Evaluation of the clinical relevance of the Biofire© FilmArray pneumonia panel among hospitalized patients.

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.

Identification of microorganisms by a rapid PCR panel from positive blood cultures leads to faster optimal antimicrobial therapy - a before-after study.

BACKGROUND: The BioFire® FilmArray® Blood Culture Identification Panel 1 (BF-FA-BCIP) detects microorganisms with high accuracy in positive blood cultures (BC) - a key step in the management of patients with suspected bacteraemia. We aimed to compare the time to optimal antimicrobial therapy (OAT) for the BF-FA-BCIP vs. standard culture-based identification. METHODS: In this retrospective single-centre study with a before-after design, 386 positive BC cases with identification by BF-FA-BCIP were compared to 414 controls with culture-based identification. The primary endpoint was the time from BC sampling to OAT. Secondary endpoints were time to effective therapy, length of stay, (re-)admission to ICU, in-hospital and 30-day mortality. Outcomes were assessed using Cox proportional hazard models and logistic regressions. RESULTS: Baseline characteristics of included adult inpatients were comparable. Main sources of bacteraemia were urinary tract and intra-abdominal infection (19.2% vs. 22.0% and 16.8% vs. 15.7%, for cases and controls, respectively). Median (95%CI) time to OAT was 25.5 (21.0-31.2) hours with BF-FA-BCIP compared to 45.7 (37.7-51.4) hours with culture-based identification. We observed no significant difference for secondary outcomes. CONCLUSIONS: Rapid microorganism identification by BF-FA-BCIP was associated with a median 20-h earlier initiation of OAT in patients with positive BC. No impact on length of stay and mortality was noted. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04156633, registered on November 5, 2019.

Higher risk for influenza-associated pulmonary aspergillosis (IAPA) in asthmatic patients: A Swiss multicenter cohort study on IAPA in critically ill influenza patients.

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.

Possible Reactivation of SARS-CoV-2 in a Patient with Acute Myeloid Leukemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation: a Case Report.

Reactivation or reinfection cases of SARS-CoV-2 are known but there is scarce evidence about reactivation in immunocompromised patients. Here, we report the case of a 61-year-old male undergoing a conditioning regimen with fludarabine, cyclophosphamide, and 2-Gy total body irradiation in preparation of a haplo-identical allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute myeloid leukemia (AML). He received the first dose of a COVID-19 vaccine 6 weeks prior allo-HSCT and was hospitalized a month prior because of a COVID-19 bilateral pneumonia. On discharge, he showed two negative SARS-CoV-2 nasopharyngeal PCR swabs as well as a high SARS-CoV-2 antibody titer. On admission for allo-HSCT, he tested negative for SARS-CoV-2 again. Conditioning with fludarabine, cyclophosphamide, and 2-Gy total body irradiation was started and the patient developed lymphopenia. During his hospital stay, he tested positive for SARS-CoV-2 in a PCR test twice but remained asymptomatic. The conditioning regimen was continued as planned. Later during his stay, the patient showed undetectable SARS-CoV-2 load four times. This case documents possible reactivation of SARS-CoV-2 and raises questions about reactivation risks among recipients of stem cell transplants and other immunocompromised patients.

Cefiderocol for Extensively Drug-Resistant Gram-Negative Bacterial Infections: Real-world Experience From a Case Series and Review of the Literature.

Cefiderocol is a new siderophore cephalosporin with activity against carbapenem-resistant gram-negative bacteria. Data on its clinical efficacy are limited to complicated urinary tract infections. We present a series of 3 patients successfully treated with cefiderocol for complicated health care-associated infections and review published case reports.

Oral antibiotic therapy in people who inject drugs (PWID) with bacteraemia.

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.

Discovery and Characterization of Mycobacterium basiliense sp. nov., a Nontuberculous Mycobacterium Isolated From Human Lungs.

Bacteria belonging to the genus Mycobacterium are predominantly responsible for pulmonary diseases; most notably Mycobacterium tuberculosis causes granulomatous pulmonary infections. Here we describe a novel slow growing mycobacterial species isolated from respiratory samples from five patients, four with underlying pulmonary disease. The isolates were characterized by biochemical and molecular techniques, including whole genome sequencing. Biochemical characteristics generally match those of M. marinum and M. ulcerans; however, the most striking difference of the new species is its ability to grow at 37°C. The new species was found to grow in human macrophages, but not amoebae, suggesting a pathogenic rather than an environmental lifestyle. Phylogenetic analysis reveals a deep-rooting relationship to M. marinum and M. ulcerans. A complete genome sequence was obtained through combining short and long-read sequencing, providing a genome of 5.6 Mb. The genome appears to be highly intact, syntenic with that of M. marinum, with very few insertion sequences. A vast array of virulence factors includes 283 PE/PPE surface-associated proteins, making up 10% of the coding capacity, and 22 non-ribosomal peptide synthase clusters. A comparison of six clinical isolates from the five patients shows that they differ by up to two single nucleotide polymorphisms, suggesting a common source of infection. Our findings are in accordance with the recognition of a new taxonomic entity. We propose the name M. basiliense, as all isolates were found in patients from the Basel area of Switzerland.

