PHARMACOTHERAPY OF

COMMON INFECTIONS OF
NOSE, PARANASAL SINUSES,
EAR AND ORAL CAVITY
Dr. Ralph Cylon M. Jacinto
Outline
 Common Infections of the:
1. Nose and paranasal sinuses
2. Oral cavity and pharynx
3. Ear
Nose and paranasal sinuses
 Purulent inflammation of the hair follicles
 Erysipelas
 Acute rhinitis/rhinosinusitis
 Chronic rhinitis
Folliculitis/Furunculosis
 Due to staphylococcal
infection
 Impt. goal is to
prevent CNS spread
 Agents:
 Anti-staph. antibiotics
 Analgesics
 NSAIDs
Antistaphylococcal penicillins
 Methicillin, nafcillin, oxacillin, dicloxacillin
 Resistant to β-lactamases (Penicillinase)
 Drug of choice:
 Penicillinase-producing staphylococci (Methicillin-
sensitive Staphylococcus aureus MSSA)
 No activity against gram (-) infections
 Methicillin – causes interstitial nephritis; withdrawn
from market
 Dicloxacillin/cloxacillin – acid-stable
Extended-spectrum penicillins
 Ampicillin, amoxicillin
 Activity similar to Pen G but more effective against
gram (-) bacilli

 High incidence to develop plasmid-mediated

penicillinase  resistant
Anti-pseudomonal penicillins
 Piperacillin, mezlocillin; ticarcillin, carbenicillin
 Activity against Pseudomonas aeruginosa
 Piperacillin– most potent; additional effect on
Bacteroides and E. faecalis.
β-lactamase inhibitors
 Clavulanic acid, sulbactam, tazobactam
 “Suicide inhibitors”
 Act by protecting the penicillin from hydrolysis 
extending the antimicrobial spectra
 Added to extended-spectrum penicillins
Resistance to penicillins
 Natural resistance
 Lack of cell wall
 Cell walls are impermeable to the drug

 Acquired resistance
 Plasmid-mediatedβ-lactamases
 Altered PBP  MRSA, Methicillin resistant S.A.
Pharmacokinetics
 Administration: Depends on acid-stability
 Depot forms (IM): Procaine pen G & benzathine pen G
 Absorption: Food decreases absorption
 Distribution: Low concentration on bones and BBB;
 Can cross the placenta
 Studies show no teratogenic effects on the fetus (Cat. B)
Pharmacokinetics
 Metabolism: Usually insignificant
 Excretion: Through organic acid secretory system
(kidneys)
 Dose adjuments in patients with renal failure
 Exceptions: Nafcillin, oxacillin  excreted through the
liver
 Probenecid: inhibits excretion of penicillins by
competing for the transporter   blood levels
 Also excreted in breast milk
Adverse Effects
 With wide therapeutic index  no need for blood level
monitoring
 Adverse reactions may occur:
 Hypersensitivity (5%)
 Diarrhea – due to disruption of intestinal normal flora
 Pseudomembranous colitis – due to Clostridium difficile
 Nephritis – esp. methicillin
 Neurotoxicity – irritant to neuronal tissues; can inhibit GABA
on its receptors
 Hematologic toxicity – decreased coagulation and
cytopenias
Tetracyclines
 MOA: binds reversibly to 30s subunit
 (-) binding of tRNA  (-) protein synthesis
 Entry is via passive diffusion
 Also
by ATP-dependent transport protein in inner
membrane
Antibacterial spectrum
 Bacteriostatic
 Broad spectrum
Resistance
  Efflux pumps  prevents accumulation inside the
cell
 Other mechanisms:
 Enzymatic inactivation
 Altered 30s subunit

 Resistance to 1 tetracycline does not confer

universal resistance to all tetracyclines.
Different agents
 Chlortetracycline - prototype
 Tetracycline
 Demeclocycline
 Doxycycline
 treatment of Chlamydia infections
 Minocycline
 Tigecycline
Pharmacokinetics
 Absorption: Good oral bioavailability
 Dairyproducts, antacids:  absorption (chelation)
 Doxy and mino: IV and oral

 Distribution: well-distributed
 Bindto tissues with  Ca2+
 Can cross the placenta

 Doxy and mino: penetrate BBB

Pharmacokinetics
 Elimination:
 Tetracycline:eliminated unchanged in the urine
 Minocycline: hepatic metabolism

