Multidrug-resistant infections: A threat to modern medicine

Introduction

Multidrug-resistant infections are infections that resist the effects of multiple antimicrobial agents used in their treatment. These infections are caused by microorganisms which have developed or acquired resistance to multiple drugs used to kill or inhibit them. In addition to the acquisition or development of resistant traits by these microorganisms, patients’ physiological conditions can also cause multidrug resistance.

Microorganisms can develop multidrug resistance through natural phenomena, mutation and transfer of genetic materials between microorganisms. Furthermore, malnutrition, diseases, drugs and genetic factors can affect patients’ physiology, leading to multidrug-resistant infection.

Similarly, multidrug-resistant infections can occur naturally, through inappropriate use of antimicrobial, poor water and sanitation, lack of proper food handling, and lack of infection prevention and control.

The development and spread of multidrug-resistant infections negatively impacts modern medicine because they increase the mortality rate, disability and the economic cost of treating these infections. Furthermore, it increases the risk of spreading infections and the capacity to carry out essential medical procedures such as surgery and cancer treatment. 1.27 million deaths globally were caused by multidrug resistant infections.¹

Mitigation of multidrug-resistant infections is essential because of the lack of sufficient new antimicrobials developed to combat these infections. This is an urgent need, and it can be achieved by the prevention and control of infections. Additionally, creating awareness on the proper use of antimicrobials, research and development of new and effective drugs, vaccines, and diagnostic tools can help in prevention.

This article explains multidrug-resistant infections, along with their risk factors, mechanisms, treatments, and prevention methods, to help reduce their threat to modern medicine.

Risk Factors

Poor water, sanitation and hygiene (WASH) facilities

People living in low-resource settings are more vulnerable to multidrug-resistant infections because of lack of access to safe water, sanitation and hygiene in schools, communities and hospitals.² In sub –Sahara Africa, approximately 680 million people do not have basic waste management services in the healthcare facilities they use. ² Therefore,the release of wastes in unsanitary ways by people taking antimicrobials can increase the environmental levels of multidrug-resistant microorganisms which increases the risk of contracting a multidrug-resistant infection.²

Improper use of antimicrobials 

Wrong prescriptions, dosages and usages, in addition to counterfeit and poor quality antimicrobials foster the development of drug resistance to pathogens. These pathogens, which grow in the presence of sub-therapeutic doses of the drugs, cause infections that resist the effects of multiple drugs. Furthermore, the use of antimicrobials for agricultural purposes can result in multidrug-resistant infections when resistant microorganisms colonize and infect human consumers.³

Climate change

Weather conditions like climate change can cause the spread of multidrug-resistant infections. Flooding, as well as storms, can spread multidrug-resistant microorganisms to new environments. Sewer overflow due to flooding can also increase the risk of water body contamination by these pathogens. Increases in temperature and carbon dioxide due to climate change can increase the survival and growth of multidrug-resistant microorganisms, in addition to increasing the rate of acquiring resistant traits by pathogens.⁴

Poor immune system and malnutrition

 People with weak immune systems and malnourishment are more vulnerable to contracting infections.⁵ Furthermore, it makes infections difficult to treat as diseases, and some medications reduce the functions of the immune system.

Healthcare associated risks 

Multidrug-resistant infections can be contracted from the hospital and medical devices such as catheters. At least 84 percent of hospital acquired infections are resistant to a minimum of one antibiotic in low and middle-income countries.⁶

Mechanisms of multidrug-resistance

Microorganisms utilize different mechanisms, such as degradation of drugs by the cellular enzyme leading to drug inactivation, prevention of drug uptake due to alteration of drug target and efflux of drugs to resist the effects of drugs.⁷ These mechanisms can be acquired naturally or genetically through mutation and transfer of genetic materials from other microorganisms.⁸ Common examples of multidrug-resistant microorganisms include Methicillin-resistant Staphylococcus aureus (MRSA), Vancomycin-resistant Staphylococcus aureus (VRSA), multidrug-resistant Mycobacterium tuberculosis (MDR-TB), Vancomycin-resistant Enterococci (VRE), Carbapenen-resistant Enterobacteriaceae (CRE), Extended-spectrum beta-lactamase (ESBL) producing Gram-negative bacteria and Multidrug-resistant Gram-negative rods (MDR GNR).⁹ These microorganisms are responsible for many multidrug-resistant infections. 

Treatment of multidrug-resistant infections

Treatment of multidrug-resistant infections can be pathogen-directed therapeutic strategies or host immune system-directed therapeutic strategies.

Pathogen-directed therapeutic strategies:

Anti-virulence compounds that neutralize bacterial virulence factors can prevent the development of infection without being bactericidal. Anti-virulence compounds can interfere with bacterial adherence to target cells, biofilm formation, quorum sensing (a process of release of auto-inducers by bacteria to increase its concentration as a function of cell density) and invasion of host cells.⁷ In addition, monoclonal antibodies can prevent bacterial toxins from binding to target cells. Phage therapy that involves using viruses to infect and lyse pathogenic bacteria is also effective in the treatment and prevention of multidrug-resistant infections.¹⁰

Host-directed therapeutic strategies

Improving bactericidal activity of phagocytic cells pharmacologically, could be an effective way of treating multidrug-resistant infections. Tamoxifen-boosted immune system was effective against Methicillin-resistant Staphylococcus Aureus.⁷

Prevention of multidrug-resistant infections

Infection prevention and control, and proper use ofantimicrobialsl can help in preventing Multidrug-resistant infections

Infection prevention and control programs

 In healthcare facilities, it helps to prevent health workers, patients and visitors to healthcare facilities from contracting and spreading multidrug-resistant infections. This can be achieved by appropriate hand hygiene, the use of personal protective equipment, an active surveillance culture, enhanced environmental cleaning, education and improvements in communication about patients with multidrug-resistant organisms between and within health care facilities. Adequate WASH facilities and vaccines are also essential.¹¹

Antimicrobial stewardship, which educates and supports healthcare workers on the appropriate ways for prescribing and administering antimicrobials, helps to reduce multidrug-resistant infections and improve patients’ treatment outcomes. Proper diagnosis helps in determining the pathogen.¹¹

Conclusion

Adoption of new therapeutic strategies to combat the threat of multidrug-resistant infections. In addition to infection prevention and control measures, antimicrobial stewardship is essential. These can be achieved by appropriate diagnosis, vaccines and availability of effective antimicrobials.

References

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