Antimicrobial resistance (AMR) has emerged as one of the principal public health problems of the 21st century. This has resulted in a public health crisis of international concern, which threatens the practice of modern medicine, animal health and food security.
Antibacterial and antifungal use in animal and agricultural industries aggravates selective pressure on microbes. A One Health approach is urgently required. The burden of AMR is difficult to quantify in some regions of the world because enhanced surveillance requires personnel, equipment and financial resources that are not always available. However the impact of AMR worldwide is significant, both in economic terms, and clinical morbidity and mortality because it may:
- lead to some infections becoming untreatable;
- lead to inappropriate empirical treatment in critically ill patients where an appropriate and prompt treatment is mandatory;
- increase length of hospital stay, morbidity, mortality and cost; and
- make necessary alternative antimicrobials which are more toxic, less effective, or more expensive.
The global nature of AMR calls for a global response, both in the geographic sense and across the whole range of sectors involved.
Emergence of AMR, combined with very few new antimicrobial agents in the drug development pipeline, indicates that awareness and understanding of antimicrobial resistance is necessary.
The World Health Organization (WHO) endorsed a global action plan to tackle antimicrobial resistance. It sets out five strategic objectives:
- to improve awareness and understanding of antimicrobial resistance;
- to strengthen knowledge through surveillance and research;
- to reduce the incidence of infection;
- to optimize the use of antimicrobial agents; and
- to develop the economic case for sustainable investment that takes account of the needs of all countries, and increase investment in new medicines, diagnostic tools, vaccines and other interventions.
The substantial problem of antimicrobial resistance is especially relevant to antibiotic resistance (ABR), although antifungal resistance is increasing at an alarming rate. Although the phenomenon of ABR can be attributed to many factors, there is a well-established relationship between antibiotic prescribing practices and the emergence of resistant bacteria.
ABR prevalence has increased alarmingly over the past decades. In 2008 the acronym “ESKAPE” pathogens which refers to Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species was proposed to highlight those pathogens where amr is of particular concern and to emphasize which bacteria increasingly “escape” the effects of antibiotics. These organisms are increasingly multi-drug- (MDR), extensive-drug- (XDR) and pan-drug- resistant (PDR) and this process is accelerating globally.
Antibiotics can be life-saving when treating bacterial infections but are often used inappropriately, specifically when unnecessary or when administered for excessive durations or without consideration of pharmacokinetic principles. Large variations in antibiotic consumption exist between countries and whilst excessive use remains a major problem in some areas of the world, elsewhere there is lack of access to many antimicrobial agents. ABR is a natural phenomenon that occurs as microbes evolve. However, human activities have accelerated the pace at which bacteria develop and disseminate resistance. Inappropriate use of antibiotics in humans and food-producing animals, as well as poor infection prevention and control practices, contribute to the development and spread of ABR.
Appropriate use of antibiotics is an integral part of good clinical practice. This attitude maximizes the utility and therapeutic efficacy of treatment, and minimizes the risks associated with emerging infections and the selection of resistant pathogens.
The indiscriminate and excess use of antibiotic drugs appears the most significant factor in the emergence of resistant bacteria in recent years.
Clinicians should be aware of their role and responsibility for maintaining the effectiveness of current and future antimicrobials. They can help tackle resistance by:
- enhancing infection prevention and control;
- controlling source of infection when it is needed
- prescribing and dispensing antimicrobials when they are truly needed; and
- prescribing and dispensing the right antimicrobial(s) to treat the illness.
An effective and cost-effective strategy to reduce ABR should involve a multi-faceted approach aimed at optimizing antibiotic use, strengthening surveillance and infection prevention and control, and improving patient and clinician education regarding the appropriate use of antibiotics. Although the current magnitude of the problem and its extent in both the community and the hospital adds to the complexity of any intervention, these are still necessary as healthcare workers play a central role in preventing the emergence and spread of resistance.
Hospital based programs dedicated to improving antibiotic use, commonly referred to as “Antimicrobial Stewardship Programs” (ASPs), can both optimize the treatment of infections and reduce adverse events associated with antibiotic use. Since physicians are primarily responsible for the decision to use antibiotics, educating them and changing the attitudes and knowledge that underlie their prescribing behavior are crucial for improving antimicrobial prescription. Successful ASPs should focus on collaboration between healthcare professionals to ensure consistency in approach, shared knowledge, and widespread diffusion of practice. The preferred means of improving antibiotic stewardship should involve a comprehensive program that incorporates collaboration between various specialties within an healthcare institution including, infectious disease specialists, hospital pharmacists, clinical pharmacologists, administrators, epidemiologists, IPC specialists, microbiologists, surgeons, anaesthesiologists, intensivists, and underutilized but pivotal stewardship team members, the surgical, anaesthetic and intensive care nurses in our hospitals.
