Microbiology, Infections, and Antibiotic Therapy

Microbiology, Infections, and Antibiotic Therapy
Elizabeth J. Rosen, MD

Francis B. Quinn, MD

March 22, 2000

Basic Bacteriology
Shape
Arrangement
Gram Staining
Cell Wall Characteristics
Gram Positive
Gram Negative
Bacterial Growth
Binary Fission = Exponential Growth
Four Phases of Growth
Normal Bacterial Flora
Host Defense Mechanisms
Nonspecific Immunity
barriers
inflammatory response
Specific Immunity
Passive
Active
humoral
cell-mediated
Clinical Microbiology
Gram Positive Cocci
Gram Positive Bacilli
Gram Negative Cocci
Gram Negative Bacilli
Anaerobes
Spirochetes
Mycobacteria
Gram Positive Cocci
Staphylococcus
Streptococcus
Staphylococcus
S. aureus, S. epidermidis, S. saprophyticus
S. aureus
Streptococcus
S. viridans
oral flora
infective endocarditis
S. pyogenes
Group A, beta hemolytic strep
pharyngitis, cellulitis
rheumatic fever
fever
migrating polyarthritis
carditis
immunologic cross reactivity
acute glomerulonephritis
edema, hypertension, hematuria
antigen-antibody complex deposition
S. pneumoniae
Gram Negative Cocci
Neisseria
meningitidis






gonorrhea
Moraxella catarrhalis
Gram Positive Bacilli
Clostridium
Bacillus
Corynebacterium
Listeria
Actinomyces
Nocardia
C. tetani
C. botulinum
Descending weakness-->paralysis
diplopia, dysphagia-->respiratory failure
C. perfringens
C. diphtheriae
Fever, pharyngitis, cervical LAD
thick, gray, adherent membrane
sequelae-->airway obstruction, myocarditis
colony morphology
L. monocytogenes
Actinomyces
Part of normal oral cavity flora
50% of infections occur in face & neck
forms abscesses with sulfur granules
draining sinus tracts
Nocardia
Gram Negative Bacilli
Facultative Anaerobes
Respiratory
Haemophilus
Bordetella
Legionella
Zoonotic
Yersinia
Francisella
Pastuerella
Enteric
Klebsiella
Serratia
Proteus
Enterobacter
Strict Aerobes
Pseudomonas


Anaerobes
Bacteroides
Enterobacteriaceae
K. rhinoscleromatis
K. rhinoscleromatis
Catarrhal
purulent rhinorrhea
Granulomatous
mucosal nodules
Cicatricial
fibrosis
stenosis
H. influenzae
Legionella
Community and Nosocomial pneumonia
contaminated water sources
B. pertussis
Zoonotic Gram Negative Rods
Yersinia
plague

Franciscella
tularemia

Pasturella
dog/cat bites
Pseudomonas
Anaerobic Bacteria
Bacteroides
Fusobacterium
Peptostreptococcus
Actinomyces
Prevotella
Spirochetes
Treponema
Borrelia
Manifestations of Syphilis
Lyme Disease
Cutaneous lesions
erythema chronicum migrans
Nonspecific symptoms
malaise, fatigue, headache, fevers, chills, myalgias, arthralgias, lymphadenopathy
Late manifestations
neurologic
cardiac
M. tuberculosis
Pulmonary disease (82%)
Extrapulmonary disease (18%)
ENT Manifestations of TB
Scrofula
matted lymphadenopathy: posterior triangle
Laryngeal TB
edema, ulcers, polypoid changes: arytenoids
Oral TB
painless ulcers: tongue
Aural TB
thickened TM-->hyperemia-->multiple perfs
thin, watery otorrhea-->thick, cheesy d/c
M. leprae
Antibiotic Therapy
Identify infecting organism
Evaluate drug sensitivity
Target site of infection
Drug safety/side effect profile
Patient factors
Cost
Classification of Antibiotics
Bacteriostatic
Bactericidal
Classification of Antibiotics
Chemical Structure
Spectrum of Activity
Mechanism of Action
Mechanism of Action
Inhibitors of Cell Wall Synthesis
Beta Lactam Antibiotics
Penicillins
Cephalosporins
Carbapenems
Monobactams
Penicllins
Derived from the fungus Penicillium
Therapeutic concentration in most tissues
Poor CSF penetration
Renal excretion
Side effects: hypersensitivity, nephritis, neruotoxicity, platelet dysfunction
Natural Penicillins
Penicillin G, Penicillin V
Antistaphylococcal Penicillins
Methicillin

