URT 2012 Handout

24/03/1436
Antimicrobial
Regimen
Selection
MIU, Infectious diseases, CDC
Prior to the discovery of penicillin

in 1927 by Sir Alexander Fleming;
Patients with infected wounds
often had to have a wounded limb
amputated.
Most patients faced death from
their infection.
Today, despite the presence of a

large number of antibiotic classes,
mortality due to infectious
diseases is increasing ????
Microbial resistance
Solution ????????
Appropriate antibiotic
regimen selection
Role of the clinical pharmacist

Terminologies
Infections are either
Exogenous.
i. Endogenous Infection:
Endogenous
or
Alteration of normal flora OR disruption of host

defense.
Do we have bacteria in our bodies? Colonizing Bacteria
ii. Exogenous Infections:

Infections acquired from an external source.
Colonization versus Infection.
Virulence versus Resistance.
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Skin
Staphylococcus
epidermidis/ aureus
Micrococci, Diphteroids.
Mouth
Oral anaerobes
Vridans streptococci
URT
Maroxella catarrhalis
Streptococcus pneumonia
Heamophilus influenza
LRT
Sterile
Other sterile anatomic

MIU,sites:
Infectious diseases, CDC
CSF, blood & urine.
Guiding Principles When

Prescribing Antimicrobials
Make Correct Diagnosis
Do No Harm
What is the Appropriate Decision

if a Culture is Required?
Infection suspected
Cultures taken
Empiric
Antibiotic started
Definitive
Culture results reviewed
Antibiotic revised if necessary
24/03/1436
Empiric
vs.
Infection not well defined
Definitive
Infection well defined
Narrow spectrum
One, seldom two drugs
Less adverse reactions
Less expensive
(best guess)
Broad spectrum
Multiple drugs
More adverse reactions
More expensive
Definitive Therapy (15%)

Empiric Therapy (85%)
Infections Where Cultures are

Routinely Useful
Complicated urinary tract infections (urine)
Blood stream infections (Blood)
Bone and joint infections
Meningitis ( CSF)
Endocarditis (blood)
Lower respiratory tract infection (sputum, blood)
Infections Where Cultures Are NOT

Routinely Useful
Intra-abdominal abscess.
Uncomplicated lower urinary tract
infection.
Infected diabetic foot ulcers.
Sinusitis
24/03/1436
Justification for Antimicrobial

Combinations
To cover many bacteria for empiric therapy.
To achieve a synergistic antibacterial effect.
To prevent the emergence of resistance.
Concentration
Concentration-Dependent
Versus Time-Dependant Killing
Conc dep (Peak to MIC ratio
MIC
Time. Dep
(Time over MIC
ratio)
Time
Concentration dependant; Aminoglycosides, Flouroquinolones
Susceptibility testing
Once the pathogen is identified susceptibility testing can be performed.
The minimum inhibitory
concentration (MIC).
The lowest concentration that

inhibit visible bacterial growth
after 24 hrs
Break point.
The concentration of AB
achieved in the serum after
a standard dose
24/03/1436
Susceptibility testing
Once the pathogen is identified susceptibility testing can be performed.
The minimum inhibitory
concentration (MIC).
Break point.
Breakpoint and MIC values determine if the

organism is susceptible (S), intermediate
(I), or resistant (R) to an antimicrobial.
If MIC is below BP
If MIC is above BP
If MIC
BP diseases, CDC
MIU,=
Infectious
24/03/1436
Reasons for Antimicrobial Failure

Use for non-bacterial infections.
The wrong antibiotic was selected.
The patient has immune system defects.
The patient did not take the medication
properly compliance.
The antibiotic did not penetrate to the
site of infection.
Infectious
diseases, CDC
The bacteriaMIU,
was
resistant.
Resistance Problems from

Antibiotic Overuse
Gram-negative
cephalosporin.
Staphylococcus
(MRSA)
bacilli
aureus
from 3rd generation

from
Methicillin
Enterococcus from vancomycin use (VRE).

