Publications by authors named "Claudio Viscoli"

232 Publications

Pneumocystis jirovecii Disease: Basis for the Revised EORTC/MSGERC Invasive Fungal Disease Definitions in Individuals Without Human Immunodeficiency Virus.

Clin Infect Dis 2021 03;72(Suppl 2):S114-S120

Infectious Disease Research Program, Center for Bone Marrow Transplantation and Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster, Muenster, Germany.

Background: Pneumocystis jirovecii pneumonia (PCP) causes substantive morbidity in immunocompromised patients. The EORTC/MSGERC convened an expert group to elaborate consensus definitions for Pneumocystis disease for the purpose of interventional clinical trials and epidemiological studies and evaluation of diagnostic tests.

Methods: Definitions were based on the triad of host factors, clinical-radiologic features, and mycologic tests with categorization into probable and proven Pneumocystis disease, and to be applicable to immunocompromised adults and children without human immunodeficiency virus (HIV). Definitions were formulated and their criteria debated and adjusted after public consultation. The definitions were published within the 2019 update of the EORTC/MSGERC Consensus Definitions of Invasive Fungal Disease. Here we detail the scientific rationale behind the disease definitions.

Results: The diagnosis of proven PCP is based on clinical and radiologic criteria plus demonstration of P. jirovecii by microscopy using conventional or immunofluorescence staining in tissue or respiratory tract specimens. Probable PCP is defined by the presence of appropriate host factors and clinical-radiologic criteria, plus amplification of P. jirovecii DNA by quantitative real-time polymerase chain reaction (PCR) in respiratory specimens and/or detection of β-d-glucan in serum provided that another invasive fungal disease and a false-positive result can be ruled out. Extrapulmonary Pneumocystis disease requires demonstration of the organism in affected tissue by microscopy and, preferably, PCR.

Conclusions: These updated definitions of Pneumocystis diseases should prove applicable in clinical, diagnostic, and epidemiologic research in a broad range of immunocompromised patients without HIV.
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http://dx.doi.org/10.1093/cid/ciaa1805DOI Listing
March 2021

Second outbreak of Trichinella pseudospiralis in Europe: clinical patterns, epidemiological investigation and identification of the etiological agent based on the western blot patterns of the patients' serum.

Zoonoses Public Health 2021 02 8;68(1):29-37. Epub 2020 Nov 8.

European Union Reference Laboratory for Parasites, Istituto Superiore di Sanità, Rome, Italy.

Trichinellosis is a zoonotic disease due to the ingestion of raw or undercooked meat from animals infected with the larvae of nematodes belonging to the genus Trichinella. In January-February 2015, an outbreak of trichinellosis occurred in Genoa, Northern Italy. The epidemiological link was traced back to a dinner served at an agritourism farm on 31 December 2014, where a majority of the 52 guests had consumed the 'beef' steak tartare. The source of infection was not traced; however, it was noted that the amount of beef purchased officially for providing at the dinner did not correspond with that served, suggesting that meat of a different origin had been added to the beef to prepare the steak tartare. Clinical and laboratory data of 30 individuals out of the 52 (57.7%), of which four were hospitalized, were consistent with that of the case definition of trichinellosis. Western blot patterns of the sera from patients with confirmed trichinellosis were similar to the diagnostic pattern identified for the reference sera of Trichinella pseudospiralis but different from those of the control sera tested for patients infected with Trichinella spiralis and Trichinella britovi. Identification of T. pseudospiralis as the aetiological agent responsible for the outbreak of trichinellosis using an indirect tool represents an advancement in the epidemiological investigation of this zoonotic disease.
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http://dx.doi.org/10.1111/zph.12761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894149PMC
February 2021

Trends in the Incidence and Antibiotic Resistance of Enterococcal Bloodstream Isolates: A 7-Year Retrospective Multicenter Epidemiological Study in Italy.

Microb Drug Resist 2021 Apr 18;27(4):529-535. Epub 2020 Sep 18.

Infectious Diseases Unit, Azienda Sanitaria Universitaria Giuliano Isontina, Trieste, Italy.

The spread of resistance to vancomycin and other last-resort drugs in spp. remains of concern. In Italy, surveillance data for enterococcal bloodstream isolates in humans are scant. The aim of our study was to assess the incidence trends of bacteremias due to species and their prevalence trends of antimicrobial resistance. We retrospectively included all consecutive not-duplicate species isolated from blood cultures, in patients from 11 Italian hospitals (2011-2017). Incidence was defined as the number of isolates per 10,000 patient-days, while resistance prevalence was defined as the number of resistant strains divided by the number of tested strains. We included 4,858 isolates (59%, 36%, and 5% due to , , and other spp., respectively). Over the study period, the incidence of bacteremias due to (incidence rate ratio [IRR]: 1.02, 95% confidence interval [CI]: 1.00-1.04,  = 0.008) and increased (IRR: 1.03, 95% CI: 1.01-1.05,  < 0.001) alongside with the whole enterococcal bacteremias trend (IRR: 1.02, 95% CIs: 1.01-1.04,  = 0.002). A progressive increase in vancomycin-resistant (VREfm) bacteremias was observed. Resistance to tigecycline and linezolid was rarely reported. The incidence of enterococcal bloodstream isolates is increasing in Italy, together with the prevalence of VREfm. Resistance to linezolid, a cornerstone drug used in the treatment of VRE bloodstream infection, remains negligible.
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http://dx.doi.org/10.1089/mdr.2020.0147DOI Listing
April 2021

Ceftolozane/Tazobactam for Treatment of Severe ESBL-Producing Infections: A Multicenter Nationwide Clinical Experience (CEFTABUSE II Study).

