Candida infections in surgical patients. Dose requirements and toxicity of amphotericin B

The natural history of candidiasis in general surgical patients has been poorly documented, and the toxicity of amphotericin B is widely heralded. For these reasons therapy for candidiasis is frequently withheld in situations where antimicrobial treatment seems indicated on clinical grounds. The clinical courses of 47 general surgical patients who received amphotericin therapy for presumed Candida infection were reviewed. Nineteen patients had had solid tumors, but 12 were either localized or resected tumors. Only nine patients had received prior cancer themotherapy. Twenty-one patients were treated for fungemic disease, 10 for Candida in peritonitis fluid, and 16 for apparent colonization associated with fever and organ failure syndromes. Pre-existing renal or other organ failure was the primary determinant of survival with 4/22 survivors (18%) in patients with renal failure compared with 17/25 (78%) survivors in patients without such organ failure. In patients with serum creatinine values less than 2.5 mg/dl, amphotericin therapy was associated with a transient 30% fall in creatinine clearance and a proportionate rise in serum creatinine. Dose response curves were determined and revealed substantial sterilization of cultures in both fungemic and nonfungemic patients receiving greater than or equal to 6 mg/kg. This was confirmed by autopsy material. We suggest that in this acutely ill patient popoulation uncontrolled infection is the primary determinant of organ failure. Short-term limited dosing with amphotericin B (6-8 mg/kg total dose) in conjunction with appraisal of clinical response is adequate therapy for most presumed Candida infections. Long-term high dose therapy, such as that recommended in immuodepressed patients, is not a routine necessity.     

Candida septic thrombosis of the great central veins associated with central catheters. Clinical features and management.

Candida septic thrombosis of the great central veins is rarely diagnosed during life, and reports of survival with this condition are exceedingly rare. Eight patients with Candida septic thrombosis of the central veins, with six survivors, are reported. Seven of eight patients had multiple organ system failure following surgery or trauma. All patients had received broad spectrum antibiotics and total parenteral nutrition via a central catheter. Every patient showed features of venous thrombosis with localizing extremity edema and high grade candidemia. Intensive amphotericin B therapy (mean daily dose: 0.7 mg/kg) in all patients, combined with 5-fluorocytosine in five cases, resulted in cure and long-term survival in six patients who received 1600 to 3435 mg (mean: 26 mg/kg) total dose. None of these patients developed renal failure, while four showed improving renal function during treatment. In contrast to Candida endocarditis, septic central vein thrombosis caused by Candida appears to be curable medically in the majority of cases with intensive amphotericin B therapy (total dose: greater than or equal to 22 mg/kg), combined when feasible with 5-fluorocytosine.     

Miconazole therapy for systemic candidiasis in a conjoined (Siamese) twin and a premature newborn.

A 2.5 kg thoracopagus (Siamese) twin and a 0.73 kg premature newborn developed systemic candidiasis and were treated with intravenous miconazole. The conjoined twin was in a state of severe metabolic acidosis, respiratory distress, jaundice, anuria, abdominal distension, and shock. The 0.73 kg premature infant was also in a state of severe metabolic acidosis, respiratory distress, and oliguria. Miconazole was used in this desperate situation for the treatment of life-threatening candidiasis. Both infants responded well to treatment and recovered. All parameters of their diseases improved during therapy despite pre-existing multiple organ dysfunction. Miconazole can be a safe alternative to amphotericin B for the treatment of systemic candidiasis in neonatal infants, including those with impaired renal function.     

