Disseminated microsporidiosis in a renal transplant recipient: case report and review of the literature.

Microsporidia are opportunistic pathogens that usually cause a limited disease in the gastrointestinal tract. Occasionally, they can cause disseminated disease. In solid organ transplant recipients, disseminated disease has been reported only rarely. We describe a 68-year-old woman who presented with fever, cough, and acute kidney injury 6 months after kidney transplantation. Dissemination was confirmed by identification of microsporidial spores in urine and bronchoalveolar lavage fluid. Polymerase chain reaction analysis identified the species as Encephalitozoon cuniculi.

Clinical predictors of relapse after treatment of primary gastrointestinal cytomegalovirus disease in solid organ transplant recipients.

Primary gastrointestinal cytomegalovirus (CMV) disease after solid organ transplantation (SOT) is difficult to treat and may relapse. Herein, we reviewed the clinical records of CMV D+/R- SOT recipients with biopsy-proven gastrointestinal CMV disease to determine predictors of relapse. The population consisted of 26 kidney (13 [50%]), liver (10 [38%]) and heart (3 [12%]) transplant recipients who developed gastrointestinal CMV disease at a median of 54 (interquartile range [IQR]: 40-70) days after stopping antiviral prophylaxis. Except for one patient, all received induction intravenous ganciclovir (mean+/-SD, 33.8+/-19.3 days) followed by valganciclovir (27.5+/-13.3 days) in 18 patients. Ten patients further received valganciclovir maintenance therapy (41.6+/-28.6 days). The median times to CMV PCR negativity in blood was 22.5 days (IQR: 16.5-30.7) and to normal endoscopic findings was 27.0 days (IQR: 21.0-33.5). CMV relapse, which occurred in seven (27%) patients, was significantly associated with extensive disease (p=0.03). CMV seroconversion, viral load, treatment duration, maintenance therapy and endoscopic findings at the end of therapy were not significantly associated with CMV relapse. In conclusion, an extensive involvement of the gastrointestinal tract was significantly associated with CMV relapse. However, endoscopic evidence of resolution of gastrointestinal disease did not necessarily translate into a lower risk of CMV relapse.

Phaeohyphomycosis due to Alternaria species in transplant recipients.

Alternaria species are members of a heterogeneous group of dematiaceous fungi that rarely cause opportunistic infections in transplant recipients. During a 20-year period from 1989 to 2008, 8 solid organ transplant recipients (63% males; median age, 48 years) developed Alternaria species infections at the Mayo Clinic. All patients were highly immunocompromised as evidenced by their receipt of multiple transplants, treatment of acute and chronic allograft rejection, and occurrence of other opportunistic infections. All patients presented with non-tender erythematous or violaceous skin papules, nodules, or pustules in exposed areas of the extremities. No case of visceral dissemination was observed. Itraconazole was the most common drug used for treatment, although voriconazole, posaconazole, and caspofungin could potentially be useful based on our limited clinical data and in vitro antifungal susceptibility testing. One patient was treated with voriconazole, while another patient who was refractory to itraconazole had rapid resolution of lesions after the addition of caspofungin. Attempts at antifungal therapy alone were unsuccessful; all patients eventually required surgical excision of lesions. In conclusion, Alternaria species are rare but increasingly recognized opportunistic infections among highly immunocompromised transplant recipients. Wide excisional surgery combined with prolonged systemic antifungal therapy and reduction in immunosuppressive regimens provided the best chance of cure. Although itraconazole remains the most common drug for treatment, this case series highlights the potential clinical utility of caspofungin, voriconazole, and posaconazole as alternative regimens.

Fatal disseminated aspergillosis following sequential heart and stem cell transplantation for systemic amyloidosis.

Infectious complications are a major cause of morbidity and mortality in transplant recipients. We describe a case of fatal disseminated aspergillosis immediately following autologous peripheral stem cell reconstitution in a patient who had undergone orthotopic heart transplantation for systemic amyloidosis. The case described suggests that the infectious risks in patients undergoing these sequential procedures may be distinct from those occurring in patients undergoing either procedure independently. Potential prophylactic and therapeutic interventions are discussed. Since this experimental and evolving approach for the management of systemic amyloidosis is potentially applicable to a limited number of patients, multicenter collaboration may be needed to further define the infectious risks in this unique subset of transplant recipients.

