Management of Necrotizing Fasciitis: Single centre experience. Retrospective analytical study

Background: Necrotizing fasciitis (NF) is a rare soft tissue infection, that is rapid and subtle. Inammation and necrosis begin at the fascia, then spread to the subcutaneous fat and the muscles, with subsequent necrosis of the overlying skin. Predominantly affecting patients suffering from immune compromise, diabetes mellitus, or vascular insuciency that prompt early diagnosis and urgent surgery. Methods: A retrospective analytical study conducted at diabetic foot surgery unit, vascular and endovascular surgery department, university hospital, including all patients diagnosed with NF, from January 2019 to December 2019. All patient's records were analyzed to determine preexisting illnesses, admitting symptoms including the length of time to access medical care, physical admission ndings, laboratory results, site of origin of the initial infection, extent and depth of spread, and microbiology of the wound cultures. The procedure of surgical management described as an aggressive debulking of infected tissue. All necrotic skin, subcutaneous tissue, fascia, and nonviable muscle were removed and sent for microbiologic and histologic examination. Viable dermis and soft tissue were saved to aid following the closure, even after undermining to remove all necrotic fascia. Study design: Retrospective analytic study Results: to 9.2 per 100,000 person/year 10–11 In this study, we report higher incidence rate of NF than those reported in other countries 12 ; 1.63 in every 100000 people per year in Dakahlia governorate at diabetic foot surgery unit, over a short period of the study where 107 (12.6%) cases of 850 patients with diabetic foot were recruited.

and signs had higher mortality (n=27, 25.2%) than cases with early presentation (n= 10, 9.4%) twenty-one patients (50 %) had undergone MRI imaging that was required and led to delay in the surgical exploration.

Conclusion:
Necrotizing fasciitis is no longer rare but a severe disease that might cause mortality, very early (within 4 hours) surgical management is recommended, especially in cases with late symptoms and signs. Female gender is a signi cant predictor of mortality. Surgical exposure should be prompt without delay for the results of Magnetic resonant imaging (MRI) once NF is suspected.

Introduction:
Necrotizing fasciitis (NF) is a rare soft tissue infection that is rapid and subtle onset of spreading in ammation and necrosis beginning at the fascia, then spread to the subcutaneous fat and the muscles, with subsequent necrosis of the overlying skin. Hippocrates (500 BC) gave an early description as "diffused erysipelas caused by trivial accidents, where esh, sinews, and bones fell away in large quantities, leading to death in many cases" . 1 The rst description of "modern" NF was made by Joseph Jones, during the American Civil war in 1871. Two thousand six hundred forty-two cases of gas gangrene were reported with a mortality rate of more than 46%. 2 Stevens reported that, among 20 patients who presented with streptococcal shock, were diagnosed as having NF. The media popularized the disease as " esh-eating bacteria syndrome" 3 . Necrotizing soft tissue infections are commonly affecting patients with underlying immune compromise, diabetes mellitus, or vascular insu ciency. Prompt diagnosis and adequate early debridement can reduce mortality and reduce the rate of amputations from necrotizing soft tissue infections. Its rarity and the scarcity of early diagnostic signs make NF a signi cant challenge 4 . Once suspected, rapid implementation of treatment, including surgical debridement and broadspectrum antibiotics with intensive care to break the infective process and avoid systemic organ affection, are the sole pathway for successful treatment [5][6] . However, the insidious nature of the disease and the similarity with other simple conditions might lead to a delay in the diagnosis and subsequent treatment. [6][7] . For this reason, mortality rates have remained almost unchanged throughout the centuries. Unfortunately, the lower prevalence of the disease is the leading cause that physicians rarely become su ciently con dent with NF diagnosis and to be able to proceed with rapid management.

Patients and Methods:
This study is a retrospective analytical study conducted at diabetic foot surgery unit, including all patients diagnosed with NF, over the year 2019. The study was approved by our Institutional Review Board at Mansoura University under number R. 19.09.605.R1, retrospectively registered Data collection: All patient's medical records were reviewed and analyzed to determine preexisting illnesses, admitting symptoms (including the length of time to accessing medical care), physical admission ndings, laboratory results, site of origin of the necrotizing infection, extent and depth of spread, and microbiology of the initial wound cultures. The diagnosis was con rmed by either histologic examination or a combination of clinical, microbiologic, and gross anatomic ndings.
The type and duration of antibiotic therapy, the frequency and type of operative procedures performed and subsequent complications.
Each patient's premorbid medical pro le, condition at admission, and subsequent treatment were also analyzed to assess the effect on mortality and development of complications.
Standard treatment after admission, including cardiovascular stabilization, assessment of the extent of the infection, administered antibiotics were collected and analyzed. The datasets during and/or analysed during the current study available from the corresponding author on reasonable request.
The procedure of surgical management Aggressive debulking of infected tissue. All necrotic skin, subcutaneous tissue, fascia, and nonviable muscle were removed and sent for microbiologic and histologic examination. Viable dermis and soft tissue were saved to aid following the closure, even after undermining to remove all necrotic fascia.

