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. Author manuscript; available in PMC: 2024 Apr 1.
Published in final edited form as: J Hosp Infect. 2023 Jan 21;134:121–128. doi: 10.1016/j.jhin.2023.01.007

Staphylococcus aureus Transmission in the Anaesthesia Work Area Has Greater Risk of Association with Development of Surgical Site Infection when Resistant to the Prophylactic Antibiotic Administered for Surgery

Randy W Loftus 1, Franklin Dexter 2, Jeremiah R Brown 3
PMCID: PMC10066826  NIHMSID: NIHMS1867501  PMID: 36693592

Structured Summary

Background:

The extent to which the transmission of prophylactic antibiotic resistant bacteria from the anaesthesia work area environment increases the risk of surgical site infection is unknown. We hypothesized that SSI risk would increase progressively from no transmission to transmission of prophylactic antibiotic resistant isolates.

Methods:

This was a retrospective analysis of archival samples collected in two previously published studies with similar inclusion criteria and sample collection methodology (observational study 2009–2010 and randomised trial 2018–2019). Archival isolates were linked by barcode to all patient demographic and procedural information, including the prophylactic antibiotic administered, transmission, and surgical site infection development. For this study, all archival isolates underwent prophylactic antibiotic susceptibility testing, and the ordered association of S. aureus transmission (no transmission, transmission of prophylactic antibiotic sensitive isolates, and transmission of prophylactic antibiotic resistant isolates) with surgical site infection was assessed.

Results:

The risk of SSI development was 2% (8/406) without S. aureus transmission, 11% (9/84) with transmission of S. aureus isolates sensitive to the patient’s prophylactic antibiotic, and 18% (4/22) with transmission of prophylactic antibiotic resistant S. aureus isolates. The Cochrane-Armitage two-sided test for ordered association was P < 0.0001. Treating these three groups as 0, 1, and 2, by exact logistic regression, there was greater odds of SSI for each unit increase (ORadj 3.59, 95% CI 1.92–6.64, P < 0.0001).

Conclusions:

Transmission of S. aureus in the anaesthesia work area reliably increases the risk of surgical site infection, especially when the isolates are resistant to the prophylactic antibiotic.

Keywords: Prophylactic antibiotic stewardship, intraoperative transmission, S. aureus, mechanisms of resistance

Introduction:

Antibiotic resistant infections are associated with increased hospital duration, repeat surgery, increased duration of antibiotic therapy, and an increase in worldwide mortality [1,2]. The importance of prevention of the spread of antibiotic resistant pathogens and infections has been emphasized as a method for improving antibiotic stewardship by decreasing the need for antibiotic use [1–4].

Perioperative (preoperative, intraoperative, and postoperative) bacterial transmission events occur via direct contamination, aerosolized particles, spread from one adjacent skin surface to another, and intravascular injection [5–12]. The conceptual framework for the importance of preventing pathogen transmission (or spread) is grounded in pathogen movement. Mapping of pathogen movement can identify breaks in aseptic practice, or improvement targets, that can result in optimization of basic preventive measures such as environmental cleaning [13,14]. For example, an anaesthesia vaporizer contaminated with Staphylococcus aureus at the start of the workday is simply contamination, while movement of that same S aureus to the patient’s nose previously measured to be negative at baseline would indicate transmission. The improvement target in this example would be to address the source of the transmission event by improving terminal cleaning to reduce the chance that pathogens contaminating the vaporizer at the start of the day could result in patient transmission events. It is important to prevent transmission events because they can lead to downstream infection via subsequent movement of the pathogen from the nonsterile site (patient nose) to one or more sterile sites (i.e., blood stream, respiratory tract, urinary tract, the incision, and/or deep organ space) via direct contamination, aerosolization of particles, and/or haematogenous spread [5–13,14]. Anaesthetists can inject up to 50,000 colony forming units of bacterial pathogens through intravascular devices (stopcocks), where the reservoir of origin is their hands [15]. Thus, patients undergoing surgery are exposed to a considerable anaesthesia work area bacterial inoculum in addition to their own flora that can be transmitted from a nonsterile site (nares) to the surgical incision [16].

