Publications by authors named "Alberto Enrico Maraolo"

54 Publications

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

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

Clinical and Research Department for Infectious Diseases, National Institute for Infectious Diseases L. Spallanzani IRCCS, 00149 Rome, 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

Choosing the appropriate pharmacotherapy for hepatitis B during pregnancy: what are the considerations?

Expert Opin Pharmacother 2021 Apr 2:1-4. Epub 2021 Apr 2.

First Division of Infectious Diseases, Cotugno Hospital, Naples, Italy.

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http://dx.doi.org/10.1080/14656566.2021.1909571DOI Listing
April 2021

Fosfomycin in continuous or prolonged infusion for systemic bacterial infections: a systematic review of its dosing regimen proposal from in vitro, in vivo and clinical studies.

Eur J Clin Microbiol Infect Dis 2021 Feb 18. Epub 2021 Feb 18.

Clinical Department of Medical, Surgical and Health Sciences, Trieste University, 34127, Trieste, Italy.

Fosfomycin (FOS) administered intravenously has been recently rediscovered for the treatment of systemic infections due to multidrug-resistant bacteria. Its pharmacokinetic properties suggest a time-dependent dosing schedule with more clinical benefits from prolonged (PI) or continuous infusion (CI) than from intermittent infusion. We revised literature concerning PI and CI FOS to identify the best dosing regimen based on current evidence. We performed a MEDLINE/PubMed search. Ninety-one studies and their pertinent references were screened. Seventeen studies were included in the present review. The activity of FOS against Gram-negative and Gram-positive bacteria was evaluated in fourteen and five studies, respectively. Six studies evaluated FOS activity in combination with another antibiotic. Daily dosing of 12, 16, 18 or 24 g, administered with different schedules, were investigated. These regimens resulted active against the tested isolates in most cases. Emergence of resistant isolates has been shown to be preventable through the coadministration of another active antibiotic. FOS is a promising option to treat systemic infections caused by multidrug-resistant bacteria. Coadministration with another active molecule is required to prevent the emergence of resistant bacterial strains. The results of our review suggest that a therapeutic regimen including a loading dose of FOS 8 g followed by a daily dose of 16 g or 24 g CI could be the best therapeutic approach for patients with normal renal function. The dosing regimens in patients with renal insufficiency and CI or PI superiority compared with intermittent infusion in clinical settings should be further investigated.
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http://dx.doi.org/10.1007/s10096-021-04181-xDOI Listing
February 2021

Incidence and Prognosis of Ventilator-Associated Pneumonia in Critically Ill Patients with COVID-19: A Multicenter Study.

J Clin Med 2021 Feb 3;10(4). Epub 2021 Feb 3.

Infectious Diseases Unit, San Martino Polyclinic Hospital-IRCCS for Oncology and Neurosciences, 16132 Genoa, Italy.

The primary objective of this multicenter, observational, retrospective study was to assess the incidence rate of ventilator-associated pneumonia (VAP) in coronavirus disease 2019 (COVID-19) patients in intensive care units (ICU). The secondary objective was to assess predictors of 30-day case-fatality of VAP. From 15 February to 15 May 2020, 586 COVID-19 patients were admitted to the participating ICU. Of them, 171 developed VAP (29%) and were included in the study. The incidence rate of VAP was of 18 events per 1000 ventilator days (95% confidence intervals [CI] 16-21). Deep respiratory cultures were available and positive in 77/171 patients (45%). The most frequent organisms were (27/77, 35%) and (18/77, 23%). The 30-day case-fatality of VAP was 46% (78/171). In multivariable analysis, septic shock at VAP onset (odds ratio [OR] 3.30, 95% CI 1.43-7.61, = 0.005) and acute respiratory distress syndrome at VAP onset (OR 13.21, 95% CI 3.05-57.26, < 0.001) were associated with fatality. In conclusion, VAP is frequent in critically ill COVID-19 patients. The related high fatality is likely the sum of the unfavorable prognostic impacts of the underlying viral and the superimposed bacterial diseases.
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http://dx.doi.org/10.3390/jcm10040555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913191PMC
February 2021

SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis.

Lancet Microbe 2021 Jan 19;2(1):e13-e22. Epub 2020 Nov 19.

MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK.

Background: Viral load kinetics and duration of viral shedding are important determinants for disease transmission. We aimed to characterise viral load dynamics, duration of viral RNA shedding, and viable virus shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in various body fluids, and to compare SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV) viral dynamics.

Methods: In this systematic review and meta-analysis, we searched databases, including MEDLINE, Embase, Europe PubMed Central, , and , and the grey literature, for research articles published between Jan 1, 2003, and June 6, 2020. We included case series (with five or more participants), cohort studies, and randomised controlled trials that reported SARS-CoV-2, SARS-CoV, or MERS-CoV infection, and reported viral load kinetics, duration of viral shedding, or viable virus. Two authors independently extracted data from published studies, or contacted authors to request data, and assessed study quality and risk of bias using the Joanna Briggs Institute Critical Appraisal Checklist tools. We calculated the mean duration of viral shedding and 95% CIs for every study included and applied the random-effects model to estimate a pooled effect size. We used a weighted meta-regression with an unrestricted maximum likelihood model to assess the effect of potential moderators on the pooled effect size. This study is registered with PROSPERO, CRD42020181914.