Efficacy and safety of Amphotericin B Lipid Complex Injection (ABLC) in solid-organ transplant recipients with invasive fungal infections

Background: Fungal infections following solid-organ transplantation are a major source of morbidity and mortality. This report describes the efficacy and safety of Amphotericin B Lipid Complex Injection (ABLC) in solid-organ transplant recipients.
Methods: Three open-label, second-line treatment studies evaluated ABLC as a treatment for severe, life-threatening mycoses in patients who were refractory to or intolerant to conventional antifungal (mostly amphotericin B [AmB]) therapy or had pre-existing renal disease.
Results: The 79 solid-organ transplant recipients (25 heart, 20 liver, 17 kidney, 11 lung, 5 multiple, 1 pancreas) who received ABLC in these studies had the following fungal infections: aspergillosis (n=39); candidiasis (n=20); zygomycosis (n=8); cryptococcosis and histoplasmosis (n=3 each); and blastomycosis, cladosporiosis, fusariosis, Bipolaris hawaiiensis , Dactylaria gallopava , and an unspecified fungal infection (n=1 each). The median duration of ABLC therapy was 28 d (1–178 d). The daily dose ranged between 1.6 and 7.4 mg/kg (median, 4.6 mg/kg). The clinical response rate for the patients who could be assessed was 58% (39/67). Clinical response rates for heart, liver, kidney, and lung recipients were 59, 60, 67, and 40%, respectively; response rates for aspergillosis and candidiasis were 47 and 71%, respectively. Forty-six of the 79 patients (58%) survived for more than 28 d after the last dose of ABLC. Mean baseline serum creatinine was 3.2 mg/dL; 64 patients (81%) had stable (n=37) or improved (n=27) serum creatinine at the end of treatment.
Conclusions: ABLC is safe and effective treatment for fungal infections in solid-organ transplant recipients. Its renal-sparing properties are particularly suited for this high-risk population for renal failure.     

The effects of amphotericin B therapy on the intrarenal vasculature and renal tubules in man. A study of biopsies by light, electron and immunofluorescence microscopy

Renal morphology was studied by light and electron microscopy in 10 patients after 25 mg/kg body weight of amphotericin B as part of a controlled study designed to evaluate the possible protective effects of mannitol against the nephrotoxicity of amphotericin B. Five patients received amphotericin B 1 mg/kg body weight every other day and five received amphotericin B and mannitol 1 g/kg body weight in the infusion. Small arterial and arteriolar changes were present in all biopsies and were characterized by focal vacuolization of medial smooth muscle cells. Electron microscopy suggested formation of these vacuoles by fusion of dilated endoplasmic reticulum. A few small vacuoles were also seen in renal biopsies of age matched patients who did not receive amphotericin B. Vacuoles in biopsies of the amphotericin treated patients were considerably larger (P less than 0.001) and much more numerous (P less than 0.001) than in controls. It is hypothesized that the vacuoles in the amphotericin B treated group represent the morphologic effect of intrarenal vasoconstriction caused by amphotericin B therapy. Nephrocalcinosis was observed in all biopsies and appeared to originate by precipitation of calcium salts in tubular casts.     

The role of percutaneous nephrostomy in the management of obstructing candidiasis of the urinary tract in infants

We report on 5 neonates with obstructive urinary tract candidiasis in whom percutaneous nephrostomy had a major role in management. The advantages of percutaneous nephrostomy in this setting include prompt drainage of the obstructed renal pelvis or ureter, direct access to obtain specimens from the renal pelvis to confirm the diagnosis, direct irrigation of the fungus balls with amphotericin B and an access route for fragmentation of fungus balls by guide wire manipulation. In 3 cases percutaneous placement of the nephrostomy tube was successful in obtaining and maintaining access to the renal pelvis, while in 2 surgical intervention was required because of problems maintaining placement of the percutaneous catheters. Percutaneous nephrostomy with antegrade amphotericin B irrigation, coupled with systemic antifungal therapy, is the mainstay of treatment. The usefulness of ultrasonography in the early diagnosis of renal candidiasis also is emphasized.     

A randomized prospective trial of amphotericin B lipid emulsion versus dextrose colloidal solution in critically ill patients.

