Necrotising fasciitis with extensive necrosis caused by Lactobacillus: A case report

doi:10.21203/rs.3.rs-3816589/v1

Download PDF

Case Report

Necrotising fasciitis with extensive necrosis caused by Lactobacillus: A case report

https://doi.org/10.21203/rs.3.rs-3816589/v1

This work is licensed under a CC BY 4.0 License

Journal Publication

published 22 Apr, 2024

Read the published version in BMC Infectious Diseases →

You are reading this latest preprint version

Background

Necrotising fasciitis (NF) is a life-threatening soft-tissue infection that rapidly destroys the epidermis, subcutaneous tissue, and fascia. Despite their low virulence, Lactobacillus spp. can cause NF, and because of its rare incidence, there is limited knowledge about its molecular and clinicopathological characteristics. We report a rare case of NF in a patient with undiagnosed diabetes mellitus and severe obesity due to infection with two types of Lactobacillus spp. that manifested in extensive necrosis.

Case presentation

A 48-year-old woman was referred to our hospital with a complaint of difficulty in walking due to severe bilateral thigh pain. She presented with pale redness, swelling, and severe skin pain extending from the pubic region to the groin. The patient was morbidly obese, had renal dysfunction and had not been diagnosed having diabetes mellitus; her LRINEC (Laboratory Risk Indicator for Necrotising Fasciitis) score was 9, indicating a high risk of NF. An exploratory surgical incision was made and NF was diagnosed based on fascial necrosis. Emergent surgical debridement was performed, and cultures of the wound and abscess revealed two types of Lactobacillus spp.: Lactobacillus salivariusand L. iners. The patient was admitted to the intensive care unit (ICU), where antibiotics were administered and respiratory and circulatory managements were performed. Diabetic ketoacidosis was detected, which was treated by controlling the blood glucose level stringently via intravenous insulin infusion. The patient underwent a second debridement on day 11 and, skin suture and skin grafting on day 36. The patient progressed well, was transferred from the ICU to the general ward on day 41, and was discharged unassisted on day 73.

Conclusions

Lactobacillus spp. are rarely pathogenic to healthy individuals and can seldom trigger NF. However, these bacteria can cause rare infections such as NF in immunocompromised individuals, such as those with diabetes and obesity, and an early diagnosis of NF is imperative; surgical intervention may be required for prevention of extensive necrosis. The LRNEC score may be useful for the early diagnosis of NF even for less pathogenic bacteria such as the Lactobacillus.

Debridement

Laboratory Risk Indicator for Necrotising Fasciitis score

Lactobacillus spp.

Necrotising fasciitis

Necrotising fasciitis (NF) is a life-threatening soft-tissue infection that rapidly destroys the epidermis, subcutaneous tissues, and fascia [1]. Its incidence is rare, with approximately 4 per 100,000 people per year, with the condition being most frequently diagnosed in individuals between 50 and 60 years of age, with a higher prevalence in men [2]. Risk factors include diabetes, immunosuppression, malnutrition, advanced age, non-steroidal anti-inflammatory drugs (NSAID) use, morbid obesity, liver cirrhosis, alcoholism, chronic renal failure, HIV/AIDS, and underlying malignancy [3]. Notably, patients with diabetes and obese individuals account for 22–59% and 17–31% of all cases, respectively. Its clinical presentation includes rapidly progressive inflammation of the skin and soft tissues, with mortality rates ranging from 30–40%. Delayed surgical intervention may worsen the prognosis, underscoring the need for prompt diagnosis and therapeutic intervention. NF is categorised according to the causative organisms into mainly two types: type I, a complex infection involving aerobic and anaerobic organisms (polymicrobial), and type II, caused by a single Gram-positive organism (monomicrobial), such as Group A Streptococcus or methicillin-resistant Staphylococcus aureus (MRSA) [1, 2]. The most common causative organisms are Streptococcus pyogenes and Staphylococcus epidermidis, followed by Gram-negative rods such as Klebsiella spp. [4]. Although less common, type III infections caused by Vibrio vulnificus have also been reported [1]. Lactobacillus spp. has rarely been documented to cause NF [5] and is not known to trigger extensive necrosis because of low virulence of the organism. In this report, we describe a case of NF in a patient, with undiagnosed diabetes mellitus and severe obesity, caused by infection with two types of Lactobacillus spp. that manifested in extensive necrosis.

