A Case of Subacute Necrotizing Fasciitis due to Serratia marcescens

Abstract

Necrotizing fasciitis (NF) is a progressive inflammatory infection of the fascia that is often aggressive and advances insidiously. NF can be preceded by traumatic injury or surgical intervention or may occur spontaneously. Here, we describe a patient who presented with monomicrobial subacute necrotizing fasciitis due to Serratia marcescens. Dermatology was consulted at the local hospital for suspected cellulitis with no resolution using appropriate antibiotics. Our patient failed to show improvement with antibiotic treatment and experienced an above-the-knee amputation. We have also included a review of the current literature on subacute necrotizing fasciitis and S. marcescens. A case review of 25 patients resulted in rates of 52.1% for overall mortality, 72% for mortality among patients treated with only antibiotics, and 40% for mortality among patients treated with surgical debridement. There needs to be a high suspicion for necrotizing fasciitis even in patients presenting with cellulitis without systemic symptoms. If S. marcescens is isolated, more aggressive treatment may be warranted. More cases of subacute necrotizing fasciitis and S. marcescens need to be reported in the literature to better understand early diagnosis and best management practices.

Necrotizing fasciitis (NF) is a progressive inflammatory infection of the fascia that is often aggressive and advances insidiously. NF can be preceded by traumatic injury or surgical intervention may occur spontaneously.1 The infection initially causes necrosis of the fascia and subcutaneous tissue, while sparing the muscle and dermal tissue. The bacteria express toxins and progress along the fascial plane, causing devascularization of muscle and cutaneous tissue.2 Devascularization occurs as a result of thrombosis of the cutaneous perforating vessels, causing rapid tissue necrosis.3 The current recommended guidelines for NF treatment are broad empiric antibiotics, clindamycin for group A Streptococcus infection, and prompt surgical consultation.4

NF most commonly affects the extremities but can involve any part of the body. The staging system proposed by Wang et al5 describes the common presentation of NF. Stage 1 (early) is frequently associated with erythema, swelling, and pain, with palpation beyond the presenting site. Stage 2 (intermediate) is evidenced by the formation of bullae or serous filled blisters. Stage 3 (late) manifests as skin anesthesia, crepitus, hemorrhagic bullae, and dusky discoloration.1,6,7

Necrotizing soft tissue infections are classified on the basis of anatomic location, depth, and microbial cause.8 The depth of infection can reach adipocytes, fascia, and muscle. There are three types of microbial classifications. Type I contains mixed microbes, including aerobic and anaerobic bacteria. Type II is monomicrobial and most commonly involves group A Streptococcus or Staphylococcus aureus. Type III involves Vibrio vulnificus, although this classification is not universally agreed upon.9 Multimicrobial infections are more common than monomicrobial infections. Monomicrobial infections tend to affect younger, healthier individuals with a history of minor trauma.10

Serratia marcescens is a rare cause of NF. S. marcescens is a motile, Gram-negative, facultative anaerobe and a member of the Enterobacteriaceae family, which is maintained in the normal colonic flora.11 In recent years, reports of S. marcescens respiratory-tract infections, urinary-tract infections, septicemia, meningitis, and wound infections have increased.11 The factors predisposing individuals to infections include but are not limited to trauma, alcoholism, peripheral vascular disease, immunosuppression, diabetes mellitus, antibiotic use, steroid use, intravenous lines, lacerations, and abscesses.12 One study reported a 52-percent mortality rate for S. marcescens NF.12

Limited reports have described a rare, subacute presentation of NF that lacks the aggressive clinical features typically seen with NF and instead demonstrates an indolent course followed by sudden, rapid deterioration.13–17 Vascular insufficiency, cellulitis, or other soft-tissue infections can easily mimic this condition due to the lack of apparent severity at onset. The definitive treatment includes surgical intervention via fasciotomy and debridement to prevent limb loss and potentially death. Establishing accepted criteria is critical to support early disease recognition.14

Here, we present a case of subacute NF that was caused by S. marcescens and resulted in partial amputation. We also discuss the current literature and diagnostic parameters.

CASE REPORT

A 73-year-old African-American female patient with a medical history of hypertension and hypercholesterolemia presented to the emergency department with a two-week history of weakness and painful swelling in her bilateral lower extremities. Seven days prior, she had sought care at a local outpatient clinic, where she received furosemide for a suspected chronic heart failure exacerbation. At that time, examination of her legs revealed erythema, tenderness to palpation, and edema, which was worse on the right leg. There was no mention of induration or bullae.