Patients are also impacted by the increased pathogenicity of organisms commonly isolated from anaesthesia work area (AWA) reservoirs. While pathogens contaminating the wound at the time of surgery are usually susceptible to prophylactic antibiotic therapy administered prior to skin incision, [17] bacterial isolates arising from AWA reservoirs (i.e. patient skin sites [16], provider hands, environmental surfaces, and intravascular devices) are often hyper-transmissible and associated with increased risk of SSI development. This is in part related to increased strength of biofilm formation and increased desiccation tolerance. These relatively common AWA strain characteristics are associated with increased risk of multidrug resistance (MDR) [6, 7, 18].

This prior work serves as the foundation for our overarching hypothesis that widespread employment of evidence-based AWA infection control measures [13, 14] will prevent the spread of these more pathogenic strain characteristics, and in turn, more difficult-to-treat SSIs associated with prolonged antibiotic use. If proven scientifically, such an approach would provide novel methodology to improve perioperative antibiotic stewardship. However, we must address a key knowledge gap before rigorously testing this hypothesis. The association of transmitted AWA S. aureus isolates with multidrug resistance is established [18], but the association of those isolates with resistance to the prophylactic antibiotic employed for the surgical procedure has not been tested. Confirmation of this association would further support the validity and clinical relevance of prior findings [6, 7, and 18].

In the current paper, we report the results of a laboratory analysis of archival isolates from two different time periods (2009–2010 and 2018–2019) that involved similar baseline infection control practices and sample collection methodologies [5,13]. Two time periods were studied in order that we could account for secular change [19] and potential differences in infection control practices across institutions. The archival isolates were stored with unique barcodes linked to de-identified patient and procedural data, including the prophylactic antibiotic employed for the surgical procedure, transmission detection, and SSI development. For the current study, we tested the archival isolates for susceptibility to the prophylactic antibiotic used prior to the skin incision. We then conducted our primary analysis of an ordered association of S. aureus transmission (no transmission, transmission of prophylactic antibiotic sensitive isolates, and transmission of prophylactic antibiotic resistance isolates) with SSI development. We hypothesized that there would be greater risk for SSI development with detection of AWA reservoir transmission of antibiotic resistant S. aureus isolates as compared to transmission of prophylactic antibiotic sensitive isolates or no transmission.

Methods:

This is a retrospective secondary analysis of samples collected in two previously published studies, a prospective observational study [5] and a randomised trial [13]. The observational study had a waiver for informed patient consent [5], while the randomised trial required informed, written patient consent [13]. The University of Iowa declared that this study of biorepository bacterial isolates from the prior work did not meet the definition of human subject’s research because it involved laboratory analysis of archival isolates associated with de-identified data.

Included Studies:

One study involved a prospective observational study conducted at the University of Iowa, Dartmouth-Hitchcock Medical Centre, and UMass Memorial in 2009–2010 [5] involving adult patients undergoing all types of surgery requiring general and/or regional anaesthesia and placement of a peripheral intravenous catheter. The aims were to identify sources of patient intravenous stopcock contamination and to validate the prior association of stopcock contamination with infection and mortality [5]. Another study involved a randomised, controlled clinical trial conducted at the University of Iowa in 2018–2019 that was designed to assess the efficacy of evidence-based anaesthesia work area infection control measures for prevention of S. aureus transmission and all-cause SSI development [13]. Adult patients scheduled to undergo orthopaedic total joint, orthopaedic spine, oncologic gynaecological, thoracic, general, colorectal, open vascular, plastic, and open urological surgery requiring general and/or regional anaesthesia were considered eligible for enrolment. Thus, for both studies, adult patients undergoing surgery requiring anaesthesia and placement of a peripheral intravenous catheter were considered eligible for enrolment, and all patients were followed postoperatively for at least 30 days [5, 13]. In addition, both accounted for seasonal variation with 12 months of implementation, and timing/selection of prophylactic antibiotics was in accordance with the Surgical Care Improvement Project (SCIP) guidelines (within one hour of incision) [5,13,20].

Given these similarities in study design, we anticipated a low likelihood of a measurable impact of change in infection control practices over time (secular change) and/or differences in infection control practices across hospitals that could in theory affect the association of transmission of resistance with SSI development. However, we utilized two studies separated by a decade, the involvement of 3 academic medical centres, and the inclusion of study (time-period) in the modelling of the primary association to control for these factors.