Streptococcus pneumoniae from penicillin.
Upper Respiratory Tract

Infections
Otitis media
Sinusitis
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The respiratory tract is the most common site for

infection by pathogens.
Most Upper respiratory tract infections

are viral & self limited
Otitis media, sinusitis and pharyingitis
Guidelines reduce AB use for viral URIs
Excess AB use for URTIs MIU,
bacterial resistance
Otitis media
Middle ear infection and inflammation
Most prevalent in young children
(0.5 5 years of age)
Most cases are viral &spontaneously resolve
Recurrence is common
OM
AOM
OME
Acute otitis media MIU, Infectious

Otitis
media with effusion
diseases, CDC
AOM:Infection & inflammation of the middle ear
24/03/1436
Otitis Media
AOM
OME
Acute Otitis Media

Otitis Media with Effusion
Rapid onset of signs & The presence of middle ear
fluids without symptoms of
symptomatic
acute illness
Presence of effusion.
the TM is typically retracted
Inflammation (indicated
or in the neutral position
by erythema or otalgia)
Tympanocentesis
TM is usually bulging
or
Tympanostomy tube insertion
ABs are useful
Effusions can be present up to 6 months
after acute episode of AOM.
Etiology
Common bacteria ( + virus)
Streptococcus pneumoniae
30-60% have reduced penicillin
susceptibility (PRSP)
Multi-drug resistance [ amoxicillin
and erythromycin, Clindamycin and
Floroquinolones. ]
Haemophilus influenzae (1-5 yr old)
up to 50% are b-lactamase positive
Moraxella catarrhalis
almost 100% b-lactamase positive
Why are children more susceptible to

AOM than adults ?
Their eustachian tubes are
shorter, more flaccid, and
more horizontal than adults.
Their immune system is still
developing
Their adenoids are larger
than adults, interfering with
the eustachian tube opening
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Risk factors
1. Day care attendance
2. Family history of AOM
3. Supine positioning during feeding allows
reflux to eutachian tube
4. Lower socioeconomic status
5. Smokers in the household
6. Craniofacial abnormality/ cleft palate
Clinical Presentation
symptoms
Young children:
- ear tugging
- irritable sleeping
- poor eating habits
Older patients
- ear pain
- ear fullness
- impaired hearing
Clinical Presentation and Diagnosis of

AOM
1. Middle ear effusion
Bulging membrane
Limited or absent mobility
Purulence
Opaque or cloudy, obscuring
visibility of middle ear
Severe: Otorrhea (middle ear
perforation with fluid
drainage
Pneumatic Otoscope
And
2. Signs of inflammation
Fever (< 25% of children)
Distinct erythema
otalgia
Normal tympanic membrane
AOM
24/03/1436
Diagnosis
How can you tell that AOM is severe
Severe AOM:
- Moderate to severe ear pain otalgia
- Otalgia > 48 hrs
- Fever 39C
Nonsevere AOM:
- Mild ear pain
- Fever < 39C
Confirmed AOM
( effusion and inflammation)
Approaches
Delayed AB
Immediate AB
Observationwatchful waiting
AOM with nonsevere symptoms
AOM with severe symptoms

- Bulging TM
According to age:
- Perforation
- 2 yrs: delayed AB
- Otorrhea
Children < 6 months,
- 6 months- 2 years, with
Children > 6 months,
unilateral AOM, or mild
with no reliable follow up
symptoms; delayed AB
6 months- 2 years, with
MIU, Infectious diseases,bilateral
CDC
AOM;
Non-pharmacological therapy
Watchful waiting and observation involves
monitoring for 48 to 72 hours after diagnosing
AOM to :
attenuate microbial resistance
to see if spontaneous resolution will occur
avoid unnecessary adverse events and costs of AB
External heat or cold to reduce postauricular pain

Analgesics are recommended in the first days
Corticosteroids, antihistamines and decongestants
are not recommended
10
24/03/1436
AOM Adjunctive Treatment

