Publications by authors named "Anna Marchese"

89 Publications

Molecular Epidemiological Investigation of a Nosocomial Cluster of : Evidence of Recent Emergence in Italy and Ease of Transmission during the COVID-19 Pandemic.

J Fungi (Basel) 2021 Feb 15;7(2). Epub 2021 Feb 15.

Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, 16132 Genoa, Italy.

is an emerging MDR pathogen raising major concerns worldwide. In Italy, it was first and only identified in July 2019 in our hospital (San Martino Hospital, Genoa), where infection or colonization cases have been increasingly recognized during the following months. To gain insights into the introduction, transmission dynamics, and resistance traits of this fungal pathogen, consecutive isolates collected from July 2019 to May 2020 ( = 10) were subjected to whole-genome sequencing (WGS) and antifungal susceptibility testing (AST); patients' clinical and trace data were also collected. WGS resolved all isolates within the genetic clade I (South Asian) and showed that all but one were part of a cluster likely stemming from the index case. Phylogenetic molecular clock analyses predicted a recent introduction (May 2019) in the hospital setting and suggested that most transmissions were associated with a ward converted to a COVID-19-dedicated ICU during the pandemic. All isolates were resistant to amphotericin B, voriconazole, and fluconazole at high-level, owing to mutations in (K143R) and (A640V). Present data demonstrated that the introduction of MDR in Italy was a recent event and suggested that its spread could have been facilitated by the COVID-19 pandemic. Continued efforts to implement stringent infection prevention and control strategies are warranted to limit the spread of this emerging pathogen within the healthcare system.
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http://dx.doi.org/10.3390/jof7020140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919374PMC
February 2021

Spread of Carbapenem-Resistant Gram-Negatives and during the COVID-19 Pandemic in Critically Ill Patients: One Step Back in Antimicrobial Stewardship?

Microorganisms 2021 Jan 3;9(1). Epub 2021 Jan 3.

Infectious Diseases Unit, Ospedale Policlinico San Martino-IRCCS per l'Oncologia, 16132 Genoa, Italy.

The possible negative impact of severe adult respiratory distress caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (COVID-19) on antimicrobial stewardship and infection control has been postulated, but few real-life data are available. The aim of this study was to report our experience with colonization/infection of carbapenem-resistant (CRPA), carbapenem-resistant (CR-Kp) and among critically ill COVID-19 patients admitted to the intensive care unit (ICU). All COVID-19 patients admitted to the ICUs at San Martino Policlinico Hospital-IRCCS in Genoa, Italy, were screened from 28 February to 31 May 2020. One-hundred and eighteen patients admitted to COVID-19 ICUs were included in the study. Among them, 12 (10.2%) became colonized/infected with CRPA, 6 (5.1%) with and 2 (1.6%) with CR-Kp. All patients with CRPA received prior treatment with meropenem, and in 11 (91.7%) infection was not preceded by colonization. Four patients (66.7%) developed candidemia. A significant spread of resistant pathogens was observed among critically ill COVID-19 patients. Dedicated strategies are warranted to prevent horizontal spread and maintain effective antimicrobial stewardship programs in the setting of COVID-19 care.
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http://dx.doi.org/10.3390/microorganisms9010095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823370PMC
January 2021

Treatment of severe infections due to metallo-β-lactamases-producing Gram-negative bacteria.

Future Microbiol 2020 11 3:1489-1505. Epub 2020 Nov 3.

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

In the last decades, there was an important paucity of agents for adequately treating infections due to metallo-β-lactamases-producing Gram-negative bacteria (MBL-GNB). Cefiderocol, a novel siderophore cephalosporin showing activity against MBL-GNB, has been recently marketed, and a combination of aztreonam and ceftazidime/avibactam has shown a possible favorable effect on survival of patients with severe MBL-GNB infections in observational studies. Other agents showing activity against MBL-GNB are currently in clinical development (e.g., cefepime/taniborbactam, LYS228, cefepime/zidebactam) that could be an important addition to our future armamentarium for severe MBL-GNB infections. Nonetheless, we should not discontinue our efforts to optimize the use of non-β-lactams agents, since they could remain an essential last-resort or alternative option in selected cases.
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http://dx.doi.org/10.2217/fmb-2020-0210DOI Listing
November 2020

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

Microb Drug Resist 2020 Sep 18. 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
September 2020

Bloodstream infections in critically ill patients with COVID-19.

Eur J Clin Invest 2020 Oct 11;50(10):e13319. Epub 2020 Aug 11.

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

Background: Little is known about the incidence and risk of intensive care unit (ICU)-acquired bloodstream infections (BSI) in critically ill patients with coronavirus disease 2019 (COVID-19).

