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Antibacterial Therapy
in
Otorhinolaryngology
Dr. Sudin Kayastha
1st Year Resident
ORL & HNS
History
Sir Alexander Fleming
History
 Sir Alexander Fleming, a Scottish researcher, is
credited with the discovery of penicillin in 1928.
 At the time, Fleming was experimenting with the
influenza virus in the Laboratory of the Inoculation
Department at St. Mary’s Hospital in London.
 Fleming returned from a two-week vacation to find
that a mold had developed on an accidentally
contaminated staphylococcus culture plate.
 Upon examination of the mold, he noticed that the
culture prevented the growth of staphylococci.
Penicillin G, V
 Penicillin G (IV & IM form), Penicillin V (oral)
 Mechanism of action
 Binds Penicillin binding proteins (transpeptidases)
 Block transpeptidase cross-linking of peptidoglycan in
cellwall
 Inhibits Cellwall Formation
 Bactericidal
Penicillin G, V
 Antibacterial Spectrum
 Gram Positive : S. pneumoniae, S. pyogenes,
Actinomyces
 Gram Negative: Neisseria meningitidis
 Spirochetes: Treponema pallidum
 Beta Lactamase Sensitive
 Adverse Effects
 Hypersensitivity reactions, Hemolytic anemia, Drug-
induced interstitial nephritis
 Resistance
 Beta-lactamase cleaves Beta-lactam ring. Mutations in
PBPs
Penicillinase-sensitive Penicillins
 Amoxicillin, Ampicillin, Aminopenicillin
 Mechanism of action
 Same as Penicillin
 Wider Spectrum
 Penicillinase sensitive
Penicillinase-sensitive Penicillins
 Antibacterial Spectrum
 Extended spectrum penicillin- H. influenzae, H. pylori,
E.coli, Listeria monocytogenes, Proteus mirabilis,
Salmonella, Shigella, Enterococci
 Adverse Effects
 Hypersensitivity reactions, rash, pseudomembranous
colitis
 Resistance
 Penicillinase cleaves Beta-lactam ring.
Penicillinase-resistant Penicillins
Dicloxacillin, Nafcillin, Oxacillin
 Mechanism of action
 Same as Penicillin
 Narrow Spectrum
 Penicillinase resistant
 Antibacterial spectrum
 Staphylococcus aureus (except MRSA)
 Adverse effects
 Hypersensitivity reactions, interstitial nephritis
 Resistance
 MRSA has altered penicillin-binding protein site
AntiPseudomonal Penicillins
Piperacillin, Ticaricillin
 Mechanism of action
 Same as Penicillin
 Extended Spectrum
 Penicillinase sensitive
 Antibacterial spectrum
 Pseudomonas spp. and Gram Negative rods
 Adverse effects
 Hypersensitivity reactions
Cephalosporins
 Mechanism of action
 Same as Penicillin
 Less Susceptible to Penicillinases
 Bactericidal
Cephalosporins
 Antibacterial Spectrum
Cephalospori
n
Drugs Coverage
1st
Generation
Cefazolin,
Cephalexin
Gram + cocci, Proteus mirabilis, E.coli, Klebsiella
pneumoniae
2nd
Generation
Cefaclor,
Cefoxitin,
Cefuroxime,
Cefotetan
Gram + cocci, Hemophilus influenzae,
Enterobacter aerogenes, Neisseria spp, Serratia
spp, Proteus mirabilis, E.coli, Klebsiella
pneumoniae
3rd
Generation
Ceftriaxone,
Cefotaxime,
Cefpodoxime,
Ceftazidime,
Ceftolozane
Serious Gram Negative Infections resistant to
other Beta-lactams
Ceftazidime- Pseudomonas
4th
Generation
Cefepime Gram negative organisms, with increased activity
against Pseudomonas and Gram positive
organisms
5th
Generation
Ceftaroline Broad Gram positive and negative organism
coverage,
Cephalosporins
 Adverse Effects
 Hypersensitivity reactions
 Hemolytic Anemia
 Disulfiram like reactions
 Resistance
 Inactivated by Cephalosporinase (a type of Beta-
lactamase)
 Structural change in Penicillin Binding Protein
(Transpeptidase)
Beta Lactamase Inhibitors
Clavulanic acid, Avibactam,
Sulbactam, Tazobactam
 Added to Penicillin antibiotics
to protect it from destruction
by Beta lactamase
Carbapenems
Doripenem, Imipenem, Meropenem, Ertapenem
 Used in Life-threatening infections
 Imipenem- Broad spectrum, Beta-lactamase resistant carbapenem
 Always administered with Cilastatin (inhibitor of renal
dehydropeptidase I) to decrease inactivation of drug in renal
tubules.
 Antibacterial spectrum
 Wide Spectrum, Gram positive cocci, Gram negative rods,
Anaerobes
 Adverse effects
 GI distress, Rash, Seizure at high plasma level
 Resistance
 Inactivated by carbapenemases produced by Klebsiella
Carbapenems
 Adverse effects
 GI distress,
 Rash,
 Seizure at high plasma level
 Resistance
 Inactivated by carbapenemases produced by
Klebsiella pneumoniae, E.coli
Vancomycin
 Mechanism
 Inhibits cellwall peptidoglycan formation
 Bacteriocidal against most bacteria, Bacteriostatic
against Clostridium difficile.
 Not susceptible to Beta-lactamase
 Antibacterial spectrum
 Gram positive bacteria only – multidrug-resistant
organisms including MRSA, Staph. epidermidis,
Enterococcus spp, Clostridium difficile
Vancomycin
 Adverse Effects
 Nephrotoxicity, Ototoxicity, Thrombophlebitis, Diffuse
flusing- Redman Syndrome, DRESS Syndrome
 Resistance
 Occurs in bacteria (eg. Enterococcus) via aminoacid
modification
Polymyxins
 Cation Polypeptide that bind to phospholipids on
bacterial cell membrane of gram negative bacteria
 Disrupts cell membrane integrity leading to leakage
of celllular components and cell death
 Two forms available: Polymixin B (commonly used),
Polymixin E
 Antibacterial spectrum
 Gram negative bacteria including Pseudomonas
aeruginosa, E.coli, Klebsiella pneumonia,
Acinetobacter spp., Enterobacter spp.
