Publications by authors named "Guido Granata"

36 Publications

Hospitalized patients with diarrhea: Rate of Clostridioides difficile infection underdiagnosis and drivers of clinical suspicion.

Anaerobe 2021 May 7;70:102380. Epub 2021 May 7.

National Institute for Infectious Diseases "Lazzaro Spallanzani", Via Portuense, 292-00149, Rome, Italy.

Objectives: Clostridioides difficile infection (CDI) represents a challenging issue, with an evolving epidemiology. Main objectives of our study were: to assess the frequency of diarrhea of overall etiology, including CDI, as a cause of hospital admission or occurring during hospital stay;- to determine the rate of underdiagnosis of community-acquired (CA-), health care associated (HCA)- and hospital onset (HO-) CDI, and explore factors associated with its clinical suspicion by physicians.

Methods: A prospective cohort study included all hospitalized patients with diarrhea at two acute-care hospitals. C. difficile (CD) tests were performed on every stool samples, irrespective of the treating physician request. Factors associated with the likelihood of CD test request by physicians were assessed.

Results: We enrolled 871 (6%) patients with diarrhea. CD test performed on all diarrheic stool samples was positive in 228 cases (26%); 37, 106, 85 cases of CA- (14%), HCA- (42%) and HO- diarrhea (24%), respectively. Treating physicians did not request CD test in 207 (24%) diarrhea cases. The rate of CDI underdiagnosis was 11% (24/228); it was higher in CA-CDI (27%, 10/37). Logistic regression analysis identified age >65 years (RR 1.1; 95 CI 1.06-1.2) and hospitalizations in the previous 3 months (RR 1.2; 95% CI 1.1-1.3) as independent factors associated with the likelihood of requesting the CD test by the physician. These risk factors differed by epidemiological classification of diarrhea and by hospital.

Conclusions: Our study confirmed the relevance of CDI underdiagnosis and provided new insights in the factors underlying the lack of CDI clinical suspicion.
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http://dx.doi.org/10.1016/j.anaerobe.2021.102380DOI Listing
May 2021

How to Treat COVID-19 Patients at Home in the Italian Context: An Expert Opinion.

Infect Dis Rep 2021 Mar 20;13(1):251-258. Epub 2021 Mar 20.

Italian College of General Practitioners and Primary Care, 50142 Florence, Italy.

The impact of the coronavirus disease (COVID-19), caused by the novel coronavirus SARS-CoV-2, continues to be widespread, with more than 100 million cases diagnosed in more than 220 countries since the virus was first identified in January 2020. Although patients with mild to moderate forms of COVID-19 could be efficiently managed at home, thus reducing the pressure on the healthcare system and minimizing socio-psychological impact on patients, no trial has been proposed, conducted, or even published on COVID-19 home therapy to date. These expert opinions provide indications on the therapeutical at home management of COVID-19 patients, based on the evidence from the literature and on current guidelines.
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http://dx.doi.org/10.3390/idr13010028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005965PMC
March 2021

Prospective Study on Incidence, Risk Factors and Outcome of Recurrent Infections.

J Clin Med 2021 Mar 8;10(5). Epub 2021 Mar 8.

Infectious Diseases, ASST Lecco Hospital, 23900 Lecco, Italy.

Background: Limited and wide-ranging data are available on the recurrent infection (rCDI) incidence rate.

Methods: We performed a cohort study with the aim to assess the incidence of and risk factors for rCDI. Adult patients with a first CDI, hospitalized in 15 Italian hospitals, were prospectively included and followed-up for 30 d after the end of antimicrobial treatment for their first CDI. A case-control study was performed to identify risk factors associated with 30-day onset rCDI.

Results: Three hundred nine patients with a first CDI were included in the study; 32% of the CDI episodes (99/309) were severe/complicated; complete follow-up was available for 288 patients (19 died during the first CDI episode, and 2 were lost during follow-up). At the end of the study, the crude all-cause mortality rate was 10.7% (33 deaths/309 patients). Two hundred seventy-one patients completed the follow-up; rCDI occurred in 21% of patients (56/271) with an incidence rate of 72/10,000 patient-days. Logistic regression analysis identified exposure to cephalosporin as an independent risk factor associated with rCDI (RR: 1.7; 95% CI: 1.1-2.7, = 0.03).

Conclusion: Our study confirms the relevance of rCDI in terms of morbidity and mortality and provides a reliable estimation of its incidence.
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http://dx.doi.org/10.3390/jcm10051127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962640PMC
March 2021

Risk and predictive factors of prolonged viral RNA shedding in upper respiratory specimens in a large cohort of COVID-19 patients admitted to an Italian reference hospital.

Int J Infect Dis 2021 Apr 3;105:532-539. Epub 2021 Mar 3.

National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy.

Background: Limited data are available about the predictors and outcomes associated with prolonged SARS-CoV-2 RNA shedding (VS).

