ANTIBIOTICS

CONTENTS – PART - I
1. Introduction

2. Bacterial Morphology, Metabolism & Physiology

3. Identification Of Infectious Agents In The Diagnostic Laboratory

4. Steps in isolation and identification

5. Antibiotic susceptibility testing

6. Immunological Methods

7. Molecular Detection Methods

1. PCR Detection

2. Real Time PCR Quantification

3. Microbial Fingerprinting

8. Whole Cell Analysis

1. Fluorescent In Situ Hybridisation (FISH)

2. Flow Cytometry

 INTRODUCTION:

 The term antibiotic came from the word antibiosis coined in 1889 by Louis Pasteur's
pupil Paul Vuillemin which means a process by which life could be used to destroy
life.
  Defined as chemical substances produced by various species of microbes such as
bacteria & fungi, in low concentrations destroy or inhibit the growth of other species
of microbes.

Anti = against

Bios = life

 Miracle Cure?

 Before the 1930s there were no treatments for bacterial infections

 Following the discovery of penicillin industry started searching for more

antibiotics in nature

 Surgeons could attempt more dangerous operations

 Miracle Cure?

 Many antibiotics prescribed by the doctor are broad spectrum

 These kill the body’s good bacteria as well as the bad

 When the good bacteria gone there is more room for bad microbes to invade!

 Classification of Bacteria

 Morphological classification

Bacteria can be classified into six major groups on morphological basis.

1. TRUE BACTERIA Cocci – These are spherical or oval cells. On the basis of
arrangement of individual organisms they can be described as

 Monococci (Cocci in singles) – Monococcus spp.

 Diplococci (Cocci in pairs) – Streptococcus pneumoniae

 Staphylococci (Cocci in grape-like clusters) – Staphylococcus aureus

 Streptococci (Cocci in chains) – Streptococcus pyogenes

  Tetrad (Cocci in group of four) - Micrococcus spp.

 Sarcina (Cocci in group of eight)

 Bacilli – These are rod-shaped bacteria. On the basis of arrangement of organisms,

they can be described as

 Diplobacilli

 Streptobacilli

 Palisades

 Chinese-letter form

 Coccobacilli

 Comma-shaped

 Arrangement of bacteria: Cocci

2. ACTINOMYCETES (actin- ray, mykes-fungus)

These are rigid organisms like true bacteria but they resemble fungi in that they
exhibit branching and tend to form filaments.

They are termed such because of their resemblance to sun rays when seen in tissue
sections.

3. Spirochaetes

These are relatively longer, slender, non-branched microorganisms of spiral shape

having several coils.

4. Mycoplasmas

These bacteria lack in rigid cell wall (cell wall lacking) and are highly pleomorphic
and of indefinite shape.

They occur in round or oval bodies and in interlacing filaments.

5. Rickettsiae and Chlamydiae

 These are very small, obligate parasites, and at one time were considered closely
related to the viruses. Now, these are regarded as bacteria.

 Based on Anatomical features

 Capsule

 Capsulate– Streptococcus pneumoniae

 Non-capsulate – Viridans streptococci

 Flagella

 Flagellate –

 Monotrichous

 Lophotrichous

 Amphitrichous

 Peritrichous

 Aflagellate – Shigella spp.

 Based on Staining reaction

 GRAM’S STAIN

 Gram-positive cocci – Staphylococcus aureus

 Gram-negative cocci – Neisseria gonorrhoeae

 Gram-positive rods – Clostridium spp.

