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Not Lectured

Rational Antibiotic Use:


The Antimicrobial
Dr. Minette Claire
HOUTLINE:
I. Treatment of Infections
A. Uses of Antibiotics in Clinical Practice
II. Antimicrobial Utilization
A. Antibiotics
B. Potential Problem: Inappropriate Antibiotic Use
C. Causal Associations between Antimicrobial Use and the
Emergence of Antimicrobial Resistance
D. General Principles of Antimicrobial Therapy: Selecting and
Initiating Antibiotic Regimen
III. Antimicrobial Stewardship
IV. Rational Antibiotic Use
V. Antibiotic Checklist
A. Q1: Is an antibiotic indicated on the basis of clinical and
laboratory findings?
B. Q2: Before antibiotics are initiated, have appropriate clinical
specimens been obtained, examined, and cultured?
C. Q3: What organisms are most likely to be causing the infection?
D. Q4: If several antibiotics are available to treat the likely or
known pathogen, which agent is best for a particular agent?
Which is antibiotic best for a particular patient?
E. Q5: Is an antibiotic combination appropriate?
F. Q6: What are the important host factors?
G. Q7: What is the appropriate dose?
H. Q8: What is the best route of administration?
I. Q9: Will initial therapy need modification after culture data are
available?
J. Q10: What is the Optimal Duration of Therapy?
VI. Treatment Failure
VII. Summary

TREATMENT OF INFECTIONS
Improvement of patient outcomes by selecting the
MOST APPROPRIATE ANTIMICROBIAL (OR
ANTIBIOTIC), which depends on the following:
o Recognized and identified site of infection
o Patients underlying illness(es) and other risk
factors
o Likely pathogens involved
o Drug resistance

Example:
Most common etiologic agent for SSTI Gram (+) cocci
Most appropriate antibiotic: -lactams (oxacillin, cloxacillin
aka Anti-Staphylococcal -lactams)
Penicillin: will not work against Staphylococcus aureus
Vancomycin: reserved for MRSA alone (to prevent drug
resistance)
If infectious agent is known: give narrow spectrum antibiotics
DM, COPD, and CKD may expand the list of suspected
microbes
[2013B]

The Antibiotic Paradox: Antibiotic therapy, if


indiscriminantly used, may turn out to be a medicinal
flood that temporarily cleans and heals, but
ultimately destroys life itself (Felix Marti-Ibanez,
1955)

ANTIBIOTICS

*The following is an enumerated list of above figure


Cell-Wall Inhibitors in bacteria, PEPTIDOGLYCAN confers
cell wall rigidity and resistance to osmotic lysis in gram (-)
and (+) bacteria [Harrisons 18th ed]
o Bacitracin cyclic peptide antibiotic [Harrisons 18th ed]

o
o

Cycloserine
Glycopeptides bind to the terminal D-alanine-Dalanine component of stem peptide inhibits addition
of subunits to peptidoglycan backbone [Harrisons]

Telavancin (lipoglycopeptide) [Harrisons 18th ed]


-lactams characterized by a four-membered lactam ring; forms an irreversible covalent acyl bond
with the transpeptidase enzyme, preventing the crosslinking of peptidoglycan [Harrisons 18th ed]

USES OF ANTIBIOTICS IN CLINICAL PRACTICE


Empiric therapy if you dont have culture results yet,
but know the likely pathogen (based on history, symptoms,
epidemiology) start antibiotic therapy immediately.
Increased risk if treatment is delayed [2013B]
Definitive therapy you have results of culture and
sensitivity. Modify the antibiotic therapy to the narrowest
spectrum and cheapest available [2013B]
Prophylactic therapy Given to selected patients to
prevent SSI and endocarditis [2013B]

ANTIMICROBIAL UTILIZATION
ANCHORES-ANDAL-ANDRADE (editor)

Vancomycin
Teicoplanin

Penicillins
Penicillin G
Methicillin-Like
Methicillin
Cloxacillin
Dicloxacillin
Flucloxacillin
Penicillin V
Cephalosporins
Broad spectrum
Cefotaxime
Ceftriaxone
Anti-pseudomonal
Ceftazidime
Cefepime
Cefpirome
Anti-haemophilus
Ceflaclor
Cefuroxime
Cefamandole
Moderate spectrum
Cephalexin
Cephazolin
Cephalothin
Anti-anaerobic
Cefoxitin
Cefotetan
Others
Monobactams

