Silvia Natoli | "Tor Vergata" University of Rome (original) (raw)

Papers by Silvia Natoli

Research paper thumbnail of Efficacy and safety profile of prolonged release oxycodone in combination with naloxone (OXN PR) in Parkinson’s disease patients with chronic pain

Journal of Neurology, 2015

Pain is a relevant and often underestimated non-motor symptom affecting the quality of life of pa... more Pain is a relevant and often underestimated non-motor symptom affecting the quality of life of patients with Parkinson's disease (PD). Although some pain symptoms can be effectively treated by dopaminergic medication, a correct diagnosis of the different types and distribution of pain in PD is challenging, and accordingly, its treatment remains troublesome. We evaluated the efficacy and the safety of a prolonged release oral formulation of oxycodone hydrochloride combined with naloxone hydrochloride dehydrate, in a fixed ratio of 2:1 (OXN PR). A total of 16 PD patients with history of pain with a minimum intensity of four on numerical rating scale (NRS) received low-dose OXN PR (5/2.5 mg twice daily) and were observed for a period of 8 weeks. The primary efficacy measure was the pain severity measured with NRS and Brief Pain Inventory (BPI). Secondary efficacy measured the safety profile by recording the occurrence of side effects, clinical global impression of change (CGI-C), Parkinson's disease sleep scale 2 (PDSS-2), Bowel function index (BFI). Data were collected and analyzed using descriptive statistics. Patients who completed the study (14 out of 16) reported a significant pain relief as observed by the reduction of NRS and BPI scores. No adjustment of dopaminergic therapy was required. No significant changes were observed in bowel function and constipation symptoms as measured by the BFI during the 8-week period. Similarly, no changes were observed in PDSS-2 score, whereas an improvement was recorded by CGI-C compared to baseline. Low-dose oral OXN PR was efficacious for the management of pain symptoms of patients with PD. More importantly, patients did not experience significant side effects, such as constipation or sedation. Our study provides evidence that opioids can be used to treat pain symptoms in PD patients.

Research paper thumbnail of Italian Oncological Pain Survey (IOPS)

The Clinical Journal of Pain, 2015

Objective: A survey of breakthrough pain (BTP) was performed in five palliative care units (PCU),... more Objective: A survey of breakthrough pain (BTP) was performed in five palliative care units (PCU), seven oncology departments (ONC), and nine pain clinics (OPC).

Research paper thumbnail of Periphery Is Central To Nociception

Research paper thumbnail of Increased blood-cerebrospinal fluid transfer of albumin in advanced Parkinson’s disease

Journal of Neuroinflammation, 2012

Background: Alterations in blood-brain barrier permeability have been proposed to represent a rel... more Background: Alterations in blood-brain barrier permeability have been proposed to represent a relevant factor contributing to Parkinson's disease progression. However, few studies have addressed this issue in patients at different stages of disease. Methods: Albumin was measured in cerebrospinal fluid and serum samples obtained from 73 non-demented subjects with idiopathic Parkinson's disease and 47 age-matched control subjects. The albumin ratio (AR) was calculated to assess blood-cerebrospinal fluid and blood-brain barrier function. The group of patients with Parkinson's disease included 46 subjects with Hoehn-Yahr staging between 1 and 2 and 27, with a score ranging from 2.5 to 4.

Research paper thumbnail of Microbiologic characteristics and predictors of mortality in bloodstream infections in intensive care unit patients: A 1-year, large, prospective surveillance study in 5 Italian hospitals

American Journal of Infection Control, 2015

Background: Bloodstream infections (BSIs) from multidrug-resistant (MDR) bacteria cause morbidity... more Background: Bloodstream infections (BSIs) from multidrug-resistant (MDR) bacteria cause morbidity and mortality in intensive care unit (ICU) patients worldwide. This study investigated the incidence of BSIs in 5 adult general ICUs in Rome, Italy, and evaluated the mortality rate and risk factors associated with these infections. Methods: Over a 12-month period, 1,318 patients were enrolled. Demographic characteristics, Simplified Acute Physiology Score II (SAPS II), comorbidities, and BSI isolate data were collected. After stratification for the outcome, statistical analysis was performed to assess the impact of patient risk factors on in-hospital mortality. Results: There were 324 BSIs in 175 patients recorded, with an in-hospital mortality rate of 46%. Univariate analysis revealed that SAPS II, cardiac comorbidity, and Klebsiella pneumoniae BSI were significantly associated with a higher risk of death. Having a K pneumoniae BSI and cardiac illness at admission were both confirmed to be associated with death by multivariate analysis (P ¼ .0162 and P ¼ .0158, respectively). Most of the K pneumoniae isolates showed high resistance rates to carbapenems. Conclusion: BSIs caused by K pneumoniae and cardiovascular comorbidity in ICU patients are associated with a higher risk of death. Thorough surveillance for MDR pathogens and stratification of the patients' risk on admission into the ICU are key to improving the outcomes of these infections.

