Antibiotics for CNS infections

Question 1

Ceftriaxone (3rd generation cephalosporin)

Answer 1

• Cell wall inhibitor, binds to penicillin binding proteins, good CNS penetration
• N. gonorrhoeae conjunctivitis
• Empiric treatment of bacterial meningitis: Ceftriaxone + vancomycin
• Definitive, Prophylactic treatment of Neisseria meningitis
• Empiric treatment of brain abscess: Ceftriaxone + metronidazole

Question 2

Penicillin

Answer 2

• Cell wall inhibitor, binds to penicillin binding proteins
• High levels of beta-lactam antibiotics in CNS block binding of GABA to receptors. The tissue becomes more excitable and prone to seizures.
• Gram positive only, intrapartum prophylaxis for Streptococcus agalactiae (Strep B)

Question 3

Amoxicillin, Ampicillin

Answer 3

Cell wall inhibitor, binds to penicillin binding proteins

Add clavulanate to inactivate enzymatic degradation by Beta-lactamases

Otitis media and sinusitis: Amoxicillin

Listeria monocytogenes meningitis: Ampicillin + Gentamicin (unless pregnant)

Question 4

Aztreonam

Answer 4

• Cell wall inhibitor, binds to penicillin binding proteins
• Empiric treatment of meningitis if beta-lactam allergy: Aztreonam + Vancomycin

Question 5

Vancomycin

Answer 5

• Cell wall inhibitor, binds to the D-ala-D-ala shielding it from the transpeptidation reaction
• Gram positives including MRSA, Empiric treatment of meningitis with ceftriaxone

Question 6

Rifampin

Answer 6

• inhibits DNA-dependent RNA polymerase, increases P-450 levels decreasing activity of other drugs
• Meningococcal prophylaxis for H. influenza type B, Mycobacterium tuberulcolosis

Question 7

Gentamicin, Amikacin (Aminoglycosides)

Answer 7

• Protein synthesis inhibitor, binds 30S ribosomal subunit, ototoxicity
• Listeria monocytogenes meningitis: Gentamicin + Ampicillin (unless pregnant)

Question 8

Acyclovir, Gancyclovir- guanosine analog

Answer 8

• Prodrugs must be phosphorylated by viral thymidine kinase leading to its selectivity
• Inhibits viral DNA polymerase and leads to chain termination
• Not effective against latent virus
• HSV-1, HSV-2(Acyclovir), CMV(Gancyclovir)

Question 9

Foscarnet

Answer 9

• Phosphonoformate binds viral DNA and RNA polymerases
• Nephrotoxic
• CMV and gancyclovir-resistant strains

Question 10

Trifluridine

Answer 10

• Prodrug must be phosphorylated by cellular kinases leading to its toxicity
• Inhibits viral DNA polymerase and leads to chain termination
• Topical use for HSV keratoconjunctivitis

Question 11

Amphotericin B

Answer 11

• Disrupts the plasma membranes allowing the leakage of electrolytes,
• Liposomal form enters CNS
• Nephrotoxic
• Also used for visceral leishmaniasis

Question 12

Flucytosine (5-FC)

Answer 12

• DNA synthesis inhibitor conversion to 5-fluorouracil
• Combined with amphotericin B to treat Cryptococcus, Candida infections

Question 13

Fluconazole

Answer 13

• Decreases ergosterol synthesis
• Used to treat fungal otitis externa caused by Candida

Question 14

Combine the following 4 drugs for the treatment of Mycobacterium tuberculosis

Answer 14

• Rifampin- inhibits DNA-dependent RNA polymerase
• Isoniazid- mycolic acid inhibitor, difference in drug half-life depending on if the individual is a fast or slow acetylator
• Pyrazinamide- Unknown
• Ethambutol- cell wall inhibitor, binds arabinosyl transferase

Question 15

Pentamidine

Answer 15

• Binds DNA minor groove, mitochondrial as well as nuclear genome replication is affected
• Trypanosoma brucei

Question 16

Suramin

Answer 16

• Unknown mechanism, highly toxic
• Trypanosoma brucei

Question 17

Melarsaprol

Answer 17

An arsenical, crosses BBB, so will treat stage 2 T. brucei infection. Super toxic!!!!

Question 18

Eflornithine

Answer 18

• ornithine decarboxylase inhibitor, crosses BBB, so will treat stage 2 T. brucei infection.

Question 19

Nifurtimox

Answer 19

• oxidative stress, impairment of membrane potential
• Trypanosoma cruzi (also Benznidazole, also a nitroaromatic), or T. brucei co-treatment with eflornithine

Question 20

Sodium stibogluconate & Meglumine antimoniate

Answer 20

• Organic antimonials
• Targets are glycolysis and fatty acid beta-oxidation
• Leishmania

Question 21

Miltefosine

Answer 21

• Mechanism unknown
• Leishmania

Question 22

Sulfadiazine+Pyrimethamine

Answer 22

• folate synthesis inhibitors, dangerous to use in pregnancy. The macrolide Spiramycin may be more appropriate in certain pregnancy situations but not approved in US so must acquire from FDA
• Toxoplasmosis

Question 23

Albendazole (roundworms, tapeworms)

Answer 23

• microtubule inhibitor
• Taenia solium- cysticercosis, Echinococcus granulosis, Toxocara cati