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1.
ERJ Open Res ; 9(4)2023 Jul.
Article de Anglais | MEDLINE | ID: mdl-37389899

RÉSUMÉ

Background: Prone positioning is routinely used among patients with COVID-19 requiring mechanical ventilation. However, its utility among spontaneously breathing patients is still debated. Methods: In an open-label randomised controlled trial, we enrolled patients hospitalised with mild COVID-19 pneumonia, whose arterial oxygen tension to inspiratory oxygen fraction ratio (PaO2/FIO2) was >200 mmHg and who did not require mechanical ventilation or continuous positive airway pressure at hospital admission. Patients were randomised 1:1 to prone positioning on top of standard of care (intervention group) versus standard of care only (controls). The primary composite outcome included death, mechanical ventilation, continuous positive airway pressure and PaO2/FIO2 <200 mmHg; secondary outcomes were oxygen weaning and hospital discharge. Results: A total of 61 subjects were enrolled, 29 adjudicated to prone positioning and 32 to the control group. By day 28, 24 out of 61 patients (39.3%) met the primary outcome: 16 because of a PaO2/FIO2 ratio <200 mmHg, five because of the need for continuous positive airway pressure and three because of the need for mechanical ventilation. Three patients died. Using an intention-to-treat approach, 15 out of 29 patients in the prone positioning group versus nine out of 32 controls met the primary outcome, corresponding to a significantly higher risk of progression among those randomised to prone positioning (HR 2.38, 95% CI 1.04-5.43; p=0.040). Using an as-treated approach, which included in the intervention group only patients who maintained prone positioning for ≥3 h·day-1, no significant differences were found between the two groups (HR 1.77, 95% CI 0.79-3.94; p=0.165). Also, we did not find any statistically significant difference in terms of time to oxygen weaning or hospital discharge between study arms in any of the analyses conducted. Conclusions: We observed no clinical benefit from prone positioning among spontaneously breathing patients with COVID-19 pneumonia requiring conventional oxygen therapy.

2.
Intensive Care Med Exp ; 11(1): 17, 2023 Mar 02.
Article de Anglais | MEDLINE | ID: mdl-36862343

RÉSUMÉ

BACKGROUND: The role of upper airways microbiota and its association with ventilator-associated pneumonia (VAP) development in mechanically ventilated (MV) patients is unclear. Taking advantage of data collected in a prospective study aimed to assess the composition and over-time variation of upper airway microbiota in patients MV for non-pulmonary reasons, we describe upper airway microbiota characteristics among VAP and NO-VAP patients. METHODS: Exploratory analysis of data collected in a prospective observational study on patients intubated for non-pulmonary conditions. Microbiota analysis (trough 16S-rRNA gene profiling) was performed on endotracheal aspirates (at intubation, T0, and after 72 h, T3) of patients with VAP (cases cohort) and a subgroup of NO-VAP patients (control cohort, matched according to total intubation time). RESULTS: Samples from 13 VAP patients and 22 NO-VAP matched controls were analyzed. At intubation (T0), patients with VAP revealed a significantly lower microbial complexity of the microbiota of the upper airways compared to NO-VAP controls (alpha diversity index of 84 ± 37 and 160 ± 102, in VAP and NO_VAP group, respectively, p-value < 0.012). Furthermore, an overall decrease in microbial diversity was observed in both groups at T3 as compared to T0. At T3, a loss of some genera (Prevotella 7, Fusobacterium, Neisseria, Escherichia-Shigella and Haemophilus) was found in VAP patients. In contrast, eight genera belonging to the Bacteroidetes, Firmicutes and Fusobacteria phyla was predominant in this group. However, it is unclear whether VAP caused dysbiosis or dysbiosis caused VAP. CONCLUSIONS: In a small sample size of intubated patients, microbial diversity at intubation was less in patients with VAP compared to patients without VAP.

