The Antibiotic Resistance in Drug Resistant Tuberculosis

The Antibiotic Resistance in Drug Resistant Tuberculosis

Introduction

Regardless of the type, drugs are made to help fight diseases through cure or pain relief, which involves either killing the disease-causing pathogens or inhibiting their activities. Unfortunately, not all drugs attain these goals because some organisms that cause illness are resistant or fight the drugs, instead. This paper examines the drug-resistance notion, with the sole focus on drug-resistant tuberculosis (TB) to antibiotics. In particular, it reviews three scholarly studies on three antibiotic drugs that have been proven to be resistant to drug-resistant tuberculosis (TB). The articles to be analyzed are those written by Stagg et al. (2017), Heep et al. (2001), and Gill et al. (2019), while the drugs discussed in each of these articles include Rifampin, Isoniazid, and Fluoquinolone.

According to WHO (2018), the bacteria (pathogens) that cause TB (tuberculosis) can become resistant to antimicrobial drugs designed to help cure this disease. When TB develops such resistance, it turns into an MDR-TB (Multidrug-resistant TB), which is a form of tuberculosis that fails to respond to some of the most powerful drugs that fight TB –  Rifampin, and Isoniazid. In some cases, such as the continued use of these drugs, the patient may develop more severe conditions of drug-resistant TB. In reviewing the findings on different studies on drug-resistant TB and the drugs to which it is resistant, this research at unraveling the reasons behind such reactions, as well as provide well-thought strategies that can help leverage the resistance. Part of finding a solution to this problem involves identifying the necessary steps to take and alternative drugs that patients can use in such cases.

Judging by the WHO’s descriptions, the resistance of bacteria (pathogens) that cause TB (tuberculosis) to drugs is relatively widespread information that many people know. Nonetheless, this narrative leaves out some crucial data. While many people are aware that two of the most powerful anti-TB drugs, Rifampin and Isoniazid, sometimes fail to cure TB or relieve the pains associated with it, they do not know that other antimicrobial drugs such as Fluoquinolone have a similar effect. The danger in this lack of knowledge is that a patient may use Fluoquinolone as a substitute for Rifampin and Isoniazid, not knowing that these drugs are likely to have a similar effect – resistance. Such a situation would lead to the development of more severe conditions of drug-resistant TB.

It stands that if the public has little to no knowledge of other drugs to which TB is resistant, and then they also do not know how to handle such a situation. It is this knowledge gap that this paper strives to bridge. Not only is adding another drug to the list of the most powerful drugs that TB fights, but also outlining the measures that both the patients and physicians should take when such situations arise. In essence, it answers the question, “What should be done when a TB patient develops Multidrug-resistant TB and becomes resistant to some of the most powerful anti-TB drugs such as Rifampin, Isoniazid, and Fluoquinolone?” The simplest answer could be to “seek alternative treatment measures.” Still, without proper guidance on which steps to take or even evaluate the necessity of other methods, such a move would only prove chaotic. The patient may develop a more severe MDR-TB condition, which is likely to lead to permanent body damages or even death. The good news is that this paper is designed to provide the most appropriate guidance.

Review of the Articles and Drugs

Stagg, H., Lipman, M., McHugh, T., & Jenkins, H. (2017). Isoniazid resistant tuberculosis- a cause for concern? Int J Tuberc Lung Dis , 129-139.

Methodology

In research to study Isoniazid resistant tuberculosis, Stagg et al. (2017) reviewed a set of data sources on different areas of study. They included the prevalence of phenotypic Isoniazid resistance, genotypic versus phenotypic INH resistance, the relative prevalence of mutations of resistance, and outcomes of treatment inactive disease. The research also focused on the regimens of treatment for active disease, progression to MDR, and regimens of treatment for LTBI.

Results

In their review of Isoniazid resistant tuberculosis, Stagg et al. (2017) posited that this drug, also referred to as INH, is crucial to the global programs used to control TB. With their sole focus on the countries of the former Soviet Union, these researchers stated that 16.1% of TB cases in these regions and 7.5% of the same incidents outside these settings are reported to have MDR (non-multidrug resistant) TB to Isoniazid. This resistance is blamed on poorer outcomes of treatment, death, and post-treatment relapse in some parts of the world. Although phenotypic resistance is pegged on multiple genetic loci, the relationship between phenotype and genotype is complicated.