 Gram-negative rods – E. coli

 ACID FAST STAIN

 Acid-fast bacilli –Mycobacterium tuberculosis

 Non-acid-fast bacilli – Staphylococcus aureus

 Based on Cultural characteristics

 Extra growth factors requirements

 Fastidious – Hemophilus influenzae

 Non-fastidious – Escherichia coli

 Hemolysis on Sheep Blood Agar

 Alpha-hemolysis – Streptococcus pneumoniae

 Beta-hemolysis – Streptococcus pyogenes

 Utilization of carbohydrates

 Oxidative - Micrococcus

 Fermentative – Escherichia coli

 Based on Cultural characteristics

 Growth rate

 Rapid growers– Vibrio cholerae

 Slow growers – Mycobacterium tuberculosis

 Pigment production

 Pigment producer – Staphylococcus aureus

 Pigment non-producer – Escherichia coli

 Based on Nutrition

• Autotrophs

• Heterotrophs

 Based on environmental factors

 Temperature
 Oxygen dependence

 pH

 Salt concentration

 Atmospheric pressure

 Temperature

• Psychrophiles (15-200C) – Pseudomonas fluorescens

• Mesophiles (20-400C) – Escherichia coli, Salmonella enterica, Staphylococcus

aureus

• Thermophiles (50-600C)- Bacillus stearothermophilus

• Extremely thermophiles (as high as 2500C)

 Oxygen dependence

• Aerobe (grow in ambient temperature, which contains 21% O2 and a small amount of
CO2, 0.03%)

• Obligate aerobes – Strictly require O2 for their growth (Pseudomonas aeruginosa)

• Microaerophilic (grow under reduced O2, 5-10% and increased CO2, 8-10%)-
Campylobacter jejuni, Helicobacter pylori

 Oxygen dependence

 Facultative anaerobe (capable of growing either in presence or absence of O 2)- E.

coli

 Obligate anaerobe – Clostridium spp.

 Capnophilic (require increased concentration of CO2, i.e., 5-10%) –

H. influenzae,

N. gonorrhoeae

 Aerotolerant
  ph

 Acidophiles (Lactobacillus acidophilus)

 Alkaliphiles (Vibrio)

 Neutralophiles (pH 6-8)

Majority of the medically important bacteria grow best at neutral or slightly alkaline reaction
(pH 7.2-7.6)

 Bacterial Cell

 Cell envelope

 Cell wall- murein sacculus

 Outer

 Cell membrane-plasma membrane, cytoplasmic membrane

 Capsule

 Difference Between Gram-Negative

and Gram-Positive Bacteria

 Special components of Gram positive cell wall

Teichoic acid

 Cell wall

 Peptidoglycan

 N acetyl glucosamine & N acetyl Muramic acid

 Protect the cell from osmotic changes

 Rigidity

 Multilayered in Gram positive

  Teichoic acid

 Mono to bi layered in Gram negative

 Cell membrane


CYTOPLASM

 Nucleiod

 Chromosomal DNA

 Plasmids

 Inclusion bodies

 Storage of excess food and energy

 Metachromatic granules/ Babes ernst granules

 Much granule

 Spores

 Resist adverse condition

 Ribosome – 70s-50s & 30s

 Capsule

 Polysaccharide

 Antiphagocytic

 antigenic

 Virulence

 Pili

 Common pili- fimbriae

  Sex pili- conjugation

 antigenic

 Pili

 Pili are hair-like projections of the cell , They are known to be receptors for certain
bacterial viruses. Chemical nature is pilin

 Classification and Function

a. Common pili or fimbriae: fine , rigid numerous, related to bacterial adhesion

b. Sex pili: longer and coarser, only 1-4, related to bacterial conjugation

 Flagella

Monotrichate/Amphitrichate/Lophotrichate/Peritrichate

 Plasmid

 Nucleus

 Lacking nuclear membrane, absence of nucleoli, hence known as nucleic material or

nucleoid, one to several per bacterium.

 Endospores

 Resistant structure

 Heat, irradiation, cold

 Boiling >1 hr still viable

 Takes time and energy to make spores

 Location important in classification

 Central, Subterminal, Terminal

 Endospores (spores)
  Spores

 Spores can also survive very high or low temperatures and high UV radiation for
extended periods. This makes them difficult to kill during sterilization.

 Spores are produced only by a few genera in the Firmicutes:

 Bacillus species including anthracis (anthrax) and cereus (endotoxin causes ~5% of
food poisoning)

 Clostridium species including tetani (tetanus), perfringens (gangrene), and botulinum

(botulism: food poisoning from improperly canned food)

 Summary of the differences between Gram positive

& Gram negative bacteria

 Polymerase Chain Reaction (PCR):

 In principle: detection of one m.o. is possible within 3 hours

 But: Only presence/absence analysis

à no quantification!