In this context, the direct involvement of surgeons in ASPs can be highly impactful. Surgeons with satisfactory knowledge in surgical infections involved in ASPs may audit antibiotic prescriptions, provide feedback to the prescribers and integrate the best practice of antimicrobial use among surgeons.
The battle against antibiotic resistance should be fought by all health care professionals. It is well known that antimicrobial restriction, including pre-prescription authorization, is not more effective than the persuasive strategy in achieving the goal of controlling antimicrobial use in the long term. Moreover, in many settings there may be inadequate personnel for a restrictive approach, and restriction strategies fail to consider the appropriateness of use of non-restricted antimicrobials, which makes up the vast majority of antimicrobials used in the hospital. The impact on surgeon autonomy with antimicrobial restriction may also create barriers to collaboration with members of the ASP resulting in less communication about stewardship. Therefore, the emphasis needs to be on surgeon incorporation into the ASP and education overall.
ASP policies should be based on both international/national antibiotic guidelines, and tailored to local microbiology and resistance patterns. Facility-specific treatment recommendations, based on guidelines and local formulary options promoted by the APS team, can guide clinicians in antibiotics selection and duration for the most common indications for antibiotic use. Standardizing a shared protocol of antibiotic prophylaxis should represent the first step of any ASP. Since physicians are primarily responsible for the decision to use antibiotics, educating them and changing the attitudes and knowledge that underlie their prescribing behavior are crucial for improving antibiotic prescription.
Education is fundamental to every ASP. A range of factors such as diagnostic uncertainty, fear of clinical failure, time pressure or organisational contexts can complicate prescribing decisions. However, due to cognitive dissonance (recognising that an action is necessary but not implementing it), changing prescribing behaviour is extremely challenging. Efforts to improve educational programs are thus required and this should preferably be complemented by active interventions such as prospective audits and feedback to clinicians to stimulate further change. It is also crucial to incorporate fundamental ASP and infection prevention and control principles in under- and post graduate training at medical faculties to equip young doctors and other healthcare professionals with the required confidence, skills and expertise in the field of antibiotic management.
Antibiotics are used to treat or prevent bacterial infections. Infections are common conditions across the surgical pathway. Some of the most common surgical conditions, such as appendicitis and cholecystitis are infectious in nature. Additionally, healthcare-associated infections, such as surgical site infections (SSIs), urinary tract infections, and pneumonia, are among the most common complications surgeons face in their clinical practice. The importance of the prevention and control of SSIs has been well recognized and the effectiveness of interventions has been extensively studied and many of them have been demonstrated as being effective, including surveillance systems, pre-operative preparation for the patient, appropriate administration of antibiotics prophylaxis before the initiation of surgery, aseptic procedures in the operating theatre, careful and skilled surgical technique, and postoperative surgical site or wound care. The use of antibiotics prophylaxis in the prevention and reduction in the incidence of SSIs is widespread and evidences have demonstrated the importance of timing of administration, selection of the agent, and duration of the prophylaxis. Despite this evidences, the recommendations are not routinely followed and antibiotics are used excessively and inappropriately for the prevention of SSIs.
Appropriate use of antibiotics, as both prophylaxis and therapy, and compliance with infection prevention and control measures should be integral to good clinical practice and standards of care. However both infection prevention and control measures and appropriate antibiotic prescribing practice among surgeons are often inadequate and a great gap exists between the best evidence and clinical practice across the surgical pathway.
In 2017 the Global Alliance for Infections in Surgery shared with over 230 experts from 83 different countries a global declaration on appropriate use of antimicrobial agents in hospitals worldwide. Within this declaration, the authors highlighted the contribution of antibiotic exposure, misuse, and overuse to antibiotic resistance and outlined the fundamental principles of appropriate antibiotic prophylaxis and therapy in surgery.
Not specifically highlighted in their declaration but of significant importance in limiting antibiotic exposure are efforts to prevent hospital-acquired infections. Prevention of hospital-acquired infections can limit significantly the need for antibiotic therapy.