Nafcillin

Oxacillin

Dicloxacillin
Aminopenicillins
Amoxicillin +/- clavulanate

Ampicillin +/- sulbactam
Antipseudomonal Penicillins
Carbenicillin
Ticarcillin +/- clavulanate
Piperacillin +/- tazobactam
Cephalosporins
Structurally similar to penicillins
Therapeutic concentration in many tissues, 3rd and 4th generation into CSF
Renal Excretion
Side Effects
allergy
disulfiram-like effect
anti-Vitamin K
Generations of Cephalosporins
Monobactams
Aztreonam
single beta lactam ring
narrow spectrum: gram-negative aerobes
Enterobacteriacea
Pseudomonas
given IV/IM
renal excretion
little cross-reactivity with other beta lactams
side effects: phlebitis, rash, elevated LFT’s
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
Vancomycin
Tricyclic glycopeptide
Inhibits synthesis of phospholipids and cross-linking of peptidoglycans
Activity 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
Protein Synthesis Inhibitors
Human Ribosome
80S
40S
60S
Bacterial Ribosome
70S
30S
50S
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
Tetracyclines
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
Aminoglycosides
Macrolides
Macrocyclic lactone structure
Irreversible binding to 50S subunit
Therapeutic concentrations in oropharyngeal and respiratory secretions
No CSF penetration
Metabolized in liver, excreted in feces and urine
Side effects: GI upset, ototoxicity, hepatotoxicity
Erythromycin
Alternate Macrolides
Clarithromycin
Azithromycin
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), eliminated in urine
Toxicities: reversible anemia, hemolytic anemia, aplastic anemia, gray baby syndrome
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 in urine
Side effects: rash, neutropenia/thrombocytopenia, pseudomembranous colitis

Inhibitors of Metabolism
Sulfonamides
Trimethoprim

Interfere with the production of folic acid coenzymes that are required for purine and pyrimidine synthesis
Sulfonamides
Derived from prontosil
Competitve antagonist of PABA
Wide distribution, penetrate CSF, cross placenta
Metabolized in liver, eliminated in urine
Side effects: rash, angioedema, Stevens-Johnson syndrome, kernicterus
Avoid in pregnancy and infants
Sulfonamides
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
Co-Trimoxazole (TMP/SMX)
Combination gives synergistic antibacterial action
Co-Trimoxazole (TMP/SMX)
Inhibitors of Nucleic 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
Fluoroquinolones
Antimycobacterial Therapy
Must address two distinct populations of tubercle bacilli
First-line treatment: regimens of 3-4 drugs for 6 months to 2 years
Second-line therapy: reserved for multi-drug resistant organisms or unresponsive infection
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
First-Line Agents
Isoniazide
Rifampin
Pyrazinamide
Ethambutol
Streptomycin
Rifampin
from Streptomyces
antibacterial and anti-tubercule
interferes with RNA transcription
wide distribution, penetrates CSF
metabolized in liver
gives orange-red color to stool, urine and tears
side effects: rash, GI upset, hepatotoxicity
First-Line Agents
Isoniazide
Rifampin
Pyrazinamide
Ethambutol
Streptomycin
Pyrazinamide
hydrolyzed to pyrazinoic acid
unclear mechanism
widely distributed, including CSF
side effects: GI upset, hepatotoxicity, hyperuricemia
First-Line Agents
Isoniazide
Rifampin
Pyrazinamide
Ethambutol
Streptomycin
Ethambutol
inhibits cell wall synthesis and maintenance
widely distributed, penetrates CSF
partially metabolized, excreted in urine
potential for optic neuritis
First-Line Agents
Isoniazide
Rifampin
Pyrazinamide
Ethambutol
Streptomycin
Streptomycin
aminoglycoside
binds 30S subunit
penetrates synovial, pleural, pericardial, and ascitic fluids but not CSF
renal excretion
side effects: hypersensitivity, paraesthesias, auditory or vestibular dysfunction, nephrotoxicity
Antimycobacterials for Leprosy
Dapsone
structurally related to sulfonamides
PABA antagonist
activity against M. leprae
also effective for pneumocystis and brown recluse spider bites
wide distribution
acetylated in liver, eliminated in urine
side effects: erythema nodosum leprosum, peripheral neuropathy, methemoglobinemia
Clofazimine
synthetic phenazine dye
binds DNA and inhibits replication and transcription
activity against M. leprai and MAI
wide distribution, does not penetrate CSF
partially metabolized, excreted in bile
side effects: GI upset, red/purple discoloration of skin and body fluids
Antibiotic Prophylaxis
Post-op wound infection is the second most common nosocomial infection.
Cost of this complication approaches $5 billion annually.
Prolongs hospital length of stay by 15 days.
Costs nearly $22,000 more for one post-op wound infection that to use prophylactic clindamycin on 100 patients.
Classification of Wounds
Class I--Clean Wounds
strict sterile technique
surgery does not involve penetration of aerodigestive tract
1-5% infection rate
prophylactic antibiotics not cost-effective and not indicated
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 may be associated with increased rates of infection--reports vary from 28-87%
Classification of Wounds
Class III--Contaminated Wounds
traumatic wounds, surgical cases involving spillage from the GI tract
inherent infection rate 15-17%
Prophylactic Antibiotics
Cover bacterial flora involved in the surgical field
Administer within 2 hours before or 3 hours after surgery has begun
Maintain therapeutic blood level during lengthy procedures
Continue prophylaxis for the 24 hour period surrounding surgery
Effective Prophylactic Regimens
Cefazolin +/- metronidazole
Cefoperozone
Clindamycin +/- gentamycin or amikacin
Amoxicillin/clavulanate
Ampicillin/sulbactam
Ticarcillin/clavulanate
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 alone and in combination with parenteral antibiotic therapy
Indications for Antibiotic Prophylaxis in ENT Surgery
Prophylaxis Indicated
Any Class II Head and Neck Procedure
Tonsillectomy
Neruotologic/Skull Base Procedures
Open Mandible Fracture Repair
Prophylaxis NOT Indicated
Basic Sinonasal Procedures
Otologic Procedures
Midface Fracture Repair
Closed Mandible Fracture Repair