Evaluation of several routine methods for fosfomycin and mecillinam susceptibility testing of Enterobacterales urine isolates.

OBJECTIVES: Performance evaluation of routine laboratory methods to determine the susceptibility of Enterobacterales urinary isolates to fosfomycin (oral administration) and mecillinam. METHODS: We collected 347 Enterobacterales isolates from monomicrobial midstream urine samples from women with significant bacteriuria and leukocyturia. Mostly non-Escherichia coli isolates (i.e. Klebsiella spp., Citrobacter koseri, Enterobacter cloacae complex and Proteus mirabilis) were included (n = 298). Performance of VITEK®2, ETEST®, and disc diffusion to determine fosfomycin and mecillinam susceptibility was evaluated following International Organization for Standardization (ISO) 20776-2:2021 (or 20776-2:2007 for disc diffusion) in comparison with the agar dilution reference method. RESULTS: For fosfomycin testing, VITEK®2 and ETEST® were close to reaching ISO requirements (essential agreement  ≥ 90%; bias  ±30%) for C. koseri, E. coli and P. mirabilis. Categorical agreement (CA) and major error rates were acceptable for disc diffusion. Fosfomycin displayed lower activity against E. cloacae complex and Klebsiella spp., with MIC50 (minimum inhibitory concentration required to inhibit the growth of 50% of tested isolates) equal to the E. coli EUCAST breakpoint (8 mg/L). For these species, the three alternative techniques overestimated MICs and resistance, and did not meet performance criteria. For mecillinam testing of Enterobacterales isolates, apart from P. mirabilis, ETEST® nearly fulfilled ISO requirements, and CA rates were acceptable for disc diffusion. ISO criteria were reached for C. koseri and E. coli testing with VITEK®2, apart from too high rates of very major errors. For P. mirabilis, performances were unacceptable, whatever the routine method used. CONCLUSIONS: Commercially available tests may serve as alternatives to agar dilution to assess fosfomycin (oral) and mecillinam susceptibility of Enterobacterales urinary isolates, with important interspecies variabilities. Additional studies comprising more fosfomycin- and mecillinam-resistant isolates are needed to strengthen our conclusions.

Multicenter Evaluation of the Novel ETEST Fosfomycin for Antimicrobial Susceptibility Testing of Enterobacterales, Enterococcus faecalis, and Staphylococcus Species.

Fosfomycin is a phosphonic acid derivative active against a wide spectrum of Gram-positive and Gram-negative pathogens. It is used for the treatment of uncomplicated urinary tract infections (uUTI) or severe infections by oral or intravenous (i.v.) administration. In order to improve its performance and robustness, the fosfomycin strip, an antibiotic gradient diffusion strip, was redeveloped and evaluated in the multicenter study summarized in this paper. ETEST fosfomycin (ETEST FO) clinical performance was evaluated by three study sites on 152 Enterococcus faecalis, 100 Staphylococcus spp. and 330 Enterobacterales in comparison with the CLSI and EUCAST agar dilution reference method. Referring to FDA performance criteria, the ETEST FO achieved 91.0% of essential (EA) and 99.0% of categorical agreement (CA) for Escherichia coli. In addition, 98.0% EA and 93.4% CA were achieved for E. faecalis, with no very major errors (VME) or major errors (ME). According to EUCAST breakpoints for intravenous fosfomycin use, Enterobacterales and Staphylococcus spp. also met ISO acceptance criteria for EA and CA (EA 91.5%, 94.0%, respectively, and CA 98.0% for both). A VME rate of 8.8% was observed for Enterobacterales but the MICs were within EA. A trend to predict lower MICs for Citrobacter spp., E. coli and Salmonella enterica and to predict higher MICs for Klebsiella pneumoniae MICs was observed, while ETEST FO should not be used for Enterobacter cloacae, because of low EA and a high VME rate. The study results support the efficiency of the novel ETEST FO, making it an easy-to-handle tool as a substitute to the classical agar dilution method.

Obliquity-paced Pliocene West Antarctic ice sheet oscillations.

