[Clinical presentation and performance of urine dipstick for diagnosis of urinary infection in geriatric population]. / Présentation clinique et performance de la bandelette urinaire pour le diagnostic d'infection urinaire en population gériatrique.

BACKGROUND: Urinary tract infections (UTI) are the second cause of community-acquired bacterial infections in the elderly. Distinguishing symptomatic UTI from asymptomatic bacteriuria is problematic, as older adults are less likely to present with localized urinary symptoms. We evaluated characteristics of patients presenting UTI among elderly with sepsis. Moreover, we aimed to evaluate the sensibility and specificity of urine dipstick tests in the diagnosis of UTI in geriatric population. PATIENTS AND METHOD: We led a prospective, monocentric, observational study between April 2017 and January 2018. We included patients hospitalized in geriatric wards, who were prescribed urine culture for UTI symptoms or/and infection without primary sites for which a urine culture was prescribed. Dipstick urinalyses were performed for all patients. Clinical and biological characteristics of all patients were compared according to the final diagnosis of UTI. Moreover, results of dipstick tests were evaluated for the diagnosis of UTI in this population. RESULTS: Among 165 patients, 67 (40.6 %) had a UTI and 98 (59.4 %) had another diagnosis. These two groups were comparable for age and daily-living activities. In the UTI group, the proportion of women was higher than in the other group (P<0.05), and mean MMSE score was lower (P<0.05). Positive urine dipstick test for leukocytes and/or nitrites had high sensitivity (92 %), but low specificity (50 %). Negative predictive value of this test was high (91 %). CONCLUSION: For suspicion of UTI among elderly, few criteria are specific. Negative dipstick tests can suggest an absence of UTI due to its high negative predictive value.

A field-pilot for passive bioremediation of As-rich acid mine drainage.

A field-pilot bioreactor exploiting microbial iron (Fe) oxidation and subsequent arsenic (As) and Fe co-precipitation was monitored during 6 months for the passive treatment of As-rich acid mine drainage (AMD). It was implemented at the Carnoulès mining site (southern France) where AMD contained 790-1315 mg L-1 Fe(II) and 84-152 mg L-1 As, mainly as As(III) (78-83%). The bioreactor consisted in five shallow trays of 1.5 m2 in series, continuously fed with AMD by natural flow. We monitored the flow rate and the water physico-chemistry including redox Fe and As speciation. Hydraulic retention time (HRT) was calculated and the precipitates formed inside the bioreactor were characterized (mineralogy, Fe and As content, As redox state). Since As(III) oxidation improves As retention onto Fe minerals, bacteria with the capacity to oxidize As(III) were quantified through their marker gene aioA. Arsenic removal yields in the pilot ranged between 3% and 97% (average rate (1.8 ±â€¯0.8) ✕ 10-8 mol L-1 s-1), and were positively correlated to HRT and inlet water dissolved oxygen concentration. Fe removal yields did not exceed 11% (average rate (7 ±â€¯5) ✕ 10-8 mol L-1 s-1). In the first 32 days the precipitate contained tooeleite, a rare arsenite ferric sulfate mineral. Then, it evolved toward an amorphous ferric arsenate phase. The As/Fe molar ratio and As(V) to total As proportion increased from 0.29 to 0.86 and from ∼20% to 99%, respectively. The number of bacterial aioA gene copies increased ten-fold during the first 48 days and stabilized thereafter. These results and the monitoring of arsenic speciation in the inlet and the outlet water, provide evidences that As(III) oxidized in the pilot. The biotreatment system we designed proved to be suitable for high As DMA. The formation of sludge highly enriched into As(V) rather than As(III) is advantageous in the perspective of long term storage.

Biological attenuation of arsenic and iron in a continuous flow bioreactor treating acid mine drainage (AMD).

