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.
Infections caused by antibiotic-resistant bacteria continue to be a challenge. Rice in 2008 coined the acronym of “ESKAPE” pathogens including Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species to emphasize that these bacteria currently cause the majority of hospital infections and effectively “escape” the effects of antibacterial drugs.
New mechanisms of resistance continue to emerge and spread globally, threatening our ability to treat common infections. Antibacterial and antifungal use in animal and agricultural industries aggravates selective pressure on microbes.
The World Health Organization (WHO) published 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
- 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.
Although most clinicians are aware of the problem of antimicrobial resistance, most underestimate this problem in their own hospital. They can help tackle resistance by:
- appropriate antibiotic prescribing practices,
- appropriate infection prevention and control and
- appropriate source control when it is needed.
The overuse of antibiotics is widely accepted as a major driver of some emerging infections (such as Clostridium difficile) and for the continued development of antimicrobial resistance (AMR). The growing emergence of multi-drug resistant organisms and the limited development of new agents available to counteract them have caused an impending public health crisis of international concern, threatening modern medicine, animal health and food security.
AMR is a natural phenomenon that occurs as microbes evolve. However, human activities have accelerated the pace at which microorganisms develop and disseminate resistance. Inappropriate use of antibiotics is contributing to the development of AMR.
Clinicians 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 elective and emergency admissions, has become increasingly urgent.
Systemic antibiotic prophylaxis (AP) is one of the most important component of a perioperative infection prevention strategy. The use of AP contributes considerably to the total amount of antibiotics used in hospitals and may be associated with increases in antibiotic resistance and healthcare costs.
Although AP plays a pivotal role in reducing the rate of surgical site infections, other factors such as attention to basic infection-control strategies may have a strong impact on surgical site infections rates.
Perioperative surgical AP should be recommended for operative procedures that have a high rate of postoperative wound infection or when foreign material is implanted.
Prophylactic antibiotic agents should be nontoxic and inexpensive and have in vitro activity against the common organisms that cause postoperative wound infection after a specific surgical procedure.
Therapeutic concentrations of antibiotics should be present in the tissue throughout the all period that the wound is open.
Below we report the 7 principles for appropriate antibiotic prophylaxis.
Principles of antibiotic prophylaxis
1 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
2 Antibiotic prophylaxis should be administered for operative procedures that have a high rate of postoperative surgical site infection, or when foreign materials are implanted.
3 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.
4 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.
5 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).
6There is no evidence to support the use of post-operative antibiotic prophylaxis.+
7 Each institution is encouraged to develop guidelines for the proper surgical prophylaxis.
Antibiotics should be used after a treatable infection has been recognized or when there is a high degree of suspicion for infection. Initial antimicrobial therapy is typically empirical in nature because they need immediate treatment (especially in critically-ill patients), and microbiological data (culture and susceptibility results) usually requires ≥24 h for the identification of pathogens and antibiotic susceptibility patterns. The decision tree for the empiric antibiotic regimen should depend mainly on three factors: presumed pathogens involved and risk factors for major resistance patterns, clinical patient’s severity and presumed/identified source of infection.
Knowledge of local rates of resistance and the risk factors that suggest resistant bacteria should be involved as essential components of the clinical decision-making process when deciding on which antibiotic regimen to use for empiric treatment of infection.
The timing, regimen, dose and duration of antimicrobial therapy should be always optimised.
Antibiotic therapy should be shortened for patients demonstrating a positive response to treatment.
Below we report the 10 principles for appropriate antibiotic therapy across the surgical pathway.
Principles of antibiotic therapy
1 The source of infection should always be identified and controlled as soon as possible.
2 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.
3 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.
4 Empirical therapy should be chosen on the basis of local epidemiology, individual patient risk factors for MDR bacteria and Candida spp., clinical severity, and infection source.
5 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 before the administration of antibiotics in critically ill patients.
6 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.
7 The appropriateness and need for antimicrobial treatment should be re-assessed daily.
8 Once source control is established, short courses of antibiotic therapy are as effective as longer courses regardless of signs of inflammation.
9 IPC measures, combined with ASPs should be implemented in surgical departments. These interventions and programs require regular, systematic monitoring to assess compliance and efficacy.
10 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.
