The Effects Of Antibiotic Resistance On Infectious Diseases

Antibiotics, composed of microorganisms such as streptomycin and penicillin, kill other infectious microorganisms in the human body. At one point, antibiotics were considered to have “basically wiped out infection in the United States”, but due to their overuse and evolutionary

“The Last Resort,” by Maryn McKenna is an article about antibiotic resistance. It explains the increase of carbapenem-resistant Enterobacteriaceae also known as CREs which are a class of antibiotic-resistant bacteria. CREs have been described as “a risk as serious as terrorism”(McKenna, 2013, p.394). CREs can cause bladder, lung, and blood infections that can develop into life-threatening septic shock. Unfortunately, it kills half of the people who contract it. This bacteria is resistant even to carbapenems, which are considered drugs of last resort because of the serious health risks in taking them. “Antibiotics have been falling to resistance for almost as long as people have been using them; Alexander Fleming, who discovered penicillin, warned about the possibility when he accepted his Nobel prize in 1945”(McKenna, 2013, p.394). Although CREs was first discovered almost 15 years ago, it did not become a public-health priority until just recently. The North Carolinan strain of Klebsiella produced an enzyme called Klebsiella pneumoniae carbapenemase or KPC for short. It broke down carbapenems which made the strongest antibiotic now resistant. “Physicians find themselves caught between using bad drugs or using no drugs at all”(McKenna, 2013,

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

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).

Science had a type of antibiotics called, carbapenems. The big guns reserved for bacteria that had become resistant to other common antibiotics. Unfortunately, bacteria found a way to resist these antibiotics as well. This resistance is known as CRE: carbapenem resistant enterobacteriaceae. K. pneumoniae, an Extended Spectrum Beta-Lactamases (ESBLs) bacteria, is also Klebsiella pneumoniae carbapenemase (KPC). This means people infected with Klebsiella pneumoniae carbapenemase have few to no options to kill the infection and recover. Infact, bacteria are developing that are resistant to most, if not all antibiotics available to man or at least approved by the FDA in the United

As we seen in the mechanism of action all beta-lactam antibiotics, share a basic chemical structure that includes a three carbon, one nitrogen cyclic amine structure is known as the beta-lactam ring. Beta-lactam ring attached with a side chain having a variable group to the core structure of by a peptide bond. The variation of the side chain contributes to antibacterial activity.FDA has approved over 34 beta-lactam compounds as active ingredients in drugs for human use. Beta-lactam antibiotics have the following five classes:

Cephalosporins are the most prescribed antibiotics because they are among the safest and the most effective broad-spectrum antimicrobial agents. In veterinary medicine, cephalosporins are widely used to treat and prevent various infectious diseases ( Puig et al. 2007). Cefoperazone is one of the parenteral third-generation semi-synthetic cephalosporins antibiotic active against a wide range of Gram-positive and Gram-negative bacteria, including β-lactamases produced by Enterobacteriaceae and Pseudomonas spp. (Johnson et al. 1988 and Hammam et al. 2006). The low level of toxicity and broad spectrum of antibacterial activity of cefoperazone may allow its use as a single agent for the treatment of intra-abdominal infections (Baird 1983).

Only a few decades ago antibiotics was a wonder drug that could cure even the most deadly diseases. Presently, numerous antibiotics have become less effective or potent to against the bacterial infections. This is due to the high effectiveness and how frequently they were used to treat diseases. Serious infections have become resistant to the commonly used antibiotics have caused a major global healthcare concern for not only the present, but also the future. These bacterial infections require more serious and long term treatments, meaning they are usually more expensive and difficult to treat. The “post-antibiotic era” is significant issue that is affecting the way doctors treat bacterial infections, furthermore the steps to slow the process

“Upon receipt of the Nobel Prize in 1945 Alexander Fleming predicted, ‘The time may come when penicillin can be bought by anyone… Then there is the danger that… under-dosing (not taking full schedule of antibiotic as prescribed) will expose microbes to non-lethal quantity of the drug, making them resistant,’” (291) Almost seventy years later and Flemings prediction has come to light. Currently there are three known bacteria strains. They are MRSA (methicillin-resistant staphylococcus aureus), VRE (vancomycin-resistant enterococci), and VISA/VRSA (vancomycin- intermediate/resistant staphylococcus aureus). These resistant strains are what we call super infections because they are a lot harder to get rid of and are highly contagious.

New discovery of antibiotics has slowed down and the select number of pathogenic bacteria in existence are continuing to increase in virulence due to increased exposure. Although advances have been made to address the issue of bacterial resistance to antibiotics, remaining exist that may not be as obvious a threat to fighting especially virulent bacterial

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

Until the 1970s, many new antibiotics found that at first is still sensitive. The last new class of antibiotics discovered in the 1980s (Figure 2.1). After the 1980s increasingly difficult to find new antibiotics, to maintain the efficacy of existing antibiotics were necessary measures to minimize the increase and spread of resistance to antibiotics, while efforts to find and develop new methods of treatment of the infection is still continued.1,15

Carbapenems are Beta lactam antibiotics used as a last resort in medical treatment against several bacterial infections as they possess the broadest spectrum of activity against various gram positive, gram negative and aerobic bacteria (Papp-Wallace et al. 2011). Originally developed from the carbapenem thienamycin which demonstrated the utmost antimicrobial activity, Carbapenems consist of six antibiotics: Doripenem, panipenem, biapenem, imipenem, meropenem and ertapenem all currently present in clinical use (Boromo et al 2011). Carbapenems all have a variety of vital roles in medicine and have helped reduce the threat of severe bacterial infections since the rise of multidrug-resistant pathogens. This can be seen with panipenem which is taken with betamipron to inhibit the uptake of panipenem into the renal tube of the kidney, proving effective in treating surgical and respiratory infections (Goa & Noble, 2003). Although Carbapenem has proved useful as a last resort of antibiotics, enterobacteriaceae a gram negative bacteria commonly consisting of Klebsiella and Escherichia species, has developed mechanisms of resistance to carbapenems (Duin and Perez 2015).These carbapenem resistant enterobacteriaceae (CRE) portray a new profound danger worldwide and require sustained efforts to control as there is little success on the elaboration of antibiotics to replace carbapenem and therefore limiting therapeutic options available to patients.

Many bacterial infections are treated with anti-bacterial agents such as antibiotics. However, due to the uncontrolled use of antibiotics, particularly the prescribing of antibiotics to treat common viral colds and flu, microbial resistance to antibiotic has dramatically increased. (The Health Gazette, n.d.). Scientist have warned that E.coli which has previously been sensitive to antibiotics, is becoming resistant to more antibiotics and in future could become as resistant to antibiotics like that of Methicillin Resistant Staphylococcus aureus (MRSA). In addition, there is a

Superbugs are various strains of bacteria that have become resistant to multiple classes of antibiotics. This resistance has stemmed from the populations overuse or misuse of unnecessary medication and it is allowing various bacteria to become unbeatable to some of today’s most potent antibiotics. An alarming statistic that was recently released, “23,000 people are killed every year out of the 2 million who are be infected by these superbugs” (NIH Feb. 2014). Extended Spectrum Beta-Lactamases (ESBLs) are currently one of the leading superbugs in the world; with a skyrocketing mortality rate and plummeting choices of antibiotics to treat the infections caused by this bacterium, the clock is ticking to find this superbug’s Achilles tendon.