Aeromonas hydrophila sepsis with septic embolism and rhabdomyolysis in a chronic iron overload haemodialysis patient treated with deferoxamine.

Aeromonas infection in humans is associated with certain underlying diseases, especially chronic liver disease or malignancy. However, Aeromonas infection associated with iron overload is rarely reported. We report a case of a 47-year-old female with end-stage renal disease on haemodialysis and on deferoxamine treatment for iron overload who developed Aeromonas sepsis with septic embolism and rhabdomyolysis. Although the patients with Aeromonas infection and rhabdomyolysis have been correlated with high mortality, this reported case survived. We suggest that a chronic haemodialysis patient on deferoxamine treatment for iron overload is vulnerable to Aeromonas infection. In such cases, the clinician should be alerted to the possibility of rhabdomyolsis, and frequent haemodialysis is necessary.

Introduction

Aeromonas hydrophila is a facultative anaerobic gram-negative bacillus that belongs to the Aeromonadaceae family. It can be found worldwide in aquatic environments including ground water, drinking water and polluted water [1]. Aeromonas infections in humans can be found in various clinical manifestations including gastroenteritis, wound infection, septicaemia, meningitis, peritonitis, respiratory tract disease and ocular infection [1]. The association between a patient with iron overload treated with deferoxamine and Aeromonas infection is rarely reported [2]. There has been no report of this association in a chronic haemodialysis patient.

Case report

A 47-year-old female was diagnosed with end-stage renal disease of unknown aetiology and on chronic haemodialysis twice weekly since 1994. She received a living-related kidney transplant in December 2003. Unfortunately, her transplant was complicated by graft rejection in December 2004 and haemodialysis became necessary in July 2005. In November 2007, she developed anaemia despite receiving 80 U/kg/week of erythropoietin. She was diagnosed with pure red cell aplasia from hypocellular bone marrow and positive anti-EPO in January 2008 and she needed chronic blood transfusions, of about 1–2 units of packed red blood cells per month. She developed iron overload in May 2008 with a serum ferritin level of 2650 ng/mL. She was treated with deferoxamine 1500 mg twice weekly.

In August 2008, the patient was struck by a fish bone in the right hand while she was boning fresh water fish. Subsequently, she developed a high-grade fever and generalized muscle pain the next day. Due to the progressive pain and redness of the wound, she presented to our hospital on the third day of fever.

On admission, the patient's body temperature was 39.2 °C, with a pulse rate of 100/min, a respiratory rate of 24/min and a blood pressure of 140/90 mmHg. The wound at the ridge of her right hand was swollen but there was no fluctuation (Figure 1). Her right hand and right arm were also swollen and tender. Marked generalized muscle tenderness was noted which caused the patient to avoid moving her arms or legs. Initial laboratory investigation revealed that her white blood cell count (WBC) was 9700 cells/ mm3 with a neutrophil predominance. The haematocrit was 22.5% and platelet count was 101 000/mm3. Blood biochemistries showed sodium 129 mEq/L, potassium 6.23 mEq/L, chloride 93 mEq/L, bicarbonate 22.8 mEq/L, blood urea nitrogen 84 mg/dL, creatinine 15.9 mg/dL, aspartate transaminase 31 U/L, alanine transaminase 35 U/ L and creatinine phosphokinase (CPK) 1218 U/L. Urinalysis was marked positive for blood with marked proteinuria without red blood cell or white blood cell sediment.

Fig. 1

Multiple lesions of septic embolism on the right arm and old wound from fish bone on the ridge of the hand.

Because of the severe sepsis, the patient received meropenem and vancomycin as empirical antibiotics. Blood cultures revealed Aeromonas hydrophila that was susceptible to the second and third generation of cepha- losporins, gentamicin, trimethoprim–sulfamethoxazole and fluoroquinolones. The antibiotics were switched to ceftriaxone after the results of the blood culture. Although fever rapidly subsided within 3 days, the WBC and CPK continued to rise. Meanwhile, she developed pustular skin lesions compatible with septic embolism over all extremities (Figure 1). On the sixth day of admission, ciprofloxacin was added. Cultures from the skin lesion also recovered A. hydrophila. WBC peaked at 43 300 cells/mm3 on the 7th day of admission and returned to a normal value on the 15th day. CPK peaked at 13 317 U/L on the fourth day of admission and returned to a normal value on the ninth day (Figure 2). She needed more frequent haemodialysis than her previous schedule during the first few days because of severe hyperkalaemia caused by rhabdomyolysis. No further skin lesion developed after the 11th day of admission. She was discharged on the 19th day of admission. The clinical course is shown in Figure 2.