Statistical analysis
The data were analyzed using Statistical Package for the Social Sciences. The numerical outcomes, e.g. age, was calculated as mean. Gender was recorded as frequency and percentage. Chi-Square test was applied to assess the association of various parameters. The results were considered statistically signi cant if the p-value is found to be less than or equal to 0.05. To assess possible risk factors for mortality, univariate analyses was completed initially to aid in determining the variables that should be included in a stepwise logistic regression model.
Mortality was reported in 37 patients (34.6%), the immediate intervention; within 4 hours, resulted to a lower mortality rate 13.1% (n = 14) than the early intervention; within 12 hours 21.5%(n = 23) (p = .001). Moreover, late symptoms and signs showed a higher mortality (25.2% (n = 27 cases) than those with early presentation (9.4% (n = 10 cases) (p = .443). MRI imaging was done in more than 50% (21) patients of the reported mortality and did not improve the outcome but otherwise resulted in a delay in surgical exposure (Table 3).

Discussion:
At the initial stage of the disease, the diagnosis is di cult in most cases, as documented in the literature.
Wilson was the rst to create the term necrotizing fasciitis in 1952 when there was rapid progressive necrosis and in ammation of subcutaneous tissue, super cial fascia and super cial part of the deep fascia with the variable presence of cutaneous gangrene. 9 The annual incidence rate varies in different regions ranging from 0.72 to 9.2 per 100,000 person/year [10][11] In this study, we report higher incidence rate of NF than those reported in other countries 12 ; 1.63 in every 100000 people per year in Dakahlia governorate at diabetic foot surgery unit, over a short period of the study where 107 (12.6%) cases of 850 patients with diabetic foot were recruited.
Although different signi cant risk factors detailed in the literature such as is trauma, illicit drug use or insect bite, liver cirrhosis, alcoholism, diabetes mellitus, immunosuppression, tuberculosis, chronic kidney diseases and malignancy. However, necrotizing fasciitis can develop without any apparent risk factors. 10 Diabetes mellitus (49.5%) was the most common identi able risk factor while, immunosuppression, trauma and postoperative complications, sh sting, drug abuse and malignancy were reported in 11.2%,10.3%, 9.3%, 8.4% and 4.7% respectively. Meanwhile, 7 cases (6.5%) were documented without apparent cause.
Liu TJ et al. observed that age and male gender had a positive correlation with the NF incidence, in our study, age and gender did not reveal any statistical signi cance as a risk factor, but female gender had an elevated mortality rate; 25 cases (68%) than the male. 13 NF may present by classic manifestations such as soft-tissue oedema (in 75% of cases), erythema (72%), severe pain (72%), tenderness (68%), fever (60%), and skin bullae and necrosis (38%) however the following symptoms and signs are highly suggestive for NF; pain out of proportion to clinical signs, hypotension, skin necrosis, and hemorrhagic bullae. [14][15] In the present study; we used Evangelos classi cation 8 were Type II infections (38.3%) had been more prevalent followed by type III (28%) then type I (20.6%) and nally type IV (13.1%). These ndings were similar to data in other studies where Type II was the commonest in contrary to other reports that experienced a similar incidence of type I and II and the other types vary considerably. [16][17][18] Topographically, NF was highest in the extremities (74.8%), followed by the trunk (14%), and lastly the perineum in 12 patients (11.2%). This is consistent with the results in other studies as wag et al. that declared that necrotizing fasciitis in extremities, trunk and perineum occurred in 74%, 13%, and 10% of patients respectively. 19 Patients usually present with the collected symptoms as pain, swelling, and fever. Erythema, tenderness, and fever are the commonest signs of early necrotizing fasciitis. In this study, early manifestations in the form of pain out of proportion, erythema and tenderness was reported in 31.8% (n = 34) wherein 10 cases died (9.4%) while Seventy-three patients (68.2%) presented with late manifestations as blisters, purple or blue skin patches (n = 30, 28%), crepitus (n = 17,15.9%), necrosis (n = 20, 18.7%) and multiorgan failure (n = 6, 5.6%); among them 27 cases died (25.2%). As the mortality was higher in the cases that were manifested with late symptoms and signs, so it is important to recognize necrotizing fasciitis at the early stages in all suspected cases that presented with pain out of proportion of physical examination, even those with minimal cutaneous manifestations. This high index of suspicion of NF must be adopted especially in patients with comorbid conditions such as diabetes mellites or liver diseases as reported at T. Goh et al. 4 Although the results of laboratory investigations are usually nonspeci c, leukocytosis, and increased CRP were the commonest ndings in all cases of NF. Highly elevated leucocytic count and CRP is highly speci c as discovered by Wong et al. 20 wherein we found that mean total leukocyte count was 26.77 ± 7.8 × 10³/ml and CRP ranged 142.8 ± 70.5.
