Post-CART-T Cell Infection: Etiology, pathogenesis, and therapeutic approaches.

Chimeric antigen receptor (CAR) T cell therapy targeting CD-19 has revolutionized the treatment of refractory B-cell malignancies. However, patients undergoing this therapy face an increased risk of infections due to compromised immune function, lymphodepleting chemotherapy, hospitalization, and therapy-related complications such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome. Patients with systemic corticosteroid use, low immunoglobulin levels, and severe CRS, are at higher risk of infection. This review article highlights the spectrum of infections encountered in CAR T cell therapy, including bacterial, viral, and fungal infections. Following consensus guidelines for vaccination and immunoglobulin replacement is recommended. Clear criteria for antibiotic usage and vaccinating household members against respiratory viruses are crucial. Understanding the risk factors, spectrum of infections, and implementing appropriate prophylactic measures are essential to optimize outcomes in patients undergoing CAR T cell therapy. By prioritizing infection prevention strategies, healthcare professionals can effectively improve patient care.

Identifying the most important data for research in the field of infectious diseases: thinking on the basis of artificial intelligence.

OBJECTIVE: Clinical data on which artificial intelligence (AI) algorithms are trained and tested provide the basis to improve diagnosis or treatment of infectious diseases (ID). We aimed to identify important data for ID research to prioritise efforts being undertaken in AI programmes. METHODS: We searched for 1,000 articlesfrom high-impact ID journals on PubMed, selecting 288 of the latest articles from 10 top journals. We classified them into structured or unstructured data. Variables were homogenised and grouped into the following categories: epidemiology, admission, demographics, comorbidities, clinical manifestations, laboratory, microbiology, other diagnoses, treatment, outcomes and other non-categorizable variables. RESULTS: 4,488 individual variables were collected, from the 288 articles. 3,670 (81.8%) variables were classified as structured data whilst 818 (18.2%) as unstructured data. From the structured data, 2,319 (63.2%) variables were classified as direct-retrievable from electronic health records-whilst 1,351 (36.8%) were indirect. The most frequent unstructured data were related to clinical manifestations and were repeated across articles. Data on demographics, comorbidities and microbiology constituted the most frequent group of variables. CONCLUSIONS: This article identified that structured variables have comprised the most important data in research to generate knowledge in the field of ID. Extracting these data should be a priority when a medical centre intends to start an AI programme for ID. We also documented that the most important unstructured data in this field are those related to clinical manifestations. Such data could easily undergo some structuring with the use of semi-structured medical records focusing on a few symptoms.

Recommendations on the use of azole antifungals in hematology-oncology patients.

The administration of antifungals for therapeutic and, especially, prophylactic purposes is virtually a constant in patients requiring hematology-oncology treatment. Any attempt to prevent or treat Aspergillus or Mucor infections requires the administration of some drugs in the azole group, which include voriconazole, posaconazole and isavuconazole, noted for their activity against these pathogens. One very relevant aspect is the potential risk of interaction when associated with one of the antineoplastic drugs used to treat hematologic tumors, with serious complications. In this regard, acalabrutinib, bortezomib, bosutinib, carfilzomib, cyclophosphamide, cyclosporine A, dasatinib, duvelisib, gilteritinib, glasdegib, ibrutinib, imatinib, nilotinib, ponatinib, prednisone, ruxolitinib, tacrolimus, all-transretinoic acid, arsenic trioxide, venetoclax, or any of the vinca alkaloids, are very clear examples of risk, in some cases because their clearance is reduced and in others because of increased risk of QTc prolongation, which is particularly evident when the drug of choice is voriconazole or posaconazole.

Carriage of multidrug-resistant Gram-negative bacilli: duration and risk factors.

