Learning Objectives

Antibiotic Classes, Spectrum of Activity and Antibiotic Reporting

Jocelyn Teo BS c(Pharm), Msc (ID), BCPS AQ ID Senior Clinical Pharmacist Singapore General Hospital

Know the common antibiotic classes Know the spectrum of activ ity of different antibiotics Understand how antibiotic susceptibility is being reported

What is an antibiotic?
Any substance of natural, synthetic or semi-synthetic origin which at low concentrations kills or inhibits the growth of microorganisms but causes little or no host bacteria damage

Properties of Antibiotics
Formulation Injection or oral Mechanism of action Spectrum of activ ity Pharmacokinetic (PK) Distribution in body, mode of clearance Pharmacodynamic (PD) bacteriostatic or bactericidal Side-effect profile

Nature Reviews Drug Discovery 2007, 6:8-12

How do antibiotics work?

Inhibit CellWall/Membrane Synthesis/ Function Beta-lactams Penicillins Cephalosporins Carbapenems Monobactams Vancomycin Daptomycin P olymyxin e
50S

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

Inhibit Protein Synthesis 50S Macrolides Clindamycin Linezolid 30S Aminoglycosides Tetracyclines Tigecycline

30s
Folate

Inhibit Nucleic Acid Synthesis/Function Inhibit DNA gyrase/topoisomerase: Quinolones Inhibit folate synthesis: Trimethoprim/Sufoxmethoxazole Create free radicals: Metronidazole

Spectrum of Activity Table

Antibiotic A Gram positive (excl. MRSA) Gram negative Pseudomona s Anaerobes Atypicals + = fair coverage ++ = excellent coverage + ++ ++ + - = poor/no coverage +/- = inconsistent coverage Antibiotic B ++ ++ + +/++

Cell Wall Inhibitors

Beta-Lactams
Diverse group of antibiotics commonly used for many different infections

Beta-Lactams

Broke n down by BETALACTAMASES

Penicillins * Natural * Penicillinaseresistant * Extendedspectrum * Beta-lactamase combination Cephalosporins * 1st Generation *2nd Generation * 3rd Generation * 4th Generation *5th Generation Carbapenems Monobactams

Re sistance de ve lops!

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

Beta-Lactamases Producing Organisms

Gram + S. aureus Enterococcus faecaelis Gram Serratia spp. Pseudomonas spp. Indole +ve : Proteus, Providencia spp. Citrobacter spp. Enterobacter spp. E. coli Klebsiella spp.

Penicillins Spectrum of Activity

Natural Penicillins Penicillin G Penicillin V Penicillinase-R Penicillins (Anti-staph) Cloxacillin Methicillin* Oxacillin* ++ + ExtendedSpectrum Penicillins Amoxicillin Ampicillin Piperacillin Ticarcillin +

MSSA Streptococcus (except viridans) Enterococcus faecalis Gramnegatives Anaerobes

+ ++

+ +

++ + +

Beta-lactamase Combinations
Brand name Extended-Spectrum Beta-lactam Amoxicillin Ampicillin Piperacillin Beta-lactamase inhibitor Clavulanate Sulbactam Tazobactam

Beta-lactamase Combinations Spectrum of Activity

Augmentin MSSA Streptococcus (except viridans) Enterococcus faecalis Gramnegatives Enterobacter, Citrobacter, Serratia Pseudomonas Acinetobacter Anaerobes ++ ++ Unasyn ++ ++ Tazocin ++ ++

Augmentin Unasyn Tazocin

++ ++ -

++ ++ -

++ ++ ++

Beta-lactamase inhibitors have similar structures to beta-lactams and are used in combination w ith beta-lactams to prevent degradation by beta-lactamases.

++

++ ++

++ ++

Cephalosporins
1st Generation
Cefazolin Cephalexin

Cephalosporins
1st Gen Gram + (excl. Enterococcus, MRSA) MRSA Gram ++ 2nd Gen ++ 3rd Gen ++ 4th Gen ++ 5th Gen ++ 5th Generation
Ceftaroline

2nd Generation
Cefuroxime Cefoxitin

3rd Generation
Ceftriaxone Ceftibuten Ceftazidime

4th Generation
Cefepime

+ + -

++ ++ -

++ ++ +

++ ++ ++

++ ++ ++ ++

Increasing Gram ve coverage Increasing resistance towards beta-lactamases

E.coli, Klebsiella, Proteus Citrobacter, Enterobacter, Serratia Pseudomonas Anaerobes

