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Antibiotic resistance is one of the main menaces to public and individual health worldwide. In the last two decades, an increase in the detection of carbapenem-resistant Enterobacterales has been reported. The treatment of infections caused by these strains is a therapeutic challenge. The use of carbapenems may be beneficial depending on MIC value and source of infection. New drugs, with different activity against the different classes of carbapenemases, are developed showing significant benefits.

Objectives: We describe the current epidemiology, causes, and outcomes of breakthrough invasive fungal infections (BtIFI) in patients with haematologic malignancies. Methods: BtIFI in patients with ≥ 7 days of prior antifungals were prospectively diagnosed (36 months across 13 Spanish hospitals) according to revised EORTC/MSG definitions. Results: 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. Conclusions: 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. This work was funded by a grant from Gilead Sciences. P.P.-A. (JR20/00012, PI21/00498, and ICI21/00103) and C.G.-V. (FIS PI21/01640 and ICI21/00103) have received research grants funded by Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union. The funders had neither a specific role in study design or collection of data, nor in writing of the paper or decision to submit. Sí

Background The use of remdesivir has demonstrated a significant reduction in the time to recovery in patients with COVID-19. However, the impact on mortality is still controversial. Therefore, it is necessary to evaluate whether there is a specific subgroup of patients in whom an active antiviral therapy also reduces the mortality. Methods Patients admitted for >48 h in our hospital for a SARS-CoV-2 confirmed or suspected infection from February 2020 to February 2021 were retrospectively analysed. The primary outcome of the study was mortality at 30 days. Univariate and multivariate analyses were performed to identify predictors of mortality. Results In total, 2607 patients (438 receiving remdesivir and 2169 not) were included with a median (IQR) age of 65 (54–77) years and 58% were male. Four hundred and seventy-six were admitted to the ICU (18.3%) and 264 required invasive mechanical ventilation (10.1%). The global 30 day mortality rate was 10.7%. Pre-admission symptom duration of 4–6 days and ≤3 days was associated with a 1.5- and 2.5-fold increase in the mortality rate, respectively, in comparison with >6 days and treatment with remdesivir was independently associated with a lower mortality rate (OR = 0.382, 95% CI = 0.218–0.671). The analysis showed that the major difference was among patients with shorter pre-admission symptom duration ( Conclusions Patients with ≤3 days and 4–6 days from symptom onset to admission are associated with a 2.5- and 1.5-fold higher risk of death, respectively. Remdesivir was associated with 62% reduced odds of death versus standard-of-care and its survival benefit increased with shorter duration of symptoms.

Invasive fungal infection often complicates patients with severe viral infection, especially those admitted to critical care units. Severe SARS-CoV-2 infection has been no exception and a significant association with Aspergillus spp. has been documented, resulting in high patient mortality. In this summary we describe the clinical presentation, the underlying diseases most commonly linked with this association, radiological manifestations and therapeutic management of CAPA.

Objective. Controversial results on remdesivir efficacy have been reported. We aimed to report our real-life experience with the use of remdesivir from its availability in Spain. Methods. We performed a descriptive study of all patients admitted for ≥48 hours with confirmed COVID-19 who received remdesivir between the 1st of July and the 30th of September 2020. Results. A total of 123 patients out of 242 admitted with COVID-19 at our hospital (50.8%) received remdesivir. Median age was 58 years, 61% were males and 56.9 % received at least one anti-inflammatory treatment. No adverse events requiring remdesivir discontinuation were reported. The need of intensive care unit admission, mechanical ventilation and 30-days mortality were 19.5%, 7.3% and 4.1%, respectively. Conclusion. In our real-life experience, the use of remdesivir in hospitalized patients with COVID-19 was associated with a low mortality rate and good safety profile.

