Urinary tract infection caused by Enterococcus spp.: Risk factors and mortality. An observational study.

BACKGROUND AND OBJECTIVE: Urinary tract infections (UTIs) are frequently caused by Enterococcus spp. This work aims to define the risk factors associated with UTIs caused by Enterococci and to determine its overall mortality and predictive risk factors. MATERIALS AND METHODS: A retrospective study was conducted on bacteremic UTIs caused by Enterococcus spp. among inpatients. We compared 106 inpatients with bacteremic UTIs caused by Enterococcus spp. vs. a random sample of 100 inpatients with bacteremic UTIs caused by other enterobacteria. RESULTS: A total of 106 inpatients with UTIs caused by Enterococcus spp. were analyzed, 51 of whom had concomitant positive blood cultures. Distribution by species was 83% E. faecalis and 17% E. faecium. The mean Charlson Comorbidity Index score was 5.9±2.9. Upon comparing bacteremic UTIs caused by Enterococcus spp. vs. bacteremic UTIs caused by others enterobacteria, we found the following independent predictors of bacteremic UTI by Enterococcus: male sex, obstructive uropathy, nosocomial infection, cancers of the urinary system, and previous antimicrobial treatment. Overall, inpatient mortality was 16.5% and was associated with a higher Sequential Organ Failure Assessment (SOFA) score (>4); severe comorbidities such as immunosuppression, malignant hemopathy, and nephrostomy; and Enterococcus faecium species and its pattern of resistance to ampicillin or vancomycin (p<0.05). Appropriate empiric antibiotic therapy was not associated with a better prognosis (p>0.05). CONCLUSIONS: Enterococcus spp. is a frequent cause of complicated UTI in patients with risk factors. High mortality secondary to a severe clinical condition and high comorbidity may be sufficient for justifying the implementation of empiric treatment of at-risk patients.

[Utility of the blood culture in infection of the urinary tract with fever in the elderly]. / Utilidad del hemocultivo en la infección del tracto urinario con fiebre en el anciano.

OBJECTIVE: Urinary tract infections are one of the most common community infections. The diagnosis of urinary infections in the elderly is complex because of its presentation and clinic. The aim of this article is to evaluate the usefulness of blood cultures in febrile urinary tract infection in elderly patients, risk factors, causes of discordance between urine and blood cultures, usefulness of biomarkers and mortality. METHODS: Observational study of patients admitted over 65 years old, with urinary infections. RESULTS: A total of 216 episodes with urinary infections and blood cultures performed. 70 (32,4%) cases with bacteremia. The most frequently detected isolates in blood cultures were: Escherichia coli 50 (71,4%) and Proteus spp. 6 (8,5%). Only septic shock was associated with a higher frequency of bacteraemia (OR=2,93, IC 95: 1,0-8,5; p=0,04). In 26 of the blood cultures a different isolation of the urine culture was detected. Overall mortality was 9.1%, with no association with the presence of bacteremia (p>0. 05). CONCLUSIONS: One third of elderly people hospitalized by tract urinary infection had bacteremia. Their detection was not associated with overall mortality. Disagree between blood and urine cultures in febrile is frequent, especially in patients with recent antibiotic treatment or recently hospitalized.

Urinary infection in the elderly. / Infección urinaria en el anciano.

INTRODUCTION: Urinary tract infections (UTIs) are one of the most frequent infections. In the elderly, they have multiple comorbidities. The objective of this work is to describe the clinical and microbiological epidemiology of elderly persons admitted for UTIs and to evaluate the suitability of empirical treatments and their implications regarding mortality. MATERIAL AND METHODS: An observational study was conducted during 2013-2015 in 4public hospitals, with patients older than 65 years who were admitted to the Internal Medicine service with a microbiological diagnosis of UTI. Cases of asymptomatic bacteriuria were excluded. In-hospital mortality was analyzed. Univariate analysis and multivariate analysis was carried out. RESULTS: A total of 349 episodes were selected, with a mean age of 82 ± 11 years, 51% female. Mortality was 10.3% and was associated with age, dementia and sepsis and septic shock (P<.05). The most frequent organisms were Escherichia coli(E. coli) (53.6%), Klebsiella spp. (8.7%) and Enterococcus spp. (6.6%). E. coli and Klebsiella spp. with extended-spectrum beta-lactamases (13% of the total isolated) were associated with the previous use of antibiotics, community care treatment and a permanent urinary catheter (P<.05). The empirical treatment was adequate only in 73.6% of cases. As these treatments were associated with higher mortality, they were not considered adequate. CONCLUSIONS: In the elderly, UTIs show a high mortality. Empirical treatment is often inadequate and may be associated with increased mortality.