+/-

++

Ceftazidime +

++ +

Carbapenems

Monobactam

AZTREONAM
Imipenem-cilastatin Meropenem
www.mims-online.c om Ertapenem Doripenem

Only available in IV 1987 1996 2001 2007 Merck Astra Zeneca Merck Janssen-Cilag Broad spectrum of coverage o Does not cover Ent erococcus, MRSA, Acinet obacter, atypicals Ertapenem does not cover Pseudomonas Imipenem-cilastatin covers Ent erococcus faecalis

Side-chan different structure reserved for penicillin-allergic patients Spectrum of activity

o Gram-negat iv es and Pseudom onas aer uginosa o No act iv it y against gram-positive & anaerobes

Vancomycin
Spectrum of activity
o MRSA o Ent er ococcus o Clost ridium difficile

M RSA - Heterogeneous population may include subpopulations w ith intermediate resistance to vancomycin Nephrotox ic, Ototoxic

Nucleic Acid Synthesis Inhibitors

Quinolones

Quinolones Spectrum of Activity

Ciprofloxacin Levofloxacin ++ ++ + +/++ Moxifloxacin ++ ++ + ++ Gram positive (excl. MRSA) Gram negative Pseudomona s Anaerobes Atypicals MSSA only ++ ++ +

Ciprofloxacin Le vofloxacin Moxifloxacin

Metronidazole

Protein Synthesis Inhibitors

Broad anaerobic coverage Clost ridium spp. (including C.difficile, Helicobact er pylori Also can cover parasites

Aminoglycosides
Spect rum of act iv ity o Gram-negat iv e: Pseudom onas, Acinet obact er, Ent er obact eriaceae spp. o Gram-posit iv es: St aphylococcus, St rept ococcus spp. (Gent amicin more act iv e) o My cobact erium spp. (Amikacin) Not used alone for Gram +v e, usually in combinat ion w ith a bet a-lact am Resist ance is rare Nephrot ox ic, Ot otoxic

Macrolides

Prima rily use d for community-a cquired respiratory infe ctions Spe ctrum of activity o Ma inly a ctive against S. pneumoniae, H. influenzae, a typical orga nisms (My coplasma, Chlamydia, Legionella ) (Clarithro/Azithro > Erythro)

Tetracyclines

ANTIBIOTIC REPORTING
Effec tive against atypic als Minoc ycline may be used for A. ba uma nnii Tigec ycline has gram ve ac tivity against A. ba uma nnii, Enteroba cteria cea e (except Proteus & Providencia ), MRS A, VRE

An Antibiotic Susceptibility Report

Site

Recommendations for Reporting

CLSI Performance Standards and Guidelines for Susceptibility Testing of Bacteria

Organism

Categorical Susceptibility

Reporting methods
General reporting
o Report ing all ant ibiot ics tested w ithout restrictions or analys is

Selective Reporting
Site of culture
o Some drugs are delivered to most sites while others primarily w ork on certain sites o E.g. Cefazolin is ex cluded from the susceptibility report of a CSF culture grow ing E. coli o E.g. Nitrofurantoin only reported for urinary isolates

Selective reporting
o Report includes ant ibiot ic useful for treat ment of that part icular organis m or t reat ment site Sit e of infect ion Safet y is s ues Effect ivenes s in clinical setting

Cascade reporting
o Ranks drugs in a clas s on t he bas is of broad-s pect rum act ivity, t he pot ent ial for overpres cribing and emergence of drug res is t ance, and cos t

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 under 12yo problems with bones, joints, and tissues o E.g. Imipenem-cilastatin not reported for CSF cultures not FDA indicated, has more potential to cause seizures

Selective Reporting
Effectiv eness in Clinical Setting
o Certain drugs w hich are effective in vit ro but are not effective clinically should not be reported o E.g. Cephalosporins, clindamycin and trimethoprimsulfamethox azole should never be reported as susceptibile for Ent erococcus o E.g. 3 rd-Generat ion cephalosporins may not be reported if an Amp-C bet a-lact amase-producing organism is suspect ed.

Cascade reporting
Antibiotic control policies Reported only the narrow -spectrum and cost-effective antimicrobial agents Only gentamicin reported as amikacin is more ex pensive Only ertapenem reported to discourage use of imipenem & meropenem

QUESTIONS?