Severe Skin Infections Due to Serratia marcescens: A Case Associated With Cat Scratch in a Patient With Liver Disease and Review of the Literature : Infectious Diseases in Clinical Practice

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Severe Skin Infections Due to Serratia marcescens

A Case Associated With Cat Scratch in a Patient With Liver Disease and Review of the Literature

Gadhiya, Kinjal Prakash MD; Goldman, John MD; Panupong, Hansrivijit MD; Balchander, Divya BS; Cook, Ellen BA, MS; Enriquez, Kathryn BA; Smith, Debi BS

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Infectious Diseases in Clinical Practice 29(3):p e146-e150, May 2021. | DOI: 10.1097/IPC.0000000000000987
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Abstract

Serratia marcescens is a gram-negative bacilli belonging to the Enterobacteriaceae family associated with high mortality septic shock. This pathogen is known to affect individuals of immunocompromised statuses, such as diabetics and advanced cirrhosis patients, as well as immunocompetent populations. Well-documented infections caused by S. marcescens include pneumonia, urinary tract infection, bacteremia, biliary tract infection, wound infection, meningitis, and endocarditis. Rarely does it present as cellulitis and necrotizing fasciitis (NF), resulting in severe sepsis and multiorgan failure. Here, we report a rare case of cellulitis, bacteremia, septic shock, and multi-organ failure caused by S. marcescens in the setting of diabetes mellitus, chronic kidney disease, and nonalcoholic steatohepatitis cirrhosis induced end-stage liver disease.

CASE

A 71-year-old White woman with multiple comorbidities, including end-stage liver disease with portal hypertension due to nonalcoholic steatohepatitis cirrhosis managed with weekly paracentesis, history of upper gastrointestinal bleed from esophageal varices, diabetes mellitus type 2, moderate aortic stenosis, and chronic kidney disease stage 4, presented to the emergency room with left calf pain, and a 1-day history of fever. A review of systems revealed worsening exertional dyspnea, poor appetite, and fatigue for the past month.

On presentation, physical examination revealed a fever of 102.7°F, tachycardia with a heart rate of 114 beats/min, tachypnea with a respiratory rate of 24 to 29 breaths/minute, and oxygen saturation of 91% on 2 L of oxygen via nasal cannula. She was ill-appearing and in respiratory distress with accessory muscle use. The respiratory examination was significant for rales in the bilateral lower lung fields. The abdominal examination revealed distension with generalized dullness to percussion; a reducible ventral hernia below the umbilicus had been present for many years. She had significant erythema and tenderness on the anterior aspects of the bilateral lower extremities, with severe tenderness of the left leg compared with the right leg. The temperature of the skin was normal bilaterally. Bilateral pedal pulses were intact. The skin examination showed linear scratch marks on the medial aspect of both legs that were attributed to scratches from the patient's cat.

Laboratory studies revealed a leukocytosis of 96,000/μL and elevated creatinine of 2.01 mg/dL, from her baseline value of 1.8 mg/dL. Chest x-ray showed retrocardiac opacification, representing likely pneumonia. Ultrasound of the abdomen showed severe ascites, and computed tomography of the abdomen was negative for an intraperitoneal abscess. Venous Doppler of the bilateral lower extremities was negative for deep vein thrombosis. The patient was admitted for sepsis secondary to pneumonia and initially started on intravenous cefepime and vancomycin. After 24 hours, the patient developed hypotension requiring norepinephrine and hypoxia requiring 15 L of oxygen via non-rebreather. The patient was subsequently transferred to the intensive care unit. Paracentesis drained 1600 mL of yellow transudative ascitic fluid and a total of 7 L over the next 24 hours. After paracentesis, the patient was weaned down to 3 L oxygen via nasal cannula. Respiratory sputum cultures were negative. Blood cultures grew gram-negative rods in 4/4 bottles. The patient had a history of shell food consumption and reported being scratched on her leg by her pet cat. Therefore, she was started on doxycycline to cover Vibrio vulnificus and azithromycin and doxycycline to cover Bartonella henselae and Pasteurella species. Cefepime was continued to cover pseudomonas species. Vancomycin was then discontinued, given a negative MRSA screen.

