Kasuistikk - Luftveisinfeksjoner Lars Heggelund, Seksjon for infeksjonssykdommer, Medisinsk avdeling, Drammen sykehus, Vestre Viken HF Spørsmål: Har han en infeksiøs bronkitt? KOLS? Reaktiv postinfeksiøs bronkitt? Anamnese: Tobakk Arbeidskarriere? TBC eksponering? Aspirasjonsproblematikk?

Diagnostiske betraktninger Lav CRP, normalt rtg thorax “Ble bra av Ery-Max” Reell endobronkial infeksjon Det naturlige forløp – tidsfaktoren Evt immunmodulerende effekt

Diagnostiske betraktninger Supplerende mikrobiologisk diagnostikk: Produktiv hoste – dyrkning + utvidet viral PCR us av “morgengruff” Serologi kan vurderes Annen diagnostikk: Klinisk us. - obstruktiv? Nytt rtg thorax. Vurder CT thorax, spesielt ved røykeanamnese Spirometri uten og med bronkodilatator

Akutt bronkitt - etiologi Oftest viralt betinget Influensa, RS Av og til: Mycoplasma, Chlamydophila, Pertussis Pneumokokker, Haemophilus, Moraxella Har antibiotika effekt? Nasjonal faglig retningslinje for antibiotikabruk i primærhelsetjenesten: ”Det er ikke dokumentert klinisk relevant effekt av antibiotika ved akutt bronkitt. Til tross for dette skrives det i Norge ut antibiotika til mer enn halvparten av de som får denne diagnosen.”

Akutt bronkitt – Cochrane Review Mars 2014: ”Antibiotic treatment for people with a clinical diagnosis of acute bronchitis” 17 randomiserte kliniske studier med ca 4000 deltakere. Inkluderer en studie med ca 1000 deltakere fra 12 land: svært liten men statistisk signifikant gunstig effekt: ½ dag kortere symptomer.  ”The available evidence suggests that there is no benefit in using antibiotics for acute bronchitis in otherwise healthy individuals though more research is needed on the effect in frail, elderly people with multimorbidities who may not have been included in the existing trials”

Jan Cato Holter, PhD. Student, 23 May 2014 Community-acquired pneumonia in Norway: etiology and value of extensive microbial diagnostic testing Pneumoniprosjektet i Buskerud Characterize the etiology of CAP in Norway Investigate potential benefit of PCR Jan Cato Holter, PhD. Student, 23 May 2014

Methods Microbiological techniques “New” Conventional Complete samling Mycoplasma pneumoniae Chlamydophila pneumoniae Bordetella pertussis Influensa virus A+B (H1N1) Parainfluensa virus 1-3 RSV hMPV Enterovirus Adenovirus Streptococcus pneumoniae Real-time PCR qPCR Blood culture Pleural fluid Streptococcus pneumoniae Legionella pneumophila BinaxNow (Binax, ME, USA) Urinary antigen BAL Dyrkning L. pneumophila real-time PCR Sputum Mycoplasma pneumoniae Chlamydophila pneumoniae Bordetella pertussis Influensa virus A+B KBR ELISA NP swab culture NP swab PCR OP swab PCR Serology

Results Etiology- filling the gap 267 Full cohort Streptococcus pneumoniae Bacteremia: 9% - S. pneumoniae 84% 11.3 25.9 30% Bordetella pertussis - - 6% Haemophilus influenzae 6.3 4 5% 63% Bacteria: 47% Copathogen: 26% Mycoplasma pneumoniae 4.1 7.5 4% Chlamydophila pneumoniae 5.9 7 3% Legionella Viruses: 34% 4.8 4.9 3% Mycoplsma epidemier: 2006 og 2011 Gram-negative enteric bacteria 5.3 2.7 2% Moraxella catarrhalis 1.2 2.5 2% Miscellaneous 8 2.2 1% Influenza virus: 15% Rhinovirus: 12% Haemophilus parainfluenza - - 1% Viruses 8.9 10.9 34% Unknown 40.7 43.8 37%

Results Seasonality- combined infection 64 Complete samples January and February (B) Monthly distribution of patients with pure bacterial, pure viral or combined bacterial and viral CAP during a 3-year period in a subset of 64 patients with complete samples collected. Coinfections= 34%, selekterer combined bacterial and viral: 25% Sesonganalyse: i. The proportion of cases with combined infection peaked in January and February to levels of 60% (not shown) and ii. was significantly different between the winter and spring than summer and fall (39.4% vs 9.7%, P = .01). iii. Combined bacterial and viral infection occurred more frequently than pure bacterial or pure viral infection during winter and spring (Figure 5B)

Results Microbial findings 64 Complete samples Antibiotic naïve (n = 43): 79% Total yield: 73% ≥ Copathogen: 47% Bacterial yield: 58% ≥ Copathogen: 57% Virus 43% Viral yield: 41% ≥ Copathogen: 65% Bacteria: 62% S. pneumonae: 35% S. pneumoniae: 31% ≥ Copathogen: 60% Virus 45% Etiology was achieved for 47 (73%) of 64 patients with complete sample collection (Figure 3). -Copathogens were detected for 22 (47%) patients. 2. A bacterial diagnosis was achieved for 37 (58%) of the 64 patients - Copathogens were detected for 21 of 37 (57%), and this was associated with a virus for 16 og 37 (43%) 3. 20 (31%) patients had detection of S. pneumoniae of whom 12 (60%) had ≥1 copathogen detected; of these 20 S. pneumoniae episodes had 9 (45%) ≥1 respiratory virus detected (i.e., 9 [75%] of the 12 coinfected S. pneumoniae episodes was attributed to ≥1 virus). 4. A total of 26 (41%) patients had a viral agent detected. 17 (65%) of these 26 patiens had at least 1 copathogen detected of which 62% (16 of 26 patients) were associtated with bacteria and 9 (35%) had identification of S. pneumoniae.

Results Methods 64 Complete samples 7% 5% 19% 15% The total diagnostic yield improved by 12% (47 vs 42 cases, P = .44) when PCR was added conventional methods; 9% (37 vs 34) for cases with bacterial etiology and 86% (26 vs 14, P = .035) for cases with viral etiology (Figure 4). Cases with detection of ≥1 copathogen increased by 83% (22 vs 12).

Conclusion 1 3/4 of patients may receive a microbiological diagnose. 2 PCR-based techniques were particularly useful in diagnosing viral infections as well as coinfection (1/3 of patients). 1. ¾ of patients may receive a microbiological diagnose. The most common single pathogens were S. pneumoniae followed by influenza virus and rhinovirus. 2. PCR-based techniques were particularly useful in diagnosing viral infections as well as coinfection, which occurred in approximately 1/3 of the patients and with majority of patients being viral agents. 3. Combined bacterial and viral infection was more common during winter and spring than either infection alone. 3 Combined bacterial and viral infection was more common during winter and spring than either infection alone.

Research group and collaborators Jan C. Holter, MD Fredrik Müller, MD, PhD Ola Bjørang, MSc Helvi H. Samdal, MD Jon B. Marthinsen, MD Pål Jenum, MD, PhD Thor Ueland, PhD Stig S. Frøland, MD, PhD Pål Aukrust, MD, PhD Einar Husebye, MD, PhD Lars Heggelund, MD, PhD.