Identification and characterization of HMBS gene mutations in Spanish patients with acute intermittent porphyria.

Acute intermittent porphyria (AIP), the most common acute hepatic porphyria, is an autosomal dominant disorder with low penetrance that results from a partial deficiency of hydroxymethylbilane synthase (HMBS), the third enzyme in the heme biosynthetic pathway. The disease is clinically characterized by acute neurovisceral attacks that are precipitated by several factors including certain drugs, steroid hormones, alcohol and fasting. Early diagnosis and counselling are essential to prevent attacks, being mutation analysis the most reliable method to identify asymptomatic carriers in AIP families. In this study we have investigated the molecular defect in 15 unrelated Spanish AIP patients. Mutation analysis of the HMBS gene revealed a total of fourteen mutations including six novel ones, two of them were on the same allele in one patient. The novel mutations were three missense (R26L, R173G and D178H), two frameshift (c.749_765dup and c.874insC) and one intronic deletion (IVS12+3_+11delAGGGCCTGT). RT-PCR and sequencing demonstrated that the intronic mutation caused abnormal splicing and exon 12 skipping. Prokaryotic expression of the novel missense mutations showed that only D178H had significant residual activity. These findings will facilitate the accurate identification of presymptomatic AIP carriers in these families and they further emphasize the molecular heterogeneity of AIP in Spain.

Epidermal growth factor receptor ligands in murine models for erythropoietic protoporphyria: potential novel players in the progression of liver injury.

Activation of the epidermal growth factor receptor (EGFR) plays an important role in liver regeneration and resistance to acute injury. However its chronic activation participates in the progression of liver disease, including fibrogenesis and malignant transformation. Hepatobiliary disease represents a constant feature in the clinically relevant Fechm1pas/Fechm1pas genetic model of erythropoietic protoporphyria (EPP). Similarly, chronic administration of griseofulvin to mice induces pathological changes similar to those found in patients with EPP-associated liver injury. We investigated the hepatic expression of the EGFR and its seven most relevant ligands in Fechm1pas/Fechm1pas mice bred in three different backgrounds, and in griseofulvin-induced protoporphyria. We observed that the expression of amphiregulin, betacellulin and epiregulin was significantly increased in young EPP mice when compared to aged-matched controls in all genetic backgrounds. The expression of these ligands was also tested in older (11 months) BALB/cJ EPP mice, and it was found to remain induced, while that of the EGFR was downregulated. Griseofulvin feeding also increased the expression of amphiregulin, betacellulin and epiregulin. Interestingly, protoporphyrin accumulation in cultured hepatic AML-12 cells readily elicited the expression of these three EGFR ligands. Our findings suggest that protoporphyrin could directly induce the hepatic expression of EGFR ligands, and that their chronic upregulation might participate in the pathogenesis of EPP-associated liver disease.

Induction of hepatic aminolevulinate acid synthetase activity by isoflurane in a genetic model for erythropoietic protoporphyria.