Otalgia/pain relief
Analgesics
Acetamenophen (paracetamol)
Ibuprofen ( longer action, but not < 6 months)
Topical anesthetics
Benzocaine drops (relief in 30 min)
Preferred over systemic analgesics
The decongestants, antihistamines and
corticosteroids have no beneficial role
Age < 6 months
Age > 2 yrs
Mild symptoms
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24/03/1436
Ig E -mediated
Amox taken within

30 days

FIGURE 692. Treatment algorithm for uncomplicated AOM in children 2 months to 12 years of age.
Otitis media Treatment

Failure after 3 days of therapy
Lack of clinical improvement after 3 days
of therapy in :
signs and symptoms of ear infection
ear pain
fever
tympanic membrane findings: redness, bulging,
otorrhea
Clindamycin+/- 3rd gen. cephaosporin

0r Tymanocentesis
Tympanostomy
tubes
MIU,
Infectious diseases,
CDCfor persistent OME
12
24/03/1436
Failure after 3 days of therapy
AOM Treatment
Avoid in children under 2 months:
Ceftriaxone
Erythromycin-sulfisoxazole
Trimethoprim- sulfamethoxazole
bilirubin displacement risk kernicterus
13
24/03/1436
AOM Treatment
Duration of therapy: according to age &
severity;
< 2yrs or severe/ recurrent symptoms; 10-day
[recurrent infections, is defined as 3 isolated episodes of otitis media in 6 month,
with resolution of each episode or 4 or more episodes of AOM in a 12-month
period that includes at least 1 episode in the preceding 6 months]
2-5 yrs, mild-moderate symptoms: 7 days

> 6 yrs mild-moderate symptoms 5 -7 days
[Exceptions: azithromycin(3-5d ) and
ceftriaxone
(3 d)]
AOM Prevention
Vaccination
Pneumococcal vaccine (Pneumovax)

Influenza vaccine Haemophilus
influenzae type B vaccine (children 2
years old)
Minimize risk factors
Tobacco smoke
Bottle feeding
Antibiotic prophylaxis is no longer recommended
for otitis-prone children
because of increasing
resistance
Patient Cases
A 5-month-old infant who was born at term and is
otherwise healthy was treated for her first case of otitis
media with amoxicillin 45 mg/kg/day for 7 days. On
follow-up examination, her pediatrician noticed fullness
in the middle ear and a cloudy tympanic membrane
with decreased mobility. She is now afebrile and eating
well. Which is the best recommendation regarding her
treatment?
A. No antibiotics warranted at this time.
B. High-dose (90 mg/kg/day) amoxicillin for 7 days.
C. Decongestant and antihistamine daily until
resolution.
D. Azithromycin. MIU, Infectious diseases, CDC
14
24/03/1436
A 4-year-old boy receives a diagnosis of his

fourth case of otitis media within 12
months. He has not shown evidence of
hearing loss or delay in language skills.
Which is the best intervention at this point?
A. Giving long-term antibiotic prophylaxis.
B. Inserting tympanostomy tubes.
C. Administering high-dose amoxicillin and
ensuring that he is up-to-date on his
pneumococcal and influenza vaccines.
D. No antibioticMIU,
therapy
warranted
A 3years-old boy presents to clinic with his

mother for a chief complaint of tugging of right
ear. His mother explained that he attends day
care and has been suffering from frequent
episodes of difficulty in sleeping associated with
excessive crying and a severe fever (39.2 ). After
consulting her pediatrician, he inspected the
child's ears and noticed that both tympanic
membranes are mobile, not bulging, but
erythematous. The child has no penicillin allergy.
What are the risk factors in this case for bacterial OM?
What is your suggested diagnosis for the presented case,
indicating criteria for AOM and severity?
Select the most appropriate treatment approach in this case.
Outcome evaluation
Assess improvement of Signs and symptoms
within 72 hrs of therapy.
Children may not improve during the first 24 hrs,
but stabilize afterwards
Presence of middle ear effusion with no symptoms
may sustain for 3 months, reevaluation is a must
Assess hearing and speech abilities
15
24/03/1436
Sinusitis
Infection or inflammation of the paranasal sinuses and
mucosal linings of the nasal passages for up to 4 weeks
Rhinosinusitis
Affects about 1 billion of people annually
Acute sinusitis: lasting < 4 weeks, resolves completely
Subacute: 4-12 weeks
Chronic: > 12 weeks
Recurrent acute: > 4 episodes per year
Occurrence related to viral URTI ( rhinovirus, influenza
virus), nasal allergies, non-allergic rhinitis, environmental
irritant
Sinusitis Common bacteria