Thirty years after oxygen isotope records from microfossils deposited in ocean sediments confirmed the hypothesis that variations in the Earth's orbital geometry control the ice ages, fundamental questions remain over the response of the Antarctic ice sheets to orbital cycles. Furthermore, an understanding of the behaviour of the marine-based West Antarctic ice sheet (WAIS) during the 'warmer-than-present' early-Pliocene epoch ( approximately 5-3 Myr ago) is needed to better constrain the possible range of ice-sheet behaviour in the context of future global warming. Here we present a marine glacial record from the upper 600 m of the AND-1B sediment core recovered from beneath the northwest part of the Ross ice shelf by the ANDRILL programme and demonstrate well-dated, approximately 40-kyr cyclic variations in ice-sheet extent linked to cycles in insolation influenced by changes in the Earth's axial tilt (obliquity) during the Pliocene. Our data provide direct evidence for orbitally induced oscillations in the WAIS, which periodically collapsed, resulting in a switch from grounded ice, or ice shelves, to open waters in the Ross embayment when planetary temperatures were up to approximately 3 degrees C warmer than today and atmospheric CO(2) concentration was as high as approximately 400 p.p.m.v. (refs 5, 6). The evidence is consistent with a new ice-sheet/ice-shelf model that simulates fluctuations in Antarctic ice volume of up to +7 m in equivalent sea level associated with the loss of the WAIS and up to +3 m in equivalent sea level from the East Antarctic ice sheet, in response to ocean-induced melting paced by obliquity. During interglacial times, diatomaceous sediments indicate high surface-water productivity, minimal summer sea ice and air temperatures above freezing, suggesting an additional influence of surface melt under conditions of elevated CO(2).

Role of EGFR family receptors in proliferation of squamous carcinoma cells induced by wound healing fluids of head and neck cancer patients.

BACKGROUND: Mounting evidence suggests that recurrence of resected head and neck squamous cell carcinomas (HNSCCs) is due to the outgrowth of unrecognized residual tumor cells as well as to the premalignant and/or precursor-field epithelial cells. We studied the impact of processes triggered by HNSCC surgery in stimulating both residual tumor cells [demonstrated to overexpress epidermal growth factor receptor (EGFR)], and premalignant cells surrounding the resected lesion. PATIENTS AND METHODS: EGFR expression/activation by immunohistochemistry/biochemistry and gene status by FISH were investigated in 23 primary HNSCCs and surrounding tissues. The ability to induce cell proliferation of wound healing drainages collected from 12 relapsed and 11 not relapsed patients was evaluated by a colorimetric assay in squamous cell carcinoma cell lines A431 (carrying EGFR amplification) and CAL27 (carrying three EGFR copies) in the presence/absence of EGFR therapeutic inhibitors. RESULTS: Primary tumors showed intermediate/high EGFR expression (91%), EGFR phosphorylation and EGFR-positive FISH (35%). Normal, metaplastic and dysplastic epithelium surrounding the resected tumor displayed EGFR overexpression. EGFR activation and gene amplification were observed in normal and dysplastic epithelium, respectively. Each tested wound healing drainage induced the cells to proliferate and the proliferation was significantly higher in relapsed compared with not relapsed HNSCC patients (P = 0.02 and P = 0.03). Anti-EGFR treatments inhibited the drainage-induced proliferation, with the highest inhibitory efficiency by cetuximab on A431 cells, while CAL27 cell growth was more efficiently inhibited by tyrosine kinase inhibitors. CONCLUSIONS: Surgery could favor the proliferation of cells showing EGFR overexpression/activation/amplification such as residual tumor cells and/or precursor-field epithelial cells already present after surgery. Treatment with anti-EGFR reagents inhibits wound-induced stimulation, according to the EGFR family status.

Prevalence, incidence and associated factors for HBV infection among male and female prisoners in Central Brazil: A multicenter study.

BACKGROUND: Prison populations are at high risk for hepatitis B virus (HBV) infection. The aim of this study was to assess the prevalence, incidence, HBV associated factors and circulating genotypes/subtypes. METHODS: A total of 3,368 prisoners from 12 closed prisons were randomly recruited for a cross-sectional study. In addition, a cohort study was conducted 12 months later and included 1,656 individuals. Participants underwent an interview and blood collection for the detection of HBV serological markers and HBV-DNA phylogenetic analysis. RESULTS: HBV exposure (anti-HBc+) was 9.8% (95% CI: 8.8-10.8); 11.2% were female and 9.6% were male. HBsAg+ was 0.6%. Only 31.4% of the participants had HBV vaccination-like profile (anti-HBs+ alone; 30.4% male vs. 36.8% female; p=0.004). Most individuals were susceptible to HBV (60.2% female vs. 52.2% male, p=0.001). HBV isolates were classified as genotypes A (45.4%), D (27.3%) and F (27.3%). In males, HBV exposure was associated with increased age. Male prisoners had more evidence of HCV/HBV co-infection (10.7%) than females (3.4%) and the frequency of Treponema pallidum infection among prisoners who had been exposed to HBV was higher in female prisoners when compared with male (39.7% vs. 19.1%). The incidence of HBV was 0.18/100 person-years (95% CI: 0.12%-0.25%). CONCLUSIONS: Our results indicate a high prevalence of HBV exposure in prisoners. Despite the low incidence of this infection, the occurrence of new cases indicates the need to implement preventive measures.

