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Original Research: Chest Infections |

Decrease in Mortality in Severe Community-Acquired Pneumococcal PneumoniaMortality in Severe Pneumococcal Pneumonia: Impact of Improving Antibiotic Strategies (2000-2013) FREE TO VIEW

Simone Gattarello, MD; Bárbara Borgatta, MD; Jordi Solé-Violán, MD, PhD; Jordi Vallés, MD, PhD; Loreto Vidaur, MD; Rafael Zaragoza, MD, PhD; Antoni Torres, MD, PhD; Jordi Rello, MD, PhD; for the Community-Acquired Pneumonia en la Unidad de Cuidados Intensivos II Study Investigators∗
Author and Funding Information

From the Critical Care Department (Drs Gattarello, Borgatta and Rello), Vall d’Hebron Hospital, Universitat Autonoma de Barcelona and Medicine Department, Vall d’Hebron Institut de Recerca (VHIR), Barcelona; Intensive Care Unit (Dr Solé-Violán), Dr Negrin University Hospital, Las Palmas de Gran Canaria; Critical Care Center (Dr Vallés), Sabadell Hospital, Consorci Hospitalari Universitari Parc Taulí, Sabadell; Intensive Care Department (Dr Vidaur), Donostia Hospital, Donostia;. Intensive Care Department (Dr Zaragoza), Dr Peset University Hospital, Valencia; Respiratory Disease Department (Dr Torres), Hospital Clínic i Provincial de Barcelona, University of Barcelona, Institut d’investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona; and Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES) (Drs Solé-Violán, Vallés, Vidaur, Torres, and Rello), Bunyola, Islas Baleares, Spain.

CORRESPONDENCE TO: Simone Gattarello, MD, Critical Care Department. Vall d’Hebron University Hospital, Ps. Vall d’Hebron, 119-129. Anexe AG - 5a planta. 08035 Barcelona, Spain; e-mail: gattarello@gmail.com


*The investigators in the Community-Acquired Pneumonia en la Unidad de Cuidados Intensivos (CAPUCI) II study group are listed in e-Appendix 1.

FOR EDITORIAL COMMENT SEE PAGE 6

FUNDING/SUPPORT: This study received support from the following: 2001/SGR414, Red Respira Instituto de Salud Carlos III [RTIC 03/11], fondo de investigación sanitaria [PI 04/1500], and Centro de Investigación en Red de Enfermedades Respiratorias (proyecto corporativo de investigación Pneumonia).

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;146(1):22-31. doi:10.1378/chest.13-1531
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OBJECTIVE:  The objective of the present study was to compare antibiotic prescribing practices and survival in the ICU for patients with pneumococcal severe community-acquired pneumonia (SCAP) between 2000 and 2013.

METHODS:  This was a matched case-control study of two prospectively recorded cohorts in Europe. Eighty patients from the Community-Acquired Pneumonia en la Unidad de Cuidados Intensivos (CAPUCI) II study (case group) were matched with 80 patients from CAPUCI I (control group) based on the following: shock at admission, need of mechanical ventilation, COPD, immunosuppression, and age.

RESULTS:  Demographic data were comparable in the two groups. Combined antibiotic therapy increased from 66.2% to 87.5% (P < .01), and the percentage of patients receiving the first dose of antibiotic within 3 h increased from 27.5% to 70.0% (P < .01). ICU mortality was significantly lower (OR, 0.82; 95% CI, 0.68-0.98) in cases, both in the whole population and in the subgroups of patients with shock (OR, 0.67; 95% CI, 0.50-0.89) or receiving mechanical ventilation (OR, 0.73; 95% CI, 0.55-0.96). In the multivariate analysis, ICU mortality increased in patients requiring mechanical ventilation (OR, 5.23; 95% CI, 1.60-17.17) and decreased in patients receiving early antibiotic treatment (OR, 0.36; 95% CI, 0.15-0.87) and combined therapy (OR, 0.19; 95% CI, 0.07-0.51).

CONCLUSIONS:  In pneumococcal SCAP, early antibiotic prescription and use of combination therapy increased. Both were associated with improved survival.