Objectives To describe the burden, epidemiology and outcomes of co-infections and superinfections occurring in hospitalized patients with coronavirus disease 2019 (COVID-19). Methods We performed an observational cohort study of all consecutive patients admitted for ≥48 hours to the Hospital Clinic of Barcelona for COVID-19 (28 February to 22 April 2020) who were discharged or dead. We describe demographic, epidemiologic, laboratory and microbiologic results, as well as outcome data retrieved from electronic health records. Results Of a total of 989 consecutive patients with COVID-19, 72 (7.2%) had 88 other microbiologically confirmed infections: 74 were bacterial, seven fungal and seven viral. Community-acquired co-infection at COVID-19 diagnosis was uncommon (31/989, 3.1%) and mainly caused by Streptococcus pneumoniae and Staphylococcus aureus. A total of 51 hospital-acquired bacterial superinfections, mostly caused by Pseudomonas aeruginosa and Escherichia coli, were diagnosed in 43 patients (4.7%), with a mean (SD) time from hospital admission to superinfection diagnosis of 10.6 (6.6) days. Overall mortality was 9.8% (97/989). Patients with community-acquired co-infections and hospital-acquired superinfections had worse outcomes. Conclusions Co-infection at COVID-19 diagnosis is uncommon. Few patients developed superinfections during hospitalization. These findings are different compared to those of other viral pandemics. As it relates to hospitalized patients with COVID-19, such findings could prove essential in defining the role of empiric antimicrobial therapy or stewardship strategies.

We analyzed risk factors for mortality in febrile neutropenic patients with bloodstream infections (BSI) presenting with septic shock and assessed the impact of empirical antibiotic regimens. A multicenter retrospective study (2010 to 2019) of two prospective cohorts compared BSI episodes in patients with or without septic shock. Multivariate analysis was performed to identify independent risk factors for mortality in episodes with septic shock. Of 1,563 patients with BSI, 257 (16%) presented with septic shock. Those patients with septic shock had higher mortality than those without septic shock (55% versus 15%, P 70 years (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.2 to 4.7), IEAT for Candida spp. or Gram-negative bacilli (OR, 3.8; 95% CI, 1.3 to 11.1), acute kidney injury (OR, 2.6; 95% CI, 1.4 to 4.9), and amikacin as the only active antibiotic (OR, 15.2; 95% CI, 1.7 to 134.5) were independent risk factors for mortality, while the combination of β-lactam and amikacin was protective (OR, 0.32; 95% CI, 0.18 to 0.57). Septic shock in febrile neutropenic patients with BSI is associated with extremely high mortality, especially when IEAT is administered. Combination therapy including an active β-lactam and amikacin results in the best outcomes.

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 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.

Assess the impact of viral load estimated by cycle threshold (Ct) of reverse transcription real time-polymerase chain reaction (rRT-PCR) and the days from symptoms onset on mortality in hospitalized patients with COVID19.Retrospective observational study of 782 patients with a positive rRT-PCR from a nasopharyngeal swab was performed within the first 24 h from admission. Demographic data, clinical manifestations and laboratory parameters were collected. Uni- and multivariate analyses were performed to identify factors associated with mortality at 60 days.Ct was divided into three groups and the mortality rate decreased from 27.3 to 20.7% and 9.8% for Ct values of ≤ 20, 21-25 and 25, respectively (P = 0.0001). The multivariate analysis identified as predictors of mortality, a Ct value 20 (OR 3.13, CI 95% 1.38-7.10), between 21-25 (OR 2.47, CI 95% 1.32-4.64) with respect to a Ct value 25. Days from symptoms onset is a variable associated with mortality as well (DSOA) ≤ 6 (OR 1.86, CI 95% 1.00-3.46), among other factors. Patients requiring hospital admission within 6 DSOA with a Ct value ≤ 25 had the highest mortality rate (28%).The inclusion of Ct values and DSOA in the characterization of study populations could be a useful tool to evaluate the efficacy of antivirals.

