Medical Pharmacology Chapter 35  Antibacterial Drugs

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Bacterial Cell Wall: Sites of Antibacterial Action

Bacterial cell wall structure

Gram-negative Bacterial Membrane Structure

Gram-negative Cell Membrane Model

  • Gram-negative bacteria are surrounded by two membranes.

  • The outer membrane functions as an efficient permeability barrier containing lipopolysaccharides (LPS) and porins.

[graphic: Linda M. Stannard used with permission]

Cell Membrane

 

Peptidoglycan

Cytoplasmic Membrane

 

Gram-positive Bacterial Membrane Structure

Gram-positive Membrane

  • The lipid bilayer cell membrane of most of the Gram-positive bacteria is covered by a porous peptidoglycan layer

[graphic: Linda M. Stannard used with permission]

Peptidoglycan Layers

 

 

Cytoplasmic Membrane

 

 

Multiple sites of inhibition by antibacterial agents

 

Gram-negative Cell Membrane Model

  • Gram-negative bacteria are surrounded by two membranes.

  • The outer membrane functions as an efficient permeability barrier containing lipopolysaccharides (LPS) and porins.

[ graphic: Linda M. Stannard used with permission]

Cell Membrane

PBP: Penicillin Binding Protein: Site of Penicillin Action

Peptidoglycan

Cytoplasmic Membrane

 

Gram-positive Membrane

  • The lipid bilayer cell membrane of most of the Gram-positive bacteria is covered by a porous peptidoglycan layer

[graphic: Linda M. Stannard used with permission]

Peptidoglycan Layers

 

Penicillin-binding Protein (PBP): Site of Penicillin action

Cytoplasmic Membrane

 

 

 

Chambers, H.F., Hadley, W. K. and Jawetz, E. Beta-Lactam and Other Inhibitors of Cell Wall Synthesis,in Basic and Clinical Pharmacology,(Katzung, B. G., ed) Appleton-Lange, 1998, p. 725.; Archer,G.L. and Polk, R.E. Treatment and Prophylaxis of Bacterial Infections, In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, p. 859.

Archer,G.L. and Polk, R.E. Treatment and Prophylaxis of Bacterial Infections, In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, p. 862-863; Chambers, H.F., Hadley, W. K. and Jawetz, E. Beta-Lactam and Other Inhibitors of Cell Wall Synthesis,in Basic and Clinical Pharmacology,(Katzung, B. G., ed) Appleton-Lange, 1998, p. 724.

Archer,G.L. and Polk, R.E. Treatment and Prophylaxis of Bacterial Infections, In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, p. 859.

 

Acid and -Lactamase Resistant Penicillins

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Chambers, H.F., Hadley, W. K. and Jawetz, E. Beta-Lactam and Other Inhibitors of Cell Wall Synthesis,in Basic and Clinical Pharmacology,(Katzung, B. G., ed) Appleton-Lange, 1998, p. 729.

 

 

Microorganisms

1Bacteriodes fragilis 

  • B. fragilis  is probably the most important of all anaerobes based on the likelihood of occurrence in clinical settings as well as because of its resistance to many antibiotics.

  • Bacteriodes fragilis is classified as a gram-negative Bacillus exhibiting rounded ends and are usually encapsulated.

  • Review: gram-negative aerobic bacilli are responsible for numerous infection types ranging from oral to bone infections.  Pathological manifestations include participation in pathologic processes such as periodontal disease and colon cancer.  Gram-negative bacteria release enzymes such as neuraminidase and collagenase which facilitate organism tissue penetration.

    • Anaerobic infections include: bite infections, oral or dental infections, empyema, lung abscess, aspiration pneumonia, post-abortion infections, appendicitis, diverticulitis, septic thrombophlebitis, and septicemia which may be associated with diabetes, cancer, "negative" blood cultures and corticosteroids.

1 Sydney M. Finegold "Anaerobic Gram-Negative Bacilli" in Medical Microbiology (4th edition) edited by Samuel Baron, M.D., The University of Texas Medical Branch

E . coli

Klebsiella pneumoniae

Serratia (a, left)  Image credit: Shirley Owens and Catherine McGowan, Microbe Zoo
Project, Comm Tech Lab, Michigan State University. Serratia (b, right) EuroMech 422 Pattern Formation by Swimming Micro-Organisms

 

 

Proteus

 

  • 2In the clinical laboratory setting, E . coli (Escherichia coli) is probably the most commonly isolated organism.  E . coli is a member of the group of pathogens called coliform bacilli which include these genera  Escherichia, Enterobacter, Citrobacter, Klebsiella, and Serratia.  Additionally, Proteus is a member of this group.  Many of these organisms are normally found in the gastrointestinal tract, thereby being considered normal flora.

