Cutibacterium species valvular and cardiac device-related infective endocarditis: contemporary data from the GAMES prospective cohort (2008-2023).

BACKGROUND: Information on infective endocarditis (IE) caused by Cutibacterium spp. is limited and new Duke-ISCVID criteria have not yet been properly assessed. We examined clinical characteristics, outcomes and performance of diagnostic tests for Cutibacterium valvular and cardiac implantable electronic device-related IE (CIED-IE). METHODS: Data corresponding to all episodes of Cutibacterium IE recorded from 2008 to 2023 in a prospective national cohort including 46 Spanish hospitals were examined. Possible IE cases were reassessed using the new criteria. The sensitivity of blood cultures, valvular and CIED cultures, and PCR of the 16SrRNA gene and sequencing (16SPCR) was evaluated. RESULTS: There were 67/6,692 (1%) episodes of IE caused by Cutibacterium spp., 85% affecting men. Of these, 50 were valve-related (45 prosthetic, 5 native) and 17 CIED-related. The new criteria identified 8 additional cases and reclassified 15 as definite IE. Intracardiac complications (abscess, pseudoaneurysm, perforation or intracardiac fistula) occurred in 23/50 (46%) valvular IE episodes, leading to 18% mortality, and up to 40% mortality if surgery was indicated but could not be performed. All CIED-IE cases underwent device removal and no deaths were recorded. Positive diagnosis rates for blood cultures, valve/device cultures and 16SPCR were 52%, 70% and 82%, respectively. CONCLUSION: Cutibacterium IE is a rare yet potentially life-threatening condition that warrants a high index of suspicion in men with endovascular prosthetic material. The new Duke-ISCVID criteria and molecular techniques are useful for its diagnosis. Considering a significant complication rate, cardiac surgery and removal of CIEDs play a key role in reducing mortality.

Current challenges in acute bacterial skin infection management.

PURPOSE OF REVIEW: There are aspects of skin and soft tissue infections (SSTIs) that remain unresolved, such as current numbers, classification criteria, how best to define severity and predict the outcome, what diagnostic tests to perform, what new treatment options are available, or what the duration of antibiotic treatment should be. We have reviewed the literature over the last 18 months to clarify these issues and provide our opinion. RECENT FINDINGS: SSTIs are common and among the top 10 most frequent infections worldwide. They represent a burden on the healthcare system and have a major impact on the quality of life of patients. Regarding classification, the Infectious Diseases Society of America (IDSA) provides a practical guide that distinguishes between uncomplicated and complicated infections, acute and chronic wound infections, and necrotising and nonnecrotizing infections based on skin extension and tissue necrosis. With new microbiological and imaging diagnostic techniques, SSTIs can now be better diagnosed. New PCR techniques are available, and mass spectrometry can be applied to samples collected in liquid transport media. Moreover, new treatment methods such as photodynamic therapy, reactive oxygen, and phages are emerging. SSTI patients can be treated with shorter antibiotic courses if they receive an active drug with good tissue penetration. Antibiotic treatment in necrotizing infections can be shortened to 48 h after the last debridement. SUMMARY: SSTIs remain a challenge regarding rapid and accurate diagnosis and clinical management.

Infectious complications following major heart surgery from the day of the surgery to hospital discharge.