3.
IJID Reg ; 6: 167-170, 2023 Mar.
Article de Anglais | MEDLINE | ID: mdl-36910842

RÉSUMÉ

Objectives: Healthcare-associated bacteraemia is defined as bacteraemia diagnosed ≤48 h after hospital admission in patients recently exposed to healthcare procedures or settings. It differs from hospital-acquired bacteraemia, which is diagnosed >48 h after hospital admission. Healthcare-associated bacteraemia is reported increasingly, often due to resistant pathogens including extended-spectrum beta-lactamase (ESBL) producers, representing a challenge to empirical treatment. This study aimed to assess the appropriateness of empirical treatment for ESBL bacteraemia at the authors' centre, to perform a descriptive analysis according to the mode of infection acquisition (community-acquired, healthcare-associated, hospital-acquired), and to assess the risk factors for mortality. Methods: A retrospective study on patients with ESBL bacteraemia was undertaken. Results: In total, 129 consecutive cases of bacteraemia due to ESBL producers were included in this study. Compared with community- and hospital-acquired bacteraemia, healthcare-associated bacteraemia affected older patients (P=0.001) and patients with higher Charlson Comorbidity Index scores (P=0.007), and was more frequently associated with piperacillin-tazobactam resistance (P=0.025) and multi-drug resistance (P=0.026). Overall, ineffective empirical treatment was common (42%). Factors associated with 30-day mortality were septic shock [odds ratio (OR) 7.096, 95% confidence interval (CI) 2.58-24.58], high Pitt score (OR 6.636, 95% CI 1.71-23.62) and unknown source of bacteraemia (OR 19.28, 95% CI 2.80-30.70). Conclusions: Antimicrobial stewardship interventions focusing on both in-hospital and community settings are advocated to better manage healthcare-associated infections due to ESBL producers.

4.
Pediatr Transplant ; 27(5): e14503, 2023 08.
Article de Anglais | MEDLINE | ID: mdl-36915258

RÉSUMÉ

BACKGROUND: In Fanconi anemia bone marrow failure is the major cause of morbidity and mortality and hematopoietic stem cell transplantation represents the only curative treatment. Liver disease, in terms of elevated liver function tests, as well as benign and malignant liver tumors, occurs especially in case of androgen treatment. We report a unique case of a child with Fanconi anemia with FANCD2 mutation who developed neonatal cryptogenic liver cirrhosis and bone marrow failure. The child successfully underwent sequential liver transplantation and hematopoietic stem cell transplantation in the first 2 years of life. Nineteen months after hematopoietic stem cell transplantation and 30 months after liver transplantation, the patient is clinically well with normal hematopoietic function and excellent liver function. CONCLUSION: This is the first FA patient who successfully received sequential LT and HSCT highlighting that successful sequential transplantation is feasible in Fanconi anemia patients.


Sujet(s)
Anémie de Fanconi , Transplantation de cellules souches hématopoïétiques , Transplantation hépatique , Pancytopénie , Enfant , Nouveau-né , Humains , Anémie de Fanconi/complications , Anémie de Fanconi/thérapie , Aplasies médullaires , Foie
5.
Open Forum Infect Dis ; 7(11): ofaa481, 2020 Nov.
Article de Anglais | MEDLINE | ID: mdl-33204761

RÉSUMÉ

BACKGROUND: Remdesivir has been associated with accelerated recovery of severe coronavirus disease 2019 (COVID-19). However, whether it is also beneficial in patients requiring mechanical ventilation is uncertain. METHODS: All consecutive intensive care unit (ICU) patients requiring mechanical ventilation due to COVID-19 were enrolled. Univariate and multivariable Cox models were used to explore the possible association between in-hospital death or hospital discharge, considered competing-risk events, and baseline or treatment-related factors, including the use of remdesivir. The rate of extubation and the number of ventilator-free days were also calculated and compared between treatment groups. RESULTS: One hundred thirteen patients requiring mechanical ventilation were observed for a median of 31 days of follow-up; 32% died, 69% were extubated, and 66% were discharged alive from the hospital. Among 33 treated with remdesivir (RDV), lower mortality (15.2% vs 38.8%) and higher rates of extubation (88% vs 60%), ventilator-free days (median [interquartile range], 11 [0-16] vs 5 [0-14.5]), and hospital discharge (85% vs 59%) were observed. Using multivariable analysis, RDV was significantly associated with hospital discharge (hazard ratio [HR], 2.25; 95% CI, 1.27-3.97; P = .005) and with a nonsignificantly lower mortality (HR, 0.73; 95% CI, 0.26-2.1; P = .560). RDV was also independently associated with extubation (HR, 2.10; 95% CI, 1.19-3.73; P = .011), which was considered a competing risk to death in the ICU in an additional survival model. CONCLUSIONS: In our cohort of mechanically ventilated patients, RDV was not associated with a significant reduction of mortality, but it was consistently associated with shorter duration of mechanical ventilation and higher probability of hospital discharge, independent of other risk factors.

