Antibiotics

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					Drug That Inhibit the Cell Wall                                                  Drugs that inhibit Microbial Protein Synthesis
Attack transpedtidase enzyme envolved in cross linking the cell                  Act on the bacterial ribosomes. 30s and 50s
wall of bacteria.
                                                                                 Tetracyclines and Doxycycline end in –cycline
    These drugs are Bacteriocidal.                                              Act on 30s
                                                                                 Bone and Joint disorders (tetracyclines, quinolones
Penicillin(s) end in –cillin.          Vancomycin                                Tetracycline is the prototype agent and doxycycline is one of several
    1. Also target penicillin                                                    derivatives.
         binding proteins. Involved                                              good oral absorbtion. causes tooth discoloration do not use if preg or under 7.
         in cell wall integrety.                                                     • Doxycycline – safest for use in patients with renal impairment, but
    2. Danger of epileptic                                                                has increased risk of photosensitivity and hepatotoxicity than
         seizures (intrathecal                                                            tetracycline
         penicillin G injections)                                                    • Hepatotoxic esp. in pregnant women
                                                                                     • Major indications in pulmonary infections are Mycoplasma
                                                                                          pneumonia and Chlamydia
Cephalosporins begin with Cef- or Ceph-                                              • Minor use – H. influenza, S.pneumoniae
   1. 1st generation – cephalothin (IV), cefazolin (IM), Cefalexin (Oral)
           a. Highly b-lactamase resistant
           b. Somewhat b-lactamase resistant                                     Aminoglycosides
           c. Best for gram +, Some activity for Klebsiella, M. catarrhalis      End in 30s
   2. 2nd generation -- cefamandole, cefoxitin (IM), cefaclor(Oral)              Bacteriostatic
           a. More active vs. certain gram negatives than 1st generation.        Remember GAS – Gentamicin, Aminoglicosides, Streptomycin
           b. Less active than 1st generation vs. gram positives                     • Ototoxicity, vestibular toxicity (aminoglycoside use)
                     i. Klebsiella, H. influenza (only pen-sensitive strains),
                        M. catarrhalis, Pseudomonas
   3. 3rd generation -- Cephalosporins: cefotaxime, ceftazidime,ceftriaxone
       (IV or IM)
           a. Gram + and Gram – activity                                         Macrolides
           b. *Ceftriaxone may be active against strains resistant to other      Act on 50s
                3rd generation cephalosporins                                    Bacteriostatic
                     i. S. Aureus (not metR), Strep. Pneumonia, Strep.           Remember MACE –
                        Pyogenes, H. influenza, H. parainfluenza, Klebsiella,        1. Azithromycin, Oral IV take on empty stomach
                        Pseudomonas (not cefatriaxone)                               2. Clarithromycine, Oral
   4. 4th generation – Cefepine (IV or IM)                                           3. Erythromycine. Oral IV
           a. Gram + and Gram – activity. Improved
           b. Gram + activity compared with 3rd Generation                       Side effects
                                                                                 photosensitivity
Metabolism is not usually an issue. Drugs are excreted via kidney largely        Liver toxicity- risk especially with estolate derivatives of erythromycin
unmetabolized.                                                                   Erythromycin is safe for use in pregnancy (category B)
Toxicity                                                                         Risk of superinfection by yeast and C. difficile
           – Allergic reactions –rare and rarely serious
           – Dose reductions recommended in patients with impaired renal         Toxicity
                function of if given in combo with other nephrotoxic drugs       Esp.Erythromycin and Clarithromycin – inhibit Cyp3A4
           – Risk of superinfection with Candida and C. difficile                Cardiac Toxicity – prolonged QT intervals, arrhythmia
                (pseudomembranous colitis) high with 3rd and 4th generation      E and C – contraindicated with cisapride, pimozide, astemizole, terfenadine,
                agents. Use cautiously with patients with colitis.               quinidine, disopyramide
Antimicrobial DNA Synthesis and Replication
Inhibitors


                                                                                     •   Blood dyscrasias
                                                                                         (granulocytopenia, fatal aplastic
                                                                                         anemia- Chloramphenicol)

                                                                                  Don’t Know where this goes yet..

FluoroQuinolones – end in –floxacin
           – In gram + micro-organisms, Topoisomerase IV
           – In gram – micro-organisms, DNA Gyrase
           – Both of these enzymes regulate the topology of DNA
               during replication. Inhibition of either enzyme results
               in DNA strand-breakage.