Page 1 of 9

Aztreonem
Carbapenems
Imipinem
-lactamase Inhibitors
Clavulanic acid
Sulbactam
Cell-Membrane Inhibitors
o Polymixins disrupt the permeability of both the

markedly reduced in an anaerobic environment


(since its uptake and penetration constitute an
aerobic, energy dependent process) [Harrisons 18th
ed]

outer and cytoplasmic membranes of gram (-)


bacteria [Harrisons 18th ed]

o
o

Polymixin B
Polymixin E

Gramicidin A form pores/channels in lipid bilayers


[Harrisons 18th ed]
Daptomycin insertion of this in gram(+) bacteria
forms a channel that causes depolarization of the
membranes by efflux of intracellular ionscell
death [Harrisons 18th ed]

DNA Inhibitors
o Transcription

Rifamycins
Rifampicin
Rifabutin
o Replication

5-nitroimidazoles
Metronidazole
Tinidazole

Quinolones
Nalidixic Acid
Norfloxacin
Ciprofloxacin
Ofloxacin
Protein Synthesis Inhibitors
o Fusidic Acid
o Muprocin
o Chloramphenicol binds reversibly to the 50S

Neomycin
Streptomycin
Kanamycin
Kanamycin
Gentamicin
Tobramycin
Amikacin
Tetracyclines interact reversibly with the

bacterial 30S ribosomal subunit, blocking binding of


aminoacyl tRNA to the mRNA-ribosome complex
(mechanism is different from aminoglycosides)
[Harrisons 18th ed]

Tetracycline

Minocycline

Doxycycline
Metabolic Analogues interfere with bacterial
synthesis of folic acid, cessation of bacterial cell
growth [Harrisons 18th ed]

o
o
o

Dapsone
Sulfonamides
Trimethoprim

POTENTIAL PROBLEM: INAPPROPRIATE


ANTIBIOTIC USE
Wrong choice, dose, or duration of therapy
Ineffective empiric treatment of bacterial infection
at the time of its identification
Use of an antibiotic to which the pathogen is
resistant

portion of the bacterial ribosome, inhibiting peptide


bond formation by blocking attachment of the
amino acid end of aminoacyl-tRNA to the ribosome
[Harrisons 18th ed]
Lincosamides bind to a site on the 50S
ribosomes nearly identical to the binding site for
macrolides [Harrisons 18th ed]

Lincomycin

Clindamycin
MASK

Azalides

Streptogramins also bind to 50S subunit and


block protein synthesis [Harrisons 18th ed]

Ketolides
Macrolides bind specifically to 50S portion of
the bacterial ribosome and inhibit protein chain
elongation [Harrisons 18th ed]

Erythromycin
Azithromycin
Clarithromycin
Roxithromycin
Aminoglycosides exert bactericidal effect by

binding irreversibly to the 30S subunit of the


bacterial ribosome and inhibiting translocation of
peptidyl-tRNA from the A to P site. Activity is

ANCHORES-ANDAL-ANDRADE (editor)

WHY DO DOCTORS USE ANTIBIOTICS


IMPROPERLY?
Altruism and perception that antibiotics can do no
harm
Lack of physicians knowledge and skills
Poor role models among seniors

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Lack of infectious disease physicians and


microbiologists
Lack of microbiology laboratory personnel
Lack of information on local resistance patterns
Fear of litigation
Patient demands
Undue influence of the industry

o
o

[2013B]

o -lactam resistant Acinetobacter species


Carbapenems
o MDR Acinetobacter baumanii (CRABCarbapenem-resistant A. baumanii) [2013B]

OTHER CONSEQUENCES OF INAPPROPRIATE


ANTIBIOTIC USE

Superinfection
Unwanted adverse reactions
Waste of efforts and resources
Increase in total cost of therapy
Emergence of antimicrobial resistance

