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SACCHAROMYCES CEREVISIAE INFECTIONS IN CHILDREN

1998; Lippincott Williams & Wilkins; Volume: 17; Issue: 12 Linguagem: Inglês

10.1097/00006454-199812000-00022

1532-0987

N. F. Fiore, James H. Conway, Karen W. West, Martin B. Kleiman,

Milk Quality and Mastitis in Dairy Cows

Saccharomyces cerevisiae, often referred to as brewer's or baker's yeast, is an ascomycetous yeast and a common plant saprophyte. Humans are frequently exposed through ingestion of foods, beverages and dietary supplements. S. cerevisiae can be a part of the normal intestinal and vaginal flora, and it rarely acts as a pathogen in humans.1 Excepting vaginitis 22 cases of clinical infection have been reported in the English language literature,2-17 the youngest of whom was 17 years old.12 Only 9 cases were associated with fungemia, with 4 patients surviving.3, 5, 6, 8, 9, 11, 13, 15 Infections are usually opportunistic.2-17 We describe 3 children with S. cerevisiae fungemia, of whom 2 survived, review previously reported fungemia cases and summarize recommendations for management. Case reports.Case 1. A 10-year-old girl with minimally symptomatic cystic fibrosis underwent evaluation for weight loss and abdominal distention during a 6-month period in 1993. She was found to have a partial bowel obstruction. Colonic biopsies showed mild inflammation and she was treated with 6-mercaptopurine and prednisone for presumed Crohn's disease. A transjugular intrahepatic portacaval shunt was required to treat refractory ascites. Six months later she was referred to the James Whitcomb Riley Hospital for Children for evaluation of malnutrition, worsening ascites and symptoms of intestinal obstruction. She had near total obstruction of the descending colon and biliary cirrhosis. During a prolonged hospitalization she developed progressive renal, hepatic and pulmonary failure and received several courses of vancomycin, tobramycin and ceftazidime for presumed sepsis. After an end ileostomy for complete colonic obstruction, S. cerevisiae was recovered from blood drawn from central and peripheral veins on all but two of the ensuing 13 postoperative days. Amphotericin B, 0.75 mg/kg/day iv, was begun on Day 4 after surgery. The central venous catheter was removed, but because of limited venous access and the presence of refractory coagulopathy, a new central venous catheter could be inserted at the same site only with the aid of a guide wire. Fungemia persisted for the entire course of amphotericin B. She developed third degree heart block and died after receiving amphotericin B for 9 days. Postmortem lung, blood and mitral valve thrombus cultures grew S. cerevisiae. Case 2. A former 28-week gestation, ventilator-dependent infant had frequent episodes of presumed sepsis treated empirically with vancomycin, cefotaxime and/or gentamicin. Underlying problems included tracheoesophageal fistula repair, gastrostomy tube placement, agenesis of the left lung, hyaline membrane disease, patent ductus arteriosus requiring surgical ligation, obstructive uropathy of a solitary kidney requiring enteral or intravenous antibiotic prophylaxis and dexamethasone therapy for chronic lung disease. At 10 weeks of age he developed agitation and feeding intolerance and was found to have a white blood cell count of 29 400 cells/mm3, with 61% neutrophils, 21% band forms and a platelet count of 512 000/mm3. Blood cultures grew Klebsiella pneumoniae and he was treated with intravenous cefotaxime and gentamicin. Cultures of peripheral venous and arterial blood also grew S. cerevisiae on 2 consecutive days. Central venous catheters were removed, and treatment with amphotericin B (1 mg/kg/day) was begun and continued for 30 days. All subsequent blood cultures were sterile. Urine and cerebrospinal fluid were normal. Echocardiogram and ultrasonography of the abdomen showed no evidence of localized infection. The patient survived and infection has not recurred. Case 3. A 7-year-old boy was referred in November, 1997, for evaluation of fever, chills and vomiting. He had gastros-chisis and a partial small bowel resection during infancy and was maintained on central venous hyperalimentation which was complicated by multiple episodes of central venous catheter infections. Initial laboratory examinations revealed a white blood cell count of 1300/mm3, with 46% neutrophils, 14% band forms, 35% lymphocytes and 4% monocytes. K. pneumoniae and Enterobacter cloacae were recovered from each of two blood cultures, and S. cerevisiae was isolated from the same cultures later. The central venous catheter was removed and amphotericin B (1 mg/kg/day) therapy was begun. Catheter tip cultures grew E. cloacae only. Echocardiography and abdominal ultrasonography were normal. All subsequent blood cultures were negative. The patient received cefotaxime and gentamicin for 14 days and amphotericin B for 21 days. Symptoms resolved promptly, and multiple blood cultures during and after treatment were sterile. Subsequent evaluation revealed T lymphopenia, with normal lymphocyte transformation by mitogen stimulation and normal humoral immunity. HIV enzyme-linked immunosorbent assay antibody testing, HIV RNA