Antibiotic. Antibiotic Classes, Spectrum of Activity & Antibiotic Reporting

Transcription

1 Antibiotic Antibiotic Classes, Spectrum of Activity & Antibiotic Reporting Any substance of natural, synthetic or semisynthetic origin which at low concentrations kills or inhibits the growth of bacteria but causes little or no host damage Jocelyn Teo BSc(Pharm), Msc (ID), BCPS AQ ID Senior Clinical Pharmacist Singapore General Hospital Nature Reviews Drug Discovery 2007, 6:8-12

2 How do antibiotics work? By inhibiting crucial life-sustaining processes in bacteria Grouped by: Antibiotic Classification Mode of action (Function) Inhibitors of cell wall synthesis Inhibitors of protein synthesis Inhibitors of membrane function Anti-metabolites Inhibitors of nucleic acid synthesis Structure Spectrum of activity Gram-positive, gram-negative, anaerobic, broad-spectrum Beta-Lactams Natural Penicillin All of the antibiotics in this group have a beta-lactam ring. Beta-lactamase combinations Penicillin Penicillinase- Resistant Penicillins Variation of the side chain - improved activity vs. Gm - bacteria Extended- Spectrum Penicillins (Aminopenicillins)

3 Natural Penicillins Penicillin G/Penicillin V Spectrum of Activity Strep. pneumoniae, Strep. pyogenes, Group B Strep., viridans group Strep Staphylococcus aureus Enterococcus faecalis, E. faecium (in combination with aminoglycosides) Neisseria meningitidis Treponema pallidum (syphilis) Listeria monocytogenes Corynebacterium diphtheriae Anaerobes - Clostridum perfringens & C. tetani, Bacteroides fragilis, Fusobacterium, Peptostreptococcus Natural Penicillins Mechanism of resistance Inactivated by penicillinases Resistance rates high Penicillinase-R Penicillins Cloxacillin, methicillin*, oxacillin* (*not used clinically) Spectrum of Activity Similar to Pen G, but includes Staphylococcus aureus & S. epidermidis Aminopenicillins Amoxicillin, ampicillin Extended-spectrum: developed to increase activity against certain gram-negative aerobes E. coli Proteus spp. Hemophilus influenzae Samonella & Shigella spp. Similar gram +ve activity as natural penicillins (slightly less active)

4 Beta-lactamase combinations Amoxicillin-clavulanate (Augmentin), Piperacillin-tazobactam (Tazocin), Ticarcillinclavulanate (Timentin), Ampicillin-sulbactam (Unasyn) Spectrum of Activity Developed to gain or enhance activity against β- lactamase producing organisms Enhanced gram-ve and anaerobic coverage compared to the other penicillins Beta-lactamase combinations Amoxicillin-clavulanate (Augmentin) Clavulanic acid extends spectrum to b-lactamaseproducing organisms e.g. in Staph.aureus and of anaerobic Bacteroides sp. Piperacillin-tazobactam (Tazocin) Added P. aeruginosa coverage Ticarcillin-clavulanate (Timentin) Added P. aeruginosa coverage Ampicillin-sulbactam(Unasyn) Can be used for Acinetobacter spp. Way of introduction Cephalosporins Generation of cephalosporin antibiotics first I second II third III fourth IV Injection Cefazolin* Cefuroxime Cefoxitin Ceftriaxone Ceftazidime Oral Cephalexin Cefuroxime Ceftibuten Cefepime Special remarks Inducers of certain betalactamases *Cephalothin used as testing drug in laboratory

5 Carbapenemss Carbapenems Imipenem-cilastatin 1987 Meropenem 1996 Ertapenem 2001 Doripenem 2007 Broad: Stable to most beta-lactamases Gram +ve(except MRSA, Enterococcus) Imipenem& Doripenem slightly better Gram ve Ertapenem does not cover P. aeruginosa& A. baumannii Anaerobic Resistance Increasing, most commonly seen in PA, AB & now enterobacteriaceae like Klebsiella, Enterobacter Merck Astra Zeneca Merck Janssen-Cilag Aztreonam Monobactam Slightly different structure can be used in most penicillin-allergic patients Gram-negatives and P. aeruginosa No activity against gram-pos Glycopeptide (Vancomycin) : MRSA (Methicillin Resistant Staph. aureus) C. difficile Streptococci including Strep pneumoniae Natural resistance to: Gram-negatives Microbiology tip: If growth around vancomycin disk possibly gram-negative

6 Aminoglycosides Aminoglycosides Gram-negative: Pseudomonas, Acinetobacter, Enterobacteriaceae spp. Gram-positives:Staphylococcus, Streptococcus spp. (Gentamicin more active) Mycobacterium spp. (Amikacin, Streptomycin) Macrolides Tetracyclines Mainly active against S. pneumoniae, S. pyogenes, atypical organism (H. influenzae, Mycoplasma, Legionella (Clarithro/Azithro > Erythro) dd

7 Quinolones Ciprofloxacin, levofloxacin, moxifloxacin Antibiotic Reporting Guidelines ANTIBIOTIC REPORTING Some considerations for the selection of antibiotic for reporting : Body site of culture Safety issues Effectiveness in clinical settings Potential for resistance development Antibiotic control policies

8 Body site of culture Different antibiotics have different properties Some are delivered to most sites while others primarily work on certain sites E.g. Cefazolin is excluded from the susceptibility report of a CSF culture growing E. coli E.g. Nitrofurantoinonly reported for urinary isolates Safety issues Certain drugs are not suitable for certain patient groups E.g. Ciprofloxacin is not reported for children under 12yo Effectiveness in Clinical Setting Potential for resistance development Certain drugs which are effective in vitro but are not effective clinically should not be reported E.g. Aminoglycosides (except high concentration), cephalosporins, clindamycin, and trimethoprimsulfamethoxazole should never be reported as susceptibile for Enterococcus.

9 Antibiotic control policies QUESTIONS? Only gentamicin reported as amikacin is more expensive Only ertapenem reported as use to discourage use of imipenem& meropenem