CAUSAL ASSOCIATIONS BETWEEN


ANTIMICROBIAL USE AND THE EMERGENCE
OF ANTIMICROBIAL RESISTANCE
Changes in antimicrobial use are paralleled by
changes in the prevalence of resistance
Antimicrobial resistance is more prevalent in
healthcare-associated bacterial infections,
compared with those from community acquired
infections
Patients with healthcare-associated infections
caused by resistant strains are more likely than
control patients to have received prior
antimicrobials history of previous antimicrobials
should be part of history [2013B]

Areas within hospitals that have the highest


rates of antimicrobial resistance also have
the highest rates of antimicrobial use
increased use of antibiotics, increased resistance
[2013B]

Increasing duration of patient exposure to


antimicrobials increases the likelihood of
colonization with resistant organisms

COLLATERAL DAMAGE
Ecological adverse effects of antibiotic
therapy
o Selection of drug-resistant organisms
o Unwanted development of colonization or
infection with multi-drug resistant organisms
elimination of non-resistant forms results in
increased prevalence of resistant forms [2013B]

Fluoroquinolones can lead to:


o Methicillin-resistant Staphylococcus aureus
(MRSA)
o
Clostridium difficile CDAD (Clostridium difficileassociated diarrhea, a.k.a pseudomembranous
colitis) [2013B]

o MDR-resistant GNB including P. aeruginosa


Third Generation Cephalosporin can lead to:
o Methicillin-resistant Staphylococcus aureus
(MRSA)
o Clostridium difficile CDAD

ANCHORES-ANDAL-ANDRADE (editor)

Vancomycin-resistant Enterococcus (VRE)


Extended-spectrum -lactamase (ESBL)
producing Klebsiella (due to Ceftazidime)

MDR Pseudomonas aeruginosa

GENERAL PRINCIPLES OF ANTIMICROBIAL


THERAPY: SELECTING AND INITIATING
ANTIBIOTIC REGIMEN
Empiric vs. Definitive Therapy
o Community-acquired
o Hospital-acquired infections

Site of infection

Organisms colonizing site

Is patient a carrier of such organism?

Local antibiogram
Every attempt should be made to narrow the
antibiotic spectrum

COMMON RISK FACTORS FOR NOSOCOMIAL


COLONIZATION/INFECTION WITH RESISTANT
S. AUREUS, ENTEROCOCCUS, GNB, C.
DIFFICILE, AND CANDIDA SPP

Advanced age
Comorbidity
Severity of illness
Inter-institutional transfer of patients (especially
from nursing homes)
Prolonged hospitalization
Gastrointestinal or transplant surgery
The presence of any invasive device (especially
central venous catheters)
Exposure to antibiotics (especially cephalosporins)

ANTIMICROBIAL STEWARDSHIP (AS)


Also known as Antimicrobial Management
Appropriate selection, dosing, and duration
of antimicrobial therapy to achieve optimal
efficacy in managing infections
An important tool in the effort to reduce
inappropriate use of antimicrobials and
subsequent development of both resistant
microorganisms and drug related adverse events
Used to describe the new attitude toward antibacterial
agents that must be adopted to preserve their
usefulness [Harrisons 18th ed]

Goals
o To optimize clinical outcomes while
minimizing unintended consequences of
antimicrobial use, including toxicity, selection
of pathogenic organisms, and emergence of
resistance
o To reduce healthcare costs without adversely
impacting quality of care

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WHY DOES IT MATTER?


200-300 million antibiotics are prescribed annually
o 45% for outpatient use
25-45% of hospitalized patients receive antibiotics
o At least 30% are unnecessary or sub-optimal
o 5% of hospitalized patients experience an
adverse reaction
>$1.1 billion spent annually on unnecessary adult
antibiotic prescriptions for URI
o 50-80% of outpatient antibiotic use is
inappropriate
Antibiotics are unlike any other drug
o Use of the agent in one patient can
compromise efficacy in another

BOTTOM LINE
Antimicrobial resistance is a critical patient safety
issue
Antimicrobial resistance is a public health threat
Antibiotics should be viewed as a limited resource
Physicians play the role of stewards
o Judicious prescription of quality antibiotics

RATIONAL ANTIBIOTIC USE


General principles

Stepwise logical approach to the selection of a


specific antibiotic

Involves antibiotic prescription using the


appropriate drug, dose, and duration
o When and only if it is beneficial to the patient
o Targeting therapy directed against specific
pathogens (use culture and sensitivity test and
gram stain) [2013B]

Goals
o To maximize therapeutic efficacy
o To minimize toxicity and the risk of developing
antimicrobial resistance

ANTIBIOTIC CHECKLIST
Q1: Is an antibiotic indicated on the basis of
clinical and laboratory findings?