Passive water treatments based on biological attenuation can be effective for arsenic-rich acid mine drainage (AMD). However, the key factors driving the biological processes involved in this attenuation are not well-known. Here, the efficiency of arsenic (As) removal was investigated in a bench-scale continuous flow channel bioreactor treating As-rich AMD (∼30-40 mg L-1). In this bioreactor, As removal proceeds via the formation of biogenic precipitates consisting of iron- and arsenic-rich mineral phases encrusting a microbial biofilm. Ferrous iron (Fe(II)) oxidation and iron (Fe) and arsenic removal rates were monitored at two different water heights (4 and 25 mm) and with/without forced aeration. A maximum of 80% As removal was achieved within 500 min at the lowest water height. This operating condition promoted intense Fe(II) microbial oxidation and subsequent precipitation of As-bearing schwertmannite and amorphous ferric arsenate. Higher water height slowed down Fe(II) oxidation, Fe precipitation and As removal, in relation with limited oxygen transfer through the water column. The lower oxygen transfer at higher water height could be partly counteracted by aeration. The presence of an iridescent floating film that developed at the water surface was found to limit oxygen transfer to the water column and delayed Fe(II) oxidation, but did not affect As removal. The bacterial community structure in the biogenic precipitates in the bottom of the bioreactor differed from that of the inlet water and was influenced to some extent by water height and aeration. Although potential for microbial mediated As oxidation was revealed by the detection of aioA genes, removal of Fe and As was mainly attributable to microbial Fe oxidation activity. Increasing the proportion of dissolved As(V) in the inlet water improved As removal and favoured the formation of amorphous ferric arsenate over As-sorbed schwertmannite. This study proved the ability of this bioreactor-system to treat extreme As concentrations and may serve in the design of future in-situ bioremediation system able to treat As-rich AMD.

Community-acquired Clostridium difficile infections in emergency departments.

OBJECTIVE: Clostridium difficile infection (CDI) has become an emerging infectious disease, especially in community settings. Little data is available on its frequency and characteristics in France. We aimed to describe CDI case patients consulting at the emergency department and to compare community-acquired and nosocomial CDIs. PATIENTS AND METHODS: We conducted a multicenter retrospective study over a three-year period of community-acquired and nosocomial CDI case patients seen at the emergency department and compared their characteristics. RESULTS: A total of 2055 patients consulted for diarrhea during the study period and had a stool culture performed: 66 (3.2%) presented with a CDI, of which 28 were community-acquired and 26 were nosocomial. Community-acquired CDI patients had a mean age of 57.7years (18-91), with a sex-ratio of 0.65. At least one risk factor was observed in 24 patients (85.7%), of whom 22 (78.6%) had been prescribed a previous antimicrobial treatment. Diabetes mellitus and renal failure were more frequently observed in patients presenting with nosocomial CDI. They required fluid replacement and needed be to re-hospitalized more often than community-acquired patients. CONCLUSION: Community-acquired CDIs in the emergency department account for approximately 1.4% of patients presenting with diarrhea. One risk factor is present in 85.7% of cases. In our study, their presentation and outcome seemed less severe than nosocomial CDIs.

Evaluating antibiotic therapies prescribed to adult patients in the emergency department.

OBJECTIVES: The proper use of antibiotics is a public health priority to preserve their effectiveness. Little data is available on outpatient antibiotic prescriptions, especially in the emergency department. We aimed to assess the quality of outpatient antibiotic prescriptions in our hospital. PATIENTS AND METHODS: Retrospective monocentric study of antibiotic prescriptions written to adult patients managed at the emergency department without hospitalization (November 15th, 2012-November 15th, 2013). Prescriptions were evaluated by an infectious disease specialist and an emergency physician on the basis of local recommendations compiled from national and international guidelines. RESULTS: A total of 760 prescriptions were reviewed. The most frequent indications were urinary tract infections (n=263; 34.6%), cutaneous infections (n=198; 26.05%), respiratory tract infections (n=101; 13.28%), and ENT infections (n=62; 8.15%). The most frequently prescribed antibiotics were fluoroquinolones (n=314; 40.83%) and amoxicillin-clavulanic acid (n=245; 31.85%). Overall, 455 prescriptions (59.86%) did not comply with guidelines. The main reasons for inadequacy were the absence of an indication for antibiotic therapy (n=197; 40.7%), an inadequate spectrum of activity, i.e. too broad, (n=95; 19.62%), and excessive treatment duration (n=87; 17.97%). Rates of inadequate prescriptions were 82.26% for ENT infections, 71.2% for cutaneous infections, 46.53% for respiratory tract infections, and 38.4% for urinary tract infections. CONCLUSION: Antibiotic prescriptions written to outpatients in the emergency department are often inadequate. Enhancing prescribers' training and handing out guidelines is therefore necessary. The quality of these prescriptions should then be re-assessed.

Increased incidence of Campylobacter jejuni-associated Guillain-Barré syndromes in the Greater Paris area.

The role of Campylobacter jejuni as the triggering agent of Guillain-Barré syndrome (GBS) has not been reassessed since the end of the 1990s in France. We report that the number of C. jejuni-related GBS cases increased continuously between 1996 and 2007 in the Paris region (mean annual increment: 7%, P = 0·007).

Diagnosis of prosthetic joint infection by beadmill processing of a periprosthetic specimen.