BACKGROUND: Amphotericin B is the agent of choice for most invasive fungal infections in critically ill patients. It is associated with at least a 50% incidence of nephrotoxicity, despite prophylactic measures such as sodium loading. Newer formulations of amphotericin B are available but are costly and have unknown bioavailability in critically ill patients. Previous trials in neutropenic and critically ill patients have demonstrated that mixing amphotericin B with 20% lipid solution (Intralipid; Clintec Nutrition, Deerfield, III) may decrease nephrotoxicity. METHODS: In this randomized, prospective clinical trial, patients with positive fungal blood cultures, tracheal/sputum cultures or peritoneal cavity cultures were randomized to receive either 0.5 mg/kg per day of amphotericin B dextrose or 1.0 mg/kg per day of amphotericin B lipid emulsion. Duration of therapy was determined by the primary care team. Weekly 24-hour creatinine clearance was measured until 2 weeks after amphotericin B therapy was completed. RESULTS: The two groups were similar based on age, white blood cell count, serum creatinine, and creatinine clearance at the beginning of therapy. The group receiving amphotericin B lipid emulsion had significantly less decrease in creatinine clearance compared with controls, despite receiving significantly more amphotericin B. CONCLUSION: Amphotericin B lipid emulsion can be given at a higher total cumulative dose than amphotericin B dextrose with less nephrotoxicity.     

Chronic amphotericin B nephrotoxicity in the rat: protective effect of calcium channel blockade

Amphotericin B is used despite predictable nephrotoxicity because it remains the most efficacious agent currently available for systemic fungal infections. It has been previously shown that calcium channel blockade prevents renal vasoconstriction and blunts the fall in glomerular filtration rate during acute amphotericin B infusion in the rat. Therefore, the effect of cotreatment with diltiazem on nephrotoxicity during chronic daily amphotericin therapy in rats was studied. Rats were given diltiazem (45 mg/kg, 1 h before and 1 h after amphotericin) or vehicle by gastric tube; and amphotericin B (5 mg/kg/day i.p.) for 10 days. Control rats received corresponding vehicles by gastric tube and daily i.p. infection. Renal function was determined 24 h after the last dose of amphotericin or vehicle. Serum creatinine rose significantly in rats receiving amphotericin alone (initial versus final, 0.50 +/- 0.07 versus 1.09 +/- 0.20 mg/dL; P less than 0.05) but not with amphotericin plus diltiazem (0.54 +/- 0.11 versus 0.84 +/- 0.23 mg/dL; P was not significant). Amphotericin rats had a marked decrease in glomerular filtration rate (amphotericin versus control, 0.28 +/- 0.04 versus 1.23 +/- 0.08 mL/min/g kidney wt; P less than 0.05) and renal plasma flow (1.63 +/- 0.19 versus 3.50 +/- 0.40 mL/min/g kidney wt; P less than 0.05). These adverse renal hemodynamic effects were prevented by cotreatment with diltiazem (amphotericin plus diltiazem; glomerular filtration rate, 0.82 +/- 0.18 mL/min/g kidney wt; P less than 0.05 versus amphotericin; P was not significant versus control; renal plasma flow, 3.24 +/- 0.63 mL/min/g kidney wt; P less than 0.05 versus amphotericin; P was not significant versus control).(ABSTRACT TRUNCATED AT 250 WORDS)     

Diagnosis and treatment of Candida vertebral osteomyelitis: clinical experience with a short course therapy of amphotericin B lipid complex

BACKGROUND: Musculoskeletal candidiasis occurs in some patients with candidemia resulting from organ infection, IV drug use, or indwelling central venous catheters. Diagnosis is often difficult because of vague symptomatology and a frequent afebrile course. CASE DESCRIPTION: Three patients with Candida vertebral osteomyelitis are presented. All followed the use of indwelling central venous access catheters and antimicrobial therapy between 6 months and 3 years earlier. In 2, fungemia with the same Candida spp. preceded the spondylodiskitis. These 3 patients bring to nearly 75 the number of reported individuals with what was once quite rare. Although IV amphotericin B doxycholate and fluconazole have usually been effective therapy over prolonged periods of time, we used liposomal amphotericin B to treat 2 of our 3 patients. Both received 5 mg/kg daily for 18-42 days that resulted in total disappearance of signs and symptoms. CONCLUSION: This relatively brief duration of therapy reduces treatment time and is cost-effective.     

