RATIONAL USE OF

ANTIBIOTICS
Hesty Utami,M.Clin Pharm,PhD.,Apt
 The rational use of medication

General principles of antibiotic use

OVERVIEW Prophylaxis use of antibiotic

Use of antibiotic in Pregnancy

Antibiotic failure

Antibiotic resistance

Antibacterial stewardship
RATIONAL USE OF MEDICATIONS
• Safety
• Efficacy
• Cost-effectiveness
• Availability
• Suitability and convenience
Efficacy & safety must be considered when evaluating the risk :
benefit ratio of a particular treatment modality. The risk :
benefit ratio depends on the following factors:
The seriousness of the diseases
The consequences of not treating the disease
The efficacy of the drug
The seriousness & frequency of adverse effects associated with drug use
The efficacy of alternative drugs or non drug therapy
The side effects profile of alternative drugs
 GENERAL PRINCIPLES OF ANTIBIOTIC
USE

• Why and When to use it?

• Which antibiotics to use?
Factors in antibiotics selection
• How to use it?
Dosing calculation, route, dosage form, duration of
treatment, single vs combination
• What are the adverse effects of the antibiotics?
GENERAL PRINCIPLES OF AB USE: WHY
AND WHEN?
• Use antibiotics only when there is clear evidence or strong
suspicion of an infection that will not be resolved unaided.
• Before starting an Ab, take a specimen for culture and
sensitivities if appropriate.
• If using empirical treatment ⇒ base the treatment on
knowledge of local patterns of likely pathogens and local
susceptibility. Consider drug allergy/ADR history and
hepatic/renal function.
• Never treat viral infections with Ab ⇒ there is no evidence that
Abs prevent secondary bacterial infection (e.g. Viral URTI)
• If the clinical situation is acute or the patient is seriously
immunocompromised, treatment should be initiated
immediately after appropriate samples of culture have been
taken.
• If the patient is stable and delaying therapy will not
adversely affect outcome ⇒ the treatment may be
postponed until a definitive diagnosis is made.
 GENERAL PRINCIPLES OF AB USE:
WHICH ABS TO USE?

Factors in Ab selection:
1. Spectrum
2. Tissue penetration
3. Concurrent diseases
4. Safety profile
5. Cost
FACTORS IN AB SELECTION: SPECTRUM

• Antibiotic spectrum refers to the range of

microorganisms an antibiotic is usually effective
against and is the basis for empiric antibiotic
therapy
• Newer, broad spectrum or more expensive
antibiotics are not necesarily better
 FACTORS IN AB SELECTION: TISSUE
PENETRATION

• Abs that are effective against a micoorganism in vitro but unable to

reach the site of infection ⇒ little/no benefit
• Ab tissue penetration depends on properties of the Ab (e.g. lipid
solubility, molecular size) and tissue (e.g. Adequacy of blood supply,
presence of tissue inflammation)
• Ab tissue penetration is rarely problematic in acute infections due to
increased microvascular permeability from local release of chemical
inflammatory mediators.
• In chronic infections often rely on chemical properties of Ab.
• Abs cannot eradicate organism for areas that are difficult to penetrate
or have impaired blood supply (e.g. Abscesses) ⇒ surgical drainage.
 FACTORS IN AB SELECTION:
CONCURRENT DISEASES

• The presence of renal and/or hepatic impairment may

influence both the choice of antibiotic and the dose.
• Drugs excreted renally will usually require some form
of dose modification (e.g. Creatinine clearance < 30
mL/minute)
• Abs that are potentially hepatotoxic (e.g. Rifampicin,
flucloxacillin) should be used with caution in patients
with underlying liver disease.
 FACTORS IN AB SELECTION: COST

• Switching early from IV to PO

• Using antibiotics with long half-lives
• Choosing monotherapy over combination
therapy if appropriate
GENERAL PRINCIPLES OF AB USE: HOW
TO USE IT? ⇨ DOSING

• Usual dose schedule is adequate for most infections.

