Characterizing the prognostic utility of isolating yeast in surgical site infections and subsequent use of antifungal therapies :Jesse Chou, Graham McLaren, Abigail W Cheng, Robert G Sawyer, World Journal of Surgical Infection

ORIGINAL ARTICLE
Year : 2022 | Volume : 1 | Issue : 2 | Page : 58--61

Characterizing the prognostic utility of isolating yeast in surgical site infections and subsequent use of antifungal therapies

Jesse Chou¹, Graham McLaren², Abigail W Cheng³, Robert G Sawyer²,
¹ Department of Surgery, Western Michigan University Homer Stryker MD School of Medicine, Kalamazoo, Michigan; Department of Plastic and Maxillofacial Surgery, University of Virginia, Charlottesville, Virginia, USA
² Department of Surgery, Western Michigan University Homer Stryker MD School of Medicine, Kalamazoo, Michigan, USA
³ Department of Surgery, Western Michigan University Homer Stryker MD School of Medicine, Kalamazoo, Michigan; Department of Surgery, Kirk Kerkorian School of Medicine at UNLV, Las Vegas, Nevada, USA

Correspondence Address:
Robert G Sawyer
1000 Oakland Drive Kalamazoo, MI 49008
USA

Abstract

Background: Whether the isolation of yeast from surgical site infections (SSIs) affects outcomes is unclear. We hypothesized that for SSI, yeasts are nonpathogenic and that neither the isolation of yeast nor the use of antifungal agents affects outcomes. Methods: Incisional SSIs from general surgery patients at a single institution between 1997 and 2017 with positive cultures were analyzed, categorized by the presence of yeast. Demographics and in-hospital mortality were compared by Student's t-test and Chi-square analysis. Independent predictors of isolation of yeast and in-hospital mortality were determined by multivariate logistic regression analysis (MV). Results: In total, 977 infections with positive cultures were identified: 190 (19.4%) with yeast and 787 (80.6%) without. By univariate analysis, cultures positive for yeast were associated with a higher severity of illness/APACHE II score (15.6 ± 0.5 versus 11.6 ± 0.2; P < 0.0001), diagnosis in the ICU (83/190, 43.6% versus 154/787, 19.5%; P < 0.0001), age (55.2 ± 1.1 versus 52.4 ± 0.5; P = 0.015), and female sex (105/190, 55.3% versus 362/787, 46.0%; P = 0.027). Independent predictors of isolation of yeast included sex, APACHE II Score, and diagnosis after discharge from index procedure, and for mortality, age, APACHE II, diagnosis after discharge, and receiving antifungal treatment. Isolation of yeast was not associated with mortality (P = 0.12). For fungal SSI, antifungal treatment was not associated with decreased mortality. Conclusion: Isolation of yeast from incisional SSI is not associated with mortality, and the use of antifungal agent is associated with higher mortality. Routine fungal cultures of SSI are not warranted.

How to cite this article:
Chou J, McLaren G, Cheng AW, Sawyer RG. Characterizing the prognostic utility of isolating yeast in surgical site infections and subsequent use of antifungal therapies.World J Surg Infect 2022;1:58-61

How to cite this URL:
Chou J, McLaren G, Cheng AW, Sawyer RG. Characterizing the prognostic utility of isolating yeast in surgical site infections and subsequent use of antifungal therapies. World J Surg Infect [serial online] 2022 [cited 2023 Jun 5 ];1:58-61
Available from: https://www.worldsurginfect.com/text.asp?2022/1/2/58/369705

Full Text

Introduction

Surgical site infections (SSIs) are a common source of morbidity and mortality among surgical patients. Conventionally, bacterial organisms are identified. The most common organisms isolated are Gram-positive cocci in clean cases and Gram-positive, -negative and anaerobic organisms in clean-contaminated cases.[1] Fungal organisms are inconsistently detected.

Each SSI has concrete institutional effects in the form of associated costs whether in the form of increased treatment or increased length of stay for the patient.[2] The effects of SSI from bacteria have been well studied.[1] However, it remains poorly understood whether detection and treatment of coexisting fungal organisms has similar benefit to the patient. Empiric coverage of Candida species has been suggested in the presence of specific risk factors such as immunodeficiency or prolonged antibacterial use.[3]

In this study, we hypothesized that for SSI, yeasts are generally nonpathogenic colonizers and that neither the isolation of yeast nor the use of antifungal agents is associated with outcomes, including mortality.

