Klebsiella pneumoniae carrying multiple alleles of antigen 43-encoding gene of Escherichia coli associated with biofilm formation

A clinical strain of Klebsiella pneumoniae typed as sequence type 307 carrying three different alleles of the flu gene encoding the Escherichia coli virulence factor antigen 43 associated with biofilm formation was detected and characterized. The flu alleles are located in the chromosome inside putative integrative conjugative elements. The strain displays the phenotypes associated with Ag43, i.e. bi-phasic colony morphology and enhanced biofilm production. Furthermore, the strain produces low amount of capsule known to affect Ag43 function. Analysis of 1431 worldwide deposited genomes revealed that 3.7% Klebsiella pneumoniae carry one or two flu alleles

Mutation of hilD in a Salmonella Derby lineage linked to swine adaptation and reduced risk to human health

Salmonella enterica variants exhibit diverse host adaptation, outcome of infection, and associated risk to food safety. Analysis of the distribution of Salmonella enterica serovar Derby (S. Derby) subtypes in human and swine identified isolates with a distinct PFGE profile that were significantly under-represented in human infections, consistent with further host adaptation to swine. Here we show that isolates with this PFGE profile form a distinct phylogenetic sub-clade within S. Derby and exhibit a profound reduction in invasion of human epithelial cells, and a relatively small reduction in swine epithelial cells. A single missense mutation in hilD, that encodes the master-regulator of the Salmonella Pathogenicity Island 1 (SPI-1), was present in the adapted lineage. The missense mutation resulted in a loss of function of HilD that accounted for reduced invasion in human epithelial cells. The relatively small impact of the mutation on interaction with swine cells was consistent with an alternative mechanism of invasion in this pathogen-host combination

Varianti della malattia da anticorpi anti-GBM (mAbGBM): malattia renale da anticorpi anti-GBM in assenza di anticorpi circolanti

