Resolutive Candida utilis fungemia in a nonneutropenic patient

We report here the second case of Candida utilis infection in humans. The patient was apparently immunocompetent, had no central catheter, and survived an 8-day fungemia. Genomic analysis confirmed the conspecificity of medical and industrial strains of C. utilis and that of the anamorphic yeast C. utilis with the teleomorphic yeast Pichia jadinii.     

Quantitative urine cultures do not reliably detect renal candidiasis in rabbits

The significance of quantitative urine cultures in patients at risk for hematogenous disseminated candidiasis is controversial. While various concentrations of Candida spp. in urine have been suggested as critical cutoff points in the diagnosis of renal candidiasis, other investigators consider quantitative cultures less critical in diagnosing upper tract infections. To determine the significance of quantitative urine cultures in renal candidiasis, we studied serial quantitative urinary cultures of Candida albicans in a rabbit model of hematogenous infection. Of 197 urine samples from 34 infected animals, 144 were culture positive, with a sensitivity of 73.1% for urine cultures and a lower limit of detection of 10 CFU/ml. The yield of urine cultures varied according to severity and duration of infection. The mean renal and urinary concentrations of C. albicans from rabbits with subacute candidiasis differed significantly from those from rabbits with acute candidiasis (P = 0.013 and P < or = 0.001, respectively). During the first 4 days of subacute renal candidiasis, more than one-half of all urine cultures were negative for C. albicans. Only 12 (8.1%) of 148 urine cultures in animals with subacute renal candidiasis had concentrations of > 10(3) CFU/ml, 2.7% had concentrations of > 10(4) CFU/ml, and none were > or = 10(5) CFU/ml. By comparison, all urine cultures from the animals with lethal acute renal candidiasis had higher concentrations of C. albicans and were positive throughout the course of infection. Urinary concentrations of C. albicans were not predictive of the amount of Candida in the kidney (r < or = 0.49) and did not correlate with survival (r = 0.0232). However, the renal concentration of C. albicans (in CFU/gram) inversely correlated with the duration of survival (in days) of rabbits with renal candidiasis (r = 0.76; P < 0.001). These findings indicate that a negative urine culture in rabbits does not preclude the presence of renal candidiasis. The interpretation of a urine culture positive at any concentration, on the other hand, must involve an analysis of the risk factors for renal candidiasis, for any urinary concentration of C. albicans may reflect kidney infection.     

Production of the carotenoids lycopene, beta-carotene, and astaxanthin in the food yeast Candida utilis

The food-grade yeast Candida utilis has been engineered to confer a novel biosynthetic pathway for the production of carotenoids such as lycopene, beta-carotene, and astaxanthin. The exogenous carotenoid biosynthesis genes were derived from the epiphytic bacterium Erwinia uredovora and the marine bacterium Agrobacterium aurantiacum. The carotenoid biosynthesis genes were individually modified based on the codon usage of the C. utilis glyceraldehyde 3-phosphate dehydrogenase gene and expressed in C. utilis under the control of the constitutive promotes and terminators derived from C. utilis. The resultant yeast strains accumulated lycopene, beta-carotene, and astaxanthin in the cells at 1.1, 0.4, and 0.4 mg per g (dry weight) of cells, respectively. This was considered to be a result of the carbon flow into ergosterol biosynthesis being partially redirected to the nonendogenous pathway for carotenoid production.     

A vaccine and monoclonal antibodies that enhance mouse resistance to Candida albicans vaginal infection