Efficacy of cyclosporin in difficult-to-treat idiopathic membranous nephropathy

SUMMARY: Poor tolerance and the potential long-term toxicity have limited the widespread use of corticosteroids and cytotoxic drugs in the treatment of idiopathic membranous nephropathy (IMN). Cyclosporin A (CyA) has been proven to be a less toxic alternative, but its efficacy needs further confirmation. Cyclosporin A (2–3mg/kg per day) in combination with low-dose methylprednisolone (4mg/day) was given to 28 nephrotic patients with IMN who had failed to respond, or tolerate, or to complete treatments with steroids and/or cytotoxic drugs. the mean duration of treatment was 11 ± 7 months. Seven patients (25%) showed a complete remission of proteinuria, 17 (60%) a partial one, and four (15%) did not respond at all. the average time to achieve optimal remission was 4.2 ± 1.4 weeks following the initiation of therapy. In those who responded completely or partially, plasma creatinine (Per) did not change significantly from pre CyA levels during follow up (1.0 ± 0.3 vs 1.2 ± 0.3mg/dL, P =NS). the remaining four patients who had renal insufficiency already before CyA (mean Per: 2.1 ± 0.8mg/dL), showed a rapid deterioration of renal function after the initiation of CyA (mean Per: 3.1 ± 1.5 mg/dL, P <0.01), and as a consequence, the drug was discontinued. A mul-tivariate analysis on the clinical and histological features demonstrated that the degree of renal function impairment ( P <0.02), the percentage of obsolete glomeruli ( P <0.01), and the severity of interstitial fibrosis ( P <0.005) independently predicted the response to therapy. Low dose CyA is an effective and safe alternative treatment for patients with IMN and normal renal function. However, the drug should be given with caution to patients with established renal insufficiency.     

Renal effects of amphotericin B lipid complex

A study was conducted to compare the renal effects of amphotericin B lipid complex (ABLC), a lipid formulation of the widely used antifungal medication, with conventional amphotericin B (AmB) in the treatment of serious fungal infections, including invasive candidiasis, cryptococcal meningitis, and aspergillosis. The clinical experience of ABLC includes two types of open-label studies: randomized comparative (ABLC 5 mg/kg/d compared with AmB 0.6 to 1 mg/kg) and emergency use. In the comparative studies, changes in serum creatinine were evaluated three ways: doubling of the baseline value, an increase from < or = 1.5 mg/dL at baseline to > or = 1.5 mg/dL, and an increase from < or = 1.5 mg/dL at baseline to > or = 2.0 mg/dL. More patients in the AmB group reached these end points than in the ABLC group (P < or = 0.007), and the time needed to reach each of these end points was significantly shorter for the AmB group (P < or = 0.02). Increased serum creatinine was reported as an adverse event more frequently by patients receiving AmB than by patients receiving ABLC. In the emergency use study, a steady and statistically significant decrease in serum creatinine was observed among patients who started ABLC treatment with serum creatinine greater than 2.5 mg/dL due to prior AmB treatment. ABLC offers the physician a valuable, less-nephrotoxic alternative to AmB for the treatment of patients with severe, invasive fungal infections.     