Study Objectives and Background:

All S. aureus isolates from these prior studies were archived for subsequent analysis at the time the original studies were performed. Unique isolate barcodes were associated with pertinent study demographic information including the prophylactic antibiotic administered for surgery, detection of transmission (defined below), and SSI development [5,13]. In the current study, our primary objective was to further analyse these isolates in order that we could test for an ordered association of transmission of S. aureus isolates from AWA reservoirs (no transmission, transmission of isolates sensitive to the prophylactic antibiotic given prior to the incision, and transmission of isolates resistant to the prophylactic antibiotic given prior to the incision) with SSI development.

Thus, archived isolates were removed from the biorepository and subjected to prophylactic antibiotic susceptibility testing (described below). Once this testing was complete, we tested for the ordered association described above. As stated previously, both studies involved similar baseline infection control practices and sample collection procedures that are described in greater detail below.

Baseline infection control practices:

Infection control practices for both study time periods included routine between-case and terminal (end of day) environmental cleaning with quaternary ammonium compounds with surface disinfection wipes [5,13]. All providers had access to alcohol dispensers located on the wall and/or anaesthesia carts. Gloves were immediately available for use [5, 13].

Hand hygiene, vascular care, environmental cleaning, and preoperative patient decolonization procedures were optimized by feedback for the randomised trial [13]. The feedback provided used cluster detection software (OR PathTrac, RDB Bioinformatics, Omaha, NE 68154) to identify S. aureus transmission events and their associated reservoirs of origin, transmission locations, portals of entry (stopcocks), and strain characteristics to identify improvement targets to facilitate process improvement measures [13,14].

Sample collection procedures:

As described below, there were few differences in sample collection between time-periods [5,13]. We controlled for these differences by modelling for study period.

Provider hand sampling:

A modified glove juice technique was utilized to sample healthcare provider hands including those of anaesthesia attending physicians, anaesthesia resident physicians, Certified-Registered Nurse Anaesthetists [CRNAs], break providers, and/or clinical anaesthesia technologists) for both studies [5,13]. Differences between the prospective observational study and the randomised trial were that the observational study involved intraoperative provider hand sampling before, during, and after patient care [5] while the randomised trial involved before and after care sampling for intraoperative and postoperative (before 10:00 A.M. on postoperative day 1) patient care periods [13].

Patient sampling:

The patient nares, axilla, and groin skin sites were sampled via use of a sterile swab (ESwab, Copan Diagnostic Inc., Corona, CA) [5,13]. The swab was inserted gently into the internal surface of each naris and to the midpoint of each axilla and rotated 360° ten times to obtain a culture. For groin samples, the entire inguinal crease was sampled bilaterally by continually rolling the swab across the crease to obtain the culture. The prospective observational study involved nares and axillary sampling [5] while the randomised trial involved nares, axilla, and groin sampling [13].

Environmental sampling:

The adjustable pressure-limiting valve and agent dial of the anaesthesia machine were sampled intraoperatively before patient entry and at case end before routine cleaning. A sterile polyester fibre-tipped applicator swab (ESwab, Copan Diagnostic Inc., Corona, CA) was rolled several times over the selected areas to obtain cultures [5,13]. The randomised trial also involved postoperative culture of the patient bed rail using the same technique [13]. For the observational study, a quaternary ammonium compound (Dimension III; Butcher’s, Sturtevant, WI) was used for active decontamination of the adjustable pressure-limiting valve and agent dial of the anaesthesia machine by study personnel prior to sampling and by usual operating room personnel according to their standard procedure for routine, between-case cleaning involving a top-down approach but without focused cleaning of the adjustable pressure-limiting valve and agent dial [5]. For the later study, a microfibre cloth (16 in × 16 in; The Rag Company) was soaked in a quaternary ammonium compound (Virex; Diversey Inc) and used to clean the anaesthesia machine and monitors before patient OR entry and before patient admission to the recovery unit. A top-down cleaning approach was used. Surface disinfection wipes, containing a quaternary ammonium compound and isopropyl alcohol (PDI Health Care), were used to clean the anaesthesia machine following induction of anaesthesia and patient stabilization [13].