We previously reported that a vaccine composed of liposome-mannan complexes of Candida albicans (L-mann) stimulates mice to produce protective antibodies against disseminated candidiasis. An immunoglobulin M (IgM) monoclonal antibody (MAb), B6.1, specific for a beta-1,2-mannotriose in the complexes protects against the disease, whereas MAb B6 does not. In the present study, the vaccine and MAbs B6.1 and B6 were tested for the ability to protect against Candida vaginal infection, established by intravaginal (i.vg.) inoculation of yeast cells in mice maintained in pseudoestrus. Fungal CFU in each vagina was determined to assess the severity of infection. Mice vaccinated before infection developed about 62% fewer vaginal CFU than nonimmunized controls. Naive mice that received polyclonal antiserum (from vaccinated mice) i.vg. before infection had 60% fewer CFU than controls. The serum protective factor was stable at 56 degreesC, but C. albicans cells absorbed this factor. Mice given MAb B6.1 i.vg. after infection was established had fewer Candida CFU in vaginal tissue than control mice given buffer instead of antibody. MAbs B6.1 and B6 given intraperitoneally before infection protected mice, but MAbs preabsorbed with yeast cells did not. MAb B6.1 also protected against C. tropicalis vaginal infection, but MAb B6 did not. The protective activities of MAbs B6.1 and B6 appeared to be specific because an irrelevant IgM carbohydrate-specific MAb and an irrelevant IgG protein-specific MAb were not protective; also, MAb B6.1 did not affect development of vaginal chlamydial infection. These studies show that an appropriate antibody response, or administration of protective antibodies, can help the host to resist Candida vaginal infection.     

Partial deletion of 18p and partial duplication of 18q caused by a paternal pericentric inversion

The frequency of urinary infection was determined using quantitative microbiology in 172 insulin-dependent diabetic patients repeatedly being tested for microalbuminuria over 18 months on at least six occasions. The point prevalence of urinary infection at first screening for microalbuminuria was 3%. Over the period of study, 20 of the patients (12%) showed evidence of urinary infection, defined as a pure growth of a recognized pathogen > 10(7)I-1. Infection was more common in women than men (20% vs 5%, p < 0.01) and was significantly associated with the presence of peripheral neuropathy (p < 0.05). Infection was not related to patient age, duration of diabetes, glycaemia, blood pressure, retinopathy or autonomic neuropathy. There were no significant within-patient differences in albumin excretion, glycaemic control or blood pressure in relation to the presence and absence of urinary infection. In only one patient (5%) did urinary infection significantly increase the urinary albumin excretion and this was associated with pyuria. We conclude that the presence of urinary infection does not apparently affect the measurement of urinary albumin excretion unless pyuria is present. Unless diabetic patients are symptomatic, examination of the urine for infection is probably unwarranted when testing for microalbuminuria.     

Safety of intrauterine contraceptive devices during MR imaging

OBJECTIVE: We report a case of candidiasis of the upper urinary tract that presented as acute renal failure associated with septic syndrome. The patient initially required hemodialysis. Right hydronephrosis and perirenal collection were observed on ultrasound examination. METHODS: A percutaneous nephrostomy was performed. Nephrostomy urine cytology and cultures were positive for Candida tropicalis. An anterograde pyelography showed a 'fungus ball' in the urinary tract. RESULTS: Therapy with oral fluconazole and percutaneous amphotericin B achieved excellent results. CONCLUSIONS: Candidiasic urinary infection of the upper urinary tract often produces obstructive uropathy requiring percutaneous nephrostomy, which can also be used to instill amphotericin B. Combination therapy with amphotericin B and fluconazole can achieve excellent results.     

Idiopathic swelling of the lower lip associated with topical anaesthesia. Report of three cases

Aim of the present study was to evaluate the effect of cefamandole, cefuroxime and cefoxitin on the level of gastrointestinal (GI) colonization by Candida albicans in humans. Twenty-eight adult patients received one of these three cephalosporins for 10 days, as treatment of infection, and were studied prospectively. Quantitative stool cultures for yeasts were performed immediately before, at the end, and 1 week after discontinuation of treatment. All three antibiotics caused an increase of the yeast concentration in the fecal flora. The increase caused by cefoxitin was the highest (2.5 log10 CFU/g of stool). Our results suggest that the cephalosporins tested cause minor increases of the colonization of the GI tract by C. albicans.     