Methods: A retrospective study including COVID-19 patients admitted to an Italian hospital between March 1 and July 1, 2020. Predictors of viral clearance (VC) and prolonged VS from the upper respiratory tract were assessed by Poisson regression and logistic regression analyses. The causal relation between VS and clinical outcomes was evaluated through an inverse probability weighted Cox model.

Results: The study included 536 subjects. The median duration of VS from symptoms onset was 18 days. The estimated 30-day probability of VC was 70.2%. Patients with comorbidities, lymphopenia at hospital admission, or moderate/severe respiratory disease had a lower chance of VC. The development of moderate/severe respiratory failure, delayed hospital admission after symptoms onset, baseline comorbidities, or D-dimer >1000ng/mL at admission independently predicted prolonged VS. The achievement of VC doubled the chance of clinical recovery and reduced the probability of death/mechanical ventilation.

Conclusions: Respiratory disease severity, comorbidities, delayed hospital admission and inflammatory markers negatively predicted VC, which resulted to be associated with better clinical outcomes. These findings highlight the importance of prompt hospitalization of symptomatic patients, especially where signs of severity or comorbidities are present.
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http://dx.doi.org/10.1016/j.ijid.2021.02.117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927669PMC
April 2021

The Burden of Clostridioides Difficile Infection during the COVID-19 Pandemic: A Retrospective Case-Control Study in Italian Hospitals (CloVid).

J Clin Med 2020 Nov 27;9(12). Epub 2020 Nov 27.

Clinical and Research Department for Infectious Diseases, Severe and Immunedepression-Associated Infections Unit, National Institute for Infectious Diseases L. Spallanzani IRCCS, 00149 Rome, Italy.

Data on the burden of infection (CDI) in Coronavirus Disease 2019 (COVID-19) patients are scant. We conducted an observational, retrospective, multicenter, 1:3 case (COVID-19 patients with CDI)-control (COVID-19 patients without CDI) study in Italy to assess incidence and outcomes, and to identify risk factors for CDI in COVID-19 patients. From February through July 2020, 8402 COVID-19 patients were admitted to eight Italian hospitals; 38 CDI cases were identified, including 32 hospital-onset-CDI (HO-CDI) and 6 community-onset, healthcare-associated-CDI (CO-HCA-CDI). HO-CDI incidence was 4.4 × 10,000 patient-days. The percentage of cases recovering without complications at discharge (i.e., pressure ulcers, chronic heart decompensation) was lower than among controls ( = 0.01); in-hospital stays was longer among cases, 35.0 versus 19.4 days ( = 0.0007). The presence of a previous hospitalisation ( = 0.001), previous steroid administration ( = 0.008) and the administration of antibiotics during the stay ( = 0.004) were risk factors associated with CDI. In conclusions, CDI complicates COVID-19, mainly in patients with co-morbidities and previous healthcare exposures. Its association with antibiotic usage and hospital acquired bacterial infections should lead to strengthen antimicrobial stewardship programmes and infection prevention and control activities.
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http://dx.doi.org/10.3390/jcm9123855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761275PMC
November 2020

Insights into the Clinical Management of Carbapenem-Resistant Gram-Negative Infections: An Italian Retrospective Clinical Chart Review

Infect Dis Rep 2020 05 5;12(2):8510. Epub 2020 Aug 5.

Clinical and Research Department, National Institute for Infectious Diseases Lazzaro Spallanzani, Scientific Institute for Treatment and Inpatient Care, Rome, Italy.

There is a lack of consensus regarding management of infections with carbapenem- resistant Gram-negative (CR-GN) pathogens. This study comprised a medical chart review to assess patient management in a high CR prevalence setting. Data was collated retrospectively from medical records of patients hospitalized between November 1, 2015 and October 31, 2016. Of 29 patients, 66% had respiratory tract infections. Median duration of hospitalization was 28 days and ~50% of patients were admitted to the intensive care unit, with 77% remaining for >2 weeks. Median time to obtain respiratory culture results was 5 days. Isolation of patients with diagnosed CR-GN infection took ≥5 days in >50% of patients. A majority (76%) of patients received ≥1 antibiotic before providing a specimen for culture; a total of 17 antibiotic treatments were used. Overall, 72% of patients, and 68% of those with respiratory infections, were discharged alive; 38% were discharged without further antibiotics. The difficulties in achieving effective management in patients with CR-GN infections are largely due to complex co-morbidities, a history of prior antibiotic treatment, and multiple referrals across health care facilities.
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http://dx.doi.org/10.4081/idr.2020.8510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7459762PMC
May 2020

Hessarek Gastroenteritis with Bacteremia: A Case Report and Literature Review.

Pathogens 2020 Aug 15;9(8). Epub 2020 Aug 15.