Increasing prevalence of infectious diseases in asylum seekers at a tertiary care hospital in Switzerland.

OBJECTIVE: The increasing number of refugees seeking asylum in Europe in recent years poses new challenges for the healthcare systems in the destination countries. The goal of the study was to describe the evolution of medical problems of asylum seekers at a tertiary care centre in Switzerland. METHODS: At the University Hospital Basel, we compared all asylum seekers during two 1-year time periods in 2004/05 and 2014/15 concerning demographic characteristics and reasons for referrals and hospitalizations. RESULTS: Hundred ninety five of 2'544 and 516 of 6'243 asylum seekers registered at the national asylum reception and procedure centre Basel were referred to the University Hospital Basel in 2004/05 and 2014/15, and originated mainly from Europe (62.3%, mainly Turkey) and Africa (49.1%, mainly Eritrea), respectively. Median age was similar in both study periods (26.9 and 26.2 years). Infectious diseases in asylum seekers increased from 22.6% to 36.6% (p<0.001) and were the main reasons for hospitalizations (33.3% of 45 and 55.6% of 81 hospitalized patients, p = 0.017) in 2004/05 compared to 2014/15. The leading infectious diseases in hospitalized patients were tuberculosis (n = 4) and bacterial skin infections (n = 2) in 2004/05; Malaria (n = 9), pneumonia (n = 6), Chickenpox (n = 5), other viral infections (n = 5) and bacterial skin infections (n = 5) in 2014/15. Infectious diseases like malaria, cutaneous diphtheria, louseborne-relapsing fever or scabies were only found in the second study period. Almost one third of the admitted asylum seekers required isolation precautions with median duration of 6-9.5 days in both study periods. CONCLUSIONS: The changing demography of asylum seekers arriving in Switzerland in the current refugee crisis has led to a shift in disease patterns with an increase of infectious diseases and the re-emergence of migration-associated neglected infections. Physicians should be aware of these new challenges.

Fungemia and necrotic lymph node infection with Sporopachydermia cereana in a patient with acute myeloid leukemia.

Sporopachydermia cereana is a rare yeast found in necrotic cactus tissue, predominantly in the Americas. Infection in humans with clinical data has only been reported in four patients so far, all of whom died, either directly from the pathogen or from other complications of immunosuppression. Treatment of the yeast is complicated by difficulties in identification of the pathogen with conventional diagnostic techniques and by intrinsic resistance to echinocandins. The first patient to survive a disseminated infection with S. cereana is presented herein. The patient had acute myeloid leukemia and was treated successfully with antifungal therapy and subsequently underwent a successful allogeneic hematopoietic stem cell transplantation.

First case of infective endocarditis caused by Helicobacter cinaedi.

BACKGROUND: Up to 20% of all infective endocarditis are blood culture-negative and therefore a diagnostic challenge. Here we present the case of an infective endocarditis due to Helicobacter cinaedi finally diagnosed using different molecular methods. This highly fastidious gram-negative spiral rod is increasingly recognized as a human pathogen, above all in immunocompromised patients. So far H. cinaedi has been associated with bacteremia, cellulitis, arthritis and meningitis. CASE PRESENTATION: A 71-year-old man presented with fever and progressive dyspnea for weeks. He was immunocompromised by long-term steroid therapy. As one major and two minor Duke's criteria (vegetation, fever and aortic valve stenosis as predisposition) were present, an infective endocarditis was suspected and an empiric therapy with amoxicillin/clavulanic acid and gentamicin was established. The persistent severe aortic regurgitation resulted in a valve replacement. Histological evaluation of the aortic valve showed a polypous-ulcerative endocarditis. Gram stain and culture remained negative. Broad-range bacterial PCR targeting the 16S rRNA gene on the biopsy of the aortic valve identified H. cinaedi as the causative agent. The antibiotic therapy was simplified accordingly to ceftriaxone and gentamicin with a recommended duration of 6 weeks. Ten days after valve replacement the patient was discharged. To complete our molecular finding, we sequenced nearly the complete 16S rRNA gene (accession number KF914917) resulting in 99.9% identity with H. cinaedi reference sequences. Based on this result, 2 species-specific PCR tests amplifying part of the ctd gene were established and applied to the valve specimen. The 2 PCRs confirmed H. cinaedi. In addition, we analyzed stool, urine and saliva from the patient using H. cinaedi PCR. The fecal and urine specimen showed a positive signal, saliva was PCR-negative. CONCLUSION: We identified H. cinaedi as causative agent of a culture-negative endocarditis in an immunocompromised patient using broad-range and specific PCR. In addition to 2 cases from Japan presented on international meetings in 2010 and 2013, our case report shows that H. cinaedi should be recognized as additional causative organism of infective endocarditis. The use of molecular diagnostic techniques proved to be a powerful complement for the detection of blood culture-negative infective endocarditis.