Findings: 79 studies (5340 individuals) on SARS-CoV-2, eight studies (1858 individuals) on SARS-CoV, and 11 studies (799 individuals) on MERS-CoV were included. Mean duration of SARS-CoV-2 RNA shedding was 17·0 days (95% CI 15·5-18·6; 43 studies, 3229 individuals) in upper respiratory tract, 14·6 days (9·3-20·0; seven studies, 260 individuals) in lower respiratory tract, 17·2 days (14·4-20·1; 13 studies, 586 individuals) in stool, and 16·6 days (3·6-29·7; two studies, 108 individuals) in serum samples. Maximum shedding duration was 83 days in the upper respiratory tract, 59 days in the lower respiratory tract, 126 days in stools, and 60 days in serum. Pooled mean SARS-CoV-2 shedding duration was positively associated with age (slope 0·304 [95% CI 0·115-0·493]; p=0·0016). No study detected live virus beyond day 9 of illness, despite persistently high viral loads, which were inferred from cycle threshold values. SARS-CoV-2 viral load in the upper respiratory tract appeared to peak in the first week of illness, whereas that of SARS-CoV peaked at days 10-14 and that of MERS-CoV peaked at days 7-10.

Interpretation: Although SARS-CoV-2 RNA shedding in respiratory and stool samples can be prolonged, duration of viable virus is relatively short-lived. SARS-CoV-2 titres in the upper respiratory tract peak in the first week of illness. Early case finding and isolation, and public education on the spectrum of illness and period of infectiousness are key to the effective containment of SARS-CoV-2.

Funding: None.
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http://dx.doi.org/10.1016/S2666-5247(20)30172-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837230PMC
January 2021

The role of asymptomatic and pre-symptomatic infection in SARS-CoV-2 transmission-a living systematic review.

Clin Microbiol Infect 2021 Apr 21;27(4):511-519. Epub 2021 Jan 21.

Division of Infection and Global Health Research, School of Medicine, University of St. Andrews, Fife, Scotland, UK. Electronic address:

Background: Reports suggest that asymptomatic individuals (those with no symptoms at all throughout infection) with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are infectious, but the extent of transmission based on symptom status requires further study.

Purpose: This living review aims to critically appraise available data about secondary attack rates from people with asymptomatic, pre-symptomatic and symptomatic SARS-CoV-2 infection.

Data Sources: Medline, EMBASE, China Academic Journals full-text database (CNKI), and pre-print servers were searched from 30 December 2019 to 3 July 2020 using relevant MESH terms.

Study Selection: Studies that report on contact tracing of index cases with SARS-CoV-2 infection in either English or Chinese were included.

Data Extraction: Two authors independently extracted data and assessed study quality and risk of bias. We calculated the secondary attack rate as the number of contacts with SARS-CoV-2, divided by the number of contacts tested.

Data Synthesis: Of 927 studies identified, 80 were included. Summary secondary attack rate estimates were 1% (95% CI 0%-2%) with a prediction interval of 0%-10% for asymptomatic index cases in ten studies, 7% (95% CI 3%-11%) with a prediction interval of 1%-40% for pre-symptomatic cases in 11 studies and 6% (95% CI 5%-8%) with a prediction interval of 5%-38% for symptomatic index cases in 40 studies. The highest secondary attack rates were found in contacts who lived in the same household as the index case. Other activities associated with transmission were group activities such as sharing meals or playing board games with the index case, regardless of the disease status of the index case.

Limitations: We excluded some studies because the index case or number of contacts were unclear.

Conclusion: Asymptomatic patients can transmit SARS-CoV-2 to others, but our findings indicate that such individuals are responsible for fewer secondary infections than people with symptoms.

Systematic Review Registration: PROSPERO CRD42020188168.
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http://dx.doi.org/10.1016/j.cmi.2021.01.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825872PMC
April 2021

Safety of hydroxychloroquine for treatment or prevention of SARS-CoV-2 infection: A rapid systematic review and meta-analysis of randomized clinical trials.

Immun Inflamm Dis 2021 03 26;9(1):31-36. Epub 2020 Nov 26.

Section of Hygiene, University Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, Roma, Italy.

Introduction: Hydroxycloroquine (HCQ) has been extensively studied for treatment and prevention of coronavirus diseases 2019 (COVID-19) from the start of the pandemic. Conflicting evidence about its usefulness has begun to accrue.

Methods: In the face of controversial results about clinical efficacy of HCQ, we performed a rapid systematic review to assess its safety in the framework of COVID-19 randomized clinical trials.

Results: Five studies investigating 2291 subjects were included. The use of HCQ was associated with higher risk of adverse event compared with placebo or standard of care: odds ratio 4.57, 95% confidence interval 2.14-9.45.

Conclusion: Safety profile of HCQ appears to be unsatisfactory when used to treat or prevent COVID-19, especially in the light of unproved clinical benefit.
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http://dx.doi.org/10.1002/iid3.374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753686PMC
March 2021

Fosfomycin as Partner Drug for Systemic Infection Management. A Systematic Review of Its Synergistic Properties from In Vitro and In Vivo Studies.

Antibiotics (Basel) 2020 Aug 10;9(8). Epub 2020 Aug 10.

Clinical Department of Medical, Surgical and Health Sciences, Trieste University, 34127 Trieste, Italy.

