Publications by authors named "Paola Della Siega"

13 Publications

  • Page 1 of 1

Approach to patients with COVID-19 disease: the procedure in Udine.

New Microbiol 2021 Jan 16;44(1):66-69. Epub 2020 Dec 16.

U.O. Malattie Infettive, Dipartimento di Medicina dell'Università di Udine - Università di Udine e Azienda Sanitaria Universitaria Integrata di Udine, Udine - Italia.

Coronavirus disease 2019 poses a serious threat to public health. The protocol developed at the Azienda Sanitaria Universitaria Friuli Centrale (Italy) is based on clinical data, laboratory tests, chest echography and HRCT. Several therapeutic options are considered, since patients vary in disease severity, evolution and co-morbidities and because so far there are no clear indications about therapeutic strategy based on randomized clinical trial. In this protocol chest echography has a central role in categorizing patient status, follow-up and decision-making.
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January 2021

Clinical presentation and immunological features of Post-Malaria Neurologic Syndrome: a case report and review of literature.

Malar J 2020 Nov 23;19(1):419. Epub 2020 Nov 23.

Infectious Diseases Division, Department of Medicine, University of Udine and Azienda Sanitaria Universitaria Integrata Di Udine, 33100, Udine, Italy.

Background: Malaria still represents a major health threat, in terms of both morbidity and mortality. Complications of malaria present a diversified clinical spectrum, with neurological involvement leading to the most serious related-conditions. The authors recently encountered a case of a 60-year old Italian man presenting with confusion, language disturbances and Parkinson-like syndrome 3 weeks after complete remission from severe Plasmodium falciparum cerebral malaria. Chemical and microbiological analysis revealed aseptic meningitis, diffuse encephalitis and abnormal immune-activation. Re-infection and recrudescence of infection were excluded. Further analysis excluded paraneoplastic and autoimmune causes of encephalitis. A diagnosis of Post-Malaria Neurological Syndrome (PMNS) was finally formulated and successfully treated with high dose of steroids.

Methods: A systematic research of current literature related to PMNS was performed.

Results: 151 cases of PMNS were included, the majority of which occurred after severe P. falciparum infections. Four main clinical pattern were identified: 37% of the cases presented as "classical" PMNS, 36% presented as delayed cerebellar ataxia (DCA), 18% resembled acute inflammatory demyelinating polyneuropathy (AIDP), and 8% presented as acute disseminated encephalomyelitis (ADEM)-like form. Differentiation between different forms was not always simple, as clinical and radiological findings frequently overlap. Overall, in almost all of the tested cases, cerebrospinal fluid was found pathological; EEG revealed nonspecific encephalopathy in 30% of classical PMNS and 67% ADEM; imaging tests were found abnormal in 92% of ADEM-like forms. Pathogenesis remains unclear. An autoimmune mechanism is the most corroborated pathogenic hypothesis. Overall, the majority of PMNS cases revert without specific treatment. In most severe forms, high dose steroids, intravenous immunoglobulins, and plasmapheresis have been shown to improve symptoms.

Conclusions: PMNS is a disabling complication of malaria. The overall incidence is not known, due to frequent misdiagnosis and under-reporting. Pathogenesis is not also fully understood, but rapid response to immune-modulating treatment along with similarities to auto-immune neurological disease, strongly support a dysregulated immunological genesis of this condition. The lack of randomized controlled studies regarding therapeutic approaches is a major unmet need in this setting. A systematic collection of all the PMNS cases would be desirable, in order to increase awareness of this rare condition and to prospectively investigate the most appropriate management.
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http://dx.doi.org/10.1186/s12936-020-03476-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7681770PMC
November 2020

Ceftobiprole and pneumonia in adults admitted to the emergency department is it time to assess a new therapeutic algorithm?

J Chemother 2021 May 30;33(3):174-179. Epub 2020 Sep 30.

Emergency Departements, Santa Maria degli Angeli Hospital, Pordenone, Italy.

Objective: Ceftobiprole is an advance generation cephalosporin which has broad-spectrum bacterial activity (both against Gram-positive and negative pathogens) and was approved for the treatment of community-acquired pneumonia (CAP) and non-ventilated hospital-acquired pneumonia (HAP) in most European countries. We aimed to evaluate the efficacy and safety of ceftobiprole in the treatment of pneumonia in a cohort of severely ill patients admitted to the emergency department (ED).