A 48-year-old woman with a history of manic depression and no history of previous NSAID or probiotic use, had been treated for bilateral cutaneous candidiasis of the thighs for 3 weeks. She visited her family physician because she had experienced severe bilateral pain in her thighs upon waking up in the morning and was unable to walk. Blood tests showed high levels of inflammation(C-reactive protein 45.94 mg/dL), and she was referred to our hospital for a detailed examination. Pale redness and swelling of the skin, extending from the pubic area to the groin, were observed, and she had persistent severe pain in that region. Her height was 158 cm, weight 101 kg, body mass index (BMI) 40.5 kg/m², Glasgow Coma Scale (GCS): E3V5M6, temperature 37.3°C, pulse 114 beats/min, blood pressure 91/58 mmHg, respiratory rate 21 breaths/min, and oxygen saturation 95% at room air. The patient was severely obese and had impaired consciousness and hypotension. Blood laboratory test values including those for Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC) were: white blood cell count 12,600/µL (76.5% neutrophils), haemoglobin 14.3 g/dL, platelet count 120,000/µL, Na⁺ 127 mEq/L, creatinine kinase 33 IU/L, lactate 3.0 mmol/L, glucose 741 mg/dL, blood urea nitrogen (BUN) 50 mg/dL, creatinine 1.9 mg/dL, creatinine clearance 57.74 mL/min, C-reactive protein 45.71 mg/dL, HbA1c 15.6%, and urine ketone 2 + positive. Diabetes mellitus was not diagnosed. Arterial blood gas analysis showed HCO₃⁻ of 9.8 mEq/L, and an anion gap of 27.6 mEq/L, indicating anion gap-opening metabolic ketoacidosis. Computed tomography showed increased adipose tissue deposition from the right abdomen to the anterior of the right thigh, with no gas-producing findings (Fig. 1). Initially, cellulitis was suspected; however, since the patient complained of severe pain and was at high risk of NF with a LRINEC score of 9, an exploratory surgical incision was made, and NF was diagnosed based on the findings of necrotic tissue in the fascia. Emergency debridement surgery was performed on the same day. Intraoperative findings revealed extensive necrotic tissue extending from the right side of the abdomen to the anterior thigh (Fig. 2). The necrosis in the right groin extended to the right femoral vein. The follicle in the medial part of the right femur was the most inflamed and considered the point of bacterial entry and the necrosis was more extensive than the skin findings. The patient was admitted to the intensive care unit (ICU). Adequate circulatory status was maintained with extracellular fluid administration, norepinephrine, and vasopressin. The patient required sedation and analgesia during daily wound care. Consequently, ventilatory management was initiated. Tight glycaemic control was maintained with administration of intravenous insulin because of diabetic ketoacidosis. Meropenem and vancomycin were empirically administered until the causative bacteria were identified. Lactobacillus salivarius and L. iners were isolated from multiple wound and abscess cultures. Since the smear staining was negative for streptococcal infection, clindamycin was not used [6]. Report of bacterial susceptibility to antibiotics was obtained on day 6; however, no drug resistance was observed. Penicillin and ampicillin sodium are first-line antibacterial agents for Lactobacillus infections However, antibiotics with a broader spectrum of coverage were chosen because the patient had an unstable circulatory status and was receiving high doses of catecholamines. A second debridement was performed on day 11. Candida infection of the wound was treated with a 9-day micafungin therapy. Pseudomembranous enteritis developed on day 18 and fidaxomicin was administered for 10 days. The patient was weaned off the ventilator on day 19. Drainage with negative-pressure wound therapy was continued from day 21 to 36. The patient’s condition improved and antibiotics were discontinued on day 25. Wound closure and skin grafting were performed on day 36. The patient was discharged from the ICU on day 41. The skin graft was successful and the patient was discharged without assistance on day 73 (Fig. 3).

We encountered a case of NF caused by Lactobacillus spp. The genus Lactobacillus comprises anaerobic facultative Gram-positive rods. To date, more than 250 species of this genus have been identified. Common species include L. rhamnosus and L. casein, which form the normal flora of the oral cavity, gastrointestinal tract, and urogenital tract as commensal bacteria [7]. L. salivarius and L. iners, detected in the present case, are indigenous bacteria in the gastrointestinal tract and vagina, respectively. Lactobacillus are lactic acid producing bacteria used frequently in commercial applications, particularly in the fermentation of cheese and other dairy products [8]. The species has probiotic functions including suppression of microbial virulence in the intestinal tract [9]. Under normal physiological conditions, they are less pathogenic and not harmful to healthy individuals. However, there have been reports of the association between the use of probiotics and bacteraemia [10], and the risk of Lactobacillus bacteraemia has been reported in patients using immunosuppressive drugs, and having diabetes and advanced cancer [11].