 Adverse Effects
 Nephrotoxicity and neurotoxicity
Protein Synthesis Inhibitors
 Specifically smaller bacterial ribosome (70s, made of
30s and 50s subunits)
 All are bacteriostatic except aminoglycosides
(bacteriocidal)
 30s Inhibitors 50s Inhibitors
Aminoglycosides Chloramphenicol
Tetracyclines Clindamycin
Erythromycin
Linezolid
Aminoglycosides
 Gentamicin, Neomycin, Amikacin, Tobramycin,
Streptomycin
 Mechanism
 Irreversible inhibition of initiation complex through binding of
30s subunit misreading of mRNA
 Also blocks translocation
 Requires O2 for uptake so ineffective against anaerobes
 Bactericidal
 Antibacterial spectrum
 Aerobic gram-negative bacilli, including those that may be
multidrug resistant, such as Pseudomonas aeruginosa,
Klebsiella pneumoniae, and Enterobacter spp.
Aminoglycosides
 Adverse Effects
 Nephrotoxicity,
 Ototoxicity,
 Neuromuscular Blockade (absolute contraindication
in myasthenia gravis)
 Teratogenicity
 Resistance
 Bacterial transferase enzymes inactivate the drug by
acetylation, phosphorylation or adenylation
Tetracyclines
 Tetracycline, Doxycycline, Minocycline
 Mechanism
 Binds to 30s and prevent attachment of aminoacyl
tRNA
 Limited CNS penetration
 Fecally eliminated so can be used in renal failure
patients
 Bacteriostatic
 Not to be taken with milk, antacids, or iron containing
preparations
Tetracyclines
 Antibacterial spectrum
 Borrelia burgdorferi, Mycoplasma pneumoniae
 Drug ability to accumulate intracellularly so effective
against Rickettsia and Chlamydia
 Adverse Effects
 GI distress, discolouration of teeth, inhibition of bone
growth in children, photosensitivity
 Resistance
 Uptake or efflux out of bacterial cells by plasmid
encoded transport pump
Chloramphenicol
 Mechanism
 Blocks peptidyltransferase at 50s ribosomal subunit
 Bacteriostatic
 Antibacterial spectrum
 Hemophilus influenzae, Neisseria meningitidis,
Streptococcus pneumoniae, Rickettsia spp.
Chloramphenicol
 Adverse Effects
 Anemia (dose dependent)
 Aplastic anemia (dose independent)
 Gray Baby Syndrome (in premature infants liver
lacks UDP-glucuronyl transferase)
 Resistance
 Plasmid encoded acetyltransferase inactivates the
drug
Clindamycin
 Mechanism
 Blocks peptidyl transfer (translocation) at 50s ribosomal
subunit
 Bacteriostatic
 Antibacterial spectrum
 Anaerobes like Bacteoides spp., Clostridium spp.,
 Group A Streptococcus
 Adverse Effects
 Fever, diarrhoea
 Pseudomembranous colitis (C. difficile overgrowth)
Oxazolidinones (Linezolid)
 Mechanism
 Inhibit protein synthesis by binding to 50s subunit
and preventing formation of initiation complex
 Antibacterial spectrum
 Gram positive species including MRSA and VRE
Oxazolidinones (Linezolid)
 Adverse Effects
 Bone marrow suppression (especially
thrombocytopenia)
 Peripheral neuropathy
 Serotonin Syndrome (due to partial MAO inhibition)
 Resistance
 Point mutation of ribosomal RNA
Macrolides
 Azithromycin, Clarithromycin, Erythromycin
 Mechanism
 Inhibit protein synthesis by blocking translocation,
binds to 23s rRNA of 50s ribosomal subunit.
 Bacteriostatic
 Antibacterial spectrum
 Mycoplasma, Chlamydia, Legionella,
 Gram positive COCCI
 Bordetella pertusis
Macrolides
 Adverse Effects
 GI disturbances
 Arrhythmia (d/t prolonged QT interval)
 Acute Cholestatic Hepatitis
 Rash
 Eosinophilia
 Clarithromycin and Erythromycin inhibit cytochrome
P450
 Resistance
 Methylation of 23s rRNA binding site prevents
binding of drug
Sulfonamides
 Sulfamethoxazole, Sulfadiazine, Sulfisoxazole
 Mechanism
 Inhibit dihydropteroate synthase thus inhibiting folate
synthesis.
 Bacteriostatic (bacteriocidal when combined with
trimethoprim)
 Antibacterial spectrum
 Gram positive, Gram negative, Nocardia
Sulfonamides
 Adverse Effects
 Hypersensitivity reactions
 Hemolysis if G6PD deficiency
 Nephrotoxicity (tubulointerstitial nephritis)
 Photosensitivity
 Stevens-Johnson Syndrome
 Kernicterus in infants
 Resistance
 Altered Enzymes
Dapsone
 Mechanism
 Similar to sulfonamides
 Antibacterial spectrum
 Mycobacterium leprae
 Pneumocystis jirovecii
 Adverse Effects
 Hemolysis if G6PD deficiency
 Methemoglobinemia
 Agranulocytosis
Trimethoprim
 Mechanism
 Inhibit bacterial dihydrofolate reductase thus
inhibiting folate synthesis.
 Bacteriostatic
 Antibacterial spectrum
 Used in combination with Sulfonamides
(sulphamethoxazole : TMP-SMX)
 Shigella, Salmonella, Pneumocystis jirovecii
Trimethoprim
 Adverse Effects
 Hyperkalemia,
 Megaloblastic anemia
 Leukopenia
 Granulocytopenia
Fluoroquinolones
 Ciprofloxacin, Ofloxacin, Norfloxacin, Levofloxacin,
Moxifloxacin
 Mechanism
 Inhibits prokaryotic enzymes Topoisomerase II (DNA
gyrase) and Topoisomerase IV
 Bactericidal
 Antibacterial spectrum
 Enterobacteriaceae, Pseudomonas aeruginosa,
Hemophilus influenzae, Neisseria spp, Chlamydia spp,
Legionella spp.
 Streptococcus spp, Methicillin susceptible
Staphylococcus, Mycobacterium spp.