‘Real Time’ quantitative PCR: fluorescence signal corresponds with the amount of
application product

 ‘Real Time’ quantitative PCR, ‘Cross over’ point:

 Number of cycles where the fluorescence signal is stronger then the

background

 Depends of the original amount of target DNA

 Benefits of Real-Time PCR:

 Accurate and reproducible nucleic acid quantification

 Large dynamic range of detection

 Closed-tube chemistries
  No electrophoresis

 No post-PCR processing

 High Sample throughput

à Mostly used for the detection of pathogens

 Fingerprinting techniques:

 Allows a separation of DNA fragments based on their sequence

 Different sequence = different species

 Fingerprinting techniques: comparison of separation techniques

Application of fingerprinting techniques

 Monitoring mixed microbial communities

 One band = one species

 Whole cell analysis

 Direct counts by fluorescent staining

Fluorescent in situ hybridisation (FISH)

DNA-probes: fluorescent labeled desoxyoligo-nucleotides specific for the target organism

 FISH: analysis of the samples with…

 Fluorescent in situ hybridisation (FISH):

 Detection limit is determined by the volume that is analysed

 Samples can be concentrated:

1 liter sample over a filter à 1 propagule/L

 Observation: microscopy

 Counting: flow cytometry (50.000 cells/sec)

  Results can be obtained in 2 to 3 hours

 Fast analysis by flow cytometry

 Principle: fluorescent stained cells are detected as single events by a laser

 Flow cytometry: live dead staining

 Application flow cytometry

 Portable detection systems:

Portable flow cytometers with automated sample preparation

 CONTENTS – PART - II

1. Antibiotics - History

2. Ideal Qualities of Antimicrobial Agent

3. Importance of Antibiotics

4. Classification of antibiotics

• MOA

• Adverse Effects

• Indication & Contraindications

5. Conditions for rational use of antibiotics

6. Principles of Antibiotic Therapy

7. Antibiotic Resistance

8. Policy to deal drug resistance

 ANTIBIOTICS

 A BRIEF HISTORY OF ANTIBIOTICS

• 1928 - Scottish microbiologist A. Fleming discovered penicillin - P. notatum.

• 1940 - British W. Florey and Chain received penicillin E.

 • In 1945, Fleming, Florey, Chain received the Nobel Prize for the discovery of
penicillin.

• 1942 - Z. Yermolyeva - Penicillin crustosum.

• 1944 - American Z. Waxman – streptomycin.

• 1960-1980 - cyclosporine, rifampicin, semisynthetic penicillins, tetracyclines,

macrolides, azalides.

• Today ≈ 6 thousand antibiotics. But, 2-3% of them are use.

• ~ recent year: modifying old drugs, finding new discipline in antibacterial combats.

IMPORTANCE OF ANTIBIOTICS:

 The elimination of the global crisis of infectious diseases (cholera, plague, dysentery).

 Effective at the dangerous diseases (sepsis, meningitis, peritonitis, pneumonia).

 ≈ 20 million people die each year from infectious diseases.

 1/3 of all hospital patients are treated with antibiotics.

 Over the past 20 years there were 20 new infectious diseases (Legionnaires' disease,
hairycell leukemia, hemorrhagic fever and others).

 Unconventional use of antibiotics: peptic ulcer, asthma, myocardial infarction,

atherosclerosis.

 In breadth of application group of antibiotics ranked the first place in the world.

 Today, there is no person at least who did not use antibiotics.

 There is no country that doesn’t threat of epidemics and pandemics.

 Antibiotics could be

 narrow-spectrum and effective only against a limited variety of pathogens or broad-

spectrum, affecting many different types of pathogens
  bactericidal if they kill the susceptible bacteria or bacteriostatic if they inhibit the
growth of bacteria

 REQUIREMENTS FOR ANTIBIOTIC

 high selectivity

 lack of toxicity

 long-term providing of therapeutic concentrations

 lack of rapid resistance development

 availability of suitable dosage forms

 Classification according SPECTRUM OF ACTION.