BACKGROUND: At some point in their lives, many people will require major heart surgery (MHS). Patients are generally older adults with various risk factors for infection. However, the incidence of infection after MHS is poorly known, as reported infection data are frequently biased due to different factors like the surgical procedure, postoperative timing, and infectious syndromes or etiologic agents, among others. In addition, most patient data are retrospectively obtained. PURPOSE AND METHODS: Data were prospectively collected regarding the incidence of all nosocomial infections produced from the time of surgery to hospital discharge in a cohort of 800 adults consecutively undergoing a MHS procedure. RESULTS: During postoperative hospitalization, 124 of the 800 participants developed one or more infections (15.5%): during their ICU stay in 68 patients (54.8%), during their stay on the general ward post ICU in 50 (40.3%), and during their stay in both wards in 6 (4.8%). The most common infections were pneumonia (related or not to mechanical ventilation), surgical site and bloodstream. As etiological agents, 193 pathogens were isolated: mostly Gram-negative bacilli (54.4%), followed by Gram-positive bacteria (30%), viruses (4.6%) and fungi (1.5%). In our cohort, all-cause mortality was recorded in 33 participants (4.1%) and 9 infection-related deaths (1.1%) were produced. Among subjects who developed infections, overall mortality was 13.7% and in those who did not, this was only 2.3%. CONCLUSION: Infection following MHS remains frequent and severe. Our data suggest that hospital-acquired infection studies should consider episodes of infection in all populations during their entire hospital stay and not only those related to specific clinical syndromes or acquired while the patient is in intensive care.

Economic Burden of Clostridioides difficile Infection in European Countries.

Clostridioides difficile infection (CDI) remains a considerable challenge to healthcare systems worldwide. Although CDI represents a significant burden on healthcare systems in Europe, few studies have attempted to estimate the consumption of resources associated with CDI in Europe. The reported extra costs attributable to CDI vary widely according to the definitions, design, and methodologies used, making comparisons difficult to perform. In this chapter, the economic burden of healthcare facility-associated CDI in Europe will be assessed, as will other less explored areas such as the economic burden of recurrent CDI, community-acquired CDI, pediatric CDI, and CDI in outbreaks.

How to manage skin and soft-tissue infections in the emergency department.

PURPOSE OF REVIEW: Our purpose is to review the state-of-the-art on the management of skin and soft tissue infections (SSTI) in emergency departments (ED).Although the information is scarce, SSTI may account for 3-30% of all cases presenting to an ED, of which 25-40% require hospital admission.SSTI include very different entities in aetiology, location, pathogenesis, extension, and severity. Therefore, no single management can be applied to them all. A simple approach is to classify them as non-purulent, purulent, and necrotising, to which a severity scale based on their systemic repercussions (mild, moderate, and severe) must be added.The initial approach to many SSTIs often requires no other means than anamnesis and physical examination, but imaging tests are an indispensable complement in many other circumstances (ultrasound, computerized tomography, magnetic resonance imaging…). In our opinion, an attempt at etiological filiation should be made in severe cases or where there is suspicion of a causality other than the usual one, with tests based not only on cultures of the local lesion but also molecular tests and blood cultures. RECENT FINDINGS: Recent contributions of interest include the value of bedside ultrasound and the potential usefulness of biomarkers such as thrombomodulin to differentiate in early stages the presence of necrotising lesions not yet explicit.New antimicrobials will allow the treatment of many of these infections, including severe ones, with oral drugs with good bioavailability and for shorter periods. SUMMARY: The ED has an essential role in managing SSTIs, in their classification, in decisions on when and where to administer antimicrobial treatment, and in the rapid convening of multidisciplinary teams that can deal with the most complex situations.

How to treat severe Acinetobacter baumannii infections.

PURPOSE OF REVIEW: To update the management of severe Acinetobacter baumannii infections (ABI), particularly those caused by multi-resistant isolates. RECENT FINDINGS: The in vitro activity of the various antimicrobial agents potentially helpful in treating ABI is highly variable and has progressively decreased for many of them, limiting current therapeutic options. The combination of more than one drug is still advisable in most circumstances. Ideally, two active first-line drugs should be used. Alternatively, a first-line and a second-line drug and, if this is not possible, two or more second-line drugs in combination. The emergence of new agents such as Cefiderocol, the combination of Sulbactam and Durlobactam, and the new Tetracyclines offer therapeutic options that need to be supported by clinical evidence. SUMMARY: The apparent limitations in treating infections caused by this bacterium, the rapid development of resistance, and the serious underlying situation in most cases invite the search for alternatives to antibiotic treatment, the most promising of which seems to be bacteriophage therapy.