Fosfomycin is being increasingly prescribed for multidrug-resistant bacterial infections. In patients with systemic involvement, intravenous fosfomycin is usually administered as a partner drug, as part of an antibiotic regimen. Hence, the knowledge of fosfomycin pharmacodynamic interactions (synergistic, additive, indifferent and antagonistic effect) is fundamental for a proper clinical management of severe bacterial infections. We performed a systematic review to point out fosfomycin's synergistic properties, when administered with other antibiotics, in order to help clinicians to maximize drug efficacy optimizing its use in clinical practice. Interactions were more frequently additive or indifferent (65.4%). Synergism accounted for 33.7% of total interactions, while antagonism occurred sporadically (0.9%). Clinically significant synergistic interactions were mostly distributed in combination with penicillins (51%), carbapenems (43%), chloramphenicol (39%) and cephalosporins (33%) in Enterobactaerales; with linezolid (74%), tetracyclines (72%) and daptomycin (56%) in ; with chloramphenicol (53%), aminoglycosides (43%) and cephalosporins (36%) against ; with daptomycin (97%) in spp. and with sulbactam (75%) and penicillins (60%) and in spp. fosfomycin-based antibiotic associations benefit from increase in the bactericidal effect and prevention of antimicrobial resistances. Taken together, the presence of synergistic interactions and the nearly total absence of antagonisms, make fosfomycin a good partner drug in clinical practice.
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http://dx.doi.org/10.3390/antibiotics9080500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460049PMC
August 2020

Risk Factors for Candidemia After Open Heart Surgery: Results From a Multicenter Case-Control Study.

Open Forum Infect Dis 2020 Aug 19;7(8):ofaa233. Epub 2020 Jun 19.

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

Background: species are among the most frequent causative agents of health care-associated bloodstream infections, with mortality >40% in critically ill patients. Specific populations of critically ill patients may present peculiar risk factors related to their reason for intensive care unit admission. The primary objective of the present study was to assess the predictors of candidemia after open heart surgery.

Methods: This retrospective, matched case-control study was conducted in 8 Italian hospitals from 2009 to 2016. The primary study objective was to assess factors associated with the development of candidemia after open heart surgery.

Results: Overall, 222 patients (74 cases and 148 controls) were included in the study. Candidemia developed at a median time (interquartile range) of 23 (14-36) days after surgery. In multivariable analysis, independent predictors of candidemia were New York Heart Association class III or IV (odds ratio [OR], 23.81; 95% CI, 5.73-98.95;  < .001), previous therapy with carbapenems (OR, 8.87; 95% CI, 2.57-30.67;  = .001), and previous therapy with fluoroquinolones (OR, 5.73; 95% CI, 1.61-20.41;  = .007). Crude 30-day mortality of candidemia was 53% (39/74). Septic shock was independently associated with mortality in the multivariable model (OR, 5.64; 95% CI, 1.91-16.63;  = .002). No association between prolonged cardiopulmonary bypass time and candidemia was observed in this study.

Conclusions: Previous broad-spectrum antibiotic therapy and high NYHA class were independent predictors of candidemia in cardiac surgery patients with prolonged postoperative intensive care unit stay.
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http://dx.doi.org/10.1093/ofid/ofaa233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397829PMC
August 2020

COVID-19: Time for Post-Exposure Prophylaxis?

Int J Environ Res Public Health 2020 Jun 4;17(11). Epub 2020 Jun 4.

UNESCO Chair for Health Education and Sustainable Development, University of Naples Federico II, 80131 Naples, Italy.

From a healthcare perspective, infection due to the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and the ensuing syndrome called COVID-19 (coronavirus disease 2019) represents the biggest challenge the world has faced in several decades. Particularly worrisome are the high contagiousness of the virus and the saturation of hospitals' capacity due to overwhelming caseloads. Non-pharmaceutical interventions such as quarantine and inter-personal distancing are crucial to limiting the spread of the virus in the general population, but more tailored interventions may be needed at an individual level on a case-by-case basis. In this perspective, the most insidious situation is when an individual has contact with a contagious subject without adequate protection. If rapidly recognized afterwards, this occurrence may be promptly addressed through a post-exposure chemoprophylaxis (PEP) with antiviral drugs. This strategy has been implemented for other respiratory viruses (influenza above all) and was successfully used in South Korea among healthcare workers against the Middle East respiratory syndrome (MERS) coronavirus, by providing people who were exposed to high-risk contacts with lopinavir-ritonavir plus ribavirin. Initial experiences with the use of hydroxychloroquine to prevent COVID-19 also seem promising. Post-exposure chemoprophylaxis might help mitigate the spread of SARS-CoV-2 in the current phase of the COVID-19 pandemic.
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http://dx.doi.org/10.3390/ijerph17113997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312384PMC
June 2020

SARS-CoV-2 and liver damage: a possible pathogenetic link.

Hepatobiliary Surg Nutr 2020 Jun;9(3):322-324

Divisions of Gastroenterology and Hepatology and of Clinical Pathology, Geneva University Hospitals, Geneva, Switzerland.

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http://dx.doi.org/10.21037/hbsn-20-437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262623PMC
June 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

Ceftolozane/tazobactam for difficult-to-treat Pseudomonas aeruginosa infections: A systematic review of its efficacy and safety for off-label indications.

Int J Antimicrob Agents 2020 Mar 8;55(3):105891. Epub 2020 Jan 8.

Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples 'Federico II', via Sergio Pansini, 5, I-80131 Naples, Italy.