As a result, the complexity of the link between these factors limits the use of various rapid sequencing techniques to improve the diagnosis for determining the most appropriate alternative for treating TB when Isoniazid fails. The burdens caused by MDR tuberculosis to Isoniazid steers the usefulness of ITP (Isoniazid Preventative Therapy). Stagg et al. (2017) argue that INH has been in use for about 70 years. Still, the public knowledge on areas such as the epidemiology of INH’s strains of resistance, clinical consequences of using INH, the exact roles of INH in catalyzing the epidemic of the MDR tuberculosis, is lacking.

Discussion and Analysis

One of the significances of the research by Stagg et al. (2017) is that it outlines both the causes of TB resistance to Isoniazid and the appropriate steps to take in handling such a situation. In the case of the latter, they caution that using rapid sequencing techniques to improve the diagnostic process of patients with MDR tuberculosis should be avoided or used sparingly. Since using sequencing techniques for an alternative to MDR tuberculosis to Isoniazid could cause harm to the patient, Stagg et al. (2017) urge that  ITP (Isoniazid Preventative Therapy) should be considered the first alternative if a patient is resistant Isoniazid. The list of possible causes of MDR tuberculosis to Isoniazid provided by Stagg et al. (2017) should be considered one of the first areas of focus when diagnosing a TB patient or prescribing Isoniazid to him/her. Physicians must show utmost keenness when prescribing these drugs to patients to avoid poor treatment outcomes of post-treatment relapse.

Heep, M., Brandstätter, B., Rieger, U., Lehn, N., Richter, E., Rüsch-Gerdes, S., et al. (2001). Frequency of rpoB Mutations Inside and Outside the Cluster I Region in Rifampin-Resistant Clinical Mycobacterium tuberculosis Isolates. J Clin Microbiol. , 107-110.

Methodology

In total, Heep et al. (2001) analyzed 93 strains of RIF-resistant TB (Mycobacterium tuberculosis) isolates. They used 80 patients that the NRC obtained in 1997. They also used 18 DNA samples of RIF-resistant strains, a pair of which comprised of culture samples. The samples were obtained from six health centers, and none of them had any known mutation of Cluster I. The researchers also identified all isolates of Mycobacterium tuberculosis in line with the requirements for gene probes identification. This is as per the manufacturer’s instructions and standard procedures for biochemical testing.

Results

The emergence and widespread of the strains of drug-resistant Mycobacterium tuberculosis (M. tuberculosis) has caused an alarming trend in the treatment of TB across the globe, as per Heep et al. (2001). Drug-resistant tuberculosis is becoming commonplace in different parts of the world. For example, many countries have reported the ever-increasing cases of both drug-resistant and MDR (multidrug-resistant) tuberculosis. Most isolates are resistant to rifampin (RIF) and isoniazid (INH). During the time of their study, Heep et al. (2001) predicted that the incidents of TB and drug-resistant TB in Germany, which had the least number of these cases by then, would change. Their reason behind this claim was based on the fact that Germany would import the strains of drug resistance from the regions with high rates. An example included the Soviet Union.

In their discussion of ways that can be used to leverage the effects of TB resistance to rifampin, Heep et al. (2001) explained that early detection of resistance to drugs (rifampin) in clinical Mycobacterium tuberculosis aids appropriate treatment and prevention of further resistance development. It also halts the spread of drug-resistant strains. Unlike the other conventional methods that use solid media, the use of both automated and manual methods for testing susceptibility in liquid media reduces the turnaround length for susceptibility, slicing the period from 4-6 weeks to about 3days to 2 weeks. One of the latest interventions for the TB resistance to rifampin at the study was the identification of different resistance mutations, such as the genetic aspects of RIF’s resistance. Heep et al. (2001) argued that identifying such mutations fostered the advancements of molecular tests for detecting the strains of resistance under one day.

