Loftus, Randy W. MD*; Brown, Jeremiah R. PhD, MS†; Koff, Matthew D. MD, MS*; Reddy, Sundara MD‡; Heard, Stephen O. MD§; Patel, Hetal M. BS, MLT*; Fernandez, Patrick G. MD*; Beach, Michael L. MD*; Corwin, Howard L. MD‖; Jensen, Jens T. MS*; Kispert, David BA*; Huysman, Bridget BA*; Dodds, Thomas M. MD*; Ruoff, Kathryn L. PhD¶; Yeager, Mark P. MD*
Health care-associated infections (HCAIs) are a major public health concern.1–5 Bacterial cross-contamination is thought to play an important role in HCAI development, but the relative importance of the known hospital bacterial reservoirs (health care provider hands, patient, and environment, including health care equipment) in this process is unknown.6–11 A better understanding of how bacterial cross-contamination occurs can provide the basis for the development of evidence-based preventive measures. The relatively controlled intraoperative environment provides a unique opportunity to examine these relationships. Studies have shown that intraoperative bacterial contamination of patient IV stopcock sets is common and is related to bacterial contamination of anesthesia provider hands before patient care.12–14 However, the relative contributions of other known intraoperative bacterial reservoirs including the patient, the patient environment, and provider hand contamination throughout the process of patient care to stopcock transmission have not been characterized. The primary aim of the current study was to examine these relationships. The secondary aims were to identify risk factors for stopcock contamination and to examine the prior association of stopcock contamination with increased 30-day postoperative infection and mortality. Additional microbiological analyses were completed to determine the frequency with which provider hands serve as vectors for transmission between intraoperative bacterial reservoirs, to examine the efficacy of current environmental decontamination practices, and to determine the prevalence of bacterial pathogens within intraoperative bacterial reservoirs and the contribution of those pathogens to 30-day postoperative infection development. The frequency of provider hourly hand decontamination events (HDEs) was also observed.
This was a prospective, randomized, observational study performed at 3 institutions, Dartmouth–Hitchcock Medical Center (DHMC) in New Hampshire, the University of Iowa Hospitals and Clinics in Iowa, and the University of Massachusetts Memorial Medical Center in Massachusetts. The study took place over 12 consecutive months (March 2009 to February 2010) with approval obtained at each study site from the respective IRB for the protection of human subjects with a waiver for informed patient consent. Adult patients undergoing surgery requiring general anesthesia and IV catheter placement were considered eligible for enrollment. Absence of an IV catheter and/or surgery requiring only monitored anesthesia care, pediatric patients, and lack of scheduled sequential operative cases were the exclusion criteria.
To identify the reservoir of origin for between-case and within-case stopcock transmission events.
To identify risk factors for stopcock contamination and to verify the prior association of stopcock contamination and increased postoperative infection and mortality.
To determine the frequency with which provider hands serve as vectors for transmission between intraoperative bacterial reservoirs, to examine the efficacy of current environmental decontamination practices, and to determine the prevalence of bacterial pathogens within intraoperative bacterial reservoirs and the contribution of those pathogens to postoperative infection development.
The frequency of provider HDEs was also observed.
Operating room selection.
A computer-generated list was used to randomly select operating rooms at each institution. The randomized unit study design was intended to include a wide variety of surgical procedures, patient comorbidities, infection control measures, and health care providers.
The first 2 consecutive patients undergoing general anesthesia in each of 274 randomly selected operating rooms at 3 institutions were studied as a case pair to identify between-case and within-case bacterial stopcock transmission events. Previously sterile stopcock sets were cultured at case end for both case 1 and case 2 of each of 274 case pairs. Bacterial reservoirs including provider hands throughout patient care, patients, and the anesthesia machine adjustable pressure-limiting (APL) valve and vaporizer agent dial, proven representatives of the intraoperative patient environment,12–14 were sampled in parallel throughout the process of intraoperative patient care for both operative cases. Reservoir isolates were then compared to stopcock bacterial isolates and the origin determined via standard microbiological techniques, biotype analysis, and temporal association (timing of transmission events linked to an appropriate reservoir exposure) using a previously validated protocol (see below).12,13 The sequence of sample acquisition events is detailed in Figure 1.
In addition, the relative efficacy of routine and active environmental cleaning procedures was assessed, the contribution of baseline and case end environmental contamination to stopcock transmission was compared, and the frequency of anesthesia provider hand decontamination was observed. Patients were followed prospectively for 30 postoperative days to assess for HCAI development and/or all-cause mortality. Bacterial pathogens isolated from intraoperative bacterial reservoirs were compared via pulsed-field gel electrophoresis (PFGE) to causative organisms of infection.
Reservoir and Stopcock Sampling
Reservoir and stopcock sampling procedures (see below) were standardized at all 3 study sites with quality assurance monitoring of sampling techniques performed on 2 separate occasions. Appendix A contains details of the sampling procedures in addition to those provided below.
Using a previously validated, modified glove juice technique, provider hands were sampled before, during, and after patient care.13,15
The patient's nasopharynx was sampled to assess the patient reservoir because nasopharyngeal pathogens have been strongly associated with postoperative surgical-site infections.16 The patient's axilla was also sampled because the axilla harbors up to 15%–30% of pathogens colonizing patient skin.17
Sampling of the anesthesia environment has been described previously.12–14,18,19 Two sites on the anesthesia machine, the APL valve and the agent dial, are proven representatives of the anesthesia environment and have been associated with an increase in the probability of bacterial contamination of the IV stopcock set.12 These sites were sampled at baseline (after active decontamination at case start for case 1 and routine decontamination at case start for case 2) and at end of the case via a standardized method described in Appendix A. Active decontamination involved targeted cleaning of the study sites by the study investigators using a quaternary ammonium compound (Dimension III; Butcher's, Sturtevant, WI) strictly according to the manufacturer's protocol, while routine decontamination was performed by the usual operating room personnel according to their standard procedure applied to the environment between operative cases. Routine decontamination also involved use of the same quaternary ammonium compound, but personnel were not asked to specifically target the APL and agent dial.
