospholipids receptorsinvolved in peptidoglycan synthesis.

Active against gram positives and negatives.Topical use only (nephrotoxicity).Adverse effects.

Contact dermatitis top 10 allergen.

Reports of anaphylaxis.Combinations

Neosporin neomycin, polymyxin B, bacitracinPolysporin polymyxin B, bacitracin


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Polymyxin

Bacillus polymyxaDecapeptide that disrupts the phospholipid layer incell membranes.Limited spectrum.

Decreased gram positive coverage.

Active against Pseudomonas, Proteus, Serratia,E. coli, Klebsiellaand Enterobacter.Cross reaction with bacitracin.

P i S h i


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Protein Synthesis

Inhibitors

Target the bacterial ribosome.Macrolides, Clindamycin, Chloramphenicol,Streptogramins.

Aminoglycosides, Tetracyclines


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Macrolides

Erythromycin (IV ; Oral),Clarithromycin (Biaxin; IV ; Claribiotic: Oral)Azithromycin (Zithromax: Oral)

Erythromycin:Gram positives: Staph.(MRSA is resistant), Strep., Bordetella,Treponema, Corynebacteria.Atypicals: Mycoplasma, Ureaplasma, Chlamydia

Clarithromycin:

Similar to erythromycin.Increased activity against gram negatives (H. flu, Moraxella) andatypicals

Azithromycin:Decreased activity against gram positive cocci.Increased activity against H. fluand M. cat.


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Macrolides

Adverse effects.10-15% of pts do not finish the prescribedcourse of erythromycin because of GI distress.

JaundiceOtotoxic (high doses)

Drug interactionsInhibits other substrates and increases their

serum concentrations.Theophylline, warfarin, astemizole,carbemazepine, cyclosporine, digoxin,terfenadine


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Erythromycin

Erythromycin is the most important of the macrolideantibiotics. Erythromycin and sulfisoxazole: (Pediazole)It is generally considered to be bacteriostatic, but can bebactericidal at higher concentrations.

It has a broad spectrum of activity againstbacteria,treponemas, and mycoplasmas.It is the agent of choice in Mycoplasma pneumoniaeinfections, Legionnaires' disease, diphtheria, and pertussis.

It also is important in treating pneumococcal pneumonia,syphilis, gonorrhea, and group A streptococcal infections inpenicillin-allergic patients.Erythromycin achieves therapeutic levels in body tissuesand fluid other than the brain and CSF.


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Erythromycin

Some 10 to 15 percent of patients refuse tocomplete the prescribed course of erythromycinbecause of gastrointestinal distress. This is a sideeffect of all erythromycins and may be minimized byadministration at mealtime

All members of this class minimally prolongtheelectrocardiographic QT-interval. They should be

used with caution in patients with arrhythmias,uncorrected hypokalemia, and with other drugswhich may prolong the QT-interval, such asquinidine, sotalol, or procainamide

Its toxicity increases with sildenafil (Viagra)


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Clindamycin

Clindamycin (dalacin c ; IV ; Oral)LincosamideAntibiotic spectrum:

Strepspecies, Staph(some MRSA), B. fragilis,anaerobesDoes not cover Clostridium difficile.

Used for deep neck space infections, chronic

tonsillo-pharyngitis, odontogenic abscesses, andsurgical prophylaxis in contaminated wounds.Concomitant use of macrolides or Chloramphenicoladds no benefit.

Causes: Pseudomembranous colitis


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Clindamycin

Lincomycin (Lincocin) andClindamycin (Cleocin)

They are well absorbed orally, toleratedparenterally.High concentrations are achieved in most bodytissues and the saliva.Cerebral spinal fluid concentrations are low.

They are active against most gram-positiveorganisms including penicillinase producingstaphylococci.Clindamycin is a first-line agent for infections with

B. fragilis.


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Clindamycin

It is the drug of choice for the treatment of osteomyelitis.It is also important for its activity against anaerobicinfections, particularly against Bacteroides fragilis

Bacteroides fragilis is a cause ofdeep tissue abscessandgram-negative septicemiawith shock.best in contaminatedneck wounds and chronic drainingears.

Clindamycin is especially useful against polymicrobial-mixedinfections of bacteroides species and other oral anaerobesthat are prevalent in chronic tonsillitis and deep neckabscess of dental or oral origin.


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Clindamycin

Clindamycin issuperior to penicillin for eradicationof streptococci in tonsillo-pharyngitis, probablybecause the polymicrobial flora (producing beta-lactamases) of such infections renders penicillinineffective.The combination of clindamycin with gentamicincovers the three main contaminating infections of

head and neck surgery: staph., anaerobes, andpseudomonasClindamycin is not useful in intracranial infectionsbecause of poor penetration of the blood-brain

barrier


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Chloramphenicol

Chloramphenicol has a broad spectrum of activity.It is active against most gram-positive and gram-negative aerobic bacteria with the exceptions ofPseudomonas aeruginosa and many Enterobacter,Serratia, and indole-positive Proteus species.It has excellent activity against anaerobic bacteria,rickettsiae, and mycoplasmas.

