Impact of antibiotic therapy in severe community-acquired pneumonia: Data from the Infauci study

doi:10.1016/j.jcrc.2017.08.048

Journal of Critical Care

Volume 43, February 2018, Pages 183-189

https://doi.org/10.1016/j.jcrc.2017.08.048 Get rights and content

Highlights

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In SCAP, combination of antibiotics that includes a macrolide is associated a better hospital and 6 months survival.
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Courses of therapy longer than 7 days are not associated with survival benefit but lead to longer ICU and hospital LOS.
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Serum lactate showed to be a good prognostic marker of hospital mortality in SCAP patients.

Abstract

Antibiotic therapy (AT) is the cornerstone of the management of severe community-acquired pneumonia (CAP). However, the best treatment strategy is far from being established.

To evaluate the impact of different aspects of AT on the outcome of critically ill patients with CAP, we performed a post hoc analysis of all CAP patients enrolled in a prospective, observational, multicentre study.

Of the 502 patients included, 76% received combination therapy, mainly a β-lactam with a macrolide (80%). AT was inappropriate in 16% of all microbiologically documented CAP (n = 177). Hospital and 6 months mortality were 34% and 35%. In adjusted multivariate logistic regression analysis, combination AT with a macrolide was independently associated with a reduction in hospital (OR 0.17, 95%CI 0.06–0.51) and 6 months (OR 0.21, 95%CI 0.07–0.57) mortality. Prolonged AT (> 7 days) was associated with a longer ICU (14 vs. 7 days; p < 0.001) and hospital length of stay (LOS) (25 vs. 17 days; p < 0.001).

Combination AT with a macrolide may be the most suitable AT strategy to improve both short and long term outcome of severe CAP patients. AT > 7 days had no survival benefit and was associated with a longer LOS.

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.

Section snippets

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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Cited by (34)