Sampling of peripheral IV tubing 3-way stopcocks.
The sampling technique for stopcock sampling at case end used in this study has been described previously.12–14 Bacterial cultures obtained from stopcock sets immediately upon removal from the packaging (at case start) were shown to be invariably negative. A positive stopcock set at case end was defined as more than or equal to 1 colony forming unit per culture plate, consistent with prior study protocols.20,21
Identification of Origin of Bacterial Stopcock Transmission Events
Any bacterial isolate from a patient IV stopcock set at case end was compared via standard microbiological techniques, biotype analysis, and temporal resolution to all bacterial isolates from the bacterial reservoirs that were monitored in parallel for that case pair throughout intraoperative patient care. Organisms were considered identical if they were of the same class of organism with an identical biotype and an appropriate temporal association of reservoir exposure and transmission. In this experimental model, transmission of potential pathogens is linked to a specific day, a specific operating room, and a specific surgical case. The timing of a transmission event in relationship to a reservoir exposure can be placed into the sequence as described in Figure 1.
Between-case bacterial transmission was assumed to have occurred if the organism isolated in the internal lumen of the case 2 patient's stopcock set was identical to an organism isolated from 1 or more of the bacterial reservoirs from case 1. Within-case transmission was assumed to have occurred if an organism isolated in a stopcock set was identical to an organism isolated from 1 of the bacterial reservoirs from the same case.
Overall stopcock contamination.
This was defined by contaminated stopcocks with and without an identified reservoir of origin.
Provider origin of contamination was assumed if the stopcock isolate was identical to an isolate from the hands of 1 or more anesthesia providers sampled upon room entry (Fig. 1) before patient care.
Environmental origin of contamination was assumed if the stopcock isolate was identical to an isolate from the environment sampled at baseline or at case end but not isolated either from the hands of providers or from the patient at case start. The hands of all providers who would potentially interact with the anesthesia environment were sampled at baseline (Fig. 1).
Patient origin of contamination was assumed if the stopcock isolate was identical to an isolate from the patient sampled at case start but was not isolated either from the hands of providers at case start (as patient samples were obtained after induction of anesthesia) or from baseline environmental samples (Fig. 1).
Comparison of Residual Baseline Contamination with Case End Contamination: An Assessment of the Efficacy of Environmental Cleaning Practices
For each case pair, residual environmental isolates after active (case 1 start) and routine (case 2 start) decontamination at baseline, and case end environmental isolates after patient care, but before decontamination between cases for case 1 and case 2 were quantified according to colony-forming units (CFUs) per culture plate and identified as described below. The relative contribution of these environmental isolates to stopcock contamination was evaluated and the number of CFUs compared.
Evaluation of Provider Hand Decontamination Frequency
Providers were directly observed regarding HDE throughout each case while within each respective operating room for each case pair. One HDE was defined as any use of a wall-mounted alcohol-based gel dispenser, a machine-mounted alcohol-based foam dispenser, or a 70% ethanol liquid dispenser located on the anesthesia carts. As described previously,14 all observations were recorded by the same research assistant(s) at each institution, and providers were unaware of observational criteria and indications. Providers were aware of the presence of the trained observer. Interobserver variability was minimized by prior training, quality assurance checks, and the simplistic nature of the required observations. We also assessed hourly frequency of glove use and the rate of hand decontamination after glove removal by the provider at each site.
Analysis of Postoperative Infections and Mortality
During the entire 30-day postoperative period, patients and/or patient charts were initially screened daily for the presence or absence of increased white blood cells, fever, anti-infective order, office visit documenting signs of infection, and/or the acquisition of bacterial cultures. The charts of patients positive for 1 or more of these initial criteria then underwent an extensive review by the principal investigator at each institution to determine whether the patient met criteria for the diagnosis of an HCAI according to National Healthcare Safety Network definitions.22 PFGE was used to examine whether pathogens isolated from intraoperative bacterial reservoirs were the original source of 30-day postoperative infections. PFGE studies were performed by Mayo Medical Laboratories using standard methodology.23
Basic patient, procedural, and provider demographic information collected included the hospital site, age, sex, case 1 or case 2, ASA physical status classification, Study on the Efficacy of Nosocomial Infection control (SENIC)24 score (an index predicting the probability of postoperative HCAI development for a given patient), case duration, patient comorbidities (Appendix B), patient origin, patient discharge location, and procedure type. Case duration of more than 2 hours was assessed given the prior association with increased risk of postoperative HCAIs.24
All microbiological processing was done at DHMC with DHMC samples placed under similar environmental conditions (ambient temperature) during the 12-hour period required for shipping of those samples obtained from the University of Iowa and University of Massachusetts on each respective day. The sample incubation period began when all samples for a given study day were present at the DHMC microbiological laboratory. The methods used for bacterial identification, including gram stain, simple rapid tests, the commercially available bioMerieux API identification system (Marcy l'Etoile, France), and PFGE23 are described in Appendix A.
Monitoring of Institutional Intraoperative Infection Control Policies
Intraoperative infection control policies at each institution were tracked and recorded during the study period. There were no changes in standardized environmental cleaning procedures across institutions during the observational period. For routine cleaning between cases, site 1 utilized surface disinfection wipes in addition to the standard quaternary ammonium compound utilized at sites 0 and 2. All providers had access to wall-mounted, 62% alcohol dispensers and to 70% alcohol dispensers located on the anesthesia carts. At site 1, a machine-mounted, foam-based alcohol dispenser was also available. Gloves were immediately available for use throughout patient care episodes at each institution. Use of preoperative chlorhexidine baths and/or nasal mupirocin by patients was infrequent across all 3 sites.