Materials And Methods: This retrospective, single-centre study was conducted in Northern Italy. The primary study objectives were as follows: (a) to assess the incidence rate of ICU-acquired BSI and (b) to assess the cumulative risk of developing ICU-acquired BSI.

Results: Overall, 78 critically ill patients with COVID-19 were included in the study. Forty-five episodes of ICU-acquired BSI were registered in 31 patients, with an incidence rate of 47 episodes (95% confidence interval [CI] 35-63) per 1000 patient-days at risk. The estimated cumulative risk of developing at least one BSI episode was of almost 25% after 15 days at risk and possibly surpassing 50% after 30 days at risk. In multivariable analysis, anti-inflammatory treatment was independently associated with the development of BSI (cause-specific hazard ratio [csHR] 1.07 with 95% CI 0.38-3.04 for tocilizumab, csHR 3.95 with 95% CI 1.20-13.03 for methylprednisolone and csHR 10.69 with 95% CI 2.71-42.17 for methylprednisolone plus tocilizumab, with no anti-inflammatory treatment as the reference group; overall P for the dummy variable = 0.003).

Conclusions: The incidence rate of BSI was high, and the cumulative risk of developing BSI increased with ICU stay. Further study will clarify if the increased risk of BSI we detected in COVID-19 patients treated with anti-inflammatory drugs is outweighed by the benefits of reducing any possible pro-inflammatory dysregulation induced by SARS-CoV-2.
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http://dx.doi.org/10.1111/eci.13319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323143PMC
October 2020

Environmental factors associated with etiology of microbiologically confirmed reconstructive breast implant infections: impact on clinical management and treatment.

New Microbiol 2020 Apr 19;43(2):78-81. Epub 2020 Apr 19.

Infection Disease Clinic, Policlinico San Martino, Largo Rosanna Benzi 10, Genoa 16132, Italy.

Even if wide differences exist in the incidence of Gram-negative infections following breast cancer implant reconstructions (2-20%), its occurrence needs to be considered to optimize antibiotic therapy, which is usually directed towards Gram-positive cocci. There is a general notion on the possible source of Gram-negative microorganisms during outdoor activities. For this reason, we administered a specific questionnaire to infected patients to investigate this aspect. In 450 consecutive implant reconstructions between January 1, 2016 and March 31, 2018, 27 patients (6%) developed proven infection. For each patient, we collected age, tumor stage and recurrence, chemo/radiotherapy, infecting microorganism, fate of implant, type and duration of antibiotic treatment, and administered a questionnaire on exposure to contaminated environments. Twenty patients (74%) had Gram-positive and 7 (26%) had implants infected by Gram-negative agents. The two groups were homogeneous as regards age and no statistically significant difference was observed for other parameters. A significant difference was detected with regard to environmental risk factors in the Gram-negative group (p=0,049). Length of antibiotic therapy was longer in the Gram-negative patients (17.4 vs 11.05 days) and antibiotic treatment was ineffective in 43% of the Gram-negative group. Environmental factors may be an element to evaluate in order to improve patient management. Surveys on larger cohorts are warranted.
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April 2020

Simultaneous photoablative and photodynamic 810-nm diode laser therapy as an adjunct to non-surgical periodontal treatment: an in-vitro study.

Minerva Stomatol 2020 Feb;69(1):1-7

Department of Surgical Sciences and Integrated Diagnostic (DISC), University of Genoa, Genoa, Italy.

Background: The use of lasers at different wavelengths has been proposed in combination with conventional non-surgical periodontal treatment in order to improve the clinical outcome of periodontal disease. However, the clinical use of laser photonic energy is still the subject of research and debate because the antibacterial activity of the laser is dependent upon method, laser parameters, quantity of bacteria, species selected and photosensitizers used.

Methods: We evaluated the in-vitro bactericidal activity of 810 nm diode-laser irradiation in simultaneous photoablative and photodynamic mode against the major pathogenic bacterial organisms associated with periodontal inflammation and disease. We used indocyanine green as photosensitizer and the high-energy density of 161.7 J/cm2 or 215.0 J/cm2 for the photoablative-photodynamic irradiation.

Results: The bacteria were drastically affected by the 215.0 J/cm2 irradiation in the presence of indocyanine green. In fact, the number of Porphyromonas gingivalis and Prevotella intermedia was reduced by 99.9% (P<0.001), while the number of Fusobacterium nucleatum, Aggregatibacter actinomycetemcomitans, Tannerella forsythia and Actinomyces viscosus decremented by 83.3% (P<0.01), 86.8% (P<0.05), 75% (P<0.01) and 78.7% (P<0.001), respectively. P. gingivalis and P. intermedia were the only bacteria that were sensitive to the treatment with indocyanine green dye and 161.7 J/cm2 of laser irradiation (P<0.001).