ANCHORES-ANDAL-ANDRADE (editor)

Q2: Before antibiotics are initiated, have


appropriate clinical specimens been obtained,
examined, and cultured?
Q3: What organisms are most likely to be causing
the infection?
Q4: If several antibiotics are available to treat the
likely or known pathogen, which agent is best for
a particular agent? Which is best for a particular
patient?
Q5: Is an antibiotic combination appropriate?
Q6: What are the important host factors?
Q7: What is the appropriate dose?
Q8: What is the best route of administration?
Q9: Will initial therapy need modification after
culture data are available?
Q10: What is the optimal duration of therapy?

Q1: IS AN ANTIBIOTIC INDICATED ON THE


BASIS OF CLINICAL AND LABORATORY
FINDINGS?
Obvious bacterial infections
Probable bacterial infections
o Problematic
o Epidemiologic clues dietary habits, diseaseendemic areas like Malaria in Palawan [2013B]

Severity of signs and symptoms


Host factors
Urgency of the situation

Septic

Elderly

Febrile leukopenic patients

Possible IE
WARNING: Unnecessary treatment of viral
infections is a major source of excess
antibiotic use. Most fevers are caused by viral
o
o
o

infections. If there are no obvious signs of bacterial


infection (i.e. bacterial pneumonia cough,
crackles/rales, focal consolidation, infiltrates on CXR),
then do not give an antibiotic! [2013B]

GENERAL PRINCIPLES OF ANTIMICROBIAL


THERAPY: SELECTING AND INITIATING
ANTIBIOTIC REGIMEN
Obtaining an accurate ID diagnosis
o Site of infection, host definition, microbiologic
diagnosis
o Most likely microbiological etiology can be
inferred
o Consider non-infectious etiologies if not clear
cut
Timing and initiation of Antimicrobial Therapy:
Guided by Urgency
o In critically ill patients?
o In stable clinical circumstances?

PRESUMPTIVE THERAPY
Severe sepsis
Immunocompromised states

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Febrile neutropenia
Possible acute endocarditis
Known or suspected meningitis
Acute necrotizing cellulitis

ANTIMICROBIAL MISUSE
Common Misuses of Antibiotics
o Prolonged empiric treatment without clear
evidence of infection
o Treatment of positive culture in absence of
disease
o Failure to narrow antimicrobial therapy when
a causative organism is identified
o Prolonged prophylaxis
o Excessive use of certain antimicrobials
Prescribers
o Not all prescribing practices are judicious

2 Pennsylvania hospitals, 2-year period:


196 patients with viral infections (labconfirmed)
125 remained on antibiotics after viral
diagnosis
63% with normal CXR findings
Outcomes of antibiotic group
Longer hospital stay
Higher incidence of C. difficile
infection
Patients
o Inappropriate antibiotic seeking

Pressures providers

Develops misconception that antibiotics


cure viral infections
o Inappropriate use when prescribed
appropriately

Incomplete course

Save some doses later and self-treat

Q2: BEFORE ANTIBIOTICS ARE INITIATED,


HAVE APPROPRIATE CLINICAL SPECIMENS
BEEN OBTAINED, EXAMINED, AND
CULTURED?

ACTIONS:

Use proper antisepsis for blood and other


cultures

Culture the blood, not the skin or catheter


hub

Use proper methods to obtain and process


all cultures

Q3: WHAT ORGANISMS ARE MOST LIKELY TO


BE CAUSING THE INFECTION?
Focal findings
Prior culture data
Age
Neonatal meningitis: Most common agents:
Streptococcus agalactiae and E.coli (from the
mother); Treatment: Ampicillin and Gentamicin
[2013B]
o
Adult meningitis: Most common agents: Neisseria
meningitides, Streptococci, Listeria [2013B]
Severity of illness expanded list of possible
pathogens for immunocompromised patients [2013B]
o