The patient later presented to the emergency department. At that time, her right lower leg and foot displayed erythema, induration, and small, tense bullae of the right lower extremity. After admission, laboratory analysis indicated a white blood cell count of 7.4×109/L, a blood glucose level of 65mg/dL, and a lactic acid level of 3.6mmol/L. She was treated empirically for cellulitis with suspected sepsis. Blood and wound cultures revealed S. marcescens. Her condition continued to deteriorate despite the addition of aztreonam and ceftriaxone. Over the course of six days, tense, painful hemorrhagic bullae with significant edema of the dorsum of the foot developed, extending into the distal phalanges (Figures 1 and 2). Induration of the tissue extended beyond clinically apparent erythema. At no point during her course did she develop an elevated white blood cell count, pyrexia, or elevated glucose levels.

FIGURE 1.

Necrosis of the right foot with surrounding erythema and significant edema

FIGURE 2.

Necrotic ulceration of the right knee and lower leg with edema

The dermatology department was consulted and a diagnosis of NF was made after examination. The surgery department was immediately consulted and the patient underwent an above-the-knee amputation of the right lower extremity. She was later transferred to a transitional care facility and was ultimately able to return home.

DISCUSSION

NF is often misdiagnosed at the time of admission to the hospital, and consequently, can lead to high morbidity and mortality rates.15 The mortality rates reported in studies are approximately 24 to 34 percent and are lower with early diagnosis and treatment.18,19 This patient’s subacute presentation was a slowly worsening leg pain of two weeks’ duration, with no additional symptoms aside from weakness. At presentation to the emergency department, she was tachycardic, without meeting Systemic Inflammatory Response Syndrome criteria. Her laboratory results also did not meet the criteria for sepsis or suggest NF and she was treated with the proper antibiotics. She had a delayed diagnosis and an acute deterioration, which resulted in an above-the-knee amputation.

The true incidence of subacute NF is likely misrepresented in the literature.14 Because of the subtle features and lack of symptomatic severity, the diagnosis of subacute NF can be exceedingly difficult.14,15 Furthermore, the point at which the clinical decline will occur is difficult to predict accurately. According to a review by Wong and Tan16 in 2006, NF features can present as early as six days or greater than one month after the onset of symptoms.16 Failure to consider NF as a diagnosis during this indolent period can be detrimental to patients because early surgical debridement is key to reducing morbidity and mortality rates.14–17 Wong and Tan16 proposed a four-stage grading system, which our patient also followed (Table 1).

TABLE 1.

Stages of subacute necrotizing fasciitis, according to Wong et al16

Stage 1	Initial indolent course without signs of systemic toxicity
Stage 2	Gradual tissue necrosis with possible overlying cutaneous findings
Stage 3	Progression despite proper use of antimicrobials
Stage 4	Sudden deterioration to NF with septic features

Our patient presented with type II monomicrobial S. marcescens NF of the right lower leg. S. marcescens has increasingly been identified as a causative pathogen in NF. A case review by Lakhani et al12 described 15 cases from 1987 to 2015, and 10 new cases have since been added to the literature (Table 2), two of which were multimicrobial.12,19,36 There is currently insufficient statistical power to understand the effects of S. marcescens on NF. The average age of infection is 49.2 (± 21.9 years) and a 52.1 percent rate of mortality has been reported, not counting two patients who were lost to follow-up after leaving the hospital against medical advice. Patients treated with only antibiotics show a 72-percent mortality rate, while those treated with surgical debridement present a 40-percent mortality rate.

TABLE 2.