Outcomes and Statistical Analysis
The primary outcomes of this study were the incidence and origin of intraoperative bacterial stopcock transmission events between and within cases. The relative contributions of the patient, environmental, and provider hand bacterial reservoirs to stopcock transmission events were compared using the Fisher exact test. An α level of P < 0.05 was defined as statistically significant.
Secondary outcomes included an assessment of risk factors for stopcock contamination, 30-day postoperative HCAIs, hourly HDE, and mortality. Nonparsimonious multivariable logistic regression with adjustment for potentially confounding variables including site, age, sex, case, ASA physical status, SENIC, case duration, patient comorbidities, origin, discharge location, and the square root of hand-washing events was used for comparisons for stopcock contamination, postoperative HCAIs, and mortality. Predictors for HDE were assessed in a multivariable model including stopcock contamination, site, age, sex, ASA, SENIC, case duration, comorbidities, origin, discharge location, and procedure. HDE was analyzed on the square root scale to achieve normality, and for consistency, this transformation was used as a covariate for models predicting stopcock contamination. Provider identity was not included in the final models because no single provider accounted for >10% of total cases. We assessed and excluded all 1-way interactions (P > 0.05), but did not evaluate all possible 2-way interactions owing to the limitations in sample size. We addressed multiple comparisons by defining P values <0.017 as statistically significant.
Additional microbiological (qualitative) analyses included an assessment of the frequency with which provider hands served as vectors for transmission between intraoperative bacterial reservoirs, an examination of the relative efficacy of current environmental decontamination practices, and an assessment of the relative prevalence of bacterial pathogens within intraoperative bacterial reservoirs and the contribution of those pathogens to 30-day postoperative HCAIs. The frequency of provider HDEs was also observed. Environmental contamination was considered continuous, with baseline and case-end CFUs compared via the Student t test. An α level of P < 0.05 was defined as statistically significant.
This study was powered to detect a rate of between-case stopcock bacterial transmission events of 5% with an alternative rate of 1%. Because prior work has demonstrated that between-case stopcock transmission events occur less frequently than within-case stopcock transmission events,13 we powered the study to assess between-case stopcock transmission to ensure that the sample size would be sufficient to examine both modes of transmission.13 We chose to design the study to detect a 5% rate of between-cases transmission with an alternative rate of 1% because we hypothesized that while between-case transmission may be as high as 5%, even a 1% rate would be clinically relevant. Given these criteria, approximately 400 patients (200 pairs) were needed for the study to be powered at 0.9 with a type 1 error rate of 0.05. We expected to enroll 100 pairs at each institution to account for anticipated missing data of up to 30% (broken plates, lost samples, etc).
A total of 274 operating room case pairs (548 cases) were included in the final analysis with 99 case pairs at site 0, 72 case pairs at site 1, and 103 case pairs at site 2. The overall rate of missing data for the study period was 9%, including 1 incomplete case pair at site 0 (2 cases) and 28 missing case pairs (56 cases) at site 1 (due to early termination with transition to a closed catheter system). The study results reflect a variety of patients, providers, and surgical procedures consistent with the usual practice of surgery with general anesthesia (Table 1).
Overall stopcock contamination was detected in 23% (126 out of 548 total cases) of cases. There were 14 between-case and 30 within-case stopcock transmission events confirmed. All 3 reservoirs were shown by microbiological analysis to contribute to between-case (64% environment, 14% patient, and 21% baseline providers; Table 2) and within-case (47% environment, 23% patient, and 30% baseline providers; Table 3) transmission events. The environment was a more likely source of stopcock contamination than provider hands (relative risk [RR] 1.91, confidence interval [CI] 1.09 to 3.35, P = 0.029) or patients (RR 2.56, CI 1.34 to 4.89, P = 0.002).
Site 0 and the second operative case (case) were significant predictors for overall stopcock contamination (Table 4). HDE either on the transformed or raw scale did not change the results. A reduced risk of stopcock contamination was associated with increased HDE (OR 0.66, CI 0.49 to 0.88, P = 0.005).
Over the 30-day postoperative period, 48 total infections occurred in 44 patients (8%) including 46% (22 of 48) urinary tract infections; 40% (19 of 48) surgical site infections; 8% (4 of 48) respiratory infections; and 6% (3 of 48) deep organ site infections. The overall HCAI, surgical site infection, and mortality rates were 8%, 3%, and 1.6%, respectively, and consistent with what is typically found in the United States.
ASA status, SENIC, and hospital site were independent predictors of increased risk of infection (Table 5). ASA status (odds ratio [OR] 74.1, CI 4.94 to 1112.2, P = 0.002) and positive stopcock sets (OR 58.5, CI 2.32 to 1477, P = 0.014) were independent predictors of increased patient mortality (Table 6).
Microbiological Analyses of Environmental Contamination, Vectors of Transmission, the Frequency of Reservoir Bacterial Pathogens, and the Contribution of Reservoir Pathogens to Postoperative Infections (Pulsed-Field Gel Electrophoresis)
The anesthesia work area, as represented by bacterial isolates obtained from the APL valve, became more contaminated at case end than baseline controls after active decontamination (mean increase of 33 CFUs, CI 7.5 to 58.4, P = 0.015). There was no apparent increase in bacterial contamination of the agent dial throughout patient care. There were 19 case-start environmental contributions to stopcock transmission events (9 after active decontamination, 10 after routine decontamination) and 26 case-end environmental contributions to stopcock transmission events.
Vectors of transmission.
Provider hands were confirmed as vectors for transmission, between the contaminated environment and contaminated stopcock sets, in 27% (12 of 44) of between-case and within-case stopcock transmission events (Tables 2 and 3).