Candida infection in surgical patients

Candida infections have become a common and serious problem in non-neutropenic general surgical patients. This paper reviews the etiologic factors, pathogenesis of systemic candidiasis, and the more common syndromes of infection in surgical patients. Prophylactic and systemic therapy is detailed. The most significant factor inCandida infections is depression of host immune function. Significant abnormalities of T-cells, monocytes, and neutrophils have been described in patients with systemicCandida infection and in patients shown to be at high risk of such infection (burned, malnourished, or septic patients). Systemic infection is a consequence of high density colonization at 1 or more sites. Topical therapy with nystatin, amphotericin B, or the imidazole derivatives is usually effective in terminating local colonization of skin lesions, the gastrointestinal tract, or the bladder. If local colonization is not controlled, the patient may progress to systemic infection. The primary diagnostic difficulty is determining when conversions to systemic infection has occurred. Serologic testing and blood culture techniques appear to be of value only late in the course of infection. For this reason, the assessment of culture results from multiple sites appears to be of value. Treatment is begun with systemic amphotericin if the patient is immunodepressed or has ≥ 3 sites positive forCandida. In nonneutropenic patients, relatively short therapy appears effective. Treatment of endocarditis requires several (4–6) weeks of therapy, and current evidence suggests that early surgery with valve replacement may improve survival.     

Cytomegalovirus infection following renal transplantation in patients administered low-dose rituximab induction therapy

Anti-CD20 antibody (rituximab) is recently being used as a B cell-depleting agent in renal transplantation (RTx). However, the incidence of infectious complications associated with rituximab therapy remains uncertain. We evaluated the incidence of cytomegalovirus (CMV) infection associated with rituximab therapy in RTx. A total of 83 patients were enrolled. The immunosuppressive regimen consisted of tacrolimus or cyclosporin, mycophenolate mofetil, methylprednisolone and basiliximab. In 54 patients, only one dose of rituximab (200 or 500 mg/kg body weight) was given before RTx. A total of 25 of 43 (58.1%) recipients who were CMV seropositive prior to RTx and who received rituximab induction therapy developed CMV infection, compared to 18 of 24 (75%) CMV seropositive recipients who did not receive rituximab therapy ( P  = 0.1676). A total of 8 of 11 patients who were CMV seronegative prior to RTx and who received rituximab developed CMV infection. However, CMV seroconversion was seen in all 8 of these infected patients. Low-dose rituximab induction therapy in renal transplant recipients appears to have no influence on the incidence of CMV infection and CMV seroconversion. However, we have to consider anti-CMV prophylaxis therapy, because of high incidents of CMV infection, especially for CMV seronegative recipients who received rituximab.     

Low-dose dopamine preserves renal blood flow in endotoxin shocked dogs treated with ibuprofen

Drugs that inhibit prostaglandin (PG) biosynthesis improve hemodynamics and survival in experimental endotoxic and septic shock. The therapeutic utility of these agents in the management of septic patients may be limited, however, by their tendency to decrease renal blood flow (RBF) in animals and humans stressed by experimental manipulations or disease states that promote renal vasoconstriction. In the present study, we addressed this question: can low-dose intravenous (iv) dopamine (4 micrograms/kg/min), a known renal vasodilator, improve renal perfusion in endotoxin-shocked dogs treated with the PG synthesis inhibitor, ibuprofen. RBF was measured in pentobarbital anesthetized dogs using an electromagnetic flow meter. After obtaining baseline hemodynamics, Escherichia coli endotoxin (1.5 mg/kg) was given iv. The dogs were randomized 30 min later into three groups: Group I received saline; Group II received ibuprofen (12.5 mg/kg, iv); Group III received ibuprofen plus dopamine. Comparison of Groups I and II revealed that ibuprofen increased mean arterial pressure (MAP) and systemic vascular resistance (SVR) (P less than 0.0001 and P = 0.002, respectively) and decreased RBF (P = 0.019). Adding low-dose dopamine (Group II vs Group III) did not significantly affect MAP or SVR, but did augment RBF (P less than 0.001). We conclude that low-dose dopamine improves renal hemodynamics in ibuprofen-treated endotoxemic dogs.     

