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Microbiology, Infections,

and Antibiotic Therapy

Elizabeth J. Rosen, MD

Francis B. Quinn, MD

March 22, 2000

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Basic Bacteriology

Shape

Arrangement

Gram Staining

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Cell Wall Characteristics

Gram Positive Gram Negative

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Bacterial Growth

Binary Fission = Exponential Growth

Four Phases of Growth

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Normal Bacterial Flora

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Host Defense Mechanisms

Nonspecific Immunity

barriers

inflammatory response

Specific Immunity

Passive

Active humoral

cell-mediated

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Clinical Microbiology

Gram Positive Cocci

Gram Positive Bacilli

Gram Negative Cocci

Gram Negative Bacilli

Anaerobes

Spirochetes

Mycobacteria

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Gram Positive Cocci

Staphylococcus

Streptococcus

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Staphylococcus

S. aureus, S. epidermidis, S. saprophyticus

S. aureus

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Streptococcus

S. viridans oral flora

infective endocarditis

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S. pyogenes

Group A, beta hemolyticstrep

pharyngitis, cellulitis

rheumatic fever fever

migrating polyarthritis

carditis

immunologic cross reactivity

acute glomerulonephritis edema, hypertension,

hematuria

antigen-antibody complexdeposition

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S. pneumoniae

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Gram Negative Cocci

Neisseria

meningitidis

gonorrhea

Moraxella catarrhalis

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Gram Positive Bacilli

Clostridium

Bacillus

Corynebacterium

Listeria

Actinomyces

Nocardia

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C. tetani

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C. botulinum

Descending weakness-->paralysis

diplopia, dysphagia-->respiratory failure

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C. perfringens

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C. diphtheriae

Fever, pharyngitis, cervical LAD

thick, gray, adherent membrane

sequelae-->airway obstruction, myocarditis colony morphology

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L. monocytogenes

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Actinomyces

Part of normal oral cavity flora

50% of infections occur in face & neck

forms abscesses with sulfur granules draining sinus tracts

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Nocardia

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Gram Negative Bacilli

Facultative Anaerobes

Respiratory Haemophilus

Bordetella Legionella

Zoonotic Yersinia

Francisella

Pastuerella

Enteric Klebsiella

Serratia

Proteus

Enterobacter

Strict Aerobes

Pseudomonas

Anaerobes

Bacteroides

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Enterobacteriaceae

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K. rhinoscleromatis

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K. rhinoscleromatis

Catarrhal

purulent rhinorrhea

Granulomatous

mucosal nodules

Cicatricial

fibrosis

stenosis

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H. influenzae

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Legionella

Community and Nosocomial pneumonia

contaminated water sources

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B. pertussis

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Zoonotic Gram Negative Rods

Yersinia

plague

Franciscella

tularemia

Pasturella dog/cat bites

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Pseudomonas

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Anaerobic Bacteria

Bacteroides

Fusobacterium

Peptostreptococcus

Actinomyces

Prevotella

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Spirochetes

Treponema Borrelia

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Manifestations of Syphilis

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Lyme Disease

Cutaneous lesions

erythema chronicum

migrans Nonspecific symptoms

malaise, fatigue,headache, fevers, chills,

myalgias, arthralgias,lymphadenopathy

Late manifestations

neurologic

cardiac

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M. tuberculosis

Pulmonary disease (82%)

Extrapulmonary disease (18%)

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ENT Manifestations of TB

Scrofula

matted lymphadenopathy: posterior triangle

Laryngeal TB edema, ulcers, polypoid changes: arytenoids

Oral TB

painless ulcers: tongueAural TB

thickened TM-->hyperemia-->multiple perfs

thin, watery otorrhea-->thick, cheesy d/c

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M. leprae

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Antibiotic Therapy

Identify infecting organism

Evaluate drug sensitivity

Target site of infection

Drug safety/side effect profile

Patient factors

Cost

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Classification of Antibiotics

Bacteriostatic Bactericidal

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Classification of Antibiotics

Chemical Structure

Spectrum of Activity Mechanism of Action

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Mechanism of Action

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Inhibitors ofCell Wall Synthesis

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Beta Lactam Antibiotics

Penicillins

Cephalosporins

Carbapenems

Monobactams

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Penicllins

Derived from the fungus Penicillium

Therapeutic concentration in most tissues

Poor CSF penetration

Renal excretion

Side effects: hypersensitivity, nephritis,neruotoxicity, platelet dysfunction

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Natural Penicillins

Penicillin G, Penicillin V

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Antistaphylococcal Penicillins

