Antibiotics Prophylaxis and Post Operative Outcomes. Deciphering the Role of Antibiotics

Contents

ABSTRACT

INTRODUCTION
Statement of problem
Aim
Research Question

LITERATURE ANALYSIS
Surgical Site Infections
Epidemiology of SSIs
Risk factors for SSIs
Microbiology of SSIs
Strategies for SSI prevention
Brief Review of Antibiotic Prophylaxis

CONCLUDING REMARKS

REFERENCES

ABSTRACT

Background: The focus of this work is to evaluate the effect of prophylactic antibiotics on patients’ post-operative outcome (as reflected in the reduction of the rate of surgical site infections and other possible adverse outcomes).

Method: A literature search was performed in MEDLINE, EMBASE, Cochrane Controlled Trials Register published in the Cochrane Library, and CINAHL databases. Outcomes of interest included presence of post-operative surgical site infections and other possible outcomes. In accordance with the PRISMA guidelines, forty full-text articles comprising of randomized controlled trials and observational studies were subjected to qualitative analysis. Data were extracted based on the PICO investigative model.

Findings: In spite of the heterogeneity of the research design of several studies; there was a general consensus on the adverse outcomes of inappropriate administration of antibiotic prophylaxis. Various studies acknowledged the significance of the pharmacokinetics and pharmacodynamics of the recommended prophylactic antibiotics (in relation to SSI risk factors) in improving or worsening the post-operative outcome of patients – notably, protection against surgical site infections.

Recommendation: This study therefore strongly recommends on the adherence to global standard guidelines on antibiotics prophylaxis in the conduct of perioperative procedures. To this end, there is a need for more evidence-based principles on the use of antibiotics in surgery and continuous update of standard guidelines.

KEYWORDS: Surgical site infection, Prophylactic antibiotics, Perioperative infection control

INTRODUCTION

Considering surgery as an integral aspect of medicine; the procedures by their nature perturbs the integrity of the tissue (intact or damaged) (Bass and Garbey, 2014). In the classical era of medicine, surgery was performed to cut, incise, and suture the body surface via simple manual methods, which also limited the areas of the body that procedures could be carried out. However, with the advancements of surgical techniques and operating instruments (such as surgical knives, including electric, microwave, ultrasonic, and laser scalpel); operation can be carried out at any site of the body (Yang et al., 2018).

Meanwhile, from literature; exposure to infection continues to be a persistent outcome resulting from in surgical procedures. In fact, infections (as a result of surgery) could arguably be considered a major obstructive factor restraining the success of surgical procedures.

In the contemporary world, the question of how to minimise or prevent these infections and other adverse consequences of surgery has been an important focus of all stakeholders including the patients who are subjected to the various burden of morbidity and mortality that could ensue from surgical site infections.

By consensus from a plethora of scholarly works, wounds appear to be an inevitable consequence of surgery and therefore, ekes out the risk of infection (Williams et al., 2008). Hence, being exposed to the ubiquitous presence of pathogens; the microenvironment of the surgical site has been found to be susceptible to infections. There exist scientific evidences that demonstrate that the likelihood of surgical site infections (SSI) developing depends on the microbial load, the ability of the microbe to produce infection (virulence), the wound micro-environment and the ability of the patient to fight infection (Phillips et al., 2014).

Infections derived from surgery have been defined in several ways ranging from their anatomical location of the infections to their characteristics such as the presence of inflammation amongst others (CDC, 2014). Furthermore, the effects of SSI have been described as being limited locally to the operative site or systemic effects due to the systemic inflammatory response syndrome (SIRS) and other complications (Phillips et al., 2014).

Meanwhile, other scholarly works have established the fact that SSI could either be one that can be managed easily via outpatient care, or one that leads to an extended inpatient stay, reoperation and associated morbidity and mortality (Bratzler et al., 2004; WHO, 2016).

Being a consequence of surgery, SSIs are a postoperative complication and has been regarded as an important aspect of hospital-acquired (nosocomial) infection (Bratzler et al., 2004: CDC, 2010; Meeks et al., 2011; Mu et al., 2011; Magill et al., 2012). Among the factors currently known to affect postoperative wound infection include (not limited to) operating room, type and duration of surgery (Medeiros et al., 2005; Kaya et al., 2006), surgical personnel, physiological states of patient (Pravinkumar, 2003; Kaya et al., 2006), and antimicrobial drug use (de Jonge et al., 1998).

