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Purpose: Panel PCR tests provide rapid pathogen identification. However, their diagnostic performance is unclear. We assessed the performance of the Biofire© FilmArray pneumonia (PN)-panel against standard culture in broncho-alveolar lavage (BAL) samples. Methods: Setting: University Hospital Basel (February 2019 to July 2020), including hospitalized patients with a BAL (± pneumonia). We determined sensitivity and specificity of the PN-panel against standard culture. Using univariate logistic regression, we calculated odds ratios (OR) for pneumonia according to PN-panel and culture status, stratifying by chronic pulmonary disease. We calculated ORs for pneumonia for different pathogens to estimate the clinical relevance. Results: We included 840 adult patients, 60% were males, median age was 68 years, 35% had chronic pulmonary disease, 21% had pneumonia, and 36% had recent antibiotic use. In 1078 BAL samples, bacterial pathogens were detected in 36% and 16% with PN-panel and culture, respectively. The overall sensitivity and specificity of the PN-panel was high, whereas the positive predictive value was low. The OR of pneumonia was 1.1 (95% CI 0.7–1.6) for PN-panel-positive only; 2.6 (95% CI 1.3–5.3) for culture-positive only, and 1.6 (95% CI 1.0–2.4) for PN-panel and culture-positive. The detection rate of Haemophilus influenzae, Staphylococcus aureus, and Moraxella catarrhalis in the PN-panel was high but not associated with pneumonia. Conclusion: While sensitivity and specificity of PN-panel are high compared to culture, pathogen detection did not correlate well with a pneumonia diagnosis. Patients with culture-positive BAL had the highest OR for pneumonia—thus the impact of the PN-panel on clinical management needs further evaluation in randomized controlled trials. [ABSTRACT FROM AUTHOR]

Background: Influenza‐associated pulmonary aspergillosis (IAPA) is an important complication of severe influenza with high morbidity and mortality. Methods: We conducted a retrospective multicenter study in tertiary hospitals in Switzerland during 2017/2018 and 2019/2020 influenza seasons. All adults with PCR‐confirmed influenza infection and treatment on intensive‐care unit (ICU) for >24 h were included. IAPA was diagnosed according to previously published clinical, radiological, and microbiological criteria. We assessed risk factors for IAPA and predictors for poor outcome, which was a composite of in‐hospital mortality, ICU length of stay ≥7 days, mechanical ventilation ≥7 days, or extracorporeal membrane oxygenation. Results: One hundred fifty‐eight patients (median age 64 years, 45% females) with influenza were included, of which 17 (10.8%) had IAPA. Asthma was more common in IAPA patients (17% vs. 4% in non‐IAPA, P = 0.05). Asthma (OR 12.0 [95% CI 2.1–67.2]) and days of mechanical ventilation (OR 1.1 [1.1–1.2]) were associated with IAPA. IAPA patients frequently required organ supportive therapies including mechanical ventilation (88% in IAPA vs. 53% in non‐IAPA, P = 0.001) and vasoactive support (75% vs. 45%, P = 0.03) and had more complications including ARDS (53% vs. 26%, P = 0.04), respiratory bacterial infections (65% vs. 37%, P = 0.04), and higher ICU‐mortality (35% vs. 16.4%, P = 0.05). IAPA (OR 28.8 [3.3–253.4]), influenza A (OR 3.3 [1.4–7.8]), and higher SAPS II score (OR 1.07 [1.05–1.10]) were independent predictors of poor outcome. Interpretation: High clinical suspicion, early diagnostics, and therapy are indicated in IAPA because of high morbidity and mortality. Asthma is likely an underappreciated risk factor for IAPA. [ABSTRACT FROM AUTHOR]

In allogeneic hematopoietic cell transplant (HCT)-recipients, prophylactic management strategies are essential for preventing CMV-reactivation and associated disease. We report on a 63-year-old male patient with a D-/R+ CMV-serostatus, who showed ongoing low-level CMV-replication post-HCT despite receiving letermovir prophylaxis. Sanger-sequencing failed to detect drug resistance mutations (DRM) until CMV-pneumonitis developed, revealing a UL56-C325R-DRM linked to high-level letermovir resistance. Retrospective analysis with next-generation-sequencing (NGS) revealed the DRM at a low frequency of 6% two weeks prior to detection by Sanger-sequencing. This study highlights the importance of advanced NGS-methods for early detection of CMV-DRMs, allowing for faster adjustments in antiviral treatment strategies., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Bacterial infections are a major cause of morbidity and mortality in people who inject drugs (PWID). Patients with bacteraemia have a particularly high risk of complications and are usually treated with intravenous antibiotics. Intravenous treatment is challenging in certain PWID because of difficult venous access and a high rate of catheter-associated complications. Therefore, oral treatment alternatives must be considered. This review discusses the potential options for oral antimicrobial treatment of gram-positive and gram-negative bacteraemia in PWID and the evidence for them. Data on oral antibiotic treatment of bacteraemia in PWID is scarce. Whenever possible, a course of intravenous antibiotic treatment should precede the switch to an oral regimen. For Staphylococcus aureus bacteraemia, there is growing evidence that initial intravenous antibiotics can be switched to oral treatment (e.g., a fluoroquinolone and rifampin or linezolid) when the patient is clinically stable and source control has been achieved. However, regimen selection remains challenging due to pharmacokinetic/pharmacodynamic issues, potential toxicity and drug-drug interactions of oral antibiotics. For some streptococcal bacteraemia, oral amoxicillin is probably a reasonable option. The best existing evidence for oral antibiotic treatment is for gram-negative bacteraemia, which, if susceptible, can be treated successfully with oral fluoroquinolones. Oral antibiotic options for fluoroquinolone-resistant gram-negative bacteraemia are very limited, although in selected patients oral trimethoprim-sulfamethoxazole can be considered. In conclusion, treatment of bacteraemia in PWID remains very complex, and an interdisciplinary approach is essential in order to select the best therapy for this vulnerable group of patients.