Review of risk factors in four cases of cryptococcosis after heart transplantation

Cryptococcosis is a rare infection with high mortality in patients who have undergone heart transplantation (HT). In this study, we report four cases of the disease selected from our 328 HT cases (1.22%) between 1987 and 2007. The purpose of this study was to review risk factors for cryptococcosis after HT. Three of the four patients were men. The mean time from HT to diagnosis was 8.5 months (range, 3-17 months). Cryptococcosis was subcutaneous in one patient, systemic in one, and meningeal in two. One patient died. The Antifungal regimens included intravenous amphotericin B (amBisone) and oral fluconazole (Diflucan). Patients with diabetes mellitus or renal insufficiency, are hepatitis B carriers, have undergone repeat HT, or are receivings steroid therapy are susceptible to cryptococcosis. The recommend anticryptococcal therapy is amphotericin B, followed by oral fluconazole for at least 6 months. Early diagnosis with aggressive diagnostic techniques and a combination of therapies must be considered to reduce the risk of death in HT recipients with cryptococcosis.     

Preemptive prophylaxis with a lipid preparation of amphotericin B for invasive fungal infections in liver transplant recipients requiring renal replacement therapy

BACKGROUND: Posttransplant renal replacement therapy has been shown to be an independently significant risk factor for invasive fungal infections after liver transplantation. We assessed the efficacy of a lipid preparation of amphotericin B as prophylaxis for invasive fungal infections, directed toward liver transplant recipients requiring renal replacement therapy. METHODS: A total of 148 patients transplanted between 1990 and 1997 received no antifungal prophylaxis. Since 1997, 38 patients underwent liver transplantation; antifungal prophylaxis with a lipid preparation of amphotericin B was used in patients requiring renal replacement therapy. RESULTS: Fifteen percent (22 of 148) of the patients transplanted before 1997 required renal replacement therapy. In this cohort, the incidence of invasive fungal infections (36% vs. 7%, P=0.0007) and invasive aspergillosis (14% vs. 2%, P=0.02) was significantly higher in patients who required renal replacement therapy compared with those who did not. Since 1997, 29% (11 of 38) of the patients required renal replacement therapy and received antifungal prophylaxis. Invasive fungal infections occurred in 36% (8 of 22) of the patients who received no prophylaxis (patients before 1997), and 0% (0 of 11, P=0.03) in those who received antifungal prophylaxis (since 1997). Antifungal prophylaxis was independently associated with protection from fungal infection (P=0.017). No reduction in mortality with antifungal prophylaxis was documented. CONCLUSION: Prophylaxis with a lipid preparation of amphotericin B was associated with a significant reduction in invasive fungal infections in high-risk liver transplant recipients, i.e., those requiring renal replacement therapy. However, no beneficial effect on survival could be documented.     

Invasive candidiasis: its predisposing factors, usefulness and limitation of cultural study in its diagnosis, and consideration on the appropriate amphotericin B therapy

We have reviewed 38 patients with invasive candidiasis and examined its predisposing factors, usefulness and limitation of cultural study in its diagnosis, and effective usage of amphotericin B in its treatment. Invasive candidiasis was diagnosed in 2.4% of the patients admitted during the past 5 years. One of the most important predisposing factors for development of invasive candidiasis was extensive use of antibiotics. Destruction of the mechanical barrier against bacteria and fungi caused by endotracheal intubations and various catheterization was another important factor. Mucosal lesion of the gastrointestinal tract, including stress ulcer, non-specific inflammatory bowel disease and esophageal ulcer, was seen in 30% of the patients. These lesions were thought to be the portal of entry for candida to systemic dissemination. AMPH is the most effective antifungal agent. Total dose of 300 to 1000 mg was effective in the patients. Dosage over 1000 mg was associated with progressive decrease in creatinine clearance. This decrease was irreversible even after discontinuation of AMPH. Candidal overgrowth within the G1 tract was considered to precede invasive candidiasis. Oral AMPH administration was effective in such conditions.     