Surgical site infections are a global healthcare problem. Although SSIs are considered preventable healthcare-associated infections, they still remain a substantial cause of morbidity, prolonged hospitalization, high death rates, and financial stress on national budgets and individual patients and have significant impact on patients’ quality of life (Allegranzi et al., 2011; Hagel et al., 2013; Badia et al., 2017; CDC, 2017). In fact, studies have revealed that they are the most frequent type of nosocomial infections in low- and middle-income countries, affecting up to one-third of operated patients, and the second most frequently reported type of healthcare-associated infections in high-income countries (Zarb et al., 2012; Badia et al., 2017; Moges et al., 2020). Whether or not, SSIs are preventable; as indicated earlier, experts have also been able to delineate important risk factors that increases the odds of contracting SSIs that complicate the surgical interventions (Shilling and Raphael, 2008; Daneman et al., 2010; Karlsson and Beck, 2010; Borens et al., 2013; Darouiche, 2016).

On the other hand, in a bid to contain complications arising from surgical operations such as SSI; there are increasing body of scholarly works that prove that patients are awfully exposed to indiscriminate or unnecessary levels of surgical antimicrobial prophylaxis. Such levels have been studied for their effect on the quality of life of the patients, sequel to surgery.

Antibiotics are arguably the most widely used antimicrobial agents. Hence, the use of this medicine is popularly lauded as the key to prevent incision infection in surgical operations (Zhou et al., 2016; Lambrini et al., 2017).

The campaign on rational or appropriate use of antibiotics as a social and behaviour intervention measure has been on the rise for some time. For instance; a number of definitions qualify as misuse of antibiotics including the use of the wrong antibiotics - in the wrong dose, for the wrong duration, and not in accordance with associated guidelines and principles (Saini et al., 2014, WHO, 2016).

Since its discovery, antibiotics have been used to contain the growth and survival of micro-organisms in the surgical environment. Many studies have therefore, advocated on its administration at various stages of surgery either based on empirical or anecdotal evidences (Yang et al., 2018).

Along the same thought line and considering the focus of the present study (that is, its use - perioperatively), researchers have attempted to classify preoperative and intraoperative administration of antibiotics under prophylactic use while categorising postoperative use of antibiotic as therapeutic use (Yang et al., 2018). Surgical antimicrobial prophylaxis (SAP) has therefore been described, the use of antibiotics before, during, or after a surgical procedure to prevent infectious complications (Misra et al., 2015; Centers for Disease Control and Prevention (CDC), 2017). According to Moges et al. (2020), it is also the use of antibiotics for prevention (excluding preoperative decolonization or treatment of established infections).

Irrespective of their presuppositions, there has been extensive research that favour the preoperative and intraoperative administration of antibiotics over the postoperative prophylactic use of antibiotics in order to prevent commonly avoidable SSIs, leading to reductions in hospitalization time and cost (Young and Lawner, 1987; Dellinger, 2007, Najjar and Smink, 2015; Purba et al., 2019; Purba, 2020).

On the other hand, it is also important to highlight that the evidence on the efficacy of antibiotics, and the optimal time for its administration for prophylaxis still remains a contentious topic amongst healthcare professionals till date (de Jonge et al., 2020).

Statement of problem

Following a systematic review of the literature and meta-analyses, the World Health Organisation (WHO) estimated in 2010 that the prevalence of hospital-acquired infections (HAIs) in low-income and middle-income countries (LMICs) was two to 20 times higher than in high-income countries (Allegranzi et al., 2011; Bagheri et al., 2011; WHO, 2011). One significant aspect of HAIs was linked to a group of surgical site infections (SSIs). SSIs as a possible perioperative outcome is today among the most frequently reported cases of HAIs in LMICs (European CDC (ECDC), 2013; WHO, 2016), affecting up to a third of patients who had surgery. In fact, certain research works have reported that patients diagnosed with SSI may face a two to 11 times increase in mortality along with prolonged hospital stays, financial burden, adverse drug reactions, and potential long-term sequelae (Najjar and Smink, 2015; Khakhkhar et al., 2016).