Open Forum Infect Dis 2020 May 21;7(5):ofaa139. Epub 2020 Apr 21.

Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Background: Few data are reported in the literature about the outcome of patients with severe extended-spectrum β-lactamase-producing (ESBL-E) infections treated with ceftolozane/tazobactam (C/T), in empiric or definitive therapy.

Methods: A multicenter retrospective study was performed in Italy (June 2016-June 2019). Successful clinical outcome was defined as complete resolution of clinical signs/symptoms related to ESBL-E infection and lack of microbiological evidence of infection. The primary end point was to identify predictors of clinical failure of C/T therapy.

Results: C/T treatment was documented in 153 patients: pneumonia was the most common diagnosis (n = 46, 30%), followed by 34 cases of complicated urinary tract infections (22.2%). Septic shock was observed in 42 (27.5%) patients. C/T was used as empiric therapy in 46 (30%) patients and as monotherapy in 127 (83%) patients. Favorable clinical outcome was observed in 128 (83.7%) patients; 25 patients were considered to have failed C/T therapy. Overall, 30-day mortality was reported for 15 (9.8%) patients. At multivariate analysis, Charlson comorbidity index >4 (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.9-3.5; = .02), septic shock (OR, 6.2; 95% CI, 3.8-7.9; < .001), and continuous renal replacement therapy (OR, 3.1; 95% CI, 1.9-5.3; = .001) were independently associated with clinical failure, whereas empiric therapy displaying in vitro activity (OR, 0.12; 95% CI, 0.01-0.34; < .001) and adequate source control of infection (OR, 0.42; 95% CI, 0.14-0.55; < .001) were associated with clinical success.

Conclusions: Data show that C/T could be a valid option in empiric and/or targeted therapy in patients with severe infections caused by ESBL-producing . Clinicians should be aware of the risk of clinical failure with standard-dose C/T therapy in septic patients receiving CRRT.
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http://dx.doi.org/10.1093/ofid/ofaa139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237821PMC
May 2020

Hepatitis E Virus Infection in an Italian Cohort of Hematopoietic Stem Cell Transplantation Recipients: Seroprevalence and Infection.

Biol Blood Marrow Transplant 2020 07 19;26(7):1355-1362. Epub 2020 Mar 19.

Division of Infectious Diseases, Department of Health Sciences, University of Genoa, Genoa, Italy; Division of Infectious Diseases, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. Electronic address:

Chronic hepatitis E virus (HEV) infection in hematopoietic stem cell transplantation (HSCT) recipients is an emerging threat. The aim of this study was to provide data on the HEV burden in an Italian cohort of HSCT recipients and analyze risk factors for HEV seropositivity. This retrospective study reports data from 596 HSCT recipients compiled between 2010 and 2019. It included patients who underwent transplantation between 2010 and 2015 for whom pretransplantation (n = 419) and post-transplantation (n = 161) serum samples were available and tested retrospectively, as well as patients in whom prospective HEV testing was performed during the standard care: pre-HSCT IgG screening in 144, pre-HSCT HEV-RNA screening in addition to IgG screening in 60, and HEV-RNA testing in case of clinical suspicion of HEV infection in 59 (26 of whom were also included in the IgG screening cohorts). The rate of pre-HSCT HEV-IgG positivity was 6.0% (34 of 563). Older age was an independent risk factor for seropositivity (P = .039). None of the 34 HEV-IgG-positive patients had detectable HEV-RNA. One case of transient HEV-RNA positivity pre-HSCT was identified through screening. Two patients were diagnosed with chronic HEV hepatitis, and 1 patient was successfully treated with ribavirin. The burden of HEV infection in HSCT recipients in Italy is limited, and pre-HSCT screening appears to be of no benefit. Timely diagnosis of HEV infection with HEV-RNA is mandatory in cases of clinical suspicion.
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http://dx.doi.org/10.1016/j.bbmt.2020.03.012DOI Listing
July 2020

Changes in the relative prevalence of candidaemia due to non-albicans Candida species in adult in-patients: A systematic review, meta-analysis and meta-regression.

Mycoses 2020 Apr;63(4):334-342

Clinica Malattie Infettive, Ospedale Policlinico San Martino - IRCCS, Genoa, Italy.

Background: Candidaemia remains associated with high mortality and increased costs worldwide.

Objective: To assess the changes over time in the relative prevalence of non-albicans candidaemia (NAC).

Methods: A systematic review, meta-analysis and meta-regression were performed. Observational studies investigating the epidemiology of consecutive, non-selected, candidaemia episodes were included. Two separated analyses were conducted: (a) whole hospital analysis and (b) intensive care unit (ICU) analysis.

