Principles of Antibiotics Therapy For CC 2ab011

Principles of Antibiotic Therapy
Dr. Tshokey, MD Clinical Microbiologist JDWNRH
Infectious Diseases Vs Other Diseases

HOST HOST Environment
Environment
Pathogen
10/4/2011
Tshokey/CC 2011
Infectious Diseases Vs Other Diseases
Other disease are due to malfunctioning or destruction of host cells / Cellular structures

Heart Failure, MI, Malignancies, Cure often with residual impairment
Infectious diseases due to action of pathogens/or their toxins
Recovery or death, Recovery without sequel- full function is restored

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Most infectious diseases are treated with antibiotics.

Antibiotics areSubstances secreted by They acts on bacterial cells with very minimal or no effect on host cells - selective advantage
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Impact of Penicillin on society
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Impact of antibiotics on Disease burden..
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Antibiotics brought..
So much success and hope in the field of infectious diseases Most experts believe that by the year 2000 viral and bacterial infections will have disappeared from our life. - US Surgeon General, Time Magazine, 25/2/66
But
most experts now say that looking at the diversity of infections and the unavailability of antibiotics and vaccines, it was a miracle for those people born before 1940s to escape those infections and survive.
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Antibiotics are.
Most commonly misused drug

Treatment failure Increased cost Poor reputation Development of antibiotic resistance
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Antibiotic resistance: Why important?

Our bugs stronger than our drugs Dominance of Bugs over Drugs Bacteria are the dominant species on the earth Rapid multiplication rate Natural mutation rate Ability to transfer or move genes via transformation, conjugation, transduction and transposition Collectively, these properties allow bacteria to survive, change and eventually flourish under intense selection pressure
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Evolution: The history

3.85 billion years old: Bacteria 210 million years old: Real Mammals 60 million years old: Human-like Mammals 30 million years old: Monkeys 2.5 million years old: Direct Ancestors 0.2 million years old: Neanderthals 0.125 million years old: Homo Sapiens
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Evolution: The history
70 years old: Antibiotics Vs
3.85
billion years old: Bacteria
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DARWINs THEAORY
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BUGS
ANTIBIOTICS
ANTIBIOTICS
BUGS
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Super Bugs- No Drugs

decreasing research and development for new classes of antibiotics Research and development on new products can take approximately 10 years to bring a new agent to market. The price ranges between $800 million to $1.7 billion dollars a large investment without a guarantee for return Not like other drugs week vs lifelong All available/possible materials for antibiotics already explored Companies dropped out of antibiotic business
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Spectrum of activity of different antibiotics and emerging resistances
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Ent ero coc cus
Clost ridiu m
Diphtheri a
Staphylo coccus
Streptoc occus
Neisseri a
Haemop hilus/ Moraxell a
Enteroba cteria
Bacteroi des
Pseudo monas
Acinetob acter
Atypical Bacteria
Penicillin Amoxycillin Ticarcillin Piperacillin
1st gen ceph Erythromycin Clarithomycin Azithromycin Gentamicin Ciprofloxacin Levofloxacin Tetracycline 10/4/2011
Tshokey/CC 2011
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Enter ococ cus
Clost ridiu m
Diphtheri a
Staphylo coccus
Streptoc occus
Neisseri a
Enteroba cteria
Bacteroi des
Pseudo monas
Acinetob acter
Atypical Bacteria
Penicillin
Amoxycillin
Ticarcillin Piperacillin
1st gen ceph
Erythromycin
Gentamicin
Ciprofloxacin Tetracycline
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Tshokey/CC 2011
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Entero coccu s
Clost ridiu m
Diphtheri a
Staphylococ cus
Strept ococc us
Neisseri a
Enteroba cteria
Bacteroi des
Pseudo monas
Acinetob acter
Atypical Bacteria
Penicillin Amoxycillin Ticarcillin Piperacillin 1st gen ceph Erythromyci n
Gentamicin
Ciprofloxacin
Tetracycline
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Enter ococ cus
Clost ridiu m
Diphtheri a
Staphylococ cus
Strept ococc us
Neisseri a
Haemop hilus/ Moraxell
Enteroba cteria
Bacteroi des
Pseudo monas
Acinetob acter
Atypical Bacteria
Penicillin
Cloxacillin
Amoxycillin
Ticarcillin Piperacillin
1st gen ceph Co amoxyclav Cefuroxime
Cefotaxime
Ceftazidime Erythromycin Gentamicin Ciprofloxacin Tetracycline 10/4/2011
Tshokey/CC 2011
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Enter ococ cus
Clost ridiu m
Diphtheri a
Staphylococ cus
Strept ococc us
Neisseri a
Enteroba cteria
Bacteroi des
Pseudo monas
Acinetob acter
Atypical Bacteria
Amoxycillin Ticarcillin Piperacillin
1st gen ceph Co amoxyclav Cefuroxime Cefotaxime Ceftazidime Erythromycin Gentamicin Ciprofloxacin Imipenem Cefepime 10/4/2011
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Types of Antibiotic Therapy
1. Empirical Therapy 2. Targeted Therapy
3. Other therapies