Stopcock sampling:

Sterile polyester fibre-tipped applicator swabs (ESwab, Copan Diagnostic Inc., Corona, CA) were used to sample the entire internal surface area of an open lumen stopcock. For a closed, disinfectable stopcock, only the surface that would come into contact with the syringe tip was sampled. Stopcocks primarily used by the providers were sampled [5, 13]. For the observational study, only the stopcock at the end of the case was sampled [5]. For the randomised trial, the stopcock at the end of the case and in the postoperative period (post anaesthesia care unit, hospital floor, or intensive care unit) before 10:00 on post operative day 1 was sampled [13].

Microbial culture conditions:

Each swab was inoculated onto a sheep’s blood agar plate plates and incubated for 48 hours at 35°C [21]. Bacterial pathogens were analysed via simple rapid tests and conventional microbiological culture techniques to identify S. aureus isolates.

Isolate analysis:

S. aureus isolates from each study period [5,13] were previously analysed according to temporal association (same day of surgery, same operating room, and the same sampling period), Kirby-Bauer prophylactic antibiotic susceptibility testing (including methicillin, ampicillin, ceftazidime, cefuroxime, ciprofloxacin, clindamycin, gentamicin, meropenem, penicillin, piperacillin-tazobactam, sulfamethoxazole-trimethoprim, linezolid, and/or tetracycline antibiotics), and analytical profile indexing [21].

For this study, isolates underwent prophylactic antibiotic susceptibility testing specific to the antibiotic employed for the procedure. In addition, transmission was analysed according to risk of aerosolization, contiguous spread, and/or haematogenous spread.

Outcome variables and variables definition:

Observational unit:

A randomly selected operating room environment, and the case immediately to follow when available, involving surgical care of an adult patient undergoing anaesthesia according to usual practice and requiring placement of an intravenous catheter [5, 13].

Transmission event:

An epidemiologically-related transmission event was previously defined by the isolation of prophylactic antibiotic resistant S aureus pathogens from at least two distinct, temporally associated AWA reservoirs, and/or the isolation of at least one resistant pathogen from a reservoir at the end of a case that was not present in that same reservoir at case start [5, 13, 14]. Reservoir samples that were found to be positive throughout care (i.e., positive anaesthesia attending provider hands at the beginning and end of a case) were not considered to be transmission events. Molecular techniques for identification of clonal transmission were used for the earlier study [5].

Provider origin of transmission was assumed if an isolate from the hands of one or more anaesthesia provider(s) before patient care was of the same pathogen class and temporally associated (epidemiologically related) to one or more subsequent, distinct reservoir isolates [5,13].

Environmental origin of contamination was assumed if an isolate from the operating environment sampled at baseline was epidemiologically related to one or more subsequent, distinct intraoperative or postoperative reservoir isolates [5,13].

Patient origin of contamination was assumed if an isolate from one or more patient skin surfaces at baseline was epidemiologically related to one or more subsequent, distinct intraoperative or postoperative reservoir isolates [5,13].

Stopcock contamination was defined by contamination of a patient intravenous stopcock set provided for the procedure at case end or in recovery.

All-Cause SSI (with or without identification of causative organism(s) of infection): SSIs were previously identified via the following methodology [5, 13]. All patient medical records were screened for evidence of elevated white blood cell count, fever, antimicrobial order, office note documentation of infection, and culture acquisition. Patients with at least 1 of the 5 criteria underwent full chart review to identify surgical site infections according to National Healthcare Safety Network definitions of SSI [6, 7, 13, 14,22,23]. Pulsed-field gel electrophoresis was used to link causative organisms of infection for SSI to reservoir pathogens for the prospective observational study [5].

Baseline demographics:

The following demographic variables were previously obtained for each observational unit: study (1=observational, 2=randomised trial), patient age, patient sex (male or female), American Society of Anesthesiologist’s (ASA) health classification >2, and Study on the Efficacy of Nosocomial Infection Control (SENIC) score, an index characterizing the risk of infection development [5, 13, and 24].

Statistics:

Stata 17.0 was used for inferential analyses (StataCorp, College Station, TX). All observational units from studies 1 and 2 were used to test the rank association between exposure to transmitted S. aureus and development of SSI using the Cochrane-Armitage test of ordered association. The following three groups were analysed using a two-sided, exact P-value: no transmission, transmission of isolates with prophylactic antibiotic sensitivity, and transmission of isolates with prophylactic antibiotic resistance. The Wilcoxon-Mann-Whitney test was used to examine the potential association of study (i.e., time period), patient age ≥ 65 years, patient sex (male or female), ASA >2, and SENIC > 2 with ordered group (no transmission, transmission of sensitive isolates, and transmission of resistant isolates). Treating these three groups as 0, 1, and 2, exact logistic regression was utilized with and without adjustment for statistically significant covariates. The two-sided P <0.05 were considered statistically significant.