Current international and national guidelines for managing skin and soft tissue infections.

PURPOSE OF REVIEW: Skin and soft tissue infections account for a significant percentage of both community and nosocomial infections. Several nosological entities are included in this concept. However, there is a very scarce body of doctrine for their treatment based on randomised trials. Therefore, we considered it necessary to review current treatment guidelines to bring new recommendations and improvements to our colleagues. In this review of recent literature, we identified updated guidelines in this area by searching the databases PubMed, evidence-based medicine online, York University reviewers group, Cochrane, MBE-Trip and Sumsearch using the terms: soft tissue infection, therapy, guideline. RECENT FINDINGS: Developments focus on using new antimicrobials and on the prescription of shorter antibiotic treatment courses. SUMMARY: With the development of new drugs and the current evidence of their use, there is a need to refine the appropriate drug's decision-making. Drugs with a long half-life, which allows weekly administration, can reduce hospital admission and length of stay with fewer healthcare resources. Shorter courses of antibiotics are recommended. The role of stewardship programmes will continue to expand. The surgical indication and its value are evident in many patients. Therefore, management should rely on a collaborative group with experience in this disease.

Controversies over the management of infections caused by Amp-C- and ESBL-producing Enterobacterales : what questions remain for future studies?

PURPOSE OF REVIEW: The continuous rise in infections caused by third-generation cephalosporin-resistant Enterobacterales (e.g. extended-spectrum beta-lactamase- or AmpC-producing Enterobacterales ) is a major health concern. Carbapenems are regarded as the antibiotics of choice for the treatment of these infections. However, their indiscriminant use is not without consequences, and has contributed to the emergence of carbapenem-resistant Enterobacterales .In this review, we discuss the available evidence supporting the use of other betalactams, nonbetalactams and the new betalactams/beta-lactamase inhibitors (BLA/BLI) to treat these infections. We also analyze unresolved issues in this field. RECENT FINDINGS: Piperacillin tazobactam (PTZ) was classically recommended as a carbapenem-sparing agent. However, data have emerged against its use and it is now a controversial recommendation. IDSA, European and British guidelines reject the empirical use of PTZ for these pathogens, reserving its use for rare clinical situations.Other issues that continue to generate debate are the use of extended infusion (3 h) PTZ, the use of older antibiotics, a shortened course of carbapenems and reserving the new BLA/BLI for these infections. SUMMARY: New treatment strategies should be based on clinical evidence, local epidemiology and the microbiological activity of these drugs.

Prevalence and clinical features of secondary skin lesions in septic patients with bloodstream infections.

Cutaneous manifestations developed in the course of sepsis are poorly documented in the medical literature beyond those related to specific pathogens or classical clinical pictures such as purpura fulminans or ecthyma gangrenosum. The objective of this study was to determine the overall prevalence of sepsis-related skin findings and evaluate their possible impact on the prognosis of septic patients. Single-centre, retrospective study of septic patients with documented bloodstream infections admitted in a tertiary hospital during 2019. Primary skin and soft tissue infections, and non-sepsis-related skin conditions diagnosed during hospital admission were excluded. Unselected sample of 320 episodes of sepsis in 265 patients. Secondary skin lesions were documented in 57 sepsis episodes (17.8%) in 47 patients. Purpura (petechiae/ecchymosis) was the most frequent cutaneous finding in septic patients (35.5%), with non-acral involvement in more than one-third of the episodes (38.5%), followed by skin and soft tissue erythema/oedema (25.8%) and maculopapular rashes (11.3%). Secondary skin lesions occurred more frequently in sepsis of respiratory (p = 0.027) and skin and soft tissue (p = 0.018) origin, as well as in sepsis caused by Pseudomonas aeruginosa and Stenotrophomonas maltophilia (p = 0.001). Mean hospital stay was 38.58 days and sepsis-related mortality 21.1%. Our results suggest that cutaneous involvement in the course of sepsis is frequent, with purpura being the main clinical sign. The semiology described in this study, easily identifiable by non-dermatologists, should alert clinicians to the potential unfavourable course of these patients.

