Abstract
Hospitalized patients with coronavirus disease 2019 (COVID-19) experiencing respiratory symptoms have different complications (inflammatory, co-infection, and thrombotic) that are ...identifiable by analytics patterns. Personalized treatment decisions decreased early mortality (odds ratio OR .144; 95% confidence interval CI .03–.686; P = .015). Increasing age (OR 1.06; P = .038) and therapeutic effort limitation (OR 9.684; P < .001) were associated with higher mortality.
Ceftazidime-avibactam has in vitro activity against Gram-negative bacilli that produce Class A, C and some D β-lactamases, and has been successfully used in the treatment of infections caused by ...cephalosporin and carbapenem-resistant Enterobacteriaceae. However, actual experience in the treatment of OXA-48 carbapenemase-producing Enterobacteriaceae (CPE) is limited.
To review the characteristics and prognosis of OXA-48 CPE infections treated with ceftazidime-avibactam since introduction of the drug to the current centre during the period October 2014 to December 2016.
Retrospective assessment of episodes of infection caused by OXA-48 CPE treated with ceftazidime-avibactam, analysing data collected from infection diagnosis until 90 days after the end of treatment.
Twenty-four episodes were analysed. Ceftazidime-avibactam was given as the initial definitive treatment in 15 (62.5%) and as salvage therapy in nine (37.5%). Intraabdominal (seven, 29%), urinary (six, 25%) and respiratory (five, 21%) were the most common sources. The 30-day and 90-day mortality rates were 8.3% and 20.8%, respectively. Clinical cure at 30 days was achieved in 62.5% of episodes. Four (16.7%) patients had adverse events, two of them were related to impaired renal function. Among patients who finished the treatment with ceftazidime-avibactam, seven (35%) were diagnosed with infection recurrence within 90 days of the end of treatment.
From experience, ceftazidime-avibactam is an effective drug for treating infections due to OXA-48 CPE. From these results a better safety profile than the current best available therapy could be expected.
There is no reliable microbiological marker to guide the indication and the response to antiviral treatment in patients with coronavirus disease 2019 (COVID-19). We aimed to evaluate the dynamics of ...subgenomic RNA (sgRNA) in patients with COVID-19 before and after receiving treatment with remdesivir.
We included consecutive patients admitted for COVID-19 who received remdesivir according to our institutional protocol and accepted to participate in the study. A nasopharyngeal swab for quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was collected at baseline and after 3 and 5 days of treatment with remdesivir. Genomic and sgRNA were analyzed in those samples and main comorbidities and evolution were collected for the analyses. The main outcomes were early discharge (≤10 days) and 30-day mortality.
A total of 117 patients were included in the study, of whom 24 had a negative sgRNA at baseline, with 62.5% (15/24) receiving early discharge (≤10 days) and no deaths in this group. From the 93 remaining patients, 62 had a negative sgRNA at day 5 with 37/62 (59.6%) with early discharge and a mortality rate of 4.8% (3/62). In the subgroup of 31 patients with positive sgRNA after 5 days of remdesivir, the early discharge rate was 29% (9/31) and the mortality rate was 16.1% (5/31). In multivariable analyses, the variables associated with early discharge were negative sgRNA at day 3 and not needing treatment with corticosteroids or intensive care unit admission.
Qualitative sgRNA could help in monitoring the virological response in patients who receive remdesivir. Further studies are needed to confirm these findings.
We describe the current epidemiology, causes, and outcomes of breakthrough invasive fungal infections (BtIFI) in patients with haematologic malignancies.
BtIFI in patients with ≥ 7 days of prior ...antifungals were prospectively diagnosed (36 months across 13 Spanish hospitals) according to revised EORTC/MSG definitions.
121 episodes of BtIFI were documented, of which 41 (33.9%) were proven; 53 (43.8%), probable; and 27 (22.3%), possible. The most frequent prior antifungals included posaconazole (32.2%), echinocandins (28.9%) and fluconazole (24.8%)—mainly for primary prophylaxis (81%). The most common haematologic malignancy was acute leukaemia (64.5%), and 59 (48.8%) patients had undergone a hematopoietic stem-cell transplantation. Invasive aspergillosis, principally caused by non-fumigatus Aspergillus, was the most frequent BtIFI with 55 (45.5%) episodes recorded, followed by candidemia (23, 19%), mucormycosis (7, 5.8%), other moulds (6, 5%) and other yeasts (5, 4.1%). Azole resistance/non-susceptibility was commonly found. Prior antifungal therapy widely determined BtIFI epidemiology. The most common cause of BtIFI in proven and probable cases was the lack of activity of the prior antifungal (63, 67.0%). At diagnosis, antifungal therapy was mostly changed (90.9%), mainly to liposomal amphotericin-B (48.8%). Overall, 100-day mortality was 47.1%; BtIFI was either the cause or an essential contributing factor to death in 61.4% of cases.
BtIFI are mainly caused by non-fumigatus Aspergillus, non-albicans Candida, Mucorales and other rare species of mould and yeast. Prior antifungals determine the epidemiology of BtIFI. The exceedingly high mortality due to BtIFI warrants an aggressive diagnostic approach and early initiation of broad-spectrum antifungals different than those previously used.
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•BtIFI are caused by non-fumigatus Aspergillus, non-albicans Candida, Mucorales and other rare species of mould and yeast.•Prior antifungals determine the epidemiology of BtIFI.•BtIFI is associated with an exceedingly high mortality.•Aggressive diagnostic approach and early change of antifungal class is warranted.