We report a microbiological process for the documentation of prosthetic joint infection (PJI). Intraoperative periprosthetic tissue samples from 92 consecutive patients undergoing revision surgery for PJI were submitted to mechanized beadmill processing: specimens were aseptically collected in polypropylene vials, filled with sterile water and glass beads and submitted to mechanized agitation with a beadmill. The documentation rate of PJI following culture on solid and liquid media was 83.7% and the contamination rate 8.7%. Final documentation was obtained after overnight culture for 51.9% of cases and with 7 days of broth culture for all documented cases.

Detection and management of late-onset 21-hydroxylase deficiency in women with hyperandrogenism.

Moderate forms of 21-hydroxylase deficiency (D21OH-NC), the so-called non-classical or late-onset forms are a frequently reported cause of hyperandrogenism in women [1-5]. The purpose of this collective and synthetic work was to provide the endocrinologist, gynecologist and dermatologist with consensual information so as to detect the maximum cases with acceptable cost-benefit ratio and to define the main lines of optimal patient management, given the data currently available in medical literature.

Phenotype-genotype correlations of 13 rare CYP21A2 mutations detected in 46 patients affected with 21-hydroxylase deficiency and in one carrier.

CONTEXT: Steroid 21-hydroxylase deficiency is the most common enzymatic defect causing congenital adrenal hyperplasia with genotype/phenotype relationships for common mutations. Novel mutations of the CYP21A2 gene must be well studied to propose right genetic counseling for patients. OBJECTIVE: Thirteen CYP21 mutations have been studied. A detailed description of phenotype was performed for all mutations (p.I77T, p.L167P, p.I230T, p.R233K, p.G291S, p.G292D, p.E320K, p.R341P, p.R354H, p.R369W, p.R408C, p.G424S, and p.R426H). In vitro and in silico studies were performed only for those not previously described (p.L167P, p.I230T, p.R233K, p.G292D, p.E320K, and p.R369W). RESULTS: Regarding phenotype, patients with 10 of these mutations had a classical form. A patient with isolated p.I230T presented with nonclassical form and a patient with the association p.I230T + p.V281L in cis presented with a more severe phenotype. The p.R233K mutation was detected in a carrier partner. A patient with p.R369W presented with an intermediate form. Functional studies showed that all mutations except p.I230T and p.R369W decreased enzyme activity more than p.P30L: severity of p.R369W was intermediate between p.P30L and p.V281L, and finally p.I230T was less severe than p.V281L. Mutation analysis in a three-dimensional model structure of the CYP21 protein explained the observed in vitro effects, severe mutations being implicated in important functional domains of the protein. CONCLUSION: According to phenotype and functional studies, 11 of the mutations described, except the isolated p.R369W and p.I230T, may be responsible for a severe phenotype underlying the necessity to manage children having them. The p.I230T is a nonclassical mutation, and for the p.R369W, we need more cases to precise its severity.

Identification of clinical coagulase-negative staphylococci, isolated in microbiology laboratories, by matrix-assisted laser desorption/ionization-time of flight mass spectrometry and two automated systems.

A study was performed to compare matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS), linked to a recently engineered microbial identification database, and two rapid identification (ID) automated systems, BD Phoenix (Becton Dickinson Diagnostic Systems, France) and VITEK-2 (bioMérieux, Marcy L'Etoile, France), for the ID of coagulase-negative staphylococci (CoNS). Two hundred and thirty-four clinical isolates of CoNS representing 20 species were analyzed. All CoNS isolates were characterized by sodA gene sequencing, allowing interpretation of the ID results obtained using the respective database of each apparatus. Overall correct ID results were obtained in 93.2%, 75.6% and 75.2% of the cases with the MALDI-TOF-MS, Phoenix and VITEK-2 systems, respectively. Mis-ID and absence of results occurred in 1.7% and 5.1% of the cases with MALDI-TOF-MS, in 23.1% and 1.3% with the Phoenix, and in 13.7% and 0.9% with the VITEK-2 systems, respectively. In addition, with the latter automate, 10.3% of the IDs were proposed with remote possibility. When excluding the CoNS species not included in the databases of at least one of the three systems, the final percentage of correct results, Mis-ID and absence of ID were 97.4%, 1.3% and 1.3% with MALDI-TOF-MS, 79%, 21% and 0% with the Phoenix, and 78.6%, 10.3% and 0.9% with the VITEK-2 system, respectively. The present study demonstrates the robustness and high sensitivity of our microbial identification database used with MALDI-TOF-MS technology. This approach represents a powerful tool for the fast ID of clinical CoNS isolates.