Healthcare-associated infections (HAIs) are infections that occur while receiving health care. Patients with medical devices (central lines, urinary catheters, ventilators) or who undergo surgical procedures are at risk of acquiring HAIs. HAIs continue to be a tremendous issue today, however most HAIs are preventable. The prevention and management of HAIs has advanced greatly over the last decade due to legislative, regulatory and organizational incentives. However, these changes have not resolved the gap between evidence base and clinical practice, particularly in healthcare workers’ behavioral change. Below we report 7 strategies to prevent healthcare-associated infections in our hospitals.
Proper hand hygiene is the most important, simplest, and least expensive means of reducing the prevalence of HAIs and the spread of AMR. Cleaning hands healthcare workers can prevent the spread of microorganisms, including those that are resistant to antibiotics and are becoming difficult, if not impossible, to treat.
The 5 Moments for (WHO) hand hygiene approach defines the key moments when healthcare workers should perform hand hygiene.
- before touching a patient,
- before clean/aseptic procedures,
- after body fluid exposure/risk,
- after touching a patient, and
- after touching patient surroundings.
Despite acknowledgement of the critically important role of hand hygiene in reducing the transmission of pathogenic microorganisms, overall compliance with hand hygiene is less than optimal in many healthcare settings worldwide. In most healthcare institutions, adherence to recommended hand-washing practices remains unacceptably low. Hand hygiene reflects awareness, attitudes and behaviors towards infection prevention and control.
Environmental hygiene is a fundamental principle of infection prevention in healthcare settings. Contaminated hospital surfaces play an important role in the transmission of micro-organisms, including Clostridium difficile, and multidrug-resistant organisms such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Therefore, appropriate hygiene of surfaces and equipment which patients and healthcare personnel touch is necessary to reduce exposure. Wvidence supports theypothesis that hospital can act as an important reservoir of many nosocomial pathogens in several environments such as surfaces, medical equipment and water system. Healthcare settings are complex realities within which there are many critical points. Microbial contamination can result from the same inpatients, relatives and healthcare workers.
The role of environmental hygiene is to reduce the number of infectious agents that may be present on surfaces and minimize the risk of transfer of micro-organisms from one person/object to another, thereby reducing the risk of cross-infection.
Screening and cohorting patients
Early detection of multidrug-resistant organisms is an important component of any infection control program. There is good evidence that active screening of preoperative patients for MRSA, with decolonisation of carriers, results in reductions in postoperative infections caused by MRSA. It has been described in patients decolonised with nasal mupirocin.
Surveillance cultures for carbapenem-resistant Enterobacteriaceae (CRE) have been advocated in a number of reports and recommendations as part of an overall strategy to combat it. Active screening for CRE using rectal surveillance cultures has been shown to be highly effective, when part of a comprehensive infection control initiative, in halting the spread of CRE in health care facilities. Isolation or cohorting of colonized/infected patients is a cornerstone of infection prevention and control. Its purpose is to prevent the transmission of microorganisms from infected or colonized patients to other patients, hospital visitors, and healthcare workers, who may subsequently transmit them to other patients or become infected or colonized themselves. Isolating a patient with highly resistant bacteria is beneficial in stopping patient-to-patient spread. Isolation measures should be an integral part of any infection prevention and control program, however they are often not applied consistently and rigorously, because they are expensive, time-consuming and often uncomfortable for patients.
It is widely acknowledged that surveillance systems allow the evaluation of the local burden of HAIs and AMR and contribute to the early detection of HAIs including the identification of clusters and outbreaks. Surveillance systems for HAIs are an essential component of both national and facility infection prevention and control programs. National surveillance systems should be integral to a public health system. However, recent data on the global situational analysis of AMR, showed that many regions reported poor laboratory capacity, infrastructure, and data management as impediments to surveillance.
Optimal infection control programs have been identified as important components of any comprehensive strategy for the control of AMR, primarily through limiting transmission of resistant organisms among patients. The successful containment of AMR in acute care facilities, however, also requires an appropriate antibiotic use. Antibiotic stewardship programs (ASPs) can help reduce antibiotic exposure, lower rates of Clostridium difficile infections and minimize healthcare costs. Most antibiotic stewardship activities effect multiple organisms simultaneously and have as a primary goal the prevention of the emergence of antibiotic resistance. Thus, ASPs can largely be viewed in the context of horizontal infection prevention. Additionally, ASPs can contribute to the prevention of surgical site infections via the optimized use of surgical antibiotic prophylaxis.
Keeping abreast of the latest findings regarding the spread of infections and strategies for prevention is essential for a successful infection prevention program.