• In general, sicker people do not require higher dose than
people with less severe infection.
• Higher dose may be necessary when:
The infecting organism is proven or suspected to have reduced
susceptibility.
Altered drug kinetics are likely (e.g. Crush injuries, serious burns)
Drug distribution to the site of infection may be compromised (e.g.
Abscess), subarachnoid space, intracellular (e.g.TB), necrotic tissue,
vitreous humor.
GENERAL PRINCIPLES OF AB USE: HOW TO USE IT & WHAT TO
CONSIDER IN RENAL IMPAIRMENT/CKD?
Patients with CKD may have alterations in their protein binding, volumes of
distribution, kidney clearance → antibiotic dose adjustment to prevent toxicity.
Dialysis comes with additional consideration → there are increased period of
clearance during dialysis followed by 48-72 hrs little antibiotic clearance
between dialysis sessions.
Different pharmacodynamic goals of different antibiotics → such as
maximizing the free peak : MIC ratio (for concentration-dependent
antibiotics) or maximizing the time that free antibiotic concentration
spend above MIC (for time-dependent antibiotics) → require different
adjustment strategies.
Knowing the pharmacodynamic properties of antibiotics can be essential to
decide whether to decrease the dose and keep the dosing frequency
constant (preferred with time-dependent antibiotics) → or keep the same
dose and prolong the dosing interval (preferred with concentration-
dependent antibiotics)
PHARMACODYNAMIC PARAMETERS ON A
CONCENTRATION-TIME CURVE
 Antibiotic Class Pharmacodynamic profile Parameters to Optimize

Aminoglycosides Concentration-dependent Peak:MIC

Penicillins Time-dependent Time>MIC

Cephalosporins Time-dependent Time>MIC

Carbapenems Time-dependent Time>MIC

Vancomycin Time-dependent AUC:MIC

Lipopeptides Concentration-dependent AUC:MIC; peak:MIC

Oxazolidinones Time-dependent AUC:MIC

Lipoglycopeptides Concentration-dependent AUC:MIC

Fluoroquinolones Concentration-dependent AUC:MIC

Macrolides Time-dependent AUC:MIC

Sulfamethoxazole- Limited data Limited data

trimethoprim
GENERAL PRINCIPLES OF AB USE: HOW
TO USE IT?

Dosing modification in hepatic impairment:

Ab dosing for patients with hepatic impairment is problematic ⇨ no
hepatic parameters to accurately assess liver function.
In practice, Ab dosing is based on clinical assessment of
the severity of liver disease.
Dosing adjustments are usually not required for mild or
moderate hepatic impairment.
For severe hepatic impairment ⇨ decrease total daily dose of
hepatically-eliminated Ab by 50%.
Alternatively ⇨ use Ab eliminated by the renal route in usual route.
MAJOR ROUTE OF ELIMINATION

Hepatobiliary Renal
Chloramphenicol Most β lactams
Ceftriaxone Aminoglycosides
Moxifloxacin Trimethoprim-
Macrolides sulfamthexazole
Clindamycin Carbopenem
INH Ciprofloxacin
Rifampin Colistin
Ethambutol Tetracycline
pyrazinamide Vancomycin
 GENERAL PRINCIPLES OF AB USE: HOW
TO USE IT? ⇨ ROUTE

• Oral route is adequate for most infections.

• Ab route of administration must be evaluated daily & conversion from
IV to oral should be attempted when there is evidence of clinical
improvement.
• Exceptions can be applied in certain conditions:
✓ The oral route is unavailable (e.g. Unconscious patient)
✓ Absorption is unreliable (e.g. Vomiting)
✓ Inadequate drug concentration at the site of infection with oral/rectal administration
✓ Serious infections (e.g. Meningitis, sepsis) or those associated with circulatory
decompensation ⇨ IV therapy
 GENERAL PRINCIPLES OF AB USE: HOW TO
USE IT? ⇨ DURATION OF TREATMENT

• Be guided by nature and severity of infection, and

clinical state of the person.
• Generally treat until major signs & symptoms of
infection have resolved, clear clinical improvement is
evident and lab indices show a trend towards normal.
• If clinical response is slower than expected ⇨review
the initial diagnosis and/or Ab choice
Duration of Treatment Indications
Short course (<5 days) Bacterial gastroenteritis, malaria,
uncomplicated UTIs