Epidemiological study of hepatitis B virus among prisoners with active tuberculosis in Central Brazil.

BACKGROUND: Due to environmental and social conditions inherent to incarceration, tuberculosis (TB) and hepatitis B virus (HBV) are major diseases among prison inmates. OBJECTIVE: To determine overall and occult HBV infection (OBI) prevalence rates, risk factors and genotype distribution among inmates with active TB. STUDY DESIGN: A cross-sectional study was conducted among 216 inmates with active TB recruited at the largest prisons in Campo Grande, Mato Grosso do Sul, Central Brazil. The participants were interviewed and tested for the presence of serological markers for HBV infection. RESULTS: The overall prevalence of HBV infection (total hepatitis B core antibodies) was 10.2% (95%CI 6.2-14.2). HBV surface antigen (HBsAg) prevalence was 1.4% (3/216). HBV DNA was detected in all three HBsAg-positive samples and in 10.5% (2/19) of the anti-HBc-positive samples (OBI), giving a HBV-TB co-infection prevalence of 2.3% (5/216). A multivariate analysis of risk factors showed that history of sharing cutting instruments, length of incarceration and homosexual sex were associated with HBV infection. CONCLUSION: Our findings indicate that HBV remains an important public health concern among prison inmates and active TB-HBV co-infection needs to be addressed for effective treatment.

[Diagnostic splenectomy. Apropos of 38 cases]. / La splénectomie à visée diagnostique. A propos de trente-huit cas.

The authors report a retrospective study of 38 splenectomies performed as a diagnostic procedure. In the first group, the diagnosis was made by surgery: 27 cases (71.1%) included the usual large number of lymphomas. In the second group, there was no conclusion: 11 cases (28.9%), patients were younger and the spleen was lighter with a statistical significance (p less than 0.006 and p less than 0.003). Three of the 11 patients in the second group subsequently developed a malignant blood disease. Morbidity was high: out of 38 cases, 14 complications occurred in 11 patients (28.9%). One patient died on the fifty fifth postoperative day. The authors consider that splenectomy for undiagnosed splenomegaly is an effective procedure for diagnosing lymphoma, but not without risk. Indications for surgery must be carefully evaluated. It is more questionable in young, asymptomatic patients or in the case of moderate splenomegaly. After surgery, with no histologic diagnosis only a long-term survey will differentiate patients with malignant blood diseases from patients with idiopathic splenomegaly.

[Pancreatic somatostatinoma and MEN 1. Apropos of a case. Review of the literature]. / Somatostatinome pancréatique et NEM 1. A propos d'une observation. Revue de la littérature.

The pancreatic somatostatinoma belongs to the type of rare endocrine tumors of the pancreas. We report the observation of a 54 year old woman. Previously she was suffering from diabetes mellitus. An abdominal ultrasonography revealed an endocrine tumor of the pancreatic tail. There was no specific symptomatology, with the exception for the hyperglycaemia. The diagnosis of somatostatinoma was certified post operatively by the immunocytochemistry of the tumor. Then, the patient developed a hypercalcaemia associated with an increase of parathyroid hormone. The surgery of the neck revealed three hyperplastic parathyroids, inducing this association as a multiple endocrine neoplasia type 1 (MEN 1). The patient did not develop pituitary tumor. Afterwards, scintigraphy with 111 Indium- octreotide showed a residual tumor at the head of pancreas. Basal levels of somatostatine and calcium, pentagastrine test, computed tomography scan, arteriography were negative. The presence of a second somatostatinoma was confirmed by surgery and immunohistology. One year after the surgery, the patient remains clinically well. The pancreatic localization of the somatostatinoma in a MEN 1 is poorly documented. Its malignant nature can only be assured by the presence of metastases. The genetic detection of the MEN 1 becomes possible. Above all, the treatment is based on surgery and/or chemotherapy (Fluoro-Uracile; Streptozotocine). In our case, 111 In-octreotide scintigraphy was the only method demonstrating a residual focus, suggesting it could be an element of reference for the diagnosis and survey of somatostatinoma the watch of patients having a treatment for somatostatinoma.

[Sigmoido-uterine fistula of diverticular origin. Review of the literature apropos of a case]. / Les fistules sigmoïdo-utérines d'origine diverticulaire. Revue de la littérature à propos d'un cas.