To this effect, there is growing interest in understanding the significance of anti-infection (or antimicrobial) agents by way of surgical antimicrobial prophylaxis in a bid to prevent infections that can complicate surgical procedures (Bowater et al., 2009; Allegranzi et al., 2016; de Jonge et al., 2020). Accordingly, various studies have indicated the beneficial effects of antimicrobial prophylaxis in preventing SSI and SSI-attributable morbidity and mortality (Bakhsh et al., 2021). In one study, patients dosed with prophylactic antibiotic have been revealed to have had lower rates of postoperative infection (Butterworth et al., 2017).On the other hand, there exists scholarly works that have documented failures of antimicrobial prophylaxis in protecting patients from infection and other adverse outcomes of surgical procedures such as organ failure amongst others (Hardman et al., 2001; Khakhkhar et al., 2016).In the same vein, certain researchers have also advanced that there were no significant changes in outcomes following perioperative antibiotic prophylaxis (Brkic et al., 2021). The concept of optimal timing and duration of perioperative antibiotic prophylaxis and other antibiotic regimen (such as route of drug administration, antibiotic selection) also tends to complicate the understanding of the effectiveness of most perioperative antibiotic prophylaxis. Hence, the study.

Aim

The purpose of this work is to evaluate the effect of prophylactic antibiotics on patients’ post-operative outcome (as reflected in the reduction of the rate of surgical site infection).

Research Question

Does prophylactic antibiotics improve the outcome of patients after surgery?

LITERATURE ANALYSIS

In a bid to answer the research question, it is pertinent to focus on the importance of the key dependent, independent and possible mediating variables (such as SSIs, antibiotic prophylaxis, surgical procedure among others) that could influence the outcome of antibiotic prophylaxis postoperatively. Hence, the literature analysis.

Surgical Site Infections

According to a report on Infection Control by Burke (2003); nosocomial or hospital-acquired infections (otherwise called healthcare–associated infections) are today by far the most common complications affecting hospitalized patients.

Data collected from various sources mentioned that four types of infection accounted for more than 80 percent of all nosocomial infections. There includes urinary tract infection (mostly catheter-associated), surgical-site infection (SSI), bloodstream infection (majorly those associated with the use of an intravascular device), and pneumonia (mainly ventilator-associated) (Haley et al., 1985; National Nosocomial Infections Surveillance (NNIS) report, 1996; Eggimann and Pittet, 2001; Burke, 2003). Of the four, SSI is ranked second according to their frequencies, associated mortality rates and cost implication (Stone et al., 2002; Wenzel and Edmond, 2011; Singh et al., 2014).

Surgical site infections (SSIs) are defined as infections occurring up to 30 days after surgery (or up to one year after surgery in patients receiving implants) affecting either the incision or deep tissue at the operation site. These infections undoubtedly have a tremendous impact on morbidity and mortality and have been reported to raise the risk of death among patients (Singh et al., 2014). Quite significantly, it is important to highlight that Staphylococcus aureus, coagulase-negative staphylococci, Enterococcus spp. and Escherichia coli have also been implicated as the most common causative pathogens (Singh et al., 2014).

Epidemiology of SSIs

SSI-related deaths account for more than one-third of postoperative mortalities worldwide (Awad, 2012; Yang et al., 2018). In several studies, the incidences of SSI in high-income countries as the United States (1.9%) (Mu et al., 2011), France (1.0%) (Saunders et al., 2014) and Italy (2.6%) (Marchi et al., 2014) have been found to be lower than those in low-income nations including Turkey (4.1%) (Isik et al., 2015), China (4.5%) (Fan et al., 2014) and India (5.0%) (Pathak et al., 2014).

Researchers have estimated that among the pathogens that cause SSI, 48% consist of gram-negative bacteria, 40.8% are gram-positive bacteria, and 11.2% are fungi (Hendren et al., 2013; Yang et al., 2018). In a study in China, Escherichia coli (25.9%), Staphylococcus aureus (14.3%), and Pseudomonas aeruginosa (11.9%) were found to be the most dominant of all the pathogens estimated (Wen et al., 2010).

