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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
Irreversible binding to 50S subunit
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
Irreversible binding to 50S subunit
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
Pyrazinamide Ethambutol
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
Pyrazinamide Ethambutol
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
Pyrazinamide Ethambutol
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
Pyrazinamide Ethambutol
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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Classification of Wounds
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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Classification of Wounds
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