All observational units from both studies [5,13] were used for the analyses. Evidence-based improvements in anaesthesia work area infection control are net cost neutral provided the incremental risk ratio for surgical site infection is less than 0.91 [13,25,26]. The incidence of surgical site infection is sufficiently small that risk ratios and odds ratios are functionally the same. We considered the sample size to be appropriate provided the confidence interval for the odds ratio excluded 1.10, where 1.10 = 1/0.91.

Results

S. aureus transmission occurred in 20% of observational units (106/512), of which 20% (22/106) were resistant to the prophylactic antibiotic administered for the procedure.

All-cause SSI and basic demographic information stratified by ordered Staphylococcus aureus transmission (no transmission, transmission of sensitive isolates, and transmission of resistant isolates) is shown in Table 1. With univariate analysis, study (P=0.0001, showing much less transmission in the later than the earlier study) and sex (P=0.027, female greater than male) were associated with transmission while ASA >2, patient age ≥ 65, and SENIC were nonsignificant (all P >0.54).

Table 1:

Surgical Site Infection and Basic Demographic Information of Patients Stratified by the Three Ordered Groups of Staphylococcus aureus Transmission

Group No Transmission (N=406) Transmission Sensitive to the Prophylactic Antibiotic (N=84) Transmission Resistant to the Prophylactic Antibiotic (N=22) Total
Surgical Site Infection No 398 75 18 512
Surgical Site Infection Yes 8 9 4
% Surgical Site Infection 2% 11% 18%
S. aureus Phenotype H No 384 63 16 512
S. aureus Phenotype H Yes 22 21 6
% S. aureus Phenotype H 5% 25% 27%
Study 1 163 62 11 512
Study 2 243 22 11
% Study 2 60% 26% 50%
ASA 1–2 268 57 15 512
ASA > 2 138 27 7
% ASA > 2 34% 32% 32%
SENIC 0–2 394 82 22 512
SENIC >2 12 2 0
% SENIC > 2 3% 2% 0%
Female 215 33 10 512
Male 191 51 12
% Female 47% 61% 55%
Age 18–64 years 285 60 12 512
Age 65+ years 121 24 10
% >64 years 30% 29% 45%
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Resistant = Resistant to the prophylactic antibiotic employed for surgery

SENIC = Study on the Efficacy of Nosocomial Infection Control (SENIC) score, an index characterizing the risk of infection development.23

The risk of SSI development was 2% (8/406) without S. aureus transmission, 11% (9/84) with transmission of prophylactic antibiotic sensitive S. aureus isolates, and 18% (4/22) with transmission of prophylactic antibiotic resistant S. aureus isolates. The Cochrane-Armitage exact two-sided test for ordered association was P < 0.0001. Treating these three groups as 0, 1, and 2, by exact logistic regression, there was 3.64-fold greater odds of SSI for each unit increase, 95% confidence interval 1.95 to 6.72, P < 0.0001. With covariate adjustment, there was 3.59-fold greater odds of SSI for each unit increase, 95% confidence interval 1.92 to 6.64, P < 0.0001 (Table 2). Neither study (i.e., time period) nor sex was significantly associated with SSI when controlling for group (P ≥ 0.86).

Table 2:

Ordered Association of Staphylococcus aureus Transmission Group and Development of Surgical Site Infection

Surgical Site Infection Odds Ratio 95% Confidence Interval P-Value
Transmission Group 3.59 per each 1-unit change 1.92 to 6.64 <0.0001
Study 1.11 0.38 to 3.26 0.999
Female 1.22 0.43 to 3.66 0.86
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Confidence intervals and P-values were calculated using exact logistic regression. The dependent variable was surgical site infection. The transmission group is an ordered variable. A 1-unit change was either (a) an increase from no Staphylococcus aureus transmission to transmission with prophylactic antibiotic sensitive S. aureus or (b) an increase from transmission with prophylactic antibiotic sensitive S. aureus to transmission of prophylactic antibiotic resistant S. aureus. A 2-unit change would be an increase from no transmission of S. aureus detected in the anaesthesia workspace to transmission and the S. aureus was resistant to the prophylactic antibiotic. The other demographic variables in Table 1 (American Society of Anesthesiologists physical status, SENIC score, and patient age) had no detected association with transmission, all Kruskal-Wallis P > 0.51.