Epidemiologic factors
o Nosocomial or healthcare-related infections
o Prior antibiotic use
o Staphylococcal infections (possibility of ORSA
Oxacillin-resistant Staphylococcus aureus)

Q4: IF SEVERAL ANTIBIOTICS ARE


AVAILABLE TO TREAT THE LIKELY OR KNOWN
PATHOGEN, WHICH AGENT IS BEST FOR A
PARTICULAR AGENT? WHICH IS ANTIBIOTIC
BEST FOR A PARTICULAR PATIENT?
WHICH AGENT IS BEST FOR A PARTICULAR
AGENT?
Drug of choice
o Literature
o Guidelines
o Clinical pathways

COMMUNITY ACQUIRED PNEUMONIA (CAP)


Potential Pathogens in CAP (2010)

Gram stain simple, cost-effective


Cultures obtain appropriate specimens
o Pre-treatment cultures can you use it? If the

o
o

patient was initially okay and doesnt have an


infection, then eventually deterioratedthen you
can use it. Make sure sample is good and reliable
[2013B]
Follow-up cultures can you use it? Most of the
time, it is not useful because you cannot do it with
a patient who is already infected [2013B]
How do you assess the quality of a sputum sample
by microscopy? If there is an epithelial cell count
of less than 10 per LPF (low power field), and a
WBC count of >25 per LPF [2013B]

Use Antimicrobials Wisely! Treat infection, NOT


contamination!
o FACT: A major cause of antimicrobial overuse
is treatment of contaminated cultures

ANCHORES-ANDAL-ANDRADE (editor)

Guidelines on the Diagnosis of CAP

Page 5 of 9

Meropenem
Fluoroquinolones

IV Ciprofloxacin

IV Levofloxacin

ANTIMICROBIAL RESISTANCE THE LOCAL


SCENARIO
Prevailing local susceptibility patterns
Use Antimicrobials Wisely! Use local data!
o FACT: The prevalence of resistance can vary
by locale, patient population, hospital unit,
and length of stay
o ACTIONS:

Know your local antibiogram

Know your patient population


Antimicrobial Resistance Surveillance Program
(ARSP)
Empiric Management of CAP (2010)

Trends in Antimicrobial Resistance among


Streptococcus pneumoniae isolates (19882009)

Benzylpenicllin

o
High Risk CAP Risk for Pseudomonas
aeruginosa infection
o History of chronic or prolonged (>7 days
within the past month)
o Use of broad spectrum antibiotic therapy
o Malnutrition
o Chronic Use of steroid therapy: >7.5mg/day
o Sever underlying bronchopulmonary disease
(COPD, bronchiectasis)
Antipneumococcal Antipseudomonal lactam
o IV antipneumococcal antipseudomonal
Cephalosporin

4th gen cephalosporin (Cefepime,


Cefpirome)
o IV antipneumococcal antipseudomonal BLIC

Cefoperazone-sulbactam

Ticarcillin-Clavulanic acid

Piperacillin-tazobactam
o IV antipneumococcal antipseudomonal
Carbapenem

Imipinem-cilastatin

ANCHORES-ANDAL-ANDRADE (editor)

Trends in Antimicrobial Resistance among


Pseudomonas aeruginosa isolates (19882009)

Ciprofloxacin (yellow square)

Ceftazidime (green triangle)

Imipinem (blue diamond)

Increasing resistance to antibiotics like


ciprofloxacin. Pathogen is most common in
alcoholics. DOC is imipinem and ceftazidime
[2013B]

Trends in Antimicrobial Resistance among


Haemophilus influenza (2003-2009)

Cotrimoxazole (green)

Chloramphenicol (purple)

Ampicillin (blue)

In 2008/2009, resistance rate of S. pneumonia


to penicillin is virtually 0%. That is why penicillin
is still the drug of choice [2013B]

There is increasing resistance to co-trimoxazole,


chloramphenicol, and ampicillin, compared to 3
years ago [2013B]

Trends in Antimicrobial Resistance among


Klebsiella spp (1992-2009)

Ceftriaxone (yellow square)

Ciprofloxacin (purple circle)

Cefepime (light blue diamond)

Imipinem (red diamond)

