urt 2012 handout
TRANSCRIPT
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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
MIU, Infectious diseases, CDC
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.
MIU, Infectious diseases, CDC
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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
MIU, Infectious diseases, CDC
Infection suspected
Cultures taken
Antibiotic started
Culture results reviewed
Antibiotic revised if necessary
Empiric
Definitive
What is the Appropriate Decisionif a Culture is Required?
MIU, Infectious diseases, CDC
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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)
MIU, Infectious diseases, CDC
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.
MIU, Infectious diseases, CDC
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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MIU, Infectious diseases, CD5
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
MIU, Infectious diseases, CDC
MIU, Infectious diseases, CDC
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MIU, Infectious diseases, CD6
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.
MIU, Infectious diseases, CDC
Upper Respiratory Tract
Infections
Otitis media
Sinusitis
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MIU, Infectious diseases, CD7
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
MIU, Infectious diseases, CDC
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
MIU, Infectious diseases, CDC
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MIU, Infectious diseases, CD8
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
MIU, Infectious diseases, CDC
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
MIU, Infectious diseases, CDC
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MIU, Infectious diseases, CD9
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
MIU, Infectious diseases, CDC
Clinical Presentation
Young children: Older patients
- ear tugging - ear pain
- irritable sleeping - ear fullness
- poor eating habits - impaired hearing
symptoms
MIU, Infectious diseases, CDC
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
MIU, Infectious diseases, CDC
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
MIU, Infectious diseases, CDC
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
MIU, Infectious diseases, CDC
Mild symptoms
MIU, Infectious diseases, CDC
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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
MIU, Infectious diseases, CDC
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
MIU, Infectious diseases, CDC
MIU, Infectious diseases, CDC
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
MIU, Infectious diseases, CDC
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MIU, Infectious diseases, CD15
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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MIU, Infectious diseases, CD16
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
MIU, 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
MIU, Infectious diseases, CDC
Acute Bacterial Rhinosinusitis (ABRS)
MIU, Infectious diseases, CDC
Diagnosis At least 2 major symptoms or
1 major + >2 minor symptoms
MIU, Infectious diseases, CDC
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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
MIU, Infectious diseases, CDC
Complications
Periorbital cellulitis
Meningitis
Clinical Presentation and Diagnosis
MIU, Infectious diseases, CDC
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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.
MIU, Infectious diseases, CDC
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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MIU, Infectious diseases, CD20
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
MIU, Infectious diseases, CDC
Antimicrobial regimen for ABRS in adults 5-7 days
MIU, Infectious diseases, CDC
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
MIU, Infectious diseases, CDC
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.
MIU, Infectious diseases, CDC
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