Severe infections caused by Lactobacillus spp. such as L. casei, L. rhamnosus and L. salivarius have been reported, including endocarditis and meningitis [7]. Although less virulent, the mortality rate may be as high as 30% if the Lactobacillus spp. are pathogenic [7]. L. rhamnosus and L. casei have potential virulence factors that produce proteins that can bind to extracellular proteins, such as fibrinogen. The ability to bind fibrinogen has also been reported to help Gram-positive pathogens escape the immune system [12]. L. salivarius cultured in the present case has also been reported to bind to human fibrinogen via a fibrinogen-binding protein and aggregate human platelets; some strains have been found to aggregate human platelets at levels comparable to those of S. aureus [13]. These mechanisms may explain the pathogenesis of Lactobacillus infections. We found two cases of severe soft-tissue infections caused by Lactobacillus spp.in literature; a brief report of a case of NF caused by L. acidophilus [5] and another case of Fournier's gangrene caused by L. acidophilus described in a review [11]. (Table 1). Notably, all three cases, including the present case, were complicated by diabetes mellitus. Immunity is an important factor in the aetiology of Lactobacillus bacteraemia, and 21% of patients with Lactobacillus bacteraemia are reported to have diabetes [11], indicating that immunosuppression due to diabetes is an important factor in NF caused by Lactobacillus.

Table 1

*Lactobacillus*-associated soft-tissue infections
Publication Year	Age (years)	Sex	Clinical symptoms	Diabetes	LB-associated infection	Species	Debridement	Other microorganisms	LRINEC Score	Outcome	Reference
2011	58	M	Sepsis	+	Fournier gangrene	L. acidophilus	N/A	Candida. glabrata	N/A	Cured	11
2018	59	F	DKA	+	Necrotising Fasciitis	L. acidophilus	+	Candida	N/A	Cured	5
2022	48	F	DKA	+	Necrotising Fasciitis	L. salivarius L. iners	+	Candida. albicans	9	Cured	This Case
LRINEC: Laboratory Risk Indicator for Necrotising Fasciitis; DKA: diabetic ketoacidosis; M: Male; F: Female

This table shows a list of soft-tissue infections associated with Lactobacillus spp. All patients were complicated by diabetes mellitus.

The present case is the only one in which a mixed infection with Lactobacillus spp. was found.

It has been reported that Lactobacillus are more frequently detected in the stool of patients with type 2 diabetes than in healthy individuals [14]. In addition, Lactobacillus including L. iners are endemic to the vagina of women [15]. In this case, the Lactobacillus may have entered the patient’s body via faeces and vaginal secretions through the folliculitis she had previously suffered, causing a mixed infection with L. iners and L. salivarius, resulting in NF. Although NF is generally more common in men [16], Lactobacillus spp. are part of vaginal microflora in women and maybe the causative organism of NF in women, especially those with diabetes.

NF caused by Lactobacillus has rarely been reported and its molecular and clinicopathological features are still unclear. In the two cases we found in the literature, the extent of necrosis was not described. The extent of NF is often difficult to determine from skin findings alone, especially in obese patients, because the infection progresses along the fascia [16]. The LRINEC score was useful for early diagnosis in this case. The LRINEC score is a clinical tool reported by Wong et al. [17] as a predictive diagnostic score for NF. The following six blood parameters are included in the score: C-reactive protein (CRP), total white blood cell count, haemoglobin, serum sodium, creatinine, and glucose. A score of ≥ 8 is considered as high risk factor for NF [17, 18]. Johnson et al. [19] reported that the sensitivity, specificity, positive predictive value, and negative predictive value of the LRINEC score in patients with diabetes were 100, 69, 16.6, and 100%, respectively. In the present case, the LRINEC score was 9, indicating the patient to be in a high-risk group and allowing for early diagnosis (Table 2). Thus, the LRINEC score may be useful for the diagnosis of NF caused by low-virulence bacteria such as Lactobacillus.

Table 2

*LRINEC score in the present case*
Parameter	Range	Score	This Case
Hb (g/dL)	> 13.5	0	0
	11–13.5	1
	< 11	2
White cell (10³/µL)	< 15	0	0
	15–25	1
	< 25	2
Sodium (mEq/L)	< 135	2	2
Creatinine (mg/dL)	> 1.58	2	2
Glucose (mg/dL)	> 180	1	1
C-reactive protein (mg/dL)	> 15	4	4

Score ≤ 5: <50% risk (low), Score 6–7 intermediate risk, Score ≥ 8: >75% risk (high)

Our patient scored 4 points for C-reactive protein, 2 points for sodium, 2 points for creatinine, and 1 point for glucose, for a total of 9 points on the LRINEC score. Thus, the patient was classified into the high-risk group.

