antibiotic classes (4)

7/28/2019 Antibiotic Classes (4)

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Antibiotic Classes,

Spectrum of Activityand

Antibiotic Reporting

Jocelyn Teo

BSc(Pharm), Msc (ID), BCPS AQ ID

Senior Clinical Pharmacist

Singapore General Hospital

Learning Objectives

Know the common antibiotic classes

Know the spectrum of activ ity of different antibiotics

Understand how antibiot ic suscept ibility is beingreported

What is an antibiotic?

Any substance of natural, synthetic or semi-syntheticorigin which at low concentrations kill s or inhibits the

growth of microorganisms but causes lit t le or no hostdamage

bacteria


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Natu re Reviews Drug Discovery 2007, 6:8-12

Properties of Antibiotics

Formulation Injection or oral

Mechanism of action Spectrum of activ ity

Pharmacokinetic (PK) Dist ribution in body, modeof clearance

Pharmacodynamic (PD) bacteriostatic or

bactericidal

Side-effect profile

How do antibiotics work?

Inhibit Cell-Wall/Membrane

Synthesis/

Function

Beta-lactamsPenicillins

CephalosporinsCarbapenemsMonobactams

VancomycinDaptomycin

P olymyxin

Folatee

Inhibit Nucleic Acid Synthesis/Function

Inhibit DNA gyrase/topoisomerase:

Quinolones Inhibit folate synthesis:Trimethoprim/Sufoxmethoxazole

Create free radicals: Metronidazole

50 S

30s

Inhibit ProteinSynthesis

50SMacrolides

ClindamycinLinezolid

30SAminoglycosides

TetracyclinesTigecycline

Antibiotic Classes

o Inhibit Cell-Wall/Membrane Synthesis/ Function

Beta-lactams

Vancomycin

o Inhibit Nucleic Acid Synthesis/Function

Quinolones

Metronidazole

o Inhibit Protein Synthesis

Macrolides

Aminoglycosides Tetracyclines


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Spectrum of Activity Table

Antibiotic A Antibiotic B

Gram positive(excl. MRSA)

+ ++

Gram negative ++ ++

Pseudomonas ++ +

Anaerobes - +/-

Atypicals + ++

+ = fair coverage

++ = e xcellent coverage

- = poor/no coverage

+/- = inconsistent coverage

Cell Wall Inhibitors

Beta-Lactams

All of the antibiotics in this group have a beta-lactam ring.

Diverse group of antibiot ics commonly used for many differentinfections

Broke n down byBETA-

LACTAMASES

Resistancedevelops!

Beta-Lactams

Penicillins

* Natural

* Penicillinase-resistant

* Extended-spectrum

* Beta-lactamasecombination

Cephalosporins

* 1st Generation

*2nd Generation

* 3rd Generation

* 4th Generation

*5th Generation

Carbapenems

Monobactams


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Beta-Lactamases Producing

Organisms

Gram +

S. aureus

Enterococcus faecaelis

Gram -

Serrat ia spp.

Pseudomonas spp.

Indole +ve: Proteus,Providencia spp.

Citrobacterspp.

Enterobacterspp.

E. coli

Klebsiella spp.

Penicillins Spectrum of

ActivityNatural

PenicillinsPenicill in GPenicill in V

Penicillinase-R

Penicillins(Anti-staph)Cloxacillin

Methicill in*Oxacillin*

Extended-

SpectrumPenicillins

AmoxicillinAmpici llinPiperacillinTicarcillin

MSSA + ++ -

Streptococcus(exceptviridans)

++ + +

Enterococcusfaecalis

+ - ++

Gram-

negatives- - +

Anaerobes + - +

Beta-lactamase Combinations

Brand nameExtended-Spectrum

Beta-lactamBeta-lactamase

inhibitor

Augmentin Amoxicillin Clavulanate

Unasyn Ampicillin Sulbactam

Tazocin Piperacillin Tazobactam

Beta-lactamase inhibitors have similar structures to beta-lactams

and are used in combination w ith beta-lactams to preventdegradat ion by beta-lactamases.

Beta-lactamase Combinations

Spectrum of ActivityAugment in Unas yn Tazoc in

MSSA ++ ++ ++

Streptococcus(exceptviridans)

++ ++ ++

Enterococcusfaecalis

++ ++ ++

Gram-negatives

++ ++ ++

Enterobacter,Citrobacter,Serratia

- - ++

Pseudomonas - - ++

Acinetobacter - ++ -

Anaerobes ++ ++ ++


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Cephalosporins

1st Generation

Cefazolin

Cephalexin

2nd Generation

Cefuroxime

Cefoxitin

3rd Generation

Ceftriaxone

Ceftibuten

Ceftazidime

4th Generation

Cefepime

5th Generation

Ceftaroline

Increasing Gram ve coverage

Increasing resistance towards beta-lactamases

Cephalosporins

1st Gen 2nd Gen 3rd Gen 4th Gen 5th Gen

Gram +(excl.Enterococcus,MRSA)

++ ++ ++ ++ ++

MRSA - - - - ++

Gram - + ++ ++ ++ ++

E.coli, Klebsiella,Proteus

+ ++ ++ ++ ++

Citrobacter,Enterobacter,

Serratia

- - + ++ ++

Pseudomonas - - Ceftazidime ++ -

Anaerobes +/- ++ + + ?

