Lower (1,3)-beta-d-glucan sensitivity and in vitro levels in Candida auris and Candida parapsilosis strains.

OBJECTIVES: The serum (1,3)-beta-d-glucan (BDG) assay gives quicker results and has higher sensitivity than blood cultures, therefore it is advised for early diagnosis of invasive candidemia and/or discontinuation of empirical therapy. Its sensitivity may depend on different factors. The aim of our study was to analyse the in vitro and in vivo BDG levels in clinical isolates of three species of Candida responsible for candidemia. METHODS: C. albicans, C. parapsilosis, and C. auris strains were collected from blood cultures of patients who had a concurrent (-1 to +3 days) serum BDG test (Fungitell assay). Supernatants of all strains were tested in quadruplicate for BDG levels. RESULTS: Twenty-two C. auris, 14 C. albicans, and ten C. parapsilosis strains were included. The median BDG levels in supernatants were 463 pg/mL (interquartile range [IQR] 379-648) for C. auris, 1080 pg/mL (IQR 830-1276) for C. albicans, and 755 pg/mL (IQR 511-930) for C. parapsilosis, with the significant difference among the species (p < 0.0001). Median serum BDG levels (IQR) were significantly lower in case C. auris and C. parapsilosis vs. C. albicans (p < 0.0001), respectively, 50 pg/mL (IQR 15-161) and 57 pg/mL (IQR 18-332), vs. 372 pg/mL (IQR 102-520). Sensitivity of serum BDG was 39% (95% confidence interval [CI], 18-64) in case of C. auris, 30% (95% CI, 8-65) C. parapsilosis and 78% (95% CI, 49-94) C. albicans candidemia. DISCUSSION: In our centre C. auris and C. parapsilosis strains have lower BDG content as compared with C. albicans, with a potential impact on serum BDG performance for the diagnosis of candidemia.

Antibiotic Strategies for Severe Community-Acquired Pneumonia.

Despite advancements in health systems and intensive care unit (ICU) care, along with the introduction of novel antibiotics and microbiologic techniques, mortality rates in severe community-acquired pneumonia (sCAP) patients have not shown significant improvement. Delayed admission to the ICU is a major risk factor for higher mortality. Apart from choosing the appropriate site of care, prompt and appropriate antibiotic therapy significantly affects the prognosis of sCAP. Treatment regimens involving ceftaroline or ceftobiprole are currently considered the best options for managing patients with sCAP. Additionally, several other molecules, such as delafloxacin, lefamulin, and omadacycline, hold promise as therapeutic strategies for sCAP. This review aims to provide a comprehensive summary of the key challenges in managing adults with severe CAP, focusing on essential aspects related to antibiotic treatment and investigating potential strategies to enhance clinical outcomes in sCAP patients.

Lower blood levels of isavuconazole in critically ill patients compared with other populations: possible need for therapeutic drug monitoring.

BACKGROUND: Isavuconazole is first-line treatment of invasive aspergillosis. Therapeutic drug monitoring (TDM) is deemed not necessary, since most patients reached therapeutic levels (>1 mg/L) in large studies. Low levels were reported in some critically ill patients admitted to the ICU. The aim was to compare isavuconazole levels between critically ill and non-critically ill patients. MATERIALS AND METHODS: Retrospective analysis of data from all patients treated with standard-dose isavuconazole between 1 January 2019 and 26 October 2022 was performed. The following data were collected: TDM results from the first 30 days of therapy; ward of admission; demographic and clinical characteristics; continuous renal replacement therapy; extracorporeal membrane oxygenation; and co-administered drugs. RESULTS: Seventy-two patients (median age 65 years) and 188 TDM measurements (mean number of samples per patient 2.6 ±â€Š1.7) were included; 33 (45.8%) were ICU patients (3 also had haematological disorders); 39 (54.2%) were non-ICU patients, of whom 31 had haematological disorders. In all patients, the mean isavuconazole blood level was 3.33 ±â€Š2.26 mg/L. Significantly lower levels were observed in the ICU versus the non-ICU population: mean 2.02 ±â€Š1.22 versus 4.15 ±â€Š2.31 mg/L (P < 0.001). Significantly higher rates of subtherapeutic levels were observed in ICU patients compared with the non-ICU population: all determinations <2 mg/L in 33.3% versus 7.7%, and all determinations <1 mg/L in 12.1% versus 0%, respectively. Predictors of lower isavuconazole levels were admission to the ICU, BMI > 25 kg/m2, bilirubin > 1.2 mg/dL and the absence of haematological disorder. CONCLUSIONS: ICU patients had significantly lower isavuconazole blood levels compared to non-ICU population. The TDM of isavuconazole for efficacy should be performed in ICU.