Methicillin

Nafcillin

Oxacillin

Dicloxacillin

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Aminopenicillins

Amoxicillin +/- clavulanate

Ampicillin +/- sulbactam

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Antipseudomonal Penicillins

Carbenicillin

Ticarcillin +/- clavulanate

Piperacillin +/- tazobactam

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Cephalosporins

Structurally similar topenicillins

Therapeutic

concentration in manytissues, 3rd and 4thgeneration into CSF

Renal Excretion

Side Effects allergy

disulfiram-like effect

anti-Vitamin K

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Generations ofCephalosporins

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Monobactams

Aztreonam

single beta lactam ring

narrow spectrum: gram-negative aerobes

Enterobacteriacea

Pseudomonas

given IV/IM

renal excretion

little cross-reactivitywith other beta lactams

side effects: phlebitis,

rash, elevated LFTs

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Carbapenems

Meropenem/Imipenem

broad spectrum

active against MRSA

given IV

penetrates CSF

renal metabolism and

excretion addition of cilastin

side effects: GI upset,eosinophilia, neutropenia,lowering of seizure threshold

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Vancomycin

Tricyclic glycopeptide

Inhibits synthesis of phospholipids and

cross-linking of peptidoglycansActivity against gram-positive organisms

Useful for beta lactam resistant infections

Widely distributed, penetrates CSF Renal elimination, follows creatinine cl.

Side effects: phlebitis, red man syndrome,

ototoxicity, nephrotoxicity

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Protein Synthesis Inhibitors

Human Ribosome

80S 40S

60S

Bacterial Ribosome

70S 30S

50S

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Tetracyclines

Isolated from Streptomyces aureofaciens

Reversibly bind 30S ribosomal subunit

Penetrate sinus mucosa, saliva and tears

Metabolized in liver-->excreted in bile-->reabsorbed-->eliminated in urine

Side effects: GI upset, hepatotoxicity,photosensitivity, bony deposition

Contraindicated in pregnant or breast

feeding women, children under 8 y/o

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Tetracyclines

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Aminoglycosides

Derived from Streptomyces and Micormonospora

Irreversible binding to 30S subunit

Actively transported into bacterial cells Variable tissue penetration, unreliable CSF levels

Concentrate within perilymph

Renal elimination

Nephrotoxicity, ototoxicity, neurotoxicity

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Aminoglycosides

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Macrolides

Macrocyclic lactone structure


Therapeutic concentrations inoropharyngeal and respiratory secretions

No CSF penetration

Metabolized in liver, excreted in feces andurine

Side effects: GI upset, ototoxicity,

hepatotoxicity

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Erythromycin

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Alternate Macrolides

Clarithromycin Azithromycin

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Chloramphenicol

Isolated from Streptomyces

Reversible binding to 50S subunit

Broad spectrum of activity Indicated for severe anaerobic infections or

unresponsive life-threatening infections

Widely distributed, enters CSF

Metabolized in liver (inhibits P-450), eliminatedin urine

Toxicities: reversible anemia, hemolytic anemia,

aplastic anemia, gray baby syndrome

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Clindamycin

Semisynthetic derivative of Lincomycin


Covers anaerobes and gram + aerobes

Widely useful for head and neck infections

Penetrates saliva, sputum, pleural fluid, and bone,but not CSF

Metabolized in liver-->reabsorbed-->eliminated inurine

Side effects: rash, neutropenia/thrombocytopenia,pseudomembranous colitis

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Inhibitors of Metabolism

Sulfonamides

Trimethoprim

Interfere with theproduction of folicacid coenzymes that

are required forpurine and pyrimidinesynthesis

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Sulfonamides

Derived from prontosil

Competitve antagonist ofPABA

Wide distribution, penetrateCSF, cross placenta

Metabolized in liver,eliminated in urine

Side effects: rash,angioedema, Stevens-Johnson syndrome,kernicterus

Avoid in pregnancy and

infants

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Sulfonamides

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Trimethoprim

Inhibits dihydrofolate reductase

1000x higher affinity for bacterial enzyme

than human enzyme Similar spectrum and pharmacokinetic

profile as sulfas

Side effects: folate deficiency anemia,leukopenia, granulocytopenia

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Co-Trimoxazole (TMP/SMX)

Combination gives synergistic antibacterialaction

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Co-Trimoxazole (TMP/SMX)

Inhibitors of Nucleic Acid

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Inhibitors ofNucleic Acid

Function/Synthesis

Fluoroquinolones

Bind bacteria DNA gyrase (topoisomerase II)

