Benjamin G.

Co, MD, FPPS, FPSECP

Executive Director, Center for Excellence in Drug Research, Evaluation and Studies, Inc.
at the Research Institute for Tropical Medicine

Medical Director, Otsuka Philippines

Pharmaceuticals, Inc.
} Executive Director, Center of Excellence for
Drug Research, Evaluation & Studies, Inc.
} Received honorarium for speaking
engagements and advisory capacity with
MSD, Abbott, Natrapharm-Patriot, Leo
Pharmaceuticals
} Consultant, RFQ for Pharmaceuticals, Metro
Pacific Investment Corporation
}

1. Provide the NINE STEPS for appropriate and

judicious use of antimicrobial therapy and
current recommendations of the RED BOOK on
antibiotic use
2. Give a brief overview on the pharmacologic
principles of antimicrobial therapy as the basis
for rational utilization
3. Enumerate the factors contributing to
resistance and discuss actions to prevent or slow
antimicrobial resistance

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Step 1: Predict the infecting organism

Step 2: Consider host defense mechanisms
Step 3: Consider the age of the child
Step 4: Perform diagnostic tests
Step 5: Consider antibiotic susceptibilities of
suspected pathogens
Step 6: Consider PK/PD properties of drugs
Step 7: Consider target attainment
Step 8: Consider empiric and definitive
therapeutic decisions separately
Step 9: Special considerations

Background:
More than half of all outpatient prescriptions for antibiotics
are given for 5 conditions otitis media, sinusitis, cough
illness/bronchitis, pharyngitis, and nonspecific URTI
Almost 90% of children receive antibiotics or
immunomodulating agents even if the infection is a viral
one, making it useless to give either

1. Antivirals are specific for indicated viral

infections! They are not blanket drugs for
general use.
2. Immunomodulating agents are drugs in
search of a disease. They dont work. Never
had. Never have. Never will.

Background:
Children treated with an antibiotic for RTIs are at increased
risk of becoming colonized with resistant respiratory tract
flora, including S. pneumoniae & H. influenzae
Children who subsequently develop RTIs are more likely to
experience failure of antimicrobial therapy & are likely to
spread resistant bacteria to close contacts, both children
and adults.

1. Condition

2. Epidemiology

3. Diagnosis

4. Management

Epidemiology

Diagnosis

Management

90-98% of cases are

viral, and antibiotics
are not guaranteed
to help even if the
causative agent is
bacterial

- Halitosis, fatigue,
headache,
decreased appetite
- Most PE findings
are non-specific &
dont distinguish
viral from bacterial.

If bacterial:
- Amoxicillin
(80mg/kg/day) or
Amoxicillinclavulanate (14:1
ratio) is first line of
therapy

Acute rhinosinusitis

Epidemiology Diagnosis

Management

Bacterial diagnosis may be

established based on the presence
of ONE of the following:
- persistent symptoms without
improvement: nasal discharge or
daytime cough > 10 days
- worsening symptoms: worsening
or new onset of fever, daytime
cough, or nasal discharge after
initial improvement of a viral URI
- severe symptoms: Fever 39oC,
purulent nasal discharge for at
least 3 consecutive days.

Penicillin allergic:
-Clindamycin + third
generation oral
cephalosporin may be
appropriate
Vomiting or cannot
tolerate oral
medications:
- Single dose
ceftriaxone

Imaging tests are no longer

recommended for uncomplicated
cases

Acute rhinosinusitis

Epidemiology

Diagnosis

Management

-Most common
childhood infection
for which antibiotics
are prescribed
- 4-10% of children
with AOM treated
with antibiotics
experience adverse
effects

AOM should not be

diagnosed in
children without
middle ear effusion
(based on
pneumatic otoscopy
and/or
tympanometry)

- Mild cases with

unilateral symptoms
in children 6-23
months of age or
unilateral or
bilateral symptoms
in children > 2 years
may be appropriate
for watchful waiting
based on shared
decision-making

Acute Otitis Media (AOM)

Epidemiology

Diagnosis

Management

Definitive diagnosis
requires:
-Moderate or severe
bulging of TM or new
onset otorrhea not due to
otitis externa
-Mild bulging of the TM
AND recent (< 48h) onset
of otalgia (holding,
tugging, rubbing of the ear
in a nonverbal child) or
intense erythema of the
TM

Amoxicillin in children
who have not received
amoxicillin within the
past 30 days.
Co amoxiclav if
amoxicillin was given
in the past 30 days, if
concurrent purulent
conjunctivitis is
present, or if the child
has a history of
recurrent AOM nonresponsive to
amoxicillin.

Acute Otitis Media (AOM)

Epidemiology

Diagnosis

Management

- Recent guidelines
aim to minimize
unnecessary
antibiotic exposure
by emphasizing
appropriate use of
RADT (rapid antigen
detection test) and
subsequent
treatment

-Clinical features
along do not
distinguish between
GAS and viral
pharyngitis

Amoxicillin &
penicillin V remain
first-line therapy

Pharyngitis

Epidemiology

Diagnosis

Management

- Streptococcal
pharyngitis is
primarily a disease
of children 5-15
years old and is rare
in preschool
children

-RADT test in children

with sore throat plus 2
or more of the
following:
1. absence of cough
2. presence of
tonsillar swelling or
exudates
3. history of fever
4. presence of
swollen & tender
anterior cervical LNs
5. age younger than
15 years

Penicillin allergic:
-cephalexin,
clindamycin,
clarithromycin or
azithromycin
Recommended
treatment course for
all lactams is 10
days

Pharyngitis

Epidemiology

Diagnosis

Management

The course of most

uncomplicated viral
URIs is 5-7 days.
Colds usually last
around 10 days.