• Narrow spectrum (mainly Gr + and Gr-):

• Natural, antistaph. penicillins

• Cephalosporins I generation, monobactams

• Polimyxins, gramicidin C

• Fuzidin

• Antifungal

• Broad-spectrum:

• Semi-synthetic penicillins and cephalosporins II -IV

• Carbapenems, Tetracyclines, Macrolides, Aminoglycosides

• Chloramphenicol

 Classification according MECHANISM OF ACTION

Bacterial cell

 Negative effects of Antibiotics:

1.The emergence of sustainability:

 • production of beta-lactamase;

• changes in the permeability of the cytoplasmic membrane;

• changes in the structure of certain portions of ribosomes proteins or enzymes

2. Superinfection;

3. Dysbiosis;

4. Allergic reactions;

5. Systemic toxicity, nephrotoxicity, hepatotoxicity.

 Penicillins are the least toxic!!!

 Conditions for rational use of antibiotics

1. Antibiotics should be given according to antibiogram.

2. Choose the most active and least toxic antibiotic.

3. To determine the optimal antibiotic dose and route of administration based on the its
pharmacokinetic and the concomitant disease. The concentration of antibiotic in the
blood should be 3-4 times bigger in comparison with minimum inhibitory
concentration for the selected pathogen.

4. Apply the first striking dose, followed by supporting.

 β-lactams Mechanism of Action

 Classification of penicillins

1.Natural penicillins:

a) Short acting:

Penicillin-G

Penicillin-sodium
 Penicillin-potassium

Penicillin V

b) Long acting:

Penicillin G. procaine

Benzathine penicillin (Bicillin-I)

Bicillin-3,-5

 Classification of penicillins

2. Semisynthetic penicillins:

I. Penicillinase resistant

Oxacillin

Dicloxacillin

Cloxacillin

Methicillin

 Classification of penicillins

III. Carboxypenicillins

Carbenicillin

Ticarcillin

IV. Ureidopenicillins

Azlocillin

Piperacillin

V. Combined penicillins

Unazin

Ampiox (Ampicillin+Oxacillin)
 Augmentin (Amoxycillin+Clavulanic acid)

Magnapen (Ampicillin+Flucloxacillin)

 Spectrum of natural penicillins

• Gr+ microorganisms include:

• staphylococci,

• streptococci (pneumoniae, pyogenes and viridans group),

• bacillus anthracis,

• clostridium perfringens,

• corynebacteria diphtheriae and listeria monocytogenes

 Spectrum of natural penicillins

• Sensitive Gr- microorganisms include:

• Neisseria gonorrhoeae,

• Neisseria meningitis,

• Leptotrichia buccalis,

• Treponema pallidum,

• Treponema partenue.

 Pharmacokinetics of natural penicillins

1. Acidic instability (exception Penicillin V)

2. Extracellular distribution mainly

3. Poor penetration through BBB

4. Crossing the placenta

5. Protein binding 60%

6. Small amount metabolizing

7. Excretion mainly by tubular secretion. It may be suppressed by probenecid (uricosuric)

 Clinical uses of natural penicillins

• Endocarditis

• Pericarditis

• Meningitis

• Pneumonia

• Septicemia caused by streptococcus pyogenes

• Gonorrhea

• Syphillis (congenital and neurosyphillis).

 Clinical uses of natural penicillins

• Anthrax,

• Actinomycosis (abdominal, cervicofacial or thoracic disease),

• Botulism,

• Gas gangrene,

• Tetanus,

• Diphtheria (prevention of carrier state),

• Empyema,

• Rheumatic fever,

• Listeriosis.

 Penicillin G (benzyl penicillin) is one of the least toxic antibiotics. It does not cause
any direct toxicity. Only in very high doses, especially injected IV, it can cause
neurotoxic effect and bleeding.

 The hypersensitivity reactions are the major problem, incidence up to 10%.

