To investigate whether daily bathing with a soap-like solution of 4% chlorhexidine (CHG) followed by water rinsing (CHGwr) would decrease the incidence of hospital-acquired infections (HAI) in ...intensive care settings.
Randomized, controlled trial; infectious diseases specialists were blinded to the intervention status. All patients admitted to the Intensive Care Unit (ICU) and to the Post-operative Cardiosurgical Intensive Care Unit (PC-ICU) of the University Hospital of Perugia were enrolled and randomized to the intervention arm (daily bathing with 4% CHGwr) or to the control arm (daily bathing with standard soap). The incidence rate of acquisition of HAI was compared between the two arms as primary outcome. We also evaluated the incidence of bloodstream infections (BSI), central-line-associated BSI (CLABSI), ventilator-associated pneumonia (VAP) and catheter-associated urinary tract infections (CAUTI), and 4% CHGwr safety.
In all, 449 individuals were enrolled, 226 in treatment arm and 223 in control arm. Thirty-four individuals of the 226 (15%) and 57 (25.6%) suffered from at least an HAI in the intervention and control arms, respectively (p 0.008); 23.2 and 40.9 infections/1000 patient-days were detected in the intervention arm and control arm, respectively (p 0.037). The incidence of all bloodstream infections (BSI plus CABSI) was significantly reduced in the intervention arm (9.2 versus 22.6 infections/1000 patient-days, p 0.027); no differences were observed in the mortality between the two arms.
Daily bathing with 4% CHGwr significantly reduced HAI incidence in intensive care settings.
NCT03639363.
Objectives
Plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9), a major regulator of cholesterol metabolism, have been reported to have an increasing trend in people living with ...HIV (PLWH) compared with controls. We assessed the impact of different antiretroviral (ARV) regimens on plasma PCSK9 levels as well as plasma lipids, systemic inflammation and immunovirological parameters.
Methods
Eighty HIV‐positive ARV therapy (ART)‐naïve PLWH and 40 uninfected controls were retrospectively enrolled. At baseline and 3, 6 and 12 months after ART initiation, plasma PCSK9 levels, lipids, high‐sensitivity C‐reactive protein (hs‐CRP), HIV‐1 RNA levels and CD4 T‐cell count were measured.
Results
Baseline PCSK9 levels were significantly more elevated in PLWH and were associated with HIV‐1 RNA levels (P < 0.001), CD4 T‐cell counts (P < 0.001), triglycerides (P < 0.001) and high‐density lipoprotein (HDL) cholesterol (P < 0.001), but not with total cholesterol, low‐density lipoprotein (LDL) cholesterol and lipoprotein(a) levels. The prescription of ART was paralleled by significant decreases in plasma PCSK9 and hs‐CRP levels, and increases in total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides and lipoprotein(a), independent of regimen.
Conclusions
PCSK9 levels, along with systemic inflammation, were progressively reduced following the initiation of an effective ART. However, at the end of the study PCSK9 levels remained higher than in controls and did not correlate with any of the lipid variables.
Summary
Methanococcoides burtonii is a member of the Archaea that was isolated from Ace Lake in Antarctica and is a valuable model for studying cold adaptation. Low temperature transcriptional ...regulation of global gene expression, and the arrangement of transcriptional units in cold‐adapted archaea has not been studied. We developed a microarray for determing which genes are expressed in operons, and which are differentially expressed at low (4°C) or high (23°C) temperature. Approximately 55% of genes were found to be arranged in operons that range in length from 2 to 23 genes, and mRNA abundance tended to increase with operon length. Analysing microarray data previously obtained by others for Halobacterium salinarum revealed a similar correlation between operon length and mRNA abundance, suggesting that operons may play a similar role more broadly in the Archaea. More than 500 genes were differentially expressed at levels up to ∼24‐fold. A notable feature was the upregulation of genes involved in maintaining RNA in a state suitable for translation in the cold. Comparison between microarray experiments and results previously obtained using proteomics indicates that transcriptional regulation (rather than translation) is primarily responsible for controlling gene expression in M. burtonii. In addition, certain genes (e.g. involved in ribosome structure and methanogenesis) appear to be regulated post‐transcriptionally. This is one of few experimental studies describing the genome‐wide distribution and regulation of operons in archaea.
Objectives
The aim of the study was to analyse the prevalence of integrase resistance mutations in integrase strand transfer inhibitor (INSTI)‐experienced HIV‐1‐infected patients and its predictors.
...Methods
We selected HIV‐1 integrase sequences from the Antiviral Response Cohort Analysis (ARCA) database, derived from INSTI‐experienced patients between 2008 and 2017. Differences in the prevalence of resistance to raltegravir (RAL), elvitegravir (EVG) and dolutegravir (DTG) were assessed by χ2 test and predictors of resistance were analysed by logistic regression.