Research paper thumbnail of Decompressive craniectomy may cause diagnostic challenges to asses brain death by computed tomography angiography

Minerva anestesiologica

Background: According to Italian legislation to diagnose brain death (BD) after the initial docum... more Background: According to Italian legislation to diagnose brain death (BD) after the initial documentation of the clinical signs, repetition of clinical testing and confirmation of the loss of bioelectrical activity of the brain (EEG) is required. However, when EEG is unreliable it is necessary to demonstrate cerebral circulatory arrest (CCA). Accepted imaging techniques to demonstrate CCA include: cerebral angiography, cerebral scintigraphy, transcranial Doppler (TCD) and computed tomography angiography (CTA). This latter technique, due to its large availability, low invasivity and easy and fast acquisition is widely used over the country. Nevertheless its diagnostic reliability is affected by some limitations in patients with decompressive craniectomy. Methods and Results: Here we report two cases of brain injury with clinical signs of BD and at the same time, opacification of intracranial arteries on CTA and a pattern consistent with flow arrest on the corresponding insonable arte...

Research paper thumbnail of ACCERTAMENTO MOLECOLARE DELLA RELAZIONE CLONALE FRA ALCUNI ISOLATI DI ACINETOBACTER BAUMANNII

Microbiologia Medica, 2006

Research paper thumbnail of Klebsiella pneumoniae KPC: first isolations in Italy

Microbiologia Medica, 2009

Research paper thumbnail of A novel mutation of varicella-zoster virus associated to fatal hepatitis

Journal of Clinical Virology, 2006

Background: Lethal varicella in immunocompetent hosts is rare and its pathogenesis is largely unk... more Background: Lethal varicella in immunocompetent hosts is rare and its pathogenesis is largely unknown. The discovery of glycoprotein E (gE) mutants showing attributes consistent with increased virulence in vitro and in animal models, provided a possible molecular mechanism underlying a more aggressive virus infection. However, these mutants have never been associated with unusually severe clinical cases. Objectives: To varicella-zoster virus (VZV) mutations that correlate with increased virulence. Results: We report a case of fatal hepatitis caused by a VZV bearing a novel mutation on the 3B3 monoclonal antibody epitope of gE in an immunocompetent host. Conclusions: This report describes a mutant VZV responsible for an aggressive clinical course in an immunocompetent host. Linking these severe clinical presentations of VZV infection to virus mutations might provide insights into the underlying pathogenic mechanisms.

Research paper thumbnail of Lipopolysaccharide desensitizes monocytes–macrophages to CD40 ligand stimulation

Research paper thumbnail of Upregulation of the inhibitory receptor ILT4 in monocytes from septic patients

Human Immunology, 2013

Sepsis-induced immune dysfunction is a complex phenomenon that involves both innate and adaptive ... more Sepsis-induced immune dysfunction is a complex phenomenon that involves both innate and adaptive responses. Upregulation of the inhibitor receptor named immunoglobulin like transcript 4 (ILT4) is crucial to the tolerogenic function of monocytes. Here, ILT4 expression, endotoxin-induced IL-12 and IL-10 production and CD86 expression were investigated in circulating monocytes from 16 patients with severe sepsis and 16 age and sex matched controls. We found that monocytes from patients with severe sepsis express significantly higher levels of ILT4 than monocytes from controls. Upregulation of ILT4 expression appeared to be induced by soluble factors present in the serum of septic patients and directly correlated with the degree of organ dysfunction. ILT4(+) monocytes from septic patients also displayed an alteration in the cytokine response to endotoxin stimulation characterized by reduced IL-12 production and increased IL-10 production, and a reduced expression of the costimulatory molecule CD86. In conclusion, the increased ILT4 expression and IL-10 production and the decreased CD86 expression and IL-12 production indicate that during sepsis monocytes undergo substantial modulation of the surface and cytokine phenotype. These phenotypic changes may interfere with the antigen presenting cell activity of monocytes, which may contribute to the impairment of adaptive immune responses that takes place during sepsis.