Increasing resistance to antibiotics like


ceftriaxone and ciprofloxacin. Pathogen is most

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common in alcoholics. DOC is imipinem and


ceftazidime [2013B]

that are within their spectrum


of activity [Harrisons 18th ed]

Depend less on host


factors
PREFERRED if host is
immunocompromised

Depend on adequate host


mechanisms
Partially inhibited
organism may survive,
replicate, produce
recurrent disease

Necessary for severe, lifethreatening infections,

Adequate for the treatment


of most infections [Harrisons
18th ed]

patients with altered immune


system, protected infectious
foci (endocarditis, meningitis)
or specific infections
[Harrisons 18th ed]

Penicillins,
cephalosporins,
aminoglycosides,
vancomycin,
aztreonam,
carbapenems,
fluoroquinolones,
metronidazole

Erythromycin,
clindamycin,
tetracycline,
sulfonamides,
chloramphenicol

Q5: IS AN ANTIBIOTIC COMBINATION


APPROPRIATE?
Infections in which multiple organisms are likely
or proved
o Intra-abdominal infections
o Complicated or life-threatening infections,
including healthcare-related forms
Synergism
o Trimethoprim-sulfamethoxazole inhibits
o

sequential steps in folic acid synthesis [2013B]


Penicillin + gentamicin against Enterococci,
Streptococci, and Pseudomonas [2013B]

Limiting or preventing emergence of resistance


Disadvantages:
o risk of drug sensitivities or toxicity
o risk of colonization with a resistant bacteria
o Possibility of antagonism

Penicillin + tetracycline tetracycline has a


negative effect on penicillin efficacy. Penicillin
is a bactericidal agent requiring active dividing
bacteria to be effective, while tetracycline is a
bacteriostatic agent, thus reducing the activity
of the bacteria, thus reducing the ability of
penicillin to affect it [2013B]

WHICH ANTIBIOTIC IS BEST FOR A


PARTICULAR PATIENT
Antibiotic allergies
Antibiotic penetration
o pH of the site of infection Aminoglycosides will
not be effective in abscesses because it will not be
active in acidic pH of that area [2013B]
Potential side effects Aminoglycosides and
vancomycin are nephrotoxic [2013B]
Cost generic drugs [2013B]

o Frequency of administration
o Number of antibiotics
o Administration costs: IV>IM>PO
o Narrow vs. Broad spectrum
Bactericidal vs. Bacteriostatic
BACTERICIDAL
Inhibit bacterial
replication; kill the bacteria

BACTERIOSTATIC
Inhibit bacterial growth

ANCHORES-ANDAL-ANDRADE (editor)

o
o

-lactam + -lactam
Higher costs
False sense of security

Q6: WHAT ARE THE IMPORTANT HOST


FACTORS?
Genetic factors G6PD deficient patients are prone
to hemolysis if given primaquine [2013B]

Pregnancy and lactation increased volume of


distribution hence need to increase dose [2013B]

o Lower overall serum drug levels


o Risk of fetal toxicity
Renal function creatinine clearance
Liver function

Page 7 of 9

EXCRETED BY THE
KIDNEYS
Aminoglycosides

EXCRETED BY THE
LIVER
Cefoperazone only
cephalosporin excreted by
the liver [2013B]

Aztreonam
Chloramphenicol
Cephalosporins
Clindamycin
Carbapenems
Doxycycline
Quinolones
Erythromycin
Penicillin
Metronidazole
Trimethoprim
Nafcillin
Vancomycin
Rifampicin
Tetracycline
Sulfamethoxazole
Presence or indwelling device
Humoral and cellular host defense mechanisms
Previous antibiotic use and response to such
Underlying illnesses
o DM
o COPD/Bronchiectasis

Q7: WHAT IS THE APPROPRIATE DOSE?


