Clinical significance of inflammatory markers of bacterial infection in critically ill patients with COVID-19 after treatment with anti-inflammatory and immunomodulatory drugs: a complex new scenario.

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

Candida auris is an emerging MDR pathogen raising major concerns worldwide. In Italy, it was first and only identified in July 2019 in our hospital (San Martino Hospital, Genoa), where infection or colonization cases have been increasingly recognized during the following months. To gain insights into the introduction, transmission dynamics, and resistance traits of this fungal pathogen, consecutive C. auris isolates collected from July 2019 to May 2020 (n = 10) were subjected to whole-genome sequencing (WGS) and antifungal susceptibility testing (AST); patients' clinical and trace data were also collected. WGS resolved all isolates within the genetic clade I (South Asian) and showed that all but one were part of a cluster likely stemming from the index case. Phylogenetic molecular clock analyses predicted a recent introduction (May 2019) in the hospital setting and suggested that most transmissions were associated with a ward converted to a COVID-19-dedicated ICU during the pandemic. All isolates were resistant to amphotericin B, voriconazole, and fluconazole at high-level, owing to mutations in ERG11(K143R) and TACB1(A640V). Present data demonstrated that the introduction of MDR C. auris in Italy was a recent event and suggested that its spread could have been facilitated by the COVID-19 pandemic. Continued efforts to implement stringent infection prevention and control strategies are warranted to limit the spread of this emerging pathogen within the healthcare system

Variazioni del filtrato glomerulare (eGFR) in una coorte di pazienti nati con HIV, risultati di uno studio osservazionale dal 2009 al 2018

Introduzione e scopo dello studio I pazienti nati con infezione da HIV rappresentano una popolazione speciale a causa dell\u2019esposizione fin dalla nascita ad HIV e alla terapia antiretrovirale di combinazione (cART). Molti pazienti hanno assunto tenofovir disoproxil fumarato (TDF) per necessit\ue0 anche se i dati in questa coorte sono scarsi. Inoltre vi sono pochi dati in letteratura relativi all\u2019andamento dell\u2019eGFR in questa popolazione. Scopo del nostro studio \ue8 di valutare le variazioni dell\u2019eGFR nei pazienti con infezione da HIV materno-fetale in follow-up nella nostra coorte. Materiali e metodi Studio osservazionale retrospettivo monocentrico nel periodo 2010-2018. Il dato \ue8 stato associato alla cART in corso. Abbiamo arruolato i pazienti con diagnosi di HIV trasmessa alla nascita ed estratto i dati delle cART e degli esami ematici dal sistema informatico ReteligureHIV (www.reteligureHIV.it) per il periodo in analisi. Abbiamo raccolto i dati del peso corporeo e altezza dalle cartelle cliniche. Abbiamo calcolato l\u2019eGFR con la formula di Cockroft-Gault nei pazienti maggiorenni al 2018, con la revised Schwartz equation nei minorenni. Abbiamo stratificato il dato con la cART effettuata (TDF, TAF, inibitore proteasi (PI), analogo non nucleosidico (NNRTI), inibitore integrasi (INI)). Risultati La nostra coorte \ue8 composta da 39 pazienti, di questi ne abbiamo arruolati 34, 5 sono stati esclusi per mancanza di dati. Il tempo di osservazione medio \ue8 di 8,8 anni (range 7-9). Le femmine 18 (53%), et\ue0 media di 18 anni nel 2010 (range 6-28). 30 pazienti (88%) hanno effettuato cART contenente TDF per almeno 1 anno, 19 (55%) hanno associato TDF+PI per almeno 1 anno, 14 (41%) TDF+NNRTI, 12 (35%) TDF+INI. 4 pazienti (12%) non hanno mai assunto TDF. Abbiamo osservato una riduzione mediana dell\u2019eGFR di 1,83 mL/min/anno (16,5 mL/min in 9 anni di studio). La riduzione \ue8 maggiore nel gruppo di pazienti in terapia con TDF+INI (3,7 mL/min/anno), minore per i pazienti in terapia con TDF+NNRTI (2,2 mL/min/anno) e TDF+PI (1,44 mL/min/anno). Abbiamo inoltre osservato un miglioramento dell\u2019eGFR mediano totale di 5 mL/min tra il 2017 e il 2018, anno in cui 23 pazienti (68%) hanno iniziato terapia con TAF. Nel solo gruppo esposto a TDF+INI abbiamo osservato un peggioramento dell\u2019eGFR anche nel 2018 (-5 mL/min). Conclusioni Il nostro studio ha evidenziato un peggioramento progressivo dell\u2019eGFR, come atteso in una popolazione esposta al virus HIV e alla cART. Il miglioramento osservato nel 2018 \ue8 un dato interessante, alla luce dell\u2019arrivo del TAF. Il peggioramento del filtrato con INI potrebbe dipendere dall\u2019associazione con DTG. Il proseguimento del follow-up \ue8 necessario per valutare l\u2019andamento negli anni futuri