Isolation and sequence analysis of the orotidine-5'-phosphate decarboxylase gene (URA3) of Candida utilis. Comparison with the OMP decarboxylase gene family

The URA3 gene of Candida utilis encoding orotidine-5'-phosphate decarboxylase enzyme was isolated by complementation in Escherichia coli pyrF mutation. The deduced amino-acid sequence is highly similar to that of the Ura3 proteins from other yeast and fungal species. An extensive analysis of the family of orotidine-5'-phosphate decarboxylase is shown. The URA3 gene of C. utilis was able to complement functionally the ura3 mutation of Saccharomyces cerevisiae.     

The surgical treatment of aneurysms of the abdominal aorta

The sputum specimens from 1363 patients at the age of 16 to 65 years with nonspecific pulmonary diseases and the pleural exudate specimens from 325 patients were tested for fungi in 1989-1994. The etiological significance of Candida was stated at a concentration of > 10(5) GFU per 1 ml of the sputum. The identification was performed by the routine methods. An increase in the rate of the fungi isolation was studied in the time course of the observation: 15.3 +/- 1.9 per cent in 1989 and 31.6 +/- 3.4 per cent in 1994. The fungi were more frequently isolated from the patients with lung abscesses (38.0 +/- 4.1 per cent of the cases). In the patients with pyothorax the fungi were isolated from the pleural exudate specimens only in 6.8 +/- 1.4 per cent of the cases. The groups of risk of the susceptibility to Candida were revealed. They included patients at the age of 21 to 30 years and above 60. Out of 484 Candida isolates 80.7 per cent belonged to C. albicans, 4.2 per cent to C. tropicalis, 2.1 per cent to C. kefyr and 1.8 per cent to C. krusei. The isolates of C. parapsilosis, C. guillermoudii, C. utilis and C. brumptii were rate. The isolates were highly susceptible to nystatin (91,8 per cent) and lowly susceptible to levorin (35.4 per cent), amphoglucamine (24.7 per cent) and ketokonazol (16.8 per cent).     

Infectious crystalline keratopathy caused by Candida guilliermondii

PURPOSE: To describe the manifestations of infectious crystalline keratopathy caused by Candida guilliermondii in a corneal transplant performed for pseudophakic bullous keratopathy. METHOD: Case report. RESULTS: Candida guilliermondii was identified as the causative organism of an indolent infectious crystalline keratopathy. Incisional lamellar biopsy provided diagnostic culture and histopathologic results. Histopathology showed aggregates of yeast elements between corneal stromal lamellae, without inflammation. The infection progressed despite a 6-week course of topical amphotericin B and an additional 6-week course of topical and oral fluconazole. Repeat penetrating keratoplasty resulted in clear graft, with no recurrent infection. CONCLUSIONS: Fungal keratopathy should be included in the differential diagnosis of infectious crystalline keratopathy. Numerous Candida species have been isolated in addition to the most common causative bacterial organism, Streptococcus viridans. Candida guilliermondii is yet one more causative agent of infectious crystalline keratopathy. Candida guilliermondii, a rare human pathogen, was resistant to medical therapy in this case.     

Evaluation of BBL CHROMagar orientation medium for detection and presumptive identification of urinary tract pathogens

The microbiological performance of BBL CHROMagar Orientation medium and CPS ID2 agar was compared to that of Columbia agar with 5% sheep blood and MacConkey agar without crystal violet for the enumeration and presumptive identification of bacteria responsible for urinary tract infections. Of a total of 658 clinical urine specimens, 118 specimens yielded no growth, 402 specimens yielded growth with cell counts of > or = 10(5) CFU/ml, and 138 specimens yielded growth with cell counts of < 10(5) CFU/ml. Of the specimens with cell counts of > or = 10(5) CFU/ml, 163 were pure cultures and 239 were mixed cultures. A total of 266 Escherichia coli organisms were isolated on both chromogenic media, 260 were isolated on blood agar, and 248 were isolated on MacConkey agar. One strain (0.4%) failed to develop the expected pink color on CHROMagar Orientation medium, and 23 strains (8.7%) failed to develop the expected pink color on CPS ID2 agar. Enterococci (CHROMagar Orientation medium, n = 266; CPS ID2 agar, n = 265) produced small blue-green colonies on both chromogenic media. Fifty of the mixed cultures contained enterococci that were detected only on the chromogenic media. The Klebsiella-Enterobacter-Serratia (KES) and the Proteus-Morganella-Providencia (PMP) groups could be identified on both chromogenic media. Of 66 isolates of the KES group, 63 grew with the expected color on CHROMagar Orientation medium and 58 of 64 isolates grew with the expected color on CPS ID2 agar. Other microorganisms required further identification. The use of chromogenic medium formulations offers a time-saving method for the reliable detection, enumeration, and presumptive identification of urinary tract pathogens. One of the greatest advantages of these media is the easy recognition of mixed cultures.     