The LOWEST dose of antibiotic that will be
EFFICACIOUS is used
o Site, type, and severity of infection
o Organisms involved
Dosage adjustment based on age, renal and
hepatic function

Q8: WHAT IS THE BEST ROUTE OF


ADMINISTRATION?
Parenteral for severe disease [2013B]
o IV vs. IM
o Continuous vs. Intermittent bolus IV infusion

Intermittent bolus IV infusion usually used for lactam antibiotics [2013B]


-lactam antibiotics and macrolides [2013B]

time-dependent bactericidal activity


Aminoglycosides and
Fluoroquinolones concentration
dependent bactericidal activity, highest
dose once a day [2013B]

Oral/Enteral for mild disease [2013B]


o For mild infections and infections treatable on
outpatient basis

Absorption may be impaired by meals,


antacids, and histamine agonists for some
drugs
o Poorly absorbed:

Amphotericin B

Vancomycin

Aminoglycosides
o Good bioavailability:

Fluoroquinolones

Metronidazole

Clindamycin

Chloramphenicol

Fluconazole

Linezolid

ANCHORES-ANDAL-ANDRADE (editor)

DETERMINED BY:
Availability and affordability
Nature and site of infection
Probable organism
o Antimicrobial resistance in the local setting
(hospital/specific unit)
Pk/Pd
o Patient tolerability and side effects

MIC = minimum inhibitory concentration concentration


that completely inhibits growth of organisms
AUC = area under the serum concentration curve
AUC:MIC = quantify serum level time course, not killing
activity
[2013B]

Q9: WILL INITIAL THERAPY NEED


MODIFICATION AFTER CULTURE DATA ARE
AVAILABLE?
Clinical response to therapy?
o Narrow- versus broad-spectrum agent
Multiple negative initial cultures
o Consider atypical pathogens (Legionella

infection for moderate to severe pneumonia)


[2013B] or non-infectious causes

Assessment after antibiotics are initiated


response and side-effects [2013B]

Differentiate between colonization and


infection colonization is presence of a pathogen,
infection is presence of a pathogen producing
disease [2013B]
If the patient is responsive to the initial treatment,
then choose a drug with good oral bioavailability
[2013B]

Q10: WHAT IS THE OPTIMAL DURATION OF


THERAPY?
Possibility of switch therapy after 24-48
hours
Duration
o Well established or empiric may be
individualized
o Treat for an adequate period to reduce
likelihood of COLLATERAL DAMAGE
Depends on:
o Type of infecting organism

For Staphylococcus, a minimum of 3 weeks


For fungal pathogens, 2 weeks after a negative
culture
For tuberculosis, 6 months

Page 8 of 9

[2013B]

Location and extent of infection

CNS infections have longer treatment durations


than pneumonia
Infective endocarditis has variable treatment
durations which depend on the etiologic agent.
Streptococcal endocarditis must be treated
for a minimum of 2 weeks. Staphylococcal
endocarditis must be treated for a minimum of
4-6 weeks

Osteomyelitis must be treated for a minimum


of 6 weeks
[2013B]

o Immunocompetence of the patient


Use Antimicrobials Wisely! Stop treatment when
infection is cured or unlikely!
o FACT: Failure to stop unnecessary
antimicrobial treatment contributes to
overuse and resistance

TREATMENT FAILURE

Pathogen resistant to the antibiotic


Wrong dose/route of administration
Wrong diagnosis
Abscess/pus/necrotic tissue
Secondary infection
Prosthetic device(s)

SUMMARY

ANCHORES-ANDAL-ANDRADE (editor)

Careful patient evaluation regarding the need for


antibiotic therapy
Antibiotic selection based on likely etiologic agent
involved
Other factors (host, drug) must be considered
Narrow-spectrum antibiotic preferred and step
down therapy once feasible
----------END OF PART 2---------QUIZ:
1. Example of concentration-dependent antibiotic
Aminoglycosides and Fluoroquinolones
2. Antibiotic that is primarily excreted in the liver
Cefoperazone, Chloramphenicol, Clindamycin,
Doxycycline, Erythromycin, Metronidazole, Naficillin,
Rifampicin, Sulfamethoxazole
3. Rational combination antibiotic therapy
Trimethoprim-sulfamethoxazole, Penicillin-gentamicin
SOURCES:
Dr. Rosarios PDF files on IC
2013 B Transcription (Lecturer: Dr
Panaligan)
Harrisons 18th ed
SHOUTOUTS:
HAPPY 50TH BIRTHDAY SIGMA BETA!!! = LOVE
LOYALTY & SISTERHOOD
HAPPY BIRTHDAY NINA CONSTANTINO!!!

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