Abstract
Background:
A notable improvement in the treatment of necrotizing soft tissue infections (NSTIs) is the development of negative pressure wound therapy (NPWT). Clinicians are still debating whether NPWT is as successful as conventional wet-to-dry dressings at removing bacteria. Recent research has revealed potential oxygen deprivation effects of NPWT in underlying wound tissues, although clinical trials regarding the effects of reduced oxygen on anaerobic bacterial soft tissue infections remain noticeably lacking.
Hypothesis:
We hypothesized that NPWT-treated patients with NSTIs who were solely infected by anaerobic bacteria would have worse outcomes than those who were infected with other bacterial species
Patients and Methods:
Our study included a retrospective examination of the 2008–2022 period of our Acute and Critical Care Surgery database. Patients who had been identified as having necrotizing fasciitis, Fournier gangrene, or gas gangrene and who had their conditions verified by positive wound cultures acquired during the initial debridement and subsequently received NPWT made up the study cohort. Comorbidities, surgical techniques, and clinical results were all covered by the data. Based on their wound infections, patients were divided into two groups: those with exclusively anaerobic NSTIs and those with different bacterial groups (such as polymicrobial and aerobic). Multiple regression, χ2 analysis, and analysis of variance (ANOVA) were among the analytical methods used.
Results:
One hundred twelve patients with NSTI who had received NPWT comprised the study cohort. Sixteen of these patients (14.3%) had NSTIs that were exclusively anaerobic, whereas the remaining 96 (85.7%) had NSTIs that were mixed aerobic, facultative, or polymicrobial. Between the two groups, there was no difference in the initial wound size. Patients with anaerobic NSTI who underwent NPWT showed a statistically significant increase in the number of debridements (3 [interquartile range {IQR},1–9] vs. 2 [IQR, 1–4]; p = 0.012) and an increased 100-day re-admission rate (37.5% vs. 12.5%; p = 0.012) when compared with patients with non-anaerobic NSTI. The 100-day re-admission rate increased three-fold in NPWT-treated anaerobic NSTIs, according to a logistic regression analysis (odds ratio [OR], 3.63; 95% confidence interval [CI], 1.06–12.44; p = 0.04).
Conclusions:
In contrast to patients with other bacterial strains, our data show that patients with NSTI treated with NPWT who only have anaerobic bacterial infections have a larger number of debridements and are much more likely to require re-admission within 100 days. We call for additional prospective studies to be conducted to identify additional risk factors and consider alternate treatment options for individuals with exclusively anaerobic NSTIs in light of these findings.
The most prevalent skin and soft tissue infections (SSTIs) can develop life-threatening consequences called necrotizing soft tissue infections (NSTIs), which have a high risk of morbidity and mortality. 1 Because of increased awareness of the illness and better care over the past few decades with evidence-based medicine, the mortality rate has gradually decreased, but the 20% to 80% worldwide mortality range is still very important. 2 Necrotizing soft tissue infections are broadly categorized into two forms, monomicrobial and polymicrobial, which include anaerobic and aerobic bacteria. The current management of NSTIs includes a tailored antibiotic approach based on the micro-organisms identified in cultures. However, all other therapies applied are not selective for micro-organisms. 3 After surgery, 100% pure oxygen is used in hyperbaric oxygen therapy (HBO) at a pressure of 2 to 4 absolute atmospheres, which improves wound healing by increasing tissue and blood oxygenation. Even though there is not enough proof to support its benefits, HBO can still be used if it is available. 4
Negative pressure wound therapy (NPWT), also referred to as vacuum-assisted closure (VAC), is an extraordinary achievement established in 1995 for the management of acute and chronic wounds. Negative pressure wound therapy accelerates the healing process by reducing edema by generating a pressure difference between wound and therapy, alternating blood flow, and diminishing inflammatory response. It also alters bacterial burden and changes wound biochemistry.5–7 The increased benefit of NPWT over traditional wound care has not yet been demonstrated clinically.8,9
Negative pressure wound therapy has several advantages over traditional wound care. It requires less frequent dressing changes and is easier to tailor and maintain in position, including circumferential extremity wounds. However, in terms of disadvantages, NPWT requires carrying a portable pump.10,11 Negative pressure wound therapy is contraindicated in wounds with exposed vital structures because of the risk of erosion and results in fistula or hemorrhage 12 and to malignant tissues because of promoting the growth of malignant tissue in presence of subatmospheric pressure and risk of bleeding. 13 The subatmospheric pressure provided by the NPWT also causes oxygen deprivation effects in underlying wound tissues. 14
We hypothesized that among patients with NSTI who received NPWT treatment, those infected exclusively with anaerobic bacteria will have worse clinical outcomes than those infected with other types of bacteria (such as polymicrobial or aerobic bacteria).