Streptococcus pneumoniae
50-60%
Haemophilus influenzae
Moraxella catarrhalis
20%
Anaerobes
0-10%
Bacteroides
Peptostreptococcus spp.
Streptococcus pyogenes
Staphylococcus aureus
5%
5%
Chronic infections are commonly polymicrobial
90 % are viral, < 10 % bacterial

16
24/03/1436
Pathophysiology
Rhinosinusitis is
caused by mucosal
inflammation and
local damage to
mucociliary clearance
mechanisms as a result
of viral infection or
allergy
Acute Bacterial Rhinosinusitis (ABRS)
Diagnosis
At least 2 major symptoms or
1 major + >2 minor symptoms
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24/03/1436
Diagnosis of ABRS
Clinical diagnosis of ABRS:
a viral URI that has not resolved after 10 days, worsens after 5 to 7
days with signs and symptoms of acute infection
Radiography: for abscess or intracranial complication
Paranasal sinus puncture: Gold Standard
not routinely performed but may be useful for complicated/chronic
cases
Lab /culture: not recommended

for routine
diagnosis
MIU, Infectious diseases,
CDC
How to differentiate between

viral and bacterial sinusitis
Clinical Presentation and Diagnosis
Complications
Periorbital cellulitis
Meningitis
18
24/03/1436
General approach to Treatment

Initial management of rhinosinusitis is
watchful waiting that focuses on symptom
relief for patients with uncomplicated mild
disease lasting less than 10 days.( mild pain,
Temp< 38.3
Routine antibiotic use is not recommended
for all patients because viral sinusitis is selflimiting and bacterial infection resolves
spontaneously in many cases.
Who should receive an Antibiotic?

Antibiotic therapy should be reserved for
persistent, worsening, or severe ABRS:
Patients with severe disease regardless of duration.
(e.g., evidence of systemic toxicity with a temp of 39C or higher and
a threat of suppurative complications)
Patients with mild to moderately severe

symptoms based on clinical judgment that have
persisted for greater than 10 days or worsened after
5 -7 days
Empirical selection is often employed and should
target likely pathogens
Treatment algorithm for ABRS in children

10-14 days
Amox-Clav
45 mg/Kg/d
bid
Amox-Clav
90 mg/Kg/d
bid
Clinda+(cifixime
or Cefopodoxime)
Or Levo
Clinda+ (cifixime
or Cefopodoxime)
Or Levo (type 1)
B-lactam allergy
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24/03/1436
Treatment algorithm for ABRS in Adults

5-7 days
+ Severe infection
Amox-Clav
2 g bid
Or Doxy 100
bid or 200 qd
Amox-Clav
500 mg Tid
Or 875 mg bid
Levo 500 mg qd
Or Moxi 400 mg qd
Amox-Clav,2g bid
Levo 500 mg qd
Or Moxi 400 mg qd
B-lactam allergy
Antimicrobial regimen for ABRS in adults
Doxy 100 bid or 200 qd

Levo 500 mg qd
Or Moxi 400 mg qd
5-7 days
Nonpharmacologic Therapy
Intranasal saline irrigations
moisturize the nasal canal and impair crusting of
secretions along and promote ciliary function
Humidifiers
vaporizers
saline nasal sprays or drops