Research paper thumbnail of Dysregulation of immune monocyte responses during sepsis

Research paper thumbnail of Coupled plasma filtration and adsorption in septic shock: a multicentric experience

Research paper thumbnail of Unexpected total recovery in a patient with post-anoxic complete alpha coma predicted by recording of cortical SEPs

Clinical Neurophysiology, 2013

Research paper thumbnail of Downregulation of CD40 Ligand Response in Monocytes from Sepsis Patients

Clinical and Vaccine Immunology, 2008

It has been suggested that a defective adaptive immune response contributes to septic immunosuppr... more It has been suggested that a defective adaptive immune response contributes to septic immunosuppression. Here, the response of monocytes to CD40 ligand (CD40L) for patients with sepsis due to infection with gram-negative organisms has been analyzed. Compared to cells from controls, monocytes from septic patients showed significantly reduced production of tumor necrosis factor alpha, interleukin-1␤ (IL-1␤), and IL-12 and were unable to acquire high levels of CD80 and CD86 molecules. These alterations were observed at the onset of sepsis and persisted at day 7. However, the ability of monocytes to respond to CD40L stimulation was partially but significantly restored in cells from patients who recovered from sepsis. In addition, costimulation of autologous CD4 ؉ T lymphocytes by CD40Lactivated monocytes from septic patients failed to induce cell proliferation and gamma interferon production. Finally, the ability of CD40L to rescue monocytes from apoptosis was severely impaired. We conclude that downregulation of the CD40L response may be an appropriate model for the monocyte alteration observed during septic immunosuppression and may help in the development of novel therapeutic strategies.

Research paper thumbnail of Emergence of KPC-producing Klebsiella pneumoniae in Italy

BMC Research Notes, 2010

Background: The emergence of KPC-producing K. pneumoniae has now become a global concern. KPC bet... more Background: The emergence of KPC-producing K. pneumoniae has now become a global concern. KPC betalactamases are plasmid-borne and, like extended spectrum beta lactamases (ESBLs), can accumulate and transfer resistance determinants to other classes of antibiotics. Therefore, infection control guidelines on early identification and control of the spread of organisms carrying these resistant determinants are needed. Findings: Klebsiella pneumoniae carbapenemase (KPC) was detected in two isolates of carbapenem-resistant K. pneumoniae obtained from patients at an Italian teaching hospital. The first strain was isolated from a culture drawn from a central venous device (CVC) in a patient with Crohn's disease who was admitted to a gastroenterology ward. The second was isolated from a urine sample collected from an indwelling urinary catheter in an intensive care unit (ICU) patient with a subdural haematoma. The patients had not travelled abroad. Both isolates were resistant to all β-lactams and were susceptible to imipenem and meropenem but resistant to ertapenem. Isolates also showed resistance to other classes of non-β-lactam antibiotics, such as quinolones, aminoglycosides (with the exception for amikacin), trimethoprim-sulfamethoxazole (TMP-SMX) and nitrofurantoin. They were determined to contain the plasmid encoding the carbapenemase gene bla-KPC and were also positive in the Hodge test. Conclusions: This is the second report of KPC-producing isolates in Italy, but the first concerning KPC type 2 gene, and it may have important implications for controlling the transmission of microorganisms resistant to antibiotics.

Research paper thumbnail of Characterization of coagulase-negative staphylococcal isolates from blood with reduced susceptibility to glycopeptides and therapeutic options