The imaging studies such as x-ray was not speci c as positive data were showed in 41 cases only where the majority of them were late presentation. However, MRI; done in more than 50% (n = 21) patients, had positive data in all cases especially in that presented early but did not improve the outcome and resulted in a delay in the surgical exposure. The ultrasonography requires highly skilled physician that could be used in the intensive care unit (ICU). However, the nger test; a 2-cm incision is made down to the deep fascia, at which level gentle probing of the index nger is applied, had not been used in this study as a bedside test but during the surgical debridement where the mainstay for investigation and treatment is the Surgical exploration. The NF ndings were characteristic "dishwater pus," along with no bleeding or tissue resistance. [21][22][23] The conservative treatment of NF through antibiotics alone has a minor role. However, they may have signi cant value with the surgical management of the infection, and broad-spectrum antibiotics must be started immediately if NF is suspected; based on the microbiological classi cation of NF. Type 1 infection, which is mainly caused by anaerobic bacteria, should be covered with; metronidazole, clindamycin, or carbapenems (imipenem) are effective antimicrobials. Type 2 infection is mainly caused by S. pyogenes and S. aureus. Ans should be covered with Vancomycin or daptomycin and linezolid in cases where S. aureus is not responding to Vancomycin. Type 3 NF, which is caused by Clostridium species, could be treated with clindamycin and penicillin. The early use of tetracyclines (including doxycycline and minocycline) and third-generation cephalosporins is of value for the patient with Vibrio infection is suspected. Type 4 NF should be managed with uoroconazole or amphotericin B. In this study, we depend mainly on the extensive surgical debridement or take the target off. However, we started triple broad-spectrum antibiotics the dosage should be adjusted, based on the results of the initial blood, wound, and tissue cultures, but continued until the infection is under control and for at least 72 h after the patient stabilized clinically and hemodynamically. [24][25][26] The high mortality rate reported in different studies (19- The authors declare that they have no competing interests Authors' contributions M S*, Principle Author, Design of the work, interpretation of data and revised the manuscript, Approved the submitted version, agreed both to be personally accountable for the author's own contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature.
A E*, acquisition, analysis, interpretation of data and drafted the work, revised the manuscript, Approved the submitted version, agreed both to be personally accountable for the author's own contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature.
R S*, acquisition, analysis, interpretation of data and drafted the work, revised the manuscript, Approved the submitted version, agreed both to be personally accountable for the author's own contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature.
KM*, professor of vascular surgery acquisition, analysis, interpretation of data and revised the manuscript, Approved the submitted version, agreed both to be personally accountable for the author's own contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature.
T K*, acquisition, analysis, interpretation of data and revised the manuscript, Approved the submitted version, agreed both to be personally accountable for the author's own contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature.
N E.*, acquisition, analysis, interpretation of data and drafted the work, revised the manuscript, Approved the submitted version, agreed both to be personally accountable for the author's own contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature.

Ethics approval and consent to participate
The study was approved by our Institutional Review Board at Mansoura University under number R. 19.09.605.R1, retrospectively registered. The consent was obtained at the time of surgery, both verbally and written, and all consent forms were revised and accepted by the approving committee mentioned above.

Consent for Publication
All included patient's images were obtained and published after getting the approval of the patient in writing, and also the ethics committee approving the study.

Availability of supporting data
All data involved in the study are available for review if requested, depending on a suitable request to the corresponding author.
Funding: Not applicable.
Competing interests: The authors declare that they have no competing interests. Anatomical site Distributions

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