Introduzione: La diagnosi di mAbGBM si basa generalmente sul riscontro di anticorpi (Ab) sierici anti-GBM. Nell'evenienza di un test ELISA negativo si esclude la patologia. Tuttavia in letteratura sono stati descritti diversi casi clinici di mAbGBM in assenza di Ab circolanti (sieronegativa) nei quali la diagnosi è stata posta con la biopsia renale (BR). Scopo: Descrizione di 4 casi clinici di mAbGBM sieronegativa seguiti presso il nostro Centro. Revisione della letteratura riguardante la mAbGBM sieronegativa. Paziente 1: donna di 19 anni ricoverata dopo 2 settimane di febbre per dolore al fianco e macroematuria. Riscontro di peggioramento della funzione renale, leucocitosi, anemia. Rx torace negativo. Sierologia per l’autoimmunità negativa, inclusi ANCA e Ab anti-GBM. Alla BR riscontro di semilune cellulari, necrosi segmentale e colorazione lineare per IgG all’immunofluorescenza (IF). Sottoposta a terapia immunosoppressiva per un anno, ha raggiunto una remissione completa e stabile. Al 7° anno di follow-up presentava una clearance della creatinina (Clcr) 99ml/min. Paziente 2: uomo di 46 anni ricoverato in rianimazione per insufficienza respiratoria acuta rapidamente ingravescente, emottisi, IRA con sindrome nefritica. Immediatamente iniziate ventilazione invasiva e CVVH. Indagini per l’autoimmunità ripetutamente negative, inclusi ANCA e Ab anti-GBM. Veniva intrapresa terapia steroidea con rapido miglioramento dell’insufficienza respiratoria. Alla BR (Fig. 1 e 2), eseguita 20 giorni dopo l'ingresso (paziente ancora emodialisi dipendente), presenza di semilune, necrosi segmentale e colorazione lineare per IgG all’IF. Veniva trattato con plasmaferesi, steroide e ciclofosfamide (CYC). Al 16° mese di follow-up: Clcr 28ml/min. Paziente 3: donna di 57 anni ricoverata per anasarca, sindrome nefrosica severa ed ematuria nel contesto di un'insufficienza renale rapidamente progressiva. Ricerca di ANCA e Ab anti-GBM negativa. Alla BR riscontro di GN membranosa (GNM) con sovrapposte semilune, necrosi del flocculo e colorazione lineare per IgG all’IF. Negativo il test per gli Ab anti-PLA2R. Veniva iniziata una terapia immunosoppressiva con boli steroidei e CYC. All'esclusione di una possibile origine paraneoplastica della GNM riscontro di una neoplasia endometriale. Sospesa la CYC, la paziente veniva sottoposta a isterectomia e chemioterapia adiuvante. Al 7° mese di follow-up: Clcr 50ml/min. Paziente 4: donna di 65 anni con diagnosi di GPA nel 1999, in completa remissione da molti anni, senza danno d’organo. In terapia solo con basse dosi di steroide (20mg/sett) per il recente riscontro di condiloma genitale HPV-associato. Ricoverata per piressia, consolidamento polmonare e nefrite con funzione renale conservata. Alla broncoscopia e al BAL non emorragie o infezioni in atto. ANCA ripetutamente negativi all'ELISA, isolata positività 2+ c-ANCA all’IFI. Alla BR (Fig. 3 e 4) semilune focali, glomerulonefrite necrotizzante e all’IF colorazione lineare per IgM e presenza di restrizione per le catene leggere λ. Ricerca degli Ab anti-GBM negativa. Elettroforesi, immunofissazione e catene leggere siero/urine negative per componenti monoclonali. Veniva trattata con steroide (1mg/Kg) e Rituximab. Al 3° mese di follow-up: Clcr 95ml/min. Letteratura: In letteratura sono stati segnalati 43 casi clinici di mAbGBM sieronegativa con mancato riscontro di Ab anti-GBM circolanti ma presenza alla biopsia renale/polmonare di deposizione lineare di immunoglobuline all'IF. Questa variante della mAbGBM può presentarsi isolata, associata alla presenza di ANCA (pazienti definiti doppi positivi), sovrapposta a GNM, associata a restrizione delle catene leggere, con Ab anti-GBM di classe IgG (variante piè tipica) ma anche IgM o IgA, paucisintomatica, o con un quadro esclusivo di coinvolgimento polmonare o renale. In Tabella sono riportati gli articoli che abbiamo ritenuto piè significativi. Conclusioni: Alla luce delle sempre maggiori evidenze di varianti della mAbGBM non è possibile escludere una mAbGBM sieronegativa solo attraverso un risultato negativo al test ELISA per gli Ab anti-GBM. Una mAbGBM sieronegativa può essere presente anche in pz con vasculite ANCA positiva ("doppio positivo istologico") pertanto, qualora l'andamento della vasculite ANCA positiva in risposta alla terapia non sia quello atteso, è necessaria l’esecuzione della biopsia renale che, in questo contesto, è l’unica opzione per una diagnosi corretta di mAbGBM

Tunneled hemodialysis central venous catheters prevalence and bloodstream infection rates in Northern Italy: A survey of the "East Lombardy Nephrological Network"