BMC Infectious Diseases, 2009

Coagulase-negative staphylococci (CoNS) are a major cause of nosocomial blood stream infection, e... more Coagulase-negative staphylococci (CoNS) are a major cause of nosocomial blood stream infection, especially in critically ill and haematology patients. CoNS are usually multidrug-resistant and glycopeptide antibiotics have been to date considered the drugs of choice for treatment. The aim of this study was to characterize CoNS with reduced susceptibility to glycopeptides causing blood stream infection (BSI) in critically ill and haematology patients at the University Hospital Tor Vergata, Rome, Italy, in 2007. Hospital microbiology records for transplant haematology and ICU were reviewed to identify CoNS with elevated MICs for glycopeptides, and isolates were matched to clinical records to determine whether the isolates caused a BSI. The isolates were tested for susceptibility to new drugs daptomicin and tigecycline and the genetic relationship was assessed using f-AFLP. Of a total of 17,418 blood cultures, 1,609 were positive for CoNS and of these, 87 (5.4%) displayed reduced susceptibility to glycopeptides. Clinical review revealed that in 13 cases (7 in haematology and 6 in ICU), CoNS with reduced susceptibility to glycopeptides were responsible for a BSI. Staphylococcus epidermidis was the causative organism in 11 instances and Staphylococcus haemolyticus in 2. The incidence of oxacillin resistance was high (77%), although all isolates remained susceptible to linezolid, daptomycin and tigecycline. Fingerprinting of CoNS identified one clonal relationship between two isolates. Multi-resistant CoNS with reduced susceptibility to glycopeptides, although still relatively infrequent in our hospital, are emerging pathogens of clinical concern. Surveillance by antibiotyping with attention to multi-resistant profile, and warning to clinicians, is necessary.

Research paper thumbnail of Acinetobacter baumannii in intensive care unit: A novel system to study clonal relationship among the isolates

BMC Infectious Diseases, 2008

The nosocomial infections surveillance system must be strongly effective especially in highly cri... more The nosocomial infections surveillance system must be strongly effective especially in highly critic areas, such as Intensive Care Units (ICU). These areas are frequently an epidemiological epicentre for transmission of multi-resistant pathogens, like Acinetobacter baumannii. As an epidemic outbreak occurs it is very important to confirm or exclude the genetic relationship among the isolates in a short time. There are several molecular typing systems used with this aim. The Repetitive sequence-based PCR (REP-PCR) has been recognized as an effective method and it was recently adapted to an automated format known as the DiversiLab system.

Research paper thumbnail of Inhibition of Persistent Sodium Current Fraction and Voltage-gated L-type Calcium Current by Propofol in Cortical Neurons: Implications for Its Antiepileptic Activity

Epilepsia, 2005

Purpose: Although it is widely used in clinical practice, the mechanisms of action of 2,6-di-isop... more Purpose: Although it is widely used in clinical practice, the mechanisms of action of 2,6-di-isopropylphenol (propofol) are not completely understood. We examined the electrophysiologic effects of propofol on an in vitro model of epileptic activity obtained from a slice preparation.

Research paper thumbnail of Efficacy and safety profile of prolonged release oxycodone in combination with naloxone (OXN PR) in Parkinson’s disease patients with chronic pain

Journal of Neurology, 2015

Pain is a relevant and often underestimated non-motor symptom affecting the quality of life of pa... more Pain is a relevant and often underestimated non-motor symptom affecting the quality of life of patients with Parkinson's disease (PD). Although some pain symptoms can be effectively treated by dopaminergic medication, a correct diagnosis of the different types and distribution of pain in PD is challenging, and accordingly, its treatment remains troublesome. We evaluated the efficacy and the safety of a prolonged release oral formulation of oxycodone hydrochloride combined with naloxone hydrochloride dehydrate, in a fixed ratio of 2:1 (OXN PR). A total of 16 PD patients with history of pain with a minimum intensity of four on numerical rating scale (NRS) received low-dose OXN PR (5/2.5 mg twice daily) and were observed for a period of 8 weeks. The primary efficacy measure was the pain severity measured with NRS and Brief Pain Inventory (BPI). Secondary efficacy measured the safety profile by recording the occurrence of side effects, clinical global impression of change (CGI-C), Parkinson's disease sleep scale 2 (PDSS-2), Bowel function index (BFI). Data were collected and analyzed using descriptive statistics. Patients who completed the study (14 out of 16) reported a significant pain relief as observed by the reduction of NRS and BPI scores. No adjustment of dopaminergic therapy was required. No significant changes were observed in bowel function and constipation symptoms as measured by the BFI during the 8-week period. Similarly, no changes were observed in PDSS-2 score, whereas an improvement was recorded by CGI-C compared to baseline. Low-dose oral OXN PR was efficacious for the management of pain symptoms of patients with PD. More importantly, patients did not experience significant side effects, such as constipation or sedation. Our study provides evidence that opioids can be used to treat pain symptoms in PD patients.

Research paper thumbnail of Italian Oncological Pain Survey (IOPS)

The Clinical Journal of Pain, 2015

Objective: A survey of breakthrough pain (BTP) was performed in five palliative care units (PCU),... more Objective: A survey of breakthrough pain (BTP) was performed in five palliative care units (PCU), seven oncology departments (ONC), and nine pain clinics (OPC).