 Doxycycline: biliary excretion

Adverse Effects
 Gastric irritation: minimized by giving with food
except tetracycline
 Effects on calcified tissues: limited use in pediatrics
 Not used in pregnants and children < 8 y/o
 Hepatotoxicity
 Phototoxicity
 Vestibular dysfunction: dizziness, vertigo
 Pseudotumor cerebri:  intracranial pressure
 Discontiue drug
Macrolides
 MOA: Binds to 50s subunit  (-) translocation
 May also inhibit transpeptidation
 Drug of choice and alternative for penicillins  β-
lactam antibiotic hypersensitivity
 Bacteriostatic
 Bactericidal in higher doses
Antibacterial spectrum
 Bacteriostatic
 Similar spectrum to penicillins
`
Erythromycin
 Prototype
 Similar in activity as penicillin G
 Alternative for Pen G
Clarithromycin
 Additional activity:
 H. influenzae
 Better activity against:
 Chlamydia, Legionella, Moraxella, Ureaplasma, H. pylori
Azithromycin
 Less effective:
 Streptococcus, Staphylococcus
 Better activity:
 H. influenzae, Moraxella, Chlamydia
 Preferred treatment: MAC
Telithromycin
 Ketolide  derivative of macrolides
 Similar activity as azithromycin
 Structure neutralizes resistance mechanisms
Resistance
 Inability to takeup antibiotic
  Efflux pumps
  Affinity of 50s subunit
 (+) Plasmid associated erythromycin esterase
Pharmacokinetics
 Absorption: Good oral absorption
 Erythro:
unstable in acidic
 Food decreases abs. except Clarithro ()

 Distribution: Well distributed

 Erythro:  CSF
 Azithro: long half life
Pharmacokinetics
 Elimination: via hepatic metabolism
 Erythro and telithro: Inhibits CYP450
 Excretion:
 Erythro and azithro: Biliary excretion as active drugs
 Clarithro: via kidneys and liver
Adverse Effects
 Gastric upset
 Increasedmotility  Erythro used in post-op ileus and
gastroparesis
 Cholestatic jaundice: if estolate form of Erythro
 Ototoxicity: transient deafness
 Azithro: irreversible sensorineural hearing loss
 QT prolongation
 Interaction with digoxin
 flora that inactivates digoxin
 Contraindications: Hepatic dysfunction
Clindamycin
 Similar mechanism as Macrolides
 Activity: gram (+), MRSA and anaerobes
 No activity: gram (-) and C. difficile
 Cross-resistance with Macrolides
 ```````````
Pharmacokinetics
 Absorption: IV and oral
 Oral: causes GI discomfort
 Distribution: Well-distributed but does not cross BBB
 Elimination: Undergoes oxidative metabolism
 Excretion:
Biliary
 Accumulation reported in renal or hepatic failure

 AE: Diarrhea (Pseudomembranous colitis)

 Give Metronidazole or Vancomycin
Fidaxomicin
 Macrocyclic antibiotic  similar to macrolides
 MOA: Acts on sigma subunit of RNA polymerase 
disrupting transcription and protein synthesis
 Narrow spectrum: gram (+) aerobes and anaerobes
 Bactericidal activity for C. difficile
 Minimally absorption  ideal for GI infections
 AE: N&V, abd. pain, hypersensitivity
Erysipelas
 Caused by β-hemolytic
group A streptococci
 Others: Staphylococcus
aureus, Klebsiella
pneumoniae
 Agents:
 Penicillins
 Macrolides/Tetracyclin
es/Fluoroquinolones –
if allergic to penicillins
Fluoroquinolones
 Nalidixic acid  predecessor
 Mechanism: Inhibition of DNA gyrase
(topoisomerase II) and Topoisomerase IV
 (-) DNA gyrase: relaxation of supercoiled DNA  DNA
breaks
 (-) Topo IV: interferes in chromosomal stabilization

 Considered alternatives for β-lactams

Antibacterial Spectrum
 Bactericidal
 Effective against gram (-), atypical, gram (+) and
some mycobacteria
 Not used in SA, gonococcal or enterococcal
infections

 Levofloxacin, moxifloxacin: respiratory FQ

``````
Classification
 1st generation: Nalidixic acid (narrow spectrum)
 2nd generation: Ciprofloxacin, norfloxacin
 3rd generation: Levofloxacin
 4th generation: Moxifloxacin
Norfloxacin
 Poor oral bioavailability
 Effective against nonsystemic infections:
 UTI

 Prostatitis

 Diarrhea
Ciprofloxacin
 Effective against gram (-) infections
 Best activity against P. aeruginosa  used in cystic
fibrosis
 Typhoid fever and traveler’s diarrhea