Adrenocortical incidentaloma with uncertain prognosis associated with an inadequately treated congenital adrenal hyperplasia.

Large adrenal tumors are rarely associated with adrenal enzymatic deficiency, except in 11-ss-hydroxylase insufficiency. These tumors are exceptionally malignant. We report here the case of a patient with a congenital 21-hydroxylase deficiency (compound heterozygote for two severe mutations in the CYP21A2 gene) untreated for 20 years. His evaluation at 36 years of age showed a four-centimeter mass in the left adrenal gland, with most characteristics suggestive of malignancy (CT and positron emission tomography [PET] scan). We performed a surgical resection that established the diagnosis of adrenocortical tumor of uncertain prognosis (Weiss's score: 3). Even though malignant tumors are unusual in adrenal deficiency, our observation shows the need for a replacement therapy during adulthood, with a regular CT scan follow up in order to diagnose early isolated adrenal adenoma and remove it in case of malignancy suspicion.

p.H62L, a rare mutation of the CYP21 gene identified in two forms of 21-hydroxylase deficiency.

CONTEXT: Steroid 21-hydroxylase deficiency is the most common enzymatic defect causing congenital adrenal hyperplasia with good genotype/phenotype relationships for common mutations. To determine the severity of rare mutations is essential for genetic counseling and better understanding of the structure-function of the cytochrome P450c21. OBJECTIVE: The p.H62L mutation was the most frequent of 60 new mutations detected in 2900 steroid 21-hydroxylase deficiency patients, either isolated or associated on the same allele with a mild mutation (p.P453S, p.P30L, or partial promoter). Because phenotypes seemed to differ between patients with isolated or associated p.H62L, a detailed phenotype description and functional studies were performed. RESULTS: Regarding phenotype, patients with isolated p.H62L had a nonclassical form, whereas patients with the association p.H62L + mild mutation had a simple virilizing form. Functional studies showed that p.H62L reduced the conversion of the two substrates, progesterone and 17-hydroxyprogesterone, in the same way as the mild p.P453S; the association p.H62L + p.P453S decreased enzymatic activity more strongly while conserving residual activity at a level intermediate between p.P453S and p.I172N. This suggested that p.H62L was a mild mutation, whereas a synergistic effect occurred when it was associated. Analysis of p.H62L in a three-dimensional model structure of the CYP21 protein explained the observed in vitro effects, the H62 being located in a domain implied in membrane anchoring. CONCLUSION: According to phenotype and functional studies, p.H62L is a mild mutation, responsible for a more severe phenotype when associated with another mild mutation. These data are important for patient management and genetic counseling.

[Campylobacter jejuni and cytomegalovirus (CMV) infections in patients with the Guillain-Barre syndrome]. / Infections à Campylobacter jejuni et à cytomégalovirus (CMV) associées au syndrome de Guillain-Barré (SGB).

Guillain-Barre syndrome (GBS) is a rare disease triggered by postinfectious mechanisms. The disease concerns all ages, and is widely distributed around the world. The principal risks are respiratory failure, especially during the initial phase of the disease, and persisting deficit at long term. Among the infectious known agents, Campylobacter jejuni and CMV represent more than 40% of GBS causes. The clinical presentation, and the long-term prognosis of GBS related to these two etiologies are different. The physiopathological mechanisms of the nervous attack are probably also different. There is no proof, at this time, that anti-infectious treatment can improve the prognosis. The treatment is based on the early use of immunomodulatory treatments like intravenous immunoglobulins or plasma exchanges.

Significance of phrenic nerve electrophysiological abnormalities in Guillain-Barré syndrome.

The authors investigated whether the amplitude and latency of diaphragm compound muscle action potential helped predict respiratory failure in Guillain-Barré syndrome. Both variables were significantly but weakly correlated with vital capacity (VC) and were similar in unventilated (n = 60) and ventilated (n = 10) patients. In ventilated patients, motor loss severity, progression, and VC reduction were significantly greater, and bulbar dysfunction was more common. Predicting respiratory failure must rely on clinical features and VC.

21-Hydroxylase deficiency: an exemplary model of the contribution of molecular biology in the understanding and management of the disease.