Research paper thumbnail of Periphery Is Central To Nociception

Research paper thumbnail of Increased blood-cerebrospinal fluid transfer of albumin in advanced Parkinson’s disease

Journal of Neuroinflammation, 2012

Background: Alterations in blood-brain barrier permeability have been proposed to represent a rel... more Background: Alterations in blood-brain barrier permeability have been proposed to represent a relevant factor contributing to Parkinson's disease progression. However, few studies have addressed this issue in patients at different stages of disease. Methods: Albumin was measured in cerebrospinal fluid and serum samples obtained from 73 non-demented subjects with idiopathic Parkinson's disease and 47 age-matched control subjects. The albumin ratio (AR) was calculated to assess blood-cerebrospinal fluid and blood-brain barrier function. The group of patients with Parkinson's disease included 46 subjects with Hoehn-Yahr staging between 1 and 2 and 27, with a score ranging from 2.5 to 4.

Research paper thumbnail of Microbiologic characteristics and predictors of mortality in bloodstream infections in intensive care unit patients: A 1-year, large, prospective surveillance study in 5 Italian hospitals

American Journal of Infection Control, 2015

Background: Bloodstream infections (BSIs) from multidrug-resistant (MDR) bacteria cause morbidity... more Background: Bloodstream infections (BSIs) from multidrug-resistant (MDR) bacteria cause morbidity and mortality in intensive care unit (ICU) patients worldwide. This study investigated the incidence of BSIs in 5 adult general ICUs in Rome, Italy, and evaluated the mortality rate and risk factors associated with these infections. Methods: Over a 12-month period, 1,318 patients were enrolled. Demographic characteristics, Simplified Acute Physiology Score II (SAPS II), comorbidities, and BSI isolate data were collected. After stratification for the outcome, statistical analysis was performed to assess the impact of patient risk factors on in-hospital mortality. Results: There were 324 BSIs in 175 patients recorded, with an in-hospital mortality rate of 46%. Univariate analysis revealed that SAPS II, cardiac comorbidity, and Klebsiella pneumoniae BSI were significantly associated with a higher risk of death. Having a K pneumoniae BSI and cardiac illness at admission were both confirmed to be associated with death by multivariate analysis (P ¼ .0162 and P ¼ .0158, respectively). Most of the K pneumoniae isolates showed high resistance rates to carbapenems. Conclusion: BSIs caused by K pneumoniae and cardiovascular comorbidity in ICU patients are associated with a higher risk of death. Thorough surveillance for MDR pathogens and stratification of the patients' risk on admission into the ICU are key to improving the outcomes of these infections.

Research paper thumbnail of Decompressive craniectomy may cause diagnostic challenges to asses brain death by computed tomography angiography

Minerva anestesiologica

Background: According to Italian legislation to diagnose brain death (BD) after the initial docum... more Background: According to Italian legislation to diagnose brain death (BD) after the initial documentation of the clinical signs, repetition of clinical testing and confirmation of the loss of bioelectrical activity of the brain (EEG) is required. However, when EEG is unreliable it is necessary to demonstrate cerebral circulatory arrest (CCA). Accepted imaging techniques to demonstrate CCA include: cerebral angiography, cerebral scintigraphy, transcranial Doppler (TCD) and computed tomography angiography (CTA). This latter technique, due to its large availability, low invasivity and easy and fast acquisition is widely used over the country. Nevertheless its diagnostic reliability is affected by some limitations in patients with decompressive craniectomy. Methods and Results: Here we report two cases of brain injury with clinical signs of BD and at the same time, opacification of intracranial arteries on CTA and a pattern consistent with flow arrest on the corresponding insonable arte...