  Semisynthetic penicillins

I. Penicillinase resistant:

 Oxacillin, Dicloxacillin, Cloxacillin, Methicillin

 The advantages of penicillinase resistant semisynthetic penicillins over natural ones

are in efficacy against penicillinase producing staphylococci and stability of some
of them (Oxacillin) in acidic medium.

 They are used in treatment of infection caused by staphylococci resistant to

penicillins.

 Semisynthetic penicillins

II. BROAD SPECTRUM PENICILLINS

a) Aminopenicillins

The aminopenicillins have identical spectrum and activity, but amoxicillin is better absorbed
orally (70–90%).

They are effective against:

streptococci, enterococci ,Gram-negative organisms (including H. pylori)

but have variable activity against staphylococci

ineffective against P. aeruginosa.

 Adverse effects

 Resistance

 5 generations of CEPHALOSPORINS

3. THIRD GENERATION

They have enhanced activity against gram-negative bacilli, including most enteric organisms
and Serratia marcescens. Ceftriaxone and cefatoxime have become agents of choice in the
treatment of meningitis.
Ceftazidime has activity against Pseudomonas aeruginosa.

V.Ceftriaxone

VI.Cefixime

VII.Cefoperazone

VIII.Ceftazidime

IX.Cefatoxime

 5 generations of CEPHALOSPORINS (cont.)

4-th generation

These drugs are in many ways similar to cephalosporins of 3rd generation

X. Cefepim

XI.Cefpirom

5-th generation

XII.Ceftobiprole

XIII. Ceftaroline

Antimicrobial activity: Ceftobiprole has powerful antipseudomonal effect and is less

susceptible to development of resistance. Ceftaroline does not have an anti-pseudomonal
activity.

 CEPHALOSPORINS

Type of action: bactericidal = penicillins

Spectrum: WIDE

 INDICATIONS

• infectious diseases of the respiratory, urinary and biliary tract, abdominal cavity, skin,
bones, joints, heart,

• Gonorrhea, burns, surgical prophylaxis,

 • Meningitis and Pseudomonas infection - III -IV generation.

Side effects: hemorrhage, hemato-, nephro-, neuro-, hepatotoxicity.

Contraindications: porphyria, epilepsy, severe liver and kidney diseases, pregnancy,

lactation.

 Sulperazon - "protected" (Cefoperazone + Sulbactam)

• Spectrum: wide G+, Gr-, anaerobes

• Resistant to β-lactamases of extended spectrum (sulperazon and carbapenems)

• Application: for severe community-acquired and hospital-acquired infective

processes: primary and secondary peritonitis, infected pancreatic necrosis, sepsis,
diabetic foot, phlegmons, nosocomial pneumonia.

 Comparison activity of CEPHALOSPORINS

 Pharmacological "face" of CEFALOSPORINES

✓ Similar to penicillin in structure and action.

✓ Wide spectrum.

✓ Powerful bactericidal effect.

✓ Low toxicity.

✓ Good compatibility with other antibacterial agents.

✓ Most resistant to staphylococcal β-lactamase.

✓ Cross allergic to penicillin.

✓ It penetrates into the tissue fluid, joints, bones.

✓ Good compatibility with other antibacterials.

 CARBAPENEMS and MONOBACTAMS

 Side effects of MONOBACTAMS AND CARBAPENEMS

CARBAPENEMS

• Cramps,

• Weakness,

• Tremor,

• Encephalopathy,

• Hypotension,

• Nausea, vomiting,

• Superinfection,

• Pseudomembranous colitis,

• Phlebitis,

• Thrombocytosis,

• Eosinophilia.