Surgeons should always optimize antibiotic management to maximise clinical outcome and minimize emergence of the development of resistance and the selection of resistant pathogens. The necessity of formalized systematic approaches to the optimization of antibiotic use in the setting of surgical general surgery units worldwide, both for prophylaxis and therapy, has become increasingly urgent.
Restriction strategies may be effective at controlling use but raise issues of prescriber autonomy and require a large personnel commitment. Encouraging multidisciplinary collaboration within the health system to ensure that the prophylactic, and therapeutic uses of antimicrobial agents result in optimal patient outcomes is mandatory in the era of antimicrobial resistance.
The principles for appropriate prophylactic and therapeutic use of antibiotics in surgery are summarized below.
Principles of appropriate antibiotic prophylaxis in surgery
Antibiotics alone are unable to prevent surgical site infections. Strategies to prevent surgical site infections should always include attention to:
- IPC strategies including correct and compliant hand hygiene practices
- Meticulous surgical techniques and minimization of tissue trauma
- Hospital and operating room environments
- Instrument sterilization processes
- Perioperative optimization of patient risk factors
- Perioperative temperature, fluid and oxygenation management
- Targeted glycemic control
- Appropriate management of surgical wounds
Antibiotic prophylaxis should be administered for operative procedures that have a high rate of postoperative surgical site infection, or when foreign materials are implanted.
Antibiotic given as prophylaxis should be effective against the aerobic and anaerobic pathogens most likely to contaminate the surgical site i.e., Gram-positive skin commensals or normal flora colonizing the incised mucosae.
Antibiotic prophylaxis should be administered within 120 minutes prior to the incision. However, administration of the first dose of antibiotics beginning within 30-60 minutes before surgical incision is recommended for most antibiotics (e.g. Cefazolin), to ensure adequate serum and tissue concentrations during the period of potential contamination. Obese patients ≥ 120 kg require higher doses of antibiotic.
A single dose is generally sufficient. Additional antibiotic doses should be administered intraoperatively for procedures >2-4 hours (typically where duration exceeds 2 half-lives of the antibiotic) or with associated significant blood loss (>1.5L).
There is no evidence to support the use of post-operative antibiotic prophylaxis.
Each institution is encouraged to develop guidelines for the proper surgical prophylaxis.
Principles of appropriate antibiotic therapy in surgery
The source of infection should always be identified and controlled as soon as possible.
Antibiotic empiric therapy should be initiated after a treatable surgical infection has been recognized, since microbiological data (culture and susceptibility results) may not be available for up to 48-72 hours to guide targeted therapy.
In critically ill patients empiric broad-spectrum therapy to cover all likely pathogens should be initiated as soon as possible after a surgical infection has been recognized. Empiric antimicrobial therapy should be narrowed once culture and susceptibility results are available and/or adequate clinical improvement is noted
Empirical therapy should be chosen on the basis of local epidemiology, individual patient risk factors for MDR bacteria and Candida, clinical severity, and infection source.
Specimens for microbiological evaluation from the site of infection are always recommended for patients with hospital-acquired or with community-acquired infections at risk for resistant pathogens (e.g. previous antimicrobial therapy, prior infection or colonization with a MDR, XDR and PDR pathogens) and in critically ill patients. Blood cultures should be performed beforethe administration of antibiotics in critically ill patients.
Antibiotics dose should be optimized to ensure that PK-PD targets are achieved. This involves prescribing of an adequate dose, according to the most appropriate and right method and schedule to maximize the probability of target attainment.
The appropriateness and need for antimicrobial treatment should be re-assessed daily.
Once source control is established, short courses of antibiotic therapy are as effective as longer courses regardless of signs of inflammation.
Failure of antibiotic therapy in patients having continued evidence of active infection may require a re-operation for a second source control intervention.
Biomarkers such as procalcitonin may be useful to guide duration and/or cessation of antibiotic therapy in critically ill patients.
Clinicians with advanced training and clinical experience in surgical infections should be included in the care of patients with severe infections.
IPC measures, combined with ASPs should be implemented in surgical departments. These interventions and programs require regular, systematic monitoring to assess compliance and efficacy.
Monitoring of antibiotic consumption should be implemented and feedback provided to all ASP team members regularly (e.g. every three-six months) along with resistance surveillance data and outcome measures.