Ceftolozane/tazobactam (C/T) is a novel β-lactam/β-lactamase inhibitor combination targeting Enterobacteriaceae and Pseudomonas aeruginosa (PA). It is approved in adult patients for complicated urinary tract infections (cUTIs) and complicated intra-abdominal infections (cIAIs) as well as for nosocomial pneumonia. It displays excellent activity against PA, even multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. The aim of this systematic review (PROSPERO protocol no. CRD42019117350) was to summarise the available evidence from observational studies regarding the efficacy and safety of off-label use of C/T when administered to treat MDR- or XDR-PA infections. The MEDLINE and Embase databases were screened from inception up to 30 June 2019. Studies were deemed eligible if they described real-life use of C/T in the case of MDR- or XDR-PA infections for non-approved indications. Exclusion criteria were cIAIs, cUTIs, pneumonia (unless occurring in a paediatric population) and infections by non-MDR/XDR-PA. Thirty articles fulfilled the inclusion criteria. In total, 130 cases of MDR- or XDR-PA infections treated with C/T in 128 patients were described. The most relevant off-label uses were skin and soft-tissue infection (49/30; 37.7%), bone and joint infection (42/130; 32.3%) and bloodstream infection (23/130; 17.7%). Five cases involved paediatric patients. The overall clinical success rate was 76.2%. The most common adverse event was hypokalaemia (4.2%, in 48 evaluable cases). C/T may be a useful therapeutic option for difficult-to-treat infections by PA even outside the framework of approved indications. Further studies are necessary to better define new indications for the drug.
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http://dx.doi.org/10.1016/j.ijantimicag.2020.105891DOI Listing
March 2020

Efficacy and safety of a fixed dose combination tablet of asunaprevir + beclabuvir + daclatasvir for the treatment of Hepatitis C.

Expert Opin Pharmacother 2020 Feb 8;21(3):261-273. Epub 2020 Jan 8.

Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, Naples, Italy.

: Hepatitis C virus (HCV) is estimated to infect approximately 70 million people worldwide. If left untreated, chronic infection can progress to cirrhosis, liver failure or hepatocellular carcinoma. The advent of new direct-acting antivirals (DAA) has revolutionized patients' chances of treatment and viral elimination. Currently, several DAA options are available on the market.: This review focuses on the pharmacokinetics, efficacy, tolerability and safety profile of DCV-TRIO, a twice-daily fixed-dose combination of daclatasvir, asunaprevir and beclabuvir approved in Japan for the treatment of genotype 1 HCV infection.: The DCV-TRIO combination achieved good response rates in genotype 1 patients (SVR12 ≥ 95% in naïve subtype 1b), independently from IL28B genotype, cirrhotic status and prior interferon exposure. On the other hand, unsatisfying response rates were reported in DAA-experienced patients and the risk of RAS selection should not be underestimated. Moreover, DCV-TRIO lacks differentiation from its earlier-launched DAA rivals, presents an inconvenient twice-daily dosing schedule and is not recommended in patients with advanced liver and kidney disease. All these drawbacks considerably limit its effective commercial potential. However, it can be a therapeutic option against HCV in tailored approaches according to the needs of different markets across the world. AE: adverse event; ALT: alanine aminotransferase; AST: aspartate aminotransferase; ASV: asunaprevir; AUC: area under the curve; BCRP: Breast Cancer Resistance Protein; BCV: boceprevir; BID: bis in die; CI: confidence intervals; CLcr: creatinine clearance; DAA: direct acting antivirals; DCV: daclatasvir; EC50: Half maximal effective concentration; GT: genotype; HCV: Hepatitis C virus; IFN: Interferon; NHL: non-Hodgkin lymphoma; OATP: Organic anion transporting polypeptides; OR: odds ratio; P-gp: P-glycoprotein; PK: pharmacokinetics; QD: quo die; RAS: resistance-associated substitutions; SVR: sustained virological response; USD: Unites States dollar.
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http://dx.doi.org/10.1080/14656566.2019.1697674DOI Listing
February 2020

Measles in pregnant women: A systematic review of clinical outcomes and a meta-analysis of antibodies seroprevalence.

J Infect 2020 02 28;80(2):152-160. Epub 2019 Dec 28.

Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples "Federico II", 80131, Naples, Italy.

Objectives: Pregnant women represent a category at high risk of severe measles infection, that negatively affects the fetus as well. A systematic review of clinical outcomes of measles infection in gravid subjects and a meta-analysis of antibodies prevalence among pregnant women was conducted.

Methods: MEDLINE and EMBASE databases were searched up to 18 June 2018. The screening focused on: (i) articles describing the outcome of measles in pregnancy, synthesized in a descriptive fashion; (ii) articles addressing the measles seroprevalence in cohorts of gravid women, analysed quantitatively.

Results: Twenty-nine articles met inclusion criteria. A total of 420 cases of measles in gravid subjects were described, from 1941 to 2012. Among women, 18 deaths (4.3%) occurred, and the most frequent complication was pneumonia (75/420, 17.9%). Prematurity was the most important complication concerning fetal outcomes (55 out of 410 cases with available data, 13.4%). The random-effects pooled seroprevalence of measles in 20,546 gravid women worldwide was 89.3% (95% CI: 87.3-91.1%), that decreased, although not in a statistically significant way, over time (p = 0.54).

Conclusions: Measles infection in pregnancy is dangerous both for the mother and the foetus. Antibody seroprevalence among gravid women on a global scale is lower than the herd immunity threshold.
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http://dx.doi.org/10.1016/j.jinf.2019.12.012DOI Listing
February 2020

Carbapenem-sparing strategy: carbapenemase, treatment, and stewardship.

Curr Opin Infect Dis 2019 12;32(6):663-673

Department of Medical Sciences, Infectious Diseases, University of Turin, Turin.

Purpose Of Review: describing the current role of carbapenems and carbapenem-sparing strategies in the setting of antimicrobial stewardship programs.