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.

Pneumocystis jirovecii pneumonia in intensive care units: a multicenter study by ESGCIP and EFISG.

BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) is an opportunistic, life-threatening disease commonly affecting immunocompromised patients. The distribution of predisposing diseases or conditions in critically ill patients admitted to intensive care unit (ICU) and subjected to diagnostic work-up for PJP has seldom been explored. MATERIALS AND METHODS: The primary objective of the study was to describe the characteristics of ICU patients subjected to diagnostic workup for PJP. The secondary objectives were: (i) to assess demographic and clinical variables associated with PJP; (ii) to assess the performance of Pneumocystis PCR on respiratory specimens and serum BDG for the diagnosis of PJP; (iii) to describe 30-day and 90-day mortality in the study population. RESULTS: Overall, 600 patients were included in the study, of whom 115 had presumptive/proven PJP (19.2%). Only 8.8% of ICU patients subjected to diagnostic workup for PJP had HIV infection, whereas hematological malignancy, solid tumor, inflammatory diseases, and solid organ transplants were present in 23.2%, 16.2%, 15.5%, and 10.0% of tested patients, respectively. In multivariable analysis, AIDS (odds ratio [OR] 3.31; 95% confidence interval [CI] 1.13-9.64, p = 0.029), non-Hodgkin lymphoma (OR 3.71; 95% CI 1.23-11.18, p = 0.020), vasculitis (OR 5.95; 95% CI 1.07-33.22, p = 0.042), metastatic solid tumor (OR 4.31; 95% CI 1.76-10.53, p = 0.001), and bilateral ground glass on CT scan (OR 2.19; 95% CI 1.01-4.78, p = 0.048) were associated with PJP, whereas an inverse association was observed for increasing lymphocyte cell count (OR 0.64; 95% CI 0.42-1.00, p = 0.049). For the diagnosis of PJP, higher positive predictive value (PPV) was observed when both respiratory Pneumocystis PCR and serum BDG were positive compared to individual assay positivity (72% for the combination vs. 63% for PCR and 39% for BDG). Cumulative 30-day mortality and 90-day mortality in patients with presumptive/proven PJP were 52% and 67%, respectively. CONCLUSION: PJP in critically ill patients admitted to ICU is nowadays most encountered in non-HIV patients. Serum BDG when used in combination with respiratory Pneumocystis PCR could help improve the certainty of PJP diagnosis.

In vivo evolution to echinocandin resistance and increasing clonal heterogeneity in Candida auris during a difficult-to-control hospital outbreak, Italy, 2019 to 2022.

A difficult-to-control outbreak of Candida auris is ongoing in a large tertiary care hospital in Liguria, Italy, where it first emerged in 2019. In a retrospective analysis, 503 cases of C. auris carriage or infection were observed between July 2019 and December 2022. Genomic surveillance identified putative cases that no longer occurred as part of one defined outbreak and the emergence of echinocandin (pandrug) resistance following independent selection of FKS1S639F and FKS1F635Y mutants upon prolonged exposure to caspofungin and/or anidulafungin.

Triple Combination Therapy With 2 Antivirals and Monoclonal Antibodies for Persistent or Relapsed Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Immunocompromised Patients.

BACKGROUND: Severely immunocompromised patients are at risk for prolonged or relapsed Coronavirus Disease 2019 (COVID-19), leading to increased morbidity and mortality. We aimed to evaluate efficacy and safety of combination treatment in immunocompromised COVID-19 patients. METHODS: We included all immunocompromised patients with prolonged/relapsed COVID-19 treated with combination therapy with 2 antivirals (remdesivir plus nirmatrelvir/ritonavir, or molnupiravir in case of renal failure) plus, if available, anti-spike monoclonal antibodies (mAbs), between February and October 2022. The main outcomes were virological response at day 14 (negative Severe Acute Respiratory Syndrome Coronavirus 2 [SARS-CoV-2] swab) and virological and clinical response (alive, asymptomatic, with negative SARS-CoV-2 swab) at day 30 and the last follow-up. RESULTS: Overall, 22 patients (Omicron variant in 17/18) were included: 18 received full combination of 2 antivirals and mAbs and 4 received 2 antivirals only; in 20 of 22 (91%) patients, 2 antivirals were nirmatrelvir/ritonavir plus remdesivir. Nineteen (86%) patients had hematological malignancy, and 15 (68%) had received anti-CD20 therapy. All were symptomatic; 8 (36%) required oxygen. Four patients received a second course of combination treatment. The response rate at day 14, day 30, and last follow-up was 75% (15/20 evaluable), 73% (16/22), and 82% (18/22), respectively. Day 14 and 30 response rates were significantly higher when combination therapy included mAbs. Higher number of vaccine doses was associated with better final outcome. Two patients (9%) developed severe side effects (bradycardia leading to remdesivir discontinuation and myocardial infarction). CONCLUSIONS: Combination therapy including 2 antivirals (mainly remdesivir and nirmatrelvir/ritonavir) and mAbs was associated with high rate of virological and clinical response in immunocompromised patients with prolonged/relapsed COVID-19.