We examined 2170 environmental sites, 2640 health care provider hands, and 1087 patient samples. From these reservoirs, more 6000 potential and 2184 true bacterial pathogens were isolated. Table 7 describes the relative frequency of bacterial pathogens within each bacterial reservoir. In comparison with patients or provider hands during or after care, provider hands before care were more likely to serve as a reservoir for vancomycin-resistant Enterococcus, while hands before, during, and after patient care were more likely to harbor methicillin-sensitive Enterococcus and Gram-negative pathogens. Patients were the more likely reservoir for methicillin-resistant and methicillin-sensitive Staphylococcus aureus (Fig. 2).
Pulsed-field gel electrophoresis.
Postoperative bacterial culture identified the causative organism of infection in 45% (20 of 44) of patients with diagnosed HCAIs in the 30-day postoperative period. In 30% (6 of 20) of these patients, PFGE analysis confirmed that the causative organism was present in at least 1 major intraoperative bacterial reservoir. Overall, 13.6% (6 of 44) of patients were diagnosed with 30-day postoperative HCAIs caused by bacterial organisms present at the time of the operation. Five of these infections were patient-derived and involved 3 cases of Staphylococcus aureus infection (2 wound infections and 1 case of pneumonia), 1 Proteus mirabilis urinary tract infection, and 1 case of Serratia liquefaciens pneumonia. One case of Enterobacter aerogenes pneumonia was linked by PFGE to the hands of a provider before patient care.
Observation of Provider HDEs and Glove Use
Anesthesia providers' hourly HDEs were observed over 1463 hours during the study period. The average number of HDEs for health care providers across all 3 sites was 0.39 ± 1.06. The site-specific average HDEs were as follows: site 0 (0.35 ± 1.01), site 1 (0.104 ± 0.36), and site 2 (0.63 ± 1.34). The site-specific hourly HDE median and range were as follows: site 0 (median 1, range 0 to 18), site 1(median 0, range 0 to 6), and site 2 (median 0, range 0 to 22).
A total of 1586 glove use events were observed during the study period with an average of 2.39 ± 1.60 events per case. In 40% (636 of 1586) of glove use events, provider hands were not washed after glove removal.
We have previously reported the overall frequency and importance of intraoperative bacterial transmission events to patient IV stopcock sets.12 The current study extends these observations by determining the relative contributions of known intraoperative bacterial reservoirs to these transmission events and by providing new insight into the underlying mechanisms of intraoperative bacterial cross-contamination.
We observed an overall stopcock contamination rate of 23%, which is within the previously reported range.12,13 Consistent with prior work,13 the providers' hands in this study served as the source of transmission to less than half of the contaminated stopcock sets. Thus, these results do not suggest that anesthesia providers are the major reservoir for intraoperative bacterial transmission. Instead, we observed that the surrounding patient environment was a more likely source. Given the number of confirmed transmission events linked to environmental contamination, residual environmental contamination could have partially explained the increased risk of stopcock contamination associated with the second case of the day across institutions. Our results clearly demonstrate a need for improvement in both active and routine environmental cleaning strategies currently used in the operative environment.
The patient reservoir also contributed to stopcock contamination less frequently than the environment. However, stopcock transmission events from patients did involve major pathogens, some of which were transmitted from one patient to another during sequential operative cases. On the basis of these findings, further studies of preventive measures involving patient decolonization are warranted. This premise is supported by earlier work demonstrating HCAI reduction after patient decolonization in surgical and dialysis patients25–28 and by work suggesting that patient bacterial flora is easily transferred to provider hands during the process of patient care.29,30
Our findings suggest that stopcock contamination occurs independently of factors associated with the severity of patient illness and/or procedural complexity. Stopcock contamination was associated with the second case of the day and hospital site. In a secondary analysis evaluating predictors for HDE, a reduced risk of stopcock contamination was also associated with increased HDE. These results are consistent with the large contribution of environmental contamination to stopcock transmission events, because the magnitude of environmental contamination is likely influenced by individual and/or institutional variation in aseptic practice, including hand hygiene compliance, environmental cleaning efficacy, and possibly patient decolonization procedures. In turn, these factors are likely influenced by the second case of the day and hospital site. Variation in these factors, including glove use, may in fact explain significant differences in stopcock contamination between hospital sites.
While anesthesia providers are not the major reservoir for intraoperative bacterial transmission to patient IV stopcock sets, multiple findings in this study strengthen the argument for the importance of hand hygiene throughout the patient care episode.8 We have provided direct microbiological evidence confirming that provider hands are vectors of transmission between bacterial reservoirs. As such, improved intraoperative hand hygiene compliance and environmental decontamination efforts may have an additive or synergistic relationship.31 In addition, we found that anesthesia provider hands are a major reservoir for enterococcal and Gram-negative organisms throughout a patient care episode, and we were able to confirm via PFGE analysis that provider hand contamination does contribute to subsequent postoperative infection development.
Consistent with prior reports,12 stopcock contamination was associated with an increase in mortality. This association should be interpreted with caution because it is a secondary outcome involving few events. However, bacterial contamination of intravascular devices has been shown to be associated with increased morbidity in other health care settings.32–37
These study results confirm that the previously reported problems of stopcock contamination, suboptimal hand hygiene, and suboptimal environmental decontamination are not limited to a single institution.12–14 Thus, there is a universal need for improvement in intraoperative infection control. This premise is further supported by the finding in this study that 13.6% (6 of 48) of 30-day postoperative HCAIs were linked by PFGE to intraoperative bacterial exposure.
After the evaluation of >6000 potential pathogen isolates, we found that staphylococcal pathogens largely reside with patients, while enterococcal and Gram-negative pathogens largely reside on provider hands before, during, and after patient care. PFGE results parallel this distribution with most patient-derived infections due to Staphylococcus aureus and the only confirmed provider-derived infection was due to Enterobacter aerogenes, a Gram-negative organism. Taken together, these results suggest that an optimal approach to improvement in intraoperative infection control would involve a multimodal program incorporating improved environmental decontamination and preventive measures targeting both patient decolonization and provider hand hygiene in parallel.
