RENAL FAILURE IN VIBRIO VULNIFICUS INFECTION

Abstract

Vibrio vulnificus infection with septicemia is a life threatening disease in the immunocompromised hosts. Renal involvement has not been documented. We reported herein 8 patients with V. vulnificus septicemia. All were immunocompromised hosts. Four patients had cirrhosis of the liver, 3 were heavy alcohol drinkers and one had systemic lupus erythematosis. Presenting symptomatology included fever, chills, leg pain and skin rash. Renal failure was observed in 6 patients. Four patients died shortly after admission. Two survived with clinical course of tubular necrosis. Renal failure is therefore common in V. vulnificus infection. This should be brought to attention, and vigorous antibiotic treatment is required. The disease may be confused with leptospirosis, scrub typhus, malaria and other forms of sepsis which also present with renal failure.

INTRODUCTION

Vibrio vulnificus is a halophilic, lactose fermenting and highly mobile gram negative bacillus found in coastal and brackish waters. The microorganism gains entry to the body either through the skin injury or oral ingestion. The incubation period varies, but is usually between 24 to 48 hours after consumption of contaminated sea food. Wound infections result from either injury to the skin in a marine environment or exposure of a preexisting wound to sea water or brackish water, and may develop within 12 to 16 hours after the insult. V. vulnificus infection in man can be expressed in 3 forms as primary sepsis, wound infection or gastrointestinal manifestation [[1]]. The presenting symptoms include fever with chills, abdominal pain, vomiting, diarrhea and intense lower extremity pain [1-8]. Skin lesions are usually at the site of injury or localized to the lower extremities and range from an ecchymotic bullous lesion to necrotic ulcers [8-12].

Primary sepsis is often associated with underlying diseases especially cirrhosis of the liver and immunocompromised conditions [10-12]. It is severe with hypotension, and development of disseminated intravascular coagulation is common. Renal complication is therefore not unexpected. Yet, in reviewing the literature including the extensive report from the Gulf Coast States in North America renal dysfunction was not brought to attention [1-13]. Tubular necrosis was described at autopsy only in one report [[10]]. We feel that renal complications should be documented, and V. vulnificus infection should be listed in the differential diagnosis of acute renal failure in cirrhotic or immunocomprised patients who present with fever, chills, jaundice and muscular pain.

PATIENTS AND RESULT

From 1995 to 1998 there were 8 patients with V. vulnificus infection who were hospitalized in the King Chulalongkorn Memorial Hospital. Seven were male and one was female, ranging in age from 31 to 50 years. They were admitted to the hospital 1 day to 8 days after the onset of symptoms. The underlying diseases include cirrhosis in 4 patients, heavy alcohol drinking in 3 and lupus nephritis in one (Table 1). Since this is a retrospective study through reviewing the medical records the history of exposure to the bacteria was available only in 3 patients. One patient consumed cockles; one had shrimps; and one fell into the brackish water. All patients had fever often with chills and pain of lower extremities upon admission. Four patients (Patients 1, 2, 4 and 5) were hypotensive. One patient (patient 6) had diarrhea, and one (Patient 4) had disseminated intravascular coagulation. In all cases hemoculture was positive for V. vulnificus. The laboratory data are summarized in Table 2. Four patients (Patients 1, 2, 6 and 8) had jaundice with a total serum bilirubin ranging from 4.9 to 7.7 mg/dL. These 4 patients had low serum albumin (1.9–2.6 g/dL). The hospital stay ranged from 45 min to 38 days. Four patients expired within 45 minutes to 60 hours after admission and four recovered giving the mortality rate of 50%.

Table 1. The clinical profile of the patient

Patient
Sex	Age	Underlying disease	History of exposure	Onset before admission	Clinical manifestation	Duration of hospitalization	Outcome
1. Male	50	Diabetes mellitus Alcoholic cirrhosis	–	2 days	Fever with chills, severe leg pain, alteration of conciousness and hypotension	115 minutes	Death
2. Male	36	Alcoholic cirrhosis	Eating cockles	8 days	Fever with chills, severe leg pain, hemorrhagic blebs of the leg and hypotension.	60 hours	Death
3. Male	40	Heavy alcohol drinking	–	1 day	Fever, dyspnea and skin rash	45 minutes	Death
4. Male	50	Diabetic mellitus Alcoholic cirrhosis	Eating shrimps	1 day	Fever wtih chills, severe leg pain, hypotension and DIC^*	20 days	Recovery
5. Male	50	Heavy alcohol drinking	Falling into the brackish water	3 days	Fever, severe leg pain, alteration of consciousness and hypotension	17 hours	Death
6. Male	47	Chronic heptatis B. with cirrhosis	–	1 day	Fever with chills, watery diarrhea and severe leg pain	19 days	Recovery
7. Female	42	SLE with lupus nephritis on prednisolone and cyclophosphamide	–	3 days	Severe leg pain, fever and erythematous rash with hemorrhagic bleb	30days	Recovery
8. Male	31	Heavy alcohol drinking	–	3 days	Fever with chills, myalgia, severe leg pain and seizure	38 days	Recovery