Methods

Over a 20-year period (1997–2017), all incisional SSIs (superficial and deep) from the inpatient general surgery services at a single quaternary referral center were prospectively identified, and those with positive cultures were included for analysis. SSIs treated without cultures were excluded. Eligible patients were 18 years of age or older with SSIs as defined by the Surgical Wound Infection Task Force, which classifies SSIs as superficial incisional, deep incisional, or organ-space infections.[4] Eligible wounds were diagnosed within 30 days of an operation. Only incisional infections were included (excluding organ-space infections) to focus on infections related to the wound itself. Infections detected and managed solely as an outpatient were excluded due to difficulty in detection and collection of accurate follow-up data. Due to its retrospective nature and use of nonidentifying data, the study was determined to be exempt by the local institutional review board.

Data analysis was designed to test the hypothesis that fungal SSI, defined as an aseptically obtained culture of fluid or tissue from a surgical incision positive for a fungal organism, was not associated with increased mortality. Patients with positive cultures were then stratified based on isolation of a fungal organism; cases with the isolation of both bacteria and fungi were categorized as fungal SSI. All fungi isolated were either Candida species or unspeciated yeast. These cohorts were then analyzed for risk factors associated with cultures positive for yeast. Then, a multivariate (MV) analysis was performed against patients without a fungal isolate to determine if there were any independent predictors of isolation of yeast.

Demographics and in-hospital mortality were compared by Student's t-test and Chi-square analysis with Yates's correction. Independent predictors of isolation of yeast and in-hospital mortality were determined by multivariate logistic regression analysis (MV). IBM® SPSS® version 27 was used for statistical analysis (IBM® SPSS® version 27, Armonk, NY, USA).

Results

In total, 2054 episodes of SSI were identified, of which 977 had positive cultures: 190 (19.4%) with yeast and 787 (80.6%) without yeast. Fungi isolated included Candida albicans in 109, Candida glabrata in 44, non-albicans non-glabrata Candida species in 25, and nonspeciated “Yeast” in 27. Fifteen surgical sites grew more than one Candida species. The most commonly isolated bacteria from SSI without fungi were Staphylococcus aureus (148; 74 were methicillin-resistant), Enterococcus faecalis (105), Escherichia coli (99), Pseudomonas aeruginosa (88), and Enterococcus faecium (61).

By univariate analysis, cultures positive for yeast were associated with a higher age, APACHE II score, acute physiology score, female sex, and a higher white blood cell count [Table 1]. In terms of outcomes, episodes with yeast isolated were more frequently treated with antifungal agents, received a longer course of antimicrobials, had a longer hospital stay, and were more likely to die prior to hospital discharge [Table 1].{Table 1}

MV analysis found that independent predictors of isolation of yeast included female sex, higher APACHE II Score, and diagnosis after discharge from the index operative procedure (Hosmer-Lemeshow test P = 0.80, receiver operating characteristic [ROC] C statistic = 0.70) [Table 2].{Table 2}

In-hospital mortality was higher among patients with yeast isolated from their SSI compared to those without (24/190 = 12.6% versus 60/787 = 7.6%, P = 0.04). Additional MV analysis [Table 3] indicated that independent predictors of mortality for all SSI with positive cultures included higher age, higher APACHE II, diagnosis after discharge from the index procedure, and receiving antifungal treatment (Hosmer-Lemeshow test P = 0.78, ROC C statistic = 0.87). Isolation of yeast was not associated with mortality (P = 0.12).{Table 3}

Finally, the 190 SSI with the isolation of yeast were analyzed separately; the overall mortality was 12.6%. Mortality for patients receiving antifungal agents was 21/142 = 14.8%, and for those not receiving antifungal agents, 3/48 = 6.3% (P = 0.20 for the difference). MV analysis for mortality was also performed, including only patients with isolation of yeast [Table 4]. Independent predictors of mortality included higher age, higher APACHE II score, and chronic immunosuppression, but not the receipt of antifungal therapy (Hosmer-Lemeshow test P = 0.87, ROC C statistic = 0.83).{Table 4}

Discussion

In this retrospective analysis of 977 patients with SSI involving fungal organisms, patients with cultures positive for yeast were more likely to have higher APACHE II scores and severity of illness. Previous studies have described risk factors for Candida infection which include both central and peripheral catheters, bladder catheters, mechanical ventilation, lack of enteral or intravenous nutrition, high severity of illness approximated by APACHE II score, sepsis, hemodialysis, and surgery.[5],[6],[7],[8],[9] Multiple comorbidities among surgical patients have been associated with increased risk of SSI.[10] In our study, multiple risk factors were found to be associated with isolation of yeast, including nonmodificable risk factors such as sex. However, upon MV analysis, the remaining prognostic factors included sex, APACHE II score, and diagnosis after discharge from the index operation. APACHE II scores encompass several of these factors and serve as a proxy for patient severity of illness. This evidence suggests little utility in routine screening for yeast as they are more likely to be present in high-acuity illness.