Aspergillus endocarditis in the recent years, report of cases of a multicentric national cohort and literature review.

OBJECTIVES: (1) To describe the incidence, clinical characteristics, treatment and outcome of Aspergillus Endocarditis (AE) in a nationwide multicentric cohort (GAMES). (2) To compare the AE cases of the GAMES cohort, with the AE cases reported in the literature since 2010. (3) To identify variables related to mortality. METHODS: We recruited 10 AE cases included in the GAMES cohort (January 2008-December 2018) and 51 cases from the literature published from January 2010 to July 2019. RESULTS: 4528 patients with infectious endocarditis (IE) were included in the GAMES cohort, of them 10 (0.2%) were AE. After comparing our 10 cases with the 51 of the literature, no differences were found. Analysing the 61 AE cases together, 55.7% were male, median age 45 years. Their main underlying conditions were as follows: prosthetic valve surgery (34.4%) and solid organ transplant (SOT) (19.7%). Mainly affecting mitral (36.1%) and aortic valve (29.5%). Main isolated species were as follows: Aspergillus fumigatus (47.5%) and Aspergillus flavus (24.6%). Embolisms occurred in 54%. Patients were treated with antifungals (90.2%), heart surgery (85.2%) or both (78.7%). Overall, 52.5% died. A greater mortality was observed in immunosuppressed patients (59.4% vs. 24.1%, OR = 4.09, 95%CI = 1.26-13.19, p = .02), and lower mortality was associated with undergoing cardiac surgery plus azole therapy (28.1% vs. 65.5%, OR = 0.22, 95%CI = 0.07-0.72, p = .01). CONCLUSIONS: AE accounts for 0.2% of all IE episodes of a national multicentric cohort, mainly affecting patients with previous valvular surgery or SOT recipients. Mortality remains high especially in immunosuppressed hosts and azole-based treatment combined with surgical resection are related to a better outcome.

The Fall in Antibody Response to SARS-CoV-2: a Longitudinal Study of Asymptomatic to Critically Ill Patients Up to 10 Months after Recovery.

The aim of this study was to assess the long-term dynamics and factors associated with the serological response against the severe acute respiratory syndrome coronavirus 2 after primary infection. A prospective longitudinal study was conducted with monthly serological follow-up during the first 4 months, and then at 6, 8, and 10 months after the disease onset of all recovered adult in- and outpatients with coronavirus disease 2019 (COVID-19) attending Udine Hospital (Italy) during the first wave (from March to May 2020). A total of 546 individuals were included (289 female, mean age 53.1 years), mostly with mild COVID-19 (370, 68.3%). Patients were followed for a median of 302 days (interquartile range, 186 to 311). The overall seroconversion rate within 2 months was 32% for IgM and 90% for IgG. Seroreversion was observed in 90% of patients for IgM at 4 months and in 47% for IgG at 10 months. Older age, number of symptoms at acute onset, and severity of acute COVID-19 were all independent predictors of long-term immunity both for IgM (ß, linear regression coefficient, 1.10, P = 0.001; ß 5.15 P = 0.014; ß 43.84 P = 0.021, respectively) and for IgG (ß 1.43 P < 0.001; ß 10.46 P < 0.001; ß 46.79 P < 0.001, respectively), whereas the initial IgG peak was associated only with IgG duration (ß 1.12, P < 0.001). IgM antibodies disappeared at 4 months, and IgG antibodies declined in about half of patients 10 months after acute COVID-19. These effects varied depending on the intensity of the initial antibody response, age, and burden of acute COVID-19.

The eternal dilemma of antitoxin antibiotics for skin and soft tissue infection.