Conclusions: Our preliminary in-vitro data suggest that simultaneous photoablative-photodynamic irradiation could be a promising therapy against a wide range of bacteria involved in periodontal disease. We believe that further additional in-vivo investigation is necessary, to enable a more complete picture of effectiveness within a clinical setting to be established. In addition, the use of a simultaneous photoablative-photodynamic therapy is suggested to reduce treatment time, without compromising the efficacy against the periodontal pathogens.
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http://dx.doi.org/10.23736/S0026-4970.19.04233-XDOI Listing
February 2020

Preliminary Results of a Combined Score Based on sIL2-Rα and TIM-3 Levels Assayed Early After Hematopoietic Transplantation.

Front Immunol 2019 7;10:3158. Epub 2020 Feb 7.

Unità di Trapianto di Midollo, Divisione di Ematologia, Azienda Ospedaliera Policlinico Vittorio Emanuele, Catania, Italy.

Assays of cytokines in the plasma at the onset of graft-vs. -host disease (GVHD) can predict disease severity and treatment-related mortality (TRM); however, the optimal time during which cytokines should be tested and the specific panel of cytokines with the highest predictive ability remain unknown. We chose a predefined time point, 18 days after hematopoietic stem cell transplantation (HSCT), to measure the levels of six cytokines in the plasma: soluble interleukin-2 receptor alpha (sIL2-Rα), T-cell immunoglobulin domain and mucin domain-3 (TIM-3), suppression of tumorigenicity-2 (ST-2), intercellular adhesion molecule (ICAM-1), interferon-gamma (IFN-γ), and interleukin-6 (IL-6). The study included 95 patients, who underwent allogeneic hematopoietic transplantation at our institution. Plasma levels of sIL2-Rα and TIM-3, measured as continuous data, had predictive value for overall survival (sIL2-Rα, = 0.002; TIM-3, = 0.0007), while TRM could be predicted by sIL2-Rα ( = 0.0005), IFN-gamma ( = 0.01), and IL-6 ( = 0.0001). No cytokine was associated with the risk of relapse. Patients were categorized into groups, according to cytokine thresholds determined by receiver operating characteristic curve analysis (sIL2-Rα ≤ or > 8,100 pg/ml; TIM-3 ≤ or > 950 pg/ml) and multivariate analysis was conducted. High levels of both TIM-3 and sIL2-Rα were significant predictors of poor survival [TIM-3 > 950 pg/ml: hazard ratio (HR) = 6.214 (95% CI 1.939-19.910), = 0.002 and sIL2-Rα > 8.100 pg/ml: HR = 2.644 (95% CI 1.308-5.347), = 0.006]. Using these cutoff thresholds, we constructed a composite scoring system that could distinguish three different groups of patients with varying rates of TRM: high risk, 41.7%; intermediate risk, 10.8%; and low risk, 7.1% (Gray's test: = 0.001). If confirmed in a validation cohort, this composite scoring system could be used to guide the modulation of post-transplant immune suppressive therapy.
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http://dx.doi.org/10.3389/fimmu.2019.03158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020780PMC
November 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

Oral microbiota and Alzheimer's disease: Do all roads lead to Rome?

Pharmacol Res 2020 01 30;151:104582. Epub 2019 Nov 30.

Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran. Electronic address:

Alzheimer's disease (AD) is a progressive neurodegenerative pathology affecting milions of people worldwide associated with deposition of senile plaques. While the genetic and environmental risk factors associated with the onset and consolidation of late onset AD are heterogeneous and sporadic, growing evidence also suggests a potential link between some infectious diseases caused by oral microbiota and AD. Oral microbiota dysbiosis is purported to contribute either directly to amyloid protein production, or indirectly to neuroinflammation, occurring as a consequence of bacterial invasion. Over the last decade, the development of Human Oral Microbiome database (HOMD) has deepened our understanding of oral microbes and their different roles during the human lifetime. Oral pathogens mostly cause caries, periodontal disease, and edentulism in aged population, and, in particular, alterations of the oral microbiota causing chronic periodontal disease have been associated with the risk of AD. Here we describe how different alterations of the oral microbiota may be linked to AD, highlighting the importance of a good oral hygiene for the prevention of oral microbiota dysbiosis.
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http://dx.doi.org/10.1016/j.phrs.2019.104582DOI Listing
January 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

Isolation of from invasive and non-invasive samples of a patient suffering from vascular disease, Italy, July 2019.

Euro Surveill 2019 Sep;24(37)

Unità Operativa di Microbiologia, University of Genoa (DISC) and Ospedale Policlinico San Martino-IRCCS, Genoa, Italy.