ImportanceIdentifying undetected clinical signs is imperative in the prevention of SARS-CoV-2.ObjectiveTo establish the prevalence of clinical gustatory and olfactory dysfunctions in patients with COVID-19 pneumonia. Clinical outcomes and recovery rates associated with gustatory and olfactory dysfunctions were also assessed.DesignA prospective study was performed in 80 patients admitted to Hospital Clínic of Barcelona (Spain) for COVID-19 pneumonia. Patients were re-evaluated in the ward daily until discharge. Gustatory and olfactory dysfunction symptoms were retrospectively collected from emergency room (ER) charts after first assessments. Follow-up was performed in telemedicine consultation.SettingThe single-centre study was performed in a hospitalisation ward at a university hospital.ParticipantsConsecutive patients meeting hospitalisation criteria for COVID-19 pneumonia were eligible. Study exclusion criteria were patients who could not speak, had previous gustatory and olfactory dysfunctions or whose PCR tests for SARS-CoV-19 were negative.InterventionsSystematic assessment of gustatory and olfactory symptoms with standardised questions.Outcome(s)Prevalence of gustatory and olfactory dysfunctions in patients with COVID-19 pneumonia.ResultsOf the 80 study subjects, 62.5% were male and the median age was 57 years. Half of the cohort (n=40) presented with comorbidities. The prevalence of chemosensitive disorder was 73.8% (n=59) (95% CI: 63.8 to 83.8), although self-reported symptoms were recorded in only 26.3% (n=21) of patients in the ER. Gustatory and olfactory dysfunctions were observed in 58.8% (n=47) and 55% (n=44) of cases, respectively. They were also the first symptoms in 25% (n=20) of patients. Anosmia was associated with ageusia, OR: 7, 95% CI: 2.3 to 21.8, p=0.001). No differences in clinical outcomes were observed when patients with and without gustatory and olfactory dysfunctions were compared. Recovery rates were 20% (n=10) and 85% (n=42) at days 7 and 45, respectively.ConclusionThe prevalence of gustatory and olfactory dysfunctions in COVID-19 pneumonia was much higher than in self-report. Presence of gustatory and olfactory dysfunctions was not a predictor of clinical outcomes.

We aimed to describe epidemiology changes in bloodstream infections (BSI) episodes in hematopoietic stem cell transplant (HSCT) recipients throughout a 25-year period (1993–2017), comparing five-year time spans, and we evaluate their impact on inappropriate empirical antibiotic treatment (IEAT) and mortality. During the study period, 1164 BSI episodes were documented in patients undergoing HSCT (71.6% allogenic and 29% autologous). A significant decrease in gram-positive cocci (GPC) and increase in gram-negative bacilli (GNB) were observed (p

Background We aimed to describe the epidemiology of catheter-related bloodstream infections (CRBSIs) in onco-hematological neutropenic patients during a 25-year study period, to evaluate the risk factors for Gram-negative bacilli (GNB) CRBSI, as well as rates of inappropriate empirical antibiotic treatments (IEAT) and mortality. Materials/Methods All consecutive episodes of CRBSIs were prospectively collected (1994–2018). Changing epidemiology was evaluated comparing five-year time spans. A multivariate regression model was built to evaluate risk factors for GNB CRBSIs. Results 482 monomicrobial CRBSIs were documented. The proportion of CRBSIs among all BSIs decreased over time from 41.2% to 15.8% (pP. aeruginosa increased and comprised up to 40% of all GNB. Independent factors related with GNB-CRBSIs were: longer duration of in-situ catheter (OR 1.007; 95%CI 1.004–1.011), older age (OR 1.016; 95%CI 1.001–1.033), prior antibiotic treatment with penicillins (OR 2.716; 95%CI 1.306–5.403), and current antibiotic treatment with glycopeptides (OR 1.931; 95%CI 1.001–3.306). IEATs were administered to 30.7% of patients, with the highest percentage among MDR P. aeruginosa (76.9%) and S. maltophillia (92.9%). Mortality rate was greater among GNB than GPC-CRBSI (14.4% vs 5.4%; p = 0.002), with mortality increasing over time (from 4.5% to 11.2%; p = 0.003). Conclusion A significant shift towards GNB-CRBSIs was observed. Secondarily, and coinciding with an increasing number of GNB-MDR infections, mortality increased over time.