Results: Starting from an initial total of 7726 records, 220 studies fulfilled inclusion criteria. The pooled prevalence of NAC in whole hospital analysis was 49.5% (95% confidence intervals [CI] 48.0-51.1, I 93.1%), while the pooled prevalence in ICU analysis was 50.6% (95% CI 46.6-54.6; I 86.7%). In meta-regression, a progressive increase in NAC prevalence was observed in whole hospital analysis, although it explained only a small portion of between-study variance (estimated yearly prevalence change +0.3%, 95% CI from +0.1% to +0.5%, P = .003; adjusted R 3.42%) and was observed only in some continents in subgroup analyses. No relevant changes over time were observed in NAC prevalence for ICU studies.

Conclusions: We registered an increasing trend in the relative prevalence of NAC, which, nonetheless, seems to be limited to some continents and to contribute only minimally to explain the observed differences in NAC prevalence across studies.
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http://dx.doi.org/10.1111/myc.13054DOI Listing
April 2020

Changing epidemiology of candidaemia: Increase in fluconazole-resistant Candida parapsilosis.

Mycoses 2020 Apr 20;63(4):361-368. Epub 2020 Feb 20.

Department of Health Sciences (DiSSal), University of Genova, Genova, Italy.

Aim: During the last decade a continuous increase in non-albicans species isolation has been observed with Candida parapsilosis being one of the leading species. Aim of this study was to describe the epidemiology of candidemia, particularly of C parapsilosis, its predictors and clinical outcome.

Materials And Methods: Incidences of candidemia was evaluated analyzing data from both a prospective collection (2012-2016) and a retrospective one (2008-2011). Predictors and outcome were based only on the prospective phase. C parapsilosis potential clusters were analysed by randomly amplified polymorphic DNA (RAPD) technique.

Results: 1240 episodes were identified. Incidences of candidemia increased from 1.97 episodes/10 000 patient-days in 2008 to 4.59/10 000 patient-days in 2016 (P < .001), mainly due to an increase of C parapsilosis (incidence rate ratio, IRR: 1.04, P < .001). 33.0% of C parapsilosis strains were resistant to fluconazole; no resistance to echinocandins was found. Independent predictors of C parapsilosis candidemia were time of infection (P = .007), previous use of echinocandins (P < .0001) and year in which the episode was registered (P < .0001). 30 days mortality was 32.4% for C parapsilosis, with a significant difference compared to C non-parapsilosis. Potential clonal C parapsilosis strains were detected by genetic analyses, showing RAPD profile A as the most represented (72.6% of isolates).

Discussion: C parapsilosis candidemia is an emerging issue in our center, possibly attributed to some extent to horizontal transmission of the pathogen, as confirmed by the analysis of isolates similarities. Further microbiological and epidemiological investigations are needed in order to identify the most effective measures to reduce the rate of this infection.
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http://dx.doi.org/10.1111/myc.13050DOI Listing
April 2020

Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium.

Clin Infect Dis 2020 09;71(6):1367-1376

Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Background: Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential.

Methods: To achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups' findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved.

Results: There is no change in the classifications of "proven," "probable," and "possible" IFD, although the definition of "probable" has been expanded and the scope of the category "possible" has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses.

Conclusions: These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk.
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http://dx.doi.org/10.1093/cid/ciz1008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486838PMC
September 2020

Epidemiology and outcome of carbapenemase-producing (KPC-KP) infections in cardiac surgery patients: a brief narrative review.

J Chemother 2019 Nov - Dec;31(7-8):359-366. Epub 2019 Nov 8.

Department of Health Sciences, University of Genoa, Genoa, Italy.

carbapenemase-producing (KPC-KP) is a difficult-to-treat pathogen due to its multidrug-resistant phenotype. Cardiac surgery patients are at increased risk of developing KPC-KP infections compared to other populations, with previous KPC-KP colonization being a critical factor in influencing the risk of subsequent infection. Two different pieces of information are essential to comprehensively assess the local characteristics of KPC-KP colonization in cardiac surgery patients: () the local prevalence of colonization; () the timing of colonization. Treatment of KPC-KP infections in cardiac surgery patients is a complex task, but more effective treatment options have recently become available. Nonetheless, implementation and full adherence to infection-control measures remain of pivotal importance for reducing the burden of KPC-KP infections in this peculiar population. The aim of this narrative review is to summarize the available literature on the epidemiology and outcome of KPC-KP infections in cardiac surgery patients.
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http://dx.doi.org/10.1080/1120009X.2019.1685794DOI Listing
April 2020

A Global View to HBV Chronic Infection: Evolving Strategies for Diagnosis, Treatment and Prevention in Immunocompetent Individuals.

Int J Environ Res Public Health 2019 09 9;16(18). Epub 2019 Sep 9.

Hygiene Unit, IRCCS Policlinico San Martino Hospital, 16132 Genoa, Italy.

Hepatitis B Virus (HBV) is a significant public health challenge. Around 250 million people live with chronic HBV infection. With a global approach to this issue, we focus on new perspective in diagnosis, management and prevention of HBV chronic infection. Precise diagnosis of HBV status is crucial to guide patient management. Although available drugs reduce the risk of liver disease progression, they are not able to definitely eradicate HBV, and new therapeutic options are urgently needed. Thus, prevention of HBV infection is still the most effective strategy to achieve the control of the disease. Key aspects of prevention programs include surveillance of viral hepatitis, screening programs and immunization strategies. In spite of the high success rate of licensed HBV vaccines, a need for improved vaccine persists, especially in order to provide coverage of current non-responders.
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http://dx.doi.org/10.3390/ijerph16183307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766235PMC
September 2019

Reduced Incidence of Carbapenem-Resistant Klebsiella pneumoniae Infections in Cardiac Surgery Patients after Implementation of an Antimicrobial Stewardship Project.