We recently isolated from a blood culture and cutaneous swabs of a patient in her mid-70s. Our routine phenotypic methods failed to identify the microorganism, but it was identified by molecular tests and MALDI-TOF MS analysis. Our report, the first from Italy, further underlines the geographically wide distribution of and the need to confirm species identification of any suspicious colony as soon as possible to stop its spread.
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http://dx.doi.org/10.2807/1560-7917.ES.2019.24.37.1900549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6749772PMC
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

Genotypes and population genetics of cryptococcus neoformans and cryptococcus gattii species complexes in Europe and the mediterranean area.

Fungal Genet Biol 2019 08 3;129:16-29. Epub 2019 Apr 3.

Centers for Disease Control and Prevention, Atlanta, USA.

A total of 476 European isolates (310 Cryptococcus neoformans var. grubii, 150 C. neoformans var. neoformans, and 16 C. gattii species complex) from both clinical and environmental sources were analyzed by multi-locus sequence typing. Phylogenetic and population genetic analyses were performed. Sequence analysis identified 74 sequence types among C. neoformans var. neoformans (VNIV), 65 among C. neoformans var. grubii (56 VNI, 8 VNII, 1 VNB), and 5 among the C. gattii species complex (4 VGI and 1 VGIV) isolates. ST23 was the most frequent genotype (22%) among VNI isolates which were mostly grouped in a large clonal cluster including 50% of isolates. Among VNIV isolates, a predominant genotype was not identified. A high percentage of autochthonous STs were identified in both VNI (71%) and VNIV (96%) group of isolates. The 16 European C. gattii species complex isolates analyzed in the present study originated all from the environment and all belonged to a large cluster endemic in the Mediterranean area. Population genetic analysis confirmed that VNI group of isolates were characterized by low variability and clonal expansion while VNIV by a higher variability and a number of recombination events. However, when VNI and VNIV environmental isolates were compared, they showed a similar population structure with a high percentage of shared mutations and the absence of fixed mutations. Also linkage disequilibrium analysis reveals differences between clinical and environmental isolates showing a key role of PLB1 allele combinations in host infection as well as the key role of LAC1 allele combinations for survival of the fungus in the environment. The present study shows that genetic comparison of clinical and environmental isolates represents a first step to understand the genetic characteristics that cause the shift of some genotypes from a saprophytic to a parasitic life style.
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http://dx.doi.org/10.1016/j.fgb.2019.04.001DOI Listing
August 2019

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

The natural plant compound carvacrol as an antimicrobial and anti-biofilm agent: mechanisms, synergies and bio-inspired anti-infective materials.

Biofouling 2018 07 1;34(6):630-656. Epub 2018 Aug 1.

j Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section , University of Pavia , Pavia , Italy.

Carvacrol (5-isopropyl-2-methyl phenol) is a natural compound that occurs in the leaves of a number of plants and herbs including wild bergamot, thyme and pepperwort, but which is most abundant in oregano. The aim of this review is to analyse the scientific data from the last five years (2012-2017) on the antimicrobial and anti-biofilm activities of carvacrol, targeting different bacteria and fungi responsible for human infectious diseases. The antimicrobial and anti-biofilm mechanisms of carvacrol and its synergies with antibiotics are illustrated. The potential of carvacrol-loaded anti-infective nanomaterials is underlined. Carvacrol shows excellent antimicrobial and anti-biofilm activities, and is a very interesting bioactive compound against fungi and a wide range of Gram-positive and Gram-negative bacteria, and being active against both planktonic and sessile human pathogens. Moreover, carvacrol lends itself to being combined with nanomaterials, thus providing an opportunity for preventing biofilm-associated infections by new bio-inspired, anti-infective materials.
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http://dx.doi.org/10.1080/08927014.2018.1480756DOI Listing
July 2018

Analysis of clinical management of infected breast implants and of factors associated to successful breast pocket salvage in infections occurring after breast reconstruction.

Int J Infect Dis 2018 Jun 13;71:67-72. Epub 2018 Apr 13.

Clinica Malattie Infettive, Programma Infettivologia dell'Ospite Immunocompromesso Policlinico San Martino, Largo Rosanna Benzi 10, Genoa 16132, Italy; Department of Health Sciences, University of Genova, 16132 Genova, Italy. Electronic address:

Objectives: Considerable efforts have been devoted so far to improve salvage procedures of infected breast implants in absence of defined guidelines or validated clinical protocols. Within a cohort of prospectively recruited patients who underwent breast reconstruction, we performed a retrospective review of proven implant infections in order to describe factors contributing to management success.

Methods: We collected data in 1293 consecutive patients who underwent two stage (expander+prosthesis) breast reconstruction with at least 12 months of follow-up. Demographic data, timing of infection, type of microorganism, intent of salvage, fate of the implant, type of antibiotic treatment and follow-up were recorded in a prospective data collection on clinical records.