National Institute for Infectious Diseases "L. Spallanzani", Via Portuense, 292, 00149 Rome, Italy.

subspecies serotype Hessarek ( Hessarek) is considered a serovar with high host specificity and is an uncommon cause of disease in humans; no cases of Hessarek bacteremia have been reported in humans to date. On 16 July 2019, a young male presented abdominal pain, vomit, diarrhea, and fever up to 41 °C, a few hours after a kebab meal containing goat meat; he went to the Emergency Room, where a Film Array GI Panel (BioFire, Biomerieux Company, Marcy-L´Étoile, France) was performed on his feces and results were positive for . The culture of the feces was negative, but the blood culture was positive for ., which was identified as Hessarek by seroagglutination assays. The patient was treated with ceftriaxone 2 g intravenously qd for 8 days; he was discharged in good general conditions, and ciprofloxacin 500 mg per os bid for 7 more days was prescribed, after exclusion of endocarditis and of clinical signs of complicated bacteremia. This case of Hessarek gastroenteritis with bacteremia is probably the first case of bloodstream human infection due to this agent ever described. Further studies are needed to ascertain the global burden of Hessarek disease in humans.
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http://dx.doi.org/10.3390/pathogens9080656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460271PMC
August 2020

Bezlotoxumab for Preventing Recurrent Clostridioides difficile Infection: A Narrative Review from Pathophysiology to Clinical Studies.

Infect Dis Ther 2020 Sep 6;9(3):481-494. Epub 2020 Jul 6.

Infectious Diseases Unit, Ospedale Policlinico San Martino, IRCCS, Genoa, Italy.

Clostridioides difficile infection (CDI) and recurrent CDI (rCDI) remain associated with a reduction in the patients' quality of life and with increased healthcare costs. Bezlotoxumab is a monoclonal antibody against toxin B of C. difficile, approved for prevention of rCDI. In this narrative review, we briefly discuss the pathophysiology of CDI and the mechanism of action of bezlotoxumab, as well as the available evidence from investigational and observational studies in terms of efficacy, effectiveness, and safety of bezlotoxumab for the prevention of rCDI. Overall, bezlotoxumab has proved efficacious in reducing the burden of rCDI, thereby providing clinicians with an important novel strategy to achieve sustained cure. Nonetheless, experiences outside randomized controlled trials (RCTs) remain scant, and mostly represented by case series without a control group. Along with the conduction of RCTs to directly compare bezlotoxumab with faecal microbiota transplantation (or to precisely evaluate the role of their combined use), further widening our post-marketing experience remains paramount to firmly guide the use of bezlotoxumab outside RCTs, and to clearly identify those real-life settings where its preventive benefits can be exploited most.
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http://dx.doi.org/10.1007/s40121-020-00314-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7452994PMC
September 2020

Preventing sepsis development in complicated urinary tract infections.

Expert Rev Anti Infect Ther 2020 01 10;18(1):47-61. Epub 2019 Dec 10.

Systemic and Immunocompromised Host Infection Unit, National Institute for Infectious Diseases "L. Spallanzani", IRCCS, Rome, Italy.

: Urinary tract infections (UTIs) are the most prevalent infections in the community and the most common reason for antimicrobial prescribing in ambulatory care. A UTI is defined as complicated when urinary tract anatomical abnormalities or urinary devices are present, when it is recurrent and when associated with immunodeficiency. Complicated UTIs (cUTIs) have a higher risk of treatment failure and often require longer antimicrobial treatment courses. cUTIs, especially those which are healthcare-associated, are often due to multidrug resistant organisms (MDROs).: This article will review the available evidence in relation to prevention of sepsis in cUTI, evaluating the risk factors associated with sepsis development. Published articles from January 2005 to September 2019 on UTIs and sepsis prevention in complicated UTIs were identified by using MEDLINE (National Library of Medicine Bethesda MD) and by reviewing the references of retrieved articles.: Prevention of sepsis relies on prompt and timely diagnosis of cUTI, early identification of the causative organism, removal of obstructions and source control, proper and adequate empirical/targeted antimicrobial treatment. In particular, source control, i.e. removal of urinary obstructions, infected stents, urinary catheters, nephrostomies, and drainage of hydronephrosis/abscess, is essential for preventing the development and progression of sepsis.
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http://dx.doi.org/10.1080/14787210.2020.1700794DOI Listing
January 2020

Present and future of siderophore-based therapeutic and diagnostic approaches in infectious diseases.

Infect Dis Rep 2019 Sep 1;11(2):8208. Epub 2019 Oct 1.

National Institute for Infectious Diseases "L. Spallanzani" - IRCCS, Rome.

Iron is an essential micronutrient required for the growth of almost all aerobic organisms; the iron uptake pathway in bacteria therefore represents a possible target for novel antimicrobials, including hybrids between antimicrobials and siderophores. Siderophores are low molecular weight iron chelators that bind to iron and are actively transported inside the cell through specific binding protein complexes. These binding protein complexes are present both in Gram negative bacteria, in their outer and inner membrane, and in Gram positive bacteria in their cytoplasmic membrane. Most bacteria have the ability to produce siderophores in order to survive in environments with limited concentrations of free iron, however some bacteria synthetize natural siderophore-antibiotic conjugates that exploit the siderophore-iron uptake pathway to deliver antibiotics into competing bacterial cells and gain a competitive advantage. This approach has been referred to as a . To overcome the increasing global problem of antibiotic resistance in Gram negative bacteria, which often have reduced outer membrane permeability, siderophore-antibiotic hybrid conjugates have been synthetized . Cefiderocol is the first siderophore-antibiotic conjugate that progressed to late stage clinical development so far. In studies on murine models the iron-siderophore uptake pathway has been also exploited for diagnostic imaging of infectious diseases, in which labelled siderophores have been used as specific probes. The aim of this review is to describe the research progress in the field of siderophore-based therapeutic and diagnostic approaches in infectious diseases.
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http://dx.doi.org/10.4081/idr.2019.8208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778818PMC
September 2019

Treatment Options for Colistin Resistant : Present and Future.