Erythropoietic Protoporphyria (EPP) is an inherited deficiency of ferrochelatase, the last enzyme of the heme pathway. Under general anaesthesia, some patients develop neurological dysfunction suggesting upregulation in heme biosynthesis similar to that described for acute porphyrias after xenobiotic administration. Our aim has been to evaluate whether Isoflurane induces alterations in the heme pathway in a mouse model for EPP. Administration of Isoflurane (a single dose of 2 ml/kg, i.p) to wild-type (+/+), heterozygous (+/Fechm1Pas) and homozygous (Fechm1Pas/Fechm1Pas) mice, was evaluated by measuring the activity of delta-aminolevulinic acid synthetase (ALA-S) and Porphobilinogen-deaminase (PBG-D) in different tissues, as well as Heme oxygenase (HO), cytochrome P-450, CYP2E1 and glutathione levels in liver. Porphyrin precursors were measured in 24 h-urine samples. Fechm1Pas/Fechm1Pas mice receiving anaesthesia show enhanced ALA-S and CYP2E1 activities in the liver and increased urinary excretion of porphyrin precursors. No alterations were found in either PBG-D or HO activities. Diminished glutathione levels suggest that anaesthesia may produce oxidative stress in these animals. In conclusion, Isoflurane induces ALA-S activity and increased excretion of porphyrin precursors in EPP mice. These findings appear to confirm our previous hypothesis and indicate that Isoflurane may be an unsafe anaesthetic not only for patients with acute porphyrias but also for individuals with non acute porphyrias.

Urinary tract infection due to Corynebacterium urealyticum in kidney transplant recipients: an underdiagnosed etiology for obstructive uropathy and graft dysfunction-results of a prospective cohort study.

BACKGROUND: Corynebacterium urealyticum is a cause of urinary tract infection and encrusting cystitis or pyelitis. Information about this infection in renal transplant recipients is based on case reports. We communicate the first prospective epidemiological study for this population. METHODS: We selected a cohort of 163 renal transplant recipients who were screened for urinary tract infection due to C. urealyticum. Long-term incubation and special media were used for culture of C. urealyticum. The cohort was observed for a mean of 26.2 months (standard deviation, 8.7; range, 1-36 months). Risk factors and outcomes were assessed. RESULTS: At baseline, 16 (9.8%) of 163 patients had C. urealyticum bacteriuria (6 were asymptomatic, 9 had acute cystitis, and 1 had encrusting pyelitis). Independent risk factors (assessed by multivariate analysis) for urinary tract C. urealyticum infection were: antibiotic administration during the previous month (odds ratio, 8.04; 95% confidence interval, 1.57-41.06; P = .012), history of nephrostomy (odds ratio, 51.59; 95% confidence interval, 3.62-736.06; P = .004), and skin colonization (odds ratio, 208.35; 95% confidence interval, 21.54-2015.22; P< .001). Presence of urinary tract infection symptoms for >1 month (odds ratio, 27.7; 95% confidence interval, 2.55-300.5; P = .006) and obstructive uropathy (odds ratio 25.9; 95% confidence interval, 4.43-152.31; P < .001) were more frequent during follow-up in patients with C. urealyticum bacteriuria. CONCLUSIONS: When specifically tested for, C. urealyticum bacteriuria is more prevalent than previously thought in renal transplant recipients, and it is closely related to obstructive uropathy. Future studies are necessary to establish the relevance of treating the infection during follow-up after renal transplantation.

Molecular heterogeneity of familial porphyria cutanea tarda in Spain: characterization of 10 novel mutations in the UROD gene.

BACKGROUND: Porphyria cutanea tarda (PCT) results from decreased hepatic uroporphyrinogen decarboxylase (UROD) activity. In the majority of patients, the disease is sporadic (S-PCT or type I) and the enzyme deficiency is limited to the liver. Familial PCT (F-PCT or type II) is observed in 20-30% of patients in whom mutations on one allele of the UROD gene reduce UROD activity by approximately 50% in all tissues. Another variant of PCT (type III) is characterized by family history of the disease although it is biochemically indistinguishable from S-PCT. OBJECTIVES: To investigate the molecular basis of PCT in Spain and to compare enzymatic and molecular analysis for the identification of patients with F-PCT. METHODS: Erythrocyte UROD activity measurement and mutation analysis of the UROD gene were carried out in a cohort of 61 unrelated Spanish patients with PCT and 50 control individuals. Furthermore, each novel missense mutation identified was characterized by prokaryotic expression studies. RESULTS: Of these 61 patients, 40 (66%) were classified as having S-PCT, 16 (26%) as having F-PCT and five (8%) as having type III PCT. Discordant results between enzymatic and molecular analysis were observed in two patients with F-PCT. In total, 14 distinct mutations were found, including 10 novel mutations: five missense, one nonsense, three deletions and an insertion. Prokaryotic expression of the novel missense mutations demonstrated that each results in decreased enzyme activity or stability. CONCLUSIONS: These results confirm the high degree of molecular heterogeneity of F-PCT in Spain and emphasize the usefulness of molecular genetic analysis to distinguish between F-PCT and S-PCT.

