A. General problem of antibiotic resistance to medicine
Antibiotics are chemical substances utilize to prevent and treat infections caused by microorganisms, such as bacteria, parasites and fungi. Medications play a role by suppressing or inhibiting the growth of microorganisms (Sanders et al. 2011). There are more than 150 antibiotics currently available, but only 125 are effectively used for treatment (Zuchora-Walske 2014). Antibiotics have shown to improve the health of an human being significantly (Fabbretti et al. 2011) by providing treatment for tuberculosis, gonorrhea, methicillin-resistant Staphylococcus aureus (MRSA), bronchitis, urinary infections and many others (Tindall et al. 2013). Yet, antibiotic resistance is a worldwide issue that has expanded and persisted among all the nations on earth. New strains of antibiotic-resistant microbes migrate easily from different places on the planet, and they often create a ‘worldwide threat’ among the society (Levy 2002).
Due to the pathogenic bacteria, the developing countries have been impacted on malnutrition, poor sanitary conditions and lack of medical sources much more than developed nations (Alanis 2005). Over the counter antibiotics can be obtained more easily in developing countries in comparison with other developed nations whereas their access is more restrict (Alanis 2005). Resistant strains evolved in the presence of climacteric instability, war and migrations due to the introduction of new strains in the communities. Antibiotics, that where effective prior to the environmental catastrophes, are no longer effective or efficient to treat infections (Baquero and Campos 2003).
The biggest challenge is when the most clinical significant pathogens become resistant towards the most widely effective drugs in the medical field (Lee et al. 2013).
One of the settings in which antibiotic resistance is most concerning is a hospital. In the United States (US), numerical data for antibiotic resistance have been collected from hospitalized patients since 2002 (Collins 2008). Yearly, more than 35 million US patients require hospital care due to infection or disease (Wenzel and Edmond 2001). Additionally, exposure to antibiotic-resistant microorganisms in intensive care units exposes patients to a 60% risk of acquiring nosocomial infections (Haddadin et al. 2002). Nearly 2 million of these patients develop hospital-acquired infections during treatment, 55% of which involve antibiotic-resistant bacteria (Stone 2009).
Some infections, such as methicillin-resistant Staphylococcus aureus (MRSA), have resist and spread throughout hospitals, clinical settings, and among the society. Nowadays, there are only a few effective drugs that can control MRSA (David and Daum 2010). With restricted options to cure infections, healthcare providers propose to increase medical fees and introduce patients to medications with potentially side effects (David and Daum 2010). Without effective antimicrobial agents, the individual is approximately 70% more susceptible to die (Frieden et al. 2013).
Researchers have seen a consistent and rapid increase in antibiotic resistance, especially in recent years. Sydnor (2011) stated that hospital epidemics can be minimized if accurate surveillance of nosocomial infections are installed, best practices are implemented to prevent and treat them, and health care personnel are trained to avoid transmission of infectious microbes from patient to patient (Sydnor et al. 2011). As of 2011, Netherlands was reported to have the lowest antibiotic consumption rate compare to any other country in Europe and believe that antibiotic resistance can be prevented by reducing the dosage of antibiotics prescribed to a patient (Vandenbroucke – Grauls 2014).
Nosocomial infections have been caused by pathogens that acquired resistant to antibiotics. In the U.S., National Nosocomial Infections Surveillance (NNIS) stated that approximately 60% of S. aureus infections that derived from intensive care units were methicillin resistant, and the number of infections rose 29% from 2005 to 49% in 2009 (Sydnor and Perl 2011). Vancomycin resistance in Enterococcus faecium infections increased from 9,829 infections in 2000 to roughly 22,000 infections in 2006 (Sydnor and Perl 2011). Enterococcus faecium is also more commonly resistant to vancomycin than other species, such as Haemophilus influenza and Neisseria gonorrhea (Wisplinghoff et al. 2004).
Community environment have also shown signs of bacterial infections that created resistance to antibiotics. For instance, Mycobacterium tuberculosis is a community-acquired pathogen responsible for tuberculosis (TB), which infects 30% of the human population and accounts for nearly 2 million deaths annually (Jensen et al. 2005). Until 2002, streptomycin antibiotic was routinely used to treat patients with tuberculosis (Gillespie 2002). Drug resistance developed because Mycobacterium tuberculosis was continuously exposed to a single drug, overcoming the power of the streptomycin. Gillespie studies (2002) showed that a combination of isoniazid, pyrazinamide, rifampin and ethambutol drugs were able to control and prevent tuberculosis from expanding (Gillespie 2002). As of 2014, a combination of multiple drugs ended up diminish the number of spontaneous mutations and increasing the treatment rate by 48% (Fonseca et al. 2015). Hence, antibiotic-resistant pathogens have become a major concern not only in the healthcare facility, but also in community settings (Tomasz 1994).
2. Mortality rate
Mortality and morbidity rate are escalating due to the prevalence of antibiotic resistance in intensive care units patients (Hanberger et al. 2014). Non resistant strains are nonpathogenic, while antibiotic resistant strains are pathogenic, leading to an increase death rate (Hanberger et al. 2014). In the US, about 2 million people develop bacterial infections from 2005 through 2008 that were resistant to more than one antibiotic, resulting to an estimated 99,000 deaths (Kallen et al. 2010). In 2011, the EU had nearly 2 million people with acquired nosocomial infections that lead to 200,000 deaths. In the EU, the segregation of vulnerable patients within the same area increase the probability for the resistant strains to pass from one person to another more than in US, because EU does not have efficient preventive measure to minimize the spread of nosocomial infections (Guggenbichler et al. 2011).