Fourteen transmission sequencies (“transmission stories”) involving S. aureus isolates resistant to the prophylactic antibiotic employed at the time of surgery were identified. All sequences (14/14) involved intraoperative reservoirs (i.e., contamination caused infection via transmission). The relationship of these transmission sequences with risk of aerosolization, contiguous spread, and/or haematogenous seeding is described in Table 3.

Table 3:

Anesthesia Work Area Reservoir Transmission of Staphylococcus aureus Isolates Resistant to the Prophylactic Antibiotic Employed for Surgery

Randomised Trial13
Event Source Contiguous Source Hematogenous Source Aerosolization Surgical Site Infection
1 Anaesthesia machine Anaesthesia machine Anaesthesia machine Yes
2 Patient nares No Patient nares Yes
3 Patient nares, axilla, groin No Patient nares, axilla, groin No
4 Anaesthesia machine Anaesthesia machine Anaesthesia machine No
5 Anaesthesia machine No Anaesthesia machine No
6 Anaesthesia assistant hand Anaesthesia assistant hand Anaesthesia assistant hand No
7 No No Unknown No
Observational Study5
Event Source Contiguous Source Hematogenous Source Aerosolization Infection
1 Patient No Patient No
2 Patient No Patient No
3 Patient No Patient Yes
4 Patient No Patient Yes
5 Anaesthesia attending hand No Anaesthesia attending hand No
6 Resident hand start No Resident hand start Yes
7 No No Attending hand No
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13

Loftus RW, Dexter F, Goodheart MJ, McDonald M, Keech J, Noiseux N, et al. JAMA Netw Open. 2020; 2:e201934. doi: 10.1001/jamanetworkopen.2020.1934.

5

Loftus R.W., Brown J.R., Koff M.D., Reddy S., Heard S.O., Patel H.M., et al. Multiple reservoirs contribute to intraoperative bacterial transmission. Anesth Analg. 2012;114: 1236–48.

Contiguous: Patient skin contamination.

Hematogenous: Patient intravenous stopcock contamination.

Aerosolization: Contamination of ≥ 1 anaesthesia work area reservoirs proven to be associated with healthcare-associated infection development, with aerosolization of contaminated particles a known route.5,12,13

Discussion

Preventing the spread of antibiotic resistant pathogens and infections is an important worldwide patient safety issue [1–4]. We show that AWA S. aureus transmission reliably increases the risk of SSI, especially when the isolates are resistant to the prophylactic antibiotic used for the surgical procedure. These results provide clinical relevance for a solid body of published data [6, 7, 18]. They also provide the scientific rationale for formally testing the impact of evidence-based AWA infection control measures [13,14] on targeted attenuation of the perioperative spread of prophylactic antibiotic resistant isolates and SSIs.

Prior work has shown that bacterial isolates transmitted from AWA reservoirs are more likely to be multidrug resistant [6, 7, 18]. The current study extends those results by assessing the association of transmission of isolates resistant to the prophylactic antibiotic employed for the surgery with SSI development. To the authors’ best knowledge, this is the first study of the clinical relevance of transmission of prophylactic antibiotic resistant isolates in the anaesthesia workspace. We found that approximately 18% of transmitted S. aureus isolates were resistant to the prophylactic antibiotic employed. These findings are concerning, especially when considering that there may be imperfect compliance with Surgical Care Improvement Project Measures that could impact the timing and choice of prophylactic antibiotic administration [27]. Further, clinical factors such as severe haemorrhage may impact tissue and plasma antibiotic levels [28]. Taken together, this evidence suggests that transmission of prophylactic antibiotic resistant organisms during routine anaesthesia care may be associated with an increased risk of SSI.