polymerase chain reactions and DiGeorge probes are all negative. The patient is now lost to further follow-up. Discussion.S. cerevisiae is a common environmental saprophyte and can colonize the pharynx, pulmonary tree, skin, intestinal tract or vagina, especially in patients with chronic illnesses.1, 18 Greer et al.19 identified Saccharomyces as a commensal in 7% of expectorated sputum samples obtained from patients with pulmonary tuberculosis. Similarly Kiehn and Armstrong18 speciated 3340 yeast specimens isolated from 2208 cancer patients; S. cerevisiae was recovered from 24 patients; 19 of the samples were from sputum. Fungemia was not reported. In instances in which S. cerevisiae has been pathogenic, the portal of entry is presumed to result from contamination of indwelling catheters, migration across damaged mucosal gastrointestinal barriers or pulmonary infection. In addition to host susceptibility data also suggest that specific genetic properties of S. cerevisiae facilitate persistence or proliferation of clinical isolates. Virulence of clinical isolates has been shown to be a genetically dominant trait associated with laboratory growth temperatures. Inoculation of mice with clinical isolates results in fungal proliferation whereas nonclinical isolates are readily cleared.20 DNA "fingerprinting" of isolates recovered from patients with vaginitis have been indistinguishable from strains used as food additives and also suggest that human-to-human transmission does occur.21 Laboratory identification of S. cerevisiae isolates is performed with standard methods.22 Technology using polymerase chain reaction ribotyping identifies strains to the species level and may prove useful for rapid diagnosis.23 S. cerevisiae isolates are relatively resistant to antifungal agents in vitro. Among 76 clinical isolates of S. cerevisiae tested with antifungal susceptibility broth microdilutions, minimum inhibitory concentrations for amphotericin B and flucytosine displayed consistent susceptibility at concentrations readily attained in serum with standard dosages. MICs for azole compounds were elevated and in the ranges seen in Candida krusei, Candida tropicalis and Torulopsis glabrata.24 The English language literature contains reports of 22 patients with opportunistic infections caused by S. cerevisiae. Predisposing features included immunosuppression, broad spectrum or extensive antibiotic therapy and indwelling foreign bodies (prosthetic heart valves, central venous catheters, peritoneal dialysis catheters). Anatomic sites of infection included kidney, peritoneum, lung and focal abscesses of liver and spleen. In some cases multifocal disease was recognized postmortem.2-17 Among surviving patients with focal infections treatment included focal debridement and amphotericin B and/or ketoconazole.11, 12 Fungemia with S. cerevisiae was reported in 9 patients, all of whom were adults.3, 5, 6, 8, 9, 11, 13, 15 Four of the 9 survived (44%). Prolonged fever in an otherwise healthy 68 year-old patient resolved without treatment after cessation of large oral doses of brewer's yeast6; the remaining 3 patients were cured with amphotericin B treatment.3, 8, 9 Of the 5 who died only 1 was treated with amphotericin B.11 Predisposing conditions among survivors included HIV infection,9 recent prosthetic valve surgery3 and hyperalimentation after burns.8 Three of 5 nonsurvivors had a hematologic or oncologic disorder.11, 15 All patients with polymicrobial sepsis died.11, 13 In our patients common risk factors for S. cerevisiae fungemia included prolonged and/or prior broad spectrum antibiotic therapy, indwelling central venous catheters and structural defects of the gastrointestinal tract with operative repair. Our patients were epidemiologically, and their illnesses temporally, unrelated. Although intestinal colonization was examined neither before nor after the illnesses, the intestine would appear to be a likely site for colonization; compromised intestinal integrity could have predisposed to invasive infection. The three children were treated with amphotericin B, and both survivors had central venous catheters removed as part of their therapy. The persistence of fungemia in our patient who died probably resulted from infective endocarditis and unsuccessful attempts to establish central venous access at an alternative site. In contrast to prior reports both survivors had polymicrobial sepsis. Invasive infections caused by S. cerevisiae are complicated by overall case fatality rates as high as 50%. Optimal management of S. cerevisiae infections includes drainage of identified foci, administration of antifungal agents and removal/replacement of infected foreign bodies, especially indwelling venous catheters. Although comparative therapeutic trials are not available for this rare pathogen, amphotericin B, with or without flucytosine, is the treatment of choice. Nicholas F. Fiore, M.D. James H. Conway, M.D. Karen W. West, M.D. Martin B. Kleiman, M.D. Section of Pediatric Surgery; Department of Surgery (NFF, KWW) Section of Infectious Diseases; Department of Pediatrics (JHC, MBK) Indiana University School of Medicine; James Whitcomb Riley Hospital for Children; Indianapolis, IN