Results: Implant infections occurred in 103 of 1293 patients (8%). Among these, 73 (71%) were proven infections with confirmed microbiology. Implant pocket salvage was attempted in 43/73 (59%). patients A higher proportion of expander implant pockets were successfully saved compared to prosthetic pocket (p=0,04). Gram-positive microrganisms represented the majority of etiologic agents, with coagulase negative staphylococci prevailing over Staphylococcus aureus. No association was observed between success rate and type of infecting microorganism. A higher proportion of patients with previous or intraoperative radiotherapy or with perioperative chemotherapy underwent an attempt of implant salvage (p=0,081 and 0,0571 trend, respectively). No single antibiotic regimen was superior to the others in terms of success rate. Implant pocket salvage was higher in expanders compared to prostheses (74% vs 33% p=0,04). Higher success rates in implant pocket salvage were evident when implant replacement was preceded and followed by antibiotic treatment compared to inpatient antibiotic treatment alone (100% versus 57%, p=0,035).

Conclusion: Patient selection in clinical practice leads to differences in patients with breast implant infection who are considered for attempts at implant salvage vs. those who are treated with implant removal. Salvage of breast implant pockets can be obtained in the majority of patients with combined one-step implant replacement surgery and antibiotic treatment. Increased efforts and protocols to recruit patients into pocket salvage management are needed.
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http://dx.doi.org/10.1016/j.ijid.2018.03.019DOI Listing
June 2018

Pharmacokinetics of high-dose extended-infusion meropenem during pulmonary exacerbation in adult cystic fibrosis patients: a case series.

New Microbiol 2018 Jan 9;41(1):47-51. Epub 2018 Jan 9.

Clinical Pharmacology and Toxicology Unit, University of Genoa (DIMI), Genoa, Italy.

This case series explored the pharmacokinetic/pharmacodynamic (PK/PD) characteristics of meropenem (MEM) in adult cystic fibrosis (CF) patients hospitalized for a pulmonary exacerbation. From January 2015 to June 2016, all adult patients with cystic fibrosis (CF) and chronic pulmonary infection due to meropenem (MEM)-susceptible/intermediate Pseudomonas aeruginosa who received at least 48 h of MEM as an extended 3-hour infusion for treating a pulmonary exacerbation were enrolled. MEM plasma concentrations were determined by high-performance liquid chromatography. Six adult CF patients with a median age of 47 years were included in the study. MEM showed a high Vd (mean 45.98 L, standard deviation [SD] ±34.45). A minimal PK/PD target of 40% T > minimum inhibitory concentration (MIC) with respect to the MEM MIC of P. aeruginosa strains isolated from sputum during exacerbation was achieved in 5/6 patients (83%). MEM failed to achieve this target only in one patient, whose strain showed the highest MEM MIC in our cohort (8 mg/L). In all patients, MEM was well tolerated, and no adverse events were reported. In conclusion, high-dose, extended-infusion MEM during pulmonary exacerbation showed a high Vd in six adult CF patients with high median age, and was well tolerated.
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January 2018

Correction to: Impact of a mixed educational and semi-restrictive antimicrobial stewardship project in a large teaching hospital in Northern Italy.

Infection 2017 12;45(6):929

U.O. Clinica Malattie Infettive, University of Genoa (DISSAL) and Ospedale Policlinico San Martino-IRCCS per L'Oncologia, L.go R. Benzi, 10, 16132, Genoa, Italy.

A technical error led to incorrect rendering of the author group in this article. The correct authorship is as follows: Daniele Roberto Giacobbe, Valerio Del Bono, Malgorzata Mikulska, Giulia Gustinetti, Anna Marchese, Federica Mina, Alessio Signori, Andrea Orsi, Fulvio Rudello, Cristiano Alicino, Beatrice Bonalumi, Alessandra Morando, Giancarlo Icardi, Sabrina Beltramini, Claudio Viscoli; On behalf of the San Martino Antimicrobial Stewardship Group.
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http://dx.doi.org/10.1007/s15010-017-1068-2DOI Listing
December 2017

Fundamental niche prediction of the pathogenic yeasts Cryptococcus neoformans and Cryptococcus gattii in Europe.

Environ Microbiol 2017 10 15;19(10):4318-4325. Epub 2017 Sep 15.

Universidad Miguel Hernández, Alicante, Spain.