Fluoroquinolones
 Adverse Effects
 GI upsets
 Skin rashes
 Headaches
 Dizziness
 Legcramps and myalgia
 May cause Tendinitis and tendon rupture in >60 yrs old &
patients taking prednisolone
 Inhibits Cytochrome P450
 Resistance
 Chromosomal encoded mutation in DNA gyrase, plasmid
mediated resistance, efflux pumps
Metronidazole
 Mechanism
 Forms toxic free radical metabolites in the bacterial
cell that damage DNA
 Bactericidal
 Antibacterial spectrum
 Anaerobes (Bacteroides, C.difficile),
 Protozoans
 Not used in Pneumonia avidly binds to and is
inactivated by surfactant
Metronidazole
 Adverse Effects
 Headache
 Metallic taste
 Nausea
 Disulfiram like reaction (severe flushing, tachycardia,
hypotension) with alcohol
Antimycobacterial drugs
 Rifampicin
 Mechanism
 Inhibit DNA dependent RNA polymerase
 Antibacterial spectrum
 Mycobacterium tuberculosis
 Mycobacterium leprae
 Neisseria meningitidis
 Hemophilus influenzae
Antimycobacterial drugs
Rifampicin
 Adverse Effects
 Hepatotoxicity,
 Orange coloured urine
 Increases Cytochrome P450  drug interaction
 Resistance
 Mutation reduce drug binding to RNA Polymerase.
 Monotherapy rapidly leads to resistance
Antimycobacterial drugs
 Isoniazid
 Mechanism
 Inhibits synthesis of mycolic acids
 Bacterial Catalase-peroxidase (encoded by KatG)
needed to convert INH to active metabolite
 Antibacterial spectrum
 Mycobacterium tuberculosis
Antimycobacterial drugs
 Isoniazid
 Adverse Effects
 Hepatotoxicity,
 Vitamin B6 Deficiency( peripheral neuropathy)
 Drug induced SLE
 Metabolic Acidosis
 Seizures (in high doses refractory to
benzodiazepines)
 Resistance
 Mutation leading to underexpression of KatG
Antimycobacterial drugs
 Pyrazinamide
 Mechanism
 Mechanism uncertain
 Converted to active form pyrazinoic acid.
 Works in acidic pH (host phagolysosomes)
 Antibacterial spectrum
 Mycobacterium tuberculosis
 Adverse Effects
 Hyperuricemia, Hepatotoxicity
Antimycobacterial drugs
 Ethambutol
 Mechanism
 Inhibit carbohydrate polymerization of
mycobacterium cellwall by blocking arabinosyl
transferase
 Antibacterial spectrum
 Mycobacterium tuberculosis
 Adverse Effects
 Optic neuropathy (Red-Green Color Blindness,
reversible)
Antimycobacterial drugs
 Streptomycin
Mechanism
 Intereferes with 30s component of ribosome
Antibacterial spectrum
 Mycobacterium tuberculosis
 Adverse Effects
 Tinnitus, vertigo, ataxia, nephrotoxicity

Infective Pathologies in ENT and
Antibacterial therapy
Furunculosis
 Bacteriology:
 Staphylococcus aureus (pathogenic strains) [Panton
Valentine Leucocidin(PVL) gene expression
Leucocidal toxin Lysis of phagocytic cells
cutaneous Infection]
 Which Antibiotic?
 Early stage  Oral Antibiotic [penicillinase
resistant penicillin, Cephalosporin, Macrolides
 If abscess drained Topical Antibiotic,
Glycerol+Ichthammol
Ottitis Externa
 Bacteriology:
 Pseudomonas spp (50-65%)
 Other Gram Negative Organism (25-35%)
 Staphylococcus aureus (15-30%)
 Streptococcus spp (9-15%)
 Which Antibiotic?
 Thorough & regular aural toileting
 Topical medication with wick (Glycerol+Ichthammol
90%:10%)
 Systemic antibiotics for complications (perichondritis,
chondritis, cellulitis, Erysipelas)
Skull Base Osteomyelitis
(Malignant Ottitis Externa)
 Bacteriology:
 Pseudomonas aeruginosa
 Staphylococcus aureus
 Staphylococcus epidermidis
 Proteus mirabilis
 Which antibiotic?
 Oral Ciprofloxacin 750mg BD for 6-8 weeks
 Alternatives: Ceftazidime, Cefepime,
Ticaricillin+clavulanate, Aminoglycosides
Perichondritis
 Bacteriology:
 Pseudomonas aeruginosa (69%)
 Polymicrobial (22%)
 Streptococcus spp (22%)
 Staphylococcus aureus (20%)
 Gram Negatives (Proteus, Enterococcus, E.coli)
 Which Antibiotic?
 Intravenous Broad Spectrum Antibiotic in high dose
 If Sub-perichondrial abscess Drainage
Send for Pus C/S
Acute Bullous Myringitis
 Bacteriology:
 Streptococcus pneumoniae
 H. influenzae
 Moraxella catarrhalis
 Which Antibiotic?
 Self limiting disease
 If inner ear involved, Broad-spectrum oral antibiotics
Granular Myringitis
 Bacteriology:
 Pseudomonas aeruginosa
 Staphylococcus aureus
 Corynebacterium
 Proteus mirabilis
 Which Antibiotic?
 Topical Antibiotic with Steroid
Ottitis Media with Effusion
 Bacteriology :
 66% Culture negative
 Streptococcus pneumoniae
 Haemophilus influenzae
 Moraxella catarrhalis
Biofilms demonstrated in most of cases.
 Which Antibiotic?
 Unlikely to be beneficial
 Useful in cases of URTIs or unresolved acute
suppurative ottitis media
Chronic Ottitis Media
 Bacteriology :
 Pseudomonas aeruginosa, Proteus mirabilis,
Staphylococcus aureus
[Pseudomonas aeruginosa less common in squamosal
type]
 Biofilms abundant in COM squamosal type (82% vs
42%)
Chronic Ottitis Media
 Which Antibiotic? (in active Cases)
 Topical Antibiotics more effective than Oral or
Intramuscular
 Topical Aminoglycoside or Quinolones with Steroids
equally effective
 Possible Ototoxicity in using topical aminoglycoside
but only be used in actively discharging ears.