Methods: 1-year observational retrospective mono-centric study. Were defined two primary endpoints: first, to evaluate the clinical cure at the test-of-cure (TOC); the second, to evaluate the early improvement, defined as a reduction of symptoms and inflammatory parameters 72 hours after the start of treatment. The secondary endpoint is to evaluate the reduction of antibiotic "burden" using ceftobiprole despite standard of care in severe hospital-acquired pneumonia.

Results: During the study period, a total of 48 patients with severe pneumonia received ceftobiprole: twenty-two patients (45.8%) as empiric therapy, 9 (18.5%) as a de-escalation option from previous combination therapies, 13 patients (27.1%) as an escalation therapy from ceftriaxone or amoxicillin/clavulanate and four patients (8.3%) as a targeted therapy based on microbiological results. Ceftobiprole mean duration therapy was 10.2 days. Forty-six patients with severe pneumonia had an early clinical improvement 72 hours after the start of treatment (95.8%). In general, ceftobiprole was well tolerated; only one patient suspended the drug because of poor tolerability. The clinical cure at TOC was 85.4% and 30-days crude mortality was 10.4%.

Conclusions: This study confirms that ceftobiprole is effective in severely ill patients with pneumonia at risk of poor outcomes.
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http://dx.doi.org/10.1080/1120009X.2020.1821486DOI Listing
May 2021

Comparative Population Pharmacokinetics of Darunavir in SARS-CoV-2 Patients vs. HIV Patients: The Role of Interleukin-6.

Clin Pharmacokinet 2020 10;59(10):1251-1260

Department of Medicine, University of Udine, Udine, Italy.

Background: Darunavir is an anti-HIV protease inhibitor repurposed for SARS-CoV-2 treatment.

Objective: The aim of this study was to assess the population pharmacokinetics of darunavir in SARS-CoV-2 patients compared with HIV patients.

Methods: Two separate models were created by means of a nonlinear mixed-effect approach. The influence of clinical covariates on each basic model was tested and the association of significant covariates with darunavir parameters was assessed at multivariate regression and classification and regression tree (CART) analyses. Monte Carlo simulation assessed the influence of covariates on the darunavir concentration versus time profile.

Results: A one-compartment model well-described darunavir concentrations in both groups. In SARS-CoV-2 patients (n = 30), interleukin (IL)-6 and body surface area were covariates associated with darunavir oral clearance (CL/F) and volume of distribution (V), respectively; no covariates were identified in HIV patients (n = 25). Darunavir CL/F was significantly lower in SARS-CoV-2 patients compared with HIV patients (4.1 vs. 10.3 L/h; p < 0.001). CART analysis found that an IL-6 level of 18 pg/mL may split the SARS-CoV-2 population in patients with low versus high darunavir CL/F (mean ± standard deviation 3.47 ± 1.90 vs. 8.03 ± 3.24 L/h; proportion of reduction in error = 0.46). Median (interquartile range) darunavir CL/F was significantly lower in SARS-CoV-2 patients with IL-6 levels ≥ 18 pg/mL than in SARS-CoV-2 patients with IL-6 levels < 18 pg/mL or HIV patients (2.78 [2.16-4.47] vs. 7.24 [5.88-10.38] vs. 9.75 [8.45-13.79] L/h, respectively; p < 0.0001). Increasing IL-6 levels affected darunavir concentration versus time simulated profiles. We hypothesized that increases in IL-6 levels associated with severe SARS-CoV-2 disease may downregulate the cytochrome P450 (CYP) 3A4-mediated metabolism of darunavir.

Conclusions: This is a proof-of-concept of SARS-CoV-2 disease-drug interactions, and may support the need for optimal dose selection of sensitive CYP3A4 substrates in severe SARS-CoV-2 patients.
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http://dx.doi.org/10.1007/s40262-020-00933-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453069PMC
October 2020

Higher fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) uptake in tuberculous compared to bacterial spondylodiscitis.

Skeletal Radiol 2017 Jun 15;46(6):777-783. Epub 2017 Mar 15.

Infectious Diseases Division, Santa Maria della Misericordia University Hospital, 50, Colugna Street, Udine, 33100, Italy.