Value of assessing cryptococcal antigen in bronchoalveolar lavage and sputum specimens from patients with AIDS

Cryptococcus neoformans has become a significant opportunistic pathogen, accounting for 8-10% of infectious complications in patients with AIDS. When encapsulated yeast cells are observed in Giemsa-stained smears of bronchoalveolar washings (BAL), or induced sputum specimens, confirmation as C. neoformans is germane to definitive therapy. We therefore studied 30 BAL and 9 induced sputum specimens for cryptococcal antigen. Of the 30 BAL, 3 specimens were positive for cryptococcal antigen, ranging in titer from 1:4 to 1:256, and 2 of 9 sputum samples were also smear, culture and antigen positive (titer 1:2) for C. neoformans. Of the 34 negative specimens, none of the seven containing Candida species or the one containing H. capsulatum or the one containing P. carinii cross-reacted with cryptococcal anticapsular antibody. Our results indicate that when yeast forms suggestive of C. neoformans are visualized on direct smears of BAL or sputum samples, rapid confirmation as C. neoformans may be achieved by assessment for cryptococcal antigen. A correlation may also exist between antigen titer in respiratory specimens and extent of cryptococcal infection.     

Effects of lactobacilli on yeast-catalyzed ethanol fermentations

Normal-gravity (22 to 24 degrees Plato) wheat mashes were inoculated with five industrially important strains of lactobacilli at approximately 10(5), approximately 10(6), approximately 10(7), approximately 10(8), and approximately 10(9) CFU/ml in order to study the effects of the lactobacilli on yeast growth and ethanol productivity. Lactobacillus plantarum, Lactobacillus paracasei, Lactobacillus #3, Lactobacillus rhamnosus, and Lactobacillus fermentum were used. Controls with yeast cells but no bacterial inoculation and additional treatments with bacteria alone inoculated at approximately 10(7) CFU/ml of mash were included. Decreased ethanol yields were due to the diversion of carbohydrates for bacterial growth and the production of lactic acid. As higher numbers of the bacteria were produced (depending on the strain), 1 to 1.5% (wt/vol) lactic acid resulted in the case of homofermentative organisms. L. fermentum, a heterofermentative organism, produced only 0.5% (wt/vol) lactic acid. When L. plantarum, L. rhamnosus, and L. fermentum were inoculated at approximately 10(6) CFU/ml, an approximately 2% decrease in the final ethanol concentration was observed. Smaller initial numbers (only 10(5) CFU/ml) of L. paracasei or Lactobacillus #3 were sufficient to cause more than 2% decreases in the final ethanol concentrations measured compared to the control. Such effects after an inoculation of only 10(5) CFU/ml may have been due to the higher tolerance to ethanol of the latter two bacteria, to the more rapid adaptation (shorter lag phase) of these two industrial organisms to fermentation conditions, and/or to their more rapid growth and metabolism. When up to 10(9) CFU of bacteria/ml was present in mash, approximately 3.8 to 7.6% reductions in ethanol concentration occurred depending on the strain. Production of lactic acid and a suspected competition with yeast cells for essential growth factors in the fermenting medium were the major reasons for reductions in yeast growth and final ethanol yield when lactic acid bacteria were present.     