Antibiotics (Basel) 2019 08 28;8(3). Epub 2019 Aug 28.

Dipartimento di Scienze Chirurgiche e Diagnostiche Integrate (DISC), University of Genoa, 16132 Genoa, Italy.

Infections due to carbapenem-resistant Klebsiella pneumoniae (CR-Kp) are associated with increased mortality in cardiac surgery patients. In this short communication, we report on the changes in the incidence of CR-Kp colonization and CR-Kp infection in cardiac surgery patients from 2014 to 2018 in a teaching hospital in Italy, after the implementation of an antimicrobial stewardship project in 2014. During the study period, 2261 patients underwent open-heart surgery. Of them, 130 were found to be colonized by CR-Kp (5.7%) and 52 developed a postoperative CR-Kp infection (2.3%). The crude in-hospital mortality in patients with CR-Kp infections was 48% (25/52). The incidences of both CR-Kp colonization (incidence rate ratio (IRR) 0.82, 95% confidence intervals (CI) 0.78-0.86, p < 0.001) and CR-Kp infection (IRR 0.76, 95% CI 0.69-0.83, p < 0.001) considerably decreased over the study period. This encouraging result should prompt further concerted efforts, directed towards retaining the positive impact of stewardship and infection-control interventions on CR-Kp-related morbidity in the long term.
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http://dx.doi.org/10.3390/antibiotics8030132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6783823PMC
August 2019

The Ligurian HIV Network: How Medical Informatics Standards Can Help Clinical Research.

Stud Health Technol Inform 2019 Aug;264:1666-1667

Department of Informatics, Bioengineering, Robotics and System Engineering, (DIBRIS), University of Genoa, Italy.

Integrating evidence from systematic research in daily clinical practice is one of the pillars of evidence-based medicine. Electronic data capture tools simplify data collection from different centers and supports the management of multicenter clinical trials. The Ligurian HIV Network (LHN) is one such tool, originating from a regional effort to integrate clinical trial capabilities for HIV and other chronic infectious diseases. In order to manually collect a complete report of all clinical tests on patients enrolled in a trial, a strenuous human effort and the allocation of great resources would be necessary. Moreover, the risk of error in a manual system is very high. The proposed system automatically extracts clinical data from the EHR of three hospitals of the LHN in a standardized way, and enhance their re-use in clinical trials. Through dedicated questionnaires, physicians reported a strongly positive feedback about the efficacy of the platform in supporting clinical research.
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http://dx.doi.org/10.3233/SHTI190587DOI Listing
August 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

Fulminant Hepatitis Associated With Echovirus 25 During Treatment With Ocrelizumab for Multiple Sclerosis.

JAMA Neurol 2019 07;76(7):866-867

Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health and Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.

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http://dx.doi.org/10.1001/jamaneurol.2019.0522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6583842PMC
July 2019

Diagnostic and therapeutic approach to infectious diseases in solid organ transplant recipients.

Intensive Care Med 2019 05 25;45(5):573-591. Epub 2019 Mar 25.

Transplant Infectious Diseases Unit, University Hospitals Geneva, Rue Gabrielle-Perret-Gentil 4, 1205, Geneva, Switzerland.

Purpose: Prognosis of solid organ transplant (SOT) recipients has improved, mainly because of better prevention of rejection by immunosuppressive therapies. However, SOT recipients are highly susceptible to conventional and opportunistic infections, which represent a major cause of morbidity, graft dysfunction and mortality.

Methods: Narrative review.

Results: We cover the current epidemiology and main aspects of infections in SOT recipients including risk factors such as postoperative risks and specific risks for different transplant recipients, key points on anti-infective prophylaxis as well as diagnostic and therapeutic approaches. We provide an up-to-date guide for management of the main syndromes that can be encountered in SOT recipients including acute respiratory failure, sepsis or septic shock, and central nervous system infections as well as bacterial infections with multidrug-resistant strains, invasive fungal diseases, viral infections and less common pathogens that may impact this patient population.

Conclusion: We provide state-of the art review of available knowledge of critically ill SOT patients with infections.
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http://dx.doi.org/10.1007/s00134-019-05597-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079836PMC
May 2019

Evaluation of Mass Spectrometry-Based Detection of Panfungal Serum Disaccharide for Diagnosis of Invasive Fungal Infections: Results from a Collaborative Study Involving Six European Clinical Centers.

J Clin Microbiol 2019 05 26;57(5). Epub 2019 Apr 26.