Fundamental niche prediction of Cryptococcus neoformans and Cryptococcus gattii in Europe is an important tool to understand where these pathogenic yeasts have a high probability to survive in the environment and therefore to identify the areas with high risk of infection. In this study, occurrence data for C. neoformans and C. gattii were compared by MaxEnt software with several bioclimatic conditions as well as with soil characteristics and land use. The results showed that C. gattii distribution can be predicted with high probability along the Mediterranean coast. The analysis of variables showed that its distribution is limited by low temperatures during the coldest season, and by heavy precipitations in the driest season. C. neoformans var. grubii is able to colonize the same areas of C. gattii but is more tolerant to cold winter temperatures and summer precipitations. In contrast, the C. neoformans var. neoformans map was completely different. The best conditions for its survival were displayed in sub-continental areas and not along the Mediterranean coasts. In conclusion, we produced for the first time detailed prediction maps of the species and varieties of the C. neoformans and C. gattii species complex in Europe and Mediterranean area.
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http://dx.doi.org/10.1111/1462-2920.13915DOI Listing
October 2017

Impact of a mixed educational and semi-restrictive antimicrobial stewardship project in a large teaching hospital in Northern Italy.

Infection 2017 Dec 30;45(6):849-856. Epub 2017 Aug 30.

U.O. Clinica Malattie Infettive, University of Genoa (DISSAL) and Ospedale Policlinico San Martino-IRCCS per L'Oncologia, L.go R. Benzi, 10, 16132, Genoa, Italy.

Background: The overuse of antimicrobials favors the dissemination of antimicrobial resistance, as well as invasive fungal diseases and Clostridium difficile infections (CDI). In this study, we assessed the impact of a mixed educational and semi-restrictive antimicrobial stewardship (AMS) project in a large teaching hospital in Italy.

Methods: The AMS project was conducted from May 2014 to April 2016. It consisted of two initiatives in two consecutive periods: (1) educational activities; (2) semi-restrictive control of antimicrobial prescribing through a computerized software. The primary endpoint was consumption of antibacterials and antifungals. Secondary endpoints were incidence of CDI, methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI), carbapenem-resistant Klebsiella pneumoniae (CRKP) BSI, and Candida BSI.

Results: During the study period, a statistically significant reduction in consumption was observed for antibacterials (-1.45 defined daily doses (DDD)/1000 patient-days monthly, 95% confidence intervals [CI] -2.38 to -0.52, p 0.004), mainly driven by reductions in the use of fluoroquinolones, third/fourth generation cephalosporins, and carbapenems. No decrease in consumption of antifungals was observed (-0.04 DDD/1000 patient-days monthly, 95% CI -0.34 to +0.25, p 0.750). A statistically significant trend towards reduction was observed for incidence of CRKP BSI (incidence rate ratio 0.96, 95% CI 0.92-0.99, p 0.013). No statistically significant variations in trends were observed for CDI, MRSA BSI, and Candida BSI.

Conclusions: The mixed AMS project was effective in reducing the use of major antibacterials and the incidence of CRKP BSI. Further research is needed to assess the extent of long-term benefits of semi-restrictive approaches.
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http://dx.doi.org/10.1007/s15010-017-1063-7DOI Listing
December 2017

Effect of combination therapy containing a high-dose carbapenem on mortality in patients with carbapenem-resistant Klebsiella pneumoniae bloodstream infection.

Int J Antimicrob Agents 2018 Feb 24;51(2):244-248. Epub 2017 Aug 24.

Institute of Infectious Diseases, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy.

Objectives: To evaluate the impact of high-dose (HD) carbapenem-based combination therapy on clinical outcome in patients with monomicrobial carbapenem-resistant Klebsiella pneumoniae (CR-KP) bloodstream-infection (BSI).

Methods: Post hoc analysis of all adult patients with CR-KP BSI who were treated with a combination antibiotic regimen, collected over a six-year period in six large Italian teaching hospitals. To control for confounding effects of HD carbapenem combination on 14-day mortality, a multivariate Cox regression analysis was performed. Due to imbalances between patients, a propensity score for receiving HD carbapenem was added to the model.

Results: 595 patients with CR-KP BSI were analysed, 77% of isolates showed a carbapenem MIC ≥16 mg/L, 428 (71.9%) received HD carbapenem-based combination therapy. Overall, 127 patients (21.3%) died within 14 days after BSI onset. Multivariate analysis showed the Charlson comorbidity index (HR 1.31, 95%CI 1.20-1.43, P <0.001), septic shock at BSI onset (HR 3.14, 95%CI 2.19-4.50, P <0.001), and colistin-resistant strain (HR 1.52, 95%CI 1.02-2.24, P = 0.03) were independently associated with 14-day mortality, whereas admission to surgical ward (HR 0.44, 95%CI 0.25-0.78, P = 0.005) and HD carbapenem use (HR 0.69, 95%CI 0.47-1.00, P = 0.05) were protective factors. When adjusted for the propensity score, HD carbapenem use showed a greater protective effect (HR 0.64, 95%CI 0.43-0.95, P = 0.03). Stratifying the model for carbapenem MIC, the benefit of HD carbapenem was also observed for strains with carbapenem MIC ≥16 mg/L.