Background: Tuberculous spondylodiscitis can be difficult to diagnose because of its nonspecific symptoms and the similarities with non-tubercular forms of spinal infection. Fluorine-18-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG PET-CT) is increasingly used for the diagnosis and monitoring of tubercular diseases.

Methods: Retrospective, case-control study comparing tuberculous spondylodiscitis with biopsy-confirmed pyogenic spondylodiscitis in the period 2010-2012.

Results: Ten cases of tuberculous spondylodiscitis and 20 controls were included. Compared to pyogenic, tuberculous spondylodiscitis was more frequent in younger patients (P = 0.01) and was more often associated with thoraco-lumbar tract lesions (P = 0.01) and multiple vertebral involvement (P = 0.01). Significantly higher maximum standardized uptake values (SUV) at FDG-PET were displayed by tuberculous spondylodiscitis compared to controls (12.4 vs. 7.3, P = 0.003). SUV levels above 8 showed the highest value of specificity (0.80). Mean SUV reduction of 48% was detected for tuberculous spondylodiscitis at 1-month follow-up.

Conclusions: Higher SUV levels at FDG-PET were detected in tuberculous compared with pyogenic spondylodiscitis. PET-CT use appeared useful in the disease follow-up after treatment initiation.
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http://dx.doi.org/10.1007/s00256-017-2615-8DOI Listing
June 2017

Might real-time pharmacokinetic/pharmacodynamic optimisation of high-dose continuous-infusion meropenem improve clinical cure in infections caused by KPC-producing Klebsiella pneumoniae?

Int J Antimicrob Agents 2017 Feb 8;49(2):255-258. Epub 2016 Dec 8.

Infectious Diseases Clinic, Santa Maria della Misericordia University Hospital, Udine, Italy.

The effect of real-time pharmacokinetic/pharmacodynamic (PK/PD) optimisation of high-dose continuous-infusion meropenem on the clinical outcome of patients receiving combination antimicrobial therapy for treatment of KPC-producing Klebsiella pneumoniae (KPC-Kp) infections was retrospectively assessed. Data for all patients with KPC-Kp-related infections who received antimicrobial combination therapy containing high-dose continuous-infusion meropenem optimised by means of therapeutic drug monitoring (TDM) were retrieved. Optimal PK/PD exposure was considered a steady-state concentration to minimum inhibitory concentration ratio (C/MIC) of 1-4. Univariate binary logistic regression analysis was performed to identify independent predictors of clinical outcome. Among the 30 eligible patients, 53.3% had infections caused by meropenem-resistant KPC-Kp (MIC ≥ 16 mg/L). Tigecycline and colistin were the two antimicrobials most frequently combined with meropenem. Mean doses of continuous-infusion meropenem ranged from 1.7 to 13.2 g/daily. The C/MIC ratio was ≥1 in 73.3% of cases and ≥4 in 50.0%. Clinical outcome was successful in 73.3% of cases after a median treatment length of 14.0 days. In univariate analysis, a significant correlation with successful clinical outcome was found for a C/MIC ratio ≥1 (OR = 10.556, 95% CI 1.612-69.122; P = 0.014), a C/MIC ratio ≥4 (OR = 12.250, 95% CI 1.268-118.361; P = 0.030) and a Charlson co-morbidity index of ≥4 (OR = 0.158, 95% CI 0.025-0.999; P = 0.05). High-dose continuous-infusion meropenem optimised by means of real-time TDM may represent a valuable tool in improving clinical outcome when dealing with the treatment of infections caused by KPC-Kp with a meropenem MIC ≤ 64 mg/L.
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http://dx.doi.org/10.1016/j.ijantimicag.2016.10.018DOI Listing
February 2017

Determination of PCT on admission is a useful tool for the assessment of disease severity in travelers with imported Plasmodium falciparum malaria.