PURPOSE OF REVIEW: In standard clinical practice, combined antibiotic treatment is used to treat severe skin and soft tissue infections (SSTIs), whereby one of the drugs is usually a protein synthesis inhibitor antibiotic. However, evidence for this practice is only based on data from 'in vitro' studies, animal models and case reports. There are no randomized controlled trials. In the light of several new drugs marketed for the treatment of these infections, there is a need to revise the state of the art. RECENT FINDINGS: New reviews and systematic appraisals of the literature exist on the use of protein synthesis inhibitor antibiotics to treat severe SSTI. Several 'in vitro' studies have assessed the efficacy of some of the new drugs. SUMMARY: Combination therapy, including an adjuvant protein synthesis inhibitor antibiotic for toxin suppression, should be used both in patients with severe SSTI and in those with moderate infection and risk factors for methicillin-resistant positive- or Panton-Valentine leukocidin positive-Staphylococcus aureus infection.

Gram-negative endocarditis: disease presentation, diagnosis and treatment.

PURPOSE OF REVIEW: Gram-negative bacilli (GNB) cause between 1% and 10% of infective endocarditis (IE). Most episodes are caused by microorganisms of the Haemophilus spp., Aggregatibacter spp. Cardiobacterium spp., Eikenella spp., and Kingella spp (HACEK) group. The frequency of IE caused by non-HACEK (GNB-IE) has increased in recent years. Uncertainties persist regarding its best medical treatment and the appropriateness and timing of surgical treatment. In addition, there are new drugs with activity against multiresistant microorganisms, of which there is little experience in this disease. We review this topic by answering the most frequently asked questions that arise among our colleagues. RECENT FINDINGS: HACEK microorganisms cause 1.5-2% of IE with only a 2% mortality. In contrast, non-HACEK GNB-IE accounts for 2.5-3% of all IE cases and is associated with nosocomial acquisition, advanced age, solid organ transplantation and 20-30% mortality. Drug addiction is important in areas with epidemic opioid abuse. SUMMARY: The frequency of IE caused by GNB has been modified in recent years. HACEK episodes are no longer treated with ampicillin and aminoglycosides. In non-HACEK GNB-IE, combination therapy with a beta-lactam and a quinolone or aminoglycoside is recommended. The surgical indication and its value are evident in many patients. Management should rely on a collaborative group with experience in this disease.

The role of new carbapenem combinations in the treatment of multidrug-resistant Gram-negative infections.

Multi-drug resistant (MDR) Gram-negative bacteria represent a growing threat, with an increasing prevalence of carbapenem-resistant Enterobacterales (CRE) infections, for which treatment options are limited. New treatment combinations composed of a ß-lactam antibiotic plus a potent ß-lactamase inhibitor (BLI) with anti-carbapenemase activity have been developed, including two carbapenem/BLI combinations that are commercially available-meropenem/vaborbactam (Vabomere® in the US, Vaborem® in Europe; Melinta Therapeutics) and imipenem/cilastatin/relebactam (Recarbrio®; Merck Sharp & Dohme), plus one other (meropenem/nacubactam) in early clinical development. This review provides a summary of the preclinical evidence supporting the use of carbapenem/BLI combinations and presents the clinical evidence across a range of MDR Gram-negative infections, with a focus on the use of meropenem/vaborbactam. All three BLIs have shown in vivo activity against Klebsiella pneumoniae carbapenemase and other class A carbapenemases. In 2019, meropenem/vaborbactam was listed in the WHO's list of essential medicines, because of its activity against priority 1 antibiotic-resistant pathogens. Meropenem/vaborbactam has considerable in vitro and in vivo activity against CRE, and in vitro evidence showing a low potential for resistance at clinically relevant doses. In randomized trials, meropenem/vaborbactam was non-inferior to piperacillin/tazobactam in patients with complicated urinary tract infection and more effective than the best-available treatment in patients with serious CRE infections. Meropenem/vaborbactam is well tolerated and, based on clinical experience, demonstrated lower toxicity compared with the combination regimens that have previously been the standard of care. In conclusion, carbapenem/BLI combinations represent an important therapeutic strategy in patients with MDR Gram-negative infections.