S. Marcescens NF cases (1966–Present)*

STUDY	YEAR	AGE (YEARS)	SEX	RISK FACTORS	PRECIPITATING FACTOR	INFECTION SITE	TYPE	S. MARCESCENS CULTURE	TREATMENT	OUTCOME
Rimailho et al.20	1987	74	M	Immunocompromised	Diclofenac use	Leg	Ca	Blister and blood	None	Died
Bornstein et al.21	1992	37	F	Renal failure on hemodialysis	Pain during dialysis	Axilla and chest wall	HA	Wound, bullae, blood	Antibiotics and SD	Survived
Zipper et al.22	1996	55	F	DM	Left below-knee amputation	Leg	CA	Wound	Antibiotics	Survived
Huang et al.23	1999	73	M	Nephrotic syndrome	Steroid therapy	Lower leg	HA	Necrotic tissue, blood	Antibiotics and SD	Survived
Huang et al.23	1999	40	M	Uremia, peritoneal dialysis, SLE	Pneumonia with positive cultures for S. marcescens, steroid and nabumetone	Left calf and thigh	CA	Necrotic tissue, blood	Antibiotics and SD	Survived
Liangpunsakul et al.24	2001	66	F	Healthy	None	Leg	CA	Blood	Antibiotics	Died
Newton et al.25	2002	2	F	Healthy	Pharyngitis	Cervical spine	CA	Wound, blood	Antibiotics and SD	Died
Bachmeyer et al.26	2004	49	M	Small-cell lung cancer, DM	Chemotherapy and cellulitis	Right leg	HA	Tissue, bullae, blood	Antibiotics	Survived
Curtis et al.27	2005	51	M	ESRD, T2DM, CHF	Scraped knee on rock in river	Left leg	CA	Wound, blood	Antibiotics and SD	Died
Statham et al.28	2009	6	M	Immunocompetent	Suspected pharyngitis	Oro-pharynx	CA	Wound, blood	Antibiotics and SD	Survived
Motsitsi et al.29	2011	37	M	Healthy	Human bite	Forearm	CA	Wound	SD	Died
Vano-Galvan et al.30	2012	57	F	ML, immunocompromised	Minor trauma	Right thigh	HA	Blister, blood	Antibiotics	Died
Prelog et al.31	2012	15	F	Acute lymphocytic leukemia	Venous access-port implantation	Left axilla, venous HA access port site	HA	Wound	Antibiotics and SD	Survived
Wen32	2012	40	F	Nephrotic syndrome, cyclosporine use	Chemotherapy 10 days prior	Left leg	CA	Wound, blood	Antibiotics	Died
Rehman et al.33	2012	54	F	SLE, ESRD	Central venous catheter, arteriovenous fistula ligation, steroid therapy	Chest wall	HA	Wound, blood	Antibiotics and SD	Died
Cope et al.31	2013	97	F	Heart failure, CKD	Heart failure exacerbation	Right leg	HA	Wound (post-mortem)	Antibiotics	Died
Lakhani et al.12	2015	51	F	DM, PVD	Bifemoral bypass and left distal femoral aneurysm repair	Lower abdomen	HA	Wound, blood	Antibiotics and SD	Survived
Majumdar et al.35	2016	54	F	DM, ESRD	Leg wound due to calciphylaxis, recent skin biopsy	Left leg	HA	Wound	Antibiotics and SD	Died
Haguiya et al.36	2016	64	M	Cirrhosis, hepatocellular carcinoma	Leg wound due to burn	Left leg	CA	Blood, Soft tissue	Antibiotics	Died
Lin et al.37	2016	56	M	DM, betel nut chewing	Tooth extraction	Oropharynx	CA	Blood	Antibiotics and SD	Died
Tuler et al.19	2016	12	F	Healthy	Left leg trauma	Left leg	CA	Wound	Antibiotics and SD	Survived
Heigh et al.38	2016	60	M	DM, CAD, cirrhosis	Laryngectomy	Left foot and leg	HA	Blood, soft tissue	Antibiotics, SD, AKA	Survived
Marin et al.39	2017	55	F	DM, CAD	None	Left foot and leg	CA	Wound, blood	Antibiotics and SD	LAMA
Marin et al.39	2017	50	M	DM	Right foot traumas	Right foot	CA	Soft tissue	Antibiotics and SD	LAMA
Current	2018	73	F	Healthy	None	Right leg	CA	Wound, blood	Antibiotics, SD, AKA	Survived

AKA, above-the-knee amputation; CA, community-acquired infection; CAD, coronary artery disease; CHF, chronic heart failure; CKD, chronic kidney disease; DM, diabetes mellitus; ESRD, end-stage renal disease; HA, health-care-associated infection; LAMA, left against medical advice; SD, surgical debridement; PVD, peripheral vascular disease; SLE, systemic lupus erythematosus; T2DM, type II diabetes mellitus

^*Adapted from Lakhani et al.12

Our case has two interesting features— subacute presentation of NF and S. marcescens as a pathogen—that must be reported more often. When S. marcescens is diagnosed, there appears to be a greater mortality rate than that in other cases of NF. S. marcescens is associated with a 52.1-percent mortality rate as compared with that of 34-percent for general NF cases.18 Factors leading to increased mortality may include an immunocompromised state, delayed treatment, or subacute presentation. This patient presented without systemic or laboratory signs, thus delaying biopsy and debridement. More of these cases must be added to the literature to expand our knowledge of how to diagnose subacute NF to decrease morbidity and mortality rates.