Results
We included 462 genotypes from INSTI‐exposed individuals: 356 ‘INSTI‐failing' patients and 106 ‘previously INSTI‐exposed' patients (obtained a median of 42 weeks after INSTI discontinuation interquartile range (IQR) 17–110 weeks). Overall, at least low‐level resistance (LLR) to any INSTI (Stanford 8.5 algorithm) was detected in 198 (42.9%) cases. The most frequent INSTI resistance mutation was N155H, followed by Q148H/K/R, G140A/C/S, E138A/K/T and Y143C/H/R. Y143R and E138A were more prevalent in viral subtype B versus non‐B 5.2 versus 1.5%, respectively (P = 0.04), and 3.1 versus 0%, respectively (P = 0.02). Overall, the Q148H/K/R plus G140A/C/S and/or E138A/K/T pattern, defining an intermediate level of resistance to DTG, was detected in 70 (15%) cases. Independent predictors of at least LLR to any INSTI were current use versus past use of INSTIs, a lower genotypic sensitivity score (GSS) for contemporary antiretroviral drugs used, and having an integrase sequence obtained in calendar year 2016 as compared to 2008–2009.
Conclusions
The results support integrase resistance testing in INSTI‐experienced patients. Emergence of INSTI resistance is facilitated by the reduced genetic barrier of the regimen as a consequence of resistance to companion drugs. However, INSTI resistance may become undetectable by standard population sequencing upon INSTI discontinuation.
•We analyzed durability and virological response to DTG-containing regimens.•After exposure to first-generation INIs, treatment with DTG showed long durability.•DTG-containing regimens did not show ...any virological rebound after suppression.•DTG discontinuation was less frequent in patients who had experienced ≥10 regimens.•Non-B HIV-1 subtype represented a greater risk for detectable HIV-RNA at the last F–U.
Dolutegravir (DTG) is a next-generation HIV integrase inhibitor (INI) with an increased genetic barrier to resistance with respect to raltegravir (RAL) or elvitegravir (EVG). Few data are available on the durability of DTG-containing regimens.
We aimed at investigating the duration of the DTG-containing regimen, the occurrence of an HIV-1 RNA blip, and factors associated with DTG virological response.
From the Antiviral Response Cohort Analysis database, we selected 89 HIV-1-positive four-class-experienced subjects who started DTG after receiving RAL or EVG. Factors associated with durability and virological response were analysed by logistic regression.
After a median duration of 18.8 0.4–76.2 months, 79/89 (88.8%) subjects were still on DTG. All subjects remaining on DTG at the end of follow-up had undetectable HIV-1 RNA, compared to 5/10 subjects who discontinued DTG. DTG discontinuation was less frequent in patients who had experienced ≥10 regimens (HR 0.11, p = 0.040). The probability of having an HIV-1 RNA positive value at the last follow-up significantly increased in patients with non-B HIV-1 subtype (HR 5.77, p < .001) and significantly decreased in patients with CD4 nadir >200/μL (HR 0.29, p = 0.038), with more than 10 previous regimens (HR 0.27, p = 0.040), and who harbored virus with IN mutations (HR 0.12, p = 0.023) at DTG start.
After previous exposure to first-generation INIs, treatment with DTG showed long durability and did not show virological rebound after virological suppression. Subjects infected with a non-B HIV-1 subtype had a greater risk of having detectable HIV-1 RNA at the last observation.
We present a case of a male Italian patient of 66 years with a history of kidney transplantation in treatment with cyclosporine and methylprednisolone. He visited an ENT clinic and was diagnosed as ...chronic left purulent otitis media. He began at-home antibiotic therapy with poor benefit. On 09/13/18, he was admitted to the hospital “S. Maria ”of Terni for persistence of left ear pain and complete hearing loss. Magnetic resonance imaging (MRI) of the brain showed “in correspondence of the petrous rock and the mastoid…presence of flogistic tissue.” Auricular swabs and later surgical drainage of the purulent material were performed and both were positive for extensively drug-resistant (XDR) Pseudomonas aeruginosa sensitive only to colistin in absence of synergism with rifampin. The patient underwent antibiotic therapy with ceftolozane-tazobactam, a new generation cephalosporin with anti-Pseudomonas activity and a β-lactamase inhibitor, that currently is indicated for the treatment of complicated urinary tract infections and complicated intra-abdominal infections, with complete healing. In literature, it is described a series of 12 patients with severe MDR (multidrug-resistant) Pseudomonas aeruginosa infections (6 pneumonia) who received salvage therapy with ceftolozane-tazobactam after inappropriate empirical and/or suboptimal treatment. This study included a case of a male patient of 45 years, affected by Burkitt lymphoma and severe neutropenia, who presented with otitis and mastoiditis, and isolation of Pseudomonas aeruginosa in surgical drainage of the purulent material of the ear (blood cultures were negative). He underwent antibiotic therapy with ceftolozane–tazobactam at a dosage of 3 g/8 h for 21.3 days. The patient was healed, but a late recurrence was described because of isolation of ceftolozane-tazobactam-resistant Pseudomonas after therapy. The possibility of acquiring resistance to ceftolozane-tazobactam should be considered in patients with previous exposure to beta-lactams and with poor response to these antibiotics.