REDS study: Retrospective effectiveness study of dalbavancin and other standard of care of the same IV antibiotic class in patients with ABSSSI.

OBJECTIVES: Acute bacterial skin and skin-structure infections (ABSSSIs) are a common source of morbidity in both the community and hospital settings. The current standard of care (SoC) requires multiple-dose intravenous (IV) regimens, which are associated with high hospitalisation rates, concomitant event risks and costs. Dalbavancin is a lipoglycopeptide, long-acting antibiotic that is effective against Gram-positive microorganisms, including methicillin-resistant Staphylococcus aureus (MRSA). Dalbavancin allows treatment of ABSSSIs with a single-shot IV administration or once weekly for 2 weeks, enabling clinicians to treat patients in an outpatient setting or to shorten the length of hospital stay. METHODS: This multicentre, observational, retrospective study compared hospitalised patients who received dalbavancin and patients treated with the three most used IV antibiotics of the same or similar class: vancomycin, teicoplanin and daptomycin. The primary outcome was the time to discharge after starting the study antibiotics. RESULTS: The primary endpoint, time to discharge from the study therapy start, was measured for both groups: the median number of days was 6.5 in the dalbavancin group vs. 11.0 days in the SoC group. Moreover, in subpopulations of patients receiving one or more concomitant antibiotics active for Gram-positives, MRSA and patients with the most prevalent comorbidity (i.e., diabetes), the advantage of dalbavancin in terms of length of stay was confirmed, with a halved time to discharge or more. Safety data on dalbavancin were consistent with data collected in clinical trials. No serious adverse drug reactions related to dalbavancin were reported and most of them were classified as skin and subcutaneous tissue disorders. One serious ADR was reported for daptomycin. CONCLUSIONS: Although the analysis was only descriptive, it can be concluded that dalbavancin may enable a remarkable reduction in length of hospital stay, also confirming the clinical effectiveness and good safety profile demonstrated in clinical trials in a real-world setting.

Short Course of Antifungal Therapy in Patients With Uncomplicated Candida Bloodstream Infection: Another Case of Less Is More in the Clinical Setting?

Background: The objective of this study was to compare the clinical outcomes of patients receiving a short course (SC) vs a prolonged course (PC) of antifungal therapy for uncomplicated Candida bloodstream infections (BSIs). Methods: All episodes of uncomplicated Candida BSI from September 1, 2018, to August 31, 2020, were reviewed. We compared the primary (all-cause 90-day mortality) and secondary study end points (1-year recurrent Candida BSI and all-cause 1-year mortality) among patients who underwent SC (5-11 days) or PC (12-24 days) therapy using propensity score analysis with the inverse probability of treatment weighting (IPTW) method. Results: A total of 114 patients with uncomplicated Candida BSI were included: 35 (30.7%) were classified into the SC group (median [interquartile range {IQR}], 9 [7-11] days) and 79 (69.3%) into the PC group (median [IQR], 14 [14-16] days). Patients in the SC group compared with the PC group had a higher rate of hospitalization in the surgical ward (40.0% vs 19.0%; P = .02) or septic shock at the time of Candida BSI onset (11.4% vs 1.3%; P = .03). The risk of 90-day mortality was not different between the SC and PC groups (n = 8 [22.9%] vs 17 [21.5%], respectively; IPTW-adjusted subdistribution hazard ratio [sHR], 0.67; 95% CI, 0.31-1.47; P = .20). The risk for recurrent Candida BSI within 1 year of completing therapy (IPTW-adjusted sHR, 1.07; 95% CI, 0.20-5.80; P = .94) or for all-cause 1-year mortality (IPTW-adjusted HR, 0.72; 95% CI, 0.35-1.50; P = .38) did not differ between groups. Conclusions: Receiving a short vs prolonged course of antifungal therapy did not affect mortality or BSI recurrence in patients with uncomplicated candidemia.