Guideline-Concordant Antibiotic Therapy for the Hospital Treatment of Community-Acquired Pneumonia and 1-Year All-Cause and Cardiovascular Mortality in Older Adult Patients Surviving to Discharge
2023, Chest
Selection of empiric antibiotic treatment for community-acquired pneumonia (CAP) that is concordant with clinical practice guidelines has been associated with improved short-term outcomes of this infection, but whether it is also associated with longer-term outcomes is unknown.
Is guideline-concordance of the initial antibiotic treatment given to older adult patients hospitalized with CAP associated with the 1-year all-cause and cardiovascular mortality risk of those patients who survive hospitalization for this infection?
A total of 1,909 older (> 65 years of age) patients were identified who survived hospitalization for CAP at The Ottawa Hospital (Ontario, Canada) between 2004 and 2015. Linking patients’ information to hospital and provincial data sets, this study analyzed whether the selection of the initial antibiotic therapy for their CAP was concordant with current clinical practice guidelines, and whether guideline-concordance was associated with 1-year all-cause and cardiovascular mortality following their index CAP hospitalization. Adjustments were made for the patients’ overall 1-year expected death risk; CAP severity; and history of previous pneumonia admissions, myocardial infarction, heart failure, or cerebrovascular disease.
Selection of guideline-concordant antibiotic therapy was associated with a trend towards lower all-cause mortality at 1 year post-CAP (hazard ratio, 0.82; 95% CI, 0.65-1.04; P = .099). Furthermore, the use of guideline-concordant antibiotic therapy was associated with a significant almost 50% reduction in cardiovascular death risk 1 year following CAP admission (hazard ratio, 0.53; 95% CI, 0.34-0.80; P = .003).
Use of guideline-concordant antibiotic therapy for CAP treatment in older hospitalized patients is associated with a significant reduction in the risk of cardiovascular death at 1 year post-CAP. This finding further supports current clinical practice guideline recommendations for CAP treatment.
The benefit of macrolide therapy in patients with pneumococcal pneumonia is only present in patients with bacteremia
2023, Pulmonology
Usefulness of β-lactam and macrolide combination therapy for treating community-acquired pneumonia patients hospitalized in the intensive care unit: Propensity score analysis of a prospective cohort study
2021, Journal of Infection and Chemotherapy
Citation Excerpt :
After adjusting by IPTW analysis, macrolide combination therapy also significantly improved 30-day mortality and 14-day mortality, though ICU mortality was not significantly different. Many previous studies reported that macrolide combination therapy improved prognosis compared with non-macrolide-containing regimens [8–13]. However, all of the studies were observational cohort studies including prospective and retrospective parts, and there were no RCTs.
Whether β-lactam and macrolide combination therapy reduces mortality in severe community-acquired pneumonia (SCAP) patients hospitalized in the intensive care unit (ICU) is controversial. The aim of the present study was to evaluate the usefulness of β-lactam and macrolide combination therapy for SCAP patients hospitalized in the ICU.
A prospective, observational, cohort study of hospitalized pneumonia patients was performed. Hospitalized SCAP patients admitted to the ICU within 24 h between October 2010 and October 2017 were included for analysis. The primary outcome was 30-day mortality, and secondary outcomes were 14-day mortality and ICU mortality. Inverse probability of treatment weighting (IPTW) analysis as a propensity score analysis was used to reduce biases, including six covariates: age, sex, C-reactive protein, albumin, Pneumonia Severity Index score, and APACHE II score.
A total of 78 patients were included, with 48 patients in the non-macrolide-containing β-lactam therapy group and 30 patients in the macrolide combination therapy group. β-lactam and macrolide combination therapy significantly decreased 30-day mortality (16.7% vs. 43.8%; P = 0.015) and 14-day mortality (6.7% vs. 31.3%; P = 0.020), but not ICU mortality (10% vs 27.1%, P = 0.08) compared with non-macrolide-containing β-lactam therapy. After adjusting by IPTW, macrolide combination therapy also decreased 30-day mortality (odds ratio, 0.29; 95%CI, 0.09–0.96; P = 0.04) and 14-day mortality (odds ratio, 0.19; 95%CI, 0.04–0.92; P = 0.04), but not ICU mortality (odds ratio, 0.34; 95%CI, 0.08–1.36; P = 0.13).
Combination therapy with β-lactam and macrolides significantly improved the prognosis of SCAP patients hospitalized in the ICU compared with a non-macrolide-containing β-lactam regimen.
Severe Community-Acquired Pneumonia
2021, Encyclopedia of Respiratory Medicine, Second Edition
Although there is no general consensus on the definition of severe community-acquired pneumonia (SCAP), the most accepted criteria are based on the 2007 Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of CAP in adults. Since pulmonary and extra-pulmonary complications increase mortality and ICU admission, early recognition and management of SCAP are of pivotal importance. Severity scores and inflammatory biomarkers may be a complementary prognostic tool. An empiric antibiotic therapy based on international and local guidelines is associated with improved outcomes. The use of corticosteroids should be considered in SCAP with high inflammatory response.
Effect of Combined β-Lactam/Macrolide Therapy on Mortality According to the Microbial Etiology and Inflammatory Status of Patients With Community-Acquired Pneumonia
2019, Chest
Antibiotic combinations that include macrolides have shown lower mortality rates than β-lactams in monotherapy or combined with fluoroquinolones in patients with community-acquired pneumonia (CAP). However, this effect has not been studied according to the levels of C-reactive protein in CAP with identified microbial cause. In patients with CAP and known microbial cause we aimed to evaluate 30-day mortality of a β-lactam plus macrolide (BL + M) compared with a fluoroquinolone alone or with a β-lactam (FQ ± BL).
We analyzed a prospective observational cohort of patients with CAP admitted to the Hospital Clinic of Barcelona between 1996 and 2016. We included only patients with known microbial cause.
Of 1,715 patients (29%) with known etiology, a total of 932 patients (54%) received BL + M. Despite lower crude mortality in the BL + M group in the overall population (BL + M, 5% vs FQ ± BL, 8%; P = .015), after adjustment by a propensity score and baseline characteristics, the combination of BL + M had a protective effect on mortality only in patients with high inflammatory response (C-reactive protein, > 15 mg/dL) and pneumococcal CAP (adjusted OR, 0.28; 95% CI, 0.09-0.93). No benefits on mortality were observed for the population without high inflammatory response and pneumococcal CAP or with other etiologies.
The combination of a β-lactam with a macrolide was associated with decreased mortality in patients with pneumococcal CAP and in patients with high systemic inflammatory response. When both factors occurred together, BL + M was protective for mortality in the multivariate analysis.
Long-Term Outcomes in Severe Community-Acquired Pneumonia
2024, Seminars in Respiratory and Critical Care Medicine

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PulmonaryImpact of antibiotic therapy in severe community-acquired pneumonia: Data from the Infauci study

Highlights

Abstract

Introduction

Section snippets

Study design and data collection

Patient characteristics

Discussion

Conclusions

Ethical approval and consent to participate

Consent for publication

Availability of supporting data

Competing interests

Authors' contributions

Acknowledgments

Financial support

Chest

Clin Microbiol Infect

Chest

Chest

Mayo Clin Proc

Clin Microbiol Infect

Am J Emerg Med

The principles and practice of medicine. Designed for the use of practitioners and students of medicine

Prognosis and outcomes of patients with community-acquired pneumonia: a meta-analysis

JAMA

Severity assessment tools to guide ICU admission in community-acquired pneumonia: systematic review and meta-analysis

Intensive Care Med

Infectious Disease Society of American/American Thoracic Society consensus guidelines for the management of community acquired pneumonia in adults

Clin Infect Dis

Guidelines for the management of adult lower respiratory tract infections- full version

Clin Microbiol Infect

BTS guidelines for the management of community acquired pneumonia in adults: update 2009

Thorax

Combination antibiotic therapy lowers mortality among severely ill patients with pneumococcal bacteremia

Am J Respir Crit Care Med

Pulmonary
Impact of antibiotic therapy in severe community-acquired pneumonia: Data from the Infauci study