Prophylaxis Pre-emptive therapy
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1. Empirical Therapy

Based on Best Guess Blind Therapy Guided by local sensitivity data Cover the Potential Pathogens Commencement- after obtaining specimens for Microbiology If, non infective cause found,- immediately cease the therapy Absence of Proven agent/organismcontinue therapy for at least 48 hrs before changing
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Empiric Therapy
Two types 1. Traditional Stepping up therapy
So called first line, second line or third line Older method ? Usefulness in severe sepsis
Many evidences of high mortality when the initial choice is wrong Depending on the patients severity, starting with high end antibiotics. Hitting hard the first time and de-escalated.
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2. Deescalation therapy/antibiotic streamlining
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Empiric therapy

After detecting the organism and knowing the ABST pattern, converted to directed therapy Stepping down therapy to narrow spectrum.
e.g Severe sepsis Imipenem started and blood culture taken. Isolated E.coli sensitive to Ampicillin ..immediately de-escalate to Ampicillin. (Directed therapy)
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The impact of appropriate antibiotic delay in septic shock.

90 80 70 60
Survival (%)
50
40 30 20 10
Each hour of delay carries 7.6% reduction in survival
0
0.5 1 2 3 4 5 6
Delay in treatment (hours) from hypotension onset

Kumar, et al. Crit Care Med 2006;34:15891596
2. Targeted/Directed Therapy
Best form of therapy Antibiotics are directed against isolated organisms Guided by ABST results Need good microbiological services (24x7) Prompt communication between the Microbiologist and the clinicians
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EMPIRIC THERAPY
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TARGETED THERAPY
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Rational Antibiotic Therapy is based on the following factors:
Knowledge of the organism Sensitivity Site involved Natural course if untreated The choice of the most appropriate antibiotics if indicated
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Rational antibiotic use 1. Is an antibiotics indicated on Clinical Grounds?
Evidence of Infection
Local effects-Pain, redness, warmth, edema, Lymphadenopathy Systemic effect Fever, WBC, CRP etc
Bacterial Involvement
Antibiotics are not effective against viral diseases Fungal involvement anti fungals
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2.Have appropriate investigations been performed?
Bacteriological Investigations Blood culture, and other relevant cultures,

CSF, sputum, urine as relevant to illness Remember, before antibiotic therapy Other tests..such as WBC/DC,CRP
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3.What organisms are likely cause?

Syndrome Likely cause
Neonatal Sepsis
Community acquired pneumonia of adults Acute Infective endocarditis with RF Cellulitis Necrotizing fascitis
Group B Streptococci, E.coli

Pneumococcus, Mycoplasma Staphyloccocuus aureus Streptococci Group A, S.aureus Streptococcus Group A , Mix flora
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4.Which Agent is best?
Disease type

Community acquired infection Hospital acquired
Static vs cidal
Long acting vs short acting
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Bacteriostatic vs Bacteriocidal
Depend on bodys defence systems for activity
When ever possible go for bactericidal drugs