Carbapenems

Imipenem-cilastatin

1987

Merck

Meropenem

1996

Astra Zeneca

Ertapenem

2001

Merck

Doripenem

2007

Janssen-Cilag

www.mims-online.com

Only available in IV

Broad spectrum of coverage

o Does not cover Ent erococcus, MRSA,Acinet obacter,atypicals

Ertapenem does not cover Pseudomonas

Imipenem-cilastatin covers Enterococcus faecalis

Monobactam

Side-chan different structure reserved for penicillin-allergicpatients

Spectrum of activity

o

Gram-negativ es and Pseudomonas aeruginosao No act iv ity against gram-positive & anaerobes

AZTREONAM


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Vancomycin

Spectrum of activityo MRSAo Enterococcus

o Clost ridium difficile

M RSA -Heterogeneouspopulation may includesubpopulations w ithintermediate resistanceto vancomycin

Nephrotox ic, Ototoxic

Nucleic Acid SynthesisInhibitors

Quinolones

Ciprofloxacin

Levofloxacin

Moxifloxacin

Quinolones Spectrum of

Activity

Ciprofloxacin Levofloxacin Moxifloxacin

Gram positive(excl. MRSA)

MSSA only ++ ++

Gram negative ++ ++ ++

Pseudomonas ++ + -

Anaerobes - +/- +

Atypicals + ++ ++


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Metronidazole

Broad anaerobic coverage Clost ridium spp. ( includingC.difficile, Helicobacter pylori

Also can cover parasites

Protein Synthesis Inhibitors

Aminoglycosides Spectrum of activity

o Gram-negative:Pseudom onas, Acinetobacter,Ent erobacteriaceae spp.

o

Gram-positives:St aphylococcus,St reptococcus spp.(Gentamicin more activ e)

o Mycobacterium spp.(Amikacin)

Not used alone for Gram +v e,usually in combination w ith abeta-lactam

Resistance is rare

Nephrotox ic, Ototoxic

Macrolides

Primarily use d for community-acquired respiratory infections

Spectrum of activity

o Mainly active against S. pneumoniae, H. influenzae, atypical

organisms (Mycoplasma, Chlamydia, Legionella) (Clarithro/Azithro> Erythro)


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Tetracyclines

Effec tive against atypicals Minocycline may be used forA. bauma nnii

Tigecycline has gram ve activity againstA. bauma nnii,Enterobacteriaceae (except Proteus & Providencia ), MRSA, VRE

ANTIBIOTIC REPORTING

An Antibiotic Susceptibility

Report

Organism

CategoricalSusceptibility

Site

Recommendations for

Reporting CLSI Performance Standards and Guidelines for

Susceptibility Testing of Bacteria


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Reporting methods

General reportingo

Report ing all ant ibiot ics tested w ithout restrictions or analys is

Selective reportingo Report includes ant ibiot ic useful for treat ment of that part icular organism

or treat ment site

Sit e of infect ion

Safety iss ues

Effect iveness in clinical setting

Cascade reportingo Ranks drugs i n a class on the basis of broad-spect rum act ivity, the

pot ent ial for overprescribing and emergence of drug resis t ance, and cost

Selective Reporting

Si te of culture

o Some drugs are delivered to most sites while othersprimarily w ork on certain sites

o E.g. Cefazolin is excluded from the susceptibility report of aCSF culture grow ing E. coli

o E.g. Nitrofurantoin only reported for urinary isolates

Selective Reporting

Safety issues

o Certain drugs are not suitable for certain patient groups

o E.g. Ciproflox acin may not be reported for children under12yo problems with bones, joints, and tissues

o E.g. Imipenem-cilastatin not reported for CSF cultures notFDA indicated, has more potential to cause seizures

Selective Reporting

Effectiveness in Clinical Set ting

o Certain drugs which are effective in vitrobut are noteffective clinically should not be reported

o E.g. Cephalosporins, clindamycin and trimethoprim-sulfamethox azole should never be reported as susceptibilefor Enterococcus

o E.g. 3rd-Generat ion cephalosporins may not be reported ifan Amp-C bet a-lact amase-producing organism issuspect ed.


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Cascade reporting

Antibiotic controlpolicies

Reported only thenarrow -spectrum andcost-effectiveantimicrobial agents

Only gentamicinreported as amikacinis more expensive

Only ertapenem

reported todiscourage use ofimipenem &meropenem

QUESTIONS?

antibiotic classes (4)

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