 2nd line of treatment for PTB

Levofloxacin
 L-isomer of ofloxacin
 Broad spectrum of activity
 Excellent activity against S. pneumoniae
 100% bioavailable with once a day dosing
Moxifloxacin
 Enhanced gram (+) activity and anaerobes
 Poor activity against P. aeruginosa
 Does not concentrate in urine
Resistance
 Altered target: chromosomal mutations
 Altered DNA gyrase or Topo IV
 Decreased accumulation
 Reduced porin channels
 Increased efflux pumps
Pharmacokinetics
 Absorption: good oral bioavailability
 Poororal abs: Norfloxacin
 IV/Ophthalmic: Cipro, Levo, Moxi

 Reduced absorption: Antacids (Al, Mg); Fe; Zn; Ca

 Distribution: Well-distributed
 Ofloxacin: good CSF penetration
 Elimination: through kidneys
 Moxifloxacin: via hepatic
Adverse Effects
 Nausea, vomiting, diarrhea
 Neurologic  headaches, dizziness, seizures
 Phototoxicity
 Articular cartilage erosion (arthropathy)
 Avoided in pregnant, lactating and < 18 y/o
 Tendinitis and tendon rupture

 Prolong QT interval
 Ciprofloxacin  inc. theophylline levels
Acute rhinitis/rhinosinusitis
 Caused by rhinovirus, coronavirus, H. influenzae, S.
pneumoniae
 Others: influenza virus, adenovirus, M. catarrhalis,
S. aureus
 Mainly supportive treatment
 Agents:
 Decongestants

 Mucolytics

*Antibacterials – if bacterial in origin

Acute rhinitis/rhinosinusitis
α-Adrenergic Agonists
☐ Acts by constricting dilated arterioles in the nasal
mucosa  reduced airway resistance
☐ Includes: Phenylephrine, pseudoephedrine and
Oxymetazoline (long-acting)
☐ Adverse effect:
☐ Rebound rhinitis (Rhinitis medicamentosa) – occurs if
used for more than 7 days
N-Acetylcysteine
☐ Cysteine derivative
☐ “Mucolytic”  Acts by reducing disulfide bridges that
bind glycoproteins such as albumin and IgA
☐ Only US-FDA approved mucolytic agent
☐ Other examples: Carbocysteine, methylcysteine,
erdosteine, bromhexine and ambroxol

☐ Otheruses: Antidote for paracetamol overdose;

Nephroprotectant after giving contrast dye
Chronic rhinitis/rhinosinusitis
 Inflammation > 12 weeks
 Infectious causes: M. tuberculosis, fungal infections,
syphilis
 Treatment would depend on the causative agent.
 Other agents:
 Decongestants – for not more than 5-7days
 Mucolytics
Chronic rhinitis/rhinosinusitis
Oral cavity and pharynx
 Infections of the oral mucosa
 Acute tonsillitis/tonsillopharyngitis
 Scarlet fever
 Diphtheria
 Acute sialadenitis
Infections of the oral mucosa
 Herpetic gingivostomatitis – due to HSV
 Severe forms – topical acyclovir
 Oral candidiasis (thrush) – if immunocompromised
 Topical antifungals
Acyclovir
 Acyclic guanosine derivative against HSV1,
HSV2, & VZV
☐ Converted to monophosphate derivative by
virus-specified thymidine kinase
☐ Selectiveactivation of acyclovir
☐ Active metabolites accumulates only in infected
cells
☐ Converted to di and triphosphate compounds
by the host’s cellular enzymes
MECHANISM OF ACTION:
☐ Acyclovir triphosphate inhibits viral DNA
synthesis
 Acts as a chain terminator because it lacks 3’
hydroxyl group
 Competitive inhibition of deoxyGTP for viral
DNA polymerase = binds to DNA template as
irreversible complex
Properties
 Half-life: 3 hours (normal renal function)
20 hours (anuria)
 Readily cleared by dialysis but not by peritoneal
dialysis
 IV- treatment of choice for herpes simplex
 Oral – herpes labialis
 Topical – high concentration in herpetic lesions

 SIDE EFFECTS: ORAL – nausea, diarrhea, rash,

headache,renal insufficiency, neurotoxicity
Amphotericin B
 Obtained from Streptomyces Nodosus
 Amphoteric in nature
Properties
 Poorly absorbed orally
 Insoluble in water so colloidal suspension
prepared with sodium deoxycholate(1:1
complex)
 90% bound to plasma proteins