Acute Ottitis Media in Adults
 Bacteriology :
Bacterium Percentage
Haemophilus influenzae 26
Streptococcus pneumoniae 21
Moraxella catarrhalis 3
Staphylococcus aureus 3
Other Bacterium 26
No growth 26
Acute Ottitis Media in Children
Bacterium Percentage
Streptococcus pneumoniae 18-55
Haemophilus influenzae 16-37
Moraxella catarrhalis 11-23
Streptococcus pyogenes 13%
Staphylococcus aureus 5%
• Bacteriology
Acute Ottitis Media
Clinical Recommendations for use of antibiotics in children
Under 6 months of age
Under 2 years of age with recurrent episodes
Failure to improve after 2 days of watchful waiting
More severe symptoms including pyrexia or vomiting or sign of complication
All high risk children including those with Down Syndrome, craniofacial
abnormalities, congenital inner ear abnormalities, immunodeficiencies
Failure to improve after 2-3days treatment should lead to change of
• Which Antibiotic ?
 Amoxicillin is first choice (80mg/kg/day)
 Macrolides (Erythromycin or Clarithromycin) for
penicillin allergic patients
 For Persistent or Resistant episodes, Amoxicillin-
Clavulanate or Cefuroxime orally , or Ceftriaxone
parenterally.
Acute Mastoiditis
 Bacteriology:
 Streptococcus pneumoniae > Streptococcus
pyogenes > Pseudomonas aeruginosa >
Staphylococcus aureus
 Less commonly Haemophilus influenzae, Moraxella
catarrhalis, Proteus mirabilis, Gram Negative
anaerobes
 Which Antibiotics?
 3rd Generation Cephalosporins
 Aminopenicillins + Beta Lactamase Inhibitor
 If Pseudomonas aeruginosa suspected—include
Ciprofloxacin, Piperacillin or Fosfomycin
Tuberculosis of Temporal Bone
 Bacteriology:
 Mycobacterium tuberculosis
 Which Antibiotic?
 Antitubercular therapy [Isoniazide, Rifampicin,
Pyrazinamide, Ethambutol] for 6 months (longer if
disseminated TB or meningitis)
Acute Epiglottitis
 Bacteriology:
 Hemophilus influenzae
 Group A Streptococci
 Pneumococci
 Hemophilus parainfluenzae
 Staphylococcus aureus
 Meningococci
 Which Antibiotic?
 3rd Generation Antibiotics for 5-7 days
 Alternatives: Chloramphenicol and Clindamycin
Acute Pharyngitis
 Bacteriology:
 Group A Streptococci (beta hemolytic)
 Gonococcus
 Diphtheria
 Which Antibiotic?
 Penicillin, Erythromycin
Diphtheria
 Bacteriology:
 Corynebacterium diphtherium
 Corynebacterium ulcerans
 Which Antibiotic?
 High Dose Benzyl Penicillin
 Antitoxin
Diphtheria
 Bacteriology:
 Corynebacterium diphtherium
 Corynebacterium ulcerans
 Which Antibiotic?
 High Dose Benzyl Penicillin
 Antitoxin
Acute Tonsillitis
 Bacteriology:
 Hemolytic Streptococcus
 Staphylococcus aureus
 Pneumococcus
 H. influenzae
 Which Antibiotic?
 Penicillin and Erythromycin
Peritonsillar Abscess
 Bacteriology:
 Streptococcus pyogenes
 Staphylococcus aureus
 Anaerobes
 Which Antibiotic?
 Incision and drainage
 Culture directed antibiotics
 Penicillins first line
Acute Lymphadenopathy with suppuration
 Bacteriology:
 Group A Beta Hemolytic Streptococcus
 Staphylococcus aureus
 Anaerobic Bacteria
 Hemophilus influenzae
 Moraxella catarrhalis
 Which Antibiotic?
 Phlegmon IV Antibiotics
 Abscess  Drainage with IV Antibiotics
Ludwig’s Angina
 Bacteriology:
 Streptococcus Spp
 Gram Negative Rods
 Anaerobes
 Which Antibiotics?
 Secure Airway
 IV Antibiotics
Deep Neck Space Infections
 Bacteriology:
 Peptostreptococcus spp
 Viridans Streptococcus
 Staphylococcus aureus
 Staphylococcus epidermidis
 Klebsiella pneumoniae
 Which Antibiotic?
 Broad spectrum  Amoxicillin/Clavulanate,or 2nd or 3rd
Generation Cephalosporins with metronidazole
 Second line: Clindamycin and Vancomycin
 Selection of antibiotic reviewed a/c to C/S report
Rhinosinusitis
 Bacteriology:
 Mostly viruses
 H. influenzae (44%)
 S.pneumoniae (27%)
 M.catarrhalis (14%)
 S.pyogenes
 S. aureus
 Which Antibiotic?
 Culture sensitivity directed
 Penicillins or Cephalosporins or Macrolides
 Doxycycline has potential antiinflammatory role in
CRS
Lemierre’s Syndrome
 Bacteriology:
 Fusobacterium necrophorum
 Which Antibiotic?
 IV Antibiotics
Actinomycosis
 Bacteriology:
 Actinomyces israelii
 Which Antibiotic?
 Penicillin Up to 6 months
Brucellosis
 Bacteriology :
 Brucella spp
 Which antibiotic?
 Adult: Tetracyclin
 Children: Trimethprim-Sulphamethoxazole
Tularemia
 Bacteriology:
 Francisella tularensis
 Which Antibiotic?
 Streptomycin
 Alternative: Tetracycline, Aminoglycoside,
Chloramphenicol
Antimicrobial Resistance
 Intrinsic Resistance
Traits common to all strains of an organism
(characteristics of cellwall or metabolism) which
render them impervious to effects of antimicrobial
 Acquired Resistance
Mutations
Mobile Genetic Elements
Mechanisms of Resistance
 Alteration or removal of antimicrobial target
eg. mecA gene of MRSA  alteration of PBP2a
 Alteration of Drug leading to loss of activity
eg. Beta lactamase enzymes cleaving
betalactam ring
 Alteration of Drug access to its Target
eg. Efflux pumps as in Gram positive makes
them resistant to tetracyclines
Principles of Antimicrobial Treatment
 Approx. 1/3rd of all Inpatients receiving antimicrobial
treatment
 Adhere to good practice to minimize unnecessary
prescribing
Principles of Antimicrobial Treatment
1. Identification of Source of Infection
2. Appropriate Sampling before treatment
3. Source Control
4. Choice of Initial Antimicrobial Agent
5. Appropriate Dosing
6. Route of Administration
7. De-escalation and oral administration of treatment
8. Completing a course of treatment
References:
1. Scott-Brown’s Otorhinolaryngology Head
& Neck Surgery, 8th Edition
2. First Aid for the USMLE STEP 1, 2019
3. Lippincott Illustrated Reviews,
Pharmacology, 7th Edition
4. Katzung and Trevor’s Pharmacology
Examination and Board Review, 11th
Edition
Thank
You

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Antibacterial therapy in Otorhinolaryngology by Dr. Sudin Kayastha

  • 1. Antibacterial Therapy in Otorhinolaryngology Dr. Sudin Kayastha 1st Year Resident ORL & HNS
  • 3. History  Sir Alexander Fleming, a Scottish researcher, is credited with the discovery of penicillin in 1928.  At the time, Fleming was experimenting with the influenza virus in the Laboratory of the Inoculation Department at St. Mary’s Hospital in London.  Fleming returned from a two-week vacation to find that a mold had developed on an accidentally contaminated staphylococcus culture plate.  Upon examination of the mold, he noticed that the culture prevented the growth of staphylococci.