Acta Parasitol 2016 Mar;61(2):412-8

Procalcitonin (PCT) and C-reactive protein (CRP) may be useful to predict complicated forms of malaria. A total of 30 consecutive travelers diagnosed with Plasmodium falciparum malaria over a two-year period were included in the study. Patients with complicated Plasmodium falciparum malaria showed higher levels of parasitemia (P = 0.0001), PCT (P = 0.0018), CRP (P = 0.0005), bilirubinemia (P = 0.004), and a lower platelet count (P<0.0001) compared with patients with uncomplicated forms. PCT levels above 5 ng/mL showed the highest value of specificity (0.86) and positive predictive factor (0.67) among other parameters, and equal sensitivity (0.67) was displayed by CRP levels above 150 mg/dl. None of the patients with complicated malaria showed PCT levels within normal limits (<0.5 ng/ml). Both PCT and CRP correlated with parasitemia (P<0.001) and showed areas under ROC curve of 0.83. At multivariate analysis, only PCT was associated with an increased risk of complicated malaria (OR 8.2, IC 95% 1.2-57.2, P = 0.03). The determination of PCT on admission showed better results compared to CRP, platelet count, and bilirubinemia and can be useful in non-endemic areas for the initial clinical assessment of disease severity in travelers with Plasmodium falciparum malaria.
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http://dx.doi.org/10.1515/ap-2016-0055DOI Listing
March 2016

Risk factors for ventilator associated pneumonia due to carbapenemase-producing Klebsiella pneumoniae in mechanically ventilated patients with tracheal and rectal colonization.

Minerva Anestesiol 2016 06 8;82(6):635-40. Epub 2016 Jan 8.

U.O. Lipidoaferesi, Fondazione Toscana Gabriele Monasterio, Pisa, Italy -

Background: The aim of this study was to identify the risk factors for ventilator associated pneumonia (VAP) due to Klebsiella pneumoniae carbapenemase-producing K (KPC-Kp) development in ICU patients with documented rectal and tracheal colonization.

Methods: We performed a retrospective, matched case-control study in a medical-surgical ICU (January 2011-December 2013) comparing 30 patients who developed KPC-Kp VAP during the ICU stay to 60 colonized patients not developing KPC-Kp VAP. Analysed risk factors included: age, sex, SAPS II and SOFA scores, comorbidities, type and length of antibiotic therapy, previous non KPC-Kp infections, time between admission to rectal and tracheal colonization.

Results: Several risk factors were more frequent among patients who developed KPC-Kp pneumonia versus matched colonized controls: previous infection not related to KPC-Kp (P<0.001), duration of previous antibiotic therapy before (P<0.001) and after (P=0.002) KPC-Kp colonization. Amoxicillin/clavulanic acid prophylaxis was administered in 17% of VAP patients versus 73% of patients not developing VAP (P<0.001). Multivariate conditional logistic regression analysis identified several significant independent risk factors favoring KPC-Kp VAP in patients colonized at multiple sites: previous non KPC-Kp infections (OR: 2.046), duration of previous antibiotic therapy before (OR: 1.309) and after (OR: 1.122) KPC-Kp colonization; antibiotic therapy with amoxicillin/clavulanic acid prophylaxis (<48 hours) was associated with reduced risk of KPC-Kp VAP (OR: 0.987).

Conclusions: In rectal and tracheal KPC-Kp colonized patients, prolonged antibiotic therapy administered for non KPC-Kp infection predisposes patients to subsequent KPC-Kp VAP. Short prophylaxis of early pneumonia with amoxicillin/clavulanic acid, reducing the need for subsequent antibiotic use, may be associated with reduced risk for KPC-Kp VAP.
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June 2016

Comparison of clinical characteristics of tuberculosis between two age groups at an Italian Tertiary Hospital.

Infection 2015 Jun 26;43(3):361-6. Epub 2015 Mar 26.

Infectious Diseases Division, Santa Maria della Misericordia University Hospital, 50, Colugna Street, 33100, Udine, UD, Italy,

Differences in clinical characteristics and outcome between elderly (>60 years) and younger (18-59 years) tuberculosis (TB) patients were retrospectively evaluated. Alcohol abuse, radiological evidence of cavitation, and cough at presentation were more frequent among younger patients. Older patients were more likely to have comorbidities, disseminated TB, longer duration of symptoms and higher TB-related mortality (19 vs 0%). Very old patients (≥80 years) showed increased liver toxicity and hospital acquired infections compared to patients aged 60-79 years.
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http://dx.doi.org/10.1007/s15010-015-0765-yDOI Listing
June 2015

Delafloxacin for the treatment of respiratory and skin infections.

Expert Opin Investig Drugs 2015 Mar 21;24(3):433-42. Epub 2015 Jan 21.