The curative treatment for NF is early surgical intervention, and the prognosis is poor if surgery is delayed [20]. Although the timing of surgery was not described in the two cases we retrieved, extensive necrosis due to Lactobacillus suggests that a delay in surgical intervention may be fatal. The present case suggests that early surgical intervention can be life-saving even in NF caused by bacteria with low virulence.

The prognosis of NF caused by Lactobacillus spp. is poorly understood. Regarding the mortality of NF caused by different types of bacteria, there was no difference between Streptococci and Staphylococci, on the other hand, there was a significant difference between Vibrio and Aeromonas in mortality [21]. In this case, the bacteria were detected by wound culture and the causative agent could be diagnosed, but it was difficult to do so based on the course of the disease and skin findings alone. It should be noted that patients with compromised immune function can develop NF caused by Lactobacillus spp. However, due to the paucity of case reports, we cannot deduce definitive pathogenesis, specific features, or mortality of NF caused by Lactobacillus spp. The LRINEC score and early surgery may be helpful, but the limitations of the present case need to be evaluated with further case accumulation in the future.

In conclusion, morbidly obese, diabetic, and immunocompromised patients are at a risk of developing NF caused by less pathogenic bacterial species including Lactobacillus. In morbidly obese patients who are at risk, skin findings alone can delay the diagnosis of NF, but screening with the LRINEC score can be useful, and early surgical debridement life-saving. The clinical features and prognosis of NF caused by Lactobacillus spp. remain unknown, and further case reports are warranted.

BMI, body mass index; BUN, blood urea nitrogen; CRP, C-reactive protein; GCS, Glasgow Coma Scale; ICU, intensive care unit; LRINEC, Laboratory Risk Indicator for Necrotising Fasciitis; NF, necrotising fasciitis; MRSA, methicillin-resistant Staphylococcus aureus; NSAID, non-steroidal anti-inflammatory drugs; NF, necrotising fasciitis.

Ethics approval

As a case report, our study did not require a referral from our institutional clinical ethics committee.

Consent to participate and for publication

Written informed consent was obtained from the patient for the publication of this case report and any accompanying data and images.

Availability of data and materials

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Funding

None.

Acknowledgements

Not applicable.

Authors' contributions

JN collected data and wrote the original draft. TS wrote, reviewed, and edited the manuscript. IT, KK, and MN reviewed the manuscript. All the authors have read and approved the final version of the manuscript.