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

INTRODUCTION: 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. AREAS COVERED: 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. EXPERT OPINION: 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.

Frequency of Detection of Candida auris Colonization Outside a Highly Endemic Setting: What Is the Optimal Strategy for Screening of Carriage?

Candida auris outbreaks are increasingly frequent worldwide. In our 1000-bed hospital, an endemic transmission of C. auris was established in two of five intensive care units (ICUs). Aims of our study were to describe the occurrence of new cases of C. auris colonization and infection outside the endemic ICUs, in order to add evidence for future policies on screening in patients discharged as negative from an endemic setting, as well as to propose a new algorithm for screening of such high-risk patients. From 26 March 2021 to 26 January 2023, among 392 patients who were diagnosed as colonized or infected with C. auris in our hospital, 84 (21.4%) received the first diagnosis of colonization or infection outside the endemic ICUs. A total of 68 patients out of 84 (81.0%) had a history of prior admission to the endemic ICUs. All were screened and tested negative during their ICU stay with a median time from last screening to discharge of 3 days. In 57/68 (83.8%) of patients, C. auris was detected through screening performed after ICU discharge, and 90% had C. auris colonization detected within 9 days from ICU discharge. In 13 cases (13/57 screened, 22.8%), the first post-ICU discharge screening was negative. In those not screened, candidemia was the most frequent event of the first C. auris detection (6/11 patients not screened). In settings where the transmission of C. auris is limited to certain wards, we suggest screening both at discharge from the endemic ward(s) even in case of a recent negative result, and at least twice after admission to nonendemic settings.

T2Bacteria and T2Resistance Assays in Critically Ill Patients with Sepsis or Septic Shock: A Descriptive Experience.

The use of rapid molecular tests may anticipate the identification of causative agents and resistance determinants in the blood of critically ill patients with sepsis. From April to December 2021, all intensive care unit patients with sepsis or septic shock who were tested with the T2Bacteria and T2Resistance assays were included in a retrospective, single center study. The primary descriptive endpoints were results of rapid molecular tests and concomitant blood cultures. Overall, 38 combinations of T2Bacteria and T2Resistance tests were performed. One or more causative agent(s) were identified by the T2Bacteria assay in 26% of episodes (10/38), whereas negative and invalid results were obtained in 66% (25/38) and 8% (3/38) of episodes, respectively. The same pathogen detected by the T2Bacteria test grew from blood cultures in 30% of cases (3/10). One or more determinant(s) of resistance were identified by the T2Resistance assay in 11% of episodes (4/38). Changes in therapy based on T2Bacteria and/or T2Resistance results occurred in 21% of episodes (8/38). In conclusion, T2Bacteria/T2Resistance results can influence early treatment decisions in critically ill patients with sepsis or septic shock in real-life practice. Large, controlled studies remain necessary to confirm a favorable impact on patients' outcomes and antimicrobial stewardship interventions.

Healthcare Worker Study Cohort to Determine the Level and Durability of Cellular and Humoral Immune Responses after Two Doses of SARS-CoV-2 Vaccination.

We prospectively studied immunological response against SARS-CoV-2 after vaccination among healthcare workers without (group A) and with previous infection (group B). The analyses were collected at T0 (before the BNT162b2), T1 (before the second dose), T2 and T6 (1 and 6 months after the second dose). For cellular immune response, the activation-induced cell marker assay was performed with CD4 and CD8 Spike peptide megapools expressed as Stimulation Index. For humoral immune response, we determined antibodies to Spike-1 and nucleocapsid protein. The linear mixed model compared specific times to T0. The CD4+ Spike response overall rate of change was significant at T1 (p = 0.038) and at T2 (p < 0.001), while decreasing at T6. For CD8+ Spike reactivity, the interaction between the time and group was significant (p = 0.0265), and the p value for group comparison was significant at the baseline (p = 0.0030) with higher SI in previously infected subjects. Overall, the anti-S Abs significantly increased from T1 to T6 compared to T0. The group B at T6 retained high anti-S titer (p < 0.001). At T6, in both groups we found a persistent humoral response and a high CD4+ T cell response able to cross recognize SARS-COV-2 variants including epsilon, even if not a circulating virus at that time.

Sensitivity of Serum Beta-D-Glucan in Candidemia According to Candida Species Epidemiology in Critically Ill Patients Admitted to the Intensive Care Unit.