Identification of risk factors influencing the duration of carriage of multidrug-resistant Gram-negative bacilli (MDR-GNB) may be useful for infection control. The aim of this study is to estimate the impact of several factors collected for routine hospital surveillance on the duration of carriage of selected MDR-GNB. From January 2015 to July 2021, patients with at least two clinical/surveillance samples positive for MDR-GNB different from ESBL-producing E. coli or AmpC - exclusively producing Enterobacterales were assessed. Microorganisms, age, number of admissions, clinical or rectal sample, sex, and admission service were evaluated as risk factors. Multivariate analysis was performed by a Cox proportional hazard model. A total of 1981 episodes of colonization were included. Involved microorganisms were ESBL-Klebsiella pneumoniae (KP) in 1057 cases (53.4%), other ESBL-non-E. coli Enterobacterales in 91 (4.6%), OXA-48-KP in 263 (13.3%), KPC-KP in 90 (4.5%), VIM-KP in 29 (1.5%), carbapenemase-producing non-KP Enterobacterales (CP-non-KP) in 124 (6.3%), and MDR Pseudomonas aeruginosa (MDR-PAER) in 327 (16.5%). No differences in duration of colonization were observed among ESBL-KP (median colonization time 320 days), ESBL-non-E. coli Enterobacterales (226 days), OXA48-KP (305 days), and MDR-PAER (321 days). For each group, duration of colonization was significantly longer than that of KPC-KP (median colonization time 60 days), VIM-KP (138 days), and CP-non-KP (71 days). Male sex (HR = 0.88; 95% CI 0.78-0.99), detection in Hepatology-Gastroenterology (HR = 0.71; 95% CI 0.54-0.93), clinical sample (HR = 0.61; 95% CI 0.53-0.69), and > 2 admissions after first detection (HR = 0.47; 95% CI 0.42-0.52) were independent predictors of longer carriage, whereas VIM-KP (HR = 1.61; 95% CI 1.04-2.48), KPC-KP (HR = 1.85; 95% CI 1.49-2.3), and CP-non-KP (HR = 1.92; 95% CI 1.49-2.47) were associated with shorter colonization time. Duration of colonization was significantly longer for ESBL-KP, other ESBL-non-E. coli Enterobacterales, OXA-48-KP, and MDR-PAER. For these microorganisms, prolonging surveillance up to 2.5-3 years should be considered. Male sex, clinical sample, multiple readmissions, admission service, and type of microorganism are independent predictors of the duration of carriage.

Antimicrobial resistance in Gram-negative bacilli in Spain: an experts' view.

BACKGROUND: Antibiotic resistance in Gram-negative bacilli poses a serious problem for public health. In hospitals, in addition to high mortality rates, the emergence and spread of resistance to practically all antibiotics restricts therapeutic options against serious and frequent infections. OBJECTIVE: The aim of this work is to present the views of a group of experts on the following aspects regarding resistance to antimicrobial agents in Gram-negative bacilli: 1) the current epidemiology in Spain, 2) how it is related to local clinical practice and 3) new therapies in this area, based on currently available evidence. METHODS: After reviewing the most noteworthy evidence, the most relevant data on these three aspects were presented at a national meeting to 99 experts in infectious diseases, clinical microbiology, internal medicine, intensive care medicine, anaesthesiology and hospital pharmacy. RESULTS AND CONCLUSIONS: Subsequent local debates among these experts led to conclusions in this matter, including the opinion that the approval of new antibiotics makes it necessary to train the specialists involved in order to optimise how they use them and improve health outcomes; microbiology laboratories in hospitals must be available throughout a continuous timetable; all antibiotics must be available when needed and it is necessary to learn to use them correctly; and the Antimicrobial Stewardship Programs (ASP) play a key role in quickly allocating the new antibiotics within the guidelines and ensure appropriate use of them.

Antiviral drugs against SARS-CoV-2.

The use of antiviral drugs represents an important progress in the therapeutic management of COVID-19, leading to a substantial reduction of SARS-CoV-2-related complications and mortality. In immunocompetent host, peak viral replication occurs around the symptom's onset, and it prolongs for 5 to 7 days that is the window of opportunity for giving an antiviral. Accordingly, early and rapid diagnostic of the infection in the outpatient clinic is essential as well as the availability of oral agents that can be easily prescribe. Remdesivir has demonstrated its efficacy in hospitalized patients requiring oxygen support and in mild/moderate cases to avoid the hospitalization, however, the intravenous administration limits its use among outpatients. Molnupiravir and nirmatrelvir/ritonavir are potent oral antiviral agents. In the present review we discuss the potential targets against SARS-CoV-2, and an overview of the main characteristics and clinical results with the available antiviral agents for the treatment of SARS-CoV-2.

New treatments for multidrug-resistant non-fermenting Gram-negative bacilli Infections.

Ceftolozane/tazobactam, ceftazidime/avibactam and cefiderocol belong to a novel generation of antibiotics that correspond with the ß-lactam family. It is necessary to having new options in treating infections caused by Gram-negative, non-fermenting multidrug-resistant bacilli due to the significant increase in multidrug resistance in the last decades. Knowing the main characteristics of each drug is key for correct use.

