Modern Medicine Has Been The Development Of Antibiotics1

Everyone knows how useful penicillin is today in the modern age as an antibiotic. Some people might even know about the story behind its discovery. What they don’t know about is the long history behind this medical discovery. They especially don’t know about the hard work of several scientists who brought the idea of penicillin to life. From the earliest discovery of penicillin in 1896 by Ernest Duchesne to the start of its mass production in 1948 and now the modern world of the twenty-first century, it has come a long way. In fact, penicillin has risen from just a bit of Penicillium mold and a mistaken discovery to the life-saving antibiotic agent it is today.

The TEM-1 type of Beta-lactamase is the most common -lactamase enzyme found in E. coli. More importantly, this enzyme is highly interactive with antibiotics by inhibiting antibiotics from accomplishing their purpose of: halting the synthesis of bacteria cell walls to cease the spread and existence of the bacteria. This makes TEM type

Gram-Negative infections are a major cause of mortality in the hospital, intensive care unit and healthcare system. For years the Carbapenems have been a major last line player in eliminating infections. Carbapenem resistance is now increasing. Two drugs Avycaz and Zerbaxa are available to fight against those microbes with Carbapenem resistance. The newly approved combination drug Avycaz is composed of Ceftazidime and Avibactam. Ceftazidime is a 3rd generation cephalosporin. It inhibits bacterial cell wall synthesis by binding to the penicillin binding protein. Avibactam is a non- Beta lactam Beta Lactamase Inhibitor. It is essential in increasing the

β-lactam antibiotics (beta-lactam antibiotics) are a class of broad-spectrum antibiotics, consisting of all antibiotic agents that contain a beta-lactam ring in their molecular structures. They kill bacteria by generally inhibiting their cell wall synthesis. They are mainly active against gram positive bacterias but many gram negative bacteria are also susceptible to amoxicillin. Staphylococcus aureus being a gram positive bacteria are highly susceptible to amoxillin.

Antibiotics have played an essential role in the fight against diseases and infections since the 1940’s. Antibiotics are a leading cause for the rise of global average life expectancy in the 20th and 21st century. They have greatly reduced illnesses and deaths due to diseases. With the introductions of antibiotics in the 1940’s, like penicillin into clinical practice, formally deadly illnesses became immediately curable and saved thousands of lives (Yim 2006). Antibiotic use has been beneficial and when prescribed and taken correctly their effects on patients are exceedingly valuable. However, because these drugs have been used so widely and for such a long period of time the bacteria that the antibiotics are designed to kill have adapted,

wall and how antibiotics work. The cell wall is designed to maintain the cell’s shape and

Before the discovery of penicillin, infection with S. aureus had a fatality rate of approximately 70%. After penicillins discovery and development, treatment of S. aureus infections became routine resulting in the death rate falling to 25%.5 However, penicillin use provided an inadvertent selection pressure which resulted in the bacteria mutating and becoming resistant to its effects. The penicillin-resistant S. aureus strains produced enzymes known as penicillinases which break penicillin down. In 1959, the antibiotic methicillin was developed to battle penicillin-resistant S. aureus infections. At first it was effective, but with increasing use of methicillin S. aureus once again acquired resistance through the process of natural selection

There is a huge need for antibacterial drugs as infectious diseases are the second leading cause of death worldwide and the third leading cause of death in developed countries (Projan, 2003). Over the past 60-70 years, most antibiotics have been discovered by screening of soil samples for natural products that kill bacteria, including known pathogens, first on culture plates and then in animal infections (Walsh, 2000). There are three proven targets for the main antibacterial drugs, bacterial cell all biosynthesis, bacterial protein synthesis, and bacterial DNA replication and

Penicillin, as well as other β- lactams, inhibits the enzyme that places essential cross-links between the individual polymer strings of the cell wall. It does this specifically by using the β-lactam ring to irreversibly block the active site of the enzyme, which catalyzes the reaction, transpeptidase. This inhibition allows the bacteria to newly synthesize a cell wall and to elongate, but not divide. This is due to the lack of cross-linking. The result is disruption of cell wall integrity, making the cell osmotically unstable and susceptible to lysis (Walsh, 2003). Penicillin reacts with the transpeptidase to form a stable acyl intermediate. The β-lactam ring acylates the hydroxyl group of one specific serine residue in the transpeptidase, producing an inactive penicilloyl-enzyme complex (Williams et al.,

Since antibiotics, such as penicillin, became widely available in the 1940s, they have been called miracle drugs. They have been able to eliminate bacteria without significantly harming the other cells of the host. Now with each passing year, bacteria that are immune to antibiotics have become more and more common. This turn of events presents us with an alarming problem. Strains of bacteria that are resistant to all prescribed antibiotics are beginning to appear. As a result, diseases such as tuberculosis and penicillin-resistant gonorrhea are reemerging on a worldwide scale (1).