The aim of this retrospective, multicentre, observational study was to assess the durability, safety, immune recovery and effectiveness on viral suppression of antiretroviral therapy (ART) in a ...maraviroc (MVC)-based cohort. We collected clinical, demographical, immunological and virological parameters of adult HIV patients who were infected by CCR5-tropic virus and started an ART regimen containing MVC from 2005 to 2012. We created a longitudinal mixed model to assess the change over time of data. We enrolled 126 drug-experienced patients; the median duration of MVC treatment was 25 months. The probability of stopping ART at one year was 13.3%, and at three years was 27.3%. Statistically significant changes were observed for CD4+ cell count increase ( p < 0.001), HIV-RNA decrease ( p < 0.001) and total cholesterol decrease ( p = 0.005). Ninety-four patients (79.7%) had CD4 ≥ 200 cells/mm
at baseline while nine of them reached this threshold at nine months (7.6%), 17 (13%) after nine months and six (5%) remained below 200 cells/mm
at the end of the study. Overall, 114 patients (90.5%) achieved an HIV-RNA ≤ 50 cp/ml. A majority of patients maintained CD4 cell counts of ≥ 200 cells/mm
and achieved an undetectable HIV viral load within three months. MVC-containing regimens are safe and appear to be a feasible therapeutic option for ART.
Purpose
Migrants account for approximately 8.7 % of the resident population in Italy. The immigration status deeply influences access to prevention and care, thus contributing to increase the burden ...of HIV/AIDS among such a fragile category. The aim of this study was to investigate socio-demographic and baseline clinical and immunological features of HIV-infected migrants, as compared to Italians.
Methods
We retrospectively analysed data for all the 1,611 HIV-infected migrant patients and a random sample of 4,230 HIV-infected Italian patients aged 18 or older who first accessed nine Italian clinical centres in 2000–2010 and were followed up at least 1 year. Differences in baseline characteristics between migrants and Italians were evaluated in univariate analysis, while factors associated with late presentation were evaluated in multivariate analysis using logistic regression models.
Results
The baseline profile differs between the HIV-infected migrant and Italian patients, substantially reflecting what reported by current statistics in terms of gender, age, risk category as well as clinical features. Late presenters were more frequent among migrants as compared to Italians (53.0 vs 45.8 %; adjusted odds ratio (AOR) = 1.55, 95 % confidence interval (CI) 1.34–1.78. Other factors associated with late presentation included increasing age, as well as undocumented legal status among foreign-born subjects (AOR = 1.41, 95 % CI 0.97–2.04), though of borderline significance.
Conclusions
Late presentation still represents a relevant problem despite the advances in the management of HIV infection. More efforts are needed to allow early diagnosis and access to care among the most vulnerable, such as undocumented foreign-born subjects in a country where migration flows are on the rise.
Introduction: Hepatitis B virus (HBV) reactivation is a majorcause of morbidity and mortality in patients with hematologicalmalignancies who receive cytotoxic chemotherapy. Wehave therefore carried ...out a prospective observational studyout to assess the incidence, prevalence, and clinical course ina cohort of these patients. Methods: HBV and HCV markers and liver function indiceswere monitored prospectively in 318 consecutive patients(171 males, 147 females; mean age 57 years) with hematologicalmalignancies, who had been referred to the HematologyDivision, Perugia University, between October 2005and March 2007 and followed up for at least 6 months. Results: At diagnosis, 32 patients (10%) had received HBVvaccination; 30 were responders. At least one HBV marker waspositive in 70/318 patients (22%): 14 (20%) were HBsAg-positive(HBV surface antigen-positive), 13 (19%) were only anti-HBc positive (antibodies to HB core antigen), and 43(61%)were anti-HBc and anti-HBs positive. Twelve HBsAg+ patientsreceived nucleoside/nucleotide analogs (adefovir six patients,lamivudine four, and combined adefovir/lamivudinetwo non-responders to lamivudine). After 6 months oftherapy, HBV-DNA was negative and transaminases were normalin nine of these 12 patients (adefovir six, lamivudinatwo, adefovir + lamivudina one). Seroreversion wasachieved in 3/13 patients (23%) who were only anti-HBc positive;all were on rituximab therapy and received adefovir.Seroreversion was not observed in any of the 43 patients whowere anti-HBc- and anti-HBs positive. Conclusions: Essential to the management of patients withhematological malignancies undergoing chemotherapy aresurveillance and prophylaxis of HBV infection together withprompt administration of nucleoside/nucleotide analogs incases of reactivation and/or seroreversion.
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