A limitation of this study is the insensitivity of the culture methods used; however, this in fact is likely to underestimate the true magnitude of the bacterial transmission problem.38 In addition, we used a previously validated method, the combination of temporal association and biotype analysis,13 as evidence for bacterial origin for stopcock contamination as opposed to molecular typing methods such as PFGE. Though PFGE has been shown to be more discriminating than biotype analysis alone,39,40 to our knowledge, the benefit of this technique has not been proven superior to the combination of biotype analysis and temporal resolution as used in this study. Finally, the source for the contaminated stopcocks without identification of a reservoir of origin remains unclear; however, patient and environmental reservoirs are more likely sources in comparison with anesthesia providers, because unlike provider hands, the number of sample sites was relatively limited.
In conclusion, the relative importance of patient, health care provider, and environmental reservoirs in bacterial cross-contamination has not been previously examined but is heavily debated.25–28,41–46 Using an intraoperative model of stopcock contamination,12–14 we have shown that several bacterial reservoirs contribute to bacterial cross-contamination and, in fact, are intricately related. We have also shown that these reservoirs harbor unique subsets of major bacterial pathogens that can contribute to postoperative infection development. As such, the results of this study strongly suggest that the impact of a multimodal program targeting each step in the cross-contamination sequence and the primary reservoir for each class of major pathogen on subsequent postoperative HCAI development should be intensely studied to improve intraoperative patient safety.
Name: Randy W. Loftus, MD.
Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.
Attestation: Randy W. Loftus has seen the original study data, reviewed the analysis of the data, approved the final manuscript, and is the author responsible for archiving the study files.
Name: Jeremiah R. Brown, PhD, MS.
Contribution: This author helped analyze the data, write the statistical sections, and revised manuscript.
Attestation: Jeremiah R. Brown has approved the final manuscript.
Name: Matthew D. Koff, MD, MS.
Contribution: This author helped design the study, conduct the study, and write the manuscript.
Attestation: Matthew D. Koff has seen the original study data, reviewed the analysis of the data, approved the final manuscript, and is the author responsible for archiving the study files.
Name: Sundara Reddy, MD.
Contribution: This author helped design the study, conduct the study, and write the manuscript.
Attestation: Sundara Reddy has approved the final manuscript.
Name: Stephen O. Heard, MD.
Contribution: This author helped design the study, conduct the study, and write the manuscript.
Attestation: Stephen O. Heard has approved the final manuscript.
Name: Hetal M. Patel, BS, MLT.
Contribution: This author helped conduct the study.
Attestation: Hetal M. Patel has approved the final manuscript.
Name: Patrick G. Fernandez, MD.
Contribution: This author helped write the manuscript.
Attestation: Patrick G. Fernandez has approved the final manuscript.
Name: Michael L. Beach, MD.
Contribution: This author helped design the study, conduct the study, and analyze the data.
Attestation: Michael L. Beach has approved the final manuscript.
Name: Howard L. Corwin, MD.
Contribution: This author helped write the manuscript.
Attestation: Howard L. Corwin has approved the final manuscript.
Name: Jens T. Jensen, MS.
Contribution: This author helped conduct the study and analyze the data.
Attestation: Jens T. Jensen has approved the final manuscript.
Name: David Kispert, BA.
Contribution: This author helped conduct the study.
Attestation: David Kispert has approved the final manuscript.
Name: Bridget Huysman, BA.
Contribution: This author helped conduct the study.
Attestation: Bridget Huysman has approved the final manuscript.
Name: Thomas M. Dodds, MD.
Contribution: This author helped write the manuscript.
Attestation: Tom M. Dodds has approved the final manuscript.
Name: Kate L. Ruoff, PhD.
Contribution: This author helped design and conduct the study.
Attestation: Kate L. Ruoff has approved the final manuscript.
Name: Mark P. Yeager, MD.
Contribution: This author helped write the manuscript.
Attestation: Mark P. Yeager has approved the final manuscript.
This manuscript was handled by: Sorin J. Brull, MD, FCARCSI (Hon).
Dartmouth–Hitchcock Medical Center Study Coordinator: Tammara A. Wood, M.T. (A.M.T.), Department of Anesthesiology.
Dartmouth–Hitchcock Medical Center Study Consultant: Megan E. Read, M.T. (A.S.C.P.), Department of Pathology.
Dartmouth–Hitchcock Medical Center Research Assistant: Rachel Barr, Department of Anesthesiology.
University of Iowa Study Coordinators: Andy Fahlgren, Medical Student, Department of Anesthesiology; Julie Weeks, Research Assistant, Department of Anesthesiology; Molly Sabers, Medical Student, Department of Anesthesiology; Donald Anciaux, Research Assistant, Department of Anesthesiology.
Michael Todd, University of Iowa, Professor of Anesthesiology.
University of Massachusetts Medical School Study Coordinators: Karen J. Longtine, RN, Department of Anesthesiology; Melissa A. O'Neill, RN, Department of Anesthesiology; Jaclyn K. Longtine, BS, Department of Anesthesiology.
Sampling of the Anesthesia Environment
Sampling of the anesthesia environment has been described previously.12–14 Following decontamination of the adjustable pressure-limiting valve complex and agent dial with Dimension III disinfectant solution according to manufacturer's recommendations, baseline cultures were obtained by utilizing sterile polyester fiber-tipped applicator swabs moistened with sterile transport medium (EsSwab, Copan Diagnostic Inc., Corona, CA) to roll several times over the selected areas followed by culturing on sheep blood agar plates with a zigzag pattern and swab rotation to detect both Gram-positive and Gram-negative bacteria. Environmental cultures were obtained once again following completion of each case in the study unit but prior to disinfection according to current protocol. Environmental isolates obtained from case start were considered to represent a baseline, such that any new pathogen cultured from the environment at the end of surgery was presumed to be acquired in the operating room during the process of patient care. Organisms found in the environment at case end but not on patients or on the hands of providers at case start were presumed to have been transmitted to the measured environmental sites from other environmental reservoirs within the surrounding patient environment. Environmental isolates were quantified as colony-forming units (CFUs) per culture plate.