J Clin Med 2019 Jun 28;8(7). Epub 2019 Jun 28.

Systemic and Immunocompromised Host Infection Unit, National Institute for Infectious Diseases "L. Spallanzani", IRCCS-Via Portuense, 292 00149 Rome, Italy.

Multidrug-resistant (MDR) represents an increasing threat to human health, causing difficult-to-treat infections with a high mortality rate. Since colistin is one of the few treatment options for carbapenem-resistant , colistin resistance represents a challenge due to the limited range of potentially available effective antimicrobials, including tigecycline, gentamicin, fosfomycin and ceftazidime/avibactam. Moreover, the choice of these antimicrobials depends on their pharmacokinetics/pharmacodynamics properties, the site of infection and the susceptibility profile of the isolated strain, and is sometimes hampered by side effects. This review describes the features of colistin resistance in and the characteristics of the currently available antimicrobials for colistin-resistant MDR , as well as the characteristics of novel antimicrobial options, such as the soon-to-be commercially available plazomicin and cefiderocol. Finally, we consider the future use of innovative therapeutic strategies in development, including bacteriophages therapy and monoclonal antibodies.
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http://dx.doi.org/10.3390/jcm8070934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678465PMC
June 2019

Use of colistin in adult patients: A cross-sectional study.

J Glob Antimicrob Resist 2020 03 15;20:43-49. Epub 2019 Jun 15.

Department of Medical and Surgical Sciences, Infectious and Tropical Diseases Unit, 'Magna Graecia' University of Catanzaro, Catanzaro, Italy.

Objectives: The aim of this study was to assess colistin use in a country endemic for multidrug-resistant Gram-negative bacteria (MDR-GNB).

Methods: Colistin prescription patterns were evaluated in 22 Italian centres. Factors associated with use of colistin in combination with other anti-MDR-GNB agents were also assessed.

Results: A total of 221 adults receiving colistin were included in the study. Their median age was 64 years (interquartile range 52-73 years) and 134 (61%) were male. Colistin was mostly administered intravenously (203/221; 92%) and mainly for targeted therapy (168/221; 76%). The most frequent indications for colistin therapy were bloodstream infection and lower respiratory tract infection. Intravenous colistin was administered in combination with at least another anti-MDR-GNB agent in 80% of cases (163/203). A loading dose of 9 MU of colistimethate was administered in 79% of patients receiving i.v. colistin and adequate maintenance doses in 85%. In multivariable analysis, empirical therapy [odds ratio (OR) = 3.25, 95% confidence interval (CI) 1.24-8.53;P = 0.017] and targeted therapy for carbapenem-resistant Enterobacterales infection (OR = 4.76, 95% CI 1.69-13.43; P = 0.003) were associated with use of colistin in combination with other agents, whilst chronic renal failure (OR = 0.39, 95% CI 0.17-0.88; P =  0.024) was associated with use of colistin monotherapy.

Conclusion: Colistin remains an important option for severe MDR-GNB infections when other treatments are not available. Despite inherent difficulties in optimising its use owing to peculiar pharmacokinetic/pharmacodynamic characteristics, colistin was mostly used appropriately in a country endemic for MDR-GNB.
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http://dx.doi.org/10.1016/j.jgar.2019.06.009DOI Listing
March 2020

Bloodstream infections caused by carbapenem-resistant Acinetobacter baumannii: Clinical features, therapy and outcome from a multicenter study.

J Infect 2019 08 28;79(2):130-138. Epub 2019 May 28.

Department of Public Health and Infectious Diseases, Sapienza University of Rome, Policlinico Umberto I, Viale dell'Università 37, 00161 Rome, Italy. Electronic address:

Objectives: bloodstream infections (BSI) due to multidrug-resistant (MDR) Acinetobacter baumannii (AB) have been increasingly observed among hospitalized patients.

Methods: prospective, observational study conducted among 12 large tertiary-care hospitals, across 7 Italian regions. From June 2017 to June 2018 all consecutive hospitalized patients with bacteremia due to MDR-AB were included and analyzed in the study.