Our results support this premise by showing that transmission of prophylactic antibiotic resistant S. aureus isolates is associated with greater risk of SSI development when compared to no transmission or to transmission of sensitive isolates. However, while transmission of prophylactic antibiotic sensitive S. aureus isolates was associated with lesser risk of SSI, it was still greater than for patients where there was no AWA transmission. Transmission of prophylactic antibiotic sensitive isolates also accounted for the most observed infections. Thus, the most important conclusion from these results is that they further validate the contribution of AWA reservoir transmission to SSI development. Prior work has definitively linked using molecular techniques AWA reservoir isolate transmission to causative organisms of SSI development [5–7]. These results further highlight the importance of implementation of evidence-based AWA infection control measures to eliminate transmission of both sensitive and resistant isolates, with particular attention to targeted attenuation of the spread of resistant pathogens [13, 14]. Healthcare systems should strive for widespread implementation of these proven measures [13,14] to improve perioperative patient safety. In parallel, the impact of widespread implementation of improved AWA infection control on targeted attenuation of highrisk bacterial strain characteristics and on the subsequent development of antibiotic resistant SSIs should be assessed [1,2].

The inclusion of two study time-periods [5,13] was deliberate in order that we could control for the potential impact of secular trends, such as improved infection control [13,14] or selection/timing of administration of prophylactic antibiotics, [20] on the analysed association of transmission all-cause SSI development. Our univariate analyses showed a significant and reliable (P = 0.0001) effect of study (i.e., period) on S. aureus transmission. This is explained by improved infection control in the intervening decade [13]. For example, in the era of the randomised trial (study #2), there was post-induction environmental cleaning with surface disinfection wipes, anaesthesia-based patient decolonization, and improved vascular care of both injection ports and syringe tips [13]. This reduction occurred despite methodological differences that may have increased detection of transmission for the randomised trial because more reservoirs were tested [5,13]. As expected, there was no impact of study period on the primary studied association between transmission and SSI (P = 0.99) because human and/or bacterial pathophysiological principles impacting SSI development are not likely to change in a 10-year period. There is therefore a solid justification to include data from the two time periods [5,13].

We leveraged use of archival pathogens. Study of archival pathogens is a valid scientific approach that can enable research to drive innovation to improve clinical patient outcomes [29]. We have shown how anaesthetists can leverage the clinical anaesthesia workspace to guide innovation, including but not limited to development of novel molecular diagnostics, that can serve to augment extra mural funding and research efforts [6, 7,26,29].

Potential Limitations: This study is limited to S. aureus. Other studies have documented the presence of a wide range of micro-organisms during anaesthetic procedures, including high-fidelity simulation [30] and clinical practice [31]. Thus, future work research and expert guidance [32] should consider both these results and extension to additional pathogens. While molecular techniques such as pulsed-field gel electrophoresis were used only in the early study [5] for assessment of clonal transmission, subsequent work has demonstrated that the platform of temporal association and systematic phenotypic analysis can identify epidemiologically-related transmission events that are tightly associated with SSI development, and that when such transmission events are reduced, so too are SSIs [13,14].

In conclusion, we show that AWA S. aureus transmission reliably increases the risk of SSI, especially when the isolates are resistant to the prophylactic antibiotic used for the surgical procedure. These results provide clinical relevance for a solid body of published data [6,7,18], and they provide the scientific rationale for formally testing the impact of evidence-based AWA infection control measures [13,14] on targeted attenuation of the perioperative spread of prophylactic antibiotic resistant isolates and SSIs. This work may yield a novel approach to improve perioperative antibiotic stewardship.

Funding:

APSF, NIAID R01AI155752, Dartmouth-Hitchcock Medical Centre

Footnotes

CRediT author statement: Randy Loftus: Conceptualization, Methodology, Investigation, Resources, Data Curation, Writing, Reviewing, and Editing. Franklin Dexter: Formal Analysis, Writing, Reviewing, and Editing. Jeremiah Brown: Conceptualization, Writing, Reviewing, and Editing

Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Conflicts of Interest:

Randy W. Loftus reported research funding from Georgia-Pacific Manufacturing, Sage Medical Inc., B. Braun, Draeger, Surfacide, and Kenall, has one or more patents pending, and is a partner of RDB Bioinformatics, LLC, and 1055 N 115th St #301, Omaha, NE 68154, a company that owns OR PathTrac, and has spoken at educational meetings sponsored by Kenall (AORN) and B. Braun (APIC). Other authors reported no conflicts of interest.

Contributor Information

Randy W. Loftus, University of Iowa.

Franklin Dexter, University of Iowa.

Jeremiah R. Brown, Dartmouth Geisel School of Medicine.

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