URT 2012 Handout

8/9/2019 URT 2012 Handout

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MIU, Infectious diseases, CD1

AntimicrobialRegimenSelection

MIU, Infectious diseases, CDC

Prior to the discovery of penicil linin 1927 by Sir Alexander Fleming; Patients with infected woundsoften had to have a wounded limbamputated.Most patients faced death fromtheir infection.

Today, despite the presence of alarge numberof antibiotic classes,mortality due to infectiousdiseasesis increasing ????

Microbial resistance

Solution ????????Appropriate antibiotic

regimen selection

Role of the clinical pharmacist


TerminologiesInfections are either Endogenous orExogenous.

i. Endogenous I nfect i on: Alteration of normal flora OR disruption of host

defense.

Do we have bacteria in our bodies? Colonizing Bacteria

ii. Exogenous I nfect i ons:

Infections acquired from an external source.

Colonizationversus Infection.

VirulenceversusResist ance.



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URT

Maroxellacatarrhalis

Streptococcus pneumonia

Heamophilus influenza

LRT

Sterile

Skin

Staphylococcus

epidermidis/ aureus

Micrococci, Diphteroids.

Mouth

Oral anaerobes

Vridans streptococci

Other sterile anatomic

sites:

CSF, blood & urine.MIU, Infectious diseases, CDC

Guiding Principles WhenPrescribing Antimicrobials

Make Correct Diagnosis

Do No Harm


Infection suspected

Cultures taken

Antibiotic started

Culture results reviewed

Antibiotic revised if necessary

Empiric

Definitive

What is the Appropriate Decisionif a Culture is Required?



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Empiric vs. Definitive

Infection not well defined

(best guess)

Broad spectrum

Multiple drugs

More adverse reactions

More expensive

Infection well defined

Narrow spectrum

One, seldom two drugs

Less adverse reactions

Less expensive

Empiric Therapy (85%) Definitive Therapy (15%)MIU, Infectious diseases, CDC

Infections Where Cultures areRoutinely Useful

Complicated urinary tract infections (urine)

Blood stream infections (Blood)

Bone and joint infections

Meningitis ( CSF)

Endocarditis (blood)

Lower respiratory tract infection (sputum, blood)


NOTInfections Where Cultures AreRoutinely Useful

Intra-abdominal abscess.

Uncomplicated lower urinary tractinfection.

Infected diabetic foot ulcers.

Sinusitis



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Justification for AntimicrobialCombinations

To cover many bacteria for empiric therapy.

To achieve a synergistic antibacterial effect.

To prevent the emergence of resistance.


Concentration-DependentVersus Time-Dependant Killing

Time

Concentration

MIC

Conc dep (Peak to MIC ratio

Time. Dep

(Time over MIC

ratio)

Concentration dependant; Aminoglycosides, FlouroquinolonesMIU, Infectious diseases, CDC

The minimum inhibitory

concentration (MIC).Break poi nt .

Once the pathogen is identified susceptibility testing can be performed.

The lowest concentration thatinhibit visible bacterial growth

after 24 hrs

Susceptibility testing

The concentration of ABachieved in the serum after

a standard dose



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The minimum inhibitoryconcentration (MIC). Break poi nt .

Once the pathogen is identified susceptibility testing can be performed.

Breakpoint and MIC values determine if the

organism is susceptible (S), intermediate(I), or resistant (R) to an antimicrobial.

If MIC is below BP S

RIf MIC is above BP

Susceptibility testing

If MIC = BP IMIU, Infectious diseases, CDC




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Reasons for Antimicrobial Failure

Use for non-bacterial infections.The wrongantibiotic was selected.

The patient has immune system defects.

The patient did not take the medicationproperly compliance.

The antibiotic did not penetrate to thesite of infection.

The bacteria was resistant.MIU, Infectious diseases, CDC

Resistance Problems fromAntibiotic Overuse

Gram-negative bacilli from 3rd generationcephalosporin.

Staphylococcus aureus from Methicillin(MRSA)

Enterococcus from vancomycin use (VRE).

St reptococcus pneumoniaefrom 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 URTIsbacterial 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 Otitis media with effusionMIU, Infectious diseases, CDC

AOM:Infection & inflammation of the middle ear



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Otitis Media

AOMAcute Otitis Media

Rapid onset of signs &symptomatic

Presence of effusion.

Inflammation (indicated

by erythema or otalgia)

TM is usually bulging

OMEOtitis Media with Effusion

The presence of middle ear fluids without symptoms of

acute illness

the TM is typically retracted

or in the neutralposition

ABs are useful

Effusions can be present up to 6 months

after acute episode of AOM.