Based on Table 1, multi-drug resistance (MDR) M. tuberculosis is one of the three organisms that cause the highest mortality in humans. Highly diverse populations and poor sanitation develops multidrug resistance which contribute to 95% of mortality rate in low and middle-income states (Drobniewski et al. 2015). Studies in Estonia showed that patients with tuberculosis are more compromised if MDR strains are present (Blondal et al. 2013). As of 2007, in India MDR TB was twice as common in TB patients living with HIV versus in TB patients without HIV because patients were showing spontaneously resistant mutants in reserve drugs, such as ofloxacin (Isaakidis et al. 2011).
Despite the fact that MDR is curable, its treatment depends upon extensive chemotherapy that is exceptionally costly for low income nations. Efforts to prevent the spread of the infection highly depend on the socioeconomic status of the country (Olson et al. 2012). Implementation of new programs, effective screening tests, and efficient therapy options assist reducing the mortality rates in U.S. patients. According to Geiter, individuals that have contract tuberculosis outside of US and move to reside in the US are responsible for the increase of 27% in 1992 to 43% in 1999 (Geiter 2000). Non- American populations infected with TB have a higher mortality rate due to the decline of resources for TB control and due to overpopulated environments such as hospitals, prisons, and homeless shelters (Keshavjee et al. 2008). Maintaining the low mortality of TB in the U.S. will demand continued prevention and control efforts, specifically fast diagnosis, guaranteed accomplishment of treatment, efficient and complete reporting (Geiter 2000).
Vancomycin-resistant Enterococcus (VRE) infections are also emerging as serious health risks. A patient who contracts VRE is considered immunosuppressed because he/she has been previously exposed to the organism during a major surgery or other medical procedures which have been treated with multiple antibiotics (Collins 2008). These infections pose a 10% risk of death in patients with graft transplant, but almost 70% in those with endocarditis, tumors and liver transplants (Kapur et al. 2000). Nonetheless, some authorities are more skeptical and tend to admit that patients might have other medical conditions that could lead to the increase of mortality and not necessarily attribute to VRE infections (Cho et al. 2013). Several drugs have been used effectively against VRE, but its mortality rate (Table 1) still spiked (Cho et al. 2013). A potential reason for high mortality rates among VRE infections is because VRE can potentially transfer genetic traits to S. aureus, another organism with high fatality rates (Cetinkaya et al. 2000). According to Table 1, VRE is the fourth most common antibiotic resistant pathogen with the highest expected annual causes in the US and the third most common with the highest annual deaths.
Antibiotic- Resistant pathogens Expected annual cases of antibiotic resistant infections in the US Expected annual
deaths in the US
Vancomycin-resistant Staphylococcus aureus (VRSA) N/A 0
Drug-resistant Mycobacterium tuberculosis 9,582 1,631
Drug-resistant Candida 3,400 220
Multidrug-resistant Acinetobacter 7,300 500
Carbapenem-resistant Enterobacteriaceae 9,000 600
Vancomycin-resistant Enterococcus 20,000 1,300
Methicillin-resistant Staphylococcus aureus (MRSA) 80,461 11,285
Drug-resistant Neisseria gonorrhoeae 246,000 N/A
Drug- resistant Campylobacter Jejuni (Gillespie et al. 2006) 310,000 120
Table 1 – Comparison of annual antibiotic resistant infections with annual deaths in U.S patients due to several types of bacteria (most data condensed from text in (Frieden 2013)).
3. Health care costs
Antibiotic resistance is a financial burden on the healthcare system. Physicians are obligated to treat individual patients with the most effective drugs for an infection. Health care institutions believe that hospital expenses is a form of reimbursing physicians for their service to the society (Roberts et al. 2009). Patients, on the other hand, demand a better healthcare service, better quality of life for them and for those around them (Roberts et al. 2009).
Antibiotics for bacterial infections are costly, and sometimes hospitalization is required until the infection is cleared, further raising costs (Roberts et al. 2009). In the US, Ventola’s (2015) statistics showed that antibiotic-resistant infections incur roughly $20 billion in annual healthcare costs (Ventola 2015). Ventola (2015) estimated that each patient with antibiotic-resistant infections from a single healthcare institution cost from $19 to $29 thousand dollars (Ventola 2015). According to a study by Dellit (2007), VRE infections required up to 17 days of hospital care with an average cost of $27,000 (Dellit et al. 2007). In the case of antibiotic-resistant Pseudomonas aeruginosa infections, the average hospital fees were $54,081 per patient, compared to $22,116 for those infected with antibiotic-vulnerable strains of P. aeruginosa (Slama 2008).
S. aureus infections are expensive to treat, and MRSA is more costly than methicillin-sensitive S. aureus infections (Singh et al. 2006). Inpatient treatment, which includes overall/basic hospitalization costs, antibacterial drugs, preliminary exams, and imaging will total close to $35,000 for patients with resistant strains (Filice 2010). Assuming that 15% of the US patients become infected annually, the costs associated for only MRSA infections would be approximately $45 million (Filice 2010).
Currently, several elements have played a vital role in the cost of controlling infection. The cost to create a new antibiotic is recently calculated at $1 billion (Slama 2008). Not only are novel antibiotics needed, but surveillance within each hospital must be augmented (Slama 2008). Hospital administration plays a vital role on controlling resistant pathogens, as well as enforcing rules to limit resistant strains from spreading. Hospitals or medical centers can only initiate surveillance programs or policy changes to improve infection control if there is financial support. Without financial support, resistant pathogens will continue to develop and spread, and the quality of health care worldwide will be drastically affected (Slama 2008).
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