Antimicrobial Resistance in Klebsiella pneumoniae:
Mechanisms and Clinical Impact and Developments
Ryan Cain
BIOM 250
Professor Heinzinger
November 27, 2015 Antimicrobial Resistance in Klebsiella pneumoniae:
Mechanisms and Clinical Impact and Developments Antimicrobial resistance is a growing problem in modern healthcare around the world. Multidrug resistant (MDR) strains of pathogenic bacteria, which are quickly becoming more common, pose a serious risk to patients. One of the most common species of bacteria that cause problems in healthcare today is Klebsiella pneumoniae. Today K. pneumoniae can be responsible for community acquired infections, but is most commonly observed as a major cause of hospital acquired infections which can be fatal. K. pneumoniae has been observed to develop resistance to antibiotics more easily than most bacteria through the production of new enzymes to break them down. As new resistance mechanisms develop, fewer and fewer treatments are available for infections by K. pneumoniae. Although some treatments still remain, few new ones are being explored, thus the best option is to control the development and spread of antimicrobial resistance.
Cellular Characteristics K. pneumoniae is a gammaproteobacterium and part of the family Enterobacteriaceae. They are facultatively anaerobic gram-negative rods that are usually encapsulated and non-motile. They are indole and ornithine decarboxylase negative, ferment lactose, and have a
In June of 2011, a woman entered the National Institutes of Health Research Hospital in Bethesda Maryland with a serious, but fairly routine infection; however the subsequent events were to prove anything but routine. The woman was suffering from an infection caused by an antibiotic-resistant organism, but it was a new strain, never before encountered. About a month after she was treated and discharged, another patient came down with the same infection, and then more and more. After many unsuccessful attempts to isolate the cause of the infections, the NIH eventually used a new technology, known as "Whole Genome Sequencing," to isolate the pattern of infection and bring it under control. (Melissa Block, Eddie Cornish) This process is a new way to quickly isolate and sequence the entire genome of a particular organism, which the NIH used to help identify the pattern of infection. Of the 17 other patients who contracted the infection, six died, but it was learned that the pathogen can be transmitted in ways never before seen. (Melissa Block, Eddie Cornish)
“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,
Klebsiella pneumoniae (contributing the ‘K’ in the ESKAPE acronym) is a strain of bacteria that has recently developed resistance against a class of β-Lactam antibiotics developed from thienamycin (a naturally derived product, discovered in 1976, of Streptomyces cattleya) known as carbapenems. K. pneumoniae is a Gram-negative bacterium compromised of straight rods 1-2 μm in length and contains lipolysaccarides (LPS) in its outer
Widespread use of antibiotics has been very controversial in the media as well in the general population. Due to these controversies, it is very misunderstood to how antibiotics work leading to many patients in the hospital setting wanting to take them when it is not necessary or refusing to take when it is necessary for their survival. Some of this controversy is due to antibiotic resistance, which has spread an alarming rate in the 21st century (Walsh, 2000). Antibiotic resistance is the result of very strong bacteria or microbes that are resistant to the antibiotic prescribed and those microbes accumulate overtime by their survival, reproduction and transfer, leading to increased levels of antibiotic resistance.