She continued to be hypotensive, requiring 3 pressors and stress dose steroids. Urine output continued to decline and she developed worsening hyperkalemia, renal failure, and lactic acidosis and was placed on continuous renal replacement therapy. Chest x-ray showed worsening pulmonary congestion and bilateral pleural effusions. Subsequently, she developed respiratory distress and required intubation and ventilation support. Echocardiogram showed severe aortic stenosis. Her left leg computed tomography scan showed severe cellulitis; subsequently, she started to develop bullae on her left leg (Fig. 1). Blood cultures grew Serratia marcescens, which was sensitive to ceftriaxone, cefepime, and piperacillin-tazobactam and resistant to cefazolin and carbapenems. Azithromycin and doxycycline were then discontinued, and cefepime was switched to ceftriaxone. Subsequent blood cultures were negative.

F1
FIGURE 1:
On day 4 development of new bullae and ruptured bullae which broke into the ulcer with erythematous base and widespread subcutaneous hemorrhages (shown from different angles).

Her left leg cellulitis worsened with the progressive development of bullae which ruptured into ulcers and new bullae ascending toward the thigh along with subcutaneous hemorrhages (Fig. 1). She also began developing subcutaneous hematomas on her right forearm. Eventually, ulcers became a clean base and continued to have subcutaneous hemorrhages (Fig. 2). Despite continued continuous renal replacement therapy, antibiotics, and pressor support, her lactic acidosis and vasopressor requirements worsened. Given the patient's poor prognosis, the family decided to withdraw care, and the patient passed away after terminal extubation.

F2
FIGURE 2:
Clear base ulcers on day 6 along with worsening subcutaneous hemorrhages.

DISCUSSION

Risk Factors

Serratia Marcescens is rarely presented as a soft tissue infection. We report a first and rare case of bullous cellulitis due to S. marcescens associated with a cat scratch in a patient with multiple comorbidities, including end-stage liver disease and stage 4 chronic kidney disease. Prior literature review of cellulitis and NF due to S. marcescens identified 16 cases from 1966 to 2015.1 To provide a review of recent cases of cellulitis and NF due to S. marcescens, we performed a systematic search of PubMed from 2015 to 2020 using the keywords Serratia marcescens and cellulitis, necrotizing fasciitis, and soft tissue infection (Table 1). Similar to earlier literature reviews, many patients in our review who developed S. marcescens cellulitis and NF were immunocompromised, most commonly with diabetes, heart failure, hypertension, lupus, malignancy, chronic venous insufficiency, chronic renal or end-stage renal disease, and advanced liver disease.1–4 Other forms of being immunocompromised in patients with S. marcescens cellulitis or NF included a history of splenectomy, chronic steroid use, and neutropenia from chemotherapy.1,5–7 In addition to an immunocompromised state, factors that are thought to predispose patients to the skin and soft tissue infections from S. marcescens include external trauma and compromised skin integrity such as chronic venous stasis.4,5 This patient had chronic kidney disease, diabetes mellitus, and end-stage liver disease, all of which have been associated with high mortality in patients with cellulitis secondary to S. marcescens.1

TABLE 1 - Published Cases of Serratia marcescens as a Cause of Soft Tissue Infections
Case No. References Age/Sex Underlying Condition Cause (Cat Bite/Dog Bite) Clinical Presentation Serratia Culture Location Antibiotics Used Outcome (Survived/Death)
1 Majumdar and Crum-cianflone1 54/F ESRD, DM, HTN Calciphylaxis associated with ESRD NF Wound Vancomycin, piperacillin-tazobactam, levofloxacin, clindamycin Died (After readmission, 51 days after initial presentation)
2 Hau et al2 68/F DM, chronic renal insufficiency, chronic venous insufficiency, left leg lymphoedema No history of trauma, ulcer, injection, or animal bite Necrotizing cellulitis Wound Amoxicillin, amoxicillin-clavulanate; switched to cefepime, amikacin Survived
3 Hagiya et al3 64/M Advanced liver cirrhosis Welding burn Necrotizing cellulitis Wound, blood Penicillin G, meropenem, clindamycin Died (25 h after admission to ICU)
4 Marin et al4 55/ F DM, CAD, HTN Diabetic foot infection Necrotizing cellulitis Wound, blood piperacillin/tazobactam, clindamycin, Ceftriaxone, fluconazole, levofloxacin Unknown, left AMA
50/M DM, peripheral vascular disease Blunt trauma Necrotic eschar with cellulitis Wound Vancomycin, piperacillin-tazobactam, Unknown, left AMA
67/M Respiratory failure 2/2 cardiac arrest, DM, HTN, ESRD, arterial occlusive disease Foot Ulcer Necrotic eschar progressing to osteomyelitis wound Cefepime Survived
5 Fournier et al5 69/M Peripheral vascular disease, Coronary artery disease, splenectomy Unknown; worked as landscaper, tinea pedis was a possible source of entry Cellulitis Wound Vancomycin, piperacillin/tazobactam, linezolid, doxycycline. ciprofloxacin, meropenem Survived
6 Biscoe and Hakeem6 80/F DM, chronic renal failure, breast cancer, heart failure, HTN Unknown Necrotizing cellulitis Blood Piperacillin-tazobactam later changed to meropenem, clindamycin Died due to heart failure and pulmonary edema
7 Pithadia et al7 55/F Primary CNS lymphoma on consolidation chemotherapy Dog scratch Cellulitis Wound Vancomycin, piperacillin/tazobactam, cefepime, voriconazole Survived
ESRD indicates end stage renal disease; DM, diabetes mellitus; HTN, hypertension; CAD, coronary artery disease; AMA, against medical advice.