Unexpected candidemia complicating ureteroscopy and urinary stenting

Two elderly patients with obstructive renal calculi who developed Candida albicans bloodstream infection within 12 h following ureteroscopy and ureteral stenting are described. Both patients were treated with prolonged courses of broad-spectrum antibiotics and were found to have urine cultures positive for Candida albicans prior to the urologic procedures. One patient also developed bilateral candidal endophthalmitis. The clinical presentation was indistinguishable from bacteremia complicating manipulation of the urinary tract. The patients were successfully treated with systemic antifungal therapy. Candiduria may present a risk for dissemination during invasive, relatively simple urologic procedures.     

Clinical evaluation of nitrite test for the detection of bacteriuria

A nitrite test for bacteriuria was compared with routine microscopic examination in 1,318 clinical urine specimens and with bacterial culture in 132. Sensitivity, specificity, positive predictive value and accuracy rate are as follows; for diagnosis of bacteriuria more than 10(4) CFU/ml, 53.4%, 88.6%, 90.4 and 65.2%, respectively; for more than 10(5) CFU/ml, 55.4%, 87.8%, 88.4% and 67.2%, respectively. The positive rate for the nitrite test was 21.4% for bacteriuria of > or = 10(4) CFU/ml in gram positive cocci and 56.9% in gram negative rods. False negative results were obtained from gram positive cocci without nitrate reductive activity or from patients with acute uncomplicated cystitis because of insufficient incubation time in urinary tract. However, this simple test is valuable in the detection of bacteriuria in clinical practice with high specificity.     

Chemoenzymatic synthesis of chiral biologically active heterocycles

During 1995, among 1105 HIV patients explored in our department, 64 presented a deep fungic infection (5.8%). The yeast was searched for in cerebrospinal fluid, blood, urine, and bronchoalveolar aspiration. Isolated germs were Cryptococcus neoformans (95%), Candida tropicalis (1 case), Saccharomyces cerevisiae (1 case) et Aspergillus fumigatus (1 case). Results of treatment with amphotericin B were: recovery (9%), clinical success (11%), out of sight (14%), letality (66%), relapse (23%) and side effects (19%). We emphasized diagnostical and therapeutical difficulties, and bad prognostic of mycoses in patients with AIDS.     

Massive and progressive hepatosplenomegaly caused by disseminated nontuberculous mycobacteriosis in a patient with acquired immunodeficiency syndrome

A 28-year-old hemophilia A patient was admitted to our hospital in July, 1991 because of high fever, chronic diarrhea and anemia. The patient had been recognized as a asymptomatic carrier of human immunodeficiency virus (HIV) in 1985 and had developed Pneumocystis carinii pneumonia and had been diagnosed as acquired immunodeficiency syndrome (AIDS) in 1990. Hematologic laboratory examinations on admission revealed pancytopenia and a CD4+ cell count of 3/mm3. X-ray findings of chest and abdomen were normal and bacterial cultures of sputum, urine, blood, stool, cerebrospinal fluid and bone marrow yielded no pathogenic microorganisms. Microscopical examination of the stained specimens showed no acid-fast bacilli. On his fifth hospital day, his liver and spleen enlarged markedly and an abdominal CT scan obtained on the 13th day revealed high-grade hepatosplenomegaly. Administration of several kinds of antibiotics, antifungal agents, antiviral agents, antituberculous agents and gamma-globulin medicines did not relieve the symptoms. On the 28th day the patient had developed a subarachnoid hemorrhage and died five days later. Retrospectively all cultures for acid-fast bacilli of the specimens on his admission yielded nontuberculous mycobacteria. The bacteria were identified as Mycobacterium avium by polymerase chain reaction and his disease was eventually diagnosed as disseminated Mycobacterium avium complex (MAC) infection. The liver and spleen weighed 2,660 g and 1,840 g respectively at autopsy. Although hepatosplenomegaly is commonly recognized in AIDS patients with disseminated MAC infection, such massive and rapid enlargement has been rarely observed. This case study emphasize the importance of diagnosis and rapid treatment at the early stage of MAC infection.     