Research paper thumbnail of ACCERTAMENTO MOLECOLARE DELLA RELAZIONE CLONALE FRA ALCUNI ISOLATI DI ACINETOBACTER BAUMANNII

Microbiologia Medica, 2006

Research paper thumbnail of Klebsiella pneumoniae KPC: first isolations in Italy

Microbiologia Medica, 2009

Research paper thumbnail of A novel mutation of varicella-zoster virus associated to fatal hepatitis

Journal of Clinical Virology, 2006

Background: Lethal varicella in immunocompetent hosts is rare and its pathogenesis is largely unk... more Background: Lethal varicella in immunocompetent hosts is rare and its pathogenesis is largely unknown. The discovery of glycoprotein E (gE) mutants showing attributes consistent with increased virulence in vitro and in animal models, provided a possible molecular mechanism underlying a more aggressive virus infection. However, these mutants have never been associated with unusually severe clinical cases. Objectives: To varicella-zoster virus (VZV) mutations that correlate with increased virulence. Results: We report a case of fatal hepatitis caused by a VZV bearing a novel mutation on the 3B3 monoclonal antibody epitope of gE in an immunocompetent host. Conclusions: This report describes a mutant VZV responsible for an aggressive clinical course in an immunocompetent host. Linking these severe clinical presentations of VZV infection to virus mutations might provide insights into the underlying pathogenic mechanisms.

Research paper thumbnail of Lipopolysaccharide desensitizes monocytes–macrophages to CD40 ligand stimulation

Research paper thumbnail of Upregulation of the inhibitory receptor ILT4 in monocytes from septic patients

Human Immunology, 2013

Sepsis-induced immune dysfunction is a complex phenomenon that involves both innate and adaptive ... more Sepsis-induced immune dysfunction is a complex phenomenon that involves both innate and adaptive responses. Upregulation of the inhibitor receptor named immunoglobulin like transcript 4 (ILT4) is crucial to the tolerogenic function of monocytes. Here, ILT4 expression, endotoxin-induced IL-12 and IL-10 production and CD86 expression were investigated in circulating monocytes from 16 patients with severe sepsis and 16 age and sex matched controls. We found that monocytes from patients with severe sepsis express significantly higher levels of ILT4 than monocytes from controls. Upregulation of ILT4 expression appeared to be induced by soluble factors present in the serum of septic patients and directly correlated with the degree of organ dysfunction. ILT4(+) monocytes from septic patients also displayed an alteration in the cytokine response to endotoxin stimulation characterized by reduced IL-12 production and increased IL-10 production, and a reduced expression of the costimulatory molecule CD86. In conclusion, the increased ILT4 expression and IL-10 production and the decreased CD86 expression and IL-12 production indicate that during sepsis monocytes undergo substantial modulation of the surface and cytokine phenotype. These phenotypic changes may interfere with the antigen presenting cell activity of monocytes, which may contribute to the impairment of adaptive immune responses that takes place during sepsis.

Research paper thumbnail of Dysregulation of immune monocyte responses during sepsis

Research paper thumbnail of Coupled plasma filtration and adsorption in septic shock: a multicentric experience

Research paper thumbnail of Unexpected total recovery in a patient with post-anoxic complete alpha coma predicted by recording of cortical SEPs

Clinical Neurophysiology, 2013

Research paper thumbnail of Downregulation of CD40 Ligand Response in Monocytes from Sepsis Patients

Clinical and Vaccine Immunology, 2008

It has been suggested that a defective adaptive immune response contributes to septic immunosuppr... more It has been suggested that a defective adaptive immune response contributes to septic immunosuppression. Here, the response of monocytes to CD40 ligand (CD40L) for patients with sepsis due to infection with gram-negative organisms has been analyzed. Compared to cells from controls, monocytes from septic patients showed significantly reduced production of tumor necrosis factor alpha, interleukin-1␤ (IL-1␤), and IL-12 and were unable to acquire high levels of CD80 and CD86 molecules. These alterations were observed at the onset of sepsis and persisted at day 7. However, the ability of monocytes to respond to CD40L stimulation was partially but significantly restored in cells from patients who recovered from sepsis. In addition, costimulation of autologous CD4 ؉ T lymphocytes by CD40Lactivated monocytes from septic patients failed to induce cell proliferation and gamma interferon production. Finally, the ability of CD40L to rescue monocytes from apoptosis was severely impaired. We conclude that downregulation of the CD40L response may be an appropriate model for the monocyte alteration observed during septic immunosuppression and may help in the development of novel therapeutic strategies.