Recent Findings: sparing carbapenems with other drugs appears to be an interesting perspective for a variety of reasons in the current context of the multidrug-resistant (MDR) pandemic. Specific algorithms should also be precisely investigated to define better how to spare carbapenems within empiric and targeted regimens, with combination treatment or monotherapies, aiming at the best use of the new drugs and improving de-escalation as soon as possible for most of the patients.

Summary: stewardship programs may be useful in reducing probable misuse and overuse of antibiotics, which has probably contributed to the emergence of carbapenem-resistant bacteria worldwide. The proposal of carbapenem-sparing strategies has then generated substantial scientific debate and, overall, the concept of sparing these drugs is well advocated together with judicious use of novel drugs, appropriate measures of infection control and prevention as well as in stewardship programs to curb the spread of MDR and XDR-strains in healthcare facilities.
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http://dx.doi.org/10.1097/QCO.0000000000000598DOI Listing
December 2019

Organization and training at national level of antimicrobial stewardship and infection control activities in Europe: an ESCMID cross-sectional survey.

Eur J Clin Microbiol Infect Dis 2019 Nov 8;38(11):2061-2068. Epub 2019 Aug 8.

APEMAC and Infectious Diseases Department, Université de Lorraine and CHRU-Nancy, Nancy, France.

Antimicrobial stewardship (AMS) and Infection prevention and control (IPC) are two key complementary strategies that combat development and spread of antimicrobial resistance. The ESGAP (ESCMID Study Group for AMS), EUCIC (European Committee on Infection Control) and TAE (Trainee Association of ESCMID) investigated how AMS and IPC activities and training are organized, if present, at national level in Europe. From February 2018 to May 2018, an internet-based cross-sectional survey was conducted through a 36-item questionnaire, involving up to three selected respondents per country, from 38 European countries in total (including Israel), belonging to the ESGAP/EUCIC/TAE networks. All 38 countries participated with at least one respondent, and a total of 81 respondents. Education and involvement in AMS programmes were mandatory during the postgraduate training of clinical microbiology and infectious diseases specialists in up to one-third of countries. IPC was acknowledged as a specialty in 32% of countries. Only 32% of countries had both guidance and national requirements regarding AMS programmes, in contrast to 61% for IPC. Formal national staffing standards for AMS and IPC hospital-based activities were present in 24% and 63% of countries, respectively. The backgrounds of professionals responsible for AMS and IPC programmes varied tremendously between countries. The organization and training of AMS and IPC in Europe are heterogeneous and national requirements for activities are frequently lacking.
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http://dx.doi.org/10.1007/s10096-019-03648-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6800847PMC
November 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 Health Sciences, University of Genoa, Genoa, Italy; Ospedale Policlinico San Martino-IRCCS, Genoa, 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

Efficacy of the "first wave" Direct Acting antivirals against HCV infection: results from the Italian LINA (Liver Network Activity) cohort.

New Microbiol 2019 Apr 29;42(2):94-100. Epub 2019 Apr 29.

Department of Mental Health and Public Medicine - Infectious Diseases Unit. University of Campania Luigi Vanvitelli.

Approximately 71 million people are chronically infected with HCV worldwide. Recently, interferonfree therapies effective against HCV became available and nowadays, therapeutic strategies include a combination of two or three drugs with different mechanisms of action. In the present study, we reported real-life SVR rates in a large cohort of four prescribing centers in a high-endemic area of Southern Italy. We conducted a prospective multicenter study among all the patients with chronic HCV infection, who received therapy with the first available interferon-free therapies between March 2015 and December 2017 and who referred to one of the 4 DAA-prescribing centers in Campania, Southern Italy. Patients with Child C cirrhosis, a diagnosis of active HCC at the baseline or who refused the consent form, were excluded. Nine-hundred fifty-three patients were enrolled. Most of the enrolled patients had HCV genotype 1b infection (66.4%), were older than 65 years (64.1%) and had advanced liver fibrosis (Metavir > F4) (73.5%). The overall SVR12 rate was 98.5%. Patients with clinical cirrhosis had a similar SVR12 rate compared with those without cirrhosis (97.8% vs 99.2%, p=0.09), while patients with decompensated cirrhosis had a significantly lower rate of SVR12 compared with those without decompensated disease (95.3% vs 99.0%, p<0.05). Patients aged more than 65 years had a similar rate of SVR12 compared with patients aged ≤ 65 years (98.6% vs 98.0%, p=0.57). Among patients >65 years, those with clinical cirrhosis, as well as those with advanced liver fibrosis, had a similar SVR12 rate compared with the patients with a Metavir score < F4 (98.3% vs 99.0%, p=0.70 and 98.6% vs 98.6%, p=1.00, respectively). In the present, real-life study, DAA regimens are effective and safe in patients with chronic HCV infection, regardless of age and stage of liver disease, providing very high rates of SVR12 (98.5%).
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April 2019

Nanobiotechnology as an emerging approach to combat malaria: A systematic review.

Nanomedicine 2019 06 21;18:221-233. Epub 2019 Mar 21.