    • Infections:

      • Enteric infections -- E . coli is a major contributor to infections, especially in the developing countries, as a major enteric (intestinal) pathogen.

      • Nosocomial infections (hospital acquired infections) are frequently (frequency = 29%  in United States) due to Coliform and Proteus bacilli. These organisms are frequently responsible for urinary tract infections (46%) and infections associated with surgical sites (24%).  E . coli is the most prominent nosocomial pathogen.

      • Community-acquired infections:

        • As noted above for nosocomial infections come E . coli is prominent as a cause of urinary tract infection's in the community acquired environment.  Urinary tract infections include prostatitis and pyelonephritis.  Other common pathogens responsible for urinary tract infection's include Proteus, Klebsiella, and Enterobacter.  Proteus mirabilis is the most likely cause of infection-related kidney stones.  Klebsiella pneumoniae  causes severe pneumonia.

2 M. Neal Buentzel "Escherichia, Klebsiella, Enterobacter, Serratia, Citrobacter, and Proteus" in Medical Microbiology (4th edition) edited by Samuel Baron, M.D., The University of Texas Medical Branch,

3Moraxella catarrhalis

  • 3Moraxella cattarrhalis, a gram-negative bacteria often found in normal human upper respiratory tract flora, are similar in appearance to Neisseria cells .  Occasionally, Moraxella cattarrhalis may cause significant lung disease such as pneumonia and acute bronchitis as well as important systemic infections including meningitis and endocarditis.  In both children and adults, this organism may be commonly responsible for otitis media, sinusitis, and conjunctivitis. (Moraxella cattarrhalis may cause as many as 20% of otitis media presentations)

    • Moraxella cattarrhalis may be responsible for lower respiratory tract infection in those adults who have chronic lung disease.

    • This organism is often found in the normal flora and children (frequency = 40%-50%).

    • Moraxella cattarrhalis can cause symptoms that are very similar, nearly indistinguishable from those caused by gonococci, so the differential assessment is quite important.  Also, many Moraxella cattarrhalis strains elaborate beta-lactamase making them resistance too many beta-lactam antibiotics.

3 Stephen A. Morse "Neisseria, Moraxella, Kingella, and Eikenella" in Medical Microbiology (4th edition) edited by Samuel Baron, M.D., The University of Texas Medical Branch, andVolk WA, Gebhardt BM, Hammarskjold M-L, et al, eds. Essentials of Medical Microbiology, 5th ed. Philadelphia, PA: Lippincott-Raven; 1996. and GlaxoSmithKline, 2001 (Augmentin use)

 

Mandell, G.L. and Petri, W. A. Antimicrobial Agents: Penicillins, Cephalosporins, and other -Lactam Antibiotics.,In, Goodman and Gillman's The Pharmacologial Basis of Therapeutics,(Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) TheMcGraw-Hill Companies, Inc.,1996, pp.1089-1092

 

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Chambers, H.F., Hadley, W. K. and Jawetz, E. Introduction to Antimicrobial Agents in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp. 732-733.

Chambers, H.F., Hadley, W. K. and Jawetz, E. Introduction to Antimicrobial Agents in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, p. 734.

Chambers, H.F., Hadley, W. K. and Jawetz, E. Introduction to Antimicrobial Agents in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp. 734-735.

Chambers, H.F., Hadley, W. K. and Jawetz, E. Introduction to Antimicrobial Agents in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp. 734-735.

Chambers, H.F., Hadley, W. K. and Jawetz, E. Introduction to Antimicrobial Agents in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp. 732-736;Chambers, H.F., Beta-Lactam Antibiotics and Other Inhibitors of Cell Wall  Synthesis in Basic and Clinical Pharmacology, (Katzung, B. G., ed), Appleton-Lange, 2001, p. 766.

 

Shannon, M.T., Wilson, B.A., Stang, C. L. In, Govoni and Hayes 8th Edition: Drugs and Nursing Implications Appleton and Lange, 1995, pp. 166-167.

Chambers, H.F., Hadley, W. K. and Jawetz, E. Introduction to Antimicrobial Agents in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, p. 737..;Shannon, M.T., Wilson, B.A., Stang, C. L. In, Govoni and Hayes 8th Edition: Drugs and Nursing Implications Appleton and Lange, 1995, pp. 614-615.

Chambers, H.F., Hadley, W. K. and Jawetz, E. Introduction to Antimicrobial Agents in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp. 736-737.