Laboratoire de Parasitologie Mycologie, CHU Lille, Université Lille, INSERM U995-LIRIC (Lille Inflammation Research International Centre), Lille, France

A mass spectrometry (MS) method that detects a serum disaccharide (DS) (MS-DS) was recently described for the diagnosis of invasive fungal infections (IFI). We carried out a European collaborative study to evaluate this assay. Patients with the following IFI were selected according to the availability of sera obtained at about the time that IFI was documented: invasive candidiasis (IC;  = 26 patients), invasive aspergillosis (IA;  = 19), and mucormycosis (MM;  = 23). Control sera originated from 20 neutropenic patients and 20 patients with bacteremia. MS-DS was carried out in blind manner for the diagnosis of IFI. A diagnosis of IC or IA was confirmed by detection of mannan (Man) or galactomannan (GM), respectively, associated with detection of (1,3)-β-d-glucan (BDG) in both infections. MM was detected by quantitative real-time PCR (qPCR). All tests discriminated sera from patients with IC from sera from control subjects with bacteremia ( ≤ 0.0009). For IC, the MS-DS sensitivity and specificity were 51% and 87%, respectively. MS-DS complemented the high specificity of Man monitoring. All tests discriminated sera from IA patients from sera from neutropenic controls ( ≤ 0.0009). For IA, MS-DS sensitivity and specificity were 64% and 95%, respectively. Only 13/36 serum samples from patients with MM were concordant by MS-DS and qPCR (6 were positive, and 7 were negative); 14 were positive by MS-DS alone. qPCR and MS-DS made a similar contribution to the diagnosis of MM. In patients undergoing long-term monitoring, the persistent circulation of serum disaccharide was observed, whereas DNA was detected only for a short period after initiation of treatment. MS-DS has an important role to play in the early diagnosis of IFI. Its panfungal nature and complementarity with other tests may justify its use in the management of IFI.
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http://dx.doi.org/10.1128/JCM.01867-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6498025PMC
May 2019

Current and emerging pharmacotherapy for the treatment of infections following open-heart surgery.

Expert Opin Pharmacother 2019 04 20;20(6):751-772. Epub 2019 Feb 20.

a Dipartimento di Scienze della Salute (DISSAL) , University of Genoa , Genoa , Italy.

Introduction: Patients undergoing open-heart surgery may suffer from postoperative complications, including severe infections. Antimicrobials to treat infectious complications in this population should be selected thoughtfully, taking into account three different and fundamental issues: (i) the site of infection; (ii) the suspected or proven causative agent and its susceptibility pattern; and (iii) the risk of suboptimal pharmacokinetic characteristics and potential toxicity of the chosen drug/s.

Areas Covered: The present narrative review summarizes the current and future antimicrobial options for the treatment of infections developing after open-heart surgery.

Expert Opinion: The pharmacological treatment of infections developing in cardiac surgery patients poses peculiar challenges, including the need for an active empirical therapy for severe events such as bloodstream infections, deep sternal wound infections, or early-onset postoperative prosthetic endocarditis. In addition, the risk for multidrug-resistant pathogens should also be taken into account in endemic areas. A multidisciplinary evaluation on a patient-by-patient basis, deeply involving infectious diseases specialists and cardiothoracic surgeons, remains essential for appropriately balancing both short-term and long-term risks and benefits of any possible surgical reintervention in combination with adequate pharmacotherapy.
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http://dx.doi.org/10.1080/14656566.2019.1574753DOI Listing
April 2019

Use of Aspergillus fumigatus real-time PCR in bronchoalveolar lavage samples (BAL) for diagnosis of invasive aspergillosis, including azole-resistant cases, in high risk haematology patients: the need for a combined use with galactomannan.

Med Mycol 2019 Nov;57(8):987-996

Division of Infectious Diseases, Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy.

Diagnosis of invasive aspergillosis (IA) is challenging, particularly in high-risk patients with lung lesions other than typical according to 2008-EORTC/MSG criteria. Even if microbiology is positive, they still remain unclassified according to 2008-EORTC/MSG. Quantitative polymerase chain reaction (qPCR) provides new mycological documentation of IA. This retrospective study assessed Aspergillus fumigatus real time qPCR (MycoGENIE®) in BAL to diagnose IA and identify azole-resistant strains. Clinical, radiological, and microbiological data from 114 hematology patients (69% HSCT recipients; 29% on mould active agents) from years 2012-2017 were collected; and 123 BAL samples were tested with qPCR (cutoff: Ct < 40) and galactomannan (GM, Platelia®, cutoff: 0.5 ODI). Patients were classified as proven/probable, possible, and no-IA. "Atypical-IA" referred to patients with lesions other than typical according to 2008-EORTC/MSG and positive mycology. Proven IA was diagnosed in two cases (1.6%), probable in 28 (22.8%), possible in 27 (22%), atypical in 14 (11.4%). qPCR was positive in 39 samples (31.7%). Sensitivity and specificity of qPCR for proven/probable IA (vs no-IA; atypical-IA excluded) were 40% (95% confidence interval [CI]: 23-59) and 69% (95%CI: 55-81), respectively. Sensitivity of qPCR was higher when combined with GM (83%, 95%CI: 65-94) and in those receiving mould-active agents at BAL (61%, 95%CI: 32-86). One sample had TR34/L98H mutation. In conclusion, in high-risk hematology patients with various lung lesions, A. fumigatus qPCR in BAL contributes to diagnosing IA, particularly if combined with GM and in patients receiving mould-active agents might allow detecting azole-resistant mutations in culture negative samples.
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http://dx.doi.org/10.1093/mmy/myz002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7107636PMC
November 2019

International Consensus Guidelines for the Optimal Use of the Polymyxins: Endorsed by the American College of Clinical Pharmacy (ACCP), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of America (IDSA), International Society for Anti-infective Pharmacology (ISAP), Society of Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP).