Prophylaxis of cytomegalovirus infection in liver transplantation: a randomized trial comparing a combination of ganciclovir and acyclovir to acyclovir. NIDDK Liver Transplantation Database.

BACKGROUND: The optimal prophylactic regimen to prevent cytomegalovirus (CMV) infection and disease in orthotopic liver-transplant patients remains to be established. We tested whether a combination of intravenous ganciclovir (GCV) followed by high dosages of oral acyclovir (ACV) for 4 months provided a higher degree of protection from CMV than oral ACV alone. METHODS: One hundred sixty-seven liver-transplant recipients were randomized to receive 120 days of antiviral treatment starting at the time of transplantation consisting of either ACV 800 mg orally four times daily (n=84) or 14 days of GCV 5 mg/kg intravenously every 12 hr followed by oral ACV 800 mg four times daily (n=83). Prospective laboratory and clinical surveillance was performed to determine primary endpoints (onset of CMV infection and CMV disease) and secondary endpoints (rates of fungal and bacterial infection, allograft rejection, and survival after transplantation). One-year event rates are presented as cumulative percentages. RESULTS: During the first year after transplantation, CMV infection developed in 57% of patients treated with ACV and in 37% of patients treated with GCV + ACV (P=0.001). CMV disease developed in 23% of patients treated with ACV and in 11% of patients treated with GCV + ACV (P=0.03). In seronegative recipients of allografts from CMV-seropositive donors (D+/R-), CMV disease developed in 58% of patients treated with ACV and in 25% of patients treated with GCV + ACV (P=0.04). In the D+/R- group, 54% of patients treated with ACV and 17% of patients treated with GCV + ACV developed infection with Candida albicans (P=0.05). CONCLUSIONS: Prophylaxis of CMV infection in liver-transplant patients with 14 days of intravenous GCV followed by high-dosage oral ACV is more effective than high-dosage oral ACV alone at reducing CMV infection and disease, even for patients in the D+/R- CMV serological group.

Clinical comparison of isolator, Septi-Chek, nonvented tryptic soy broth, and direct agar plating combined with thioglycolate broth for diagnosing spontaneous bacterial peritonitis.

Spontaneous bacterial peritonitis is a life-threatening complication of cirrhotic ascites. Optimal patient management depends on the isolation of the causal organism from ascitic fluid. To evaluate culture techniques for the diagnosis of spontaneous bacterial peritonitis, we prospectively compared three blood culture system, the Isolator system, a lysis-centrifugation system, the Septi-Chek system, a biphasic culture system, and a nonvented tryptic soy broth system, all inoculated at the bedside, and our standard method of direct inoculation of specimens after transport to the laboratory onto agar plates and into thioglycolate broth. The results showed that the Septi-Chek and nonvented tryptic soy broth systems each recovered statistically significantly more pathogens than either the Isolator system (P = 0.0084) or the standard method (P = 0.00098). The Isolator system recovered more pathogens than the standard plate method, but this difference was not statistically significant. Both the Isolator system and the standard plate method recovered more contaminating microorganisms than the Septi-Chek or nonvented tryptic soy broth system. The Isolator system required the most processing time compared with the processing times required by any other method.

A case of Aspergillus fumigatus peritonitis complicating liver transplantation.

A 55-year-old male underwent orthotopic liver transplantation for sub-fulminant hepatitis B/delta infection superimposed on probable genetic hemochromatosis with early cirrhosis. Pre-operatively, he demonstrated serologic evidence of cytomegalovirus reactivation and developed cytomegalovirus viremia when ganciclovir was discontinued post-operatively. His post-operative course was complicated by chronic ductopenic rejection, biliary anastomotic leak, and persistent confusion and malaise. At the time of laparotomy for repair of the bile leak, nodular peritoneal lesions were noted, with biopsy and culture showing angioinvasive Aspergillus fumigatus. Despite administration of amphotericin B, the patient continued to have culture-confirmed evidence of infection at follow-up peritoneoscopy. Oral itraconazole was begun, but the patient died of liver failure secondary to progressive ductolpenic rejection. At autopsy, Aspergillus organisms were seen in histologic sections taken from the small bowel; there was no evidence of disseminated disease.