  • 4.
  • 5.
  • 6. Penicillin G, V  Penicillin G (IV & IM form), Penicillin V (oral)  Mechanism of action  Binds Penicillin binding proteins (transpeptidases)  Block transpeptidase cross-linking of peptidoglycan in cellwall  Inhibits Cellwall Formation  Bactericidal
  • 7. Penicillin G, V  Antibacterial Spectrum  Gram Positive : S. pneumoniae, S. pyogenes, Actinomyces  Gram Negative: Neisseria meningitidis  Spirochetes: Treponema pallidum  Beta Lactamase Sensitive  Adverse Effects  Hypersensitivity reactions, Hemolytic anemia, Drug- induced interstitial nephritis  Resistance  Beta-lactamase cleaves Beta-lactam ring. Mutations in PBPs
  • 8. Penicillinase-sensitive Penicillins  Amoxicillin, Ampicillin, Aminopenicillin  Mechanism of action  Same as Penicillin  Wider Spectrum  Penicillinase sensitive
  • 9. Penicillinase-sensitive Penicillins  Antibacterial Spectrum  Extended spectrum penicillin- H. influenzae, H. pylori, E.coli, Listeria monocytogenes, Proteus mirabilis, Salmonella, Shigella, Enterococci  Adverse Effects  Hypersensitivity reactions, rash, pseudomembranous colitis  Resistance  Penicillinase cleaves Beta-lactam ring.
  • 10. Penicillinase-resistant Penicillins Dicloxacillin, Nafcillin, Oxacillin  Mechanism of action  Same as Penicillin  Narrow Spectrum  Penicillinase resistant  Antibacterial spectrum  Staphylococcus aureus (except MRSA)  Adverse effects  Hypersensitivity reactions, interstitial nephritis  Resistance  MRSA has altered penicillin-binding protein site
  • 11. AntiPseudomonal Penicillins Piperacillin, Ticaricillin  Mechanism of action  Same as Penicillin  Extended Spectrum  Penicillinase sensitive  Antibacterial spectrum  Pseudomonas spp. and Gram Negative rods  Adverse effects  Hypersensitivity reactions
  • 12. Cephalosporins  Mechanism of action  Same as Penicillin  Less Susceptible to Penicillinases  Bactericidal
  • 13. Cephalosporins  Antibacterial Spectrum Cephalospori n Drugs Coverage 1st Generation Cefazolin, Cephalexin Gram + cocci, Proteus mirabilis, E.coli, Klebsiella pneumoniae 2nd Generation Cefaclor, Cefoxitin, Cefuroxime, Cefotetan Gram + cocci, Hemophilus influenzae, Enterobacter aerogenes, Neisseria spp, Serratia spp, Proteus mirabilis, E.coli, Klebsiella pneumoniae 3rd Generation Ceftriaxone, Cefotaxime, Cefpodoxime, Ceftazidime, Ceftolozane Serious Gram Negative Infections resistant to other Beta-lactams Ceftazidime- Pseudomonas 4th Generation Cefepime Gram negative organisms, with increased activity against Pseudomonas and Gram positive organisms 5th Generation Ceftaroline Broad Gram positive and negative organism coverage,
  • 14. Cephalosporins  Adverse Effects  Hypersensitivity reactions  Hemolytic Anemia  Disulfiram like reactions  Resistance  Inactivated by Cephalosporinase (a type of Beta- lactamase)  Structural change in Penicillin Binding Protein (Transpeptidase)
  • 15. Beta Lactamase Inhibitors Clavulanic acid, Avibactam, Sulbactam, Tazobactam  Added to Penicillin antibiotics to protect it from destruction by Beta lactamase
  • 16. Carbapenems Doripenem, Imipenem, Meropenem, Ertapenem  Used in Life-threatening infections  Imipenem- Broad spectrum, Beta-lactamase resistant carbapenem  Always administered with Cilastatin (inhibitor of renal dehydropeptidase I) to decrease inactivation of drug in renal tubules.  Antibacterial spectrum  Wide Spectrum, Gram positive cocci, Gram negative rods, Anaerobes  Adverse effects  GI distress, Rash, Seizure at high plasma level  Resistance  Inactivated by carbapenemases produced by Klebsiella
  • 17. Carbapenems  Adverse effects  GI distress,  Rash,  Seizure at high plasma level  Resistance  Inactivated by carbapenemases produced by Klebsiella pneumoniae, E.coli
  • 18. Vancomycin  Mechanism  Inhibits cellwall peptidoglycan formation  Bacteriocidal against most bacteria, Bacteriostatic against Clostridium difficile.  Not susceptible to Beta-lactamase  Antibacterial spectrum  Gram positive bacteria only – multidrug-resistant organisms including MRSA, Staph. epidermidis, Enterococcus spp, Clostridium difficile
  • 19. Vancomycin  Adverse Effects  Nephrotoxicity, Ototoxicity, Thrombophlebitis, Diffuse flusing- Redman Syndrome, DRESS Syndrome  Resistance  Occurs in bacteria (eg. Enterococcus) via aminoacid modification
  • 20. Polymyxins  Cation Polypeptide that bind to phospholipids on bacterial cell membrane of gram negative bacteria  Disrupts cell membrane integrity leading to leakage of celllular components and cell death  Two forms available: Polymixin B (commonly used), Polymixin E  Antibacterial spectrum  Gram negative bacteria including Pseudomonas aeruginosa, E.coli, Klebsiella pneumonia, Acinetobacter spp., Enterobacter spp.  Adverse Effects  Nephrotoxicity and neurotoxicity
  • 21. Protein Synthesis Inhibitors  Specifically smaller bacterial ribosome (70s, made of 30s and 50s subunits)  All are bacteriostatic except aminoglycosides (bacteriocidal)  30s Inhibitors 50s Inhibitors Aminoglycosides Chloramphenicol Tetracyclines Clindamycin Erythromycin Linezolid
  • 22.