Mouse NK1.1+ T cells: a new family of T cells

A ligase chain reaction (LCR) DNA amplification assay that targeted the cryptic plasmid of Chlamydia trachomatis was developed to detect C. trachomatis urogenital tract infection. The objectives of this study were to determine the cutoff and analytic performance of the LCR assay and to characterize the effectiveness of its postdetection contamination control method. The assay's cutoff was determined after receiver-operator characteristic (ROC) analysis of 4660 clinical data points. The assay detected one infectious unit per reaction of each of the 15 C. trachomatis serovars and did not cross-react with 13 Chlamydia pneumoniae strains, 13 Chlamydia psittaci strains, and 87 other bacteria, fungi, parasites, or viruses. In addition, the assay did not detect 77 processed urine specimens collected from patients with urinary tract infections caused by yeast or bacteria other than C. trachomatis. The assay was sufficiently precise to detect consistently two infectious units of C. trachomatis per reaction. False-positive assay results attributable to contamination with amplified product were minimized by the use of standard procedures as well as by a postdetection chemical inactivation method that could reduce the amount of amplified LCR product by a factor of > or = 10(7).     

Significance of the antibacterial agent assay of urine for bacteriological diagnosis and control of chemotherapy of urinary tract infections (author's transl)

The disc agar-diffusion-test using Bacillus subtilis ATCC 6051 as test organism is a simple and rapid method for routine testing of antibacterial agents in urine specimens. The test records urine levels which are expected under medium dosage, and in many cases even lower concentrations of renal excreted antibiotics. Out of 5655 analysed urine samples 22% contain antibacterial substances. In urine specimens over which information was volunteered that either no chemotherapy had been administered or that more than a three day's interval free of therapy existed, inhibitory substances are found in 8% and 27% respectively. Urine specimens which are supposedly collected from patients under current chemotherapy do not show therapeutic relevant antibiotic levels in 26%. Between urine specimens with and without antibacterial activity there is no significant difference in the incidence of viable counts of 10-4-10-5/ml and 10-5/ml. From urine samples with antibacterial content increases in the numbers of multiple resistant strains of E. coli, Proteus spp., Pseudom. aerug. and Enterobacter spp. together with high numbers of Candida spp. are observed.     

Trends in antifungal use and epidemiology of nosocomial yeast infections in a university hospital

This report describes both the trends in antifungal use and the epidemiology of nosocomial yeast infections at the University of Iowa Hospitals and Clinics between fiscal year (FY) 1987-1988 and FY 1993-1994. Data were gathered retrospectively from patients' medical records and from computerized databases maintained by the Pharmacy, the Program of Hospital Epidemiology, and the Medical Records Department. After fluconazole was introduced, use of ketoconazole decreased dramatically but adjusted use of amphotericin B decreased only moderately. However, the proportion of patients receiving antifungal therapy who were treated with amphotericin B declined markedly. In FY 1993-1994, 26 patients of the gastrointestinal surgery service received fluconazole. Among these patients, fluconazole use was prophylactic in 16 (61%), empiric in 3 (12%), and directed to a documented fungal infection in 7 (27%). Rates of nosocomial yeast infection in the adult bone marrow transplant unit increased from 6.77/1,000 patient days in FY 1987-1988 to 10.18 in FY 1989-1990 and then decreased to 0 in FY 1992-1993. Rates of yeast infections increased threefold in the medical and surgical intensive care units, reaching rates in FY 1993-1994 of 6.95 and 5.25/1,000 patient days, respectively. The rate of bloodstream infections increased from 0.044/1,000 patient days to 0.098, and the incidence of catheter-related urinary tract infections increased from 0.23/1,000 patient days to 0.68. Although the proportion of infections caused by yeast species other than Candida albicans did not increase consistently, C. glabrata became an important nosocomial pathogen.