Figures in this Article

Community-acquired pneumonia (CAP) is a major health problem associated with high morbidity and mortality.1,2 Despite geographic differences, Streptococcus pneumoniae is the most common cause of pneumonia worldwide.1 Over the years, CAP studies have focused on risk factors,3 microbiology,4,5 biomarkers,6,7 and mortality8; more recently, they have addressed the introduction of new antibiotic policies and the availability of new drugs.9,10

In Western countries, despite improved survival due to changes in antibiotic policies,1113 poor prognosis is seen in older people with more comorbidities and chronic illness in whom life expectancy has been prolonged.1417 On the other hand, it has been shown that septic shock mortality has decreased.1820 The aggregate impact of these demographic and clinical trends on the CAP survival rate is of great importance to clinicians, but no recent data are available in the literature, especially in critical patients with severe community-acquired pneumonia (SCAP).

Our hypothesis was that improvement in antibiotic policies contributed to reduced mortality due to SCAP in the ICU setting. For this reason, the primary objective of the present study was to compare ICU mortality due to SCAP caused by S pneumoniae in two different periods (2000-2002 and 2008-2013). The secondary objective was to identify changes in antibiotic strategies in pneumococcal SCAP.

This was a matched case-control study of two cohorts of patients prospectively recorded in Europe (the Community-Acquired Pneumonia en la Unidad de Cuidados Intensivos [CAPUCI] studies). CAPUCI I and II are two European, prospective, multicenter studies conducted in patients admitted to the ICU for CAP. The CAPUCI I study recorded data from 33 hospitals from 2000 to 2002. Data from this cohort have been reported elsewhere.11 The CAPUCI II study was a follow-up project endorsed by the European Critical Care Research Network. Data were recorded from patients admitted for SCAP from 2008 to 2013 in 29 European ICUs. Demographic data, and clinical presentation, outcome, and antibiotic therapy data were registered; antibiotic prescription was left to the discretion of the attending physician. Patients were admitted to the ICU either to undergo mechanical ventilation or because they were critically ill,21 in accordance to Infectious Disease Society of America/American Thoracic Society guidelines.1 People with severe chronic illness in whom pneumonia was an expected terminal event were not included; patients were observed until ICU discharge or death. The study was approved by the ethics board of the coordinating center (REF 2005/NA), in accordance with national regulations, and informed consent was waived due to the observational nature of the studies. Definitions are given in e-Appendix 2.

Eighty patients (case group, n = 80) from the CAPUCI II database who were diagnosed with SCAP caused by S pneumoniae were matched with 80 patients with similar clinical characteristics from the CAPUCI I database (control group, n = 80). For each patient in the case group, one patient with identical clinical features was selected from the control group. Matching variables were the following: presence of shock at ICU admission, need for mechanical ventilation, immunosuppression, and age (age cutoff: 65 years),22 as these are the main determinants for mortality in CAP,23,24 and COPD, given its high prevalence in Western populations and its controversial role in the increase in mortality in SCAP.25,26

Continuous variables were compared with Student t test for normally distributed variables, or the Mann-Whitney U test for nonnormally distributed variables. Categorical variables were evaluated with the χ2 or two-tailed Fisher exact test. Results are expressed as median and interquartile range (IQR) for continuous variables or as percentages of the group from which they were derived for categorical variables. Two-tailed tests were used to determine statistical significance; a P value < .05 was considered significant.

The Kaplan-Meier product limit method was used to construct survival curves for patients receiving combination and monotherapy regimens and early vs late antibiotic administration. All data management and statistical analysis were performed using the SPSS 15 processor (IBM).

One hundred and sixty patients were enrolled: 80 patients from the 2008 to 2013 cohort (case group) paired with 80 from the 2000 to 2002 cohort (control group). Figure 1 shows the algorithm for the selection of the patients and the ICU mortality for each subgroup; incidence of severe pneumococcal pneumonia increased significantly (43.9% vs 27.0%; OR, 1.30; 95% CI, 1.15-1.48). Table 1 shows the variables used to match patients. The groups presented identical prevalence of the items evaluated: Shock at ICU admission was present in 60.0% of patients, while 65.0% had received mechanical ventilation. Thirty-three percent of patients were aged > 65 years, 32.2% received a diagnosis of COPD, and 7.5% presented immunosuppression. The cause of immunosuppression was HIV infection in seven of 12 patients.