Highlights • Almost two thirds of patients with SARS-CoV-2 infection present with hypocalcemia at hospital admission. • Hypocalcemia at admission is related to high oxygen support requirement any time during hospitalization. • Patients with hypocalcemia at admission had two times more probability to be admitted to the Intensive Care Unit during hospitalization than patients with normal calcium at admission., Background Calcium is an essential ion for pathogen survival and virulence and is involved in the regulation of the inflammatory response. Hypocalcemia is a common laboratory finding in critically ill patients. Data regarding levels of calcium in SARS-CoV-2 infection is scarce. Patients with SARS-CoV-2 infection who present with hypocalcemia could have a worse outcome. Methods We performed a retrospective analysis of hospitalized patients with SARS-CoV-2 infection and included all patients who had any serum calcium measurement in the first 72 hours since hospital admission. Main objective was to investigate the relation of low serum calcium with adverse outcome, measured by the requirement of high oxygen support – defined as high flow nasal cannula oxygen, non-invasive mechanical ventilation and/or invasive ventilation-, intensive care unit admission or death. Results A total of 316 patients were included in the study. Median age was 65 years (IQR 55-74), 65% were men. Hypocalcemia within 72 hours since hospital admission was present in 63% of patients. A higher number of patients in the hypocalcemia group required high oxygen support during hospitalization (49% vs 32%; p = 0,01) and were admitted to the ICU (42% vs 26%; p = 0,005). No differences in mortality were observed between groups. Conclusions Hypocalcemia is frequent in hospitalized patients with SARS-CoV-2 infection and can identify patients with worse outcome. More studies are needed to understand the role of calcium metabolism in SARS-CoV-2 infection and to address the clinical implications and therapeutic interventions it might have.

Around 2·5 million deaths and more than 110 million COVID-19 cases have been reported globally. Although it initially appeared that HIV infection was not a risk factor for COVID-19 or more severe disease, more recent large studies suggest that people living with HIV (particularly with low CD4 cell counts or untreated HIV infection) might have a more severe clinical course than those who are HIV-negative. Moreover, the COVID-19 pandemic has disrupted HIV prevention and treatment services worldwide, creating huge challenges to the continuity of essential activities. We have reviewed the most relevant features of COVID-19 in people living with HIV and highlighted topics where further research is required.

In recent years, important epidemiologic changes have been described in hematopoietic stem cell transplantation (HSCT) recipients with bloodstream infection (BSI), with increases in gram-negative bacilli and multidrug resistant (MDR) gram-negative bacilli. These changes have been linked to a worrisome increase in mortality. We aimed to define the risk factors for mortality of HSCT patients experiencing BSI. All episodes of BSI in patients with HSCT between 2008 and 2017 were prospectively collected. Multivariate analyses were performed. A total of 402 BSI episodes were documented in 293 patients who had undergone HSCT (75.4% allogenic, 32.3% autologous, 19.3% second HSCT). The median time from HSCT to BSI was 62 days (interquartile range, 9 to 182 days). Gram-positive cocci accounted for 56.7% of the episodes; gram-negative bacilli, for 42%. The most common microorganisms were coagulase-negative staphylococci (30.6%) and Pseudomonas aeruginosa (15.9%). MDR gram-negative bacilli caused 11.9% of all episodes. Clinical characteristics, source of BSI, etiology, and outcomes changed depending on time since HSCT. Globally, 26.6% of episodes were treated with inappropriate empiric antibiotic therapy, more frequently in BSI episodes caused by P. aeruginosa, MDR P. aeruginosa, and MDR gram-negative bacilli. The 30-day mortality was 19.2%. Independent risk factors for mortality were BSI occurring ≥30 days after HSCT (odds ratio [OR], 11.21; 95% confidence interval [CI], 4.63 to 27.19), shock (OR, 7.10; 95% CI, 2.98 to 16.94), BSI caused by MDR P. aeruginosa (OR, 4.45; 95% CI, 1.12 to 17.72), and inappropriate empiric antibiotic therapy for gram-negative bacilli or Candida spp. (OR, 3.73; 95% CI, 1.27 to 10.89). HSCT recipients experiencing BSI have high mortality related to host and procedure factors, causative microorganism, and empiric antibiotic therapy. Strategies to identify HSCT recipients at risk of MDR P. aeruginosa and reducing inappropriate empiric antibiotic therapy are paramount to reduce mortality.