  • 23. Aminoglycosides  Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin  Mechanism  Irreversible inhibition of initiation complex through binding of 30s subunit misreading of mRNA  Also blocks translocation  Requires O2 for uptake so ineffective against anaerobes  Bactericidal  Antibacterial spectrum  Aerobic gram-negative bacilli, including those that may be multidrug resistant, such as Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterobacter spp.
  • 24. Aminoglycosides  Adverse Effects  Nephrotoxicity,  Ototoxicity,  Neuromuscular Blockade (absolute contraindication in myasthenia gravis)  Teratogenicity  Resistance  Bacterial transferase enzymes inactivate the drug by acetylation, phosphorylation or adenylation
  • 25. Tetracyclines  Tetracycline, Doxycycline, Minocycline  Mechanism  Binds to 30s and prevent attachment of aminoacyl tRNA  Limited CNS penetration  Fecally eliminated so can be used in renal failure patients  Bacteriostatic  Not to be taken with milk, antacids, or iron containing preparations
  • 26. Tetracyclines  Antibacterial spectrum  Borrelia burgdorferi, Mycoplasma pneumoniae  Drug ability to accumulate intracellularly so effective against Rickettsia and Chlamydia  Adverse Effects  GI distress, discolouration of teeth, inhibition of bone growth in children, photosensitivity  Resistance  Uptake or efflux out of bacterial cells by plasmid encoded transport pump
  • 27. Chloramphenicol  Mechanism  Blocks peptidyltransferase at 50s ribosomal subunit  Bacteriostatic  Antibacterial spectrum  Hemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae, Rickettsia spp.
  • 28. Chloramphenicol  Adverse Effects  Anemia (dose dependent)  Aplastic anemia (dose independent)  Gray Baby Syndrome (in premature infants liver lacks UDP-glucuronyl transferase)  Resistance  Plasmid encoded acetyltransferase inactivates the drug
  • 29. Clindamycin  Mechanism  Blocks peptidyl transfer (translocation) at 50s ribosomal subunit  Bacteriostatic  Antibacterial spectrum  Anaerobes like Bacteoides spp., Clostridium spp.,  Group A Streptococcus  Adverse Effects  Fever, diarrhoea  Pseudomembranous colitis (C. difficile overgrowth)
  • 30. Oxazolidinones (Linezolid)  Mechanism  Inhibit protein synthesis by binding to 50s subunit and preventing formation of initiation complex  Antibacterial spectrum  Gram positive species including MRSA and VRE
  • 31. Oxazolidinones (Linezolid)  Adverse Effects  Bone marrow suppression (especially thrombocytopenia)  Peripheral neuropathy  Serotonin Syndrome (due to partial MAO inhibition)  Resistance  Point mutation of ribosomal RNA
  • 32. Macrolides  Azithromycin, Clarithromycin, Erythromycin  Mechanism  Inhibit protein synthesis by blocking translocation, binds to 23s rRNA of 50s ribosomal subunit.  Bacteriostatic  Antibacterial spectrum  Mycoplasma, Chlamydia, Legionella,  Gram positive COCCI  Bordetella pertusis
  • 33. Macrolides  Adverse Effects  GI disturbances  Arrhythmia (d/t prolonged QT interval)  Acute Cholestatic Hepatitis  Rash  Eosinophilia  Clarithromycin and Erythromycin inhibit cytochrome P450  Resistance  Methylation of 23s rRNA binding site prevents binding of drug
  • 34. Sulfonamides  Sulfamethoxazole, Sulfadiazine, Sulfisoxazole  Mechanism  Inhibit dihydropteroate synthase thus inhibiting folate synthesis.  Bacteriostatic (bacteriocidal when combined with trimethoprim)  Antibacterial spectrum  Gram positive, Gram negative, Nocardia
  • 35. Sulfonamides  Adverse Effects  Hypersensitivity reactions  Hemolysis if G6PD deficiency  Nephrotoxicity (tubulointerstitial nephritis)  Photosensitivity  Stevens-Johnson Syndrome  Kernicterus in infants  Resistance  Altered Enzymes
  • 36. Dapsone  Mechanism  Similar to sulfonamides  Antibacterial spectrum  Mycobacterium leprae  Pneumocystis jirovecii  Adverse Effects  Hemolysis if G6PD deficiency  Methemoglobinemia  Agranulocytosis
  • 37. Trimethoprim  Mechanism  Inhibit bacterial dihydrofolate reductase thus inhibiting folate synthesis.  Bacteriostatic  Antibacterial spectrum  Used in combination with Sulfonamides (sulphamethoxazole : TMP-SMX)  Shigella, Salmonella, Pneumocystis jirovecii
  • 38. Trimethoprim  Adverse Effects  Hyperkalemia,  Megaloblastic anemia  Leukopenia  Granulocytopenia
  • 39. Fluoroquinolones  Ciprofloxacin, Ofloxacin, Norfloxacin, Levofloxacin, Moxifloxacin  Mechanism  Inhibits prokaryotic enzymes Topoisomerase II (DNA gyrase) and Topoisomerase IV  Bactericidal  Antibacterial spectrum  Enterobacteriaceae, Pseudomonas aeruginosa, Hemophilus influenzae, Neisseria spp, Chlamydia spp, Legionella spp.  Streptococcus spp, Methicillin susceptible Staphylococcus, Mycobacterium spp.