A prospective study of the polymerase chain reaction for detection of herpes simplex virus in cerebrospinal fluid submitted to the clinical virology laboratory.

Polymerase chain reaction (PCR) was prospectively performed with cerebrospinal fluid (CSF) from 51 patients whose CSF was available for analysis and was submitted for viral culture and/or herpes simplex virus (HSV) serology and 20 patients whose CSF was submitted exclusively to the Clinical Biochemistry Laboratory. Primers were used that flanked a 92 bp segment of the HSV DNA polymerase gene (35 cycles). Amplified products were electrophoresed on agarose gel, blotted onto nylon membrane, and probed with a 32P-labelled sequence internal to the primers. For nested PCR, 1 microliter of PCR product was amplified for an additional 35 cycles before electrophoresis and Southern blot analysis. Review of the clinical records revealed that 15 patients had central nervous system (CNS) infections. Specific HSV DNA sequences were detected in CSF specimens of three of the individuals [PCR(2), nested PCR(1)]. Two of these patients had disseminated HSV infection including encephalitis and one patient had aseptic meningitis. The diagnoses of the 12 patients with CNS infection who did not have HSV DNA detected in CSF included encephalitis [varicella-zoster virus (1), cytomegalovirus (1), Mycoplasma pneumoniae (1)], meningitis [Neisseria meningitidis (1), Coccidioides immitis (1), Enterovirus (1), aseptic meningitis (1)], varicella-zoster radiculitis (2), human immunodeficiency virus dementia (2), and transverse myelitis due to Epstein-Barr virus (1). Importantly, HSV DNA was also not detected in the CSF of the 36 patients who did not have CNS infection and 20 samples submitted exclusively to the Clinical Biochemistry Laboratory. Our findings demonstrate the utility of PCR as a rapid, non-invasive method for the routine laboratory diagnosis of CNS infection due to HSV.

Strategies for prevention of infection after cardiac transplantation.

Infection remains a major cause of morbidity and mortality after cardiac transplantation. Most infections occur during the first few months after transplantation. Although late infection does occur, the risk of infection during maintenance immunosuppression is low in the absence of recurrent rejection that necessitates augmentation of suppression of the immune response. Before cardiac transplantation, the risk factors for infectious disease in potential candidates should be assessed. A detailed history of past infections should be elicited, and patients should be screened for the presence of active indolent infection. In addition, potential donors must be thoroughly assessed for organ-transmittable infection. Many common infections that may occur after cardiac transplantation can be prevented with the use of appropriate prophylactic regimens directed toward cytomegalovirus, Toxoplasma gondii, Pneumocystis carinii, and herpes simplex virus. Periodic surveillance serologic tests and cultures after cardiac transplantation facilitate early diagnosis and prompt institution of appropriate therapy.

Vancomycin.

Vancomycin is a glycopeptide antibiotic that is active against staphylococci, streptococci, and other gram-positive bacteria. It is the drug of choice for the treatment of infections due to methicillin-resistant staphylococci, Corynebacterium jeikeium, and multiply resistant strains of Streptococcus pneumoniae. Vancomycin is an alternative treatment for serious staphylococcal and streptococcal infections, including endocarditis, when allergy precludes the use of penicillins and cephalosporins. Vancomycin is bactericidal against most strains of staphylococci and nonenterococcal streptococci. Although rare strains of staphylococci and enterococci that are resistant to vancomycin have been reported, bacterial resistance has thus far not emerged as a major clinical problem despite widespread use of vancomycin. When therapy is monitored by periodic determinations of serum concentrations of the drug and rapid infusion rates are avoided, vancomycin is rarely associated with serious toxicity.

De novo systemic vasculitis in a renal transplant recipient.