A systematic literature review and expert consensus on risk factors associated to infection progression in adult patients with respiratory tract or rectal colonisation by carbapenem-resistant Gram-negative bacteria.

OBJECTIVE: Risk factors (RFs) associated with infection progression in patients already colonised by carbapenem-resistant Gram-negative bacteria (CRGNB) have been addressed in few and disperse works. The aim of this study is to identify the relevant RFs associated to infection progression in patients with respiratory tract or rectal colonisation. METHODS: A systematic literature review was developed to identify RFs associated with infection progression in patients with CRGNB respiratory tract or rectal colonisation. Identified RFs were then evaluated and discussed by the expert panel to identify those that are relevant according to the evidence and expert's experience. RESULTS: A total of 8 articles were included for the CRGNB respiratory tract colonisation and 21 for CRGNB rectal colonisation, identifying 19 RFs associated with pneumonia development and 44 RFs associated with infection progression, respectively. After discussion, the experts agreed on 13 RFs to be associated with pneumonia development after respiratory tract CRGNB colonisation and 33 RFs to be associated with infection progression after rectal CRGNB colonisation. Respiratory tract and rectal colonisation, previous stay in the ICU and longer stay in the ICU were classified as relevant RF independently of the pathogen and site of colonisation. Previous exposure to antibiotic therapy or previous carbapenem use were also common relevant RF for patients with CRGNB respiratory tract and rectal colonisation. CONCLUSIONS: The results of this study may contribute to the early identification of CRGNB colonized patients at higher risk of infection development, favouring time-to-effective therapy and improving health outcomes.

Correction to: Early Stepdown From Echinocandin to Fluconazole Treatment in Candidemia: A Post Hoc Analysis of Three Cohort Studies.

[This corrects the article DOI: 10.1093/ofid/ofab250.].

COVID-19 and fungal infections: Etiopathogenesis and therapeutic implications.

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.

Early Stepdown From Echinocandin to Fluconazole Treatment in Candidemia: A Post Hoc Analysis of Three Cohort Studies.

BACKGROUND: There are no clear criteria for antifungal de-escalation after initial empirical treatments. We hypothesized that early de-escalation (ED) (within 5 days) to fluconazole is safe in fluconazole-susceptible candidemia with controlled source of infection. METHODS: This is a multicenter post hoc study that included consecutive patients from 3 prospective candidemia cohorts (2007-2016). The impact of ED and factors associated with mortality were assessed. RESULTS: Of 1023 candidemia episodes, 235 met inclusion criteria. Of these, 54 (23%) were classified as the ED group and 181 (77%) were classified as the non-ED group. ED was more common in catheter-related candidemia (51.9% vs 31.5%; P = .006) and episodes caused by Candida parapsilosis, yet it was less frequent in patients in the intensive care unit (24.1% vs 39.2%; P = .043), infections caused by Nakaseomyces glabrata (0% vs 9.9%; P = .016), and candidemia from an unknown source (24.1% vs 47%; P = .003). In the ED and non-ED groups, 30-day mortality was 11.1% and 29.8% (P = .006), respectively. Chronic obstructive pulmonary disease (odds ratio [OR], 3.97; 95% confidence interval [CI], 1.48-10.61), Pitt score > 2 (OR, 4.39; 95% CI, 1.94-9.20), unknown source of candidemia (OR, 2.59; 95% CI, 1.14-5.86), candidemia caused by Candida albicans (OR, 3.92; 95% CI, 1.48-10.61), and prior surgery (OR, 0.29; 95% CI, 0.08-0.97) were independent predictors of mortality. Similar results were found when a propensity score for receiving ED was incorporated into the model. ED had no significant impact on mortality (OR, 0.50; 95% CI, 0.16-1.53). CONCLUSIONS: Early de-escalation is a safe strategy in patients with candidemia caused by fluconazole-susceptible strains with controlled source of bloodstream infection and hemodynamic stability. These results are important to apply antifungal stewardship strategies.

Impact of the Inclusion of an Aminoglycoside to the Initial Empirical Antibiotic Therapy for Gram-Negative Bloodstream Infections in Hematological Neutropenic Patients: a Propensity-Matched Cohort Study (AMINOLACTAM Study).