Microbiology

Serratia marcescens is a gram-negative motile facultative anaerobic bacteria belonging to Enterobacteriaceae family and known to cause hospital as well as community-acquired infections, including bacteremia, pneumonia, endocarditis, meningitis, and septic arthritis, but is a rare cause of cellulitis or NF especially in the setting of the immunocompromised state. Community-acquired infections have also been described, as the bacteria is found in fresh, stagnant water, soil, and animals. Around half (47%) of Serratia bacteremia is due to community-acquired infection.6 Colonization may occur during previous hospitalizations or procedures, as seen with our patient, who had undergone weekly paracentesis for end-stage liver disease and recent catheterization for moderate aortic stenosis.3,8

Pathogenesis

It is known to produce prodigiosin, a red pigment.1 Pathogenesis is attributed to various virulence factors including the production of serralysin (a protease enzyme), hemolysin Sh1A (a pore-forming exotoxin), and production of biofilm. A mice model has shown that cell-mediated immunity in the spleen helps clear Serratia marcescens and so splenectomized patients are at high risk of developing severe soft tissue infection.5

Clinical Presentation and Diagnosis

Serratia soft tissue infection is usually very rare and immunocompromised status is the main and usual risk factor. It is usually associated with severe septic shock and high mortality in immunocompromised patients especially renal disease, chemotherapy, immunosuppressants, steroid, and liver disease.1 In immunocompromised individuals, the onset is typically very rapid with the development of pain, erythema, and edema occurring within 24 hours of direct tissue injury and can present as painful nodules, isolated plaques, ulcer, cellulitis, abscess, granulomatous ulcer, pyoderma gangrenosum, and NF. High-risk patients can rapidly develop severe bacteremia and septic shock due to resistant Serratia spp. Necrotizing fasciitis is associated with high mortality (60%).2

Bullous cellulitis is usually caused by gram-positive (staph and strep spp.) and gram-negative (Enterobacter cloacae, E. coli, and Salmonella enteritidis).5 It can also be associated with rare and unusual pathogens including Vibrio vulnificus which has high susceptibility in patients with cirrhosis. Testing of bullous fluid can help isolate the pathogen.

To our knowledge, this is the first documented case of S. marcescens cellulitis which is associated with cat scratch. Animal bites from iguana, insects, and snakes and 1 case from leeches have previously been associated with the development of S. marcescens cellulitis.7 A previous case report also documented bullous cellulitis similar to the current patient after a dog scratch in a patient that had neutropenia secondary to chemotherapy.7

Treatment

Cat bite and dog bite are associated with Pasteurella spp, Bartonella spp, Capnocytophaga spp, and anaerobes. For these infections, amoxicalvulinic acid is the drug of choice for oral therapy and β-lactamase inhibitors (ampicillin-sulbactam/piperacillin-tazobactam) is the preferred intravenous regimen. The most common pathogen associated with cat scratch disease is Bartonella spp., and the preferred antibiotic regimen depends on clinical presentation, for example, high-dose azithromycin for lymphadenitis and azithromycin plus rifampin for disseminated liver and spleen infection or fever of unknown origin.

Serratia marcescens has intrinsic resistance to penicillin, macrolide, and first-generation cephalosporin, linezolid, and rifampin same as other groups of Enterobacteriaceae.5,6 Resistance can be either chromosomal mediated or plasmid-mediated producing either AmpC-β-lactamase, extended-spectrum β-lactamase, or carbapenemase, which provide resistance to penicillins, cephalosporins, and carbapenems.