While many infection control interventions focus on reducing the transmission of organisms, it is as important to identify measures to reduce the risk of infection. Both the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) have published guidelines for the prevention of surgical site infections (SSIs). However, knowledge, attitude, and awareness of infection prevention and control measures are often inadequate and a great gap exists between the best evidence and clinical practice with regards to SSIs prevention. Despite evidence supporting the effectiveness of best practices, many clinicians fail to implement them, and evidence-based processes and practices that are known to reduce the incidence of SSIs tend to be underused in routine practice.
The 2016 WHO Global guidelines for the prevention of surgical site infection are evidence-based including systematic reviews presenting additional information in support of actions to improve practice. The guidelines include 13 recommendations for the pre-operative period, and 16 for preventing infections during and after surgery. They range from simple precautions such as ensuring that patients bathe or shower before surgery, appropriate way for surgical teams to clean their hands, guidance on when to use prophylactic antibiotics, which disinfectants to use before incision, and which sutures to use.
Patient safety is described the absence of preventable harm to a patient during the process of health care and reduction of risk of unnecessary harm associated with health care to an acceptable minimum. Improving patient safety in today’s hospitals worldwide requires a systematic approach to combating healthcare-associated infections and antimicrobial resistance. The two go hand-in-hand. The occurrence of HAIs such as central line-associated bloodstream infections, catheter-associated urinary tract infections, surgical site infections, hospital-acquired/ventilator associated pneumonia and C. difficile infection, continues to escalate at an alarming rate. These infections develop during the course of health care treatment and result in significant patient illnesses and deaths (morbidity and mortality); prolong the duration of hospital stays; and necessitate additional diagnostic and therapeutic interventions, which generate added costs to those already incurred by the patient’s underlying disease. HAIs are considered an undesirable outcome, and as many are preventable, they are considered an indicator of the quality of patient care, an adverse event, and a patient safety issue.
Appropriate control of the source of infection is of outmost importance in the management of surgical infections. Intra-abdominal infections along with soft tissues infections are the sites where a source control is more feasible and more impactful. In these settings an appropriate source control can improve patients’ outcome and reduce antibiotic pressure allowing short course of antibiotic therapy.
Source control encompasses all measures undertaken to eliminate the source of infection, reduce the bacterial inoculum and correct or control anatomic derangements to restore normal physiologic function. In critically ill patients with severe sepsis these principles can be applied at different times in the same patient. Appropriate source control are of outmost importance in the management of surgical infections. Intra-abdominal infections along with soft tissues infections are the sites where a source control is more feasible and more impactful. In these settings an appropriate source control can improve patients’ outcome and reduce antibiotic pressure allowing short course of antibiotic therapy. Source control generally involves drainage of abscesses or infected fluid collections, debridement of necrotic or infected tissues and definitive control of the source of contamination.
Early control of the septic source can be achieved using both operative and non-operative techniques. An operative intervention remains the most viable therapeutic strategy for managing surgical infections in critical ill patients.
As a general principle, every verified source of infection should be controlled as soon as possible. The level of urgency of treatment is determined by the affected organ(s), the relative speed at which clinical symptoms progress and worsen, and the underlying physiological stability of the patient. Non-operative interventional procedures include percutaneous drainages of abscesses. Ultrasound and CT guided percutaneous drainage of abdominal and extraperitoneal abscesses in selected patients are safe and effective. The principal cause for failure of percutaneous drainage is misdiagnosis of the magnitude, extent, complexity, location of the abscess. Surgery is the most important therapeutic measure to control surgical infections.
In the setting of intra-abdominal infections the primary objectives of surgical intervention include a) determining the cause of peritonitis, b) draining fluid collections, c) controlling the origin of the abdominal sepsis. In patients with intra-abdominal infections, surgical source control entails resection or suture of a diseased or perforated viscus (e.g. diverticular perforation, gastroduodenal perforation), removal of the infected organ (e.g. appendix, gallbladder), debridement of necrotic tissue, resection of ischemic bowel and repair/resection of traumatic perforations with primary anastomosis or exteriorization of the bowel. Intra-abdominal lavage is a matter of ongoing controversy. Some authors have favoured peritoneal lavage because it helps in removal as well as in dilution of peritoneal contamination by irrigation with great volumes of saline. However, its application with or without antibiotics in abdominal sepsis is largely unsubstantiated in the literature. In certain circumstances, infection not completely controlled may trigger an excessive immune response and local infection may progressively evolve into sepsis, septic shock, and organ failure. Such patients can benefit from immediate and aggressive surgical re-operations with subsequent re-laparotomy strategies, to curb the spread of organ dysfunctions caused by ongoing peritonitis. Surgical strategies following an initial emergency laparotomy include subsequent “re-laparotomy on demand” (when required by the patient’s clinical condition) as well as planned re-laparotomy in the 36-48-hour post-operative period.