Discussion and Analysis

Although they did not particularly identify the causal factors of TB resistance to rifampin, Heep et al. (2001) alluded that migration could expose TB patients to drug resistance. This viewpoint resonates with the fact that TB in itself is airborne and can infect people through inhalation of Mycobacterium tuberculosis. For that reason, if patients with drug-resistant TB get closer to those with normal TB or even the TB-free patients, then everyone who inhales the TB bacteria from the patients with drug-resistant TB is likely to develop the same health problems. The research also highlights a set of measures that medics and patients can use to leverage the effects of TB resistance to rifampin.

Gill, A., Ugalde, I., Febres-Aldana, C. A., & Tudac, C. (2019). Fluoroquinolone resistant tuberculosis: A case report and literature review. Respir Med Case Rep.

Methodology

In a study to demonstrate drug-resistant TB to fluoroquinolone, Gill et al. (2019) reviewed a case report of a young man of 23years old with a medical background of treated TB. He was presented to a hospital’s emergency unit for a week and suffered from hemoptysis at the time of admission. The symptoms for this health problem started with a dry cough, after which the patient produced a tinge of blood that progressed large volumes of blood in three weeks. In addition to subjective weight loss, he had night sweats, chills, and fever. He traveled to the US from Nepal after the resolution of his symptoms one year before the hospital admission.

Results of the Case Review

On the seventh day of his hospitalization, the Health Department of the US confirmed that the patient’s TB was resistant to fluoroquinolone after running a NAAT (nucleic acid amplification testing). As a result, the hospital discounted the other renown antimicrobial drugs for TB, namely moxifloxacin, rifampin, and isoniazid. The patient was then started on other drugs such as ethionamide, para-aminosalicylic acid, meropenem, linezolid, and clavulanate amikacin. The CDC (Centers for Disease Prevention and Control) was also requested to provide bedaquiline for the patient. The Health Department stated that he would be subjected to an intensive care unit for monitoring after the lobectomy. This verdict resonated with the fact that the patient was incapable of tolerating extubation trials and many mucous plugging, especially given that the plugging process involved the use of multiple bronchoalveolar lavages.

Discussion and Analysis

Gill et al. (2019) posit that a strain of TB that is resistant only to the fluoroquinolone drug is referred to as fluoroquinolone-resistant tuberculosis or the formerly pre- extensively drug-resistant (XDR) TB. An intensive review of the findings of Gill et al. (2019) reveals that a drug-resistant TB that resists fluoroquinolone requires the use of other drugs such as ethionamide, para-aminosalicylic acid, and meropenem, linezolid, and clavulanate amikacin. Bedaquiline can also help reduce the effects of the body’s resistance to fluoroquinolone.

Conclusion

Not all drugs fight diseases or reduce their severity because some organisms that cause illness are resistant or fight the drugs, instead. In the case of tuberculosis, Rifampin, Isoniazid, and Fluoquinolone-which are considered powerful anti-TB drugs- often prove less productive when the patient’s phenotypes and genotypes are resistant to them. Judging by the findings of this study, the effects of the incompatibility between these and the patient’s body can be leveraged through different treatment measures and drugs. For the latter, bedaquiline is considered the ultimate drug for effects caused by the incompatibility between the patient’s body and these drugs.

References

Gill, A., Ugalde, I., Febres-Aldana, C. A., & Tudac, C. (2019). Fluoroquinolone resistant tuberculosis: A case report and literature review. Respir Med Case Rep. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446130/

Heep, M., Brandstätter, B., Rieger, U., Lehn, N., Richter, E., Rüsch-Gerdes, S., et al. (2001). Frequency of rpoB Mutations Inside and Outside the Cluster I Region in Rifampin-Resistant Clinical Mycobacterium tuberculosis Isolates. J Clin Microbiol. , 107-110. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC87688/

Stagg, H., Lipman, M., McHugh, T., & Jenkins, H. (2017). Isoniazid resistant tuberculosis- a cause for concern? Int J Tuberc Lung Dis , 129-139. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5479083/

WHO. (2018, Jan). What is multidrug-resistant tuberculosis (MDR-TB), and how do we control it? . Retrieved Dec 2, 2019, from WHO: https://www.who.int/features/qa/79/en/