Infectious and Tropical Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:

Mosquitoes (Diptera; Culicidae) present a major threat to millions of people and animals worldwide, as they act as vectors for various pathogens, especially parasites and viruses. Resistance to insecticides, such as organophosphates and microbial control agents, and insufficient adherence to application guidelines are common reasons for insecticide treatment failure. Therefore, there is an urgent need for exploration of safer, cheaper, and more effective agents, with novel modes of action, to improve mosquito control. Biosynthesized nanoparticles (NPs) have recently been considered as a potential approach for combating vectors of malaria and also as a treatment for malaria. Here, we present current knowledge about the characterization and effectiveness of biogenic NPs against major vectors of malaria, including avian malaria (which may also provide useful insights on vectors of human malaria). This article is the first systematic review of the effects of biosynthesized nanoparticles on both malaria parasites (Plasmodium spp.) and relevant vectors.
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http://dx.doi.org/10.1016/j.nano.2019.02.017DOI Listing
June 2019

Risk of professional accidental exposure to biological agents in health care workers: a retrospective analysis carried out in a southern Italian tertiary hospital.

Infez Med 2019 Mar;27(1):40-45

Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University Federico II of Naples, Italy.

Worldwide the needlestick injuries of health care workers (HCWs) still represent a major health problem. The authors aimed to evaluate the risk of HCW needlestick injuries in a tertiary university hospital in southern Italy in relation to some HCW characteristics (age, sex, professional profile, work department) and the source of infection. All HCWs of the University Hospital "Federico II" in Naples, Italy, attending the Infectious Diseases Unit after potential accidental contact to blood-borne viruses through needlestick injuries were enrolled during a 22-year period. HCWs underwent clinical analysis and were administered a specific questionnaire to collect (in anonymous fashion) data about age, sex, professional profile and work department. From 1995 to 2016 1,477 needlestick injuries in the same number of people (one accident per person) were recorded by our service. The HCWs were predominately males (n = 806, 55%) and the mean age was 39.4 years (±10.1 SD). The job categories most involved were: physicians (41%), followed by nurses (33%) and healthcare assistants (HCAs, 10%). The incidence proportion was calculated for these highest-risk categories in three defined time points (at the beginning, in the middle and at the end of the study period): 104/2149 (4.86%) in 1995, 41/2498 (1.64%) in 2005 and 25/2057 (1.22%) in 2015. Most injuries occurred in General Surgery (14.21%), Gynecology and Obstetrics (9%) and Pediatrics (6.49%). In about 34% the HCWs had been exposed to HCV infected fluids. Over time, a significant decrease in accidental exposure was recorded for physicians (p= 0.019), nurses (p< 0.0001) and HCAs (p< 0.0001). Our results confirm that some profiles, namely physicians, nurses and healthcare assistants, are still at risk of needlestick injuries, especially in surgical areas, including obstetric wards. Further primary and secondary prevention strategies are needed to decrease the incidence of new cases of needlestick injuries.
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March 2019

Hepatitis C screening in the Emergency Department of a large hospital in southern Italy: results of a pilot study.

Infez Med 2019 Mar;27(1):32-39

Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy.

Around 71 million people worldwide are chronically infected with hepatitis C. HCV prevalence among individuals born in the United States between 1945 and 1965 is estimated to be about 3%. In Italy, about 2% of the population is chronically infected with HCV. Since chronic HCV infection is often asymptomatic, many patients require access to medical care only in an advanced phase of the disease. The best strategy for bringing out hidden chronic HCV infection remains uncertain. The aim of the study was to evaluate the feasibility of an FDA-approved rapid salivary, point-of-care (POC) assay for anti-HCV, performed in patients aged between 45 and 80 years old who were referred to the emergency department of a large hospital in southern Italy and were all unaware of their HCV serostatus. In all, 966 patients were interviewed during the study period. Among them, 220 patients were enrolled. Notably, 25/588 (4%) reported to be anti-HCV positive. Of these, 19 were already being treated with direct-acting antivirals (DAA). Among the enrolled patients, two (0.9%) tested anti-HCV positive and 218 (99.1%) were negative at screening. Both patients with a positive test were male, below the age of 54, with a previous history of intravenous drug abuse, a low level of education, and who had had at least one experience of unprotected sex. We scheduled a visit for treatment evaluation for every positive patient who was not on treatment. Neither of the two de novo patients and 3/6 (50%) patients who were aware of their anti-HCV positivity came to the follow-up visit. Our study shows that a screening strategy for HCV infection in ED is feasible and that about 1% of patients attending the ED and who are unaware of their conditions are anti-HCV positive. Moreover, a non-negligible proportion of subjects, though aware of their condition, was not linked to any hepatologic center.
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March 2019

Real-World Efficacy and Safety of Pangenotypic Direct-Acting Antivirals Against Hepatitis C Virus Infection.

Rev Recent Clin Trials 2019 ;14(3):173-182

Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, Naples, Italy.

Background: Advances in the development of Direct-Acting Antivirals (DAAs), particularly pangenotypic drugs, have led to a high rate of hepatitis C virus (HCV) eradication. Notably, real- world studies have confirmed the efficacy and safety of pangenotypic DAA combinations reported in registration trials. The aim of this study was to review the treatment recommendations, and the efficacy and safety data of anti-HCV pangenotypic drugs reported in registration clinical trials and in recent real-life cohort studies.

Methods: We reviewed the efficacy and safety data of pangenotypic anti-HCV drug combinations reported in original articles and in online conference abstracts.

Results: Current pangenotypic drug combinations resulted in very high rates of sustained virologic response and few adverse reactions in real-life settings. SVR12 rates in real-life studies ranged from 90-100% depending on the pangenotypic combination, the HCV genotype and the stage of liver disease. Most adverse reactions reported in real-life settings were mild in intensity and rarely led to treatment discontinuation. These results are in accordance with those of clinical trials.