On-demand laparotomy should be performed only when absolutely necessary and only for those patients who would clearly benefit from additional surgery. Planned relaparotomies, on the other hand, are performed every 36–48 hours for purposes of inspection, drainage, and peritoneal lavage of the abdominal cavity. The concept of a planned relaparotomy for severe peritonitis has been debated for over thirty years. Re-operations are performed every 48 hours for reassessing the peritoneal inflammary process until the abdomen is free of ongoing peritonitis; then the abdomen is closed. The advantages of the planned re-laparotomy approach are optimization of resource utilization and reduction of the potential risk for gastrointestinal fistulas and delayed hernias.
An open abdomen (OA) procedure is the best way of implementing re-laparotomies. The role of the OA in the management of severe peritonitis has been a controversial issue. Although guidelines suggest not to routinely utilize the open abdomen approach for patients with severe intra-peritoneal contamination undergoing emergency laparotomy for intra-abdominal sepsis, OA has now been accepted as a strategy in treating physiologically deranged. patients with acute peritonitis. The OA concept is closely linked to damage control surgery (DCS), and may be easily adapted to patients with advanced sepsis and can incorporate the principles of the Surviving Sepsis Campaign. Similarly to the trauma patient with the lethal triad of acidosis, hypothermia and coagulopathy, many patients with sepsis or septic shock may present in a similar fashion. For those patients, DCS can truly be life saving.
Skin and soft tissue infections include a variety of pathological conditions involving the skin and underlying subcutaneous tissue, fascia, or muscle and ranging from simple superficial infections to severe necrotizing infections. Necrotizing soft tissue infections are potentially life-threatening infections of any layer of the soft tissue compartment associated with widespread necrosis and systemic toxicity.
Source control for soft tissue infections includes drainage of infected fluids, debridement of infected soft tissues and removal of infected devices or foreign bodies.
Skin and subcutaneous abscesses are typically well circumscribed and respond to incision and drainage. Necrotizing soft tissue infections always require surgical intervention including drainage and debridement of necrotic tissue in addition to antibiotic therapy. Delay in source control for patients with necrotizing soft tissue infections has been repeatedly associated with a greater mortality. In these patients removal of all non-viable tissue should be accomplished including muscle, fascial layers, subcutaneous tissue, and skin if they are compromised, and the incision should be extended until healthy viable tissue is seen. Planning a first re-exploration within 12–24h and repeating re-exploration(s) until the patient is free of necrosis should be always considered.
The infection of medical devices like meshes are very insidious in clinical practices. The use of a mesh has become the standard in hernia repair surgery worldwide due to the reduced rates of recurrence and technical ease of the operation. However, mesh-related complications have become increasingly more frequent. Post-operative mesh infections are rare but troublesome complications that cause considerable morbidity and necessitate mostly mesh removal. Antibiotics and mesh-saving operations are not generally sufficient to eradicate the infection in the majority of cases.The pathogenesis of mesh infection is a complex process involving many factors including, but not limited to, bacterial virulence, surface physicochemical properties of the prosthetic material, and alterations in host defense mechanisms. Bacterial adherence and biofilm formation on the surface of synthetic materials are essential steps in the sequence leading to mesh infections. The first stage of mesh infection is bacterial adherence to the prosthesis. The result of adherence to hernia prosthetics is the formation of the bacterial biofilm. Biofilm produced by the bacteria have a pivotal role in mesh infection. Several studies have documented in vitro that multiple species of bacteria can attach to prosthetic mesh surfaces and form biofilm including coagulase-negative staphylococci, Stapylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Embedded in self-secreted extracellular polymeric substances, biofilm can provide bacteria an effective barrier against host immune cells and antibiotics. Biofilm has been documented in association with a wide variety of implanted materials, such as central venous catheters, urinary catheters, heart valves, orthopedic joint prostheses and internal fixation devices and also in non-absorbable meshes. The nature of biofilm structure makes micro-organisms difficult to eradicate and confer an inherent resistance to antimicrobial agents. Although, several studies have shown that in certain instances a conservative approach may be successful for salvaging a contaminated mesh, in most cases antibiotics and wound drainage are not sufficient to eradicate the infection. If conservative treatment fails, the complete surgical removal of the mesh is mandatory.