Concentrate in sinus and middle ear mucosa,penetrate cartilage and bone

Partially metabolized in liver-->GI or renal excretion

Side effects: nausea, dizziness, phototoxicity,nephrotoxicity

Avoid in pregnant or nursing women

? Use in children--possible effect on articular cartilage

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Fluoroquinolones

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Antimycobacterial Therapy

Must address two distinct populations oftubercle bacilli

First-line treatment: regimens of 3-4drugs for 6 months to 2 years

Second-line therapy: reserved for multi-

drug resistant organisms or unresponsiveinfection

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First-Line Agents

Isoniazide

Rifampin

Pyrazinamide Ethambutol

Streptomycin

Isoniazide

most potent drug

inhibits formation of

outer mycolic acid widely distributes and

penetrates CSF

metabolized in liver,

excreted in urine,saliva, and sputum

side effects:hypersensitivity,neruopathy,

hepatotoxicity

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First-Line Agents

Isoniazide

Rifampin


Streptomycin

Rifampin from Streptomyces

antibacterial and anti-tubercule

interferes with RNAtranscription

wide distribution, penetratesCSF

metabolized in liver

gives orange-red color tostool, urine and tears

side effects: rash, GI upset,hepatotoxicity

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First-Line Agents

Isoniazide

Rifampin


Streptomycin

Pyrazinamide

hydrolyzed topyrazinoic acid

unclear mechanism

widely distributed,including CSF

side effects: GI upset,

hepatotoxicity,hyperuricemia

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First-Line Agents

Isoniazide

Rifampin


Streptomycin

Ethambutol

inhibits cell wallsynthesis and

maintenance

widely distributed,penetrates CSF

partially metabolized,

excreted in urine potential for optic

neuritis

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First-Line Agents

Isoniazide

Rifampin


Streptomycin

Streptomycin

aminoglycoside

binds 30S subunit

penetrates synovial,pleural, pericardial, andascitic fluids but not CSF

renal excretion

side effects:hypersensitivity,paraesthesias, auditoryor vestibular dysfunction,nephrotoxicity

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Antimycobacterials forLeprosy

Dapsone structurally related to

sulfonamides

PABA antagonist

activity against M. leprae

also effective forpneumocystis and brownrecluse spider bites

wide distribution

acetylated in liver, eliminatedin urine

side effects: erythemanodosum leprosum,peripheral neuropathy,

methemoglobinemia

Clofazimine synthetic phenazine dye

binds DNA and inhibitsreplication and transcription

activity against M. leprai andMAI

wide distribution, does notpenetrate CSF

partially metabolized,excreted in bile

side effects: GI upset,red/purple discoloration ofskin and body fluids

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Antibiotic Prophylaxis

Post-op wound infection is the second mostcommon nosocomial infection.

Cost of this complication approaches $5billion annually.

Prolongs hospital length of stay by 15 days.

Costs nearly $22,000 more for one post-opwound infection that to use prophylacticclindamycin on 100 patients.

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Classification of Wounds

Class I--Clean Wounds

strict sterile technique

surgery does not involve penetration ofaerodigestive tract

1-5% infection rate

prophylactic antibiotics not cost-effective andnot indicated

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Class II--Clean-contaminated Wounds

the surgical procedure involves entrance into

the aerodigestive or genitourinary tracts contact with bacterial contaminated secretions

8-11% inherent infection rate

increased length or complexity of surgery maybe associated with increased rates of infection--reports vary from 28-87%

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Class III--Contaminated Wounds

traumatic wounds, surgical cases involving

spillage from the GI tract inherent infection rate 15-17%

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Prophylactic Antibiotics

Cover bacterial flora involved in thesurgical field

Administer within 2 hours before or 3hours after surgery has begun

Maintain therapeutic blood level during

lengthy procedures Continue prophylaxis for the 24 hour

period surrounding surgery

Effective Prophylactic

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Effective Prophylactic

Regimens

Cefazolin +/- metronidazole

Cefoperozone

Clindamycin +/- gentamycin or amikacin

Amoxicillin/clavulanate

Ampicillin/sulbactam

Ticarcillin/clavulanate

Topical Antibiotic

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Topical Antibiotic

Prophylaxis

Clindamycin or Peridex oral rinses

significantly reduce bacterial counts in the

oral cavity both immediate effect and prolonged

effect for approximately 4 hours

reduce post-op wound infections aloneand in combination with parenteralantibiotic therapy

Indications for Antibiotic

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Indications for Antibiotic

Prophylaxis in ENT Surgery

Prophylaxis Indicated

Any Class II Head andNeck Procedure

Tonsillectomy

Neruotologic/SkullBase Procedures

Open Mandible

Fracture Repair

Prophylaxis NOT Indicated

Basic Sinonasal Procedures

Otologic Procedures

Midface Fracture Repair

Closed Mandible FractureRepair

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