DIC = Dissiminated intravascular coagulopathy

Table 2. Laboratory data on admission

	Patient
Laboratory data	1	2	3	4	5	6	7	8
Hematocrit (%)	24	25	39.3	24	39.1	32.3	37.5	31.5
White blood cell (/mm^3)	35,000	10,890	10,500	14,900	2,600	4,430	13,200	7,110
Neutrophil (%)	84	84	81	71	67.6	40	93	77.4
Lymphocyte (%)	12	11	12	15	17.5	44	3	14
Platelet (/mm^3)	18,200	49,200	61,000	31,000	39,300	227,000	150,000	80,600
BUN (mg/dL)	36	39	27	25	46	17	19	32
Serum creatinine (mg/dL)	3.3	5.4	3.2	1.9	2.8	1	1.2	3.2
Serum Na^+ (mmol/L)	135	132	140	130	128	132	140	142
Serum K^+ (mmol/L)	5.2	5	4.7	4	4.3	4.2	5.9	3.1
Serum Cl^− (mmol/L)	106	99	110	91	92.7	104	107	111
Serum HCO^−3(mmol/L)	10	15	6.4	11	19.9	22	28.2	15.1
Total serum bilirubin (mg/dL)	5.9	4.9	–	1.0	–	7.4	–	7.7
Direct serum bilirubin (mg/dL)	4.3	3.3	–	0.6	–	3.7	–	6.1
Serum albumin (gm/dL)	2.4	1.9	–	2.1	–	2.5	–	2.6
Serum globulin (gm/dL)	4.1	4.3	–	3.7	–	3.6	–	2.9
Serum aspartate aminotransferase (u/L)	829	149	–	241	–	145	–	125
Serum alanine aminotransferase (u/L)	186	56	–	110	–	103	–	74
Prothrombin time (second) (control)	25(11.6)	26.1(12.7)	–	15.2(13.6)	18.8(12.9)	20.9(12.1)	12.5(13.1)	18.0(12.6)
Partial thromboplastin time (second) (control)	78.2(28.5)	56.5(28.2)	–	34.3(31.2)	67.3(31.2)	56.3(29)	28.4(30.7)	38.2(33.1)

Acute renal failure was present in 6 patients (Patients 1, 2, 3, 4, 5 and 8) whose serum creatinine level ranged from 1.9 to 5.4 mg/dL and blood urea nitrogen from 25 to 46 mg/dL. Urinalysis showed nonspecific urinary sediment with few granular casts. Four patients (Patients 1, 2, 3 and 5) died shortly after admission. In the patients 4 and 8 who recovered the clinical course was that of acute tubular necrosis.

DISCUSSION

It is not surprising to observe renal insufficiency in the patient with septicemia. V. vulnificus septicemia is not an exception. Acute renal dysfunction can range from pre-renal failure to tubular necrosis. As in the other forms of sepsis renal failure is due to renal hemodynamic alteration induced by cytokines and mediators. Disseminated intravascular coagulation and hypovolemia, either due to low serum albumin secondary to cirrhosis or fluid leakage from the intravascular compartment induced by the vascular permeability factor of the microorganism [[8]], further contribute to decreased renal blood flow. Renal failure is therefore ischemic in origin. V. vulnificus can also cause cellular injury through the effects of cytolysin, collagenase, elastolytic protease, metalloprotease and phospholipases [14-17]. Virulence of this microrganism is related to the acidic polysaccharide capsule which is resistant to bactericidal activity of human serum and to phagocytosis [18-19].

It is rare for people in good health to develop primary septicemia from this microorganism. The microorganism is not highly virulent for normal animals, but its virulence was greatly increased by injection of iron compounds. V. vulnicifus is killed by normal human blood but grows rapidly in blood from patients with hemochromatosis [[20]]. The increased availability of iron in the blood of patients with chronic iron overload is responsible for their enhanced susceptibility to V. vulnificus infection [20-21]. Chronic alcohol consumption may affect iron availability either by increased iron absorption through gastric acid stimulation or by decreased production of transferrin for circulating iron [[22]].

Increased virulence of V. vulnificus in cirrhotic patients is explained on the basis of immune system dysfunction including decreased serum complement levels and reduced activity of phagocytosis, chemotaxis and opsonization. In addition, in the presence of portal hypertension, the organisms that enter the body through the portal system may bypass the hepatic reticuloendothelial system. The increased iron storage in alcoholic cirrhosis, thalassemia and hemochromatosis can enhance the growth of V. vulnificus. Our report corroborates the association of cirrhosis with V. vulnificus infection.

Two interesting points should be emphasized. First, since V. vulnificus does not usually infect normal people but only those with underlying diseases especially cirrhosis, hemochromatosis or the patients with decreased immune activity, V. vulnificus septicemia is thus very severe.

Renal failure is therefore common especially in those with cirrhosis whose renal hemodynamics may already be compromised. In our report renal failure was noted in 75%, a figure which is higher than renal failure in septicemia due to the other causes. Second, characteristically, tenderness of lower extremities, erythema, edema and urticarial plagues develop sequentially. In this respect, at the early stage V. vulnificus septicemia can be confused with several diseases that cause fever with chills, muscular pain, jaundice and renal failure. In the tropics, the usual diseases included in differential diagnosis would be leptospirosis, malaria, scrub typhus, dengue hemorrhagic fever, hantan virus infection and sepsis [[23]]. Based on this report fever with chills, muscular pain and renal failure in a patient with cirrhosis or immunocompromised patient with a history of consumption of sea food or exposure to sea water or brackish water would call attention to V. vulnificus infection. Treatment should be geared to this disease. Without having thought of this life threatening disease treatment may be delayed and death can ensue.