6.
Expert Rev Anti Infect Ther ; 18(12): 1271-1279, 2020 12.
Article de Anglais | MEDLINE | ID: mdl-32797758

RÉSUMÉ

OBJECTIVES: We evaluated the efficacy and safety of dalbavancin in ABSSSI and 'other sites' infections' (OTA). METHODS: Observational study involving 11 Italian hospitals including patients that received ≥1 dose of dalbavancin in 2016-2019. The outcome was end-of-treatment efficacy and safety in ABSSSI and OTA in a real-life setting. RESULTS: 206 patients enrolled (males 50%, median age 62 [IQR 50-76] years), 60.2% ABSSSI, 39.8% OTA. 69.7% ABSSSI vs 90.7% OTA (p = 0.003) and 46.3% ABSSSI vs 37.2% OTA (p = 0.786) received previous and concomitant antibiotics, respectively. 82.5% reached clinical cure . Eleven (5.4%) patients had non-serious adverse events (AE). OTA patients showed longer hospitalization (13.5 days, 5.5-22 vs 3, 0-11.7; p<0.0001) and received longer previous (18 days, 9-30 vs 11, 7-19; p = 0.007)/concomitant antibiotic treatments (21 days, 14-52 vs 11, 8-14; p < 0.0001), compared to ABSSSI. ABSSSI and OTA showed similar efficacy (85.5% vs 75%, p = 0.459) and safety (no AE: 81.5% vs 64.3%, p = 0.258); efficacy was independent of previous/concomitant therapies. CONCLUSIONS: Dalbavancin demonstrated a success rate of >80%, with similar efficacy/safety in ABSSSI and off-label indications. The preferential use of dalbavancin as second-line or combination therapy would seem to suggest the need for in-depth studies focused on its off-label use.


Sujet(s)
Antibactériens/administration et posologie , Hospitalisation/statistiques et données numériques , Dermatoses bactériennes/traitement médicamenteux , Téicoplanine/analogues et dérivés , Maladie aigüe , Sujet âgé , Antibactériens/effets indésirables , Femelle , Humains , Italie , Mâle , Adulte d'âge moyen , Utilisation hors indication , Études rétrospectives , Dermatoses bactériennes/microbiologie , Téicoplanine/administration et posologie , Téicoplanine/effets indésirables
7.
Antivir Ther ; 25(2): 73-81, 2020.
Article de Anglais | MEDLINE | ID: mdl-32242526

RÉSUMÉ

BACKGROUND: In patients treated for HCV infection, potential drug-drug interactions (DDIs) can occur among direct-acting antiviral drugs (DAAs) and comedications used. The real-life effectiveness and safety of elbasvir/grazoprevir (ELB/GZR) among co-medicated HCV patients was evaluated. METHODS: We prospectively evaluated consecutive patients from 15 clinical centres participating in PITER who were treated with ELB/GZR and had been followed for at least 12 weeks after treatment. Data were prospectively collected on the use of comedications (including discontinuation, dose modification and addition of drugs) and potential DDIs with DAAs. RESULTS: Of the 356 patients with at least 12-week post-treatment follow-up (median age 67, range 50-88 years), 338 (95%) achieved sustained virological response. Of these, 219 (60%) had at least one comorbidity (median 2, range 1-6); information on comedication was available for 212 of them. Of 190 comedications used, 15 (8%) drugs were modified during ELB/GZR therapy, specifically in 9 (4%) patients they were interrupted, in 2 (1%) of whom, the comedication was interrupted before the DAA therapy because of potential DDI (that is, patients treated with carbamazepine); in 12 (6%) patients the comedications were modified in terms of dosage. In 29 (14%) patients, the comedications required monitoring when used with ELB/GZR, as well as with all available DAAs. Of the 190 drugs, 27 (14%) used in 67% of patients were free of DDIs when used with ELB/GZR, whereas they required monitoring if used with other DAA regimens. CONCLUSIONS: The results of this prospective study support findings that ELB/GZR is effective and safe in most treated patients.