Longer course (5-10 days) Bacteremia, cellulitis, meningitis,

peritonitis, pneumonia, tonsillitis

Extended course (> 10 days) Bacterial endocarditis, TB, neutropenic

fever, osteomyelitis, infections in
immunocompromised people (e.g.
SLE, HIV, cancer)
 GENERAL PRINCIPLES OF AB USE: HOW TO
USE IT? ⇨ SINGLE VS COMBINED TREATMENT

• Monotherapy is preferred to combination therapy for

nearly all infections.
• In addition to cost savings, monotherapy results in less
chance of medication error and fewer drug
interactions.
• Combination therapy may be useful for drugs synergy
or for extending spectrum beyond what can be
obtained with a single drug (e.g. Prevent resistance in
TB, skin and soft tissue infections in diabetics).
 MONITORING THERAPEUTIC RESPONSE

• All patients receiving Abs should be monitored for resolution of

infectious signs & symptoms (e.g decreased temperature & white cell
count) and adverse drug events (e.g nephrotoxicity with
aminoglicosides)
• Patients not responding to an appropriate Ab treatment in 2-3 days
should be re-evaluated to ensure:
✓ The correct diagnosis
✓ That therapeutic drug concentrations are being achieved
✓ That the patient is not immunocompromised
✓ That the patient does not have isolated infection e.g abscess
✓ That the resistance has not developed
 PROPHYLAXIS USE OF ANTIBIOTICS

• Restrict to certain clinical conditions for example surgical procedure

with high risk of infections or where the consequences of infections
are severe (e.g. Prosthesis)
• Base drug choice on knowledge of local patterns of likely pathogens
and local susceptibility data.
• Ab prophylaxis can be used in non-surgical and surgical settings.
• Non-surgical prophylaxis may include frequent recurrent UTIs,
contacts of people with meningococcal or h. Influenzae type b
meningitis, selected contacts of active Tb, post splenectomy, certain
cancer, primary & secondary prophylaxis of opportunistic infections in
HIV infected individuals.
 SURGICAL AB PROPHYLAXIS

• Cover is not required for all possible pathogens.

• Aim to prevent infection by achieving high drug tissue
concentration at the time of surgical procedure and
maintain throughout “the vulnerable period” (i.e time
between skin incision and skin closure) .
• When no infection exists prior to surgery ⇨ single doses
are usually sufficient.
• Second dose or up to 24 hrs treatment may be required
when procedures are delayed or prolonged.
SURGICAL PROCEDURES REQUIRING
AB PROPHYLAXIS

• Amputation of gangrenuous limb

• Coronary artery bypass and cardiac valve surgery
• Insertion of prosthetic devices
• Selected obstetric and gynaecological procedures
• Deep laceration penetrating to joint cavities
 USE OF ANTIBIOTICS IN PREGNANCY

• Antibiotics such as beta-lactams, vancomycin,

nitrofurantaoin, metronidazole, clindamycin and Fosfomycin
are generally considered safe and effective in pregnancy.
• Fluoroquinolones and tetracyclines are generally avoided.
• Physiologic changes in pregnancy lead to an increase in GFR,
increased total body volume and enhanced cardiac output
→ pharmacokinetic alteration that may require dose
adjustment or careful monitoring & assessment
 CAUSE OF ANTIBIOTIC FAILURE
Microbiological ✓In vitro susceptibility but ineffective in vivo
factors ✓Ab tolerance with gram + cocci
✓Treating colonization (not infection)

Antibiotic factors ❑Inadequte spectrum/coverage

❑Inadequate Ab blood level

Antibiotic penetration ❖Undrained abscess

problems ❖Foreign-body related infection
❖Protected areas (e.g. Cerebrospinal fluid)
❖Diminished blood supply (e.g. Chronic osteomyelitis)
Non-infectious disease Medical diorders mimicking infections (e.g. SLE)

Antibiotic-unresponsive ▪ viral infections

infectious disease ▪Fungal infections
 ANTIBIOTIC RESISTANCE

• Bacterial resistance to antibiotic may be classified as

natural/intrinsic or acquired.
• Pathogens not covered by the usual spectrum of an antibiotic
are termed naturally/intrinsically resistant (e.g. 25% of
S.pneumoniae are naturally resistant to macrolide)
• Acquired resistance refers to a previously susceptible
pathogen that is no longer susceptible to an antibiotic e.g.
Ampicillin-resistant H. Influenzae.
• Any use of antibiotic allows the development of resistance to
it.
 ANTIBIOTIC RESISTANCE

