This document discusses antibiotics used to treat bacterial meningitis. It describes four main mechanisms of antibiotic action: inhibiting cell wall synthesis, disrupting cell membranes, inhibiting protein synthesis, and inhibiting nucleic acid synthesis. Specific antibiotics are discussed for each category, including penicillins, cephalosporins, vancomycin, chloramphenicol, ciprofloxacin, and sulfisoxazole. Administration methods and dosages are provided. The case study discussed involved treating a patient with intravenous vancomycin and cefotaxime, while contacts received rifampin prophylaxis.

1. Antibiotics in Bacterial
Meningitis
by Mario Wilmath, MD

2. Objectives
 Describe the general mechanisms of antibiotic action.
 Understand the antibiotics used in bacterial meningitis.
 Describe the parenteral dosage forms and routes of
administration of antibiotics.
 Relate to case of John D.

3. Cell Wall Synthesis Blockade
Cephalosporins (3rd generation)
Example: cefotaxime
Overview:
 Beta-lactam
 Increased activity and
distribution
MOA:
 Interference with cell wall
synthesis (transpeptidation)
 Activating autolytic enzymes
Penicillins
Example: PenG, oxacillin
Overview:
 Beta-lactam
 Resistance and allergy
MOA:
 Interference with final step in cell
wall synthesis (transpeptidation)
 Activating autolytic enzymes
http://www.itqb.unl.pt
http://www.itqb.unl.pt

4. Cell Wall Synthesis Blockade
Example: Vancomycin
Overview:
 Treat beta-lactamase resistance
 Wide distribution
MOA:
 Large glycopeptide
 Hydrogen bonds to NAM and NAG subunits
 Inhibits murein synthesis and peptidoglycan cell wall
http://www.itqb.u
nl.pt
http://www.itqb.unl.pt

5. Disruption of Cell Membranes
Overview:
Selective toxicity to
bacterial membrane.
MOA:
May disrupt membrane
structure (sterols) or
function (pores).
Examples: Polymixins
Imidazoles
http://content.answers.com

6. Inhibition of Protein Synthesis
Chlormaphenicol
Overview:
 Broad spectrum
 Used for penicillin allergy
 Bacteriostatic only
MOA:
 Binds 50S ribosomal unit
 Block peptidyl transferase
 Inhibit mitochondrial synthesis.
Rifampin
Overview:
 Wide distribution into CNS
 Prophylaxis for meningitis
MOA:
 DNA-dependent RNA polymerase inhibition
http://wpcontent.answers.com

7. Inhibition of Nucleic Acid Synthesis
Example: Ciprofloxacin
Overview:
» Quinolone
» Poor CNS penetration
» Cannot be used: Children or pregnancy
MOA:
» Inhibits bacterial DNA gyrase
» Supercoiled DNA cannot relax
» Transcription and replication
blocked
http://www.pharmainfo.net
www.pharmainfo.ne

8. Inhibition of Nucleic Acid Synthesis
Example: Sulfisoxazole
Overview:
» Sulfonamide: PABA-like structure
» Only moderate tissue penetration
MOA:
» Dihydropeteroate synthase:
 Competitive inhibitor
 Substrate becomes nonfunctional folic acid analogue
http://www.elmhurst.edu

9. Penicillin G
 Powder
 Frozen solution
 IV preferred, supplement IM
 250000 U/kg/d IV or IM q4-6h x
7-14d
http://userweb.port.ac.uk/~norrismj/antimicrobial_agents/
Penicillins.html
http://www.drsfostersmith.com/product/prod_display.cfm
?pcatid=16196

10. Cefotaxime
 Powder
 Frozen solution
 ADD-Vantage System
 IV or IM
 150–225 mg/kg/d IV or IM q6-8h
 Case study: 250mg/kg/d IV q12h
http://www.appdrugs.com/ProductDetail.html?pfid=18&name=Cefotaxi
me_for_Injection_USP
Courtesy of Dr. Mobley’s lecture on parenteral
delivery systems

11. Vancomycin
 Powder
 Frozen solution
 IV
 Intrathecal / Intraventricular
 50 – 60 mg/kg/d IV q6 – 8 h
 Case study: 60mg/kg/d IV q6h
http://www.mrsapedia.com/vancomycin-and-mrsa/

12. Chloramphenicol
 Powder
 IV or PO
 75 – 100 mg/kg/d IV or
PO q6h
http://www.supplierlist.com/photo_images/53922/Chloramphenicol_Caps.jpg
http://www.apppharma.com/ProdJPGs/Chl
oramphenicolLg.jpg

13. Ciprofloxacin
 Oral
 Nasal carrier state
 Prophylaxis
 500 mg PO q12h X 5d
http://onlyhealth.wordpress.com/2009/09/16/generic-cipro-is-
preeminent-antibacterial-drug/

14. Conclusion
The 4 mechanisms of action for antibiotics:
1. inhibit cell wall synthesis
2. membrane permeability
3. protein synthesis
4. nucleic acid synthesis
 Case study received vancomycin + cefotaxime
and his contacts received rifampin prophylaxis

15. References
 Acute Bacterial Meningitis. Mace, SE. Emergency Medical Clinics of North America. Volume
26, issue 2, May 2008. Accessed Tuesday March 30, 2010 from
http://www.mdconsult.com.lp.hscl.ufl.edu/das/article/body/192106220-
2/jorg=journal&source=&sp=20587149&sid=0/N/638565/1.html?issn=0733-8627#tblfn3
 Clinical Pharmacology. Accessed on Sunday March 28, 2010 from
http://www.clinicalpharmacology-ip.com.lp.hscl.ufl.edu/default.aspx
 Katzung BG and Trevor AJ. Examination and Board Review Pharmacology, 4th edition. Appleton
& Lange. Norwalk, Connecticut. 1995.
 RX List. Accessed on Sunday March 28, 2010 from http://www.rxlist.com/bicillin-c-r-drug.htm