In our review, cultures positive for Serratia marcescens were generally susceptible to third- and fourth-generation cephalosporins, piperacillin/tazobactam, fluoroquinolones, aminoglycosides, and carbapenems.1–3,5,7 This patient's organism was sensitive to ceftriaxone, cefepime, and piperacillin/tazobactam but resistant to cefazolin and carbapenems. Later, it showed carbapenemase positive activity but no β-lactamase activity. Despite appropriate initial coverage for S. marcescens, this patient ultimately succumbed to infection despite the effectiveness of ceftriaxone. This is most likely secondary to the patient's advanced comorbid conditions.5,9,10

Over the past few decades, antimicrobial therapy for S. marcescens has vacillated due to the development of varying resistance among different strains. Because of high mortality and emergent resistance, empiric treatment with piperacillin-Tazobactam, third-generation cephalosporins, carbapenems, and aminoglycosides is recommended; however, culture sensitivity should guide the final therapy.1,5,10

Serratia often induces AmpC β-lactamase activity, which is often undetected in standard sensitivity tests. Therefore, fourth-generation cephalosporin, quinolones, or carbapenem are preferred therapy even in the presence of apparent sensitivity. In our case, the patient was treated with ceftriaxone and repeat blood cultures were negative. In S. marcescens isolates with the high likelihood or evidence of cephalosporin resistance, that is, induced AmpC enzyme activity and/or extended spectrum beta lactamase production, carbapenems have become the choice.

CONCLUSIONS

Here, we describe a first and rare case of bullous cellulitis from S. marcescens associated with a cat scratch in an immunocompromised patient. Given the high morbidity and mortality of cellulitis and NF from S. marcescens, clinicians should maintain a high index of suspicion in immunocompromised patients especially liver cirrhosis, renal failure, diabetes, and chemotherapy patients presenting with a history of cat scratch and soft tissue infection. Recent invasive procedures and hospitalization predispose patients to the colonization of this nosocomial pathogen, and so history provides a very important clue for possible Serratia marcescens infection. Empiric treatment with third-generation cephalosporins, carbapenems, and extended-spectrum penicillins and aminoglycosides is recommended, along with susceptibility testing to determine antibiotic resistance. Necrotizing fasciitis and abscess should have surgical debridement on the earliest bases. Our case highlights the emerging importance of S. marcescens as a cause of cellulitis, leading to significant morbidity and mortality in immunocompromised patients.

REFERENCES

1. Majumdar R, Crum-cianflone NF. Necrotizing fasciitis due to Serratia marcescens: case report and review of the literature. Infection. 2016;44(3):371–377.
2. Hau E, Bouaziz JD, Lafaurie M, et al. Necrotizing cellulitis with multiple abscesses on the leg caused by Serratia marcescens. Cutis. 2016;97(3):E8–E12.
3. Hagiya H, Ojima M, Yoshida T, et al. Necrotizing soft tissue infection caused by Serratia marcescens: a case report and literature review. J Infect Chemother. 2016;22(5):335–338.
4. Marin L, Rowan R, Mantilla A, et al. Lower-extremity infections caused by Serratia marcescens a report of three cases and a literature review. J Am Podiatr Med Assoc. 2017;107(3):231–239.
5. Fournier JB, Dabiri G, Thomas V, et al. Serratia marcescens bullous cellulitis in a splenectomized patient: a case report and review of the literature. Int J Low Extrem Wounds. 2016;15(2):161–168.
6. Biscoe AL, Hakeem L. Severe soft tissue infection in a patient with type 2 diabetes mellitus caused by Serratia marcescens as a single pathogen. Br J Diabetes. 2016;16:202–205.
7. Pithadia DJ, Weathers EN, Colombo RE, et al. Severe and progressive cellulitis caused by Serratia marcescens following a dog scratch. J Investig Med High Impact Case Rep. 2019;7:2324709619832330.
8. Villarino ME, Jarvis WR, O'Hara C, et al. Epidemic of Serratia marcescens bacteremia in a cardiac intensive care unit. J Clin Microbiol. 1989;27(11):2433–2436.
9. Harris PN, Ferguson JK. Antibiotic therapy for inducible AmpC β-lactamase-producing gram-negative bacilli: what are the alternatives to carbapenems, quinolones and aminoglycosides?Int J Antimicrob Agents. 2012;40(4):297–305.
10. Simsek M. Determination of the antibiotic resistance rates of Serratia marcescens isolates obtained from various clinical specimens. Niger J Clin Pract. 2019;22(1):125–130.
Keywords:

Serratia marcescens; bullous cellulitis; cat scratch

Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.