Endotracheal tubes coated with a broad-spectrum antibacterial ceragenin reduce bacterial biofilm in an in vitro bench top model.

BACKGROUND: Ventilator-associated pneumonia is one of the most common nosocomial infections, caused mainly by bacterial/fungal biofilm. Therefore, it is necessary to develop preventive strategies to avoid biofilm formation based on new compounds. OBJECTIVES: We performed an in vitro study to compare the efficacy of endotracheal tubes (ETTs) coated with the ceragenin CSA-131 and that of uncoated ETTs against the biofilm of clinical strains of Pseudomonas aeruginosa (PA), Escherichia coli (EC) and Staphylococcus aureus (SA). METHODS: We applied an in vitro bench top model using coated and uncoated ETTs that were treated with three different clinical strains of PA, EC and SA for 5 days. After exposure to biofilm, ETTs were analysed for cfu count by culture of sonicate and total number of cells by confocal laser scanning microscopy. RESULTS: The median (IQR) cfu/mL counts of PA, EC and SA in coated and uncoated ETTs were, respectively, as follows: 1.00 × 101 (0.0-3.3 × 102) versus 3.32 × 109 (6.6 × 108-3.8 × 109), P < 0.001; 0.0 (0.0-5.4 × 103) versus 1.32 × 106 (2.3 × 103-5.0 × 107), P < 0.001; and 8.1 × 105 (8.5 × 101-1.4 × 109) versus 2.7 × 108 (8.6 × 106-1.6 × 1011), P = 0.058. The median (IQR) total number of cells of PA, EC and SA in coated and non-coated ETTs were, respectively, as follows: 11.0 [5.5-not applicable (NA)] versus 87.9 (60.5-NA), P = 0.05; 9.1 (6.7-NA) versus 62.6 (42.0-NA), P = 0.05; and 97.7 (94.6-NA) versus 187.3 (43.9-NA), P = 0.827. CONCLUSIONS: We demonstrated significantly reduced biofilm formation in coated ETTs. However, the difference for SA was not statistically significant. Future clinical studies are needed to support our findings.

Low risk of reinfections and relation with serological response after recovery from the first wave of COVID-19.

The aim of the study was to assess reinfection rates in relation to long-term antibody dynamics against SARS-CoV-2 after the first wave. A prospective longitudinal study with monthly serological follow-up during the first 4 months, and then at 6, 8, and 10 months after the disease onset of all recovered adult in- and outpatients with COVID-19 attending Udine Hospital (Italy) from March to May 2020. During the follow-up, reinfections were collected. A total of 546 unselected individuals with COVID-19 acquired from March to May 2020 were included (292 female, mean age 53 years). After a median follow-up of 10 months (IQR 6.2-10.4), reinfection occurred in 6 (1.1%) patients, median age of 44.5 years (IQR 33‒49). All had a previous history of mild COVID-19 (all were healthcare workers) and reinfection occurred a median of 9 months (IQR 8.2‒10.2) after the onset of the first episode. Patients with reinfection were either seronegative (2/56, n = 3.6%), seroreverted (2/137, 1.5%), or seropositive (2/353, 0.6%) (p = 0.085). All reinfections were mild (n = 5) or asymptomatic (n = 1). After reinfection, none of patients developed IgM response and only two had a transitory boosted IgG immunization response. In an unselected population after the first wave of COVID-19, after a prolonged observation period (mean 10 months), reinfection was very uncommon; occurred in patients with a previous history of mild infection, mostly with weak or absent serological response; and manifested with mild or asymptomatic clinical presentation.

Disseminated lomentosporiosis in a heart transplant recipient: Case report and review of the literature.