Data from the United States Center for Disease Control National Nosocomial Infections Surveillance (CDC NNIS) system show that SSIs are the third most frequently reported nosocomial infections, accounting for 14-16% of such infections among hospitalised patients and 38% among surgical patients (Emori and Gaynes, 1993; Mangram et al., 1999; Owens and Stoessel, 2008). Similarly, European data suggest that the incidence of SSIs may be as high as 20% depending on the procedure, the surveillance criteria used and the quality of data collection (Leaper et al., 2005; Owens and Stoessel, 2008).

According to a report by Najjar and Smink (2015); some studies suggest that 40% to 60% of these surgery-related infections may be preventable. Further, there are also reports that stress that less invasive surgery may be associated with reduced risk of SSIs. For example, in patients undergoing cholecystectomy, the SSI rate following laparoscopic procedures was reported to be 1.1%, compared with 4% following open procedures (Boni et al., 2006). Similarly, in patients with acute appendicitis, the SSI rate has been reported to be 2% with minimally invasive procedures and 8% with open procedures (Boni et al., 2006). Possible reasons for the lower incidence of SSIs with minimally invasive procedures have been attributed to the smaller incision, earlier mobilisation, reductions in postoperative pain, better preservation of immune system function, and decreased use of central venous catheters (Boni et al., 2006).

From various literature, one of the common challenges encountered in epidemiological studies involving SSIs has been linked to the heterogeneous nature of these infections. Some of the issues often reported include the estimated incidence varying widely across procedures, between hospitals, between surgeons and between patients (Nichols, 2001; Owens and Stoessel, 2008).

Risk factors for SSIs

This section highlighted various scholarly works on antibiotic prophylaxis in relation to patient-, pathogen- and procedure-related risk factors that could interfere with the postoperative outcomes of patients (as depicted in Table 1).

Summarily, from various sources; while the patient-associated factors often constitute older age, pre-existing infection, colonization with Staphylococcus aureus and other potential pathogens, diabetes and smoking; the procedure-associated factors were limited to poor surgical technique, the duration of the operation, the quality of preoperative skin preparation and inadequate sterilisation of surgical instruments (Mangram et al., 1999; Dominioni et al., 2006). There is also a myriad of pathogen-related causes of SSIs indicated in the present work. Meanwhile, a number of studies have also pointed out the fact that patient-related factors lead to increased cases of SSI compared to procedure-related factors (Dominioni et al., 2006; Owens and Stoessel, 2008).

Table 1: Patient-, pathogen- and procedure-related factors influencing SSIs (Source: the author)

Abbildung in dieser Leseprobe nicht enthalten

As represented in table 1, the presence of certain pathogens from endogenous and exogenous sources have been implicated in increasing the odds of contracting SSI. Microorganisms from the skin and nasal passages for example; have been found to be the most common sources of surgical site infection in clean operations (Wenzel, 2019). As such, reduction of the skin microbiome by application of skin antisepsis and nasal decolonization are considered primary strategies for reduction of surgical site infection (Wenzel, 2019).

The human skin is replete with millions of microorganisms, which outnumbers the human cells. The human gut is likewise a host to a diverse microbial community. In disease and injury (for instance; via surgery), the microbial density and metabolite production can change dramatically (Gilbert et al., 2016; Alverdy et al., 2017). Numerous planned and unplanned interventions in the perioperative period directly influence the gut microbiota. For example, both enteral and parenteral antibiotics have been known to cause dysbiosis by killing commensal organisms (Decker et al., 2020).

Microbiology of SSIs

Considering the above suggestion on SSIs; researchers have found that most SSIs arise from disease-causing agents among the patient’s endogenous flora (Mangram et al., 1999) - the most commonly isolated organisms are S. aureus, coagulase-negative staphylococci, Enterococcus spp. and Escherichia coli (Owens and Stoessel, 2008). As it was mentioned earlier, these pathogens differ from procedure to procedure (Table 2).

