Antibiotic Classes

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Antibiotic Classes, Spectrum of Activity and Antibiotic Reporting
Jocelyn Teo BS c(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 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”

Nature Reviews Drug Discovery 2007, 6:8-12

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 • • • •

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

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

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

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

Broke n down by BETALACTAMASES

Re sistance de ve lops!

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

Beta-Lactams

Penicillins * Natural * Penicillinaseresistant * Extendedspectrum * Beta-lactamase combination

Cephalosporins * 1st Generation *2nd Generation * 3rd Generation * 4th Generation *5th Generation

Carbapenems

Monobactams

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

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.

Beta-lactamase Combinations Spectrum of Activity
Augmentin™ MSSA Streptococcus (except viridans) Enterococcus faecalis Gramnegatives Enterobacter, Citrobacter, Serratia Pseudomonas Acinetobacter Anaerobes ++ ++ Unasyn™ ++ ++ Tazocin™ ++ ++

++ ++ -

++ ++ -

++ ++ ++

++

++ ++

++ ++

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 Gram + (excl. Enterococcus, MRSA) MRSA Gram E.coli, Klebsiella, Proteus Citrobacter, Enterobacter, Serratia Pseudomonas Anaerobes ++ 2nd Gen ++ 3rd Gen ++ 4th Gen ++ 5th Gen ++

+ + -

++ ++ -

++ ++ +

++ ++ ++

++ ++ ++ ++

+/-

++

Ceftazidime +

++ +

?

Carbapenems

Imipenem-cilastatin

Meropenem

www.mims-online.com Ertapenem Doripenem

• •

• •

Only available 1987 in IV 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

Monobactam

AZTREONAM

• •

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

• Ciprofloxacin • Le vofloxacin • Moxifloxacin

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

Metronidazole



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



Protein Synthesis Inhibitors

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

• •

Primarily use d for community-acquired respiratory infe ctions Spe ctrum of activity o Mainly active against S. pneumoniae, H. influenzae, atypical organisms (My coplasma, Chlamydia, Legionella ) (Clarithro/Azithro > Erythro)

Tetracyclines

• 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

ANTIBIOTIC REPORTING

An Antibiotic Susceptibility Report
Site

Organism

Categorical Susceptibility

Recommendations for Reporting
• CLSI Performance Standards and Guidelines for Susceptibility Testing of Bacteria

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

• 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
• 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
• 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





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