Congenital adrenal hyperplasia (CAH) is a family of autosomal recessive disorders caused by mutations in genes encoding the enzymes involved in one of the various steps of adrenal steroid synthesis. Steroid 21-hydroxylase deficiency (21-OHD) is responsible for over 95% of the 5 forms of CAH, and results due to enzymatic defect owing to mutation in the CYP21 gene. The disease has two major clinical presentations. The "classical" form is severe, and divided into a salt wasting (SW) and simple virilizing (SV) subgroups. In both, affected female fetuses undergo virilization of the external genitalia prenatally and present at birth with sexual ambiguity. In addition, in both sexes infants with SW CAH are at risk of life-threatening adrenal crisis without treatment. This is why it is so important to make a diagnosis and to counsel the families. The diagnosis is easy by measuring the plasma levels of 17-hydroxyprogesterone (17-OHP) in antenatal (amniotic fluid), or perinatal samples (peripheral blood). Confirmation by molecular genetic analysis is advised. The second form of 21-OHD is called "non classical" because the presentation is much less severe and the onset of clinical expression occurs long after birth, often in the peripubertal period, as non-specific symptoms of hyperandrogeny. The unambiguous diagnosis of the latter requires a simple short ACTH test, with the measurement of 17-OHP at 60 min. In both forms, the mutations on the gene CYP21 responsible for the disease are now well known and can be identified by molecular biology techniques. There is a good correlation between phenotypes and genotypes, due to variable amount of the 21-hydroxylase-enzyme activity left (null to 50-60%). SW, SV and NC forms are associated with distinct mutations or combination of mutations. Nowadays, by combining hormonal and molecular tests, it is possible to predict the clinical form of the disease in a given family in the context of a prenatal diagnosis, which can lead to a prenatal treatment. Therefore, 21-OHD genotyping also appears essential for a new approach of genetic counseling, prediction of clinical form after postnatal screening and to define the post-ACTH 17-OHP values indicating the cut-off lines between NC, heterozygote and normal subjects.

Follow-up of 68 children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency: relevance of genotype for management.

The phenotype of congenital adrenal hyperplasia (CAH) varies greatly. The purpose of this study was to optimize diagnosis and follow-up by comparing phenotype with genotype. Sixty-eight patients with CAH due to 21-hydroxylase deficiency were studied by clinical, hormonal, and molecular genetic methods. Patients were classified according to predicted mutation severity: group 0, null mutation (17.6%); group A, homozygous for IVS2 splice mutation or compound heterozygous for IVS2 and null mutations (33.8%); group B, homozygous or compound heterozygous for I172N mutation (14.7%); group C, homozygous or compound heterozygous for V281L or P30L mutations (26.5%); and group D, mutations with unknown enzyme activity (7.4%). All group 0 and A patients had the salt-wasting form, and group C had nonclassical forms. Group B included five salt-wasting and five simple virilizing forms. Groups 0 and A were younger at diagnosis (P < 0.02), and females were more virilized than those in group B. Group B had higher basal plasma 17-hydroxyprogesterone (564 +/- 162 nmol/liter) and testosterone (11 +/- 3 nmol/liter) levels than group C [59 +/- 13 nmol/liter (P < 0.001) and 1.4 +/- 0.2 nmol/liter (P < 0.005), respectively]. Hydrocortisone doses given to groups 0, A, and B were similar at all ages, but lower in group C (P < 0.01). Final height was below target height in classical (n = 16; -2 +/- 0.2 SD score; P < 0.02) and nonclassical (n = 11; -1.2 +/- 0.4 SD score; P < 0.03) forms. The severity of the genetic defects and the clinical-laboratory features are well correlated. Genotyping, combined with neonatal screening and optimal medical and surgical treatment, can help in the management of CAH.

Phenotype-genotype correlation in 56 women with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

Complete analysis of the CYP21 gene was performed in 56 unrelated French women with symptomatic nonclassical congenital adrenal hyperplasia. The mutational spectrum and the phenotype-genotype correlation were examined. The overall predominant mutation was V281L, which was present on 51% of alleles and in 80% of women. Three novel mutations were found: L317M, R435C, and a 5'-end gene conversion. Sixty-three percent of the women were carrying a severe mutation of the CYP21 gene, and hence risk giving birth to children with a classical form of the disease. In such cases, screening for heterozygosity in the partner is crucial. Potential genotype/phenotype correlations were examined by classifying the patients into three groups according to the CYP21 allelic combinations: A (mild/mild), B (mild/severe), and C (severe/severe). Primary amenorrhea was more frequent, and mean basal and stimulated 17-hydroxyprogesterone levels were higher in compound heterozygotes for mild and severe mutations (group B) compared with women with two mild mutations (group A), but there was a considerable overlap for individual values. Surprisingly, in two women, a severe mutation was found on both alleles (group C). Therefore, the phenotype cannot be accurately predicted from the genotype. Variability in phenotypic expression may be conditioned by mechanisms other than genetic heterogeneity at the CYP21 locus.