Sujet(s)
Antiviraux/usage thérapeutique , Benzofuranes/usage thérapeutique , Hépatite C chronique/traitement médicamenteux , Imidazoles/usage thérapeutique , Quinoxalines/usage thérapeutique , Facteurs âges , Sujet âgé , Sujet âgé de 80 ans ou plus , Antiviraux/administration et posologie , Antiviraux/effets indésirables , Benzofuranes/effets indésirables , Association médicamenteuse , Interactions médicamenteuses , Femelle , Humains , Imidazoles/effets indésirables , Mâle , Adulte d'âge moyen , Études prospectives , Quinoxalines/effets indésirables , Résultat thérapeutique
8.
Hepatol Int ; 14(3): 362-372, 2020 May.
Article de Anglais | MEDLINE | ID: mdl-32279177

RÉSUMÉ

BACKGROUND: Liver disease progression after Hepatitis C Virus (HCV) eradication following direct-acting antiviral (DAA) treatment in the real-life setting according to Human Immunodeficiency Virus (HIV) coinfection was evaluated. METHODS: Patients consecutively enrolled in PITER between April 2014 and June 2019 and with at least 12-weeks follow-up following treatment were analysed. Cox regression analysis were used to evaluate HIV coinfection and factors independently associated with liver disease outcomes following viral eradication in DAA treated patients with pre-treatment liver cirrhosis. RESULTS: 93 HIV/HCV coinfected and 1109 HCV monoinfected patients were evaluated during a median follow-up of 26.7 (range 6-44.6) and 24.6 (range 6.8-47.3) months, respectively. No difference in the cumulative HCC incidence and hepatic decompensation was observed between coinfected and monoinfected patients. Age (Hazard Ratio [HR] = 1.08; 95% CI 1.04-1.13), male sex (HR = 2.76; 95% CI 1.28-5.96), lower albumin levels (HR = 3.94; 95% CI 1.81-8.58), genotype 3 (HR = 5.05; 95% CI 1.75-14.57) and serum anti-HBc positivity (HR = 1.99, 95% CI 1.01-3.95) were independently associated with HCC incidence. Older age (HR = 1.03; 95% CI 1.00-1.07), male sex (HR = 2.13; 95% CI 1.06-4.26) and lower albumin levels (HR = 3.75; 95% CI 1.89-7.46) were independently associated with the appearance of a decompensating event after viral eradication. CONCLUSION: Different demographic, clinical and genotype distribution between HIV coinfected vs those monoinfected, was observed in a representative cohort of HCV infected patients in Italy. Once liver cirrhosis is established the disease progression is decreased, but still persists regardless of viral eradication in both coinfected and monoinfected patients. In patients with cirrhosis, HIV coinfection was not associated with a higher probability of liver complications, after viral eradication.


Sujet(s)
Antiviraux/usage thérapeutique , Carcinome hépatocellulaire , Infections à VIH , Hépatite C chronique , Cirrhose du foie , Tumeurs du foie , Foie , Carcinome hépatocellulaire/anatomopathologie , Carcinome hépatocellulaire/physiopathologie , Carcinome hépatocellulaire/virologie , Co-infection , Évolution de la maladie , Femelle , Infections à VIH/diagnostic , Infections à VIH/traitement médicamenteux , Infections à VIH/épidémiologie , Hépatite C chronique/diagnostic , Hépatite C chronique/traitement médicamenteux , Hépatite C chronique/épidémiologie , Humains , Incidence , Italie/épidémiologie , Foie/physiopathologie , Foie/virologie , Cirrhose du foie/diagnostic , Cirrhose du foie/physiopathologie , Cirrhose du foie/virologie , Tumeurs du foie/anatomopathologie , Tumeurs du foie/physiopathologie , Tumeurs du foie/virologie , Mâle , Adulte d'âge moyen , Pronostic , Réponse virologique soutenue
9.
Liver Int ; 40(4): 769-777, 2020 04.
Article de Anglais | MEDLINE | ID: mdl-31970845