To test the hypothesis that the addition of an aminoglycoside to a ß-lactam antibiotic could provide better outcomes than ß-lactam monotherapy for the initial empirical treatment of hematological neutropenic patients with subsequently documented Gram-negative bacillus (GNB) bloodstream infection (BSI), a multinational, retrospective, cohort study of GNB BSI episodes in hematological neutropenic patients in six centers (2010 to 2017) was conducted. Combination therapy (ß-lactam plus aminoglycoside) was compared to ß-lactam monotherapy. The primary endpoint was the case fatality rate, assessed at 7 and 30 days from BSI onset. Secondary endpoints were nephrotoxicity and persistent BSI. Propensity score (PS) matching was performed. Among 542 GNB BSI episodes, 304 (56%) were initially treated with combination therapy, with cefepime plus amikacin being most common (158/304 [52%]). Overall, Escherichia coli (273/304 [50.4%]) was the main etiological agent, followed by Pseudomonas aeruginosa, which predominated in the combination group (76/304 [25%] versus 28/238 [11.8%]; P < 0.001). Multidrug resistance rates were similar between groups (83/294 [28.2%] versus 63/233 [27%]; P = 0.95). In the multivariate analysis, combination therapy was associated with a lower 7-day case fatality rate (odds ratio [OR], 0.37; 95% CI, 0.14 to 0.91; P = 0.035) with a tendency toward lower mortality at 30 days (OR, 0.56; 95% CI, 0.29 to 1.08; P = 0.084). After PS matching, these differences remained for the 7-day case fatality rate (OR, 0.33; 95% CI, 0.13 to 0.82; P = 0.017). In addition, aminoglycoside use was not significantly associated with renal function impairment (OR, 1.12; 95% CI, 0.26 to 4.87; P = 0.9). The addition of an aminoglycoside to the initial empirical therapy regimen for febrile neutropenic hematological patients should be considered.

Experience with the use of siltuximab in patients with SARS-CoV-2 infection.

OBJECTIVE: The study aims to describe characteristics and clinical outcome of patients with SARS-CoV-2 infection that received siltuximab according to a protocol that aimed to early block the activity of IL-6 to avoid the progression of the inflammatory flare. METHODS: Retrospective review of the first 31 patients with SARS-CoV-2 treated with siltuximab, in Hospital Clinic of Barcelona or Hospital Universitario Salamanca, from March to April 2020 with positive polymerase-chain reaction (PCR) from a nasopharyngeal swab. RESULTS: The cohort included 31 cases that received siltuximab with a median (IQR) age of 62 (56-71) and 71% were males. The most frequent comorbidity was hypertension (48%). The median dose of siltuximab was 800 mg ranging between 785 and 900 mg. 7 patients received siltuximab as a salvage therapy after one dose of tocilizumab. At the end of the study, a total of 26 (83.9) patients had been discharged alive and the mortality rate was 16.1% but only 1 out of 24 that received siltuximab as a first line option (4%). CONCLUSIONS: Siltuximab is a well-tolerated alternative to tocilizumab when administered as a first line option in patients with COVID-19 pneumonia within the first 10 days from symptoms onset and high C-reactive protein.

Tocilizumab reduces the risk of ICU admission and mortality in patients with SARS-CoV-2 infection.

OBJECTIVE: In some patients the immune response triggered by SARS-CoV-2 is unbalanced, presenting an acute respiratory distress syndrome which in many cases requires intensive care unit (ICU) admission. The limitation of ICU beds has been one of the major burdens in the management around the world; therefore, clinical strategies to avoid ICU admission are needed. We aimed to describe the influence of tocilizumab on the need of transfer to ICU or death in non-critically ill patients. METHODS: A retrospective study of 171 patients with SARS-CoV-2 infection that did not qualify as requiring transfer to ICU during the first 24h after admission to a conventional ward, were included. The criteria to receive tocilizumab was radiological impairment, oxygen demand or an increasing of inflammatory parameters, however, the ultimate decision was left to the attending physician judgement. The primary outcome was the need of ICU admission or death whichever came first. RESULTS: A total of 77 patients received tocilizumab and 94 did not. The tocilizumab group had less ICU admissions (10.3% vs. 27.6%, P=0.005) and need of invasive ventilation (0 vs 13.8%, P=0.001). In the multivariable analysis, tocilizumab remained as a protective variable (OR: 0.03, CI 95%: 0.007-0.1, P=0.0001) of ICU admission or death. CONCLUSIONS: Tocilizumab in early stages of the inflammatory flare could reduce an important number of ICU admissions and mechanical ventilation. The mortality rate of 10.3% among patients receiving tocilizumab appears to be lower than other reports. This is a non-randomized study and the results should be interpreted with caution.