We aimed to determine the role of serum cytokine expression in invasive aspergillosis (IA) diagnosis and outcome prediction in hematologic patients. In this multicenter study, serum cytokines (IL6, ...IL10, INF-gamma, IL12, IL4, TNF-alpha, IL17 and IL23) were prospectively recruited from all consecutive patients with hematologic malignances at IA diagnosis and compared to control patients matched by center, age, baseline disease and therapeutic regimen. We included 36 patients with IA and 36 controls. Serum levels of IL6 and IL10 cytokines on day 0 were significantly increased in patients with IA when compared to controls (p = 0.001 and p = 0.025, respectively), even in those who were neutropenic. No differences were observed for the other cytokines. IL6 and IL10 predicted IA with an area under the ROC curve of 0.74 (95% CI 0.62-0.86) and 0.64 (95% CI 0.51-0.77), respectively. The best cut-off point in predicting IA was 20.85 pg/mL for IL6 (sensitivity 72.2%; specificity 77.8%; PPV 76.5% and NPV 73.7%), and 0.045 pg/mL for IL10 (sensitivity 62.9%; specificity 63.9%; PPV 62.9% and NPV 63.9%). IL6 levels were associated with increased mortality, with the best cut-off value being 65.59 pg/mL in mortality prediction. In conclusion, in addition to current tests in place, IL6 and IL10 levels-as measured in plasma-may help clinicians diagnose IA. High levels of IL6 at IA diagnosis are related with worse outcomes.
•De-escalation from echinocandins to azoles is a safe strategy.•De-escalation showed no higher 30-day mortality compared with non-de-escalation.•De-escalation showed and a trend toward greater ...clinical and microbiological cure.•Our results support ESCMID and IDSA recommendations to step-down antifungals.
De-escalation (DES) from echinocandins to azoles is recommended by several medical societies in Candida infections. We summarise the evidence of DES on clinical and microbiological cure and 30-day survival and compare it with continuing the treatment with echinocandins (non-DES).
We searched MEDLINE, Embase, Web of Science and Scopus. Studies describing DES in inpatients and reporting any of the outcomes evaluated were included. Pooled estimates of the tree outcomes were calculated with a fixed or random-effects model. Heterogeneity was explored stratifying by subgroups and via meta-regression. This systematic review is registered with PROSPERO (CRD42023475486).
Of 1853 records identified, 9 studies were included, totalling 1575 patients. Five studies stepped-down to fluconazole; one to voriconazole and three to any of azoles. The mean day of DES was 5.2 (4.6-6.5) days. The clinical cure OR was 1.29 (95% CI: 0.88-1.88); the microbiological cure 1.62 (95% CI: 0.71-3.71); and 30-day survival 2.17 (95% CI: 1.09-4.32). The 30-day survival data into subgroups showed higher effect on critically ill patients and serious-risk bias studies. Meta-regression did not identify significant effect modifiers.
DES is a safe strategy; it showed no higher 30-day mortality and a trend towards greater clinical and microbiological cure.
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We aimed to describe the clinical outcomes and duration of viral shedding in high-risk patients with haematological malignancies hospitalized with COVID-19 during Omicron variant predominance who ...received early treatment with antivirals.
We conducted a prospective observational study on high-risk haematological patients admitted in our hospital between December 2021 and March 2022. We performed detection techniques on viral subgenomic mRNAs until negative results were obtained to document active, prolonged viral replication.
This analysis included 60 consecutive adults with high-risk haematological malignancies and COVID-19. All of these patients underwent early treatment with remdesivir. Thirty-two (53%) patients received combined antiviral strategies, with sotrovimab or hyperimmune plasma being added to remdesivir. The median length of viral replication-as measured by real-time RT-PCR and/or subgenomic RNA detection-was 20 (IQR 14-28) days. Prolonged viral replication (6 weeks after diagnosis) was documented in six (10%) patients. Only two patients had prolonged infection for more than 2 months. Overall mortality was 5%, whereas COVID-19-related mortality was 0%.
Current outcomes of high-risk patients with haematological malignancies hospitalized with COVID-19 during Omicron variant predminance are good with the use of early antiviral strategies. Persistent viral shedding is uncommon.
Abstract
Objectives
To describe current resistance to the β-lactams empirically recommended in the guidelines in bloodstream infection (BSI) episodes caused by Gram-negative bacilli (GNB).
Methods
...Retrospective, multicentre cohort study of the last 50 BSI episodes in haematological patients across 14 university hospitals in Spain. Rates of inappropriate empirical antibiotic therapy (IEAT) and impact on mortality were evaluated.
Results
Of the 700 BSI episodes, 308 (44%) were caused by GNB, mainly Escherichia coli (141; 20.1%), Klebsiella spp. (56; 8%) and Pseudomonas aeruginosa (48; 6.9%). Among GNB BSI episodes, 80 (26%) were caused by MDR isolates. In those caused by Enterobacterales, 25.8% were ESBL producers and 3.5% were carbapenemase producers. Among P. aeruginosa BSI episodes, 18.8% were caused by MDR isolates. Overall, 34.7% of the isolated GNB were resistant to at least one of the three β-lactams recommended in febrile neutropenia guidelines (cefepime, piperacillin/tazobactam and meropenem). Despite extensive compliance with guideline recommendations (91.6%), 16.6% of BSI episodes caused by GNB received IEAT, which was more frequent among MDR GNB isolates (46.3% versus 6.1%; P < 0.001). Thirty day mortality was 14.6%, reaching 21.6% in patients receiving IEAT.
Conclusions
Current resistance to empirical β-lactams recommended in febrile neutropenia guidelines is exceedingly high and IEAT rates are greater than desired. There is an urgent need to adapt guidelines to current epidemiology and better identify patients with a high risk of developing MDR GNB infection.
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