Sampling of Anesthesia Provider Hands
Using a previously validated glove juice technique, provider hands were sampled before, during, and after patient care for each provider caring for the patient in each operating room. Operating suites were randomized to either dominant or nondominant hand sampling. In addition, provider hands were sampled upon entry to the operating room following every departure. The procedure for hand sampling has been described previously.13,15 Participants submerged their dominant hand for 60 seconds into a sterile polyethylene bag of modified glove juice formula containing 50 mL of sampling solution (pH 7.9, containing 3.0 g/L NaCl, 0.1 g/L CaCl, 0.2 g/L KCl, 0.1 g/L MgCl2, 0.2 g/L KH2orally4, 1.15 g/L K2HPO4). This solution was intended to neutralize residual antiseptic on the skin and facilitate identification and quantification of microorganisms by dispersing the colonies into single cells, which were then counted as CFUs. The sterility of glove juice solution was evaluated and confirmed at regular intervals.
Sampling of the Patient Nasopharynx and Axilla
Immediately following induction of general anesthesia, the nasopharynx and axilla of each patient were cultured.
A sterile nasopharyngeal swab moistened with sterile transport medium was inserted gently into the internal surface of each nasopharynx bilaterally and rotated 360° 10 times to obtain a culture. Each swab was inoculated onto a sheep's blood agar plate using a zigzag pattern and swab rotation.
A sterile nasopharyngeal swab moistened with sterile transport medium was inserted gently into the axilla bilaterally and rotated 360° 10 times to obtain a culture. Each swab was inoculated onto a sheep's blood agar plate using a zigzag pattern and swab rotation.
Sampling of Peripheral IV tubing 3-way stopcocks
The sampling technique for stopcock sampling at case end used in this study has been described previously.12–14 A sterile nasopharyngeal swab (ESwab) moistened with sterile transport medium was inserted into the internal surfaces of each injection port of the 3-way stopcocks and rotated 360° 10 times to culture. Each bacterial swab of the injection port lumen was inoculated on a sheep blood agar plate using a zigzag pattern and swab rotation. Bacterial cultures obtained from stopcock sets immediately upon removal from the packaging (at case start) were shown to be invariably negative. A positive stopcock set was defined as greater than or equal to 1 colony per surface area sampled, consistent with prior study protocols.21,22
Microbial Culture Conditions
All culturing was done in the same laboratory at Dartmouth–Hitchcock Medical Center. Samples shipped from the University of Iowa and University of Massachusetts were placed under similar environmental conditions (ambient temperature) during the 12 hours required for shipping. Samples collected on the same day at Dartmouth–Hitchcock Medical Center did not require shipping but were kept at ambient temperature to mimic the environment of those samples being shipped. No samples for a given study day were incubated until all samples for that day from all research sites were present at Dartmouth–Hitchcock Medical Center.
Bacterial isolates obtained from the anesthesia environment, IV stopcock sets, provider hands before, during, and after patient care, and patients were initially identified by colony morphology, Gram stain, and simple rapid tests. Bacterial organisms were then identified and isotypes specified using the commercially available bioMerieux API identification system (Marcy l'Etoile, France). The API (analytical profile index) system is a standardized protocol for identification of Gram-negative (nonfastidious, nonenteric as well as enteric), Gram-positive (staphylococcus and streptococcus) and coryneform bacteria. Using this system, we identified organisms on the basis of modified conventional and chromogenic tests utilizing pH changes, substrate utilization, and growth in the presence of antimicrobial agents under specified incubation conditions. Interpretation of the samples following incubation resulted in a 7- to 9-digit identification number; this number was then cross-referenced using the API database to obtain the final organism biotype. Pulsed-field gel electrophoresis was used to compare reservoir isolates to causative organisms of 30-day postoperative infections. 23Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) were confirmed by agar dilution minimal inhibitory concentration.
APPENDIX B: LIST OF COMORBIDITIES ASSESSED AS PART OF PATIENT DEMOGRAPHICS
1. Cardiovascular: history of hypertension, coronary artery disease (ASCVD, coronary artery bypass graft, angina), major vascular disease (aortoocclusive disease, abdominal aortic aneurysm [AAA], peripheral vascular disease [PVD], carotid stenosis, carotid endarterectomy, major vascular surgery, or transplant).
2. Neurological: history of cerebral aneurysm, stroke (CVA), and/or brain tumor.
3. Pulmonary: history of chronic obstructive pulmonary disease (COPD), congestive heart failure, severe asthma (on chronic steroid treatment: daily steroids such as prednisone), recurrent pneumonias, cystic fibrosis [CF], pulmonary fibrosis, transplant, cancer (bronchogenic carcinoma–squamous cell, small cell, mesothelioma, etc.).
4. Renal: history of renal failure or insufficiency, transplant, dialysis, and/or renal cell carcinoma.
5. Endocrine: diabetes type I or II, adrenal insufficiency on steroid replacement, and/or history of multiple endocrine neoplasia (MEN).
6. Infectious disease: history of suppressed immune system (on steroids, history of splenectomy, and/or malignancy). Active respiratory, wound, or blood stream infections.
7. Hematological: history of acute or chronic myelogenous leukemia, acute or chronic lymphocytic leukemia, multiple myeloma, polycythemia vera, and/or essential thrombophilia. A history of anemia requiring transfusions.
8. Rheumatological: history of rheumatoid arthritis, sarcoidosis, Sjogren's syndrome, systemic lupus erythematous (SLE), vasculitis (Wegener's granulomatosis, Good Pasteur's syndrome, polyarteritis nodosa, dermatomyositis, and seronegative spondyloarthropathy).