Early versus delayed antiretroviral therapy based on genotypic resistance test: Results from a large retrospective cohort study

Rapid start of antiretroviral therapy (ART) pending genotypic resistance test (GRT) has been recently proposed, but the effectiveness of this strategy is still debated. The rate of virological success (VS), defined as HIV-RNA\u2009<\u200950 copies/ml, with and without GRT was compared in drug-na\uefve individuals enrolled in the Italian ARCA cohort who started ART between 2015 and 2018. 521 individuals started ART: 397 without GRT (pre-GRT group) and 124 following GRT (post-GRT group). Overall, 398 (76%) were males and 30 (6%) were diagnosed with AIDS. In the pre-GRT group, baseline CD4+\u2009cell counts were lower (p\u2009<\u20090.001), and viral load was higher (p\u2009<\u20090.001) than in the post-GRT group. The estimated probability of VS in pre-GRT versus post-GRT group was 72.54% (CI95 : 67.78-76.60) versus 66.94% (CI95 : 57.53-74.26) at Week 24 and 92.40% (CI95 : 89.26-94.62) versus 92.92% (CI95 : 86.35-96.33) at Week 48, respectively (p\u2009=\u20090.434). At Week 48, VS was less frequent among individuals with baseline CD4+\u2009cell counts <200 versus >500 (90.33% vs. 97.33%), log viral load <5.00 versus >5.70 log10 cps/ml (97.17% vs 78.16%; p\u2009<\u20090.001), and those treated with protease inhibitors or non-nucleoside reverse transcriptase inhibitors versus those treated with integrase strand transfer inhibitors (p\u2009<\u20090.001). The rate of VS does not seem to be affected by an early ART initiation pending GRT results, but it could be influenced by the composition of the ART regimen, as well as immuno-virological parameters

Barriers to HCV micro-elimination in a cohort of people living with HIV (PLWH)

: To achieve the World Health Organization goal of hepatitis C virus (HCV) eradication, barriers to treatment should be investigated and overcome. The aim of this study was to identify those barriers and describe the strategies adopted to achieve HCV micro-elimination in a cohort of coinfected people living with HIV (PLWH-HCV). Adult PLWH-HCV followed at our hospital with detectable serum HCV-RNA in 2018 were enrolled. After a three-year follow-up, barriers to HCV treatment were investigated and strategies to overcome them were described. Of 492 PLWH-HCV seen in 2018, 29 (5.9%) had detectable serum HCV-RNA. Eight out of 29 (27.6%) were excluded because they were already under treatment, while 2 others were excluded because they moved to other outpatient clinics. Among the remaining 19 study participants, the most common barriers to treatment were poor adherence to therapies and follow-up visits (n=9, 47%), recent HCV diagnosis awaiting proper staging (n=3, 16%) and treatment hesitancy (n=2, 10%). During the following three years, direct-acting antivirals (DAAs) treatment was completed in 11/19 (58%) cases, with achievement of sustained virological response in 100% of cases. For the remaining cases, 2/19 (10.5%) were lost to follow-up, 2/19 (10.5%) died before treatment initiation and 4/19 (21.0%) are still awaiting treatment. Despite 3 years of effort, HCV micro-elimination has not been achieved at our center. We observed that poor adherence and treatment hesitancy were the main barriers to treatment. Strategies addressing these issues need to be implemented