Viral URIs often

characterized by
nasal discharge &
congestion or
cough. Usually nasal
discharge begins as
clear and changes
throughout the
course of illness.

Focus on symptomatic
relief. Antibiotics should
not be prescribed for
these conditions.

At least 200 viruses

can cause the
common cold.

FEVER, if present,
occurs early in the
illness.

Potential for harm and NO

proven benefit from OTC
cough and cold medicines
in children < 6 years.
Low-dose inhaled
corticosteroids and oral
prednisolone DO NOT
improve outcomes in nonasthmatic children.

Common cold or nonspecific URI

Epidemiology

Diagnosis

Management

-Most common
lower RTI in infants

-Occurs in children
< 24 months and is
characterized by:
rhinorrhea, cough,
wheezing,
tachypnea, and/or
decreased
respiratory effort

-Antibiotics are not

helpful & should not be
used
-Nasal suctioning is the
mainstay of therapy
-Salbutamol can be tried
but should only be
dispensed if there is
documented
improvement.
-Racemic epinephrine can
also be used.
-No role for
corticosteroids, ribavirin,
or chest physiotherapy

- Most often caused

by RSV but can be
caused by many
other respiratory
viruses

Bronchiolitis

Epidemiology

Diagnosis

-Common in
In infants: fever &/
children affecting 8% or strong smelling
of girls and 2% of
urine are common
boys by age 7
In school-aged
-Most common
children: dysuria,
pathogen is E. coli
frequency, or
(85% of cases)
urgency are
common

Management
Initial should be
based on local
susceptibility:
(2014, ARSP) DOC
is Co Amoxiclav.
Duration of therapy
7-14 days
Antibiotic treatment
of asymptomatic
bacteriuria in
children is not
recommended

UTIs

Epidemiology

Diagnosis

Management

Definitive diagnosis requires

urinalysis suggestive of
infection and at least 50,000
CFUs/mL of a single
uropathogen from urine
obtained through
catheterization or suprapubic
aspiration (NOT urine
collection bag)

Antibiotic prophylaxis
to prevent recurrent
UTI is not
recommended.

Urine testing for all children

2-24 months with
unexplained fever is no
longer recommended.

Febrile infants with

UTIs should undergo
renal and bladder
ultrasound during or
following their first
UTI. Abnormal
imaging results require
further testing.

UTIs

Use of multiple drugs for treatment of

seriously ill patients increases the probability
of drug-drug interactions
} Produces changes in drug concentrations (PK)
or changes in drug effect/safety profile (PD)
} PK: can result from alterations in ADME of a
drug resulting in changes in concentrations
} PD: may produce synergistic, additive or
antagonistic drug effects or toxicities
}

SINGLE MOST IMPORTANT FACTOR USING IT

WHEN IT SHOULD NOT BE USED!
UP TO 50-90% ARE USED INAPPROPRIATELY
Antimicrobial resistance has disproportionately
escalated compared to new drugs being developed

Overuse in animals

Not to treat infections but fed regularly to speed

growth and compensate for unsanitary and crowded
conditions

Urgent threats

Serious threats

Concerning threats

Cabapenem resistant
-Enterobacteriaceae
-Antibiotic resistant gonorrhea
-Clostridium difficile

Methicillin resistant
-S. aureus

Vancomycin-resistant
-S. aureus

Drug resistant TB

Erythromycin-resistant
-Group A streptococci

Drug resistant
-S. pneumoniae
ESBL-producing
-Enterobacteriaceae
Multidrug resistant
-Acinetobacter spp
Drug-resistant
-Campylobacter species
Fluconazole-resistant
-Candida spp.
Vancomycin-resistant
-Enterococcus spp
MDR Pseudomonas aeruginosa
DR nontyphoidal Salmonella spp
DR Salmonella typhi
DR Shigella spp.

Clindamycin-resistant
-Group A streptococci

1. Prevent infections & prevent the spread of

resistance
2. Track antibiotic resistance infections
3. Improve antimicrobial use & promote
antimicrobial stewardship
4. Develop drugs & improved diagnostic tests

At the practice level, pediatricians can

integrate key recommendations that focus on
antibiotic prescribing for common infections
in children:

1. Confirm UTI by documenting that the patient is

symptomatic & has properly obtained a urinalysis &
quantitative culture with each episode, with a
positive result based on the strain of the bacteria
isolated and the colony count. Once the infection is
established, susceptibility data should be used to
prescribe the narrowest spectrum appropriate
antimicrobial agent.

 2. Before treating a patient for bacterial pneumonia,

ensure that there is not an alternate diagnosis or
explanation for radiologic findings. The vast
majority of RSV infections in infants are not
complicated by bacterial infection, but migratory
atelectasis is common. For infants with
uncomplicated bronchiolitis, antimicrobial agents
are not indicated.

 3. Limit the use of vancomycin for treatment of

MRSA infections or other methicillin-resistant
pathogens to those cases when there is no suitable
alternative. Pediatricians should standardize their
own processes & ensure that appropriate cultures &
other diagnostic tests are obtained before
antimicrobial agents are administered. They also
should know hot to access their local antibiograms
& be aware of antimicrobial resistance patterns.
Antimicrobial agents should be initiated promptly
for suspected or proven infection, and indication,
dose, timing and anticipated duration should be
documented.

 4. Reassess response to therapy within 48 hours,

taking into account new clinical and laboratory
data. Focus definitive therapy to use the most
appropriate narrow-spectrum agent, and
discontinue therapy when a treatable infection is
excluded. Pediatricians also can collaborate with
their antibiotic stewardships team and use formal
ID consultation for cases in which the patient has
comorbidities or a severe illness or if the diagnosis
is uncertain.

Specific

Measureable

Attainable

Realistic

Time-related