Patients and Methods
After obtaining Institutional Review Board approval, our prospectively maintained Acute and Critical Care Surgery database spanning from 2008 to 2022 was queried for patients with NSTI with a diagnosis of necrotizing fasciitis, Fournier gangrene, or gas gangrene using both International Classification of Diseases (ICD)-9 and ICD-10 codes. We included patients with a positive culture taken during initial debridement. Based on usual protocol, which involves starting wound vacuum installation after infection clearance and when further debridement is not indicated, all of the patients in our study received NPWT. Patients who did not have a positive culture and not reported the initial size of wounds were excluded. Demographic data, comorbidities, microbiologic data, region of wounds, initial size of wounds after first debridement, and hospital outcomes were extracted. The post-operative day of initital wound closure was defined as the amount of time needed for wound closure after the initial debridement. Operative data including wound measurements, closure type, and use of NPWT were manually extracted from operative reports.
Operative information, including wound measures, closure technique, NPWT use, how frequently dressings were changed or NPWT was applied, and the number of debridement procedures, were manually extracted as unique variables from operative reports. Mortality and re-admission for additional wound care within 100 days were considered complications. We did not include re-admissions that had nothing to do with concerns about wounds in our analysis.
We stratified patients based on wounds infected with anaerobic versus other group of bacteria (i.e., polymicrobial, aerobic, etc.). Data were analyzed using SPSS Statistics (IBM, Armonk, NY). Univariable analysis was performed using analysis of variance (ANOVA) and Pearson χ 2 . Categorical results are reported as percentages and absolute values and continuous variables as mean and standard deviations. A p value of less than 0.05 was considered statistically significant. Multivariable logistic regression models were used to estimate the effect of the use of NPWT on the re-admission rate within 100 days.
Results
Demographic data
Sixteen of the 112 eligible patients had an anaerobic NSTI, comprising 14.3% of the population under study. Conversely, 96 individuals (85.7%) who met the inclusion criteria had a mix of either aerobic or polymicrobial NSTIs. The average age of those with anaerobic NSTI was 59.56 (±15.74) years, which was older than the average age of those in the other group, which was 50.45 (±14.42) years.
No statistically significant differences were found between the two groups in terms of demographic factors such ethnicity, gender, and comorbidities. Patients with anaerobic NSTI were mostly female (62.5%) and Caucasian (62.5%). The prevalence of diabetes mellitus, smoking, intravenous drug use, and peripheral vascular disease did not differ between the two groups.
Particularly in the anaerobic group, in which a higher prevalence was noted in the lower extremities, the distribution of NSTI locales showed variation. On the other hand, the group that had been exposed to other bacteria displayed a disproportionately greater frequency of NSTIs in the groin, perineum, and buttock areas. However, the fact that these variations lacked statistical significance must be emphasized (Table 1).
Demographics and Past Medical History
NSTI = necrotizing soft tissue infection; SD = standard deviation; PMH = past medical history; DM = diabetes mellitus; ETOH = alcohol consumption; IVDU = intravenous drug use; PVD = peripheral vascular disease; qSOFA = Quick Sepsis-Related Organ Failure Assessment.
Aerobic or polymicrobial.
Microbiology data
Bacteroides fragilis was identified as the leading pathogen among anaerobic NSTIs, accounting for 43.8% of cases, followed by Actinomyces at 18.8%. The cohort that also included additional NSTIs had a varied microbial composition, with Staphylococcus aureus comprising 18.5% and group F Streptococcus comprising 13.6% of the most common pathogens in this group (Table 2)
Most Common Pathogens
NSTI = necrotizing soft tissue infection; MRSA = methicillin-resistant Staphylococcus aureus.
Aerobic or polymicrobial.