Recent advances and future perspectives in the pharmacological treatment of Candida auris infections

Introduction Candida auris is responsible for hospital outbreaks worldwide. Some C. auris isolates may show concomitant resistance to azoles, echinocandins, and polyenes, thereby possibly leaving clinicians with few therapeutic options. Areas covered Antifungal agents both in early and in late phases of clinical development showing anti-C. auris activity. Expert opinion The research on antifungal agents active against C. auris has made important steps forward in recent years: (i) the development of drugs with novel mechanisms of action, such as ibrexafungerp and fosmanogepix, could provide a valid option against C. auris strains resistant to one or more older antifungals, including pan-resistant strains; (ii) rezafungin could allow once weekly administration of an active drug in the case of echinocandin-susceptible isolates, providing an effective outpatient treatment, while at the same time relieving selective pressure on novel classes; (iii) the development of oral formulations could allow step-down therapy and/or early discharge, or even to avoid hospitalization in mild or noninvasive diseases; (iv) according to available data, these novel agents show a good safety profile and a low potential for drug-drug interactions

How relevant is the HIV low level viremia and how is its management changing in the era of modern ART? A large cohort analysis

Background: It is still unclear what might be the best management of people living with HIV (PLWHIV) with low level viremia (LLV) despite being on antiretroviral treatment (ART). Objectives: Aim of our study is to describe the clinical management of PLWHIV with LLV followed in a large cohort. Study design: Retrospective cohort study. Results: We included 1607 adult patients over a three-year period (2015\u20132017). Follow up continued until June, 30th 2019 or last available visit. We observed a low incidence of LLV (0.9 % in 2015, 0.7 % in 2016 and 0.4 % in 2017), with a total of 21 patients with persistent LLV (pLLV), i.e. two consecutive HIV-RNA determinations of 50\u2013500 copies/ml after at least 4 months of viral suppression. Among them, 12 had low compliance to treatment. Genotype resistance test (GRT) was performed in 14 patients and demonstrated at least one resistance mutation in 85.7 %. We described three categories of patients with pLLV: i) those whose ART regimen was not adequate based on GRT; ii) those with presumed suboptimal drug exposure, consequence of low adherence and/or drug-drug interactions and iii) those in which pLLV remained unexplained. For the first two categories, optimization or intensification of ART regimen led to viral suppression in >80 % of patients. We observed only 2 (9.5 %) virological failures and 1 (4.8 %) persistence of LLV in patients who did not switch ART. Conclusions: In our cohort, the rate of LLV showed a decline in most recent years. Adherence and previous GRT should be carefully considered with the aim of further reducing the phenomeno

Current and emerging drug treatment strategies to tackle invasive community-associated methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) infection: what are the challenges?

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections represent a leading cause of purulent skin and soft tissue infections in some geographical regions. Traditionally, ‘old antibiotics’ such as trimethoprim-sulfamethoxazole, tetracyclines, clindamycin, chloramphenicol,vancomycin, and teicoplanin have been used to treat these infections, but these were often associated with low efficacy and excessive side effects and toxicity, especially nephrotoxicity. Along with the development of new compounds, the last decade has seen substantial improvements in the management of CA-MRSA infections. In this review, the authors discuss the current and emerging drug treatment strategies to tackle invasive CA-MRSA infections. Articles reported in this review were selected from through literature searches using the PubMed database. The availability of new drugs showing a potent in vitro activity against CA-MRSA represents a unique opportunity to face the threat of resistance while potentially reducing toxicity. All these compounds represent promising options to enhance our antibiotic armamentarium. However, data regarding the use of these new drugs in real-life studies are limited and their best placement in therapy and in terms of optimization of medical resources and balance of cost-effectiveness requires further investigation.</p