The authors report one case of sigmoid-uterine fistula of diverticular origin with a favorable outcome after an ideal colectomy associated with subtotal hysterectomy. They emphasize the rarity of this complication, due to the resistance of the uterine tissue. Its diagnosis is primarily clinical, and other examinations are required only to establish the etiological diagnosis. Surgery must be curative, ideally in one stage including the treatment of the diverticular disease and that of its gynecological consequences, which may vary according to the local conditions.

[Splenectomy for massive splenomegaly. Apropos of 36 cases]. / Splénectomie pour splénomégalie massive. A propos de 36 observations.

Thirty-six splenectomies for splenomegaly exceeding 1000 grams are reported. The enlargement of the spleen most often was related with a malignant disease (n = 32). Cytopenia was the main indication in 14 cases, and splenectomy was contemplated for diagnosis (n = 12), initial treatment (n = 6), or due to pain (n = 3) or spontaneous rupture (n = 1). Ten patients (27.8%) had an associated surgical treatment. One patient died postoperatively (2.8%) and 12 patients presented with 14 complications (33%) usually with a rapidly favorable evolution. In 11 of 12 cases (91.6%), the operation allowed establishing the diagnosis in cases of splenomegaly with an unknown origin. Lastly, it was always effective to relieve pain and in most cases improved cytopenia. The authors conclude that the patients with massive splenomegaly are improved by splenectomy, although it most often is merely a palliative treatment in cases of malignant hemopathy.

[A new case of cystic lymphangioma of the pancreas]. / Un nouveau cas de lymphangiome kystique du pancréas.

The authors describe a new case of cystic lymphangioma of the pancreas treated surgically by cephalic duodeno-pancreatectomy associated with right hemicolectomy. Following a review of the literature, they recall the anatomo-pathological and clinical characteristics of vascular connective tissue tumors of the pancreas. From a therapeutic viewpoint, they conclude on the necessity for complete removal of these unusual tumors, either by tumor resection or by appropriate pancreatic resection, which are the only guarantees of a definitive curve.

[Predictive factors of mortality and morbidity in colectomy patients over 75 years of age. Report of 69 cases]. / Facteurs prédictifs de mortalité et de morbidité dans la chirurgie colique d'exérèse chez les sujets de plus de 75 ans. A propos de 69 observations.

Sixty nine patients over 75 years old who had a colectomy were retrospectively studied. The carcinoma of the colon represented the main indication for 42 cases (60.9%) and 22 patients (31.9%) were immediately operated. The influence of parameters such as age, sex, visceral defects, emergency, performance of a colostomy or associated intervention, type of colic pathology, was statistically studied. The age (p less than 0.05), emergency (p less than 0.03) and the number of defects greater than or equal to 3 (p less than 0.04) contribute to mortality. The number of defects greater than or equal to 3 (p less than 0.006) contributes to general morbidity. Only complications connected with the operation by itself significantly prolong the duration of hospitalization (p less than 0.02). The authors draw the conclusion that the age by itself is not a contra-indication for operation except in case of associated polyvisceral failure. In addition, it is required to carry out an early detection of colic lesions in elderly subjects in order to contemplate surgery before complications whose prognosis is fearsome (54.5% of death in emergency operation).

Prevalence and epidemiology of chronic hepatitis C among prisoners of Mato Grosso do Sul State, Brazil

In Mato Grosso do Sul state, Brazil, the number of prisoners has increased in the recent years and the control of hepatitis C virus (HCV) has become more complex. The aim of the present study was to estimate the prevalence and identify the genotypes of HCV in prisoners as well as the factors associated with this infectious disease. Thereby, 443 men and 243 women from prisons were interviewed and subjected to blood collection. Anti-HCV reactive samples were analyzed by RT-PCR and genotyped. The overall seroprevalence of HCV infection was 4.8 percent (95 percentCI: 3.4 to 6.8 percent). Furthermore, the prevalence was higher in: men, injecting drug users, tattooed persons, those who were more than 50 years old, individuals who have been arrested multiple times, people with previous history of sexually transmitted disease (STD), persons who received blood transfusions or those with HIV/AIDS. The prevalence of RNA HCV by PCR was 3.0 percent (95 percentCI: 1.7 to 4.2 percent). Moreover, the coinfection of HIV and HCV was 33.3 percent. In addition, genotype 1 was the most frequent (85 percent) followed by genotype 3 (15 percent). The screening strategy for HCV and other infectious diseases in inmates is important as it establishes an early diagnosis, opportunity for treatment and allows the breaking of the transmission chain.