 Principles of Antibiotic Therapy

1. Spectrum of coverage

2. Patterns of resistance

3. Evidence or track record for the specified infection

4. Achievable serum, tissue, or body fluid concentration (e.g. cerebrospinal fluid, urine)

5. Allergy

6. Toxicity

7. Formulation (IV vs. PO); if PO assess bioavailability

8. Adherence/convenience (e.g. 2x/day vs. 6x/day)

9. Cost

 Principles of Antibiotic Therapy

Directed Therapy (15%)

 Infection well defined

 Narrow spectrum

 One, seldom two drugs

 Evidence usually stronger

 Less adverse reactions

 Less expensive

Empiric Therapy (85%)

 Infection not well defined (“best guess”)

 Broad spectrum

 Multiple drugs

 Evidence usually only 2 randomized controlled trials

 More adverse reactions

 More expensive

 Why Empiric Therapy?

 Need for prompt therapy with certain infections

 Life or limb threatening infection

 Mortality increases with delay in these cases

 Cultures difficult to do to provide microbiologic definition (i.e. pneumonia, sinusitis,

cellulitis)

 Negative cultures

 Provider Beliefs

 Fear of error or missing something

  Not believing culture data available

 “Patient is really sick, they should have ‘more’ antibiotics”

 Myth of “double coverage” for gram-negatives e.g. pseudomonas

 “They got better on drug X, Y, and Z so I will just continue those”

 Why - Empiric Therapy?

 Need for prompt therapy with certain infections

• Life or limb threatening infection

• Mortality increases with delay in these cases

 Cultures difficult to do to provide microbiologic definition (i.e. pneumonia, sinusitis,

cellulitis)

 Negative cultures

 Provider Beliefs

• Fear of error or missing something

• Not believing culture data available

• “Patient is really sick, they should have ‘more’ antibiotics”

• Myth of “double coverage” for gram-negatives e.g. pseudomonas

• “They got better on drug X, Y, and Z so I will just continue those”

 Antibiotic Use Leads to Antibiotic Resistance

• Resistant bacteria or their genetic determinates are selected when colonizing or

infecting bacteria are exposed to antibiotics

• Resistant bacteria can then be transmitted between patients

• Highest risk patients:

• Immunocompromised
 • Hospitalized

• Invasive devices

• (central venous catheters)

 POLICY TO DEAL DRUG RESISTANCE

 Mechanisms Of Antibiotic Resistance

 Can be related back to how the antibiotic works

 Bacteria are capable of becoming resistant through several mechanisms

 One or many mechanisms may exist in an organism

 Multidrug-resistant bacteria often have multiple mechanisms

 Genes encoding resistance may exist on plasmid or chromosome

 Mechanisms of Resistance

Antibiotic Degrading Enzymes

 Sulfonation, phosphorylation, or esterifictation

• Especially a problem for aminoglycosides

 β-lactamases

• Simple, extended spectrum β-lactamases (ESBL), cephalosporinases,

carbapenemases

• Confer resistance to some, many, or all beta-lactam antibiotics

• May be encoded on chromosome or plasmid

• More potent in gram-negative bacteria

• Examples: S. aureus, H. influenzae, N. gonorrhoeae, E. coli, Klebsiella sp.,

Enterobacter sp., Serratia sp., other enteric bacteria, anaerobes

 Multidrug Resistant Gram-Negative Organisms

 Development of resistance to multiple antimicrobial classes severely limits treatment
options and the incidence of resistance is rising

 Proportion of isolates resistant to three antibiotic classes ranged from 10 to 60% for
different gram-negative bacteria, while some are resistant to four antibiotic classes

 Multidrug Resistant Gram-Negative Organisms

• Widespread use of cephalosporins and beta-lactam combination antibiotics has led to

extended-spectrum beta-lactamases (ESBLs), which are resistant to both classes

• Carbapenems have been the only effective agents for ESBLs

• Emergence of carbapenemases, such as Klebsiella pneumoniae carbapenemase

(KPCs) are threatening carbapenems as the antibiotics of last resort

• Significant issue for many military personnel due to the high amount of
Acinetobacter in the desert

• NO NEW ANTIBIOTICS ON THE HORIZON!!!