Clinical course and outcomes
Because of variations in each patient's rate of wound healing, different patient groups received wound vacuums at different times. Whereas some patients had the wound vacuum administered after additional debridements and infection elimination, others had NPWT performed concurrently with the first debridement. Based on the particular clinical circumstances of each case, the surgical team decided when to install the wound vacuum. Compared with another group on NSTI, fewer patients on anerobic NSTI received wound vacuum at initial debridement (12.5% vs. 30.2%; Table 3).
Clinical Outcomes
NSTI = necrotizing soft tissue infection; SD = standard deviation; LOS = length of stay; ICU = intensive care unit; NPWT = negative pressure wound therapy; POD = post-operative day.
Aerobic or polymicrobial;
Secondary to wound complications and infections.
The initial wound size (491.6 cm2 vs. 522.8 cm2), the post-operative day of initital wound closure (8 vs. 8), the hospital stay (17.4 days vs. 17.7 days), and the intensive care unit (ICU) stay (4.6 days vs. 4.8 days) revealed a noticeable consistency between the two groups (Table 3). Nevertheless, despite the fact that wound care procedures remained the same, more patients with anaerobic NSTI than the other group (50% vs. 40.6%) were discharged with open wounds. Along with this, the anaerobic NSTI cohort saw a higher number of debridements (3 [IQR, 1–9] vs. 2 [IQR, 1–4]) and a higher 100-day re-admission rate for further wound care (37.5% vs. 12.5%). Subanalysis shows the incidence of debridement that occurred after NPWT was found to be higher among patients with anaerobic NSTI (81.3% vs. 77.1%) than among the other group of NSTI. Furthermore, compared with the other NSTI group, anaerobic NSTI cases had more debridements (2 vs. 1) after the insertion of wound vacuums (Table 3).
After controlling for age, the size of the initial wound, and the history of diabetes mellitus using logistic regression analysis, it was observed that patients with anaerobic NSTI had a three-fold higher 100-day re-admission rate compared with other bacterial groups (OR, 3.63; 95% CI, 1.06–12.44; p = 0.04; Table 4).
Logistic Regression: Outcome as a Re-Admission within 100 Days
OR = odds ratio; CI = confidence interval;
Aerobic or polymicrobial.
Discussion
Necrotizing soft tissue infections are a class of bacterial diseases that are very uncommon but extremely dangerous. They are infamous for having high death and morbidity rates and for being difficult to diagnose and treat on multiple levels. In this challenging environment, rapid surgical debridement, prudent antibiotic medication, and extensive supportive care continue to be the fundamental management pillars. The variation in patient survival rates, however, nonetheless highlights the complex interplay between illness features and treatment-related variables despite these well-established guiding principles. 1
Negative pressure wound therapy, also known as VAC, has emerged as a promising treatment for accelerating wound healing, even in the presence of infections, among the variety of interventions. As shown in recent studies,15,16 this strategy does not completely reduce the persistence of the bacterial burden after NPWT treatment. Notably, a thorough investigation carried out by Glass et al. 17 revealed intriguing evidence of NPWT's species selectivity, placing a discernible restraint on the spread of the infamous Pseudomonas aeruginosa. 18
The impact of NPWT resonates in a variety of tones within the intricate fabric of NSTIs. In cases of Fournier gangrene, there is an interesting dichotomy: patients undergoing NPWT with disseminated presentations show considerable differences in wound closure rates, whereas their counterparts with localized forms do not show comparable advantages. 19 Prior study emphasizes the prudent use of NPWT in the area of medical decision-making, particularly on wounds with expanding surfaces and in patients suffering from many concurrent medical diseases. It can be challenging to weigh possible therapeutic benefits against financial costs, particularly when trying cross-country or hospital-to-hospital cost comparisons. 20
A fascinating dynamic emerges, showing that patients who receive VAC experience lengthier hospital stays and undergo an increased number of debridement treatments, illustrative of the complex interplay between therapeutic efficacy and potential side effects. 21 The domain of NPWT's comparative efficacy against anaerobic pathogens and other pathogen groups is still relatively unexplored, as is the effects of NPWT on biofilms, virulence factors, and movement inside wound settings.
