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
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
• Blood dyscrasias
(granulocytopenia, fatal aplastic
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
• The pharmacokinetic properties of the fluoroquinolones are
– 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)
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.
Cefaclor (H. influenza, M. Fluoroquinolones (Levo, Gat, Moxi) – all active against all
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)
Cefaclor (H. influenza, M. Azithromycin (H.influenza, M.
catarrhalis, variable for S. If unresponsive-
catarrhalis) 3rd Generation Cephalosporin + Macrolide (erythromycin or
Gatifloxacin, Moxifloxacin are
active against all three infectious
• 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
• 1st and 3rd generation Cephalosporins
• Imipenem (in penicillin-resistant disease)
• Vancomycin (in penicillin-resistant disease)
• Doxycycline (in penicillin-resistance/allergy)
• Macrolides (legionella, mycobacterium)
• Levofloxacin (legionella, also others in penicillin-resistance/allergy)
• Gentamicin (in gram-negative infections)
Treatment of Bacterial
• 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
• Africa, SE Asia Mefloquine,Doxycycline
• Carribean, Central
America, Middle East Chloroquine
Any relapse Primaquine (gametocidal)
Chloroquine – Not for used in patients with
Persons taking amiodarone or halofantrin
Cautious use of chloroquine in patients
Long term use can result in blindness
Mefloquine– Not for used in patients with
1st trimester of pregnancy
Children under 5 kg
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
Glucose-6-phosphate deficiency (hemolytic anemia)
Pyrimethamine-sulfadoxine- Not for use in patients with
Allergic reactions to any sulfa drug
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
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
Treatment – trimethoprim-sulfisoxazole
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
– 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
• 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-sulfadiazine- toxoplasmosis
• 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
• Diphyllobothrium, fish tapeworm native to U.S. Risk factor- eating raw or undercooked fish from northern U.S. rivers and lakes,
• 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.
Treatment-Surgical removal is most effective management of the slowly growing cysts that occur in lung and liver of human hosts.