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Systemic or Tropical
When ever possible prescribe systemic drugs
Tropical agents wound agents soframycin, Polymyxin etc enhance resistance build up
Not only to drug itself but other systemic drugs of same class
Uncomplicated cystis Nitrofurantoin, Nalidixic Acid gives same results without systemic toxicity
Nitrofurantoin- a drug used for >50yrs and still no significant development of bacterial resistant
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Short Acting Vs Long Acting
Long acting drugs- better bio availability and risk of toxicity
Amoxycillin Vs Ampicillin Erythromycin Vs Clarithromycin Erythro Vs Azithro
Long acting drugs need to be given very carefully- blood concentration of drug persistent and low
higher chances of development of resistance
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Some drugs usually given as BD or TDS can be given once daily or once in two days without much toxicity

once daily Aminoglycoside Therapy Instead of Gentamicin 1.5-2 mg/kg 8 hrly Gentamicin 5-7 mg/kg daily
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Higher Bacterial Killing with less oto and nephrotoxicity
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5.Is an appropriate combinations best?
Mono therapy is better Combination therapy where appropriate

Febrile neutropaenic patients Patients with Pulmonary TB Pneumococcal Meningitis Advanced Pseudomonas infections
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6.Is any host factors relevant?
May need to adjust dose
Renal Failure- for renal excreted drugs Liver Failure- liver metabolized drugs
History of hypersensitivity/allergy
Major Minor Possibility of cross hypersensitivity- penicillins and cephalosporins
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7.What is the best route of Administration?

Oral or IV IV or IM Need for topical agents
TB- Oral drugs BHS Pharyngitis- Oral Infective Endocarditis IV Rheumatic Fever Prophylaxis- IM Primary or Early Secondary Syphylis- IM
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Oral Vs Parenteral
Choice depends on patients clinical presentation
Bacterial Pneumonia Clinical Classification (PSI) Class I,II Can Manage with oral antibiotics
Class IV,V Need IV therapy

Skin and Soft tissue Infections SSSI Class I can manage with orals while rest need IV
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8.What is the appropriate dose?
Higher dose required for areas of reduce blood supply

Endocarditis IV Penicillin 3-4 mu 4hourly IV Cloxacillin 2g - 4 hourly CSF infection Vs Otitis Media/Epiglottitis H.influenzae Pharyngitis O.Pen 250-500 mg 6 hourly and very low dose for prevention
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8. Appropriate dose..
Biofilms- infections in prosthetic implants-may need removal antibiotics doesn't achieve high
concentrations
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Appropriate dose
Some drugs (time dependent killing agents) when increase the dose above recommended do not have a higher killing effect

CRO 1g daily, 2g daily would results the same killing effect
Microbiological input necessary
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9.Can therapy be modified when lab results are available?
Stepping down IV oral switching -
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10.Optimal duration of therapy?

Most duration of treatments driven by tradition (5 days?? 6 days or 4 days?) No well proven trials of durationexcept comparators by pharmaceuticals. Longer duration drives resistance..hospital pathogens like physicians prescribing long term antibiotics Most clinical response in hospital infections occur by 6 days of antibiotics.
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Bacteriological cure Clinical cure
Pharyngitis clinical cure precedes, stopping will result recurrence TB- Bacteriological cure later than clinical cure Meningitis Bacterial cure early Enteric fever-Bacterial cure early
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Golden Rule in antibiotic therapy
Appropriate drug Appropriate route Appropriate dose Appropriate time/frequency Appropriate duration
Always remind yourself ; where we will be in next 5-10 yrs..if we prescribe irrationally
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A dream antibiotic