It is also important to mention that an increasing number of SSIs have been linked to antibiotic-resistant pathogens such as methicillin-resistant S. aureus (MRSA) or Candida albicans coli (Owens and Stoessel, 2008). Such indications may partly suggest an increasing number of severely ill or immunocompromised surgical patients, and the widespread indiscriminate use of broad-spectrum antibiotics (Mangram et al., 1999).

In addition to the patient’s endogenous flora, SSI pathogens may originate from exogenous sources such as members of the surgical team, the operating theatre environment, and instruments and materials brought within the sterile field during the procedure. Such pathogens have been found to be predominantly aerobes, particularly gram-positive organisms such as staphylococci and streptococci (Mangram et al., 1999; Owens and Stoessel, 2008).

Pathogens have also been found to originate from preoperative infections at sites remote from the operative site, particularly in patients undergoing insertion of a prosthesis or other implants (Mangram et al., 1999).

A number of researchers worked a mathematical expression to illustrate the relationship between the risk of developing SSIs and independent variables such as dose of contamination, resistance of individuals and the virulence of the pathogen. This is depicted below.

Looking at the relationship between the variables in the equation; the risk of SSI is considered elevated when the level of contamination exceeds 105 organisms per gram of tissue (Krizek and Robson, 1975), although lower doses may be required if foreign material such as sutures is present (Mangram et al., 1999). The virulence of the organism relates to its ability to produce toxins or other factors that increase its ability to invade or damage tissue. As such, mortality rates in patients infected with highly virulent pathogens such as MRSA have been reported to be as high as 74% (Dohmen, 2006).

Table 2: Pathogens commonly associated with different surgical procedures (adopted from Mangram et al., 1999)

Abbildung in dieser Leseprobe nicht enthalten

Note: CoNS: coagulase-negative staphylococci

Strategies for SSI prevention

As suggested above by Owens and Stoessel in their report on SSI, strategies for the prevention of SSIs are based both on reducing the risk of bacterial contamination and on improving the patient’s defenses against infection (2008). This requires a holistic approach which considers multiple patient-, pathogen- and procedure-related risk factors as indicated above. Several studies in a variety of clinical settings have in fact shown that such approaches can produce significant reductions in SSI rates during follow-up periods of up to two years (Weinberg et al, 2001; Gastmeier et al., 2002; Borer et al., 2004; Lutarewych et al., 2004; Schelenz et al., 2005; Haycock et al., 2005; Dellinger et al., 2005).

Although there are standard recommendations for the prevention of SSIs by global health organisations such as the CDC, WHO among others; the implementation of such guidelines is made complicated by the heterogeneous nature of SSIs (making it difficult to generalise findings from a study in a specific patient population (such as orthopaedic surgery patients) to a broader clinical setting), and by the presence of confounding factors such as the adherence to standard precautions (e.g. wearing surgical gloves) (Mangram et al., 1999; Owens and Stoessel, 2008).

Originally published in 2015, Najjar and Smink in their report discussed the negative implications of SSI on the patients and their caregivers. It was found that those diagnosed with an SSI faced a 2 to 11 times increase in mortality (Anderson et al., 2001; Astagneau et al., 2001). More so, although most survive their infection, prolonged hospital stays and secondary risks associated with treatment were often recorded (Kirkland et al., 1999). Even when patients recover, many find their overall quality of life is significantly impacted over the long term (Urban, 2006). In addition to these clinical concerns, the financial costs can range from forty dollars for superficial SSI to upward of 30,000 dollars for organ/space SSIs leading to system-wide excess costs of more than $7 billion per year (Stone et al., 2005; Urban, 2006).

Also critical to SSI prevention is understanding how the wound created by surgical operation can affect patients’ mortality and morbidity. For instance; based on the level of invasiveness of the procedure, presence of inflammation, with/without microbe inoculation; researchers have classified wounds as clean, clean-contaminated, contaminated, and dirty or infected (CDC, 2013; Najjar and Smink, 2015). Alternatively, wounds are generally being categorised in terms of anatomical location of the SSI. These includes superficial incisional SSI, deep incisional SSI, organ/space SSI (Horan et al., 1996; Najjar and Smink, 2015) as depicted in figure 1 below. Their incidence has been reported to have significant impact upon patient morbidity and outpatient resources – according to Phillips et al. (2014).

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