Klebsiella pneumoniae, is a gram negative bacillus bacteria, that is nonmobile, encapsulated, bacteria that is hard to treat because of the Multi drug Klebsiella pneumoniae strand that is already grown past antibiotic control (Evaluation 1). To obtain a good view of this bacteria you would do a gram stain to determine if positive or negative,
The overuse and misuse of antibiotics contributes to antibiotic resistance, which persists as a problem because it can further result in a patient’s death. Inpatients are frequently affected by infections in hospitals and antibiotics are given to treat these patients. However, due to the overuse and misuse of antibiotics in
it also belongs to the normal intestinal flora of humans Many bacteria from this genus, including Klebsiella pneumonia are capable of nitrogen fixation. This bacteria is an extremely virulent bacteria in part due to its polysaccharide capsule which makes it more difficult for phagocytosis to occur and also allows the bacteria to easily adhere to and colonize the respiratory and urinary tracts. This virulent bacteria has been given the title of superbug which refers to its resistance to many antibiotics. Its resistance to antibiotics is related to the presence of carbapenemase, an enzyme, in the organism which makes it resistance to carbapenamase. It is only pathogenic when the immune system is compromised due to a chronic illness or debilitation and therefore it is acquired mostly in healthcare settings, mainly long-term care facilities. When it is pathogenic, the bacteria is commonly the causative agent of bacterial pneumonia, a necrotizing lobar pneumonia, and urinary tract infections. Since this bacteria is resistant to many antibiotics and is very virulent, a combination of antibiotics are used to treat it including levofloxacin, ampicillin, meropenem, terizidone and many others. The control of this bacteria is aimed at the prevention of transmission in hospitals with strategies that include contact isolation precautions, proper hand washing and textbook nursing
According to previous, excessive use of antibiotics is one of the causes of drug resistance in different pathogens, this concern has caused many hospitals around the world develop guidelines and strategies to use appropriate antibiotics and are committed themselves to
Mutations and genetic evolutions in the bacteria are two ways resistance is growing. These mutations and genetic evolutions get passed down to the next generation, which makes it difficult for scientists to create antibiotics that work each specific strain of bacteria ("Facts about Antibiotic Resistance" 2016). Many resistant antibiotics have targeted the cells by inhibiting the enzymes that usually stop the spread of the bacteria (Diekema 2016). Scientists need to look into preventing these enzymes from getting blocked so the antibiotics can stop the replicating
to spread, millions of people each year experience chronic infections (Figure 1). , The effectiveness of conventional antibiotics is restrained due to resistance and the difficulty of culturing the bacteria to determine the species causing the infection. If the infection becomes chronic, typically, removal and replacement of the joint is required, resulting in a total joint explant surgery. However, loss of function of the affected body part or life-threatening complications can also ensue. Furthermore, slow growing, small, temporary populations of bacteria that appear to be multidrug-tolerant, called persisters, present in some of these infections. These are highly tolerant to antibiotics, and can form a later, chronic infection from their ability to persist and re-establish.
In-spite of comprehensive efforts to control the spread of mul¬tidrug-resistant organisms (MDROs), the incidence of infections attributed to drug resistant microbes is rising considerably. Infections caused by these resistant microbes have resulted in significant deterioration in clinical outcomes, including an increased death risk and cost of treatment, mostly attributable to increased LOS of patient.
Klebsiella pneumoniae strains that were resistant to third-generation cephalosporins and amikacin were recovered from 62 of 395 patients (15.7%) during 1986. 25 isolates (40%) caused urinary tract infections. The outbreak involved three intensive care units (54 isolates), and spread from one unit to another and then to four wards (8 isolates). K pneumoniae of various serotypes and strains of different Enterobacteriaceae demonstrating the same antibiotic resistance pattern were isolated, which suggests dissemination of an R-factor. The isolates had low-level resistance to third-generation cephalosporins (mode minimum inhibitory concentration of cefotaxime, 2 mg/l) but remained sensitive to cephamycins. Cefotaxime was effective in cases of uncomplicated
This current wide spread of KPC enzymes makes them a potential threat to currently available antibiotic-based treatment protocols (4).
Antibiotic resistance is an ongoing critical threat to the health of patients worldwide. With the advent of mass produced antibiotics, the prevalence of resistance to them seems to have positively correlated with the increasing amount of different antibiotic classes available on the market. This means that another method of erradicating these resistant bacteria must be sought, so not to worsen the situation the world is already in. This must be implemented sooner rather than later, as already in Europe several countries have reported MRSA with a level of 50% resistance present (HM Government, 2014, p.5).
The question of antibiotic resistance is a growing phenomenon in contemporary society and modern medicine; it pertains to pathogenic organisms and is one of the most eminent issues of public health in the twenty-first century. Though resistant genes are ancient, its increasing prevalence poses a threat. It demands a greater need for antibiotic therapies. New resistance mechanisms may spread globally and limit our ability to treat disease and lead to a giant hole in the pillars of modern medicine.