RÉSUMÉ

BACKGROUND & AIMS: In the direct-acting antiviral era, treatment of genotype-3 HCV (HCV-GT3) is still challenging. Real-life comparisons between recommended regimens, sofosbuvir (SOF)+daclatasvir (DAC), SOF/velpatasvir (VEL), glecaprevir/pibrentasvir (GLE/PIB), are scarce. We aimed at filling this data gap. METHODS: Sustained virological response 12 weeks after treatment completion (SVR12) was assessed for all HCV-GT3 patients consecutively treated within the Lombardia web-based Navigatore HCV-Network; differences in SVR12 across regimens were evaluated by logistic regression. RESULTS: Of the 2082 subjects with HCV-GT3, 1544 were evaluable for comparisons between regimens: SOF + DAC (1023, 66.2%), SOF/VEL (369, 23.9%), GLE/PIB (152, 9.8%). Patients treated with former regimens were more frequently male, cirrhotic, HIV-positive, pretreated, used ribavirin in their regimen, and had lower baseline HCV-RNA. SVR12 was similar across groups: 94.8% in SOF + DAC, 97.6% in SOF/VEL, 96.7% in GLE/PIB (P = .065). At univariate analysis, SVR12 was associated with female gender (97.9% vs 94.8%, P = .007) and lower median pretreatment Log10 HCV-RNA (5.87 vs 6.20, P = .001). At multivariate logistic regression analysis, treatment with SOF/VEL was associated with a higher likelihood of SVR12 than SOF + DAC, but only in the absence of ribavirin (98% vs 90.3%). Female gender and lower pretreatment HCV-RNA were independently associated with SVR12. CONCLUSIONS: In a large real-life setting of HCV-GT3-infected patients with a high proportion of cirrhosis, the success rate was remarkable. The slight advantage of SOF/VEL on SOF + DAC was significant only without ribavirin. The current prescription shift towards novel regimens (ie SOF/VEL and GLE/PIB) in easier-to-treat patients allows ribavirin-free and shorter schedules without mining SVR12 in this <> genotype.


Sujet(s)
Hépatite C chronique , Hépatite C , Antiviraux/usage thérapeutique , Association de médicaments , Femelle , Génotype , Hepacivirus/génétique , Hépatite C/traitement médicamenteux , Hépatite C chronique/traitement médicamenteux , Humains , Mâle , Ribavirine/usage thérapeutique , Sofosbuvir/usage thérapeutique , Résultat thérapeutique
10.
AIDS ; 34(1): 53-61, 2020 01 01.
Article de Anglais | MEDLINE | ID: mdl-31567160

RÉSUMÉ

BACKGROUND: Efavirenz (EFV) association with neurocognitive impairment is debated. Whether switching away from EFV improves neurocognitive performances is still controversial. METHODS: In a randomized open-label controlled trial, patients under effective treatment with tenofovir disoproxil-fumarate (TDF), emtricitabine (FTC) and EFV, who had altered neurocognitive assessment (z-transformed score below -1 in at least one cognitive domain), depression, anxiety or low sleep-quality, were randomized 1 : 1 to immediate or delayed (24-weeks) switch to TDF/FTC/rilpivirine (RPV). Treatment efficacy, neurocognitive function, symptoms and quality of life were evaluated 12, 24 and 48 weeks after randomization. FINDINGS: Seventy-four patients were randomized to immediate (36 patients) or delayed switch (38 patients). At baseline, 63 and 25% of patients had z-scores below -1 in at least one or two neurocognitive domains, 31.1, 17.6 and 44.6% had significant depression or anxiety symptoms or low sleep quality. At week 24 (primary end-point), overall neurocognitive improvement was observed, with no statistically significant differences between arms, neither considering the global z score (between arms difference +0.1; P = 0.458), nor domain-specific z scores. Patients switching away from EFV had significant greater improvement of sleep quality index (between-arm difference -1.5; P = 0.011), self-reported cognitive failures (-6.2; P = 0.001) and CNS symptoms score (-5; P = 0.002), but not of anxiety or depression. No protocol defined virological failure, grade at least 3 lab abnormalities or drug-related serious adverse events were reported. CONCLUSION: Our results do not support the hypothesis that switching to RPV improves cognitive function in patient under stable treatment with EFV. Nonetheless, improvements in neuropsychiatric symptoms, sleep quality and self-perceived cognition were observed.