Conclusions: In patients receiving combination therapy for CR-KP BSI, the use of HD carbapenem seems to be associated with better outcome, even in the presence of high-level carbapenem resistance.
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http://dx.doi.org/10.1016/j.ijantimicag.2017.08.019DOI Listing
February 2018

Update on Monoterpenes as Antimicrobial Agents: A Particular Focus on p-Cymene.

Materials (Basel) 2017 Aug 15;10(8). Epub 2017 Aug 15.

Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran 19395-5487, Iran.

p-Cymene [1-methyl-4-(1-methylethyl)-benzene] is a monoterpene found in over 100 plant species used for medicine and food purposes. It shows a range of biological activity including antioxidant, anti-inflammatory, antinociceptive, anxiolytic, anticancer and antimicrobial effects. This last property has been widely investigated due to the urgent need for new substances with antimicrobial properties, to be used to treat communicable diseases whose diffusion in developed countries has been facilitated by globalization and the evolution of antimicrobial resistance. This review summarizes available scientific data, as reported by the most recent studies describing the antimicrobial activity of p-cymene either alone, or as the main component of plant extracts, as well as addressing the mechanisms of action of cymenes as antimicrobial agents. While p-cymene is one of the major constituents of extracts and essential oils used in traditional medicines as antimicrobial agents, but considering the limited data on its in vivo efficacy and safety, further studies are required to reach a definitive recommendation on the use and beneficial effects of p-cymene in human healthcare and in biomedical applications as a promising candidate to functionalize biomaterials and nanomaterials.
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http://dx.doi.org/10.3390/ma10080947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578313PMC
August 2017

Impact of carbapenem-resistant Klebsiella pneumoniae (CR-KP) infections in kidney transplantation.

Transpl Infect Dis 2017 Dec 28;19(6). Epub 2017 Sep 28.

Kidney Transplant Unit, IRCCS San Martino University Hospital - IST National Institute for Cancer Research, Genoa, Italy.

Background: Carbapenem-resistant Klebsiella pneumoniae (CR-KP) infections in solid organ transplant patients are progressively increasing and are associated with worse outcomes, although potential risk factors and therapeutic strategies are still not well defined.

Methods: We conducted a retrospective matched-pair analysis in which we compared 26 recipients CR-KP-positive after kidney transplantation (KT) with 52 CR-KP-negative patients transplanted in the same period, during a CR-KP outbreak that occurred in our hospital. Twenty-one patients (80%) received a combined antibiotic treatment. At the end of the follow-up, of the 26 CR-KP infected patients, 11 (42.3%) experienced at least one episode of re-infection, 9 (34.6%) remained colonized, and 6 (23.0%) had a symptomatic infection. Two of the 11 patients with re-infection died, while 9 were colonized at the end of the study.

Results: A significantly better patient (P = .043) and graft (P < .001) survival was observed in CR-KP-negative patients. Univariate analysis identified the following variables as potential risk factors associated with CR-KP infection after KT: lower body mass index (P = .020); higher creatinine levels at post-transplant days 7 (P = .009), 15 (P = .026), and 30 (P = .019); longer hospital stay (P = .007); longer cold ischemia time (P = .004); delayed graft function (P = .020); and higher Clavien-Dindo score (P = .006).

Conclusion: The study confirmed that a CR-KP positivity may affect the outcome of a kidney transplant population. In severe CR-KP infections with sepsis, a combined antibiotic treatment seems to be advisable.
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http://dx.doi.org/10.1111/tid.12757DOI Listing
December 2017

Combined use of serum (1,3)-β-D-glucan and procalcitonin for the early differential diagnosis between candidaemia and bacteraemia in intensive care units.

Crit Care 2017 Jul 10;21(1):176. Epub 2017 Jul 10.

Infectious Diseases Division, University of Genoa (DISSAL) and Ospedale Policlinico San Martino - IRCCS per l'Oncologia, L.go R. Benzi, 10 - 16132, Genoa, Italy.

Background: This study aimed to assess the combined performance of serum (1,3)-β-D-glucan (BDG) and procalcitonin (PCT) for the differential diagnosis between candidaemia and bacteraemia in three intensive care units (ICUs) in two large teaching hospitals in Italy.

Methods: From June 2014 to December 2015, all adult patients admitted to the ICU who had a culture-proven candidaemia or bacteraemia, as well as BDG and PCT measured closely to the time of the index culture, were included in the study. The diagnostic performance of BDG and PCT, used either separately or in combination, was assessed by calculating the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and positive and negative likelihood ratios (LR+ and LR-). Changes from pre-test probabilities to post-test probabilities of candidaemia and bacteraemia were inferred from Fagan's nomograms.