(ciprofloxacin, levofloxacin gatifloxacin, moxifloxacin                           Clindamycin
) generally bacterialsidal

Bone and Joint disorders (tetracyclines, quinolones                            Don’t Know where this goes
                                                                               yet..
    •   The pharmacokinetic properties of the fluoroquinolones are
        excellent
            – Excellent oral absorption and tissue distribution
            – Tissues concentrate the drug leading to it’s utility in
                 urinary tract infections as well as infections in the lung,
                 prostate, bone, cerebral spinal fluid.
    •   Adverse Side-effects are infrequent with agents found on the                            Sulfa Drugs
        DRUG LIST                                                                               Generally bacreriostatic
            – Dose reduction of ciprofloxacin in renal deficits
            – Photosensitivity, rash
            – Generally not recommended for children under 16 due to                            Sulfamethoxazole
                 possible adverse effects on joints. In serious infections,                     Trimethoprim-
                 drug use is recommended.
General Pulmonary infections
Acute Bronchitis                                                           Pneumonia
Likely infectious agents                                                   Likely infectious agents
     Streptococcus pneumoniae                                                  Streptococcus pneumoniae
     Haemophilus influenza                                                     Haemophilus influenza
     Moraxella catarrhalis                                                     Moraxella catarrhalis (smokers)
                                                                                Mycoplasma pneumoniae
Manage mild cases in otherwise       Management of severe cases                 Chlyamydia pneumoniae
healthy persons                                                                 Legionella pneumoniae

Amoxicillin (S. pneumoniae, but be   Amoxicillin-clavulante (Penicillin-   Management
wary of drug resistance)             resistant S. pneumoniae, M.               Azithromycin (active against all; be wary of resistant
                                     catarrhalis)                                S.pneumoniae;1st choice for L. pneumoniae)
Doxycycline (S. pneumoniae, H.
influenza
                                     Cefaclor (H. influenza, M.                   Fluoroquinolones (Levo, Gat, Moxi) – all active against all
)
Trimethoprim-sulfamethoxazole        catarrhalis)
                                                                                  2nd Generation Cephalosporins (H.influenza, M. catarrhalis)
(S. pneumoniae, H.influenza,
M.catarrhalis)                       Cephalothin (S. Pneumoniae, pen
                                     sensitive)                                   1st or 3rd Generation Cephalosporins (S. pneumoniae)
Cephalothin (S. pneumoniae , pen                                                  Doxycycline or Erythromycin (M. pneumoniae, C.
sensitive strains only)              Cefotaxime (S. pneumoniae)
                                                                                   pneumonia,L.pneum.)
Cefaclor (H. influenza, M.           Azithromycin (H.influenza, M.
                                     catarrhalis, variable for S.          If unresponsive-
catarrhalis)                                                               3rd Generation Cephalosporin + Macrolide (erythromycin or
                                     pneumoniae)
                                                                           azithromycin)
                                     Fluoroquinolones, Levofloxacin,
                                     Gatifloxacin, Moxifloxacin are
                                     active against all three infectious
                                     agents




Pneumocystis (carinii)
Pneumocystis jivroveci
    • Prophylaxis in HIV+ – 3 months of Trimethoprim-
        sulfamethoxazole if CD4+ <200 cells/ml
    • Treatment – High dose Trimethoprim-sulfamethoxazole
Alternative – Clindamycin-Primaquine
From block 8 lectures
Antibacterials Used to
Treat Pneumonia
   • Penicillins
   • 1st and 3rd generation Cephalosporins
   • Imipenem (in penicillin-resistant disease)
   • Vancomycin (in penicillin-resistant disease)
   • Doxycycline (in penicillin-resistance/allergy)
   • Sulfamethoxazole-trimethoprim
   • Macrolides (legionella, mycobacterium)
   • Levofloxacin (legionella, also others in penicillin-resistance/allergy)
   • Gentamicin (in gram-negative infections)
Treatment of Bacterial
Meningitis
   • Pediatric and adult – Empiric Therapy
Ampicillin + vancomycin + ceftriaxone

   •   Immunocompromised adults
        (L. monocytogenes) Ampicillin

   •   Neisseria meningitis – Doxycycline, parenteral Penicillin G

Treatment of Endocarditis
   • Viridans Streptococcus –Penicillin G + gentamicin
   • Cornebacterium – Pencillin G + gentamicin
   • S. aureus- Nafcillin, vancomycin

Treatment of Gastroenteritis
   • Campylobacter- Ciprofloxacin

   •   Salmonella- Ciprofloxacin

   •   Shigella- Ciprofloxacin

   •   Vibrio cholera- Doxycycline, ciprofloxacin

  • Clostridium- Metronidazole, vancomycin
Malaria Chemoprophylaxis
   •   Africa, SE Asia      Mefloquine,Doxycycline
                                  (pyrimethamine-                                      sulfadoxine)


   • Carribean, Central
  America, Middle East  Chloroquine

Any relapse          Primaquine (gametocidal)

Chloroquine – Not for used in patients with
Epilepsy
Myasthenia gravis
Psoriasis
Persons taking amiodarone or halofantrin

Cautious use of chloroquine in patients
Hepatic disorder
Blood dyscrasias
Glucose-6-phosphate deficiency
Long term use can result in blindness

Mefloquine– Not for used in patients with
1st trimester of pregnancy
Children under 5 kg
Neuropsychiatric conditions
Seizure disorders
Concurrently with chloroquine, quinine or quinidine due to increased cardiotoxicity.
 Doxycycline – not for use in pregnant women or children under age 8