9. Other: history of lung, breast, renal cell, urinary tract, uterine, or extensive skin carcinoma requiring radiation and/or chemotherapy.
10. Gastrointestinal: history of bowel, liver, or gastric malignancy, pancreatitis, ulcerative colitis, Crohn's disease, and other inflammatory bowel disease.
1. National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2004, issued October 2004. Am J Infect Control 2004;32:470–85
2. Klevens RM, Morrison MA, Nadle J, Petit S, Gershman K, Ray S, Harrison LH, Lynfield R, Dumyati G, Townes JM, Craig AS, Zell ER, Fosheim GE, McDougal LK, Carey RB, Fridkin SK. Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA 2007;298:1763–71
3. Department of Health and Human Services and Centers for Medicare & Medicaid Services. Medicare Program; Proposed Changes to the Hospital Inpatient Prospective Payment Systems and Fiscal Year 2008 Rates; Proposed Rule part II. 42 CFR Parts 411, 412, 413, and 489 [CMS-1533-P] RIN 0938-A070. Fed Reg 2008, ; 72:38–48
4. Dellinger E, Gordon S. Surgical-associated infection in today's operating room. In: Special Report, Anesthesiology, General Surgery, and OB/GYN News. New York: McMahon Publishing Group, 2006: 1–10.
5. Kirkland KB, Briggs JP, Trivette SL, Wilkinson WE, Sexton DJ. The impact of surgical-site infections in the 1990s: attributable mortality, excess length of hospitalization, and extra costs. Infect Control Hosp Epidemiol 1999;20:725–30
6. Centers for Disease Control and Prevention. Guideline for prevention of nosocomial pneumonia. Respir Care 1994;39:1191–236
7. Boyce JM, Pittet D. Guideline for hand hygiene in health-care settings. Recommendations of the Healthcare Infection Control Practices Advisory Committee and the HICPAC/SHEA/APIC/ IDSA Hand Hygiene Task Force. Society for Healthcare Epidemiology of America/Association for Professionals in Infection Control/Infectious Diseases Society of America. MMWR Recomm. Rep. 2002;51:1–45
8. WHO guidelines on hand hygiene in health care (advanced draft). World Health Organization health system policies and operations evidence and information for policy,. 2005: 9–13-0007
9. Hota B. Contamination, disinfection, and cross-colonization: are hospital surfaces reservoirs for nosocomial infection? Clin Infect Dis 2004;39:1182–9
10. Dettenkofer M, Wenzler S, Amthor S, Antes G, Motschall E, Daschner FD. Does disinfection of environmental surfaces influence nosocomial infection rates? A systematic review. Am J Infect Control 2004;32:84–9
11. Coates T, Bax R, Coates A. Nasal decolonization of Staphylococcus aureus with mupirocin: strengths, weaknesses and future prospects. J Antimicrob Chemother 2009;64:9–15
12. Loftus RW, Koff MD, Burchman CC, Schwartzman JD, Thorum V, Read ME, Wood TA, Beach ML. Transmission of pathogenic bacterial organisms in the anesthesia work area. Anesthesiology 2008;109:399–407
13. Loftus RW, Muffly MK, Brown JR, Beach ML, Koff MD, Corwin HL, Surgenor SD, Kirkland KB, Yeager MP. Hand contamination of anesthesia providers is an important risk factor for intraoperative bacterial transmission. Anesth Analg 2011;112:98–105
14. Koff MD, Loftus RW, Burchman CC, Schwartzman JD, Read ME, Elliot H, Beach ML. Reduction in intraoperative bacterial contamination of peripheral intravenous tubing through the use of a novel device. Anesthesiology 2009;110:978–85
15. Zuckerman JB, Zuaro DE, Prato BS, Ruoff KL, Sawicki RW, Quinton HB, Saiman L. Bacterial contamination of cystic fibrosis clinics. J Cyst Fibros 2009;8:186–92
16. Kluytmans JA, Mouton JW, VandenBergh MF, Manders MJ, Maat AP, Wagenvoort JH, Michel MF, Verbrugh HA. Reduction of surgical-site infections in cardiothoracic surgery by elimination of nasal carriage of Staphylococcus aureus. Infect Control Hosp Epidemiol 1996;17:780–5
17. Bhalla A, Aron DC, Danskey CJ. Staphylococcus aureus intestinal colonization is associated with increased frequency of S. aureus on skin of hospitalized patients. BMC Infectious Disease 2007;7:105
18. Lemmen SW, Hafner H, Zolldann D, Stanzel S, Lutticken R. Distribution of multi-resistant Gram-negative versus Gram-positive bacteria in the hospital inanimate environment. J Hosp Infect 2004;56:191–7
19. Wikler M, Cockerill F, Bush K, Dudley M, Eliopoulos G, Hardy D, Hecht D, Hindler J, Patel J, Powell M, Turnidge J, Weinstein M, Zimmer B, Ferraro M, Swenson J. Clinical and Laboratory Standards Institute: Performance Standards for Antimicrobial Disk Susceptibility Tests. Approved standard—10th ed. Wayne, PA: Clinical and Laboratory Standards Institute, 2009.
