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Chapter 1 : Antibiotics: Initial Concepts and Considerations

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Antibiotics: Initial Concepts and Considerations, Page 1 of 2

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Abstract:

Infectious diseases kill about 14.9 million people a year worldwide, with pneumonia and related lower lung infections responsible for more than 3 million deaths (Fig. 1.1) (Morens et al., 2004). Diarrheal diseases cause about 1.8 million deaths and tuberculosis about 1.5 million deaths. In the United States alone, about 53,000 people succumb to pneumonia (http://www.cdc.gov/nchs/fastats/pneumonia.htm) and more than 130,000 to septicemias (http://www.hcup-us.ahrq.gov/reports/statbriefs/sb122.pdf) each year (http://who.int/mediacentre/factsheets/fs310/en/). While some bacterial diseases are largely prevented by vaccination campaigns, many others require acute treatment once a person is infected. Those acute treatments are courses of antibiotic therapy. Figure 1.2 illustrates graphically that resistant bacterial, viral, and parasitic pathogens are global phenomena. Outbreaks in one part of the world spread to other regions and continents with air and sea travel.

Citation: Walsh C, Wencewicz T. 2016. Antibiotics: Initial Concepts and Considerations, p 4-15. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch1
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Figures

Image of Figure 1.0
Figure 1.0

Decrease in the number of companies producing antibiotics from 1980s–2010s (Kinch et al., 2014).

Citation: Walsh C, Wencewicz T. 2016. Antibiotics: Initial Concepts and Considerations, p 4-15. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch1
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Image of Figure 1.1
Figure 1.1

Infectious diseases remain major killers of humans in the 21st century. STD, sexually transmitted disease. (Reprinted from Morens et al. [2004] with permission.)

Citation: Walsh C, Wencewicz T. 2016. Antibiotics: Initial Concepts and Considerations, p 4-15. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch1
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Image of Figure 1.2
Figure 1.2

Infectious disease outbreaks occur in all parts of the globe, including reports of drug-resistant pathogens. SARS, severe acute respiratory syndrome; vCJD, variant Creutzfeldt-Jakob disease. (Reprinted from Morens et al. [2004] with permission.)

Citation: Walsh C, Wencewicz T. 2016. Antibiotics: Initial Concepts and Considerations, p 4-15. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch1
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Image of Figure 1.3
Figure 1.3

The sulfonamide antibacterial drugs have been in continuous use for 80 years. The founding member of the class is -aminobenzenesulfonamide, arising from metabolic reduction of the prodrug prontosil. The active drug blocks bacterial DNA synthesis by denying access to deoxythymidylate, a key building block for DNA replication.

Citation: Walsh C, Wencewicz T. 2016. Antibiotics: Initial Concepts and Considerations, p 4-15. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch1
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Image of Figure 1.4
Figure 1.4

The Gram stain, a venerable cytological test, groups bacteria into two large classes, Gram negative and Gram positive, based on the structures of the cell walls and the resultant permeability barriers. (a) Schematic of staining procedure; (b) micrograph of stained Gram negative and Gram positive bacteria; (c) electron micrographs showing the distinct layers of cell wall architecture of Gram-negative and Gram-positive bacteria.

Citation: Walsh C, Wencewicz T. 2016. Antibiotics: Initial Concepts and Considerations, p 4-15. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch1
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Image of Figure 1.5
Figure 1.5

Flow chart for discovery and development of a prototypical antibiotic. Timelines and projected costs are estimates in line with industry standards. NDA, New Drug Application. (Ryan and Patterson, 2002)

Citation: Walsh C, Wencewicz T. 2016. Antibiotics: Initial Concepts and Considerations, p 4-15. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch1
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Image of Figure 1.6
Figure 1.6

Timeline for discovery and commercialization of new antibiotic classes in human clinical use from 1940 to 2014. An innovation gap from 1960 to 2000 is shown.

Citation: Walsh C, Wencewicz T. 2016. Antibiotics: Initial Concepts and Considerations, p 4-15. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch1
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Image of Figure 1.7
Figure 1.7

Chart showing the growing incidence of three drug-resistant bacterial pathogens over the 25-year period from 1980 to 2005. MRSA, methicillin-resistant ; VRE, vancomycin-resistant enterococci; FQRP, fluoroquinolone-resistant pseudomonal infections. (Reprinted from Infectious Diseases Society of America [2004] with permission.)

Citation: Walsh C, Wencewicz T. 2016. Antibiotics: Initial Concepts and Considerations, p 4-15. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch1
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