Precipitating/aggravating factors of porphyria cutanea tarda in Spanish patients.

Erythrocyte uroporphyrinogen decarboxylase (UROD) activity was measured to classify 118 Spanish patients with porphyria cutanea tarda (PCT) into three subtypes: sporadic-, familial- and type III-PCT. Seventy-four patients (63%) had eythrocyte UROD activity within the normal range (74% to 126% of the mean activity of 43 healthy controls) and were classified as sporadic-PCT (47%) or as type III-PCT (16%) whenever a family history of PCT was documented. Forty-four patients (37%) had decreased UROD activity and were classified as familial-PCT. The frequency of both familial-PCT and type III-PCT was higher than reported in other countries. The clinical expression of PCT was associated with the coexistence of two or more risk factors in 80% of the sporadic-PCT patients and in 89% of the familial-PCT patients. Hepatitis C virus and alcohol abuse were risk factors frequently found in these patients, being unrelated to age of onset of skin lesions. A heavy alcohol intake was the main risk factor for type III-PCT. Estrogens appeared as a precipitating factor for women with familial-PCT. The H63D mutation in the hemochromatosis type 1 gene was more frequently found than the C282Y mutation. Both mutations appeared to play a role as precipitating factors in sporadic-PCT when associated with hepatitis C virus infection and alcohol abuse.

Age changes in the activity of liver 3-hydroxy-3-methylglutaryl-CoA reductase in female rats: influence of mammary pathology.

Hydroxymethylglutaryl-Coenzyme A (HMG-CoA) reductase is a highly regulated enzyme which shows a marked circadian rhythmicity. We studied the impact of aging on this rhythm as well as the degree of correlation between age changes in circulating pituitary hormone levels and liver reductase activity in young (4 months) and old (33 months) Sprague-Dawley female rats. Lipid composition was also assessed in plasma and liver microsomes. The maximal activity (midnight) of HMG-CoA reductase fell from 864 +/- 28 pmol mevalonate/min/mg protein in the young rats to 552 +/- 45 pmol/min/mg protein in the old animals, whereas significant change was not observed in the basal (noon) activity levels of the enzyme. Noon serum cholesterol, but not midnight values, was significantly higher in the old rats. Liver cholesterol levels were similar in young and old rats. In old rats, fatty acid composition of liver microsomes revealed an increase in linoleic acid concurrently with a significant decrease in arachidonic acid (AA). A significant correlation was not detected between the age changes in pituitary hormone (GH, PRL, TSH, FSH) serum levels and those in reductase activity. On the other hand, a significant positive correlation was found in the old rats between hepatic reductase activity and the severity of mammary pathology. We conclude that, like most biological rhythms, HMG-CoA reductase circadian fluctuation decreases in amplitude with age. This change does not seem to be linked to the alterations of neuroendocrine function associated with the aging process. The presence of growing mammary tumors seems to stimulate liver reductase activity, which may constitute an adaptive response of the enzyme to cholesterol demand by the growing neoplastic tissue.

Influence of external factors in resistance of Corynebacterium urealyticum to antimicrobial agents.

Corynebacterium urealyticum is usually resistant to multiple antibiotics. We analyzed whether previous hospitalization and/or the use of antibiotics was a factor associated with the appearance of resistance to different antibiotics in C. urealyticum. Our findings suggest that resistant strains of C. urealyticum are likely to be acquired directly from the hospital environment and that the use of antibiotics in the hospital setting could favor the appearance of multiresistant strains.

[Corynebacterium urealyticum in kidney transplant patients]. / Corynebacterium urealyticum en pacientes con transplante renal.

