Invasive and Non-Invasive Diagnostic Approaches for Microbiological Diagnosis of Hospital-Acquired Pneumonia

Otavio T. Ranzani; Tarek Senussi; Francesco Idone; Adrian Ceccato; Gianluigi Li Bassi; Miquel Ferrer; Antoni Torres


Crit Care. 2019;23(51) 

In This Article

Materials and Methods

Study Population

We conducted a retrospective analysis of a prospective cohort including patients from six medical and surgical ICUs at an 800-bed teaching hospital in Spain. Patients older than 18 years admitted to these ICUs for 48 h or more with clinical suspicion of HAP or VAP were prospectively and consecutively included. Patients with severe immunosuppression (neutropenia after chemotherapy or hematopoietic transplant, drug-induced immune suppression in solid-organ transplant or cytotoxic therapy, and HIV-infected patients) were excluded. The institution's internal review board approved the study (Comite Etic d'Investigacio Clinica, registry number 2009/5427), and written informed consent was obtained from patients or their next of kin.

Definition of Pneumonia

Clinical suspicion of pneumonia was based on clinical criteria as suggested in the guidelines:[1,5,19] (1) new or progressive radiologic pulmonary infiltrate, (2) together with at least two of the following: temperature > 38 °C or < 36 °C, leukocytosis > 12,000/mm3 or leukopenia < 4000/mm3, or purulent respiratory secretions. HAP was defined in patients who developed pneumonia after 48 h of hospitalization when not receiving invasive mechanical ventilation (iMV).[1,20]

Data Collection

All relevant data were collected upon ICU admission and at the onset of pneumonia from the medical records and bedside flow charts, including clinical, laboratory, radiological, and microbiological information. Patients' follow-up was extended to death, to hospital discharge, or up to 90 days after the diagnosis of pneumonia. The assessment of severity included the Acute Physiology and Chronic Health Evaluation (APACHE)-II[21] and the Sequential Organ Failure Assessment (SOFA) score,[22] calculated upon ICU admission and at HAP diagnosis.

Microbiologic Assessment and Methods

We tried to assess all patients upon clinical diagnosis of HAP, aiming to establish a microbiological diagnosis. Lower respiratory airway samples that could be collected for quantitative bacterial and fungal cultures were (1) sputum, (2) endotracheal aspirate (EAT), (3) bronchial aspirate through a fiberoptic-bronchoscopy (FBAS), and (4) bronchoalveolar lavage (BAL), blinded or through a fiberoptic-bronchoscopy. Only samples of sputum or tracheal aspirates of high quality (i.e. < 10 squamous cells and > 25 leukocytes per optical microscopy field) were processed for culture. Additionally, blood cultures (recommended to all patients) and pleural fluid (if a pleural puncture was indicated) could be collected, as well as urinary antigens of Legionella sp. and Streptococcus pneumoniae(mainly recommended for early-onset HAP). Pathogen identification and susceptibility testing were performed by standard methods.[23] Microbiological diagnosis was defined by the presence of at least one potentially pathogenic microorganism (PPM) in respiratory samples above predefined thresholds (sputum, EAT, FBAS > 105 colony-forming units/mL or BAL > 104, or any count if the patient was receiving a new systemic antibiotic treatment). Blood cultures were considered positive if an alternative cause of bacteremia was ruled out.[23]

Polymicrobial pneumonia was defined when more than one PPM was identified as causative agents. The initial empiric antimicrobial treatment was chosen following a local adaptation of the 2005 ATS/IDSA guidelines,[5] based on the most frequently isolated pathogens and their patterns of antimicrobial sensitivity at our institution. The empiric antimicrobial treatment was considered appropriate when the isolated pathogens were susceptible in vitro to at least one of the antimicrobials administered. Multi-drug-resistant pathogens were defined based on consensus definition.[24]

Antibiotic de-escalation was considered when physicians changed the antibiotic regimen to a narrower spectrum regimen, stopped the coverage for a class of pathogens (e.g., Staphylococcus aureus), or reduced the number of antibiotics prescribed.[25–27] Escalation was considered when physicians introduced a new regimen with broader coverage. We further divided the patients whom the empiric antibiotic scheme was maintained in those that no change was done, and in those whom an additional antibiotic was added to the empiric regimen.

Statistical Analysis

To analyze the diagnostic yield of the sampling method, we divided HAP patients into those who were subsequently intubated and those who were not, since in patients under iMV, the airway is easy to reach for lower respiratory sampling collection. We also compared patients who received a fiberoptic-bronchoscopy when undergoing or not undergoing iMV.

Data were presented as numbers (proportions) and as means ± SD or medians [p25-p75]. Qualitative or categorical variables were compared with the chi-square test or Fisher's exact test, as appropriate. Quantitative continuous variables were compared using the unpaired Student t test, one-way ANOVA, and Mann-Whitney or Kruskal Wallis tests as appropriate. All tests were two-sided, and Stata 13.1 was used for all analyses.