Sujet(s)
Alcynes/usage thérapeutique , Agents antiVIH/usage thérapeutique , Benzoxazines/usage thérapeutique , Cognition/effets des médicaments et des substances chimiques , Cyclopropanes/usage thérapeutique , Substitution de médicament , Infections à VIH/traitement médicamenteux , Rilpivirine/usage thérapeutique , Sommeil/effets des médicaments et des substances chimiques , Adulte , Alcynes/effets indésirables , Agents antiVIH/effets indésirables , Benzoxazines/effets indésirables , Cyclopropanes/effets indésirables , Emtricitabine , Femelle , Infections à VIH/psychologie , Humains , Mâle , Adulte d'âge moyen , Qualité de vie , ARN viral , Rilpivirine/effets indésirables , Ténofovir , Charge virale
11.
Can J Cardiol ; 36(1): 127-134, 2020 01.
Article de Anglais | MEDLINE | ID: mdl-31813674

RÉSUMÉ

The introduction of combination of antiretroviral therapy and advancement in care of HIV have dramatically changed the natural history of patients living with HIV. Today, HIV+ patients have a life expectancy not significantly different from HIV uninfected people. However, concerns remain about all the comorbidities associated with aging and the effects of chronic therapies in such high-risk patients. HIV+ subjects exhibited accelerated atherosclerosis and have a 1.5- to 2-fold increased risk of having coronary artery disease (CAD), usually presenting early and aggressively with acute coronary events. Furthermore, HIV+ patients with CAD often complain recurrent acute coronary events, and they are plagued by major adverse cardiac outcomes. This review will focus on the current understanding of the CAD phenotype in HIV+ patients highlighting the topic of acute coronary event recurrence and underscoring the role of percutaneous management strategies in the light of information derived from invasive coronary imaging.


Sujet(s)
Maladie des artères coronaires/épidémiologie , Infections à VIH/complications , VIH (Virus de l'Immunodéficience Humaine) , Appréciation des risques/méthodes , Maladie chronique , Coronarographie , Maladie des artères coronaires/complications , Maladie des artères coronaires/diagnostic , Santé mondiale , Humains , Incidence , Récidive , Facteurs de risque
13.
Pathog Immun ; 4(2): 180-194, 2019.
Article de Anglais | MEDLINE | ID: mdl-31538132

RÉSUMÉ

BACKGROUND: Invasive mold infections in children with hematological malignancies are associated with high mortality rates. The use of combination antifungal therapy in cases with a severe clinical course is increasing, although information on the efficacy and safety of this approach is limited. METHODS: We present a case series of 13 children affected by hemato-oncological disorders who received combination antifungal therapy for invasive mold infections at our center (Pediatric Hematology, San Gerardo Hospital, Monza, Italy) from 2011 to 2016, with the aim of describing their clinical characteristics, types of infections, treatment regimens, clinical outcomes, and treatment safety. Medical records were retrospectively reviewed in order to describe patients' characteristics. RESULTS: Combination antifungal therapy included liposomal amphotericin associated with caspofungin (5/13, 38.4%), voriconazole (5/13, 38.4%), or posaconazole (3/13, 23.1%). The 12-week treatment response rate was 69.2% (6/13 patients showed complete response, 3/13 partial response). The crude mortality was 30.7% (4/13): half was related to invasive mold infections (2/13, 15.38%) and half to disease progression (2/13, 15.38%). Overall, treatment was well tolerated, and we did not observe any permanent discontinuation of antifungals due to related side effects. CONCLUSIONS: In our experience, combination antifungal therapy seems to be a safe option in immunocompromised children with invasive mold infections. Well-designed studies are needed to confirm the safety of this approach and to better understand its efficacy in the pediatric setting.