BACKGROUND: Lomentospora prolificans (formerly S prolificans) is a saprophyte fungi that causes opportunistic infections in solid organ transplant (SOT) recipients. Resulting disseminated infections are difficult to treat and have a high mortality. Indications for antifungal prophylaxis after heart transplantation (HT) include CMV disease, reoperation, renal replacement therapy, extracorporeal membrane oxygenation (ECMO), and high environmental exposure to Aspergillus spores. However, the risk of breakthrough infections, such as Lomentosporiosis, remains a cause of concern. METHODS: We report the clinical findings, microbiology, treatment and outcome of a disseminated Lomentosporiosis in a heart transplant recipient with ECMO and antifungal prophylaxis. RESULTS: A 25-year-old male with complex grown-up congenital heart disease (GUCHD) was admitted for HT. He presented severe post-surgical complications including acute kidney injury and right heart and respiratory failure requiring venoarterial-ECMO, continuous renal replacement therapy (CCRT) and later on (+14) a ventricular assist device (VAD). Ganciclovir, cotrimoxazole, and antifungal prophylaxis with anidulafungin at standard doses had been started on day + 3 post HT. The patient presented seizures (+4), pancytopenia with mild neutropenia (days + 6 to + 11), influenza B (+7), and bacteremic Pseudomonas aeruginosa ventilator associated pneumonia (VAP) (+10). On days + 14 to + 16 Lomentospora prolificans was recovered from blood cultures, broncho aspirate, catheter tip, and skin biopsy. Despite treatment with L-AMB, voriconazole and terbinafine the patients died on day 17 after HT. Necropsy revealed disseminated infection with fungal invasion in central nervous system, heart, lung, cutaneous, and subcutaneous tissue. Broth microdilution tests demonstrated resistance to all antifungals. CONCLUSIONS: Lomentosporiosis is a rare complication that may emerge as a breakthrough invasive fungal infection in heart transplant recipients on ECMO despite antifungal prophylaxis.

Invasive pulmonary aspergillosis in the COVID-19 era: An expected new entity.

OBJECTIVES: Information on the recently COVID-19-associated pulmonary aspergillosis (CAPA) entity is scarce. We describe eight CAPA patients, compare them to colonised ICU patients with coronavirus disease 2019 (COVID-19), and review the published literature from Western countries. METHODS: Prospective study (March to May, 2020) that included all COVID-19 patients admitted to a tertiary hospital. Modified AspICU and European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria were used. RESULTS: COVID-19-associated pulmonary aspergillosis was diagnosed in eight patients (3.3% of 239 ICU patients), mostly affected non-immunocompromised patients (75%) with severe acute respiratory distress syndrome (ARDS) receiving corticosteroids. Diagnosis was established after a median of 15 days under mechanical ventilation. Bronchoalveolar lavage was performed in two patients with positive Aspergillus fumigatus cultures and galactomannan (GM) index. Serum GM was positive in 4/8 (50%). Thoracic CT scan findings fulfilled EORTC/MSG criteria in one case. Isavuconazole was used in 4/8 cases. CAPA-related mortality was 100% (8/8). Compared with colonised patients, CAPA subjects were administered tocilizumab more often (100% vs. 40%, p = .04), underwent longer courses of antibacterial therapy (13 vs. 5 days, p = .008), and had a higher all-cause mortality (100% vs. 40%, p = .04). We reviewed 96 similar cases from recent publications: 59 probable CAPA (also putative according modified AspICU), 56 putative cases and 13 colonisations according AspICU algorithm; according EORTC/MSG six proven and two probable. Overall, mortality in the reviewed series was 56.3%. CONCLUSIONS: COVID-19-associated pulmonary aspergillosis must be considered a serious and potentially life-threatening complication in patients with severe COVID-19 receiving immunosuppressive treatment.

Clinical Relevance and Prognostic Value of Persistently Negative (1,3)-ß-D-Glucan in Adults With Candidemia: A 5-year Experience in a Tertiary Hospital.