Serum beta-D-glucan (BDG) determination plays an important role in the diagnosis of candidemia among critically ill patients admitted to the intensive care unit (ICU). However, BDG levels measured may be lower in the case of infections caused by some non-albicans species, such as C. parapsilosis and C. auris. The aim of this single-center study was to investigate the sensitivity of serum BDG for the diagnosis of candidemia stratified according to causative Candida species in ICU patients. This was a single-center, retrospective study, including all adult patients admitted to ICU during the period 2018-2021. All episodes of candidemia with a determination of BDG available within 3 days before or after positive blood culture were recorded. The preplanned primary objective was to investigate the sensitivity of serum BDG to detect candidemia early and the effect of different Candida species. The secondary objective was to measure serum BDG in patients with candidemia from different Candida species. In total, 146 candidemia episodes in 118 patients were analyzed. Median BDG value for C. albicans candidemia (182 pg/mL) was higher than that observed for C. parapsilosis (78 pg/mL, p = 0.015) and C. auris (48 pg/mL, p = 0.022). The overall sensitivity of BDG for the diagnosis of candidemia was low (47%, 95% CI 39-55%). In conclusion, in critically ill patients admitted to ICU, serum BDG levels for candidemia were different among species, with lower levels confirmed for C. parapsilosis and C. auris. Serum BDG sensitivity for early detection of candidemia was lower than previously reported in other ICU populations.

Candida auris Candidemia in Critically Ill, Colonized Patients: Cumulative Incidence and Risk Factors.

INTRODUCTION: Candida auris (C. auris) is an emerging nosocomial pathogen, and a sharp rise in cases of colonization and infection has been registered in intensive care units (ICUs) during the ongoing coronavirus disease 2019 (COVID-19) pandemic. The unfavorable resistance profile of C. auris and the potential high mortality of C. auris infections represent an important challenge for physicians. METHODS: We conducted a single-center retrospective study including all patients admitted to ICUs with isolation of C. auris in any non-sterile body site between February 20, 2020, and May 31, 2021. The primary aim of the study was to assess the cumulative incidence of C. auris candidemia in colonized patients. The secondary aim was to identify predictors of C. auris candidemia in the study population. RESULTS: During the study period, 157 patients admitted to ICUs in our hospital became colonized with C. auris; 59% of them were affected by COVID-19. Overall, 27 patients (17%) developed C. auris candidemia. The cumulative risk of developing C. auris candidemia was > 25% at 60 days after first detection of C. auris colonization. Seven patients with C. auris candidemia (26%) also developed a late recurrent episode. All C. auris blood isolates during the first occurring episode were resistant to fluconazole and susceptible to echinocandins, while 15 (56%) were resistant to amphotericin B. During late recurrent episodes, emergent resistance to caspofungin and amphotericin B occurred in one case each. In the final multivariable model, only multisite colonization retained an independent association with the development of C. auris candidemia. CONCLUSION: Candida auris candidemia may occur in up to one fourth of colonized critically ill patients, and multisite colonization is an independent risk factor for the development of candidemia. Implementing adequate infection control measures remains crucial to prevent colonization with C. auris and indirectly the subsequent development of infection.

Real-Life Use of Ceftolozane/Tazobactam for the Treatment of Bloodstream Infection Due to Pseudomonas aeruginosa in Neutropenic Hematologic Patients: a Matched Control Study (ZENITH Study).