Stevens DL, Bryant AE. Necrotizing soft-tissue infections. N Engl J Med. 2017;377(23):2253-65. doi: 10.1056/NEJMra1600673.
Peetermans M, de Prost N, Eckmann C, Norrby-Teglund A, Skrede S, De Waele JJ. Necrotizing skin and soft-tissue infections in the intensive care unit. Clin Microbiol Infect. 2020;26(1):8-17. doi: 10.1016/j.cmi.2019.06.031.
Salati SA. Necrotizing fasciitis a review. Pol Przegl Chir. 2022 Feb 23;95(2):1-8. doi: 10.5604/01.3001.0015.7676.
Anaya DA, Dellinger EP. Necrotizing soft-tissue infection: diagnosis and management. Clin Infect Dis. 2007;44(5):705-10. doi: 10.1086/511638.
Hubbard J, Jariwala B, Hill A, Gega A, Palesty JA. A new Bacterium, Lactobacillus acidophilus, causing necrotizing fasciitis. Am Surg. 2018;84(2):e61-3. PMID 30454480.
Zimbelman J, Palmer A, Todd J. Improved outcome of clindamycin compared with beta-lactam antibiotic treatment for invasive Streptococcus pyogenes infection. Pediatr Infect Dis J. 1999;18(12):1096-100. doi: 10.1097/00006454-199912000-00014.
Cannon JP, Lee TA, Bolanos JT, Danziger LH. Pathogenic relevance of Lactobacillus: a retrospective review of over 200 cases. Eur J Clin Microbiol Infect Dis. 2005;24(1):31-40. doi: 10.1007/s10096-004-1253-y.
Aguirre M, Collins MD. Lactic acid bacteria and human clinical infection. J Appl Bacteriol. 1993;75(2):95-107. doi: 10.1111/j.1365-2672.1993.tb02753.x.
María Remes Troche J, Coss Adame E, Ángel Valdovinos Díaz M, Gómez Escudero O, Eugenia Icaza Chávez M, Antonio Chávez-Barrera J et al. J, Rafael Aceves Tavares G, Antonio Lira Pedrín M, Cerda Contreras E, Carmona Sánchez RI, Guerra López H, Solana Ortiz R. Lactobacillus acidophilus LB: a useful pharmabiotic for the treatment of digestive disorders. Therap Adv Gastroenterol. 2020 Nov 24;13:1756284820971201. doi: 10.1177/1756284820971201.
Kullar R, Goldstein EJC, Johnson S, McFarland LV. Lactobacillus bacteremia and probiotics: a review. Microorganisms. 2023;11(4). doi: 10.3390/microorganisms11040896.
Franko B, Fournier P, Jouve T, Malvezzi P, Pelloux I, Brion JP, et al. Lactobacillus bacteremia: pathogen or prognostic marker? Med Mal Infect. 2017;47(1):18-25. doi: 10.1016/j.medmal.2016.04.003.
Fitzgerald JR, Foster TJ, Cox D. The interaction of bacterial pathogens with platelets. Nat Rev Microbiol. 2006;4(6):445-57. doi: 10.1038/nrmicro1425.
Collins J, van Pijkeren JP, Svensson L, Claesson MJ, Sturme M, Li Y, et al. Fibrinogen-binding and platelet-aggregation activities of a Lactobacillus salivarius septicaemia isolate are mediated by a novel fibrinogen-binding protein. Mol Microbiol. 2012;85(5):862-77. doi: 10.1111/j.1365-2958.2012.08148.x.
Sato J, Kanazawa A, Ikeda F, Yoshihara T, Goto H, Abe H, et al. Gut dysbiosis and detection of ”live gut bacteria” in blood of Japanese patients with type 2 diabetes. Diabetes Care. 2014;37(8):2343-50. doi: 10.2337/dc13-2817.
Zheng N, Guo R, Wang J, Zhou W, Ling Z. Contribution of Lactobacillus iners to vaginal health and diseases: A systematic review. Front Cell Infect Microbiol. 2021;11:792787. doi: 10.3389/fcimb.2021.792787.
Wong CH, Wang YS. The diagnosis of necrotizing fasciitis. Curr Opin Infect Dis. 2005;18(2):101-6. doi: 10.1097/01.qco.0000160896.74492.ea.
Wong CH, Khin LW, Heng KS, Tan KC, Low CO. The LRINEC (Laboratory Risk Indicator for Necrotizing fasciitis) score: a tool for distinguishing necrotizing fasciitis from other soft tissue infections. Crit Care Med. 2004;32(7):1535-41. doi: 10.1097/01.ccm.0000129486.35458.7d.
Bechar J, Sepehripour S, Hardwicke J, Filobbos G. Laboratory risk indicator for necrotising fasciitis (LRINEC) score for the assessment of early necrotising fasciitis: a systematic review of the literature. Ann R Coll Surg Engl. 2017;99(5):341-6. doi: 10.1308/rcsann.2017.0053.
Johnson LJ, Crisologo PA, Sivaganesan S, Caldwell CC, Henning J. Evaluation of the Laboratory Risk Indicator for Necrotizing fasciitis (LRINEC) score for detecting necrotizing soft tissue infections in patients with diabetes and lower extremity infection. Diabetes Res Clin Pract. 2021;171:108520. doi: 10.1016/j.diabres.2020.108520.
Childers BJ, Potyondy LD, Nachreiner R, Rogers FR, Childers ER, Oberg KC, et al. Necrotizing fasciitis: a fourteen-year retrospective study of 163 consecutive patients. Am Surg. 2002;68(2):109-16. doi: 10.1177/000313480206800201.
Al-Qurayshi Z, Nichols RL, Killackey MT, Kandil E. Mortality risk in necrotizing fasciitis: national prevalence, trend, and burden. Surg Infect. 2020;21(10):840-52. doi: 10.1089/sur.2019.277.

No competing interests reported.

Download PDF

Journal Publication

published 22 Apr, 2024

Read the published version in BMC Infectious Diseases →

Editor invited by journal
03 Jan, 2024
Submission checks completed at journal
03 Jan, 2024
First submitted to journal
28 Dec, 2023

You are reading this latest preprint version

Necrotising fasciitis with extensive necrosis caused by Lactobacillus: A case report

Status:

Journal Publication

Version 1

Abstract

Figures

Background

Case presentation

Discussion and Conclusions

Abbreviations

Declarations

References

Additional Declarations

Status:

Journal Publication

Version 1