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