We sought to assess the characteristics and outcomes of neutropenic hematologic patients with Pseudomonas aeruginosa (PA) bloodstream infection (BSI) treated with ceftolozane-tazobactam (C/T). We conducted a multicenter, international, matched-cohort study of PA BSI episodes in neutropenic hematologic patients who received C/T. Controls were patients with PA BSI treated with other antibiotics. Risk factors for overall 7-day and 30-day case fatality rates were analyzed. We compared 44 cases with 88 controls. Overall, 91% of episodes were caused by multidrug-resistant (MDR) strains. An endogenous source was the most frequent BSI origin (35.6%), followed by pneumonia (25.8%). There were no significant differences in patient characteristics between groups. C/T was given empirically in 11 patients and as definitive therapy in 41 patients. Treatment with C/T was associated with less need for mechanical ventilation (13.6% versus 33.3%; P = 0.021) and reduced 7-day (6.8% versus 34.1%; P = 0.001) and 30-day (22.7% versus 48.9%; P = 0.005) mortality. In the multivariate analysis, pneumonia, profound neutropenia, and persistent BSI were independent risk factors for 30-day mortality, whereas lower mortality was found among patients treated with C/T (adjusted OR [aOR] of 0.19; confidence interval [CI] 95% of 0.07 to 0.55; P = 0.002). Therapy with C/T was associated with less need for mechanical ventilation and reduced 7-day and 30-day case fatality rates compared to alternative agents in neutropenic hematologic patients with PA BSI. IMPORTANCE Ceftolozane-tazobactam (C/T) has been shown to be a safe and effective alternative for the treatment of difficult to treat infections due to Pseudomonas aeruginosa (PA) in the general nonimmunocompromised population. However, the experience of this agent in immunosuppressed neutropenic patients is very limited. Our study is unique because it is focused on extremely immunosuppressed hematological patients with neutropenia and bloodstream infection (BSI) due to PA (mainly multidrug resistant [MDR]), a scenario which is often associated with very high mortality rates. In our study, we found that the use of C/T for the treatment of MDR PA BSI in hematological neutropenic patients was significantly associated with improved outcomes, and, in addition, it was found to be an independent risk factor associated with increased survival. To date, this is the largest series involving neutropenic hematologic patients with PA BSI treated with C/T.

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 < 50 copies/ml, with and without GRT was compared in drug-naïve 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+ cell counts were lower (p < 0.001), and viral load was higher (p < 0.001) 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 = 0.434). At Week 48, VS was less frequent among individuals with baseline CD4+ cell 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 < 0.001), and those treated with protease inhibitors or non-nucleoside reverse transcriptase inhibitors versus those treated with integrase strand transfer inhibitors (p < 0.001). 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.

Levels of beta-D-glucan in Candida auris supernatants, an in vitro and in vivo preliminary study.

OBJECTIVES: Serum (1,3)-beta-d-glucan (BDG) assay is a non-culture-based test recommended for the diagnosis of invasive candidiasis owing to its faster results and higher sensitivity than blood cultures. Its performance might vary for different Candida species. The aim of this study was to determine in vitro levels of BDG in Candida auris culture supernatants and evaluate BDG levels in patients with C. auris candidemia sustained by these stains. METHODS: C. auris strains were collected from blood cultures of patients who had a concomitant (-24 to +72 hours) serum BDG test (Fungitell assay). Supernatants of broth media culture of C. auris strains and two Candida albicans (controls) strains were prepared and tested for BDG. RESULTS: Ten C auris strains were included. Supernatants of two C. albicans considered as controls had a mean BDG level of 1155 pg/mL (considered 100% reactivity). The median BDG level in supernatants of C. auris strains was 275 pg/mL (IQR 165-523 pg/mL), with a median reactivity of 24% (range 6%-72%). In vivo, the median BDG level was 129 pg/mL (IQR, 28-199 pg/mL). Sensitivity of BDG for C. auris candidemia was 60%. All patients received antifungal treatment with an echinocandin initiated a median of 2 days (IQR -8 to 0) before blood collection for BDG. DISCUSSION: Our C. auris strains released lower amounts of BDG when compared to C. albicans. Clinical implications include lower sensitivity of serum BDG for the diagnosis of C. auris candidemia with a consequent impact on management protocols in settings with high prevalence of this species.

Reactivation of Herpes Simplex Virus Type 1 (HSV-1) Detected on Bronchoalveolar Lavage Fluid (BALF) Samples in Critically Ill COVID-19 Patients Undergoing Invasive Mechanical Ventilation: Preliminary Results from Two Italian Centers.

Reactivation of herpes simplex virus type 1 (HSV-1) has been described in critically ill patients with coronavirus disease 2019 (COVID-19) pneumonia. In the present two-center retrospective experience, we primarily aimed to assess the cumulative risk of HSV-1 reactivation detected on bronchoalveolar fluid (BALF) samples in invasively ventilated COVID-19 patients with worsening respiratory function. The secondary objectives were the identification of predictors for HSV-1 reactivation and the assessment of its possible prognostic impact. Overall, 41 patients met the study inclusion criteria, and 12/41 patients developed HSV-1 reactivation (29%). No independent predictors of HSV-1 reactivation were identified in the present study. No association was found between HSV-1 reactivation and mortality. Eleven out of 12 patients with HSV-1 reactivation received antiviral therapy with intravenous acyclovir. In conclusion, HSV-1 reactivation is frequently detected in intubated patients with COVID-19. An antiviral treatment in COVID-19 patients with HSV-1 reactivation and worsening respiratory function might be considered.