[A systematic review and expert's analysis of risk factors of infections in adults due to carbapenem-resistant Pseudomonas aeruginosa or Acinetobacter baumannii in Spain]. / Revisión sistemática de la literatura y análisis de expertos sobre los factores de riesgo asociados a infecciones causadas por Pseudomonas aeruginosa o Acinetobacter baumannii resistentes a carbapenémicos en pacientes adultos en España.

OBJECTIVE: The aim of the study is to identify risk factors associated to infections caused by carbapenem-resistant Pseudomonas aeruginosa (CRPA) and carbapenem-resistant Acinetobacter baumannii (CRAB) in adult patients through a systematic literature review, classify them according to their importance and provide recommendations by experts in the Spanish context. METHODS: We developed a systematic literature review to identify risk factors associated to CRPA or CRAB infections and they were evaluated and discussed by a multidisciplinary panel of experts. RESULTS: There were included 29 studies for P. aeruginosa and 23 for A. baumannii out of 593 identified through systematic literature review. We identified 38 risk factors for P. aeruginosa and 36 for A. baumannii. After risk factor evaluation by the panel of experts, results for CRPA were: 11 important, 10 slightly important and 15 unimportant risk factors; and for CRAB were: 9 important, 5 slightly important and 19 unimportant risk factors. For both pathogens, previous use of antibiotics and hospitalization were important risk factors. CONCLUSIONS: We could identify the main risk factors associated to CRPA and CRAB through literature review. There is a need for developing additional studies with higher levels of evidence to identify sooner and better infected patients through associated risk factors.

Real-life use of remdesivir in hospitalized patients with COVID-19.

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. CONCLUSIONS: 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.

Recomendaciones para la vacunación en pacientes con esclerosis múltiple candidatos a terapias inmunosupresoras: documento de consenso español / Recommendations for vaccination in patients with multiple sclerosis who are eligible for immunosuppressive therapies: Spanish consensus statement

ANTECEDENTES: La reciente aparición de terapias de alta efectividad para el tratamiento de la esclerosis múltiple (EM), con potencial riesgo de complicaciones infecciosas, obliga plantear estrategias de prevención y minimización de riesgos. La vacunación constituye una parte esencial del manejo de estos pacientes. Este consenso recoge una serie de pautas y escenarios prácticos de vacunación en pacientes adultos con EM candidatos a tratamiento inmunosupresor. METODOLOGÍA: Se llevó a cabo un consenso de tipo formal. Tras definir el alcance del documento, se realizó una búsqueda bibliográfica de vacunación en pacientes con EM, así como guías de vacunación específicas de pacientes inmunosuprimidos y en tratamiento biológico con otras enfermedades. Para la formulación de las recomendaciones se empleó la metodología de Modified Nominal Group Technique. DESARROLLO: La vacunación en pacientes candidatos a tratamiento inmunosupresor se debe plantear antes de iniciar un tratamiento inmunosupresor siempre que la situación clínica del paciente lo permita. Se recomendarán tanto aquellas indicadas en el calendario vacunal del adulto, como algunas específicas, en función de la inmunidad previa. Si ya está instaurado el tratamiento inmunosupresor las vacunas vivas atenuadas estarán contraindicadas. Para aquellas vacunas que dispongan de un correlato de protección se recomienda monitorizar la respuesta serológica transcurridos de uno a 2 meses de la última dosis

BACKGROUND: The recent development of highly effective treatments for multiple sclerosis (MS) and the potential risk of infectious complications require the development of prevention and risk minimisation strategies. Vaccination is an essential element of the management of these patients. This consensus statement includes a series of recommendations and practical scenarios for the vaccination of adult patients with MS who are eligible for highly effective immunosuppressive treatments. METHODOLOGY: A formal consensus procedure was followed. Having defined the scope of the statement, we conducted a literature search on recommendations for the vaccination of patients with MS and specific vaccination guidelines for immunosuppressed patients receiving biological therapy for other conditions. The modified nominal group technique methodology was used to formulate the recommendations. DEVELOPMENT: Vaccination in patients who are candidates for immunosuppressive therapy should be considered before starting immunosuppressive treatment providing the patient's clinical situation allows. Vaccines included in the routine adult vaccination schedule, as well as some specific ones, are recommended depending on the pre-existing immunity status. If immunosuppressive treatment is already established, live attenuated vaccines are contraindicated. For vaccines with a correlate of protection, it is recommended to monitor the serological response in an optimal interval of 1-2 months from the last dose