Pharmacotherapy 2019 01;39(1):10-39

Division of Infectious Diseases, University of Michigan Medical School, Ann Arbor, Michigan.

The polymyxin antibiotics colistin (polymyxin E) and polymyxin B became available in the 1950s and thus did not undergo contemporary drug development procedures. Their clinical use has recently resurged, assuming an important role as salvage therapy for otherwise untreatable gram-negative infections. Since their reintroduction into the clinic, significant confusion remains due to the existence of several different conventions used to describe doses of the polymyxins, differences in their formulations, outdated product information, and uncertainties about susceptibility testing that has led to lack of clarity on how to optimally utilize and dose colistin and polymyxin B. We report consensus therapeutic guidelines for agent selection and dosing of the polymyxin antibiotics for optimal use in adult patients, as endorsed by the American College of Clinical Pharmacy (ACCP), Infectious Diseases Society of America (IDSA), International Society of Anti-Infective Pharmacology (ISAP), Society for Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP). The European Society for Clinical Microbiology and Infectious Diseases (ESCMID) endorses this document as a consensus statement. The overall conclusions in the document are endorsed by the European Committee on Antimicrobial Susceptibility Testing (EUCAST). We established a diverse international expert panel to make therapeutic recommendations regarding the pharmacokinetic and pharmacodynamic properties of the drugs and pharmacokinetic targets, polymyxin agent selection, dosing, dosage adjustment and monitoring of colistin and polymyxin B, use of polymyxin-based combination therapy, intrathecal therapy, inhalation therapy, toxicity, and prevention of renal failure. The treatment guidelines provide the first ever consensus recommendations for colistin and polymyxin B therapy that are intended to guide optimal clinical use.
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http://dx.doi.org/10.1002/phar.2209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7437259PMC
January 2019

Desirability of outcome ranking (DOOR) for comparing diagnostic tools and early therapeutic choices in patients with suspected candidemia.

Eur J Clin Microbiol Infect Dis 2019 Feb 30;38(2):413-417. Epub 2018 Nov 30.

Infectious Diseases Unit, Ospedale Policlinico San Martino - IRCCS per l'Oncologia, University of Genoa, Largo R. Benzi, 10, 16132, Genoa, Italy.

Desirability of outcome ranking (DOOR) has been developed for assessing desirability of outcome in interventional studies. However, its possible use in observational studies of the diagnosis and early treatment of infectious diseases has not been explored so far, and it might introduce interesting features in specific scenarios. This was a post hoc analysis of a prospective observational study in intensive care unit patients with sepsis and at risk of candidemia. The probabilities that a randomly selected patient would have a more, less, and equally cost-effective early therapeutic choice following a BDG-based diagnostic strategy rather than the empirical administration of antifungals to all patients were calculated using DOOR methods. The probability of a more cost-effective therapeutic choice following the BDG-based rather than the empirical strategy was 67.81% (95% CI 67.32-68.30), whereas the probabilities of a less and equally cost-effective early therapeutic choice were 19.68% (95% CI 19.27-20.10) and 12.50% (95% CI 12.16-12.85), respectively. The application of DOOR methods to observational studies focused on diagnosis and early treatment is a novel field that could merit further investigation.
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http://dx.doi.org/10.1007/s10096-018-3441-1DOI Listing
February 2019

Implementing TB control in a rural, resource-limited setting: the stop-TB Italia project in Senegal.

Multidiscip Respir Med 2018 9;13:41. Epub 2018 Nov 9.

Stop TB Italy Onlus, Milan, Italy.

Background: Since 2013 StopTB Italia Onlus supports the Senegalese National Tuberculosis Programme by improving diagnostic capability with technological interventions, ameliorating educational programs for health care personnel, rising awareness among civil society and providing economical support for patients during treatment. The purpose of our study was to assess the preliminary results of an interventional cooperation project in a peripheral health care facility in Senegal.

Methods: An observational, retrospective, pre-post study was conducted to compare Tuberculosis (TB) retention in care and outcome between a one-year period before and a four-year period after.

Results: Overall, 239 patients with active TB were included, 196 (82%) of whom after the starting of the collaboration project. At diagnosis 35/43(81.4%) vs 151/196 (77%) patients were smear sputum positive before and after the beginning of the project, respectively.At 2 months follow up 23/35 (65.7%) patients in 2012 vs. 139/151 (92%) patients in 2013-2016 had negative control AFB stain ( = 0.249), 4/35 (11.4%) vs 12/151 (8%) patients remained AFB stain positive ( = 0.17), 7/35 (20%) vs 0/151 died before the 2 months follow up ( <  0.0001). TB treatment outcome was more frequently favourable after the beginning of cooperation 29/43 (67.4%) vs. 176/196 (89.8%) patients, (  0.0001). Patients' mortality during treatment decreased from 8/43 (18.6%) in 2012 to 11/196 (5.6%) patients in the following years ( = 0.009).