Primaquine– Not used in patients with
Active rheumatoid arthrits
Lupus erythematosis
Glucose-6-phosphate deficiency (hemolytic anemia)
 Pyrimethamine-sulfadoxine- Not for use in patients with
Allergic reactions to any sulfa drug
Nursing mothers
Infants less than 2 months old
Quinoline Antimalarial Drugs
Chloroquine, Quinine, Quinidine, Amodiaquin, Primaquine, Mefloquine
High doses are cardiotoxic (prolonged QT intervals) – acute arrhythmias

Artemisinin and Derivatives
Cautious use in pregnant women,
Some neurotoxicity, cardiotoxicity (prolonged QT intervals)
                     And bone marrow depression
Treatment Options for CLQR Malaria
   • CLQR Malaria endemic to Africa
          – 1st choice: Pyrimethamine/sulfadoxine
          – 2nd choice: amodiaquine
          – 3rd choice: quinine/doxycycline
          – 4th choice: mefloquine
          – 5th choice: artemisinin
Treatment Options for MDR* Malaria
   • MDR Malaria endemic to SE Asia
          – 1st choice: mefloquine**
          – 2nd choice: artemisinin
MDR = Multi-drug resistant

Babesiosis
clindamycin or azithromycin + quinine sulfate;

Giardiasis –Giardia lamblia- contaminated U.S.A. stream waters in Western Pa, Adirondacks, NY, Colorado
      Treatment - metronidazole, paromomycin (for pregnancy)

* Treatment usually only required in immunocompromised persons
*Cryptosporidiosis- Cryptosporidium – outbreaks of community contaminated water have occurred in the U.S.A.
       Treatment – paromomycin is partially effective
*Cyclosporosis –Cyclospora-
       Treatment – trimethoprim-sulfisoxazole
*Microsporidiosis-Microsporidia-
       Treatment – atovaquone
Protozoal Infections Transmitted by Oral/Oral-Fecal Route
   • Toxoplasmosis –Toxoplasma gondii. Risk Factor: Cats, the natural host! .
   • Pathological consequences:
          – pregnant women – congenital toxoplasmosis ocular disease.
          –   Treatment in pregnant women – spiramycin 1st 20 weeks gestation; pyrimethamine-sulfadiazine for remainder of
              pregnancy.
          –   HIV patients- toxoplasmic encephalitis (lethal)
          –   Treatment – pyrimethamine + sulfadiazine

   •   Amebiasis- Entamoeba histolytica- Risk Factor: institutionalized persons, crowded and unsanitary conditions.
           – Intestinal disease = Amebic dysentery
           – Treatment- paromomycin
           – Systemic infection (liver, brain) Brain cysts cause brain abscesses usually occurs along with intestinal disease
           – Treatment –metronidazole
Antibiotics Used in the Chemotherapy of Protozoan Infections
   • Metronidazole-amebicidal. All routes of administration. Caution – neuropathies warrant drug discontinuation; contraindicated in
       pregnant women.
   • Paromomycin- amebicidal aminoglycoside. Administer orally for treatment of GI parasites. Efficacy based upon poor systemic
       absorption from GI tract. Safe in pregnant women.

Metronidazole and paromomycin are also active antibacterial agents.
Folate Antagonists inhibit DNA Synthesis

   •   Pyrimethamine –inhibits dhfr*
   •   Sulfa- competitive inhibitor of PABA**
   •   Pyrimethamine-sulfadoxine-malaria
   •   Pyrimethamine-sulfadiazine- toxoplasmosis

Helminthic Infections
   • Pinworms or Roundworms – pyrantel, mebendazole, albendazole

   • Threadworms- ivermectin > mebendazole, albendazole
   • Hookworms– mebendazole, albendazole (pyrantel)
Pyrantel is safe for use during pregnancy.
Mebendazole, albendazole are teratogenic.

Antihelminthic Chemotherapy with Benzimidazoles
   • Mechanism – bind beta-tubulin in worm and block beta-tubulin polymerization and chromosomal segregation during mitosis.
   • Contraindicated in pregnant women
Trematodes (schistosomes)
   • Diphyllobothrium, fish tapeworm native to U.S. Risk factor- eating raw or undercooked fish from northern U.S. rivers and lakes,
      esp. pike.
   •  Other Schistosomal infections- Risk factor- eating undercooked shell fish or fish from a wide variety of tropical and sub-tropical
      regions (e.g. Sushi).
   • Treatment – Praziquantel
Antihelminthic Chemotherapy Target Neurotransmission Mechanisms
   • Praziquantel – stimulates Ca++ influx and spastic paralysis of tapeworms.
   • Pyrantel Pamoate – stimulates cation influx via non-selective cation channels resulting in spastic paralysis of worms. Sustained
      activation of nicotinic receptors due to inhibition of acetylcholinesterase.
   • Ivermectin- activates worm Cl- channels.

Selective toxicity is achieved by oral adminstration and poor drug
Absorption from the GI tract thereby targeting the parasitic worms.

Tapeworms
Cestodes (Flatworms)

Treatment-Surgical removal is most effective management of the slowly growing cysts that occur in lung and liver of human hosts.

				
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posted:1/31/2013
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