MRSA toxic shock syndrome associated with surgery for left leg fracture and co-morbid compartment syndrome

Taro Shimizu, Yufu Yamamoto, Takahiro Hosoi, Kensuke Kinoshita, Yasuharu Tokuda

1Nerima Hikarigaoka Hospital, Hospitalist Division, Department of Medicine, Tokyo, Japan

2Tsukuba University Affiliated Mito Medical Center, Department of Medicine, Mito, Ibaraki, Japan

MRSA toxic shock syndrome associated with surgery for left leg fracture and co-morbid compartment syndrome

Taro Shimizu1, Yufu Yamamoto2, Takahiro Hosoi2, Kensuke Kinoshita2, Yasuharu Tokuda2

1Nerima Hikarigaoka Hospital, Hospitalist Division, Department of Medicine, Tokyo, Japan

2Tsukuba University Affiliated Mito Medical Center, Department of Medicine, Mito, Ibaraki, Japan

We report the case of a 46-year-old Japanese man who was brought to the hospital with fever, hypotension and diffuse erythematous rash with multiple organ damage. Three weeks before he had undergone orthopaedic surgery for left leg fracture and comorbid compartment syndrome. Fasciorrhaphy was performed successfully 2 weeks before, but the next day he became feverish and hypotensive with signs of systemic low perfusion. He was referred to the hospital for further evaluation and treatment. On arrival, high fever, hypotension and diffuse erythroderma were observed. Lab results revealed multi-organ dysfunction. Clinical manifestations led to the diagnosis of toxic shock syndrome (TSS). The patient was treated with extensive hydration, local drainage and antibiotics. After 2 weeks of intensive care, he recovered and was successfully discharged from the hospital. A culture of the wound tissue revealed the presence of MRSA with positive TSST-1.

ARTICLE INFO

Article history:

Received 15 October 2013

Received in revised form 19 December 2013

Accepted 15 January 2013

Available online 20 March 2014

MRSA

1. Introduction

The staphylococcal toxic shock syndrome (TSS) is a fatal infectious disease caused by the enterotoxins (toxic shock syndrome toxin-1 (TSST-1) and other toxins) released byStaphylococcus aureus (S. aureus). The exotoxin serves as a superantigen, which directly interacts with the invariant region of the class II MHC molecule, thereby activating large numbers of T cells, often up to 20% of all T cells at a time. This results in massive cytokine production[1]. Released cytokines including interleukin (IL)-1, IL-2, tumour necrosis factors (TNF)-α and -β and interferon (IFN)-γ cause the symptoms of TSS. Clinical manifestations are often characterized by fever, rash (erythema)/desquamation (1-2 weeks after the onset of rash) and hypotension. Furthermore, TSS causes multisystem involvement including that of GI, muscular, mucous membrane, renal, hepatic, haematological and central nervous systems. The majority of cases of staphylococcal TSS are caused by methicillinsusceptibleS. aureus(MSSA). However, as rates of infection due to methicillin-resistantS. aureus(MRSA) have increased, the number of cases of TSS due to MRSA have also increased[2,3].

Half of all TSS cases are not reported to be associated with menstruation[4,5]. Non-menstrual TSS has been observed in a wide variety of clinical settings including postoperative and postpartum wound infections, sinusitis, respiratory infections following influenza, mastitis, osteomyelitis, arthritis, burns, cutaneous/subcutaneous lesions and enterocolitis[6-13]. Postoperative cases increased from 14% in 1979-1986 to 27% in 1987-1996[14].

Patient fatalities have been attributed to cardiac problems (arrhythmias and cardiomyopathy), respiratory failure or DIC. Mortality due to non-menstrual TSS is higher than that in menstrual cases (5% versus 1.8%)[14,15]. Death usually occurs within the first few days, but in some cases it occurs 15 d after hospital admission[16,17].

2. Case report

A previously healthy 46-year-old baseball player with no remarkable past medical or family history, no known drug allergy and no prior medications was referred to our hospital by an orthopaedic surgeon. The patient presentedwith fever, hypotension and watery diarrhoea. He had smoked for 28 pack-years and consumed 500 mL of beer per day. Three weeks before, he had undergone orthopaedic surgery because of left fibular and tibial fracture during a baseball game. Open reduction and internal fixation (ORIF) and fasciotomy were performed to treat his fracture and the compartment syndrome that occurred concurrently. Two weeks before, fasciorrhaphy was performed successfully. However, the next day the patient passed loose brownish stools; his blood pressure dropped to 60 mmHg (systolic blood pressure), and fever rose to 39 ℃. Blood tests revealed BUN to be 50 mg/dL and Cr to be 2.5 mg/dL. The patient was referred to our hospital. He had taken cefazolin for 2 weeks after surgery.