Figure Jump LinkFigure 1  Flow diagram of patient selection and mortality in the different subgroups. CAPUCI = Community-Acquired Pneumonia en la Unidad de Cuidados Intensivos.Grahic Jump Location
Table Graphic Jump Location
TABLE 1  ] Description of Matched Variables

Data are given as No. (%).

Medical history and clinical presentation were comparable in the two cohorts (Table 2). Estimated probability of death was 31.0% in the case group and 24.0% in the control group (P = .35). ICU length of stay was similar: Median (IQR) was 10.0 days (4-19) vs 10.0 days (4-17.8), respectively (P = .97). Blood cultures were positive in 36.2% of the case group and 40.0% of the control group (P = .75). As shown in Table 3, bacteremia was significantly associated with the presence of septic shock (P = .05). Acute kidney injury was observed in 44 patients (55.0%) in the case group vs 31 (39.2%) in the control group (P = .06), while rapid radiographic spread was recorded in 48.8% and 51.2%, respectively (P = .87).

Table Graphic Jump Location
TABLE 2  ] Other Demographics Data and Clinical Presentations

Data given as No. (%) unless otherwise indicated. IQR = interquartile range.

Table Graphic Jump Location
TABLE 3  ] Comparison Between Bacteremic and Nonbacteremic Patients

Data given as No. (%) unless otherwise indicated. AB = antibiotic. See Table 2 legend for expansion of other abbreviation.

ICU mortality was significantly different between the groups: 14 patients (17.5%) from the case group died compared with 27 (32.5%) in the control group, with an OR of ICU mortality of 0.82 (95% CI, 0.68-0.98; P = .04). Most deaths were late and due to multiorgan dysfunction syndrome. Figure 1 shows ICU mortality of the different subgroups. Mortality was comparable between matched and nonmatched patients in CAPUCI I (22.6% vs 33.8%, P = .26) and in CAPUCI II (17.5% vs 14.3%, P = 1.00). Figure 2 shows changes in ICU mortality between the two time periods in the whole population and in the subgroups of patients with shock (OR, 0.67; 95% CI, 0.50-0.89) and those receiving mechanical ventilation (OR, 0.73; 95% CI, 0.55-0.96). Kaplan-Meier survival analysis was performed in the global cohort and in the subgroups of patients with shock and under mechanical ventilation, stratifying by monotherapy vs combined therapy (log-rank P < .01, .02, and .01, respectively) (Fig 3) and early vs non-early antibiotic treatment (log-rank P < .01, .01, and .02, respectively) (Fig 4).

Figure Jump LinkFigure 2  ICU mortality in the whole population and in different subgroups of patients. IMV = invasive mechanical ventilation.Grahic Jump Location
Figure Jump LinkFigure 3  Kaplan-Meier survival curve stratified for monotherapy vs combined therapy. A, The whole population. B, Patients with shock. C, Patients receiving mechanical ventilation.Grahic Jump Location
Figure Jump LinkFigure 4  Kaplan-Meier survival curve stratified for early vs nonearly antibiotic treatment. A, The whole population. B, Patients with shock. C, Patients receiving mechanical ventilation.Grahic Jump Location

Combined therapy differed significantly between the groups: 70 patients (87.5%) from the case group received combined therapy vs 53 (66.2%) from the control group (P < .01) (Table 4). The first dose of antibiotic was administered within 3 h of admission to the ED in 70.0% of the case group but in only 27.5% of the control group (P < .01). Compliance with 2007 Infectious Disease Society of America/American Thoracic Society guidelines1 was obtained in 64 patients (80.0%) in the case group and in 38 (47.5%) in the control group (P < .01).

Table Graphic Jump Location
TABLE 4  ] Characteristics of Antibiotic Treatment

Data given as No. (%) unless otherwise indicated. IDSA/ATS = Infectious Diseases Society of America/American Thoracic Society. See Table 3 for expansion of other abbreviation.