Conclusion: The implementation of diagnostic procedures, if integrated in a socio-economical intervention, impacts favourably on TB retention in care and treatment outcomes.
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http://dx.doi.org/10.1186/s40248-018-0154-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6225657PMC
November 2018

Recent advances in the pharmacological management of infections due to multidrug-resistant Gram-negative bacteria.

Expert Rev Clin Pharmacol 2018 Dec 6;11(12):1219-1236. Epub 2018 Dec 6.

a Dipartimento di Scienze della Salute (DISSAL) , University of Genoa , Genoa , Italy.

Introduction: The emergence and diffusion of multidrug-resistant Gram-negative bacteria (MDR-GNB) is an unprecedented threat, with prevalences as high as 10-50% being reported in many countries. Areas covered: In the present review, we discuss the management of infections due to MDR-GNB, focusing in particular on current strategies and novel agents with already available results from phase 3 randomized controlled trials. Expert commentary: Some new drugs, such as ceftolozane/tazobactam, ceftazidime/avibactam, and meropenem/vaborbactam, which have become available in the past months, have increased our chance of improving survival in severe carbapenem-resistant Pseudomonas aeruginosa and carbapenem-resistant Enterobacteriaceae infections; while others, with potent activity against carbapenem-resistant Acinetobacter baumannii which is currently the highest priority regarding the need for novel agents, will become available in the near future. In the meantime, the focus of both clinical practice and research is slowly but steadily widening from efficacy and tolerability of new treatment options to also future preservation of their antimicrobial activity. This is reflected in clinical practice by more attention paid to antimicrobial stewardship initiatives, and in clinical research by growing interest in exploring resistance development as a major endpoint in both preclinical and clinical studies.
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http://dx.doi.org/10.1080/17512433.2018.1549487DOI Listing
December 2018

Successful recovery of associated interstitial nephritis and focal segmental glomerulosclerosis in patients with HCV and HIV treated with sofosbuvir and daclatasvir and revision of literature.

Clin Nephrol Case Stud 2018 26;6:31-35. Epub 2018 Oct 26.

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

In this report, we describe the coexistence of two rare and debated complications of hepatitis C virus (HCV) infection: interstitial nephritis, with associated focal glomerulosclerosis, and autoimmune hepatitis, in a 55-year-old HIV/HCV-coinfected woman. The patient was treated for the immune-mediated manifestations with mycophenolate mofetil, which she continued for 9 years, as symptoms relapsed at every attempt to discontinue immunosuppression. The patient finally cleared HCV infection thanks to new direct-acting agents and could discontinue immunosuppressive therapy maintaining stable conditions and laboratory parameters after 24-weeks follow-up.
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http://dx.doi.org/10.5414/CNCS109221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6218875PMC
October 2018

Isavuconazole Versus Caspofungin in the Treatment of Candidemia and Other Invasive Candida Infections: The ACTIVE Trial.

Clin Infect Dis 2019 05;68(12):1981-1989

Department of Medicine, University of California Davis.

Background: Isavuconazole was compared to caspofungin followed by oral voriconazole in a Phase 3, randomized, double-blind, multinational clinical trial for the primary treatment of patients with candidemia or invasive candidiasis.

Methods: Adult patients were randomized 1:1 to isavuconazole (200 mg intravenous [IV] three-times-daily [TID] for 2 days, followed by 200 mg IV once-daily [OD]) or caspofungin (70 mg IV OD on day 1, followed by 50 mg IV OD [70 mg in patients > 80 kg]) for a maximum of 56 days. After day 10, patients could switch to oral isavuconazole (isavuconazole arm) or voriconazole (caspofungin arm). Primary efficacy endpoint was successful overall response at the end of IV therapy (EOIVT) in patients with proven infections who received ≥1 dose of study drug (modified-intent-to-treat [mITT] population). The pre-specified noninferiority margin was 15%. Secondary outcomes in the mITT population were successful overall response at 2 weeks after the end of treatment, all-cause mortality at days 14 and 56, and safety.

Results: Of 450 patients randomized, 400 comprised the mITT population. Baseline characteristics were balanced between groups. Successful overall response at EOIVT was observed in 60.3% of patients in the isavuconazole arm and 71.1% in the caspofungin arm (adjusted difference -10.8, 95% confidence interval -19.9--1.8). The secondary endpoints, all-cause mortality, and safety were similar between arms. Median time to clearance of the bloodstream was comparable between groups.

Conclusions: This study did not demonstrate non-inferiority of isavuconazole to caspofungin for primary treatment of invasive candidiasis. Secondary endpoints were similar between both groups.

Clinical Trials Registration: NCT00413218.
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http://dx.doi.org/10.1093/cid/ciy827DOI Listing
May 2019

Efficacy of lamivudine prophylaxis in preventing hepatitis B virus reactivation in patients with resolved infection undergoing allogeneic SCT and receiving rituximab.

Infection 2019 Feb 19;47(1):59-65. Epub 2018 Sep 19.

Division of Infectious Diseases, Department of Health Sciences, University of Genoa, Genoa, Italy.