Broad spectrum Given orally Once a day
Novel compound
Bactericidal
Non-toxic
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Remember MIND ME
M Microbiology guide therapy whenever possible I - Indication -should be evidence based N Narrowest Possible Spectrum D Dosage appropriate for the site of infection M- Minimize the duration E Ensure Mono-therapy in most cases
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Antibiotics for different infections
Upper respiratory infections - Pharyngitis Streptococcus pyogenes
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Ent ero coc cus
Clost ridiu m
Diphtheri a
Staphylococ cus
Strep tococ cus
Neisseri a
Enteroba cteria
Bacteroi des
Pseudo monas
Acinetob acter
Atypical Bacteria
Penicillin
Cloxacillin
Amoxycillin Ticarcillin Piperacillin 1st gen ceph Co amoxyclav Pip / Taz Tic / Clav Cefuroxime Cefotaxime Ceftazidime Erythromycin Clarithromcyin Azithromycin Gentamicin Ciprofloxacin Levofloxacin Tetracycline Imipenem Meropenem Vancomycin 10/4/2011 Linezolid
Tshokey/CC 2011
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Respiratory tract infections
Middle ear infection (otitis media) / Sinusitis / Acute on chronic bronchitis Moraxella catarrhalis Streptococcus pneumoniae Haemophilus influenzae
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Ent ero coc cus
Clost ridiu m
Diphtheri a
Staphylococ cus
Strep tococ cus
Neisseri a
Enteroba cteria
Bacteroi des
Pseudo monas
Acinetob acter
Atypical Bacteria
Penicillin Cloxacillin Amoxycillin Ticarcillin Piperacillin 1st gen ceph
Co amoxyclav Pip / Taz Tic / Clav

Cefuroxime Cefotaxime Ceftazidime Erythromycin Clarithromcyin Azithromycin Gentamicin Ciprofloxacin Levofloxacin Tetracycline
Imipenem Meropenem
Vancomycin 10/4/2011 Linezolid
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Pneumonia
Typical pneumonia Streptococcus pneumoniae Haemophilus influenzae
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Ent ero coc cus
Clost ridiu m
Diphtheri a
Staphylococ cus
Strep tococ cus
Neisseri a
Enteroba cteria
Bacteroi des
Pseudo monas
Acinetob acter
Atypical Bacteria

Imipenem Meropenem
Tshokey/CC 2011
61
Pneumonia
Atypical pneumonia Mycoplasma pneumoniae Chlamydia pneumoniae Legionella pneumophila
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Ent ero coc cus
Clost ridiu m
Diphtheri a
Staphylococ cus
Strep tococ cus
Neisseri a
Enteroba cteria
Bacteroi des
Pseudo monas
Acinetob acter
Atypical Bacteria

Imipenem Meropenem
Tshokey/CC 2011
63
Pneumonia Typical pneumonia Streptococcus pneumoniae Haemophilus influenzae
Atypical pneumonia Mycoplasma pneumoniae Chlamydia pneumoniae Legionella pneumophila

Tshokey/CC 2011
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Ent ero coc cus
Clost ridiu m
Diphtheri a
Staphylococ cus
Strep tococ cus
Neisseri a
Enteroba cteria
Bacteroi des
Pseudo monas
Acinetob acter
Atypical Bacteria

Imipenem Meropenem
Tshokey/CC 2011
65
Urinary tract infections
Escherichia coli Other Enterobacteria Klebsiella Proteus Enterococcus Coagulase negative staphylococci
Tshokey/CC 2011
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10/4/2011
Ent ero coc cus
Clost ridiu m
Diphtheri a
Staphylococ cus
Strep tococ cus
Neisseri a
Enteroba cteria
Bacteroi des
Pseudo monas
Acinetob acter
Atypical Bacteria

Imipenem Meropenem
Tshokey/CC 2011
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Skin and soft tissue infections
Staphylococcus aureus Streptococcus pyogenes
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Ent ero coc cus
Clost ridiu m
Diphtheri a
Staphylococ cus
Strep tococ cus
Neisseri a
Enteroba cteria
Anaerob es
Pseudo monas
Acinetob acter
Atypical Bacteria

Imipenem Meropenem
Tshokey/CC 2011
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Abdominal infections
Anaerobes Bacteroides sp
Escherichia coli
Enterococcus
Tshokey/CC 2011
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10/4/2011
Ent ero coc cus
Clost ridiu m
Diphtheri a
Staphylococ cus
Strep tococ cus
Neisseri a
Enteroba cteria
Bacteroi des
Pseudo monas
Acinetob acter
Atypical Bacteria