 Methicillin resistant Staphylococcus aureus

(MRSA)

 Healthcare-associated

 Endemic in hospitals, old age homes

 Risk factors

• Hospitalization in previous 1 year

• Recent surgery

• Old age home residence

• Renal dialysis

• Exposure to invasive devices

• Employment in a healthcare institute

 Community-associated
  Do not have usual risk factors associated with HA-MRSA

 More common in the following in overseas countries

• Children with chronic skin condition

• Prisoners

• Military personnel

• Aboriginals

• Injection drug users

• The homeless

• Contact sports athletes

IMPACT (Interhospital Multi-disciplinary Programme on Antimicrobial

ChemoTherapy)

 IMPACT guideline

 Contents of IMPACT guideline

• Local antibiotic resistance

• Guidelines for selected antimicrobial use, e.g.

• Vancomycin

• Ceftazidime

• Imipenem/meropenem/ertapenem

• Once daily aminoglycosides

• Selected antifungal agents

 IMPACT guideline

 Contents of IMPACT guideline

• Recommendations for empirical therapy of common infections

 • Guidelines for known pathogen therapy

• Guidelines for surgical prophylaxis

• Cost and recommended dosage of commonly used antimicrobial agents

 BIG GUN AUDIT

 Big gun audit

Targets 2 types of antibiotics

1. Broad-spectrum antibiotics

Tienam, Meropenem, Ceftazidime, Cefepime, Tazocin, Sulperazon

All these agents have good Gram-negative as well as Pseudomonas coverage

1. Anti Gram-positive antibiotics

Vancomycin and teicoplanin

Active vs. methicillin-resistant Staphylococcus aureus

To be used as second-line agents

 Big gun audit

• Data collection form completed and faxed with MAR on first order of big gun

• Encourage physicians to prescribe big guns only when clinically indicated

 Big gun audit

 Big gun audit

 Useful guides to antimicrobial therapy

 Sanford Guide

• Covers a broad range of infectious diseases

 IMPACT
 • With commonly prescribed empirical therapy and useful local resistance
information

 Local antibiogram

• Bacterial resistance specific to an institution or a cluster of institutions

 ANTIMICROBIAL STEWARDSHIP

 What Is Antimicrobial Stewardship?

• Antimicrobial stewardship is a mutlidisciplinary approach for rational antibiotic

therapy

• Must be based on evidence-based guidelines

• Must be based on data

• Must apply to all practitioners

 Core Actions to Prevent Antibiotic Resistance

1. Preventing infections

2. Prevent the spread of resistance

3. Tracking and surveillance

4. Improve antibiotic prescribing through stewardship

5. Development of new antibiotics and new diagnostic tests for resistance bacteria

 Principles of Antibiotic Stewardship

• Re-evaluate, de-escalate or stop therapy at 48-72 hours based on diagnosis and

microbiologic results

• Re-evaluate, de-escalate or stop therapy with transitions of care (e.g. ICU to step-
down or ward)

• Do not give antibiotic with overlapping activity

• Do not “double-cover” gram-negative rods (i.e. Pseudomonas sp.) with 2 drugs with
overlapping activity

• Make sure that all prescriptions/orders for antibiotics have the appropriate dose,
duration, and indication

 Principles of Antibiotic Stewardship

• Limit duration of surgical prophylaxis to <24 hours perioperatively

• Use rapid diagnostics if available

• (e.g. respiratory viral PCR)

• Prevent infection

 Use good hand hygiene and infection control practices

 Remove catheters

• Consult infectious disease

 Conclusion

 Antibiotics clearly save lives

 Poor prescribing of antibiotics are putting patients at unnecessary risk

 Adverse reactions

 Development of resistant organisms

 Every time an antibiotic is prescribed

 If at all possible, order recommended cultures before antibiotics are given

 Make sure an indication, dose, and expected duration are part of the
prescription order

 Reassess within 48 hours and adjust antibiotic or discontinue if warranted

 Pay for performance indicators

 Conclusion

 New antibiotics intended to treat complicated diseases are under investigation

 Need to protect our antibiotic arsenal

 Justified use of antimicrobials not only treats infections, but also improves patient
outcomes and reduces the risk of development of bacterial resistance

 Adherence to clinical guidelines, antimicrobial stewardship program and education

helps to promote appropriate antimicrobial use

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