Purpose: Hepatitis B virus (HBV) reactivation during immunosuppressive therapy is common in patients with hematological malignancies, even in case of resolved infection. Prophylaxis of HBV reactivation is universally recommended in stem cell transplant (SCT) recipients and patients treated with anti-CD20 agents (i.e., rituximab). Despite its well-established favorable safety profile, lamivudine (LAM) use in prophylaxis has been debated because of the possible emergence of resistant viral strains. The aim of this study was to investigate the efficacy of LAM in preventing HBV reactivation in allogeneic SCT recipients with a resolved HBV infection.

Methods: Patients who received first allogeneic SCT in years 2009-2016 were evaluated. Sixty-three patients with resolved infection received LAM prophylaxis and were included in the study. Baseline and post-SCT characteristics were recorded, including rituximab exposure, length of LAM prophylaxis, and time from transplant to the last clinical and virological follow-up.

Results: Overall, 39 patients (62%) were male, 39 (62%) had acute myeloid leukemia, 38 (60%) received transplant from haploidentical donor, 29 (53%) received myeloablative conditioning, and 15 (24%) received rituximab post-transplant. Median clinical follow-up was 24 months after SCT (range 0.3-97); median virological follow-up 16 months (range 0.3-78), and median length of LAM prophylaxis of 14.5 months (range 0.3-78). No patient experienced HBV reactivation while on LAM prophylaxis. One patient experienced reactivation 8 months after discontinuing prophylaxis.

Conclusions: In this high-risk population, LAM prophylaxis was effective in preventing HBV reactivation in patients with resolved infection. It should be considered a reasonable first-line prophylactic agent to be administered in this setting.
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http://dx.doi.org/10.1007/s15010-018-1214-5DOI Listing
February 2019

How has the cost of antiretroviral therapy changed over the years? A database analysis in Italy.

BMC Health Serv Res 2018 Sep 6;18(1):691. Epub 2018 Sep 6.

Infectious Diseases Unit, Department of Internal Medicine, Policlinico Hospital San Martino, Genoa, Italy.

Background: The number of human immunodeficiency virus (HIV)-related hospitalizations has decreased worldwide in recent years, due to the availability of combined antiretroviral therapies (cART). The present analysis aimed to analyse the economic, and clinical burden of HIV management, after the introduction of systematic use of cART.

Methods: Data from HIV-infected patients, treated at Policlinico San Martino Hospital in Genova (Italy) were retrospectively collected. A comparison between years 2009 and 2015 was performed. HIV-related admissions were identified by using the Diagnosis-Related Group (DRG) codes. The resource consumption of outpatient services was derived by using a modelling approach. Expenditure for drugs was also analysed, as aggregate data.

Results: The number of HIV-infected patients was 898 in 2009 and 1006 in 2015. Overall, the virological success rate improved from 2009 to 2015, as the percentage of patients with HIV-RNA < 50 copies/mL increased from 79 to 89% (P < 0.05). The average incidence of hospitalizations per-patient decreased from 0.30 in 2009, to 0.13 in 2015. Average expenditure per-patient decreased from €10,107 in 2009 to €9063 in 2015.

Conclusions: The present analysis confirmed the role of cART in controlling HIV viral load and, consequently, in reducing hospitalizations, admissions to day-hospital and the use of outpatient services. Clinical improvements and economic savings more than compensated the investments required to treat HIV-infected patients with cART. Health Authorities should invest in modern cART supply and universal treatment, to use at best the available resources and obtain a cost-effective improvement of health in people living with HIV. Additional research, with the involvement of different centers and the use of patient-specific data, are recommended to consolidate the findings of this analysis.
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http://dx.doi.org/10.1186/s12913-018-3507-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127985PMC
September 2018

Hypoalbuminemia as a predictor of acute kidney injury during colistin treatment.

Sci Rep 2018 08 10;8(1):11968. Epub 2018 Aug 10.

Infectious Diseases Department, Azienda Sanitaria Universitaria Integrata di Trieste, Trieste, Italy.

This study aimed to assess the predictors of acute kidney injury (AKI) during colistin therapy in a cohort of patients with bloodstream infections (BSI) due to colistin-susceptible Gram-negative bacteria, focusing on the role of serum albumin levels. The study consisted of two parts: (1) a multicentre retrospective clinical study to assess the predictors of AKI during colistin therapy, defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria; and (2) bioinformatic and biochemical characterization of the possible interaction between human serum albumin and colistin. Among the 170 patients included in the study, 71 (42%), 35 (21%), and 11 (6%) developed KDIGO stage 1 (K1-AKI), KDIGO stage 2 (K2-AKI), and KDIGO stage 3 (K3-AKI), respectively. In multivariable analyses, serum albumin <2.5 g/dL was independently associated with K1-AKI (subdistribution hazard ratio [sHR] 1.85, 95% confidence interval [CI] 1.17-2.93, p = 0.009) and K2-AKI (sHR 2.37, 95% CI 1.15-4.87, p = 0.019). Bioinformatic and biochemical analyses provided additional information nurturing the discussion on how hypoalbuminemia favors development of AKI during colistin therapy. In conclusion, severe hypoalbuminemia independently predicted AKI during colistin therapy in a large cohort of patients with BSI due to colistin-susceptible Gram-negative bacteria. Further study is needed to clarify the underlying causal pathways.
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http://dx.doi.org/10.1038/s41598-018-30361-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6086859PMC
August 2018