• Multidrug resistance to common clinical pathogens is a

growing problem worldwide. Widespread and indiscriminate
use of broad-spectrum antibiotic is a major contributor.
• Succesful antibiotic resistance control strategies including:
Judicious use of antibiotics narrow spectrum for proven clinical situation
Eliminating antibiotics from animal feeds
Microbial surveillance to detect resistance problems early.
Antibacterial stewardship
 ANTIBACTERIAL STEWARDSHIP (AS)

• Multidrug resistance is a significant issue ⇨

increased morbidity, mortality and
healthcare costs.
• IN 2010, the WHO recognised Ab
resistance as 1 of the 3 greatest threats
“Antibacterial resistance is a global problem, and
to human health.
antibiotic stewardship programs are the global
• 50% of Ab use is inappropriate.
solution”

Pharmacy Practice news, August 2012

 WHAT IS ANTIBIOTIC STEWARDSHIP?

“Coordinated interventions designed to improve

& measure the appropriate use of antibacterial
agents by promoting the selection of the optimal
antibacterial drug regimen including dosing,
duration of therapy and route of administration”

The Society of Healthcare Epidemiology of America (SHEA), the

Infectious Disease Society of America (IDSA) & the Pediatric
Infectious Disease Society (PIDS) Policy Statement on Antibacterial
Stewardship, April 2012
 GOAL OF ANTIBACTERIAL
STEWARDSHIP

• Primary goal: to optimise outcomes while

minimising unintended consequences of
antibacterial use.
• Secondary goal: to reduce health-care costs
without adversely impacting quality of care.
 IT

Supplemental Microbiology
strategies lab

6 elements
of AS

Monitor
Active process &
strategies measure
outcome

Multidisciplinary
team approach
 1. ACTIVE STRATEGIES

• Prospective audit of antibacterial use

• Formulary restriction and preauthorization
requirement for specific agents (e.g. Utilise the
Pharmacy and Therapeutic Committee)
 2. SUPPLEMENTAL STRATEGIES

• Education
o Most frequently employed intervention
o Will enhance the acceptance of stewardship strategies
• Dose optimisation
• Guidelines and Clinical Pathway
Development of evidence-based practice guidelines that
incorporate local microbiology and resistance pattern
• IV to PO conversion
 3.IT

• Clinical decision support e.g. Computerised

physician order entry/CPOE, electronic medical
record
• Computer surveillance: tracking of resistance
pattern, identification of nosocomial infections.
 4. MICROBIOLOGY LABORATORY

• Timely identification of pathogens

• Performance of susceptibility testing
• Assists infection control efforts in resistance
surveillance
 5. MONITORING OF PROCESS AND
MEASUREMENT OF OUTCOME
Useful in
Did the intervention determining the
result in the desired impact on Ab use
Process
change in antibiotic use & resistance
Monitoring
pattern

Did the process

Outcome implemented
Measure reduce/prevent
unintended
consequences
6. MULTIDISCIPLINARY TEAM APPROACH

Care Team
Members
✓Infectious Disease
(ID)Physician
✓Clinical pharmacist with
ID training
✓Clinical microbiologist
✓Information system
specialist
✓Hospital epidemiologist
 PHARMACIST ROLE IN ANTIBACTERIAL
STEWARDSHIP
• Promoting optimal use of antibacterial agents
Work within the P&T Committee to ensure the availability of Ab
Work with lab personnel to ensure timely reporting of susceptibility test
Facilitate safe medication management process

• Reducing transmission of infections

Participate in the Infection & Prevention Control Committee
Establish internal pharmacy policies to prevent contamination of pharmacy products

• Educating health professionals, patients and the public

Provide educational forums for healthcare personnel on stewardship-related topics
Educate & counsel patients regarding adherence to prescribed Ab
Participate in public health education & awareness program
FIND & DISCUSS ANTIBIOTIC USE AS THE
PART OF TREATMENT GUIDELINES FOR:

• Surgical prophylaxis
• Recurrent urinary tract infection
• Pneumonia (Hospital-acquired)
• Community-acquired)
• Bacterial meningitis
• Neutropenic fever
• Peritonitis
• HIV co-infection (TB, Hep B)
• Septic Shock