Fig. 2

Clinical course of the patient. Temperature (°C), white blood count (cell/mm3), creatinine phosphokinase (U/L), square box with ‘HD’ = haemodialysis.

Discussion

Aeromonas bacteraemia is associated with certain underlying diseases such as chronic liver disease (48%) and malignancy (24%) [3] and is predominant in males (2:1) for unknown reasons [4]. The overall mortality rate in these patients has ranged from 36 to 64% [3,4]. In this reported case, the patient had been struck by a fish bone at the right hand prior to development of Aeromonas bacteraemia. This could be the most likely portal of entry of the organism. Previous studies have described that A. hydrophila septicaemia is commonly caused by minor skin and soft-tissue trauma from freshwater fish and the environment [5,6]. A. hydrophila has been identified from environmental sources, i.e. fresh water, in Thailand [7].

Iron overload treated with deferoxamine has been reported to be associated with certain infections. Systemic Y. enterocolitica infection and zygomycosis are well-known clinical infections associated with iron overload and deferoxamine therapy [8,9]. In addition, a thalassaemic patient with iron overload treated with deferoxamine has also been reported to be associated with A. hydrophila infection [2].

Interestingly, Lin et al. [10] reported the association between a fatal outcome from Aeromonas bacteraemia and deferoxamine use in a haemodialysis patient with aluminium bone disease, not iron overload. The authors believed that the iron–deferoxamine complex accumulated in the uraemic patient after intravenous administration of deferoxamine alone [11]. They also demonstrated that only the iron–deferoxamine complex, and not any other chelator complex, enhanced Aeromonas growth in an iron-restricted environment in vitro [10]. Moreover, Ho et al. [12] showed that the flexible pilin expression, believed to be one of the virulence factors of A. hydrophila, was increased in the presence of deferoxamine in iron-replete media. Rabsch et al. [13] demonstrated in vitro that A. hydrophila could use ferrioxamine (iron–deferoxamine complex) as an additional iron source. Taken together, it seems that the iron–deferoxamine complex, rather than iron overload alone, is a risk factor for this infection due to the additional iron source and the enhancement of some virulent properties. More data are required to explain the relationship between iron overload, deferoxamine and Aeromonas infection.

Rhabdomyolysis has been associated with a wide variety of infections including those from viruses, bacteria, fungus and parasites [14]. A prospective study by Betrosian et al. [15] found that about two-thirds of bacterial sepsis patients complicated with rhabdomyolysis were caused by gram-positive organisms and about one-third of the cases were caused by gram-negative organisms including Pseudomonas aeruginosa (20%), Escherichia coli (8.5%) and Klebsiella pneumoniae (2.8%). To the best of our knowledge, there have been three reported cases of rhabdomyolysis associated with Aeromonas infection with high mortality [16,17] (Table 1). In this case, we first experienced rhabdomyolysis associated with Aeromonas infection in a chronic haemodialysis patient on deferoxamine treatment for iron overload. Although the patient may have liver disease, there was no significant compromised liver or malignancy in this case. Iron overload and deferoxamine may be responsible for this susceptible infection.

Table 1

Clinical characteristics of Aeromonas infection with rhabdomyolysis of the present case and review of the literatures

Reference	Age (years)	Sex	Underlying conditions	Organism	Peak CPK (U/L)	Outcomes
[16]	49	M	Alcoholic liver disease	A. sobria	24 085	Dead on day 2
[17]	50	M	ANLL post-SCT	A. sobria	24 000	Dead on day 3
[17]	41	F	ANLL	A. hydrophila	1 006	Improved
This case	47	F	Chronic haemodialysis with iron overload	A. hydrophila	13 317	Improved

CPK: creatinine phosphokinase; ANLL: acute non-lymphoblastic leukaemia; SCT: stem cell transplantation.

Fever is generally a good indicator for a treatment response. However, the process of infection still progressed with septic embolism despite the resolution of the fever in this present case. While white blood cell count did not rise significantly in the first few days, it had a good correlation with treatment response.

In conclusion, this reported case presents a clinical course of A. hydrophila sepsis that was complicated by rhabdomyolysis and septic embolism in a chronic haemodialysis patient on deferoxamine treatment for iron overload. We suggest that, in addition to Yersinia and Mucormycosis, Aeromonas sepsis should be suspected in chronic haemodialysis patients on deferoxamine treatment for iron overload who present with sepsis. Clinicians should be alerted to rhabdomyolysis in this clinical setting, and frequent haemodialysis is necessary.