Tympanocentesis

or

Tympanostomytube insertion


EtiologyCommon 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 positiveMIU, Infectious diseases, CDC

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 attendance2. 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

Young children: Older patients

- ear tugging - ear pain

- irritable sleeping - ear fullness

- poor eating habits - impaired hearing

symptoms


Clinical Presentation and Diagnosis of

AOM

1. Middle ear effusion

Bulging membrane

Limited or absent mobility

Purulence

Opaque or cloudy, obscuring

visibility of middle earSevere: Otorrhea (middle ear

perforation with fluiddrainage

And2. Signs of inflammation

Fever (< 25% of children)

Distinct erythema otalgia

Normal tympanic membrane AOM

Pneumatic Otoscope



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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)

Immediate ABDelayed ABObservationwatchful waiting

AOM with nonsevere symptoms

According to age:

- 2 yrs: delayed AB

- 6 months- 2 years, with

unilateral AOM, or mild

symptoms; delayed AB

AOM with severe symptoms- Bulging TM

- Perforation

- Otorrhea

Children < 6 months,

Children > 6 months,

with no reliable follow up

6 months- 2 years, withbilateral AOM;

Approaches


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 recommendedMIU, Infectious diseases, CDC


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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 roleMIU, Infectious diseases, CDC

Age < 6 months

Age > 2 yrs


Mild symptoms



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

Amox taken within

30 days

IgE -mediated


Otitis media Treatment

Failure after3 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 MIU, Infectious diseases, CDC

Clindamycin+/- 3rd gen. cephaosporin

0r TymanocentesisTympanostomy tubes for persistent OMEMIU, Infectious diseases, CDC


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Failure after 3 days of therapy



AOM Treatment

Avoid in children under 2 months:

Ceftriaxone

Erythromycin-sulfisoxazole

Trimethoprim- sulfamethoxazolebilirubin displacement risk kernicterus



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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)]MIU, Infectious diseases, CDC

AOM Prevention

Vaccination

Pneumococcal vaccine (Pneumovax)

Influenza vaccineHaemophilus

influenzae type B vaccine (children 2years old)

Minimize risk factors

Tobacco smoke

Bottle feeding

Antibiotic prophylaxis is no longer recommended

for otitis-prone children because of increasing

resistanceMIU, Infectious diseases, CDC

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 eatingwell. 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.

Patient Cases



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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 antibiotic therapy warranted.MIU, Infectious diseases, CDC

A 3years-o ld 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

consult ing 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.

Whatare the risk factors inthis case for bacterial OM?

What is your suggested diagnosis for the presented case,

indicating criteriafor AOM and severity?

Select the most appropriate treatment approach in this case.MIU, Infectious diseases, CDC

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



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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

irritantMIU, Infectious diseases, CDC


Sinusitis Common bacteriaStreptococcus pneumoniae 50-60%

Haemophilus influenzae

Moraxella catarrhalis 20%

Anaerobes 0-10%

Bacteroides

Peptostreptococcus spp.

Streptococcus pyogenes 5%

Staphylococcus aureus 5%

Chronic infections are commonlypolymicrobial

90 % are viral, < 10 % bacterialMIU, Infectious diseases, CDC


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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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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 diagnosisMIU, Infectious diseases, CDC

How to differentiate between

viral and bacterial sinusitis


Complications

Periorbital cellulitis

Meningitis

Clinical Presentation and Diagnosis



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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 self-

limiting 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 39 C or higher anda 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 shouldtarget likely pathogensMIU, Infectious diseases, CDC

Treatment algorithm for ABRS in children

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

10-14 days



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Treatment algorithm for ABRS in Adults

Amox-Clav

500 mg Tid

Or 875 mg bid

Amox-Clav

2 g bid

Or Doxy 100bid or 200 qd

Amox-Clav,2g bid

Levo 500 mg qd

Or Moxi400 mg qd

Levo 500 mg qdOr Moxi400 mg qd

B-lactam allergy

Doxy 100 bid or 200 qd

Levo 500 mg qd

Or Moxi400 mg qd

5-7 days

+ Severe infection


Antimicrobial regimen for ABRS in adults 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 dropsMIU, Infectious diseases, CDC


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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

Adjunctive (supportive) Therapy


Outcome evaluation

Clinical improvement should be evident by 7 days of therapy

demonstrated by reduction in nasal congestion and discharge,

and improvement s in facial pain or pressure and other

symptoms.

Patientsshould be monitored for common adverse events.

Referral is also important for:

Recurrent / chronic sinusitis

Failurewith first- or second-line therapy

Acutedisease 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?



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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 anddenies 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.MIU, Infectious diseases, CDC

Documents

URT 2012 Handout