Abdominal pain, oligoarthritis, macular skin rash, and urine sediment with more than 100 erythrocytes per high-power field and proteinuria developed in a renal transplant recipient who had no prior history of an underlying connective tissue disease. A polyarteritis-type necrotizing vasculitis was detected in the small bowel mesentery. A search for other etiologic factors revealed none. This case demonstrates that de novo vasculitis can develop in renal transplant recipients despite adequate immunosuppressive regimens and may respond to increased dosages of corticosteroids.

Pancreas transplantation at Mayo: III. Multidisciplinary management.

Although pancreas transplantation is a complicated procedure, a good level of success has been achieved because of the introduction of cyclosporine for immunosuppression, improved methods for diagnosing rejection, and a multidisciplinary approach to management. Our immunosuppressive regimen was quadruple therapy with induction by using Minnesota antilymphoblastic globulin. A biopsy technique was instituted in which the pancreas specimens were obtained under cystoscopic direction during episodes of hypoamylasuria. The criteria for rejection episodes were not only biochemical abnormalities but also histologic confirmation and a follow-up to exclude other causes of graft dysfunction. Infectious disease management included use of oral selective bowel decontamination for 3 weeks after transplantation. At the Mayo Clinic between October 1987 and December 1988, 16 patients received pancreaticoduodenal allografts (both kidney and pancreas in 13 and pancreas only in 3 after a prior successful kidney transplantation). In two pancreas and one kidney allograft, function was lost. One patient died of multiorgan failure. The cystoscopically directed biopsy technique was performed 23 times with minimal complications and a 93% success rate. The metabolic results have been excellent; the glycosylated hemoglobulin level was normal 3 to 6 months after transplantation. The quality of life was significantly improved in almost all patients. Nutritional assessment revealed little deterioration after transplantation. With a multidisciplinary approach, the needed answers about the effect of pancreas transplantation on the degenerative complications of diabetes should be forthcoming.

Antimicrobial agents in urinary tract infections.

Urinary tract infections are commonly encountered in clinical practice and are usually readily treatable. Although many antimicrobial agents that have been available for some time remain effective in the eradication of bacteriuria, the recent introduction of the fluoroquinolone norfloxacin represents an important addition to the therapeutic armamentarium. The efficacy of single-dose therapy with antimicrobial agents such as trimethoprim-sulfamethoxazole or amoxicillin has been shown to be similar to that with conventional (7- to 10-day) treatment in women with uncomplicated lower urinary tract infections. The long-term administration of agents such as trimethoprim-sulfamethoxazole or nitrofurantoin in low doses is usually effective for suppression or prophylaxis of recurrent bacteriuria.

Vancomycin.

Vancomycin is a narrow-spectrum bactericidal antibiotic used primarily for treatment of serious staphylococcal infections. It is the alternative therapy of choice when the penicillins and cephalosporins cannot be used. Vancomycin is also used in (1) methicillin-resistant Staphylococcus aureus infections; (2) streptococcal endocarditis in conjunction with an aminoglycoside in patients intolerant of penicillin or ampicillin; (3) infections, including those involving prosthetic devices, caused by gram-positive organisms with multiple antibiotic resistance; (4) antibiotic-induced enterocolitis caused by Clostridium difficile; and (5) prophylaxis for endocarditis in patients who are at risk and cannot tolerate a penicillin, cephalosporin, or erythromycin. The major toxic effect associated with the use of vancomycin is ototoxicity, which may develop when serum levels exceed 30 micrograms/ml.

Bacterial interference by anaerobic species isolated from human feces.

Eighty-four anaerobic fecal isolates obtained from five healthy volunteers were tested for their ability to inhibit in vitro growth of eight species of Enterobacteriaceae, four species of faculative gram-positive cocci, and Pseudomonas aeruginosa. Forty-nine of the 84 anaerobic isolates (58%) inhibited the growth of at least one indicator bacterium. Isolates of Bacteroides and Bifidobacterium spp. were most consistently inhibitory. Anaerobic cocci and clostridia were infrequently inhibitory; eubacteria showed no inhibitory activity. Serratia marcescens was the indicator most often inhibited; 54% of all anaerobic isolates tested, all of nine Bifidobacterium isolates and 33 of 43 Bacteroides isolates inhibited this organism. No anaerobes inhibited the growth of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Citrobacter freundii, Citrobacter diversus or Streptococcus faecalis.