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By Loo Li Wen, Pharmacist, Antimicrobial Stewardship Program (ASP), Singapore General Hospital, 16 January 2017
The war against resistant organisms is getting real. In a recent news article, researchers reported the discovery of a drug-resistant “superbug” for the first time in the United States. The bacterium has genetic changes that made it resistant to a last-ditch antibiotic called colistin. The biggest fear is when this resistant gene gets transmitted from one species of bacteria to another. Increasingly, worldwide emergence of antimicrobial resistance has become a threat to patient safety in the healthcare settings, both locally and globally. The increasing prevalence of multi-drug resistant organisms resulted in the loss of therapeutic efficacy for the antibiotics that were previously thought to be effective. Rising rates of infection due to multi-drug resistant organisms (MDROs) not only limit therapeutic options, but it also has substantial impact on patients and cost of care. More recently, the World Health Organization (WHO) reported that resistance to common bacteria has reached alarming levels in many parts of the world and member states are urged to coordinate and strengthen efforts towards global antimicrobial surveillance. In order to tackle the situation, multi-pronged approach has been suggested – integration of Antimicrobial Stewardship Program, rapid diagnostics, education, infection control policies, surveillance and policies for antibiotic use in farming.
Globally, effective ASP has shown to reduce antibiotic use by 20 – 40%, decreased the incidence of healthcare associated infections such as Clostridium difficile, Methicillin-resistant Staphylococcus aureus (MRSA) et cetera, reduced cost of care and improved overall patients’ outcomes. In a small nation like Singapore, ASP was implemented in 2011 across various public hospitals. Singapore General Hospital (SGH), the nation’s largest acute–tertiary care hospital with a capacity of 1,700 beds, holds the largest ASP team in Singapore. The team comprises of 15 infectious diseases (ID) trained clinical pharmacists, an infection control director, ID physicians as well as microbiologists. Hospital–wide audit of patients initiated on broad spectrum intravenous antibiotics were subjected to a two–stage prospective audit with immediate and concurrent feedback (Figure 1). A recent study conducted locally also revealed that ASP interventions were safe and associated with significant reduction in length of hospital stay and infection-related re-admissions. Diagnostic (viral or bacterial cause) or prognostic (life-threatening or self-limiting infection) uncertainty makes it difficult for physicians to know exactly when to provide and when to withhold antibiotic treatment. More often than not, broad spectrum antibiotics or combinations of antibiotics are prescribed upfront with the mentality of “better be safe than sorry”. This common mindset of physicians is not unfounded, as studies have demonstrated that in patients with septic shock, every hour of delay in appropriate antibiotics (in the first six hours) have led to a 7.6% reduction in survival. As the ASP team and prescribing physicians depend on information and guidance from the clinical microbiology laboratory to optimise therapy, rapid diagnostics is a vital component to patient care and success of ASPs.
Rapid microbiological tests allows for timely antimicrobial optimisation and this in turn led to decreased mortality, shortened hospital stay and lower hospitalisation costs.Standard techniques for identification of organisms are based on phenotypic methods, which require at least 48 hours for final results, as compared to rapid diagnostic tests, which provide final results within hours of growth (Figure 2). Various rapid diagnostic tests include – polymerase chain reaction (PCR) assays, multiplex PCR, nanoparticle probe technology (nucleic acid extraction and PCR amplification) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). With rapid diagnostics, ASP can play an important role as the ‘middle man’ between clinical microbiology laboratory and prescribing physicians. Microbiological results are conveyed to the physicians via the ASP to ensure accurate interpretation and selection of appropriate antibiotics. Furthermore, ASP also works hand in hand with clinical microbiologists to review microbiological reporting procedures, especially with the introduction of new diagnostic test. The ASP team reviews patients on a daily basis and is also part of the multi-disciplinary team doing daily ward rounds. As such, the ASP team is able to provide feedback on how the reported data will likely be interpreted and allow for selective reporting of microbiological results. In various case reports, selective reporting has demonstrated a significant improvement in the appropriateness of antibiotic prescription and majority of physicians involved in the studies have also reported that selective reporting made their antibiotic choice easier. In addition, the ASP team is pivotal in timely communication of microbiological results to physicians to guide them on the selection of appropriate antibiotics – antibiotic chosen must be able to penetrate to the site of infection sufficiently, and the ASP team can also recommend the right dose, right route of administration and required monitoring parameters.
Clinical microbiology laboratories worldwide conduct surveillance on local antimicrobial resistance trends among microbial pathogens. Cumulating antimicrobial resistance data aids in the development of institution–specific antibiogram. Antibiograms are critical in the development of institutional antibiotic guidelines, to guide physicians on prescribing the appropriate empiric antibiotic therapy that is broad enough to cover for the likely causative pathogens. Henceforth, in SGH, the ASP team works closely with the clinical microbiologists to develop antibiotic guidelines. Additionally, the ASP team audits the use of antibiotics to reduce the unnecessarily broad empiric therapy used. Local antibiograms also provide important information to decide if an antimicrobial should or should not be included in the institution’s formulary.
The blanket use of antibiotics plays a major role in fuelling the selection of resistant organisms. To combat rising antimicrobial resistance, effective communication between the ASP team, clinical microbiologists and physicians is essential. The ASP team serves as important messengers to educate physicians on the need to change their inappropriate mindset that ‘bigger is always better’. Overprescribing antibiotics comes with great implications that may not be apparent but growing evidence has demonstrated otherwise. The effort to combat antimicrobial resistance is not a lone effort, it requires the collaboration of all players – ASP team, microbiologist and prescribing physicians. It is important to remember that laboratory medicine is not cumbersome and antibiotics are not quick solutions!
References available on request