PulmonaryImpact of antibiotic therapy in severe community-acquired pneumonia: Data from the Infauci study
Introduction
Community-acquired pneumonia (CAP), described in 1892 as the “Captain of the men of Death” by Sir William Osler [1], represents a major cause of morbidity, mortality and healthcare costs [2], [3], [4]. It remains one of the leading causes of hospital admission and 5–15% of the hospitalized patients will be admitted to an Intensive Care Unit (ICU) [5], largely owing to complications such as shock or respiratory failure.
Severe community-acquired pneumonia (SCAP) is undoubtedly a life threatening infection with a mortality rate around 30% [6]. Antibiotic therapy is definitely the cornerstone of its treatment but the best antibiotic strategy has not been established yet. The combination of a macrolide or a “respiratory” fluoroquinolone with a β-lactam, is advocated by international guidelines [7], [8], [9]. Those who seem to benefit most from this combination therapy are patients with bacteremic pneumococcal pneumonia [10], [11], [12], septic shock [13] and invasive mechanical ventilation [14]. However controversy persists since this recommendation is supported mostly by retrospective and observational nonrandomized studies [10], [11], [12], [15], [16]. Furthermore, empiric use of combination therapy to all patients with SCAP may lead to antibiotic overuse and consequently to the emergence of antimicrobial resistance in addition to increased risk for Clostridium difficile associated diarrhea and adverse drug events.
The aim of this study was to evaluate the impact of different features of antibiotic therapy (timing, mono vs combination therapy, macrolide use, appropriateness and duration) on short (hospital) and long term (6 months) outcome of SCAP patients admitted to the ICU.
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Study design and data collection
The Infection on Admission to the ICU (INFAUCI) study was a prospective, observational, cohort, multicentre study [17]. The study protocol was described elsewhere [17]. Briefly all adult patients (age ≥ 18 years) consecutively admitted during one year to one of the 14 Portuguese participating units were included and followed until death or 6 months after ICU admission. The Hospital Research and Ethics Committee of Centro Hospitalar S. João approved the study design. Infections and sepsis criteria
Patient characteristics
A total of 3766 consecutive patients were included in the INFAUCI study. Infection on ICU admission was present in 44%, including 536 admitted with SCAP (14.2%). The final study population consisted of 502 patients with SCAP who had antibiotic therapy data available (Fig. 1).
Most of the patients (66%) were male with a mean age of 58 ± 17 years and a Simplified Acute Physiology Score II (SAPS II) score of 46 ± 18. On the day of ICU admission, the mean Sequential Organ Failure Assessment (SOFA) score
Discussion
The main findings of this study are the following: 1) Globally, combination therapy did not improve survival in this cohort of critically ill patients; 2) However, combination therapy with a macrolide was independently associated with a lower hospital and 6 months mortality, namely in patients with septic shock; 3) Inappropriate empiric antibiotic therapy was independently associated with hospital mortality in the overall population, but this association was not observed in the subset of
Conclusions
In SCAP patients, the only antibiotic strategy that seems to improve significantly both hospital and 6 months mortality is the use of combination of antibiotics that includes a macrolide. Appropriate empiric antibiotic therapy improved short term survival (but not in the subgroup of patients with septic shock). Courses of appropriate antibiotic therapy longer than 7 days are not associated with a survival benefit but may lead to longer ICU and hospital LOS. Serum lactate showed to be a good
Ethical approval and consent to participate
The Hospital Research and Ethics Committee of Centro Hospitalar S. João approved the study design which has therefore been performed in accordance with ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Informed consent was waived due to the observational nature of the study.
Consent for publication
Not applicable.
Availability of supporting data
OR takes responsibility for archiving the data.
Competing interests
None of the authors have any competing interests in the manuscript.
Authors' contributions
JG-P, JMP, JPB, FF and J-AP conceived the study, participated in its design and coordination and served as the steering committee. J-AP acted as chair of the steering committee. JMP reviewed the database, and checked for implausible values and inconsistencies in the data. OR supervised data analysis and takes responsibility for archiving the data. All authors read, contributed and approved the final manuscript.
Acknowledgments
Members of the INFAUCI study group: Conceição Sousa Dias, José Manuel Pereira, José-Artur Paiva, Serviço Medicina Intensiva, Centro Hospitalar S. João (Porto); Lurdes Santos, Alcina Ferreira, UCI - Doenças Infecciosas, Centro Hospitalar S. João (Porto); Richard Maul, Serviço de Medicina Intensiva, Centro Hospitalar Funchal (Funchal); Vasco Tavares, Ana Josefina Mendes, Serviço de Cuidados Intensivos, Centro Hospitalar Vila Nova Gaia/Espinho (Gaia); Paulo Marçal, Piedade Amaro, Unidade de
Financial support
This work was supported by an unrestricted grant from GIS (Grupo de Infecção e Sepsis, Porto, Portugal).
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