Results: During the study period 281 episodes of BSI due to MDR-AB were observed: 98 (34.8%) episodes were classified as primary bacteremias, and 183 (65.2%) as secondary bacteremias; 177 (62.9%) of them were associated with septic shock. Overall, 14-day mortality was observed in 172 (61.2%) patients, while 30-day mortality in 207 (73.6%) patients. On multivariate analysis, previous surgery, continuous renal replacement therapy, inadequate source control of infection, and pneumonia were independently associated with higher risk of septic shock. Instead, septic shock and Charlson Comorbidity Index >3 were associated with 14-day mortality, while adequate source control of infection and combination therapy with survival. Finally, septic shock, previous surgery, and aminoglycoside-containing regimen were associated with 30-day mortality, while colistin-containing regimen with survival.

Conclusions: BSI caused by MDR-AB represents a difficult challenge for physicians, considering the high rates of septic shock and mortality associated with this infection.
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http://dx.doi.org/10.1016/j.jinf.2019.05.017DOI Listing
August 2019

Novel Antimicrobials for the Treatment of Infection.

Front Med (Lausanne) 2018 16;5:96. Epub 2018 Apr 16.

Clinical and Research Department for Infectious Diseases, Unit Systemic and Immunedepression-Associated Infections, National Institute for Infectious Diseases L. Spallanzani, Rome, Italy.

The current picture of infection (CDI) is alarming with a mortality rate ranging between 3% and 15% and a CDI recurrence rate ranging from 12% to 40%. Despite the great efforts made over the past 10 years to face the CDI burden, there are still gray areas in our knowledge on CDI management. The traditional anti-CDI antimicrobials are not always adequate in addressing the current needs in CDI management. The aim of our review is to give an update on novel antimicrobials for the treatment of CDI, considering the currently available evidences on their efficacy, safety, molecular mechanism of action, and their probability to be successfully introduced into the clinical practice in the near future. We identified, through a PubMed search, 16 novel antimicrobial molecules under study for CDI treatment: cadazolid, surotomycin, ridinilazole, LFF571, ramoplanin, CRS3123, fusidic acid, nitazoxanide, rifampin, rifaximin, tigecycline, auranofin, NVB302, thuricin CD, lacticin 3147, and acyldepsipeptide antimicrobials. In comparison with the traditional anti-CDI antimicrobial treatment, some of the novel antimicrobials reviewed in this study offer several advantages, i.e., the favorable pharmacokinetic and pharmacodynamic profile, the narrow-spectrum activity against CD that implicates a low impact on the gut microbiota composition, the inhibitory activity on CD sporulation and toxins production. Among these novel antimicrobials, the most active compounds in reducing spore production are cadazolid, ridinilazole, CRS3123, ramoplanin and, potentially, the acyldepsipeptide antimicrobials. These antimicrobials may potentially reduce CD environment spread and persistence, thus reducing CDI healthcare-associated acquisition. However, some of them, i.e., surotomycin, fusidic acid, etc., will not be available due to lack of superiority versus standard of treatment. The most CD narrow-spectrum novel antimicrobials that allow to preserve microbiota integrity are cadazolid, ridinilazole, auranofin, and thuricin CD. In conclusion, the novel antimicrobial molecules under development for CDI have promising key features and advancements in comparison to the traditional anti-CDI antimicrobials. In the near future, some of these new molecules might be effective alternatives to fight CDI.
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http://dx.doi.org/10.3389/fmed.2018.00096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5911476PMC
April 2018

Paraneoplastic Pemphigus: Insight into the Autoimmune Pathogenesis, Clinical Features and Therapy.

Int J Mol Sci 2017 Nov 26;18(12). Epub 2017 Nov 26.

Dipartimento di Medicina Interna e Specialità Mediche, Dermatologia, Sapienza Università di Roma, Piazzale Aldo Moro, 5, 00185 Roma, Italy.

Paraneoplastic pemphigus is a rare autoimmune skin disease that is always associated with a neoplasm. Usually, oral, skin, and mucosal lesions are the earliest manifestations shown by paraneoplastic pemphigus patients. The pathogenesis of paraneoplastic pemphigus is not yet completely understood, although some immunological aspects have been recently clarified. Because of its rarity, several diagnostic criteria have been proposed. Besides, several diagnostic procedures have been used for the diagnosis, including indirect immunofluorescence, direct immunofluorescence, and ELISA. We reviewed the most recent literature, searching on PubMed "paraneoplastic pemphigus". We included also papers in French, German, and Spanish. We found 613 papers for "paraneoplastic pemphigus". Among them, 169 were review papers. Because of its varying clinical features, paraneoplastic pemphigus still represents a challenge for clinicians. Furthermore, diagnosis and management of paraneoplastic pemphigus requires close collaboration between physicians, including dermatologist, oncologist, and otorhinolaryngologist.
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http://dx.doi.org/10.3390/ijms18122532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5751135PMC
November 2017

Clostridium difficile infection: new approaches to prevention, non-antimicrobial treatment, and stewardship.

Expert Rev Anti Infect Ther 2017 11 9;15(11):1027-1040. Epub 2017 Oct 9.

a Clinical and Research Department , National Institute for Infectious Diseases 'L. Spallanzani' , Rome , Italy.

