Emerging Paradigms in the Prevention of Surgical Site Infection

The Patient Microbiome and Antimicrobial Resistance

Dustin R. Long, M.D.; John C. Alverdy, M.D., F.A.C.S.; Monica S. Vavilala, M.D.

Disclosures

Anesthesiology. 2022;137(2):252-262. 

In This Article

Paradigm 1: Role of the Patient Microbiome in Surgical Site Infection

Germ theory, modern hospital sanitation measures, and advances in operating room sterility have led to substantial declines in perioperative infection over the preceding centuries. These improvements arose primarily from targeting environmental reservoirs of "exogenous" infection. Under this traditional model, surgical site infections are "healthcare-associated" via a causal relationship with nosocomial pathogens in the healthcare environment (Figure 3A). The ongoing importance of preventing exogenous infection continues to be underscored by studies demonstrating the role of perioperative sources such as the anesthesia workspace[11] and ultrasound probes[12] in clusters of common-source infection.

Figure 3.

Exogenous and endogenous routes of infection and evolving approaches to surgical site infection prevention. Traditional conceptions of healthcare-associated infection are hospital-centered, emphasizing the role of "exogenous" infection with bacteria newly acquired through contact with the hospital environment (A). Under this model, infection occurs when pathogens are transmitted from nosocomial reservoirs (surfaces, hands, ventilation systems, instruments) to the patient through contact that occurs in the course of clinical care. Exogenous sources are frequently implicated in common-source outbreaks, which attract significant attention; however, bacterial genetic analyses now demonstrate that, in routine clinical circumstances, the vast majority of healthcare-associated infections are "endogenous," arising from the patient microbiome rather than the hospital environment (B). Under this complementary model, bacteria colonizing the patient before contact with the healthcare system become pathogens when procedures (1), exposures (2), and stresses (3) that occur in the hospital disrupt normal regulation of the microbiome. The evolution of surgical site infection prevention strategies over time (C) can be conceptualized through this perspective. Fio2, fraction of inspired oxygen; IV, intravenous.

While maintaining clean perioperative environments, sterile technique, and hand hygiene remain cornerstones of infection prevention,[13] attention has increasingly turned to another important source as key to achieving further improvements in surgical site infection: the patient's own microbiome.[14–16] Under this complementary model, patients "bring their own" bacteria to the hospital, and "endogenous" infection occurs when commensal microbes shift from states of colonization to infection because of factors that perturb the microbiome (Figure 3B). While not arising from pathogens newly acquired from the hospital environment, these endogenous infections retain their classification as "healthcare-associated" events because of their relationship with procedures, medications, and physiologic stresses that uniquely occur in healthcare settings.

Exogenous and endogenous infection may be caused by similar organisms (e.g., Staphylococcus, Klebsiella, Escherichia, Enterococcus, and Proteus species) and cannot reliably be distinguished based on taxonomy or antimicrobial resistance patterns. However, studies using molecular techniques capable of tracking individual strains of Staphylococcus aureus have shown that upward of 80% of surgical site infections arise from the preoperative patient microbiome. This finding has been consistent across a range of patient, procedural, and geographic contexts.[17–20] While S. aureus is simpler to selectively isolate from preoperative patient samples for comparison with subsequent infection, accumulating evidence suggests that endogenously acquired infection may be the predominant mode of surgical site infection generally (not unique to S. aureus).[14,15,21] From this perspective, wound infection in the era of modern surgical practice has been described as a "failure to control the host-microbiome during surgery."[15]

The host microbiome may contribute to surgical site infection in the following ways.

Direct Contamination

The composition of the human microbiome varies dramatically by anatomic site, even differing significantly across various regions of the skin[22] (Figure 2C). Procedures such as surgical incision, intubation, and intravascular or urinary catheter insertion disrupt the normal anatomic separation of these compartments, resulting in mechanical translocation of bacteria from their normal sites of colonization (skin, oropharynx, gut) into new anatomic niches (deep tissue, lung, bloodstream, urinary tract; Figure 3B1). In this new microenvironment with differences in temperature, nutrient availability, immune activity, and competition from other species, quiescent bacteria can rapidly evolve to express pathogenic phenotypes and hence become "pathogens."

Prevention measures targeting endogenous wound contamination (e.g., skin preparation, antibiotic prophylaxis) are highly effective, but have important limitations. For example, traditional approaches to surgical skin preparation effectively sterilize the epidermis; however, the skin microbiome extends into subepidermal layers, with pathogens such as Pseudomonas aeruginosa observed as deep as dermal or adipose tissue.[23] This limitation is particularly well described in shoulder surgery: Cutibacterium acnes, which heavily colonizes the shoulders of male patients and is a leading cause of chronic infection and arthroplasty failure, evades topical antiseptics through sequestration in sebaceous glands.[15]

Trojan-horse Hypothesis

In addition to direct contamination of the surgical field, bacteria from anatomically distant compartments of the human microbiome may indirectly seed an otherwise sterile operative site (Figure 3B2). The "Trojan-horse hypothesis" is based on the observation that some pathogens, most notably S. aureus, can invade neutrophils at remote sites of colonization (e.g., nares, gastrointestinal tract) and remain viable intracellular pathogens after re-entering systemic circulation.[14] As part of the normal immune response to surgery, these pathogen-laden neutrophils migrate to sites of traumatized tissue and foreign material (which may be sterile in the case of a surgical procedure), where they release this infectious payload in parallel with other inflammatory mediators via exocytosis.[24,25]

"Awakening" the Microbiome

Bacteria already natively present within the microbiome of the surgical site may also undergo phenotypic switching from commensalism to virulence without the need for translocation (Figure 3B3). Common perioperative exposures such as opioids,[26] anesthetic agents,[27,28] increased fraction of inspired oxygen (FIO2),[29] and physiologic stress[30] may dramatically impact the microbiome, triggering expression of pathogenic phenotypes among "normal" microbes resident in the surgical site.

In mice, morphine administration has been shown to rapidly induce a state of gut dysbiosis (reduced diversity, predominance of Enterococcus faecalis),[26] and trigger P. aeruginosa virulence and gut-derived sepsis.[31] These effects can be attenuated by administration of opioid-receptor antagonists such as methylnaltrexone.

Brief periods of volatile anesthetic exposure, on par with a typical anesthetic, have also been shown to collapse microbiome diversity with reductions in protective organisms such as Lactobacillus and selection for potential pathogens such as Bacteroides species. These changes begin within a day of exposure, peak at approximately 1 week, and are similar for sevoflurane[27] and isoflurane.[28] Delivery of increased FIO2, once recommended as a routine prevention measure, has recently been demonstrated to increase proliferation of aerobic bacteria (e.g., S. aureus) and pathologic inflammation in the lung and gut[29] with little or no overall impact on rates of surgical site infection.[32,33]

In addition to their direct influences on the microbiome, many of these same factors simultaneously affect the host immune response (Figure 2E). Commonly used intravenous opioids[34] and volatile anesthetics[35] have potent immunosuppressive potential, the clinical sequelae of which have not been adequately studied. Soluble factors in plasma and wound fluids from trauma patients that peak within the first day of injury in response to tissue damage suppress neutrophil function,[36] and may similarly increase susceptibility to infection after major surgery. Interestingly, recent proteomic analyses have demonstrated that the immunologic stage for postoperative surgical site complications may be set well in advance of surgery. In a study of patients undergoing noncancer bowel resection, individual differences in preoperative immune and inflammatory phenotypes improved prediction of postoperative outcomes compared with the National Surgical Quality Improvement Program Surgical Risk Calculator, which utilizes traditional clinical predictors.[37]

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