Background We aimed to describe the current rates of inappropriate empirical antibiotic treatment (IEAT) in oncohematological patients with febrile neutropenia (FN) and its impact on mortality. Methods This was a multicenter prospective study of all episodes of bloodstream infection (BSI) in high-risk FN patients (2006–2017). Episodes receiving IEAT were compared with episodes receiving appropriate empirical therapy. Adherence to Infectious Diseases Society of America (IDSA) recommendations was evaluated. Multivariate analysis was performed to identify independent risk factors for mortality in Pseudomonas aeruginosa episodes. Results Of 1615 episodes, including Escherichia coli (24%), coagulase-negative staphylococci (21%), and P. aeruginosa (16%), 394 (24%) received IEAT despite IDSA recommendations being followed in 87% of cases. Patients with multidrug-resistant gram-negative bacilli (MDR-GNB), accounting for 221 (14%) of all isolates, were more likely to receive IEAT (39% vs 7%, P < .001). Overall mortality was higher in patients with GNB BSI who received IEAT (36% vs 24%, P = .004); when considering individual microorganisms, only patients with infection caused by P. aeruginosa experienced a significant increase in mortality when receiving IEAT (48% vs 31%, P = .027). Independent risk factors for mortality in PA BSI (odds ratio [95% confidence interval] were IEAT (2.41 [1.19–4.91]), shock at onset (4.62 [2.49–8.56]), and pneumonia (3.01 [1.55–5.83]). Conclusions IEAT is frequent in high-risk patients with FN and BSI, despite high adherence to guidelines. This inappropriate treatment primarily impacts patients with P. aeruginosa–related BSI mortality and in turn is the only modifiable factor to improve outcomes.

Objectives To assess risk factors for multidrug-resistant Pseudomonas aeruginosa (MDR-PA) infection in neutropenic patients. Methods Single-centre retrospective analysis of consecutive bloodstream infection (BSI) episodes (2004–2017, Barcelona). Two multivariate regression models were used at BSI diagnosis and P. aeruginosa detection. Significant predictors were used to establish rules for stratifying patients according to MDR-PA BSI risk. Results Of 661 Gram-negative BSI episodes, 190 (28.7%) were caused by P. aeruginosa (70 MDR-PA). Independent factors associated with MDR-PA among Gram-negative organisms were haematological malignancy (OR 3.30; 95% CI 1.15–9.50), pulmonary source of infection (OR 7.85; 95% CI 3.32–18.56), nosocomial-acquired BSI (OR 3.52; 95% CI 1.74–7.09), previous antipseudomonal cephalosporin (OR 13.66; 95% CI 6.64–28.10) and piperacillin/tazobactam (OR 2.42; 95% CI 1.04–5.63), and BSI occurring during ceftriaxone (OR 4.27; 95% CI 1.15–15.83). Once P. aeruginosa was identified as the BSI aetiological pathogen, nosocomial acquisition (OR 7.13; 95% CI 2.87–17.67), haematological malignancy (OR 3.44; 95% CI 1.07–10.98), previous antipseudomonal cephalosporin (OR 3.82; 95% CI 1.42–10.22) and quinolones (OR 3.97; 95% CI 1.37–11.48), corticosteroids (OR 2.92; 95% CI 1.15–7.40), and BSI occurring during quinolone (OR 4.88; 95% CI 1.58–15.05) and β-lactam other than ertapenem (OR 4.51; 95% CI 1.45–14.04) were independently associated with MDR-PA. Per regression coefficients, 1 point was assigned to each parameter, except for nosocomial-acquired BSI (3 points). In the second analysis, a score >3 points identified 60 (86.3%) out of 70 individuals with MDR-PA BSI and discarded 100 (84.2%) out of 120 with non-MDR-PA BSI. Conclusions A simple score based on demographic and clinical factors allows stratification of individuals with bacteraemia according to their risk of MDR-PA BSI, and may help facilitate the use of rapid MDR-detection tools and improve early antibiotic appropriateness.