Conclusion: Pangenotypic DAAs result in very high rates of sustained virologic responses and are well tolerated. However, they are contraindicated in patients with decompensated cirrhosis or advanced chronic kidney disease who failed previous DDA-based treatment. Further research is required to customize treatment to "unpackage" current DAA combinations and to develop generic drugs against HCV.
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http://dx.doi.org/10.2174/1574887114666190306154650DOI Listing
May 2020

Extended Infusion of β-Lactams for Bloodstream Infection in Patients With Liver Cirrhosis: An Observational Multicenter Study.

Clin Infect Dis 2019 10;69(10):1731-1739

Infectious Diseases Unit, Department of Medical and Surgical Sciences, Sant'Orsola-Malpighi Hospital, University of Bologna, Italy.

Background: We analyzed the impact of continuous/extended infusion (C/EI) vs intermittent infusion of piperacillin-tazobactam (TZP) and carbapenems on 30-day mortality of patients with liver cirrhosis and bloodstream infection (BSI).

Methods: The BICRHOME study was a prospective, multicenter study that enrolled 312 cirrhotic patients with BSI. In this secondary analysis, we selected patients receiving TZP or carbapenems as adequate empirical treatment. The 30-day mortality of patients receiving C/EI or intermittent infusion of TZP or carbapenems was assessed with Kaplan-Meier curves, Cox-regression model, and estimation of the average treatment effect (ATE) using propensity score matching.

Results: Overall, 119 patients received TZP or carbapenems as empirical treatment. Patients who received C/EI had a significantly lower mortality rate (16% vs 36%, P = .047). In a Cox-regression model, the administration of C/EI was associated with a significantly lower mortality (hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.11-0.936; P = .04) when adjusted for severity of illness and an ATE of 25.6% reduction in 30-day mortality risk (95% CI, 18.9-32.3; P < .0001) estimated with propensity score matching. A significant reduction in 30-day mortality was also observed in the subgroups of patients with sepsis (HR, 0.21; 95% CI, 0.06-0.74), acute-on-chronic liver failure (HR, 0.29; 95% CI, 0.03-0.99), and a model for end-stage liver disease score ≥25 (HR, 0.26; 95% CI, 0.08-0.92). At competing risk analysis, C/EI of beta-lactams was associated with significantly higher rates of hospital discharge (subdistribution hazard [95% CI], 1.62 [1.06-2.47]).

Conclusions: C/EI of beta-lactams in cirrhotic patients with BSI may improve outcomes and facilitate earlier discharge.
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http://dx.doi.org/10.1093/cid/ciz032DOI Listing
October 2019

Epidemiology and Microbiology of Skin and Soft Tissue Infections: Preliminary Results of a National Registry.

J Chemother 2019 Feb 3;31(1):9-14. Epub 2018 Dec 3.

y UOC Medicina Interna , Ospedale Umberto I , Enna , Italy.

Skin and soft tissue infections (SSTIs) represent a wide range of clinical conditions characterized by a considerable variety of clinical presentations and severity. Their aetiology can also vary, with numerous possible causative pathogens. While other authors previously published analyses on several types of SSTI and on restricted types of patients, we conducted a large nationwide surveillance programme on behalf of the Italian Society of Infectious and Tropical Diseases to assess the clinical and microbiological characteristics of the whole SSTI spectrum, from mild to severe life-threatening infections, in both inpatients and outpatients. Twenty-five Infectious Diseases (ID) Centres throughout Italy collected prospectively data concerning both the clinical and microbiological diagnosis of patients affected by SSTIs via an electronic case report form. All the cases included in our database, independently from their severity, have been managed by ID specialists joining the study while SSTIs from other wards/clinics have been excluded from this analysis. Here, we report the preliminary results of our study, referring to a 12-month period (October 2016-September 2017). During this period, the study population included 254 adult patients and a total of 291 SSTI diagnoses were posed, with 36 patients presenting more than one SSTIs. The type of infection diagnosed, the aetiological micro-organisms involved and some notes on their antimicrobial susceptibilities were collected and are reported herein. The enrichment of our registry is ongoing, but these preliminary results suggest that further analysis could soon provide useful information to better understand the national epidemiologic data and the current clinical management of SSTIs in Italy.
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http://dx.doi.org/10.1080/1120009X.2018.1536320DOI Listing
February 2019

Unsolved Issues in the Treatment of Spontaneous Peritonitis in Patients with Cirrhosis: Nosocomial Versus Community-acquired Infections and the Role of Fungi.

Rev Recent Clin Trials 2019 ;14(2):129-135

Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, 80131, Naples, Italy.

Introduction: Historically, spontaneous bacterial peritonitis (SBP) has represented one of the most frequent and relevant infectious complications of advanced liver disease, and this is still valid today. Nevertheless, in recent years the role of fungi as causative pathogens of primary peritonitis in patients with cirrhosis has become not negligible. Another issue is linked with the traditional distinction, instrumental in therapeutic choice, between community-acquired and nosocomial forms, according to the onset. Between these two categories, another one has been introduced: the so-called "healthcare-associated infections".

Objective: To discuss the most controversial aspects in the management of SBP nowadays in the light of best available evidence.

Methods: A review of recent literature through MEDLINE was performed.