  • 40. Fluoroquinolones  Adverse Effects  GI upsets  Skin rashes  Headaches  Dizziness  Legcramps and myalgia  May cause Tendinitis and tendon rupture in >60 yrs old & patients taking prednisolone  Inhibits Cytochrome P450  Resistance  Chromosomal encoded mutation in DNA gyrase, plasmid mediated resistance, efflux pumps
  • 41. Metronidazole  Mechanism  Forms toxic free radical metabolites in the bacterial cell that damage DNA  Bactericidal  Antibacterial spectrum  Anaerobes (Bacteroides, C.difficile),  Protozoans  Not used in Pneumonia avidly binds to and is inactivated by surfactant
  • 42. Metronidazole  Adverse Effects  Headache  Metallic taste  Nausea  Disulfiram like reaction (severe flushing, tachycardia, hypotension) with alcohol
  • 43. Antimycobacterial drugs  Rifampicin  Mechanism  Inhibit DNA dependent RNA polymerase  Antibacterial spectrum  Mycobacterium tuberculosis  Mycobacterium leprae  Neisseria meningitidis  Hemophilus influenzae
  • 44. Antimycobacterial drugs Rifampicin  Adverse Effects  Hepatotoxicity,  Orange coloured urine  Increases Cytochrome P450  drug interaction  Resistance  Mutation reduce drug binding to RNA Polymerase.  Monotherapy rapidly leads to resistance
  • 45. Antimycobacterial drugs  Isoniazid  Mechanism  Inhibits synthesis of mycolic acids  Bacterial Catalase-peroxidase (encoded by KatG) needed to convert INH to active metabolite  Antibacterial spectrum  Mycobacterium tuberculosis
  • 46. Antimycobacterial drugs  Isoniazid  Adverse Effects  Hepatotoxicity,  Vitamin B6 Deficiency( peripheral neuropathy)  Drug induced SLE  Metabolic Acidosis  Seizures (in high doses refractory to benzodiazepines)  Resistance  Mutation leading to underexpression of KatG
  • 47. Antimycobacterial drugs  Pyrazinamide  Mechanism  Mechanism uncertain  Converted to active form pyrazinoic acid.  Works in acidic pH (host phagolysosomes)  Antibacterial spectrum  Mycobacterium tuberculosis  Adverse Effects  Hyperuricemia, Hepatotoxicity
  • 48. Antimycobacterial drugs  Ethambutol  Mechanism  Inhibit carbohydrate polymerization of mycobacterium cellwall by blocking arabinosyl transferase  Antibacterial spectrum  Mycobacterium tuberculosis  Adverse Effects  Optic neuropathy (Red-Green Color Blindness, reversible)
  • 49. Antimycobacterial drugs  Streptomycin Mechanism  Intereferes with 30s component of ribosome Antibacterial spectrum  Mycobacterium tuberculosis  Adverse Effects  Tinnitus, vertigo, ataxia, nephrotoxicity 
  • 50.
  • 51. Infective Pathologies in ENT and Antibacterial therapy
  • 52. Furunculosis  Bacteriology:  Staphylococcus aureus (pathogenic strains) [Panton Valentine Leucocidin(PVL) gene expression Leucocidal toxin Lysis of phagocytic cells cutaneous Infection]  Which Antibiotic?  Early stage  Oral Antibiotic [penicillinase resistant penicillin, Cephalosporin, Macrolides  If abscess drained Topical Antibiotic, Glycerol+Ichthammol
  • 53. Ottitis Externa  Bacteriology:  Pseudomonas spp (50-65%)  Other Gram Negative Organism (25-35%)  Staphylococcus aureus (15-30%)  Streptococcus spp (9-15%)  Which Antibiotic?  Thorough & regular aural toileting  Topical medication with wick (Glycerol+Ichthammol 90%:10%)  Systemic antibiotics for complications (perichondritis, chondritis, cellulitis, Erysipelas)
  • 54. Skull Base Osteomyelitis (Malignant Ottitis Externa)  Bacteriology:  Pseudomonas aeruginosa  Staphylococcus aureus  Staphylococcus epidermidis  Proteus mirabilis  Which antibiotic?  Oral Ciprofloxacin 750mg BD for 6-8 weeks  Alternatives: Ceftazidime, Cefepime, Ticaricillin+clavulanate, Aminoglycosides
  • 55. Perichondritis  Bacteriology:  Pseudomonas aeruginosa (69%)  Polymicrobial (22%)  Streptococcus spp (22%)  Staphylococcus aureus (20%)  Gram Negatives (Proteus, Enterococcus, E.coli)  Which Antibiotic?  Intravenous Broad Spectrum Antibiotic in high dose  If Sub-perichondrial abscess Drainage Send for Pus C/S
  • 56. Acute Bullous Myringitis  Bacteriology:  Streptococcus pneumoniae  H. influenzae  Moraxella catarrhalis  Which Antibiotic?  Self limiting disease  If inner ear involved, Broad-spectrum oral antibiotics
  • 57. Granular Myringitis  Bacteriology:  Pseudomonas aeruginosa  Staphylococcus aureus  Corynebacterium  Proteus mirabilis  Which Antibiotic?  Topical Antibiotic with Steroid
  • 58. Ottitis Media with Effusion  Bacteriology :  66% Culture negative  Streptococcus pneumoniae  Haemophilus influenzae  Moraxella catarrhalis Biofilms demonstrated in most of cases.  Which Antibiotic?  Unlikely to be beneficial  Useful in cases of URTIs or unresolved acute suppurative ottitis media
  • 59. Chronic Ottitis Media  Bacteriology :  Pseudomonas aeruginosa, Proteus mirabilis, Staphylococcus aureus [Pseudomonas aeruginosa less common in squamosal type]  Biofilms abundant in COM squamosal type (82% vs 42%)
  • 60. Chronic Ottitis Media  Which Antibiotic? (in active Cases)  Topical Antibiotics more effective than Oral or Intramuscular  Topical Aminoglycoside or Quinolones with Steroids equally effective  Possible Ototoxicity in using topical aminoglycoside but only be used in actively discharging ears.