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24/03/1436
Adjunctive (supportive) Therapy

Analgesics and antipyretics: fever and pain of sinus
pressure
( acetaminophen and NSAID)
Decongestant lack evidence for effectiveness
For allergic patients only
Antihistamines should be avoided as they thicken
mucus and impair its clearance but they may be useful
in patients with predisposing allergic rhinitis or chronic
sinusitis
Intranasal corticosteroid are for allergic patients and
those with chronic sinusitis
Outcome evaluation
Clinical improvement should be evident by 7 days of therapy
demonstrated by reduction in nasal congestion and discharge,
and improvements in facial pain or pressure and other
symptoms.
Patients should be monitored for common adverse events.
Referral is also important for:
Recurrent / chronic sinusitis
Failure with first- or second-line therapy
Acute disease in immunocompromised patients.
A 5 years old boy presents to the clinic with

mild nasal congestion, sinus pain and
pressure that have begun 4 days ago for the
first time. He is coming to you to fill a
prescription of
Rx: Amoxicillin , Loratadin
Do you agree on dispensing this prescription?
If 7 days have passes and the patient did not
improve, will the prescription be appropriate?
21
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A 15 yrs-old man presents with mild S&S of

definite ABRS for the first time that have lasted
for more than 7 days with no obvious
improvement. He comes to your pharmacy to fill
the following prescription and declares having
experienced severe urticaria from penicillin and
denies having received an antibiotic in the
previous period.
What are your recommendations in this case? Indicate a
first line and second line therapy. ( He is given Sulfa/
Trimeth) or a macrolide
What are classes of drugs that are not recommended in this
case (Telithromycin and Floroqinolones, Clindamycin and
probably Doxycycline).
What is the duration of therapy? 10 to 14 days.
22

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24/03/1436

MIU, Infectious diseases, CDC

Prior to the discovery of penicillin

Today, despite the presence of a

Role of the clinical pharmacist

Alteration of normal flora OR disruption of host

ii. Exogenous Infections:

MIU, Infectious diseases, CDC

Other sterile anatomic

Guiding Principles When

MIU, Infectious diseases, CDC

What is the Appropriate Decision

MIU, Infectious diseases, CDC

Infection not well defined

Infection well defined

One, seldom two drugs

Less adverse reactions

More adverse reactions

Definitive Therapy (15%)

Infections Where Cultures are

MIU, Infectious diseases, CDC

Infections Where Cultures Are NOT

MIU, Infectious diseases, CDC

Justification for Antimicrobial

MIU, Infectious diseases, CDC

Concentration dependant; Aminoglycosides, Flouroquinolones

The lowest concentration that

MIU, Infectious diseases, CDC

MIU, Infectious diseases, CDC

Breakpoint and MIC values determine if the

MIU, Infectious diseases, CDC

MIU, Infectious diseases, CDC

MIU, Infectious diseases, CDC

Reasons for Antimicrobial Failure

Resistance Problems from

from 3rd generation

Enterococcus from vancomycin use (VRE).

MIU, Infectious diseases, CDC

Upper Respiratory Tract

MIU, Infectious diseases, CDC

MIU, Infectious diseases, CDC

The respiratory tract is the most common site for

Most Upper respiratory tract infections

Acute otitis media MIU, Infectious

AOM:Infection & inflammation of the middle ear

MIU, Infectious diseases, CDC

MIU, Infectious diseases, CDC

Acute Otitis Media

MIU, Infectious diseases, CDC

Why are children more susceptible to

MIU, Infectious diseases, CDC

MIU, Infectious diseases, CDC

Clinical Presentation and Diagnosis of

MIU, Infectious diseases, CDC

AOM with severe symptoms

External heat or cold to reduce postauricular pain

MIU, Infectious diseases, CDC

AOM Adjunctive Treatment

Age < 6 months

Age > 2 yrs

MIU, Infectious diseases, CDC

MIU, Infectious diseases, CDC

MIU, Infectious diseases, CDC

Amox taken within