Results: One hundred and sixty-six patients were included, 73 with candidaemia (44%) and 93 with bacteraemia (56%). When both markers indicated candidaemia (BDG ≥80 pg/ml and PCT <2 ng/ml) they showed higher PPV (96%) compared to 79% and 66% for BDG or PCT alone, respectively. When both markers indicated bacteraemia (BDG <80 pg/ml and PCT ≥2 ng/ml), their NPV for candidaemia was similar to that of BDG used alone (95% vs. 93%). Discordant BDG and PCT results (i.e. one indicating candidaemia and the other bacteraemia) only slightly altered the pre-test probabilities of the two diseases.

Conclusions: The combined use of PCT and BDG could be helpful in the diagnostic workflow for critically ill patients with suspected candidaemia.
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http://dx.doi.org/10.1186/s13054-017-1763-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5504626PMC
July 2017

Antimicrobial activity of eugenol and essential oils containing eugenol: A mechanistic viewpoint.

Crit Rev Microbiol 2017 Nov 27;43(6):668-689. Epub 2017 Mar 27.

h Faculty of Nutrition Science and Food Technology , National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences , Tehran , Iran.

Eugenol is a hydroxyphenyl propene, naturally occurring in the essential oils of several plants belonging to the Lamiaceae, Lauraceae, Myrtaceae, and Myristicaceae families. It is one of the major constituents of clove (Syzygium aromaticum (L.) Merr. & L.M. Perry, Myrtaceae) oil and is largely used in both foods and cosmetics as a flavoring agent. A large body of recent scientific evidence supports claims from traditional medicine that eugenol exerts beneficial effects on human health. These effects are mainly associated with antioxidant and anti-inflammatory activities. Eugenol has also shown excellent antimicrobial activity in studies, being active against fungi and a wide range of gram-negative and gram-positive bacteria. The aim of this review is to analyze scientific data from the main published studies describing the antibacterial and antifungal activities of eugenol targeting different kind of microorganisms, such as those responsible for human infectious diseases, diseases of the oral cavity, and food-borne pathogens. This article also reports the effects of eugenol on multi-drug resistant microorganisms. On the basis of this collected data, eugenol represents a very interesting bioactive compound with broad spectrum antimicrobial activity against both planktonic and sessile cells belonging to food-decaying microorganisms and human pathogens.
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http://dx.doi.org/10.1080/1040841X.2017.1295225DOI Listing
November 2017

Phytochemicals for human disease: An update on plant-derived compounds antibacterial activity.

Microbiol Res 2017 Mar 19;196:44-68. Epub 2016 Dec 19.

Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran. Electronic address:

In recent years, many studies have shown that phytochemicals exert their antibacterial activity through different mechanisms of action, such as damage to the bacterial membrane and suppression of virulence factors, including inhibition of the activity of enzymes and toxins, and bacterial biofilm formation. In this review, we summarise data from the available literature regarding the antibacterial effects of the main phytochemicals belonging to different chemical classes, alkaloids, sulfur-containing phytochemicals, terpenoids, and polyphenols. Some phytochemicals, besides having direct antimicrobial activity, showed an in vitro synergistic effect when tested in combination with conventional antibiotics, modifying antibiotic resistance. Review of the literature showed that phytochemicals represent a possible source of effective, cheap and safe antimicrobial agents, though much work must still be carried out, especially in in vivo conditions to ensure the selection of effective antimicrobial substances with low side and adverse effects.
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http://dx.doi.org/10.1016/j.micres.2016.12.003DOI Listing
March 2017

eReply. Diagnostic intricacies and fortuitous treatment approaches for carbapenem-resistant Klebsiella pneumoniae.

Interact Cardiovasc Thorac Surg 2016 11;23(5):768

Division of Cardiac Surgery, IRCCS San Martino-IST, Genoa, Italy.

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http://dx.doi.org/10.1093/icvts/ivw289DOI Listing
November 2016

Fatal Donor-Derived Carbapenem-Resistant Infection in a Combined Kidney-Pancreas Transplantation.

Case Rep Transplant 2016 16;2016:7920951. Epub 2016 Oct 16.

Kidney Transplant Unit, IRCCS San Martino University Hospital, IST National Institute for Cancer Research, Genoa, Italy.

Carbapenem-resistant (CR-KP) infections in solid organ transplant recipients are associated with high morbidity and mortality. We report a case of a fatal donor-derived CR-KP infection in a combined kidney-pancreas transplant. Given the short interval of time between donor hospitalization and organ procurement, information concerning the donor CR-KP positivity arrived only 72 hours after transplant. Based on this experience, we believe that knowledge of the donor's CR-KP status should be mandatory before procurement and, if positive, pancreas donation should be contraindicated.
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http://dx.doi.org/10.1155/2016/7920951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5086363PMC
October 2016