Research paper thumbnail of Emergence of KPC-producing Klebsiella pneumoniae in Italy

BMC Research Notes, 2010

Background: The emergence of KPC-producing K. pneumoniae has now become a global concern. KPC bet... more Background: The emergence of KPC-producing K. pneumoniae has now become a global concern. KPC betalactamases are plasmid-borne and, like extended spectrum beta lactamases (ESBLs), can accumulate and transfer resistance determinants to other classes of antibiotics. Therefore, infection control guidelines on early identification and control of the spread of organisms carrying these resistant determinants are needed. Findings: Klebsiella pneumoniae carbapenemase (KPC) was detected in two isolates of carbapenem-resistant K. pneumoniae obtained from patients at an Italian teaching hospital. The first strain was isolated from a culture drawn from a central venous device (CVC) in a patient with Crohn's disease who was admitted to a gastroenterology ward. The second was isolated from a urine sample collected from an indwelling urinary catheter in an intensive care unit (ICU) patient with a subdural haematoma. The patients had not travelled abroad. Both isolates were resistant to all β-lactams and were susceptible to imipenem and meropenem but resistant to ertapenem. Isolates also showed resistance to other classes of non-β-lactam antibiotics, such as quinolones, aminoglycosides (with the exception for amikacin), trimethoprim-sulfamethoxazole (TMP-SMX) and nitrofurantoin. They were determined to contain the plasmid encoding the carbapenemase gene bla-KPC and were also positive in the Hodge test. Conclusions: This is the second report of KPC-producing isolates in Italy, but the first concerning KPC type 2 gene, and it may have important implications for controlling the transmission of microorganisms resistant to antibiotics.

Research paper thumbnail of Characterization of coagulase-negative staphylococcal isolates from blood with reduced susceptibility to glycopeptides and therapeutic options

BMC Infectious Diseases, 2009

Coagulase-negative staphylococci (CoNS) are a major cause of nosocomial blood stream infection, e... more Coagulase-negative staphylococci (CoNS) are a major cause of nosocomial blood stream infection, especially in critically ill and haematology patients. CoNS are usually multidrug-resistant and glycopeptide antibiotics have been to date considered the drugs of choice for treatment. The aim of this study was to characterize CoNS with reduced susceptibility to glycopeptides causing blood stream infection (BSI) in critically ill and haematology patients at the University Hospital Tor Vergata, Rome, Italy, in 2007. Hospital microbiology records for transplant haematology and ICU were reviewed to identify CoNS with elevated MICs for glycopeptides, and isolates were matched to clinical records to determine whether the isolates caused a BSI. The isolates were tested for susceptibility to new drugs daptomicin and tigecycline and the genetic relationship was assessed using f-AFLP. Of a total of 17,418 blood cultures, 1,609 were positive for CoNS and of these, 87 (5.4%) displayed reduced susceptibility to glycopeptides. Clinical review revealed that in 13 cases (7 in haematology and 6 in ICU), CoNS with reduced susceptibility to glycopeptides were responsible for a BSI. Staphylococcus epidermidis was the causative organism in 11 instances and Staphylococcus haemolyticus in 2. The incidence of oxacillin resistance was high (77%), although all isolates remained susceptible to linezolid, daptomycin and tigecycline. Fingerprinting of CoNS identified one clonal relationship between two isolates. Multi-resistant CoNS with reduced susceptibility to glycopeptides, although still relatively infrequent in our hospital, are emerging pathogens of clinical concern. Surveillance by antibiotyping with attention to multi-resistant profile, and warning to clinicians, is necessary.

Research paper thumbnail of Acinetobacter baumannii in intensive care unit: A novel system to study clonal relationship among the isolates

BMC Infectious Diseases, 2008

The nosocomial infections surveillance system must be strongly effective especially in highly cri... more The nosocomial infections surveillance system must be strongly effective especially in highly critic areas, such as Intensive Care Units (ICU). These areas are frequently an epidemiological epicentre for transmission of multi-resistant pathogens, like Acinetobacter baumannii. As an epidemic outbreak occurs it is very important to confirm or exclude the genetic relationship among the isolates in a short time. There are several molecular typing systems used with this aim. The Repetitive sequence-based PCR (REP-PCR) has been recognized as an effective method and it was recently adapted to an automated format known as the DiversiLab system.

Research paper thumbnail of Inhibition of Persistent Sodium Current Fraction and Voltage-gated L-type Calcium Current by Propofol in Cortical Neurons: Implications for Its Antiepileptic Activity

Epilepsia, 2005

Purpose: Although it is widely used in clinical practice, the mechanisms of action of 2,6-di-isop... more Purpose: Although it is widely used in clinical practice, the mechanisms of action of 2,6-di-isopropylphenol (propofol) are not completely understood. We examined the electrophysiologic effects of propofol on an in vitro model of epileptic activity obtained from a slice preparation.