Microbiological diagnosis of pleural infections: a comparative evaluation of a novel syndromic real-time PCR panel.

Current microbial diagnostics for pleural infections are insufficient. Studies using 16S targeted next-generation sequencing report that only 10%-16% of bacteria present are cultured and that 50%-78% of pleural fluids containing relevant microbial DNA remain culture negative. As a rapid diagnostic alternative suitable for clinical laboratories, we wanted to explore a PCR-based approach. Based on the identification of key pathogens, we developed a syndromic PCR panel for community-acquired pleural infections (CAPIs). This was a pragmatic PCR panel, meaning that it was not designed for detecting all possibly involved bacterial species but for confirming the diagnosis of CAPI, and for detecting bacteria that might influence choice of antimicrobial treatment. We evaluated the PCR panel on 109 confirmed CAPIs previously characterized using culture and 16S targeted next-generation sequencing. The PCR secured the diagnosis of CAPI in 107/109 (98.2%) and detected all present pathogens in 69/109 (63.3%). Culture secured the diagnosis in 54/109 (49.5%) and detected all pathogens in 31/109 (28.4%). Corresponding results for 16S targeted next-generation sequencing were 109/109 (100%) and 98/109 (89.9%). For bacterial species included in the PCR panel, PCR had a sensitivity of 99.5% (184/185), culture of 21.6% (40/185), and 16S targeted next-generation sequencing of 92.4% (171/185). None of the bacterial species present not covered by the PCR panel were judged to impact antimicrobial therapy. A syndromic PCR panel represents a rapid and sensitive alternative to current diagnostic approaches for the microbiological diagnosis of CAPI.IMPORTANCEPleural empyema is a severe infection with high mortality and increasing incidence. Long hospital admissions and long courses of antimicrobial treatment drive healthcare and ecological costs. Current methods for microbiological diagnostics of pleural infections are inadequate. Recent studies using 16S targeted next-generation sequencing as a reference standard find culture to recover only 10%-16% of bacteria present and that 50%-78% of samples containing relevant bacterial DNA remain culture negative. To confirm the diagnosis of pleural infection and define optimal antimicrobial therapy while limiting unnecessary use of broad-spectrum antibiotics, there is a need for rapid and sensitive diagnostic approaches. PCR is a rapid method well suited for clinical laboratories. In this paper we show that a novel syndromic PCR panel can secure the diagnosis of pleural infection and detect all bacteria relevant for choice of antimicrobial treatment with a high sensitivity.

"The challenge is the complexity" - A qualitative study about decision-making in advanced lung cancer treatment.

INTRODUCTION: The value of shared decision-making and decision aids (DA) has been well documented yet remain difficult to integrate into clinical practice. We wanted to investigate needs and challenges regarding decision-making about advanced lung cancer treatment after first-line therapy, focusing on DA applicability. METHODS: Qualitative data from separate, semi-structured focus groups with patients/relatives and healthcare professionals were analysed using systematic text condensation. 12 patients with incurable lung cancer, seven relatives, 12 nurses and 18 doctors were recruited from four different hospitals in Norway. RESULTS: The participants described the following needs and challenges affecting treatment decisions: 1) Continuity of clinician-patient-relationships as a basic framework for decision-making; 2) barriers to information exchange; 3) negotiation of autonomy; and 4) assessment of uncertainty and how to deal with it. Some clinicians feared DA would steal valuable time and disrupt consultations, arguing that such tools could not incorporate the complexity and uncertainty of decision-making. Patients and relatives reported a need for more information and the possibility both to decline or continue burdensome therapy. Participants welcomed interventions supporting information exchange, like communicative techniques and organizational changes ensuring continuity and more time for dialogue. Doctors called for tools decreasing uncertainty about treatment tolerance and futile therapy. CONCLUSION: Our study suggests it is difficult to develop an applicable DA for advanced lung cancer after first-line therapy that meets the composite requirements of stakeholders. Comprehensive decision support interventions are needed to address organizational structures, communication training including scientific and existential uncertainty, and assessment of frailty and treatment toxicity.

Pleural Empyema Caused by Streptococcus intermedius and Fusobacterium nucleatum: A Distinct Entity of Pleural Infections.

BACKGROUND: Many community-acquired pleural infections are caused by facultative and anaerobic bacteria from the human oral microbiota. The epidemiology, clinical characteristics, pathogenesis, and etiology of such infections are little studied. The aim of the present prospective multicenter cohort study was to provide a thorough microbiological and clinical characterization of such oral-type pleural infections and to improve our understanding of the underlying etiology and associated risk factors. METHODS: Over a 2-year period, we included 77 patients with community-acquired pleural infection, whereof 63 (82%) represented oral-type pleural infections. Clinical and anamnestic data were systematically collected, and patients were offered a dental assessment by an oral surgeon. Microbial characterizations were done using next-generation sequencing. Obtained bacterial profiles were compared with microbiology data from previous investigations on odontogenic infections, bacteremia after extraction of infected teeth, and community-acquired brain abscesses. RESULTS: From the oral-type pleural infections, we made 267 bacterial identifications representing 89 different species. Streptococcus intermedius and/or Fusobacterium nucleatum were identified as a dominant component in all infections. We found a high prevalence of dental infections among patients with oral-type pleural infection and demonstrate substantial similarities between the microbiology of such pleural infections and that of odontogenic infections, odontogenic bacteremia, and community-acquired brain abscesses. CONCLUSIONS: Oral-type pleural infection is the most common type of community-acquired pleural infection. Current evidence supports hematogenous seeding of bacteria from a dental focus as the most important underlying etiology. Streptococcus intermedius and Fusobacterium nucleatum most likely represent key pathogens necessary for establishing the infection.

Francisella tularensis bacteraemia causing multi-organ failure.

Tularemia is a zoonosis caused by the gram-negative coccobacillus Francisella tularensis. The bacterium can be transmitted in several ways including direct contact with animal reservoirs, ingestion, inhalation and bites, and typical clinical symptoms are headache, fever, diarrhea and dyspnea. Francisella tularensis has two predominant subspecies (ssp), namely ssp. tularensis and ssp. holarctica. Ssp. holarctica is less virulent and does usually not cause fatal disease. We here present a 51-year-old male with sepsis and multi-organ failure caused by F. tularensis ssp. holarctica infection suggesting that atypical agents including F. tularensis should be considered in patients presenting symptoms of infections without response to standard treatments.