Introduction: Despite the large amount of scientific publications exploring the epidemiology and the clinical management of Clostridium difficile (CD) infection, some issues remain unsolved or need further studies. The aim of this review is to give an update on the hot topics on CD prevention, including stewardship programs, and on the non-microbiological treatment of CD infection. Areas covered: This article will review the importance of minimizing the CD spore shedding in the healthcare environment for potentially reducing CD transmission. Moreover, antimicrobial stewardship programs aimed to reduce CD incidence will be reviewed. Finally, new strategies for reducing CD infection recurrence will be described. Expert commentary: Besides the basic infection control and prevention practices, including hand hygiene, contact isolation and environmental cleaning, in the prevention of CD infection other issues should be addressed including minimizing the spread of CD in the healthcare setting, and implementing the best strategy for reducing CD infection occurrence, including tailored antimicrobial stewardship programs. Regarding new advancements in treatment and management of CDI episodes, non-antimicrobial approaches seem to be promising in reducing and managing recurrent CD infection.
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http://dx.doi.org/10.1080/14787210.2017.1387535DOI Listing
November 2017

Resistance to Colistin in : A 4.0 Strain?

Infect Dis Rep 2017 May 31;9(2):7104. Epub 2017 May 31.

Clinical and Research Department, National Institute for Infectious Diseases "L. Spallanzani" - IRCCS, Rome, Italy.

The global rise of multidrug-resistant gram-negative bacteria represents an increasing threat to patient safety. From the first observation of a carbapenem-resistant gram-negative bacteria a global spread of extended-spectrum beta-lactamases and carbapenemases producing has been observed. Treatment options for multidrug-resistant are actually limited to combination therapy with some aminoglycosides, tigecycline and to older antimicrobial agents. Unfortunately, the prevalence of colistin-resistant and tigecycline-resistant is increasing globally. Infection due to colistin-resistant represents an independent risk factor for mortality. Resistance to colistin in may be multifactorial, as it is mediated by chromosomal genes or plasmids. The emergence of transmissible, plasmid-mediated colistin resistance is an alarming finding. The absence of new agents effective against resistant Gram-negative pathogens means that enhanced surveillance, compliance with infection prevention procedures, and antimicrobial stewardship programs will be required to limit the spread of colistin-resistant
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http://dx.doi.org/10.4081/idr.2017.7104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5472342PMC
May 2017

Antibacterial Prophylaxis for Surgical Site Infection in the Elderly: Practical Application.

Drugs Aging 2017 07;34(7):489-498

Clinical Department, National Institute for Infectious Diseases "Lazzaro Spallanzani", via Portuense 292, 00149, Rome, Italy.

Surgical site infections are among the most common healthcare-associated infections and are linked with increased length of hospitalization, re-admission, mortality and significant financial burden. Risk factors for the occurrence of surgical site infections include variables related to the surgical procedure as well as host factors. Increasing age is associated with the occurrence of surgical site infections. The aim of this review is to give an update on the antibiotic prophylaxis for surgical site infection in elderly people. We focused on specific issues and practical applications, such as the importance of targeting the antimicrobial agent to the susceptibility pattern of colonizing flora in selected cases and the need for dosage modifications.
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http://dx.doi.org/10.1007/s40266-017-0471-9DOI Listing
July 2017

P075. Secondary headache due to bilateral dissection of vertebral arteries.

J Headache Pain 2015 Dec;16(Suppl 1):A129

U.O.C. Immunologia Clinica A, Dipartimento di Medicina Clinica, Policlinico Umberto I, Sapienza Università di Roma, Rome, Italy.

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http://dx.doi.org/10.1186/1129-2377-16-S1-A129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4715197PMC
December 2015

Evaluation of estimated glomerular filtration rate and clinical variables in systemic sclerosis patients.

Clin Nephrol 2016 Jun;85(6):326-31

Objectives: The most important renal complication of systemic sclerosis (SSc) is scleroderma renal crisis (SRC). Many patients demonstrate less severe renal complications, most likely associated with reduced renal blood flow and a consequent reduction in glomerular filtration rate (GFR). The mechanism of this slowly progressive form of chronic renal disease is unclear. The aim of this study was to evaluate GFR by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and the 7-variable Modification of Diet and Renal Disease (MDRD) equations in SSc patients and to correlate estimated GFR (eGFR) with clinical variables of the disease.

Methods: 105 unselected and consecutive patients with SSc were enrolled. Serum creatinine was measured in all patients and GFR was estimated by 7-variable MDRD and CKD-EPI equations. Nailfold videocapillaroscopy was performed in all patients.

Results: The mean value of eGFR evaluated by both 7-variable MDRD and CKD-EPI was significantly different (p < 0.0001) in the three capillaroscopic groups and correlated negatively with the severity of capillaroscopic damage (early: 95 ± 16 mL/min and 101 ± 12 mL/min, active: 86 ± 25 mL/min and 95 ± 17 mL/min, late: 76 ± 21 mL/min and 82 ± 21 mL/min). The mean value of eGFR evaluated by 7-variable MDRD (97 ± 23 mL/min vs. 74 ± 15 mL/min, p < 0.0001) and CKD-EPI< (0.83 ± 0.20 mL/min vs. 0.68 ± 0.10 mL/min, p < 0.0001) was significantly higher in SSc patients without history of digital ulcers than in those with.