Recommendations for vaccination in patients with multiple sclerosis who are eligible for immunosuppressive therapies: Spanish consensus statement. / Recomendaciones para la vacunación en pacientes con esclerosis múltiple candidatos a terapias inmunosupresoras: documento de consenso español.

BACKGROUND: The recent development of highly effective treatments for multiple sclerosis (MS) and the potential risk of infectious complications require the development of prevention and risk minimisation strategies. Vaccination is an essential element of the management of these patients. This consensus statement includes a series of recommendations and practical scenarios for the vaccination of adult patients with MS who are eligible for highly effective immunosuppressive treatments. METHODOLOGY: A formal consensus procedure was followed. Having defined the scope of the statement, we conducted a literature search on recommendations for the vaccination of patients with MS and specific vaccination guidelines for immunosuppressed patients receiving biological therapy for other conditions. The modified nominal group technique methodology was used to formulate the recommendations. DEVELOPMENT: Vaccination in patients who are candidates for immunosuppressive therapy should be considered before starting immunosuppressive treatment providing the patient's clinical situation allows. Vaccines included in the routine adult vaccination schedule, as well as some specific ones, are recommended depending on the pre-existing immunity status. If immunosuppressive treatment is already established, live attenuated vaccines are contraindicated. For vaccines with a correlate of protection, it is recommended to monitor the serological response in an optimal interval of 1-2 months from the last dose.

Healthcare-associated pneumonia: a prospective study in Spain.

OBJECTIVE: The aim of the study was to describe the epidemiological characteristics and factors related to outcome in Streptococcus pneumoniae and methicillin-resistant Staphylococcus aureus (MRSA) healthcare-associated pneumonia (HCAP). METHODS: A 3-year prospective observational epidemiological case study of HCAP was conducted in seven Spanish hospitals. Microbiological and patient characteristics and outcomes were collected and classified by causative pathogen into 4 categories: "S. pneumoniae", "MRSA", "Others" and "Unknown". Patients were followed up 30 days after discharge. RESULTS: A total of 258 (84.6%) patients were enrolled (170 were men [65.9%]). Mean age was 72.4 years ± 15 years (95% CI [70.54-74.25]). The etiology of pneumonia was identified in 73 cases (28.3%): S. pneumoniae in 35 patients (13.6%), MRSA in 8 (3.1%), and other microorganisms in 30 patients (11.6%). Significant differences in rates of chronic obstructive pulmonary disease (p < 0.05), previous antibiotic treatment (p<0.05), other chronic respiratory diseases, inhaled corticosteroids (p <0.01), and lymphoma (p < 0.05) were observed among the four groups. Patients with MRSA pneumonia had received more previous antibiotic treatment (87.5%). Thirty-three (12.8%) patients died during hospitalisation; death in 27 (81.2%) was related to pneumonia. CONCLUSIONS: The etiology of HCAP was identified in only one quarter of patients, with S. pneumoniae being the most prevalent microorganism. Patients with chronic respiratory diseases more frequently presented HCAP due to MRSA than to S. pneumoniae. Death at hospital discharge was related in most cases to pneumonia.

Combination antifungal therapy for breakthrough invasive mould disease in patients with haematological malignancies: when management reasoning eclipses evidence-based medicine.

Timely diagnosis and treatment of invasive mould disease is challenging in severely immunocompromised patients, particularly for patients who develop breakthrough infections while on antifungal prophylaxis. Currently, there are no high-quality data on how to best diagnose and treat these infections. Many essential decisions affecting the management of breakthrough mould disease are made before a definitive diagnosis is established. In this scenario, sound management reasoning often favours the use of combination antifungal therapy, especially when antifungal resistance, suspicion of undetected sites of infection or pharmacokinetic/pharmacodynamic limitations at the site of infection are likely. In these scenarios, pre-emptive use of antifungal combination therapy with frequent re-evaluation with an aim of de-escalation could be justified for many high-risk patients.