15.
Open Forum Infect Dis ; 4(4): ofx256, 2017.
Article de Anglais | MEDLINE | ID: mdl-29308407

RÉSUMÉ

A 50-year-old man was admitted to intensive care unit because of acute respiratory failure due interstitial pneumonia; after admission, a diagnosis of acute human immunodeficiency virus (HIV)-1 infection was made. Clinical and radiological improvement was observed only after introduction of antiretroviral treatment. We discuss the hypothesis of interstitial pneumonia induced by the acute HIV-1 infection.

16.
Pathog Immun ; 1(2): 352-370, 2016.
Article de Anglais | MEDLINE | ID: mdl-30993245

RÉSUMÉ

BACKGROUND: During the last decade, the spread of Klebsiella pneumoniae-carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) has increased dramatically worldwide. In this scenario, growing interest has been addressed to genotyping of KPC-Kp strains, which emerged as an important tool for a better understanding of the epidemiological and clinical characteristics of the outbreaks. METHODS: We performed a retrospective cohort study on patients infected with KPC-Kp during a 28-month outbreak period (January 2010-April 2012) at San Gerardo Hospital (Monza, Italy), investigating KPC-Kp genotypes by means of repetitive element sequence-based polymerase chain reaction (Rep-PCR). RESULTS: We enrolled 97 patients infected with KPC-Kp. Rep-PCR analysis identified 5 distinct clone types, with different distribution over time. During the first 12 months of the outbreak period, only 1 clone was detected (clone A, in 47 patients), while the 4 other clones were identified over the remaining 16 months (clones C, E, and F/L in 23, 24, and 3 patients respectively). Mechanical ventilation was less frequent in patients infected with clones C/E/F/L (OR = 0.14; 95% CI: 0.05-0.37) compared to clone A, and the Charlson comorbidity index (CI) was more likely to have a score >5 in patients infected with clones C/E/F/L (OR = 7.21; 95% CI: 2.24-23.14) compared to clone A.Overall mortality was higher in patients infected with clones C/E/F/L (13/20 patients, 65%) compared to those infected with clone A (7/20, 35%). Mortality in patients infected with clones C/E/F/L remained significantly higher even after adjusting for the potential confounding effect of comorbidities (ie, CI), with a hazard ratio (HR) of 4.65 (95% CI: 1.83-11.89). CONCLUSIONS: Our results suggested a close relationship between strain genotype and clinical outcome.

18.
BMC Res Notes ; 7: 504, 2014 Aug 07.
Article de Anglais | MEDLINE | ID: mdl-25100510

RÉSUMÉ

BACKGROUND: Host genetic factors are thought to modulated the severity of disease caused by infection with the 2009 H1N1 pandemic influenza virus (H1N1pdm09). The human CCR5 gene encodes a cytokine receptor important for cell-mediated immune response against H1N1pdm09. A 32-bp polymorphic deletion in the coding sequence of CCR5, the so-called CCR5Δ32 allele, segregates in populations of European ancestry with a frequency of 8-15%. A high proportion of CCR5Δ32 heterozygotes was reported in a sample of white Canadian critically-ill H1N1pdm09 infected subjects, suggesting an association with disease severity. METHODS: We recruited 29 H1N1pdm09 infected subjects from Southern Europe (mostly Italians) with a wide clinical spectrum of disease symptoms; the sample included 7 subjects who developed acute respiratory distress syndrome requiring extracorporeal membrane oxygenation. The CCR5Δ32 variant was genotyped in all subjects. RESULTS: The CCR5Δ32 allele was found in one single subject, who developed a very mild form and was not hospitalized. CONCLUSIONS: The CCR5Δ32 allele was not found to be associated with the risk of H1N1pdm09 infection or with a severe disease course.