Imipenem Meropenem
Tshokey/CC 2011
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Central nervous system infections
Streptococcus pneumoniae
Haemophilus influenzae Neisseria meningitidis
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Ent ero coc cus
Clost ridiu m
Diphtheri a
Staphylococ cus
Strep tococ cus
Neisseri a
Enteroba cteria
Bacteroi des
Pseudo monas
Acinetob acter
Atypical Bacteria

Imipenem Meropenem
Tshokey/CC 2011
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Hospital Acquired A infections
Pseudomonas aeruginosa
Acinetobacter ESBL producing enterobacteria
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Ent ero coc cus
Clost ridiu m
Diphtheri a
Staphylococ cus
Strep tococ cus
Neisseri a
Enteroba cteria
Bacteroi des
Pseudo monas
Acinetob acter
Atypical Bacteria

Imipenem Meropenem
Tshokey/CC 2011
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Hospital Acquired infections
MRSA Enterococcus
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Ent ero coc cus
Clost ridiu m
Diphtheri a
Staphylococ cus
Strep tococ cus
Neisseri a
Enteroba cteria
Bacteroi des
Pseudo monas
Acinetob acter
Atypical Bacteria

Imipenem Meropenem
Tshokey/CC 2011
77
10/4/2011
Tshokey/CC 2011
Knowing the futurehelps us change!

10/4/2011
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79

Principles of Antibiotics Therapy For CC 2ab011

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Principles of Antibiotic Therapy

Dr. Tshokey, MD Clinical Microbiologist JDWNRH

Infectious Diseases Vs Other Diseases

Infectious Diseases Vs Other Diseases

Heart Failure, MI, Malignancies, Cure often with residual impairment

Infectious diseases due to action of pathogens/or their toxins

Recovery or death, Recovery without sequel- full function is restored

Most infectious diseases are treated with antibiotics.

Impact of Penicillin on society

Impact of antibiotics on Disease burden..

Most commonly misused drug

Treatment failure Increased cost Poor reputation Development of antibiotic resistance

Antibiotic resistance: Why important?

Evolution: The history

Evolution: The history

70 years old: Antibiotics Vs

billion years old: Bacteria

Super Bugs- No Drugs

Spectrum of activity of different antibiotics and emerging resistances

Ent ero coc cus

Haemop hilus/ Moraxell a

Penicillin Amoxycillin Ticarcillin Piperacillin

Enter ococ cus

Haemop hilus/ Moraxell a

1st gen ceph

Haemop hilus/ Moraxell a

Penicillin Amoxycillin Ticarcillin Piperacillin 1st gen ceph Erythromyci n

Enter ococ cus

Haemop hilus/ Moraxell

Enter ococ cus

Haemop hilus/ Moraxell a

Amoxycillin Ticarcillin Piperacillin

Types of Antibiotic Therapy

1. Empirical Therapy 2. Targeted Therapy

Prophylaxis Pre-emptive therapy

2. Deescalation therapy/antibiotic streamlining

The impact of appropriate antibiotic delay in septic shock.

Each hour of delay carries 7.6% reduction in survival

Delay in treatment (hours) from hypotension onset

Rational Antibiotic Therapy is based on the following factors:

Rational antibiotic use 1. Is an antibiotics indicated on Clinical Grounds?

2.Have appropriate investigations been performed?

Bacteriological Investigations Blood culture, and other relevant cultures,

3.What organisms are likely cause?

Group B Streptococci, E.coli

4.Which Agent is best?

Community acquired infection Hospital acquired

Depend on bodys defence systems for activity

When ever possible go for bactericidal drugs

When ever possible prescribe systemic drugs

Short Acting Vs Long Acting

Long acting drugs- better bio availability and risk of toxicity

Amoxycillin Vs Ampicillin Erythromycin Vs Clarithromycin Erythro Vs Azithro

higher chances of development of resistance

Higher Bacterial Killing with less oto and nephrotoxicity

5.Is an appropriate combinations best?

Mono therapy is better Combination therapy where appropriate

6.Is any host factors relevant?

May need to adjust dose

7.What is the best route of Administration?

Oral or IV IV or IM Need for topical agents

Choice depends on patients clinical presentation

Class IV,V Need IV therapy