Our retrospective investigation into the nuances of anaerobic NSTI therapy has revealed a puzzling correlation between NPWT and clinical outcomes that begs for additional investigation. Notably, compared with their NSTI counterparts, the use of NPWT was associated with less favorable clinical trajectories and a higher frequency of sequelae within this subset of anaerobic NSTIs. Our data show a high rate of 100-day re-admissions in patients with anaerobic NSTI, which frequently calls for repeated debridement treatments. The important thing to note is that we remain cautious despite the small sample size and statistical insignificance in death rates, attributing this to the study's intrinsic constraints.
A more thorough investigation is required to shed light on the potential link between NPWT and increased mortality in the context of anaerobic NSTIs. Our study adds an important feature because there are currently few studies in the clinical literature that compare the outcomes of NPWT specifically for anaerobic NSTIs to those of other NSTI categories. Scholarly investigation is encouraged into the uncharted realm of NPWT-induced subatmospheric pressure, which can unintentionally generate an oxygen-deprived niche within underlying wound tissues, potentially promoting the colonization of anaerobic bacteria.
Necrotizing soft tissue infections present a challenging dilemma within the range of infectious diseases, requiring a careful approach. Although our study sheds a nuanced light on NPWT's interaction with anaerobic NSTIs, it nevertheless shines as a beacon of promise on the road of wound healing. The complexity of this phenomenon calls for ongoing investigation, emphasizing the necessity for extensive research that might shed more light on the advantages and disadvantages of NPWT in such complex situations. The pursuit of solid research projects serves as a vital compass guiding evidence-based procedures, ultimately guiding us toward improving patient outcomes as we traverse this complex maze of NSTI therapy.
Limitations of the study
The study acknowledges its limited sample size, particularly in the anaerobic NSTI cohort, which might affect the robustness of the findings. A larger sample size would provide more statistical power and confidence in the observed associations.
The study focused on the outcomes of NPWT-treated patients with anaerobic NSTI but did not compare this treatment modality against standard therapy. The lack of a comparative arm limits the ability to draw direct comparisons or infer superiority of NPWT over other treatment approaches. The investigation did not delve into the potential impact or role of instillation therapy in the management of anaerobic NSTIs. This represents an area in which further research could offer insights into its efficacy compared with NPWT or standard therapies.
As a recognition of the difficulties in applying NPWT, we included patients with complicated perineal infections in our study. We included cases in which wound vacuums were used in these places despite possible issues with wound sealing, as shown in Table 1, even though retrospective data made it difficult to definitively confirm perineal wound sealing with NPWT. These limitations highlight areas in which future research efforts could contribute to a more comprehensive understanding of the management strategies and outcomes in patients with anaerobic NSTIs.
Conclusions
Despite the potential advantages of NPWT, our research reveals a concerning tendency in the case of NSTIs caused only by anaerobic bacteria: noticeably worse clinical outcomes. Our results show a marked increase in the 100-day re-admission rate and the requirement for re-debridement among patients exclusively affected by anaerobic bacteria when treated with NPWT.
With regard to the subset of patients who only have anaerobic infections and receive NPWT treatment, our study highlights an astounding three-fold increase in the rate of 100-day re-admissions and re-debridement required. When compared with patients dealing with other bacterial strains, such as polymicrobial or aerobic bacteria, this stark contrast becomes clear.
We suggest that there is an urgent need for additional investigation through prospective studies in light of these important revelations. Such studies would help to clarify the complexities underlying this concerning trend by exploring potential risk factors and alternative treatment options for those who are faced with the difficult diagnosis of anaerobic-only NSTIs. The intricate interplay of factors impacting outcomes and therapy responses, as well as the complexity of these infections themselves, need for a comprehensive knowledge that goes beyond their immediate clinical presentation. As we set out on this quest, we have the expectation that better understanding may open the door for more successful interventions, enhancing patient care, and ultimately improving their prognosis.
Footnotes
Authors' Contributions
Data curation: Afzal, Dawson, Fonseca, Canas, Diaz, De Filippis. Formal analysis: Afzal. Investigation: Afzal, Dawson, Fonseca, Canas, Diaz, De Filippis. Writing—original draft: Afzal. Writing—review and editing: Afzal, G.V. Bochicchio. Visualization: Afzal, G.V. Bochicchio. Project administration: K. Bochicchio. Supervision: K. Bochicchio, G.V. Bochicchio. Validation: G.V. Bochicchio. Conceptualization: G.V. Bochicchio.
Funding Information
The authors have no funding to report.
Author Disclosure Statement
The authors have no conflict of interest to report.