BACKGROUND: Corynebacterium urealyticum may produce severe urinary tract infections (UTI) in patients with renal transplantation (RT). The aim of this study was to define the prevalence, clinical spectrum and risk factors for the development of symptomatic UTI in RT receptors with bacteriuria by C. urealyticum. METHODS: The clinical data of RT patients with bacteriuria by C. urealyticum diagnosed in the Hospital Doce de Octubre in Madrid from January 1990 to September 1993 were retrospectively reviewed. The patients corresponded to two clearly differentiated periods. In the first, the presence of C. urealyticum was not actively sought in the urine sample while in the second an intentional search was carried out in all the RT with a selective culture medium containing different antibiotics, Tween-80 and urea to facilitate C. urealyticum identification and growth. RESULTS: C. urealyticum was isolated in the urine of 46 patients (14% of the RT performed in the study period). In the first phase 16 cases were diagnosed with 30 being found in the second with the selective medium. Bacteriuria by C. urealyticum was symptomatic in 18 patients (39%): 12 acute cystitis, one encrusted cystitis (IC), and 5 encrusted pyelitis (IP). Of the symptomatic patients 39% had a history of prolonged vesical catheterization, 27% carried ureteral catheterization and 50% had undergone other urologic manipulations. The clinical consequences were important with development of obstructive uropathy and alteration in renal function (28%), need for surgery (33%) and graft loss (5.5%). All the C. urealyticum strains were sensitive to vancomycin and teicoplanin which were useful in the treatment although the most severe cases (IC, IP) required surgery. CONCLUSIONS: The prevalence of UTI by Corynebacterium urealyticum is high in RT patients. Occasionally, these infections may have severe consequences, particularly in patients with a history of urologic manipulation, if early diagnosis is not performed and adequate antibiotic treatment given. A selective culture medium should be used to isolate C. urealyticum in RT patients.

Conventional viral cultures and shell vial assay for diagnosis of apparently culture-negative Coxiella burnetii endocarditis.

A patient with culture-negative endocarditis was diagnosed with Q fever endocarditis based on the results of serological tests and positive leukocyte cultures obtained using conventional viral cultures and the shell vial technique. This case report suggests that isolation of Coxiella burnetii from blood may allow better diagnostic and therapeutical evaluation of patients with Q fever endocarditis. The use of both conventional and shell vial viral cultures is recommended for the isolation of Coxiella burnetii from the blood of patients with apparently culture-negative endocarditis.

[Comparison of the Bacter system and Löwenstein-Jensen medium for cultivation of Mycobacterium tuberculosis in clinical samples]. / Comparación del sistema Bactec y medio de Löwenstein-Jensen para el cultivo de Mycobacterium tuberculosis en muestras clínicas.

Over a period of two years, 1364 clinical samples from pulmonary sources, were studied in order to compare the Bactec-TB system with the Löwenstein-Jensen medium, for isolation of mycobacteria. Within this period of time, 93 strains of Mycobacterium tuberculosis were isolated, 71 (76%) were isolated by the Bactec system, and 69 (74%) were isolated by the Löwenstein-Jensen. The number of contaminations was lower for the Bactec system (3.2%) than for the Löwenstein-Jensen medium (5.3%). The mean time of isolation with the Bactec was 16.4 days. The mean time of isolation with Löwenstein-Jensen medium was 21.9 days. Identification of the strains with the Bactec system by the p-nitro-a-acetilamin-beta-hidroxipropiphenone inhibition test gave a 100% correlation with the conventional biochemical methods used for the identification of the same strains growth of Löwenstein-Jensen.

Experience with amorolfine in the treatment of dermatomycoses.

In a double-blind randomized comparative study, 75 patients were treated with amorolfine cream 0.125, 0.25 or 0.5%. At the end of treatment clinical cure rates of 80, 76 and 84%, respectively, and mycological cures of 72, 64 and 76% were obtained. At 2 months posttherapy follow-up relapse rates were 0, 12 and 12%, respectively. There was no significant difference between the three groups in terms of clinical and mycological response, duration of treatment or tolerance. In a double-blind parallel study, 40 patients were treated topically with either 0.5% amorolfine cream or 1% bifonazole cream. The percentages of combined clinical and mycological cures were 83.3 and 78.95%, respectively. There was no significant difference in terms of tolerance and clinical and mycological cure rates. All treatments were applied once daily. Posttreatment MIC values did not indicate development of resistance to either amorolfine or bifonazole.