Antimicrobial resistance - Integrated solutions for the global conundrum

Integrated solutions for the global conundrum

The control of multi-resistant organisms (MROs) is a contentious contemporary issue, and one of our greatest foreseeable healthcare challenges, writes Dr Ramon Z. Shaban.

There is little, if any, doubt about the importance of antimicrobial therapy for the treatment of infection. Countless lives have been saved and many more treated with these agents. Our reliance on antimicrobial therapy in a sense, however, renders humanity something of a slave to its master. The control of multi-resistant organisms (MROs) is a contentious contemporary issue, and one of our greatest foreseeable healthcare challenges. Arguably, our greatest and most well-known adversary in this regard is Staphylococcus aureus. First reported in 1961, MRSA is internationally endemic and a pervasive bacterial pathogen.¹ It is the leading cause of healthcare associated pneumonia and surgical site infections, and the second leading cause of healthcare associated bloodstream infections. MRSA continues to challenge the safety and quality of modern healthcare and in some settings, MRSA can constitute as many as 20% of all hospital-acquired infections. It is estimated that approximately 30 per cent of all S. aureus infections present with some form of drug resistance. More recently, community-acquired MRSA (CA-MRSA) presents particular challenges. It occurs in otherwise healthy individuals with no risk factors for MRSA (such as recent hospitalisation, surgical procedure or antibiotic administration).² Antimicrobial resistance emerges somewhat systematically, presenting seemingly intractable challenges for in healthcare. Few have not heard of Vancomycin-resistant Enterococci (VRE), and there are many others. Drug resistance is on the rise, and is an inevitable consequence of its use.³

Generally speaking, the drivers of antibiotic resistance are considered to be two-fold. First, there is increasing antibiotic selective pressure whereby the more exposed bacteria are to antibiotics the more resistance they develop using the mechanisms outline previous. Second, the spread of existing strains with variable drug resistance enhances further drug resistance.⁴ These drivers of increased antibiotic usage and inappropriate prescribing coupled with the mechanisms that enable resistance to occur paints a dire picture. Such mechanisms and drivers meant that following introduction of the first antibiotic penicillin in the 1940s, evidence of resistance began to emerge in comparatively no time at all. For the majority of antimicrobials, resistance has emerged within years of administration.^{1, 3} In many settings, some antibiotics, such as penicillin, have become obsolete.³ Such facts and the costs and challenges of multi-drug resistant organisms are well documented.^{3, 5} Moreover, the sophistication of health and the manner in which it is provided means that challenges of antimicrobial resistance are no longer exclusive to hospitals. Community-acquired infections are of increasing consequence, of which antimicrobial resistance plays it part. Although the drivers for antimicrobial resistance are thought to be different in the community than for the hospital setting, the stewardship of antimicrobial use in all settings is required, particularly in the global context.

While there is no real dispute that the spread of antimicrobial resistance is due to fuelled by increased antibiotic usage and inappropriate prescribing, it is by the mechanisms of resistance that such problems emerge. The challenges of antibiotic resistance began almost immediately after the discovery and use of the antibiotics.^{1, 6} Little did Fleming, Florey, and Chain and others suspect that bacteria possess sophisticated mechanisms of resistance. The mechanisms of resistance are intrinsic or acquired. A combination of antibiotic inactivation, alteration in antibiotic target sits within the organisms, decreased antibiotic cell wall permeability leading to reduced antibiotic influx, and finally active antibiotic efflux from the bacterial cell contribute individually and collectively in bacterial drug resistance.⁴ Some suggests that the ability of microorganisms to exert resistance is ancient, and that antibiotic resistance is in fact a natural phenomenon that predates the modern selective pressure of clinical antibiotic use.⁷ Such evidence highlights the importance of establishing comprehensive, responsive, integrated global antibiotic stewardship programs. The great panacea to MROs is antibiotic stewardship coupled with rigorous evidence-based infection prevention and control practice.⁴ Stewardship and monitoring programs are emerging in jurisdictions around the world. In developed countries, such programs are well established. In others, they are in their infancy or do not exists. The establishment of such programs is critical, particularly in jurisdictions with little regulation of antibiotic access and prescribing. In some countries around the world, consumers can readily purchase antibiotics over-the-counter with little more than basic screening and advice from a pharmacist or suitably qualified registered health professionals. The increasing mobility of the human and animal populations, particularly through more affordable international travel, fuels the spread of drug resistance organisations with relative ease, particularly community-acquired infections.