Conclusion: We can conclude that in SSc patients without renal involvement, eGFR decreases with the progression of digital vascular damage.
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http://dx.doi.org/10.5414/CN108580DOI Listing
June 2016

Otologic evaluation of patients with primary antibody deficiency.

Eur Arch Otorhinolaryngol 2016 Nov 2;273(11):3537-3546. Epub 2016 Mar 2.

'Organi di Senso' Department, 'Sapienza' University of Rome, Via Gregorio VII n. 80, 00165, Rome, Italy.

Common variable immunodeficiency (CVID) represents the most frequent primary immunodeficiency, often encountered in the ENT clinical practice. The clinical spectrum of CVID is quite broad, but otitis media are certainly among the most common clinical manifestations. This prospective study enrolled 60 patients (34 males, 26 females) with a previous diagnosis of CVID with the aim of performing an otologic evaluation and a more precision characterization of incidence, diagnosis, and treatment of otitis media in this group of patients. In consideration that Eustachian tube dysfunction (ETD) could be the 'primum movens' of otitis media, we wanted to assess whether a Eustachian tube dysfunction was present in these patients. Besides, we propose a possible diagnostic algorithm of middle ear pathologies to use in all cases of primary antibody deficiency patients. Results of our otologic examination showed that: 5 % of patients had chronic suppurative otitis media, 25 % bilateral otitis media with effusion and 10 % reported unilateral OME with associated contralateral ETD. There was bilateral isolated ETD and unilateral isolated ETD in 5 and 15 % of patients, respectively. All patients with unilateral OME had associated contralateral ETD. Finally, 40 % of patients were bilaterally negative at otoscopic examination and all otologic tests.
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http://dx.doi.org/10.1007/s00405-016-3956-yDOI Listing
November 2016

Immunoglobulin-induced hemolysis, splenomegaly and inflammation in patients with antibody deficiencies.

Expert Rev Clin Immunol 2016 Jul 3;12(7):725-31. Epub 2016 Mar 3.

a Centre for Primary Immune Deficiencies, Department of Molecular Medicine , Sapienza University of Rome , Rome , Italy.

IgG replacement for primary antibody deficiencies is a safe treatment administered to prevent recurrent infections and reduce mortality. Recently, several reports described acute hemolytic episodes following IgG administration due to a passive transfer of blood group alloantibodies, including anti-A, anti-B, as well as anti-Rh antibodies. Here, we reviewed and discussed the consequences of passively transferred RBCs antibodies. The chronic passive transfer of alloantibodies might also cause a subclinical condition due to a compensated extravascular chronic hemolysis with poorly understood consequences. This phenomenon might possibly represent an unrecognized cause of splenomegaly and might contribute to inflammation in patients with primary antibody deficiencies.
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http://dx.doi.org/10.1586/1744666X.2016.1151787DOI Listing
July 2016

Granulomatosis with polyangiitis and facial palsy: Literature review and insight in the autoimmune pathogenesis.

Autoimmun Rev 2016 Jul 4;15(7):621-31. Epub 2016 Feb 4.

Organi di Senso Department University, Sapienza University of Rome, Viale del Policlinico,151-00161, Rome, Italy. Electronic address:

Granulomatosis with polyangiitis (GPA) is an autoimmune systemic necrotizing small-vessel vasculitis associated with the presence of anti-neutrophil cytoplasmic antibodies (ANCA). Oto-neurological manifestations of ANCA-associated vasculitis according to PR3-ANCA positivity and MPO-ANCA positivity are usually reported. Facial nerve palsy is usually reported during the clinical course of the disease but it might appear as the presenting sign of GPA. Necrotizing vasculitis of the facial nerve 'vasa nervorum' is nowadays the most widely accepted etiopathogenetic theory to explain facial damage in GPA patients. A central role for PR3-ANCA in the pathophysiology of vasculitis in GPA patients with oto-neurological manifestation is reported. GPA requires prompt, effective management of the acute and chronic manifestations. Once the diagnosis of GPA has been established, clinicians should devise an appropriate treatment strategy for each individual patient, based on current clinical evidence, treatment guidelines and recommendations.
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http://dx.doi.org/10.1016/j.autrev.2016.02.005DOI Listing
July 2016

Vitiligo: Pathogenesis, clinical variants and treatment approaches.

Autoimmun Rev 2016 Apr 23;15(4):335-43. Epub 2015 Dec 23.