Background: Tunneled central venous catheter (tCVCs) is a vascular access frequently employed in hemodialysis patients. Catheter-related bloodstream infections (CRBSI) are potentially life-threatening complications. Methods: We performed a retrospective survey regarding tCVCs prevalence as well as the CRBSI incidence and management within five hospitals in the Brescia province belonging to the "East Lombardy Nephrological Network"; this study was based upon 18 queries regarding the years 2020 and 2021. Results: The data collected refer to an overall hemodialysis population of 736 patients in 2020 and 745 patients in 2021. The prevalence of tCVCs was respectively 22.1% and 24.2% with the initial placement being performed with fluoroscopy support in 80% of the centers. CRBSI incidence was respectively 0.88 and 0.77 episodes per 1000 days of tCVC use. When the CRBI was caused by Staphylococcus Aureus (SA) or Pseudomonas, differently from the recommendation of the KDOQI guidelines, the removal or the substitution of the tCVC did not occur immediately at the time of the diagnosis of the infection but only when the specific antibiotic therapy failed. A nose swab aimed at identifying SA carriers was performed in 60% of centers. The policy regarding the referral to other specialists (infectious disease specialist and microbiologist) was heterogenous across the centers according to their specific logistics. Conclusions: This retrospective survey performed by the "East Lombardy Nephrological Network" within the Brescia province describes the prevalence of tCVCs use as well as the incidence and management of CRBSIs in the hemodialysis patients of this area. The clinical impact of the differences in terms of clinical approach detected compared to the KDOQI guidelines will need to be clarified ideally in prospective studies

[Managing patients in dialysis and with kidney transplant infected with Covid-19]

We are in the midst of a health emergency that is totally new for us all and that requires a concerted effort, especially when it comes to safeguarding patients on hemodialysis, and kidney transplant recipients. Brescia is currently a very active cluster of infections (2918 cases on the 17/03/2020), second only to Bergamo. The way our structure is organised has allowed us to treat nephropathic patients directly within the Nephrology Unit, following of course a great deal of reshuffling; at the moment, we are treating 21 transplanted patients and 17 on hemodialysis. This has led us to adopt a systematic approach to handling this emergency, not only in managing inpatients, but also in researching the new disease. Our approach is mirrored in the guidelines attached to this article, originally intended for internal use only but potentially very useful to our colleagues, as they face the same exact problems. We have also started collecting data on our positive patients with the aim of understanding better the functioning of this disease and how best to manage it. If anyone is interested, we ask you to please get in touch with us, so we can coordinate our efforts

Effects of different membranes and dialysis technologies on patient treatment tolerance and nutritional parameters

There is increasing evidence that the biochemical and cellular phenomena induced by blood/membrane/dialysate interactions contribute to dialysis-related intradialytic and long-term complications. However, there is a lack of large, prospective, randomized trials comparing biocompatible and bioincompatible membranes, and convective and diffusive treatment modalities. The primary aim of this prospective, randomized trial was to evaluate whether the use of polysulfone membrane with bicarbonate dialysate offers any advantages (in terms of treatment tolerance, nutritional parameters and pre-treatment beta(2)-microglobulin levels) over a traditional membrane (Cu-prophan(R)). A secondary aim was to assess whether the use of more sophisticated methods consisting of a biocompatible synthetic membrane with different hydraulic permeability at different ultrafiltration rate (high-flux hemodialysis and hemodiafiltration) offers any further advantages. Seventy-one Centers were involved and stratified according to the availability of only the first two or all four of the following techniques: Cuprophan(R) hemodialysis (Cu-HD), low flux polysulfone hemodialysis (LfPS-HD), high-flux polysulfone high-flux hemodialysis (HfPS-HD), and high-flux polysulfone hemodiafiltration (HfPS-HDF). The 380 eligible patients were randomized to one of the two or four treatments (132 to Cu-HD, 147 to LfPS-HD, 51 to HfPS-HD and 50 to HfPS-HDF). The follow-up was 24 months. No statistical difference was observed in the algebraic sum of the end points between bicarbonate dialysis with Cuprophan(R) or with low-flux polysulfone, or among the four dialysis methods under evaluation. There was a significant decrease in pre-dialysis plasma beta(2)-microglobulin levels in high-flux dialysis of 9.04+/-10.46 mg/liter (23%) and in hemodiafiltration of 6.35+/-12.28 mg/liter (16%), both using high-flux polysulfone membrane in comparison with Cuprophan(R) and low-flux polysulfone membranes (P=0.032). The significant decrease in pre-dialysis plasma beta(2)-microglobulin levels could have a clinical impact when one considers that beta(2)-microglobulin accumulation and amyloidosis are important long-term dialysis-related complications