Santa Maria Misericordia University Hospital, Infectious Diseases Division , Piazzale S. Maria della Misericordia, n. 15, 33100, Udine , Italy + 86 21 38804518; extn. 8319 ; + 39 0432 559360 ;

Introduction: There has been a striking increase in the emergence of multidrug-resistant pathogens in recent times. Delafloxacin is a novel, broad-spectrum fluoroquinolone with antimicrobial activity against resistant Gram-positive, Gram-negative and anaerobic organisms. It has the potential to treat a variety of infections including complicated skin and skin structure infections and respiratory tract infections.

Areas Covered: In this review, the authors report the microbiological spectrum of activity of delafloxacin as well as its pharmacokinetic characteristics. They also report the results of recent studies investigating its safety and efficacy.

Expert Opinion: The profile of delafloxacin offers several advantages. Delafloxacin presents a broad spectrum of activity against pathogens involved in respiratory infections and complicated skin and skin structure infections (SSSIs), including methicillin-resistant Staphylococcus aureus. It has also shown activity against Gram-negative pathogens, such as quinolone-susceptible and -resistant strains of Escherichia coli and Klebsiella pneumoniae and quinolone-susceptible Pseudomonas aeruginosa. The availability of an oral formulation supports its use in sequential therapy. The efficacy and tolerability of delafloxacin have been demonstrated in Phase II clinical trials in comparison with moxifloxacin for respiratory infections and linezolid and vancomycin in SSSIs. Compared with other quinolones such as moxifloxacin, delafloxacin showed comparable efficacy and a lower rate of adverse effects. The results of new Phase III studies are awaited to confirm delafloxacin's future applications in the treatment of SSSIs.
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http://dx.doi.org/10.1517/13543784.2015.1005205DOI Listing
March 2015

Linezolid-resistant staphylococcal bacteraemia: A multicentre case-case-control study in Italy.

Int J Antimicrob Agents 2015 Mar 30;45(3):255-61. Epub 2014 Dec 30.

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

The aim of this multicentre study was to analyse the characteristics of patients with bloodstream infections due to staphylococcal strains resistant to linezolid. This was a retrospective case-case-control study of patients hospitalised in three large teaching hospitals in Italy. A linezolid-resistant (LIN-R) Staphylococcus spp. group and a linezolid-susceptible (LIN-S) Staphylococcus spp. group were compared with control patients to determine the clinical features and factors associated with isolation of LIN-R strains. All LIN-R Staphylococcus spp. strains underwent molecular typing. Compared with the LIN-S group, central venous catheters were the main source of infection in the LIN-R group. The LIN-R and LIN-S groups showed a similar incidence of severe sepsis or septic shock, and both showed a higher incidence of these compared with the control group. Overall, patients in the LIN-R group had a higher 30-day mortality rate. Multivariate analysis found previous linezolid therapy, linezolid therapy >14 days, antibiotic therapy in the previous 30 days, antibiotic therapy >14 days, previous use of at least two antibiotics and hospitalisation in the previous 90 days as independent risk factors associated with isolation of a LIN-R strain. The G2576T mutation in domain V of 23S rRNA was the principal mechanism of resistance; only one strain of Staphylococcus epidermidis carried the cfr methylase gene (A2503), together with L4 insertion (71GGR72) and L3 substitution (H146Q). LIN-R strains are associated with severe impairment of clinical conditions and unfavourable patient outcomes. Reinforcement of infection control measures may have an important role in preventing these infections.
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http://dx.doi.org/10.1016/j.ijantimicag.2014.12.008DOI Listing
March 2015

Current and future therapies for invasive aspergillosis.

Pulm Pharmacol Ther 2015 Jun 30;32:155-65. Epub 2014 Jun 30.

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

Invasive fungal infections have increase worldwide and represent a threat for immunocompromised patients including HIV-infected, recipients of solid organ and stem cell transplants, and patients receiving immunosuppressive therapies. High mortality rates and difficulties in early diagnosis characterize pulmonary fungal infections. Invasive pulmonary aspergillosis has been reviewed focussing on therapeutic management. Although new compounds have become available in the past years (i.e., amphotericin B lipid formulations, last-generation azoles, and echinocandines), new diagnostic tools and careful therapeutic management are mandatory to assure an early appropriate targeted treatment that represents the key factor for a successful conservative approach in respiratory fungal infections.
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http://dx.doi.org/10.1016/j.pupt.2014.06.002DOI Listing
June 2015
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