Effect of IN Hospital PCR Based Assessment of Patients With Lower Respiratory Tract Infections on LEngth of Stay

Does the use of the BIOFIRE® FILMARRAY® Pneumonia Panel plus in hospitalized patients with lower respiratory infections lead to a reduction in length of hospital stay (LOS) and customized antibiotic treatment (higher amount of specific vs empiric treatment, shorter treatment duration, less antibiotic treatment, lower incidence of side effects) compared to the standard of care?

Lower respiratory tract infections (LRTIs) like pneumonia, exacerbations of COPD or bronchitis are caused by several viral and/or bacterial pathogens. Even in huge epidemiological studies the causative pathogen can just be detected in approximately 50% of pneumonia cases. In clinical practice the pathogen is only known in few cases, e.g. Legionella via urine antigen test. It is impossible to distinguish the triggering bacteria by clinical parameters and even accurate differentiation between bacterial and viral infections is often not possible. The same problem exists for other LRTIs.

The lack of knowledge of the causative pathogen leads to several problems:

First, clinicians tend to observe patients after treatment initiation for a longer period than probably necessary, which may lead to an increased length of hospital stay. Secondly, the antibiotic treatment has to be broad enough to cover all possible pathogens empirically. This might lead to an overuse of broad-spectrum antibiotics, an increased risk of side effects, the development of antibiotic resistance or even delayed treatment of the causative agent. Finally, antibiotics are prescribed erroneously for viral infections, which have been misinterpreted as bacterial infections by clinicians.

The BIOFIRE® FILMARRAY® Pneumonia Panel plus can help to solve these problems by identifying the causative pathogen in LRTIs within 1.5 hours. The decision of the treatment and its duration would be pathogen driven and no longer just empirically based on a lot of unknown factors.

The investigators would like to perform the following study with two groups: standard of care (control group) vs Pneumonia panel plus (intervention group). Both groups will receive the standard of care treatment but the intervention group will additionally have their sputum analyzed via the BIOFIRE® FILMARRAY® Pneumonia Panel plus.

Additional information empiric vs specific treatment:

* empiric therapy - every antimicrobial therapy prescribed without knowing the pathogen

  o Amoxicillin/Clavulanic acid or Cefuroxime or Ceftriaxone/Cefotaxime or Piperacillin/Tazobactam or Levofloxacin
* Specific therapy - pathogen driven, prescribed knowing the pathogen; narrowed spectrum of agent

  * Pneumococcus - Penicillin G
  * H. influenzae - Cefuroxime or Doxycycline
  * Moraxella - Cefuroxime or Doxycycline
  * MSSA - Cefazolin or Flucloxacillin
  * MRSA - Linezolid or Vancomycin
  * Pseudomonas - Ceftazidime
  * E. coli - Cefuroxime or third generation Cephalosporin or Ciprofloxacin
  * Klebsiella - Cefuroxime or third generation Cephalosporin or Ciprofloxacin
  * Proteus, Serratia - third generation Cephalosporin or Ciprofloxacin
  * Enterobacter cloacae - Ertapenem
  * Legionella - Levofloxacin or Azithromycin
  * Mycoplasma - Azithromycin or Doxycycline
  * In case of ESBLs - Ertapenem or Meropenem
  * In case of carbapenemases - Ceftazidime/Avibactam (OXA48, KPC) or Meropenem/Vaborbactam (KPC) or Aztreonam +/- Ceftazidime/Avibactam (MBL +- others)

Eligibility Criteria:
Inclusion Criteria:

* Age ≥18 years
* Hospitalised patients on a general ward
* Ability to give consent
* Ability to produce sputum

AND (one of the following diagnosis)

* acute exacerabation of COPD (defined as known COPD and worsening of symptoms like dyspnea +/- wheezing +/- increased sputum purulence and the need for additional treatment)
* Pneumonia (diagnosed via chest X-ray)

OR

Lower respiratory infection (which does not belong to one of the two former diagnosis) with following symptoms:

At least one criterion Cough (more than usual if smoker) Dyspnea Increased sputum purulence

AND (at least one criterion) Respiratory rate ≥22/min Reduced oxygen saturation (\<95%) (or worsening of oxygen saturation by 3% (e.g. in patients with COPD) Fever (temp \>38°C) Rales/wheezing Chest pain upon breathing

Exclusion Criteria:

* Other proven or suspected systemic diseases which require antibiotic treatment, like:

  * Intraabdominal infections (appendicitis, cholecystitis, diverticulitis, peritonitis)
  * C. difficile associated diarrhea (only if existing on admission otherwise it will be identified as a side effect)
  * Urinary tract infections like pyelonephritis, urosepsis, cystitis + fever (asymptomatic bacteriuria is NOT an exclusion criterion)
  * Acute bacterial skin and skin structure infections (erysipelas, abscess with systemic symptoms, diabetic foot infection, osteomyelitis)
  * Another single cause which can explain the respiratory symptoms better than an infection (acute heart failure, pulmonary embolism, hypertension induced lung edema)
* Proven respiratory infection via another PCR based system (e.g. influenza or tuberculosis)
* Inability to give consent
* Inability to produce sputum
* Moribund and palliative patients