Patients with mortality attributable to candidemia have been documented to be anywhere from 5% to 71%.[11],[12],[13] However, isolation of Candida from surgical wounds has not been associated with invasive fungal infection.[11] We found no difference in mortality on the basis of isolation of yeast, suggesting that in the absence of disseminated disease, there is little to no utility in isolating yeast. Though, it is worth considering that some authors have found differences in mortality according to species of fungal infection.[14]

Given that fungal cultures are relatively common but only a small proportion of patients will develop disseminated disease, the question remains: Should patients be treated with empiric antifungal agents? Some authors describe a mortality benefit associated with empiric antifungal treatment prior to culture results.[15] Other studies found, as in the case of ours, no significant mortality benefit associated with antifungal treatment.[11] Part of the difficulty with assessing Candida cases lies in the discernment of cases due to infection from those due to mere colonization.

There are several limitations that warrant further discussion. Namely, the retrospective nature of this study introduces a degree of bias that would be lessened were this a prospective review. In addition, data acquisition through chart review rather than direct diagnosis introduces a greater degree of potential misdiagnosis. Furthermore, while the study was adequately powered, the data reflect that of a single institution and would be strengthened by data from additional institutions to escape the trappings of inter-institutional variability in empiric therapy practices and antibiogram.

Conclusion

Isolation of yeast from incisional SSI is not associated with mortality, and the use of antifungal agents is associated with higher mortality. Therefore, fungal cultures from SSI should not be routinely obtained or treated. The authors suggest the careful consideration of these observations when discerning how and whom to treat for SSIs.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1	Hedrick TL, Anastacio MM, Sawyer RG. Prevention of surgical site infections. Expert Rev Anti Infect Ther 2006;4:223-33.
2	Engemann JJ, Carmeli Y, Cosgrove SE, Fowler VG, Bronstein MZ, Trivette SL, et al. Adverse clinical and economic outcomes attributable to methicillin resistance among patients with Staphylococcus aureus surgical site infection. Clin Infect Dis 2003;36:592-8.
3	Blot S, De Waele JJ. Critical issues in the clinical management of complicated intra-abdominal infections. Drugs 2005;65:1611-20.
4	CDC, NHSN. CDC/NHSN Surveillance Definitions for Specific Types of Infections. <<https://www.cdc.gov/nhsn/pdfs/pscmanual/17pscnosinfdef_current.pdf>>: Surveill Defin Published online; 2014.
5	Charles PE, Doise JM, Quenot JP, Aube H, Dalle F, Chavanet P, et al. Candidemia in critically ill patients: Difference of outcome between medical and surgical patients. Intensive Care Med 2003;29:2162-9.
6	León C, Ruiz-Santana S, Saavedra P, Almirante B, Nolla-Salas J, Alvarez-Lerma F, et al. A bedside scoring system (“Candida score”) for early antifungal treatment in nonneutropenic critically ill patients with Candida colonization. Crit Care Med 2006;34:730-7.
7	Pittet D, Monod M, Suter PM, Frenk E, Auckenthaler R. Candida colonization and subsequent infections in critically ill surgical patients. Ann Surg 1994;220:751-8.
8	McKinnon PS, Goff DA, Kern JW, Devlin JW, Barletta JF, Sierawski SJ, et al. Temporal assessment of Candida risk factors in the surgical intensive care unit. Arch Surg 2001;136:1401-8.
9	Lipsett PA. Surgical critical care: Fungal infections in surgical patients. Crit Care Med 2006;34:S215-24.
10	Korol E, Johnston K, Waser N, Sifakis F, Jafri HS, Lo M, et al. A systematic review of risk factors associated with surgical site infections among surgical patients. PLoS One 2013;8:e83743.
11	Marchena-Gomez J, Saez-Guzman T, Hemmersbach-Miller M, Conde-Martel A, Morales-Leon V, Bordes-Benitez A, et al. Candida isolation in patients hospitalized on a surgical ward: Significance and mortality-related factors. World J Surg 2009;33:1822-9.
12	Wey SB, Mori M, Pfaller MA, Woolson RF, Wenzel RP. Risk factors for hospital-acquired candidemia. A matched case-control study. Arch Intern Med 1989;149:2349-53.
13	Falagas ME, Apostolou KE, Pappas VD. Attributable mortality of candidemia: A systematic review of matched cohort and case-control studies. Eur J Clin Microbiol Infect Dis 2006;25:419-25.
14	Dimopoulos G, Ntziora F, Rachiotis G, Armaganidis A, Falagas ME. Candida albicans versus non-albicans intensive care unit-acquired bloodstream infections: Differences in risk factors and outcome. Anesth Analg 2008;106:523-9.
15	Parkins MD, Sabuda DM, Elsayed S, Laupland KB. Adequacy of empirical antifungal therapy and effect on outcome among patients with invasive Candida species infections. J Antimicrob Chemother 2007;60:613-8.