Caspofungin in the treatment of azole-refractory esophageal candidiasis in kidney transplant recipients

BACKGROUND: Infection is a common cause of morbidity and mortality in kidney transplant recipients. The incidence of esophageal and urogenital candidiasis in kidney and kidney-pancreas transplant recipients has not been well documented. Azoles are safe, effective agents to treat esophageal candidiasis. However, resistance to azoles is now becoming common. This study reports the use of caspofungin for the treatment of azole-resistant esophageal and urogenital candidiasis in kidney transplant recipients. PATIENTS AND METHODS: The incidence of esophageal and urogenital candidiasis was evaluated among 140 kidney transplantations and four combined kidney-pancreas transplants performed over a 2-year period. RESULTS: Twenty-two patients (15.7%) presented with esophageal candidiasis, while seven patients (5%) showed urogenital candidiasis. Thirteen patients with esophageal candidiasis (59%) and four patients (57%) with urogenital candidiasis did not improve after a week of azole treatment. A regimen of caspofungin was started in these patients, who tolerated the treatment. Urogenital candidiasis recurred in two patients 2 and 3 months after the treatment. One patient with esophageal candidiasis did not improve with caspofungin and was switched to amphotericin B therapy. There were no other recurrences of candidiasis among patients treated with caspofungin for a median follow-up of 8 months. CONCLUSIONS: Renal transplant patients remain at high risk for fungal infections. Although the number of patients was limited, the results of this study indicated that caspofungin is an effective, well-tolerated alternative for difficult-to-treat, azole-resistant candida infections in kidney and pancreas transplant recipients. The high costs of the drug limit the use of caspofungin as first-line antifungal therapy, reserving its use to recipients who had undergone unsuccessful azole therapy.     

Renal zygomycosis: an under-diagnosed cause of acute renal failure.

BACKGROUND: Invasive zygomycosis (mucormycosis) occurs predominantly in immunocompromised patients in whom it carries a grave prognosis. While renal involvement is not so uncommon in disseminated infection, isolated renal zygomycosis is rare. METHODS AND RESULTS: Forty-five patients with systemic zygomycosis were seen over a 12-year period from January 1986 to December 1997. Among these, 18 had renal involvement, nine with disseminated disease and nine with isolated renal zygomycosis. No underlying predisposing disease was identified in the majority of patients (72%). Renal involvement was confirmed at autopsy in 13 and by ante-mortem renal biopsy in five patients. The infection involved one kidney in five patients and was bilateral in the remaining. The manifestations included fever, flank pain, haematuria and pyuria with evidence of enlarged non-functioning kidneys on computerised tomography (CT). Of those with bilateral disease, 12 (92.3%) had anuric acute renal failure. Anti-fungal therapy was given to six patients (amphotericin B in mean total dose of 1.1 g) and of these only two with unilateral disease who also underwent nephrectomy survived while all the other 16 died. CONCLUSION: This study shows that renal zygomycosis has emerged as a cause of acute renal failure in the last decade since no patient with renal involvement was identified at our centre prior to 1986 even though autopsies have been done regularly in patients dying of unknown causes. Bilateral renal zygomycosis should be suspected in any patient who presents with haematuria, flank pain and otherwise unexplained anuric renal failure. Characteristic CT findings and an early renal biopsy can confirm the diagnosis and help in effective management of this serious disease.     

A new ancient irrigation therapy for childhood renal candidiasis

Methylene blue (MB) alone, MB metabolites in the urine and the effect of MB plus alkalization on Candida species were determined. MB was used for the treatment of childhood renal candidiasis (CRC) in 3 patients as an irrigating solution. Besides irrigation, fluconazole 3 mg/kg/day intravenously and MB 0.2 mg/kg/day were administered perorally. Urine cultures were cleared of Candida. DMSA scans obtained after 6 months showed no evidence of scarring. MB can be used for irrigation of the urinary tract, with fewer side effects than amphotericin B (AB). Additionally we advocate the use of ureteral catheters instead of nephrostomy in the treatment of CRC.