BACKGROUND: The clinical relevance and the potential prognostic role of persistently negative (1,3)-ß-D-glucan (BDG) in adults with proven candidemia is unknown. METHODS: This retrospective study included all adults diagnosed with candidemia our tertiary university hospital from 2012-2017 who had at least 2 serum BDG determinations throughout the episode of fungemia (Fungitell Assay; positive cut-off ≥80pg/mL). Epidemiology and clinical outcomes were compared between patients with all negative versus any positive BDG tests. Poor clinical outcomes included complications due to candidemia or 30-day all-cause mortality. RESULTS: Overall, 26/148 (17.6%) candidemic adults had persistently negative BDG tests. These patients were less likely to present Candida growth in all 3 sets of blood cultures (15.4% vs 45.1%; P = .005) and had less severe clinical presentations (median Pitt score, 0 [interquartile range {IQR} 0-1] vs 1 [IQR 0-2] in patients with any positive BDG test; P = .039). Although adequate treatment was equally provided to both groups (96.2% in persistently negative group vs 93.4 in positive group; P = .599), the persistently negative group had a higher rate of microbiological clearance in the first follow-up blood cultures (92.3% vs 69.7% in positive group; P = .005), fewer complications due to candidemia (7.7% vs 33.6% in positive group; P = .008), a lower 30-day mortality rate (3.8% vs 23.8% in positive group; P = .004), and a shorter in-hospital stay (34 days [IQR 18-55] vs 51 days [IQR 35-91] in positive group; P = .003). In the multivariate analysis, persistently negative BDG tests were independently associated with better prognoses (odds ratio 0.12, 95% confidence interval 0.03-0.49; P = .003). CONCLUSIONS: Candidemic patients with persistently negative BDG tests present a better prognosis than the comparative group, probably due to a lower systemic fungal burden. In this context, the appropriate use of persistently negative BDG results could be an aid to individualize therapeutic management in the near future.

Etiology and Prognosis of Pneumonia in Patients with Solid Tumors: A Prospective Cohort of Hospitalized Cases.

BACKGROUND: Data on the incidence, etiology, and prognosis of non-ventilator-associated pneumonia in hospitalized patients with solid tumors are scarce. We aimed to study the characteristics of non-ventilator-associated pneumonia in hospitalized patients with solid tumors. MATERIALS AND METHODS: This was a prospective noninterventional cohort study of pneumonia in patients hospitalized in an oncology ward in a tertiary teaching hospital. Pneumonia was defined according to the American Thoracic Society criteria. Patients were followed for 1 month after diagnosis or until discharge. Survivors were compared with nonsurvivors. RESULTS: A total of 132 episodes of pneumonia were diagnosed over 1 year (9.8% of admissions to the oncology ward). They were health care-related (67.4%) or hospital-acquired pneumonia (31.8%). Lung cancer was the most common malignancy. An etiology was established in 48/132 episodes (36.4%). Knowing the etiology led to changes in antimicrobial therapy in 58.3%. Subsequent intensive care unit admission was required in 10.6% and was linked to inappropriate empirical therapy. Ten-day mortality was 24.2% and was significantly associated with hypoxia (odds ratio [OR], 2.1). Thirty-day mortality was 46.2%. The independent risk factors for 30-day mortality were hypoxia (OR, 3.3), hospital acquisition (OR, 3.1), and a performance status >1 (OR, 2.6). Only 40% of patients who died within 30 days were terminally ill. CONCLUSION: Pneumonia is a highly prevalent condition in hospitalized patients with solid tumors, even with nonterminal disease. Etiology is diverse, and poor outcome is linked to inappropriate empirical therapy. Efforts to get the empirical therapy right and reach an etiological diagnosis to subsequently de-escalate are warranted. IMPLICATIONS FOR PRACTICE: The present study shows that pneumonia is a prevalent infectious complication in patients admitted to oncology wards, with a very high mortality, even in non-terminally ill patients. Etiology is diverse, and etiological diagnosis is reached in fewer than 40% of cases in nonintubated patients. Intensive care unit admission, a marker of poor outcome, is associated with inappropriate empirical therapy. These results suggest that, to improve prognosis, a more precise and appropriate antimicrobial empirical therapy for pneumonia in patients with solid tumors is necessary, together with an effort to reach an etiological diagnosis to facilitate subsequent de-escalation.