Organi di Senso Department, Sapienza University of Rome, Viale del Policlinico 151, 00161 Rome, Italy. Electronic address:

Vitiligo is a common chronic acquired disease of pigmentation whose etiology is unknown, which usually occurs with asymptomatic whitish patch or macule. Although several hypotheses have been proposed in the literature, the leading theory is still the auto-immune etiology linked to specific genetic mutations. Vitiligo can also be associated with several autoimmune diseases, including autoimmune thyroid diseases, alopecia areata, and halo nevi. Sensorineural hearing loss was reported in several vitiligo patients due to a reduction in the number of melanocytes contained in the membranous labyrinth of the inner ear. Because of its complexity, several therapeutic options are available to treat this systemic disease.
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http://dx.doi.org/10.1016/j.autrev.2015.12.006DOI Listing
April 2016

Lung magnetic resonance imaging with diffusion weighted imaging provides regional structural as well as functional information without radiation exposure in primary antibody deficiencies.

J Clin Immunol 2015 Jul 12;35(5):491-500. Epub 2015 Jun 12.

Department of Molecular Medicine, Sapienza University of Rome, Viale dell'Università 37, Rome, Italy.

Purpose: Primary antibody deficiency patients suffer from infectious and non-infectious pulmonary complications leading over time to chronic lung disease. The complexity of this pulmonary involvement poses significant challenge in differential diagnosis in patients with long life disease and increased radio sensitivity. We planned to verify the utility of chest Magnetic Resolution Imaging with Diffusion-Weighted Imaging as a radiation free technique.

Methods: Prospective evaluation of 18 patients with Common Variable Immunodeficiency and X-linked Agammaglobulinemia. On the same day, patients underwent Magnetic Resonance Imaging with Diffusion Weighted Imaging sequences, High Resolution Computerized Tomography and Pulmonary Function Tests, including diffusing capacity factor for carbon monoxide. Images were scored using a modified version of the Bhalla scoring system.

Results: Magnetic Resonance Imaging was non-inferior to High Resolution Computerized Tomography in the capacity to identify bronchial and parenchymal abnormalities. HRCT had a higher capacity to identify peripheral airways abnormalities, defined as an involvement of bronchial generation up to the fifth and distal (scores 2-3). Bronchial scores negatively related to pulmonary function tests. One third of consolidations and nodules had Diffusion Weighted Imaging restrictions associated with systemic granulomatous disease and systemic lymphadenopathy. Lung Magnetic Resolution Imaging detected an improvement of bronchial and parenchymal abnormalities, in recently diagnosed patients soon after starting Ig replacement.

Conclusions: Magnetic Resonance Imaging with Diffusion Weighted Imaging was a reliable technique to detect lung alterations in patients with Primary Antibody Deficiencies.
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http://dx.doi.org/10.1007/s10875-015-0172-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4502290PMC
July 2015

Macrophage Activation Syndrome as Onset of Systemic Lupus Erythematosus: A Case Report and a Review of the Literature.

Case Rep Med 2015 7;2015:294041. Epub 2015 May 7.

UOC Immunologia Clinica A, Dipartimento di Medicina Clinica, Policlinico Umberto I, Sapienza Università di Roma, 00185 Roma, Italy.

Macrophage activation syndrome (MAS) is a potentially fatal condition. It belongs to the hemophagocytic lymphohistiocytosis group of diseases. In adults, MAS is rarely associated with systemic lupus erythematosus, but it also arises as complication of several systemic autoimmune disorders, like ankylosing spondylitis, rheumatoid arthritis, and adult-onset Still's disease. Several treatment options for MAS have been reported in the literature, including a therapeutic regimen of etoposide, dexamethasone, and cyclosporine. Here we report a case of 42-year-old woman in whom MAS occurred as onset of systemic lupus erythematosus.
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http://dx.doi.org/10.1155/2015/294041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4439481PMC
June 2015

Posterior reversible encephalopathy syndrome--Insight into pathogenesis, clinical variants and treatment approaches.

Autoimmun Rev 2015 Sep 18;14(9):830-6. Epub 2015 May 18.

Organi di Senso Department University, Sapienza University of Rome, Viale del Policlinico, 151, 00161 Rome, Italy. Electronic address:

Posterior reversible encephalopathy syndrome is a rare clinicoradiological entity characterized by typical MRI findings located in the occipital and parietal lobes, caused by subcortical vasogenic edema. It was first described as a distinctive syndrome by Hinchey in 1996. Etiopathogenesis is not clear, although it is known that it is an endotheliopathy of the posterior cerebral vasculature leading to failed cerebral autoregulation, posterior edema and encephalopathy. A possible pathological activation of the immune system has been recently hypothesized in its pathogenesis. At clinical onset, the most common manifestations are seizures, headache and visual changes. Besides, tinnitus and acute vertigo have been frequently reported. Symptoms can be reversible but cerebral hemorrhage or ischemia may occur. Diagnosis is based on magnetic resonance imaging, in the presence of acute development of clinical neurologic symptoms and signs and arterial hypertension and/or toxic associated conditions with possible endotheliotoxic effects. Mainstay on the treatment is removal of the underlying cause. Further investigation and developments in endothelial cell function and in neuroimaging of cerebral blood flow are needed and will help to increase our understanding of pathophysiology, possibly suggesting novel therapies.
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http://dx.doi.org/10.1016/j.autrev.2015.05.006DOI Listing
September 2015