Sujet(s)
Allèles , Prédisposition génétique à une maladie , Sous-type H1N1 du virus de la grippe A/isolement et purification , Grippe humaine/génétique , Récepteurs CCR5/génétique , Séquence nucléotidique , Amorces ADN , Humains , Grippe humaine/virologie , Réaction de polymérisation en chaîne
19.
Folia Neuropathol ; 50(3): 293-9, 2012.
Article de Anglais | MEDLINE | ID: mdl-23023344

RÉSUMÉ

The presence of an angiitis process in the central nervous system (CNS) characterizes different groups of conditions: from idiopathic pachymeningitis to lymphoproliferative disorders. In absence of specific infections, inflammatory and neoplastic diseases, the term "PACNS" (Primary Angiitis of the CNS) was proposed to indicate a peculiar vascular inflammation of unknown origin of meningeal vessels extending to the brain or spinal cord parenchyma. We report two cases of PACNS with peculiar and atypical features: the first one with a possible Epstein Barr Virus (EBV) relationship, the second one with spinal cord involvement only, treated surgically. We also hypothesize a correlation between EBV chronic infection and possible subtypes of PACNS stressing the importance of EBER (EBV-encoded RNA) test in the routine examination of brain biopsies suspicious for PACNS.


Sujet(s)
Vascularite du système nerveux central/diagnostic , Vascularite du système nerveux central/chirurgie , Adulte , Issue fatale , Femelle , Humains , Jeune adulte
20.
J Med Microbiol ; 61(Pt 5): 653-661, 2012 May.
Article de Anglais | MEDLINE | ID: mdl-22282459

RÉSUMÉ

Acinetobacter baumannii is a Gram-negative organism reported worldwide as a cause of health-care-associated infections, particularly in intensive care units (ICUs). The aim of this study is to describe the emergence and spread of carbapenem-resistant A. baumannii (CRAB) isolates in hospitalized patients. From March to November 2009, multidrug-resistant CRAB isolates were obtained from 21 patients hospitalized in different wards (mostly ICUs). Antimicrobial susceptibility was determined by using the Etest method. Carbapenem and aminoglycoside resistance determinants were studied by PCR and sequencing. Genetic relatedness was investigated by pulsed-field gel electrophoresis and multiplex PCR identification of sequence groups. Clinical records of patients were examined retrospectively. CRAB isolates were consistently resistant to multiple drugs including fluoroquinolones and aminoglycosides, whereas they retained a susceptibility to colistin. Molecular analysis revealed that 19 of the 21 CRAB isolates belonged to a single clone producing both the carbapenemase OXA-23 and the 16S rRNA methylase ArmA. Based on clinical data, the patients included in the study were classified as infected (n=13) or colonized (n=8). Colistin alone or in combination with ampicillin-sulbactam was administered to 11 of the 13 infected patients. A complete or partial response was obtained in eight cases, whereas a failure to respond was observed in one patient and a relapse was observed in two patients. An A. baumannii clone producing both OXA-23 and ArmA has been identified as an emerging and rapidly spreading pathogen. To our knowledge, this is the first report of the ArmA enzyme in A. baumannii in Italy and is the first report of hospital dissemination of A. baumannii carrying both bla(OXA-23) and armA genes.


Sujet(s)
Infections à Acinetobacter/épidémiologie , Infections à Acinetobacter/microbiologie , Acinetobacter baumannii/classification , Acinetobacter baumannii/enzymologie , Protéines bactériennes/génétique , Multirésistance bactérienne aux médicaments , Methyltransferases/génétique , bêta-Lactamases/génétique , Acinetobacter baumannii/génétique , Acinetobacter baumannii/isolement et purification , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Antibactériens/pharmacologie , Enfant d'âge préscolaire , Analyse de regroupements , Infection croisée/épidémiologie , Infection croisée/microbiologie , Électrophorèse en champ pulsé , Femelle , Génotype , Humains , Italie/épidémiologie , Mâle , Tests de sensibilité microbienne , Adulte d'âge moyen , Épidémiologie moléculaire , Typage moléculaire , Réaction de polymérisation en chaîne
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