 Metabolized in liver slowly excreted in urine

 T ½ = 15 days
• Adverse events:
– Acute reaction:
– Chills, fever, headache, pain all over,
nausea, vomiting, dyspnoea lasting 2-5 hrs
because of release of IL & TNF
– can be treated with hydrocortisone
0.6mg/kg
– Long term toxicity:
– Nephrotoxicity: Azotemia, Hypokalemia,
acidosis, ↓ GFR
– anemia
– CNS toxicity : intrathecal administration,
headache, vomiting, nerve palsies
– Hepatotoxicity rarely
Nystatin

 Obtained from S. noursei

 Similar to AMB in antifungal properties, high systemic toxicity
so used locally only
 Poorly absorbed from mucus membrane
 Available as ointment ,cream , powder, tablet
 Uses:
 intestinal moniliasis
 vaginitis
 Prevention of oral candidiasis
 Can be used in oral, cutaneous, conjunctival candidiasis
 Adverse events:
 Gastointestinal disturbances with oral tablets
Acute tonsillitis/tonsillopharyngitis
 Caused by β-hemolytic
group A streptococci
 Others: Staphylococcus
aureus, Klebsiella
pneumoniae
 Agents:
 Penicillins
 Macrolides/Tetracyclines
/Fluoroquinolones – if
allergic to penicillins
 Chronic - tonsillectomy
Scarlet fever
 Caused by β-hemolytic
group A streptococci
 Agents:
 Penicillins

 Macrolides/Tetracyclin
es/Fluoroquinolones –
if allergic to penicillins
Diphtheria
 Caused by Corynebacterium diphtheriae
 Can be prevented by active immunization
 Agents:
 Penicillins
and alternatives
 Diphtheria antitoxin
Acute sialadenitis
 Viral cause: Mumps
 Tx: Supportive
 Bacterial causes: S.
aureus, H. influenzae,
streptococci
 Tx:antibiotics,
analgesics
Ear
 Infections of the external ear
 Otitis media
Infections of the external ear
 Can be cellulitis, otitis
externa
 Management depends
on the underlying cause:
 Bacterial
 Viral

 Fungal

 Must be cleansed first

before instilling the
meds; Aural hygiene
Otitis media
 Common in children
 Caused by:
 2/3: S. pneumoniae, H.
influenzae, M. catarrhalis
 1/3: Viruses

 Agents:
 Analgesics
 Decongestants

 Antibacterials/antivirals
 Generic Name Mechanism of Indication Side Effect Contrainidcation
Action / Special
precaution
Ciprofloxacin quinolone For Acute otitis Ear pain, ear Patients with
antimicrobial externa, chronic pruritus, and hypersensitivity
that works suppurative otitis headache to ciprofloxacin,
against Staph. media Pregnant
Aureus and mothers; Nursing
Pseudomonas mothers
aeruginosa

Ciprofloxacin + Quinolone For acute otitis Ear pain, ear Patients with
Dexamethasone antimicrobial externa, post pruritus, hypersensitivity
with steroid operative headache, and to ciprofloxacin,
component that inflammation, fungal infection Pregnant
works against steroid mothers; Nursing
Staph. Aureus responsive mothers
and dermatoses of
Pseudomanas the external ear,
aeruginosa; and chronic
suppurative otitis
media
Generic Name Mechanism of Indication Side Effect Contrainidcation
Action / Special
precaution
Ofloxacin carboxyquinolone For Acute otitis Ear pain, ear Patients with
antimicrobial that externa, Chronic pruritus, and hypersensitivity
works against suppurative otitis headache to ciprofloxacin,
aerobes such as media Pregnant
Staph. Aureus mothers; Nursing
and Pseudomonas mothers
aeruginosa

Polymyxin + An antimicrobial For acute otitis Ear pain, ear Patients with
Neomycin + otic drop with externa, chronic pruritus, tuberculous
Dexamethasone steroid component suppurative otitis headache, and lesions of the
media, and fungal infection ear, chicken pox,
allergic herpes simplex;
inflammatory Pregnant
conditions of the mothers; Nursing
external mothers
auditory canal
 Generic Name Mechanism of Indication Side Effect Contrainidcation
Action / Special
precaution

Polymyxin + quinolone For Acute otitis Ear pain, ear Patients with
Neomycin + antimicrobial externa and pruritus, and hypersensitivity
Fluocinolone that works Chronic headache to ciprofloxacin,
against Staph. suppurative otitis Pregnant
Aureus and media mothers; Nursing
Pseudomonas mothers
aeruginosa

Clotrimazole Antifungal with For Otomycosis Ear pain, ear Patients with
that is effective pruritus hypersensitivity
against Candida to clotrimazole,
sp. and Pregnant
Aspergillus sp. mothers; Nursing
mothers