20. Casey AL, Burnell S, Whinn H, Worthington T, Faroqui MH, Elliott TS. A prospective clinical trial to evaluate the microbial barrier of a needleless connector. J Hosp Infect 2007;65:212–8
21. Danzig LE, Short LJ, Collins K, Mahoney M, Sepe S, Bland L, Jarvis WR. Bloodstream infections associated with a needleless intravenous infusion system in patients receiving home infusion therapy. JAMA 1995;273:1862–4
22. Edwards JR, Peterson KD, Mu Y, Banerjee S, Allen-Bridson K, Morrell G, Dudeck MA, Pollock DA, Horan TC. National Healthcare Safety Network (NHSN) report: data summary for 2006 through 2008, issued December 2009. Am J Infect Control 2009;37:783–805
23. Tenover FC, Arbeit RD, Goering RV, Mickelsen PA, Murray BE, Persing DH, Swaminathan B. Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing. J Clin Microbiol 1995;33:2233–9
24. Haley RW, Quade D, Freeman HE, Bennett JV. The SENIC Project. Study on the efficacy of nosocomial infection control (SENIC Project). Summary of study design. Am J Epidemiol 1980;111:472–85
25. Konvalinka A, Errett L, Fong IW. Impact of treating Staphylococcus aureus nasal carriers on wound infections in cardiac surgery. J Hosp Infect 2006;64:162–8
26. von Eiff C, Becker K, Machka K, Stammer H, Peters G. Nasal carriage as a source of Staphylococcus aureus bacteremia. Study group. N Engl J Med 2001;344:11–6
27. Bode LG, Kluytmans JA, Wertheim HF, Bogaers D, Vandenbroucke-Grauls CM, Roosendaal R, Troelstra A, Box AT, Voss A, van der Tweel I, van Belkum A, Verbrugh HA, Vos MC. Preventing surgical-site infections in nasal carriers of Staphylococcus aureus. N Engl J Med; 362:9–17
28. Boelaert JR, Van Landuyt HW, Godard CA, Daneels RF, Schurgers ML, Matthys EG, De Baere YA, Gheyle DW, Gordts BZ, Herwaldt LA. Nasal mupirocin ointment decreases the incidence of Staphylococcus aureus bacteraemias in haemodialysis patients. Nephrol Dial Transplant 1993;8:235–9
29. Hayden MK. Insights into the epidemiology and control of infection with vancomycin-resistant enterococcus. Clin Infect Diseases 2000;31:1058–65
30. Hayden MK. Vancomycin-resistant enterococcus: a threat for the ICU? U.S. perspective. In: Weinstein RA, Bontem MJM eds. Infection Control in the ICU Environment. Boston: Kluwer Academic, 2002: 33–56
31. Wilson AP, Smyth D, Moore G, Singleton J, Jackson R, Gant V, Jeanes A, Shaw S, James E, Cooper B, Kafatos G, Cookson B, Singer M, Bellingan G. The impact of enhanced cleaning within the intensive care unit on contamination of the near-patient environment with hospital pathogens: a randomized crossover study in critical care units in two hospitals. Crit Care Med 2011;39:651–8
32. Graham DR, Keldermans MM, Klemm LW, Semenza NJ, Shafer ML. Infectious complications among patients receiving home intravenous therapy with peripheral, central, or peripherally placed central venous catheters. Am J Med 1991; 91:95S–100S
33. Lorente L, Jimenez A, Iribarren JL, Jimenez JJ, Martin MM, Mora ML. The micro-organism responsible for central venous catheter related bloodstream infection depends on catheter site. Intensive Care Med 2006;32:1449–50
34. Sirvent JM, Vidaur L, Garcia M, Ortiz P, de BJ, Motje M, Bonet A. Colonization of the medial lumen is a risk factor for catheter-related bloodstream infection. Intensive Care Med 2006;32:1404–8
35. Dezfulian C, Lavelle J, Nallamothu BK, Kaufman SR, Saint S. Rates of infection for single-lumen versus multilumen central venous catheters: a meta-analysis. Crit Care Med 2003;31: 2385–90
36. Tega L, Raieta K, Ottaviani D, Russo GL, Blanco G, Carraturo A. Catheter-related bacteremia and multidrug-resistant Acinetobacter lwoffii. Emerg Infect Dis 2007;13:355–6
37. Kaufman JL, Rodriguez JL, McFadden JA, Brolin RE. Clinical experience with the multiple lumen central venous catheter. J Parenter Enteral Nutr 1986;10:487–9
38. Muffly MK, Beach ML, Tong YCI, Yeager MP. Stopcock lumen contamination does not reflect the full burden of bacterial intravenous tubing contamination: analysis using a novel injection port. Am J Infect Control 2010;38:734–9
39. Tenover FC, Arbeit R, Archer G, Biddle J, Byrne S, Goering R, Hancock G, Hébert GA, Hill B, Hollis R. Comparison of traditional and molecular methods of typing isolates of Staphylococcus aureus. J Clin Microbiol 1994;32:407–15
40. Chetoui H, Melin P, Struelens MJ, Delhalle E, Nigo MM, De Ryck R, De Mol P. Comparison of biotyping, ribotyping, and pulsed-field gel electrophoresis for investigation of a common-source outbreak of Burkholderia pickettii bacteremia. J Clin Microbiol 1997;35:1398–403
41. Garner JS, Favero MS. CDC guideline for handwashing and hospital environmental control, 1985. Infect Control 1986;7: 231–43
42. Barker J, Vipond IB, Bloomfield SF. Effects of cleaning and disinfection in reducing the spread of Norovirus contamination via environmental surfaces. J Hosp Infect 2004;58:42–9
43. Boyce JM, Potter-Bynoe G, Chenevert C, King T. Environmental contamination due to methicillin-resistant Staphylococcus aureus: possible infection control implications. Infect Control Hosp Epidemiol 1997;18:622–7
44. Denton M, Wilcox MH, Parnell P, Green D, Keer V, Hawkey PM, Evans I, Murphy P. Role of environmental cleaning in controlling an outbreak of Acinetobacter baumannii on a neurosurgical intensive care unit. J Hosp Infect 2004;56:106–10
45. Griffiths R, Fernandez R, Halcomb E. Reservoirs of MRSA in the acute hospital setting: a systematic review. Contemp Nurse 2002;13:38–49
46. Otter JA, Cummins M, Ahmad F, van Tonder C, Drabu YJ. Assessing the biological efficacy and rate of recontamination following hydrogen peroxide vapour decontamination. J Hosp Infect 2007;67:182–8