The excellent penetration of chloramphenicol intothe CSF makes it the initial drug of choice in mostcases of meningitis.It also achieves therapeutic levels in other body

tissues and fluids, including the aqueous humor


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Aminoglycosides

Neomycin, Gentamicin, Tobramycin, AmikacinOnly active against anaerobes because an oxygendependent system is required to transport themolecules into the cell.Synergism with cell wall inhibitors is seen becausethey increase the permeability of the cellAntibacterial spectrum:

Gram negatives: Pseudomonas, Proteus,Serratia, E. coli, Klebsiella

NeomycinS. aureusand Proteus

Pseudomonasand Strepare resistant


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Aminoglycosides

OtotoxicCochlear and vestibular.Concentrates in endolymph and perilymph.

Nephrotoxic.

Proximal tubule damage


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Aminoglycosides

GentamicinGentamicin is the agent of choice for many gram-negative bacterial infections, and is combined with penicillin or semi-synthetic

penicillin to treat staphylococcal and enterococcalendocarditis.

TobramycinTobramycin has a similar spectrum of activity togentamicin. It is the preferred agent forpseudomonas infection, and

has a synergy with carbenicillin for Pseudomonas.


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Aminoglycosides

AmikacinAmikacin has a similar spectrum of activity to gentamicinand tobramycin. It is active against hospital-acquired resistant gram-

negative bacteria.This drug should be reserbved for bacteria resistant togentamicin and tobramicin.

BacitracinBacitracin is for topical use only.It is active against most gram-positive organisms includingstaphylococci and streptococci. Gram-negative bacteria areresistant.

It is a topical agent not absorbed systemically like neomycin


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Aminoglycosides

NeomycinNeomycin is used for topical administration only.It usually is combined with polymyxin B and

bacitracin in creams and sprays such as Neosporinointment.Its activity is against staphylococci and most gram-negative bacteria except Pseudomonas.

As a topical agent it may be systematicallyabsorbed to cause progressive nerve deafness.It also may cause deafness when instilled in theotic canal with a perforated tympanic membrane


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Tetracyclines

This group of broad-spectrum bacteriostatic agents aregenerally administered orally.They are active against many gram-positive and gram-negative bacteria excluding most Enterococcus and Proteus,

Pseudomonas, and Klebsiella species.Rickettsiae, chlamydiae, and mycoplasmas also aresusceptible to tetracyclines.The tetracyclines are divided into three pharmacologically

distinct groups:(1) shortacting: tetracycline, chlortetracycline,oxytetracycline;

(2) intermediate: demeclocycline;(3) long-acting: doxycycline and minocycline.


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Tetracyclines

Absorption of these compounds from thegastrointestinal tract is hindered by milk andcalcium, magnesium, and aluminium-containing

drugs.Tetracycline achieves adequate levels in mosttissues and body fluids except the CSF.However, only minocycline reaches high enough

levels in the saliva to cure meningococcal carriersTetracycline suspension is empirically used in atopical mixture (mouthwash, gargle, and swallow) torelieve the pain of aphthous stomatitis


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Miscellaneous

FluoroquinolonesRifampin

Metronidazole


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FluoroquinolonesCiprofloxacin (Cipro; IV ; cipromax oral), Ofloxacin

(tarivan tab; Floxin; Topical), Levofloxacin (Levaquin; IV; Oral).Inhibits DNA gyrase, causing permanent DNAcleavage.

Wide distribution - CSF, saliva, bone, cartilageEffective vs. gram +, gram -, atypicals, andPseudomonas.Decreased activity against anaerobes.

treatment of pseudomonas sinusitis (polyposis) &Necrotizing (malignant) otitis externa can be treated(intravenously in the acute stage, then orally on anoutpatient basis in the convalescent stage) with

ciprofloxacin


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FluoroquinolonesRespiratory quinolones (levofloxacin).

Active against Strep(including penicillin-resistant forms),S. aureus(including MRSA), H. flu, M. cat(includingpenicillin-resistant strains), and atypicals.Used in AOM, sinustiis, pharyngitis

Antipseudomonas quinolones (ciprofloxacin/ofloxacin)Active against Pseudomonas, H. flu, M. cat.Strep pyogenes,Strep pneumoniae, and MRSA are

resistant.Used in children with Cystic Fibrosis.Topicals used for otitis media.

Levofloxacin and Moxifloxacin (Avelox: oral/IV )have

increased Staphactivity even against cipro-resistant strains.

Fl i l


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Fluoroquinolones

Adverse effects.Headache, dizziness, nausea, lightheadednessprolong the electro cardiographic Q-T intervalLimit use in pregnancy, nursing mothers, and children

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Antibiotics and Otolaryngologists