Results: The difference between community-acquired and nosocomial infections is crucial to guide empiric antibiotic therapy, since the site of acquisition impact on the likelihood of multidrug-resistant bacteria as causative agents. Therefore, third-generation cephalosporins cannot be considered the mainstay of treatment in each episode. Furthermore, the distinction between healthcare-associated and nosocomial form seems very subtle, especially in areas wherein antimicrobial resistance is widespread, warranting broad-spectrum antibiotic regimens for both. Finally, spontaneous fungal peritonitis is a not common but actually underestimated entity, linked to high mortality. Especially in patients with septic shock and/or failure of an aggressive antibiotic regimen, the empiric addition of an antifungal agent might be considered.

Conclusion: Spontaneous bacterial peritonitis is one of the most important complications in patients with cirrhosis. A proper empiric therapy is crucial to have a positive outcome. In this respect, a careful assessment of risk factors for multidrug-resistant pathogens is crucial. Likewise important, mostly in nosocomial cases, is not to overlook the probability of a fungal ascitic infection, namely a spontaneous fungal peritonitis.
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http://dx.doi.org/10.2174/1574887114666181204102516DOI Listing
January 2020

Current evidence on the management of hepatitis B in pregnancy.

World J Hepatol 2018 Sep;10(9):585-594

Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Italy.

Hepatitis B virus (HBV) infection is one of the main public health problems across the globe, since almost one third of the world population presents serological markers of contact with the virus. A profound impact on the epidemiology has been exerted by universal vaccination programmes in many countries, nevertheless the infection is still widespread also in its active form. In the areas of high endemicity (prevalence of hepatitis B surface antigen positivity > 7%), mother-to-child transmission represents the main modality of infection spread. That makes the correct management of HBV in pregnancy a matter of utmost importance. Furthermore, the infection in pregnancy needs to be carefully assessed and handled not only with respect to the risk of vertical transmission but also with respect to gravid women health. Each therapeutic or preventive choice deserves to be weighed upon attentively. On many aspects evidence is scarce or controversial. This review will highlight the latest insights into the paramount steps in managing HBV in pregnancy, with particular attention to recommendations from recent guidelines and data from up-do-date research syntheses.
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http://dx.doi.org/10.4254/wjh.v10.i9.585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6177570PMC
September 2018

Current and emerging pharmacotherapy for the treatment of bacterial peritonitis.

Expert Opin Pharmacother 2018 Aug 2;19(12):1317-1325. Epub 2018 Aug 2.

a Department of Clinical Medicine and Surgery, Section of Infectious Diseases , University of Naples Federico II , Naples , Italy.

Introduction: Spontaneous bacterial peritonitis (SBP) is the quintessential model of bacterial infection in cirrhotic patients. In these particularly frail subjects, infections clearly worsen prognosis increasing substantially mortality. Furthermore, treatment of SBP has become more challenging because of the growing impact of multidrug-resistant (MDR) bacteria.

Areas Covered: This review addresses the reasons behind the change in therapeutic recommendations for SBP that have occurred in the past few years, by focusing on the following aspects: the importance of an early appropriate empirical treatment, the difference between nosocomial and non-nosocomial forms and the overall microbiological shift (rise of Gram-positive bacteria and MDR strains) that have affected SBP.

Expert Opinion: Until recently, third-generation cephalosporins have represented the cornerstone of SBP treatment, a safe choice covering the most important causative agents, namely Enterobacteriaceae. Unfortunately, massive exposure to health systems makes cirrhotic patients prone to MDR infections, which poses significant challenges, all the while not forgetting to strike a balance between effective antimicrobial activity and the risk of toxicity in these fragile subjects. Moreover, there is sparse information about new antibiotics in cirrhotic patients and about drugs levels in ascitic fluid. Therefore, further research is needed to optimize the treatment of SBP.
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http://dx.doi.org/10.1080/14656566.2018.1505867DOI Listing
August 2018

Management of chickenpox in pregnant women: an Italian perspective.

Eur J Clin Microbiol Infect Dis 2018 Sep 25;37(9):1603-1609. Epub 2018 May 25.

Department of Clinical Medicine and Surgery- Section of Infectious Diseases, University Federico II of Naples, Naples, Italy.

Chickenpox is a highly contagious disease caused by primary infection of varicella zoster virus (VZV). The disease is spread worldwide and is usually benign but, in some groups of population like pregnant women, can have a severe outcome. Due to a not optimal vaccination coverage, a relatively high number of childbearing-aged women in a European country such as Italy tested seronegative for VZV and so are currently at risk of acquiring chickenpox during pregnancy, especially if they live in contact with children for family or work reasons. Only few data are available about the risk of infection in this setting: the incidence of chickenpox may range from 1.5 to 4.6 cases/1000 childbearing females and from 1.21 to 6 cases/10,000 pregnant women, respectively. This review is aimed to focus on the epidemiology and the clinical management of exposure to chickenpox during pregnancy. Particular emphasis is given to the accurate screening of childbearing women at the time of the first gynecological approach - the females who tested susceptible to infection can be counseled about the risks and instructed on procedure should contact occur - and to the early prophylaxis of the at-risk exposure. Lastly, the achievement of adequate vaccination coverage of the Italian population remains a cornerstone in the prevention of chickenpox in pregnancy.
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http://dx.doi.org/10.1007/s10096-018-3286-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101639PMC
September 2018

Response to: 'Letter to the Editor: "Management of multidrug-resistant Pseudomonas aeruginosa in the Intensive Care Unit: state of the art"'.

Expert Rev Anti Infect Ther 2018 05;16(5):369-371

a Department of Clinical Medicine and Surgery, Section of Infectious Diseases , University of Naples Federico II , Naples , Italy.

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http://dx.doi.org/10.1080/14787210.2018.1473082DOI Listing
May 2018