  • 61. Acute Ottitis Media in Adults  Bacteriology : Bacterium Percentage Haemophilus influenzae 26 Streptococcus pneumoniae 21 Moraxella catarrhalis 3 Staphylococcus aureus 3 Other Bacterium 26 No growth 26
  • 62. Acute Ottitis Media in Children Bacterium Percentage Streptococcus pneumoniae 18-55 Haemophilus influenzae 16-37 Moraxella catarrhalis 11-23 Streptococcus pyogenes 13% Staphylococcus aureus 5% • Bacteriology
  • 63. Acute Ottitis Media Clinical Recommendations for use of antibiotics in children Under 6 months of age Under 2 years of age with recurrent episodes Failure to improve after 2 days of watchful waiting More severe symptoms including pyrexia or vomiting or sign of complication All high risk children including those with Down Syndrome, craniofacial abnormalities, congenital inner ear abnormalities, immunodeficiencies Failure to improve after 2-3days treatment should lead to change of • Which Antibiotic ?  Amoxicillin is first choice (80mg/kg/day)  Macrolides (Erythromycin or Clarithromycin) for penicillin allergic patients  For Persistent or Resistant episodes, Amoxicillin- Clavulanate or Cefuroxime orally , or Ceftriaxone parenterally.
  • 64. Acute Mastoiditis  Bacteriology:  Streptococcus pneumoniae > Streptococcus pyogenes > Pseudomonas aeruginosa > Staphylococcus aureus  Less commonly Haemophilus influenzae, Moraxella catarrhalis, Proteus mirabilis, Gram Negative anaerobes  Which Antibiotics?  3rd Generation Cephalosporins  Aminopenicillins + Beta Lactamase Inhibitor  If Pseudomonas aeruginosa suspected—include Ciprofloxacin, Piperacillin or Fosfomycin
  • 65. Tuberculosis of Temporal Bone  Bacteriology:  Mycobacterium tuberculosis  Which Antibiotic?  Antitubercular therapy [Isoniazide, Rifampicin, Pyrazinamide, Ethambutol] for 6 months (longer if disseminated TB or meningitis)
  • 66. Acute Epiglottitis  Bacteriology:  Hemophilus influenzae  Group A Streptococci  Pneumococci  Hemophilus parainfluenzae  Staphylococcus aureus  Meningococci  Which Antibiotic?  3rd Generation Antibiotics for 5-7 days  Alternatives: Chloramphenicol and Clindamycin
  • 67. Acute Pharyngitis  Bacteriology:  Group A Streptococci (beta hemolytic)  Gonococcus  Diphtheria  Which Antibiotic?  Penicillin, Erythromycin
  • 68. Diphtheria  Bacteriology:  Corynebacterium diphtherium  Corynebacterium ulcerans  Which Antibiotic?  High Dose Benzyl Penicillin  Antitoxin
  • 69. Diphtheria  Bacteriology:  Corynebacterium diphtherium  Corynebacterium ulcerans  Which Antibiotic?  High Dose Benzyl Penicillin  Antitoxin
  • 70. Acute Tonsillitis  Bacteriology:  Hemolytic Streptococcus  Staphylococcus aureus  Pneumococcus  H. influenzae  Which Antibiotic?  Penicillin and Erythromycin
  • 71. Peritonsillar Abscess  Bacteriology:  Streptococcus pyogenes  Staphylococcus aureus  Anaerobes  Which Antibiotic?  Incision and drainage  Culture directed antibiotics  Penicillins first line
  • 72. Acute Lymphadenopathy with suppuration  Bacteriology:  Group A Beta Hemolytic Streptococcus  Staphylococcus aureus  Anaerobic Bacteria  Hemophilus influenzae  Moraxella catarrhalis  Which Antibiotic?  Phlegmon IV Antibiotics  Abscess  Drainage with IV Antibiotics
  • 73. Ludwig’s Angina  Bacteriology:  Streptococcus Spp  Gram Negative Rods  Anaerobes  Which Antibiotics?  Secure Airway  IV Antibiotics
  • 74. Deep Neck Space Infections  Bacteriology:  Peptostreptococcus spp  Viridans Streptococcus  Staphylococcus aureus  Staphylococcus epidermidis  Klebsiella pneumoniae  Which Antibiotic?  Broad spectrum  Amoxicillin/Clavulanate,or 2nd or 3rd Generation Cephalosporins with metronidazole  Second line: Clindamycin and Vancomycin  Selection of antibiotic reviewed a/c to C/S report
  • 75. Rhinosinusitis  Bacteriology:  Mostly viruses  H. influenzae (44%)  S.pneumoniae (27%)  M.catarrhalis (14%)  S.pyogenes  S. aureus  Which Antibiotic?  Culture sensitivity directed  Penicillins or Cephalosporins or Macrolides  Doxycycline has potential antiinflammatory role in CRS
  • 76. Lemierre’s Syndrome  Bacteriology:  Fusobacterium necrophorum  Which Antibiotic?  IV Antibiotics
  • 77. Actinomycosis  Bacteriology:  Actinomyces israelii  Which Antibiotic?  Penicillin Up to 6 months
  • 78. Brucellosis  Bacteriology :  Brucella spp  Which antibiotic?  Adult: Tetracyclin  Children: Trimethprim-Sulphamethoxazole
  • 79. Tularemia  Bacteriology:  Francisella tularensis  Which Antibiotic?  Streptomycin  Alternative: Tetracycline, Aminoglycoside, Chloramphenicol
  • 80. Antimicrobial Resistance  Intrinsic Resistance Traits common to all strains of an organism (characteristics of cellwall or metabolism) which render them impervious to effects of antimicrobial  Acquired Resistance Mutations Mobile Genetic Elements
  • 81. Mechanisms of Resistance  Alteration or removal of antimicrobial target eg. mecA gene of MRSA  alteration of PBP2a  Alteration of Drug leading to loss of activity eg. Beta lactamase enzymes cleaving betalactam ring  Alteration of Drug access to its Target eg. Efflux pumps as in Gram positive makes them resistant to tetracyclines
  • 82. Principles of Antimicrobial Treatment  Approx. 1/3rd of all Inpatients receiving antimicrobial treatment  Adhere to good practice to minimize unnecessary prescribing
  • 83. Principles of Antimicrobial Treatment 1. Identification of Source of Infection 2. Appropriate Sampling before treatment 3. Source Control 4. Choice of Initial Antimicrobial Agent 5. Appropriate Dosing 6. Route of Administration 7. De-escalation and oral administration of treatment 8. Completing a course of treatment
  • 84. References: 1. Scott-Brown’s Otorhinolaryngology Head & Neck Surgery, 8th Edition 2. First Aid for the USMLE STEP 1, 2019 3. Lippincott Illustrated Reviews, Pharmacology, 7th Edition 4. Katzung and Trevor’s Pharmacology Examination and Board Review, 11th Edition