Two main mechanisms are responsible for resistance to aminopenicillins: enzymatic hydrolysis of the antibiotic and a change in penicillin-binding proteins (PBPs). The more frequent is the production of β-lactamase, usually of the TEM-1 type but sometimes of the ROB-1 type [2]. The incidence of strains producing β-lactamase is particularly high in many countries [3;

Infections and illnesses that were once fatal could now be easily treated with Penicillin (Eickhoff 1). Before the antibiotic boom, people’s lives succumbed to infections and diseases while in the 21st century a simple antibiotic and rest could cure within a couple of days. From the beginning of time disease and infection consumed people's thoughts and fears. They were sickened by the thought of ever catching a horrendous illness. Every cold and cough could their last, but because of penicillin and antibiotics, people of today are not frightened for their lives over a slight fever. One Patient with Ludwig’s angina on the floor of her mouth could barely breathe. Usual patients would suffocate but with the aid of Penicillin, she could breathe again within a 36 hour period (Koop 1). Once again proving the potency of the miraculous drug. Moreover, “the technologies developed for the production of penicillin, including both microbial strain selection and improvement plus chemical engineering methods responsible for successful submerged fermentation production. These became the basis for production of all subsequent antibiotics in use today (Demain 1)”. Penicillin is perhaps one of the greatest things to happen to the world. It has prolonged so many lives by not only as a drug but as jumpstarting the technology and machinery for the ever evolving world of health and medicine. Penicillin is one of the

Polymyxin B1 (PMB1) is a small antimicrobial lipopeptide first derived from the bacterial species Bacilus Polymyxa in 1947[25, 29, 189]. It’s structure is made up of a cyclic polypeptide ring and a fatty acid tail with sequence: DabC-Thr-Leu-DPhe-Dab-DabC-Dab-Thr-Dab-OC9H17. Some of the residues forming the peptide segments are irregular amino acids such as D-Phenylalanine and α, γ-Diamino Butyric acid (DAB). DAB amino acids carry a charge of +1, and with five DABs present this gives the cationic peptide a total charge of +5 [34]. PMB1 is known to be highly potent and is selective principally to gram-ve bacteria, it is effective against all but the Proteus group [190]. It has been shown to successfully treat infections caused by Pseudomonas aeruginosa, with only limited confirmation of resistant strains developing [25, 191-193]. It has been referred to as a “last hope” antibiotic, due to it’s potency and resilience against resistance [193]. It also possesses the unconventional trait (among AMPs) of showing anti-endotoxin activity, meaning it has

The advent of penicillin forever changed the world of medicine at its discovery with its ability to treat diseases, deadly at the time, that are now considered commonplace and easily treatable. Penicillin was one of the greatest discoveries of the twentieth century, as antibiotics are one of the most highly prescribed drugs in the world today. Although its discovery is often described as serendipitous, the process by which it was cultivated was quite meticulous, and continued attention has been paid to penicillin's further development. It is because penicillin and its derivatives have played such a vital role in everyday medicine that it is such an important topic.

B-lactam antibiotics, characterized by a four membered B-lactam ring, have treated infectious diseases since their discovery in 19281. B-lactam antibiotics currently occupy more than 65% of the world’s antibiotic market and consist of a variety of different drug classes such as penicillins, cephalosporins, carbapenems, and monobactams. They treat a variety of bacterial infections caused by bacterial organisms. The B-lactam antibiotics target bacteria, both Gram-positive and Gram-negative, by attacking the cell walls8 of bacterial enzymes, more commonly known as penicillin-binding proteins (PBPs), in a mecha-nism that is currently unknown. The ever-increasing inefficacy of B-lactams has led scientists to begin studying B-lactamases – the culprit