The challenges and consequences of drug resistant are clear. Tackling the challenges to prevent the consequences requires a concerted global action. The origin of antibiotic resistance is antibiotic use.³

Gottlieb and Nimmo⁸ remind us that the long held antidote of new drug discovery as the panacea for antimicrobial resistance a falsehood due to an alarming decline in development of new antimicrobial compounds. As notes earlier, experience suggests that antimicrobial resistance long predated modern practices⁷, and in that regard is here to stay. As such, efforts to prevent and control antimicrobial resistance necessitates global integration. Urgent interventions are required to avert the disasters that antimicrobial resistance will bring.⁸ Gottlieb and Nimmo⁸ and others³ call for the establishment of a national antimicrobial resistance management program. The program would be managed by a body that: (i) implements a comprehensive national resistance monitoring and audit system; (ii) implements infection prevention and control guidelines relevant to resistance; (iii) expands funding for research into antibiotic resistance; and (iv) reviews and improves the regulation of antibiotic use.⁸ Implementing models that integrate surveillance, research, and interventions for antimicrobial resistance are critical to diverting the seemingly inevitable public health crisis of antimicrobial resistance.

References

1. Bishop P. Antimicrobial therapy. In: Lee G, Bishop P, eds. Microbiology and infection control for health professionals. Frenchs Forest, NSW, Australia: Pearson; 2010:249-275.


2. Bishop P. Infection control in heallth-care facilities. In: Lee G, Bishop P, eds. Microbiology and infection control for health professionals. Frenchs Forest, NSW, Australia: Pearson; 2010:275-310.


3. Australian Commisson for Safety and Quality in Health Care. Windows into safety and quality in health care 2010. Canberra: Author; 2010.


4. Grayson L, Howden B. Antibacterial agents. In: Yung A, Spelman D, Street A, McCormack K, Sorrell T, Johnson P, eds. Infectious diseases: A clinical approach. Vol Melbourne, Australia: IP Communications; 2011:585-608.


5. National Health and Medical Research Council. Australian guidelines for the prevention and control of infection in healthcare: Commonwealth of Australia; 2010.


6. Lee G, Bishop P, eds. Microbiology and infection control for health professionals. Frenchs Forest, NSW, Australia: Pearson; 2010.


7. D’Costa VM, King CE, Kalan L, Morar M, Sung WWL, Schwarz C, Froese D, Zazula G, Calmels F, Debruyne R, Golding GB, Poinar HN, Wright GD. Antibiotic resistance is ancient. Nature. 2011;477:457-461.


8. Gottlieb T, Nimmo GR. Antiobiotic resistance is an emerging threat to public health: an urgent call to action at the Antimicrobial Resistance Summitt 2011. Medical Journal of Australia. 2011;194(6):281-283.

Dr Ramon Z. Shaban

Dr Ramon Z. Shaban is Senior Research Fellow (Infection Control and Infectious Diseases) within the Griffith Health Institute at Griffith University and Convenor of the Griffith Graduate Infection Control Program, and is also Senior Research Fellow within the Department of Emergency Medicine at the Princess Alexandra Hospital. He has particular interests and expertise in public health, infectious diseases and infection prevention and control in emergency and community care settings. Ramon is a Credentialed Infection Control Professional (CICP) and is Editor-in-Chief of the Australasian Emergency Nursing Journal.