On examination, the vital signs of the patient were as follows: blood pressure, 70/48 mmHg; heart rate, 107 beat per min; body temperature, 39.0 ℃; respiratory rate, 24 and SpO2, 95% in ambient air. Diffuse macular erythema was observed on the trunk (Figure 1), extremities and face. The left leg was markedly swollen, with the presence of warmth and redness and the surgical scar (Figure 2). External Juglar vein collapse was evident even in the supine position. Other physical findings were unremarkable. His blood test results were as follows: WBC 189 800/μL, Hb 11.1 g/dL, Ht 30.5%, Plt 11.2×104/μL, T-P 5.1 g/dL, Alb 2.3 g/dL, AST 136 IU/L, ALT 71 IU/L, T-bil 1.5 mg/dL, LDH 452 IU/L, CPK 5 026 IU/ L, ALP 43 IU/L, GGT 14IU/L, Amy 103 IU/L, UN 53 mg/dL, Cr 2.5 mg/dL, BS 121 mg/dL, Na 129 mEq/L, K 4.0 mEq/L, Cl 96 mEq/L, CRP 23.0 mg/dL, FDP 40.8 mg/dL, FIB 339 mg/dL, D-dimer 26.5 μg/mL. An X-ray of the left lower extremity revealed no gas collection beneath the soft tissue.

Figure 1. Diffuse macular erythema was found on his trunk.

Figure 2. Left leg was markedly swollen with warmth and redness with surgical scar.

On the basis of his clinical manifestations, the patient was diagnosed with TSS. Aggressive fluid replacement therapy (infused fluid volume, 5-8 L/d for the first 3 d) with administration of vancomycin (1 g) and ceftriaxone (2 g) plus clindamycin (1 200 mg qd) were immediately initiated. Surgical inspection was performed, but no necrotic tissue was observed. Local drainage was performed.

After supportive antibiotic therapy, TSS symptoms resolved. One week later, desquamation was complete. Two weeks after the day of admission, the patient was stabilised and discharged from the hospital. A culture of the wound tissue revealed MRSA with positive TSST-1.

3. Discussion

Sex distribution was equal in a study of 130 TSS cases in which vaginal and postpartum-associated cases were excluded[18]. Patients with non-menstrual TSS are significantly older (mean age, 26.8 years versus 23 years in patients with menstrual TSS) and more often non-white compared with patients with menstrual TSS[5,11,18]. The case-fatality rate for non-menstrual TSS was reported to be 5% and did not decrease over time[14]. TSST-1 was the first exotoxin isolated fromS. aureusin TSS in 1981[19,20]. It is found in over 90% of menstrual TSS cases and in 40%-60% of strains from non-menstrual cases. Our patient was a middle-aged Asian male suffering from postoperative TSS caused by TSST-1.

The diagnosis of TSS is established based on clinical presentation that satisfies the CDC case definition[21,22]: patients must have fever ＞38.9 ℃, hypotension, diffuse erythema, desquamation (unless the patient dies before desquamation can occur) and involvement of at least three organ systems. A probable case is defined as a patient who is missing one of the characteristics of the confirmed case definition. Our patient satisfied all the aforementioned criteria with GI, muscular, renal and hepatic involvement. Eighty to ninety percent of TSS patients have S. aureus isolated from mucosal or wound sites, while this is not required for the diagnosis of staphylococcal TSS[23]. On the other hand,S. aureusis rarely isolated (5%) from blood cultures compared with streptococcal TSS[18]. In our patient,S. aureuswas isolated from the wound site, and not from blood cultures.

The mainstay of treatment for TSS is supportive, while the patient presents hypotension. Rapid fluid replacement and/ or vasopressors are also necessary. In addition to supportive therapy, removal, drainage or debridement of any possible infectious focus is imperative. Exploration of surgical wounds is important for patients with postoperative TSS because signs of infection may be masked because of the decreased inflammatory response.

Whether antibiotics alter the course of acute TSS remains unclear although antibiotic therapy has been revealed to reduce the likelihood of recurrent TSS by eliminating the carrier state[23]. Clindamycin plus either vancomycin or linezolid may typically be administered to patients with TSS due to MRSA for 10-14 d even in the absence of overtS. aureusinfection. Clindamycin is a pivotal and efficacious drug for adrained postoperative infected focus, acting by suppressing bacterial protein synthesis[24]. Vancomycin and linezolid are effective drugs for treating MRSA. In our patient, vancomycin and ceftriaxone were administered in addition to clindamycin at the beginning of the therapy because it was uncertain whether the causative agent wasStreptococcusorStaphylococcus. Hence, we covered both of the organisms since TSS is the fatal condition and the dual coverage should be required unless the causative organism is uncertain.

Intravenous immunoglobulin (IVIG) therapy has been suggested in severe cases that have been recognized early in their course and have not responded to supportive therapy[25]. However, no controlled trials of IVIG therapy in staphylococcal TSS have been conducted in humans[25,26]. On the other hand, IVIG treatment may be efficacious in streptococcal TSS[27,28]. A report from Sweden noted that culture supernatants containing the superantigen fromS. aureuswere less efficiently inhibited by IVIG than those fromS. pyogenes[29]. Another additional therapy corticosteroid is not recommended because of the limited clinical evidence with this therapy. We did not use both of IVIG and corticosteroids in our case.

Conflict of interest statement

We declare that we have no conflict of interest

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ment heading

10.1016/S2221-6189(14)60021-4

*Corresponding author: Taro Shimizu, MD, MPH, 2-11-1, Hikarigaoka, Nerima-ku, Tokyo 179-0072, Japan.

Tel: +81-3(3979)3611

Fax: +81-3(3979)3787

E-mail: shimizutaro7@gmail.com

Toxic shock syndrome

Surgical site infection