The most frequent pattern of antibiotic use was a combination of a cephalosporin with a macrolide (Table 5), which was administered in 65 patients (40.6%): 38 (47.5%) in the case group and 27 (33.8%) in the control group (P = .11). The most frequent combination in the case group was ceftriaxone and azithromycin (26 patients, 32.5%), while in the control group it was ceftriaxone and clarithromycin (20 patients, 25.0%). The second most frequently administered antibiotic pattern was a cephalosporin and a quinolone; cefotaxime/ceftriaxone plus levofloxacin was the most used combination (case group: 24 patients [30.0%]; control group: nine patients [11.3%]).

Table Graphic Jump Location
TABLE 5  ] Most Frequent Patterns of Antibiotic Treatment

Data given as No. (%) unless otherwise indicated.

a 

P value calculated between case group and control group.

Table 6 shows the univariate analysis for determining variables associated with ICU mortality. COPD (P = .05), estimated probability of death (P < .01), shock at ICU admission (P < .01), invasive mechanical ventilation (P < .01), acute kidney injury (P = .02), rapid radiographic spread (P = .02), combined therapy (P = .02), and early antibiotic administration (P = .02) differed significantly between survivors and nonsurvivors.

Table Graphic Jump Location
TABLE 6  ] Univariate Analysis to Assess Risk Factors for ICU Mortality Due to Pneumococcal SCAP

Data given as No. (%) unless otherwise indicated. SCAP = severe community-acquired pneumonia. See Table 2 and 3 legends for expansion of other abbreviations.

Multivariate analysis was performed to identify risk factors for mortality (Table 7). Variables with significant differences from the univariate model (Table 6) were introduced in this model. The need for invasive mechanical ventilation was associated with a higher risk of ICU mortality (OR, 5.23; 95% CI, 1.60-17.17). In contrast, first dose of antibiotic within 3 h (OR, 0.36; 95% CI, 0.15-0.87) and combined therapy (OR, 0.19; 95% CI, 0.07-0.51) were associated with a lower risk of ICU mortality in pneumococcal SCAP. The model remained similar when the variable “macrolide use” was added as a dependent variable in the multivariate analysis (macrolide use OR for death, 1.52; 95% CI, 0.56-4.16).

Table Graphic Jump Location
TABLE 7  ] Multivariate Analysis to Assess Risk Factors for ICU Mortality Due to SCAP

See Table 3 and 6 legends for expansion of abbreviations.

The main finding of this study was a 15% decrease in ICU mortality due to SCAP caused by S pneumoniae during the study period. Several changes in antibiotic prescription practices were detected, and an association between improved survival and both earlier antibiotic administration and increased combined antibiotic therapy was identified.

The World Health Organization’s annual reports stress the minimal decrease in worldwide mortality secondary to lower respiratory infection: from 4.1 million (1993) to 3.9 million (2002).27,28 Mortality due to all-source infectious diseases has increased in recent decades,29 up to 58% in the United States.30 However, its translation to clinical practice is difficult because no differentiation has been made between mild and severe infection, or local infection, sepsis or septic shock, considering that complicated infection with systemic inflammatory response syndrome bears higher mortality than local infection.31

In accordance with our results, there is evidence supporting a decrease in severe sepsis and septic shock mortality in the last years32: Overall mortality from any-source severe sepsis had decreased in the last decade up to 12%.19,20 Explanations for this trend include higher compliance with international guidelines,33,34 better hemodynamic management,35 improved ventilator setting in mechanical ventilation,36,37 decreased ICU admissions of patients with extremely poor prognosis,19 and changes in medical treatment.35,3840

Studies showing that early antibiotic administration seems to be unrelated to better outcomes did not differentiate between critical and noncritical patients.41,42 It has consistently been demonstrated that early antibiotic administration is a determinant of the outcome in severe sepsis and shock, regardless the source of infection,3840 supporting the 2012 Surviving Sepsis Campaign’s recommendation on initiation of antibiotics within the first hour of the diagnosis of severe sepsis.35

Our results show that combined antibiotic therapy is associated with lower ICU mortality, which is supported by other studies4346; however, most of these enrolled patients with pneumonia and shock. Our data show improved survival in patients receiving combined therapy, both in the general population and in patients with shock or receiving mechanical ventilation (Fig 3), suggesting that the benefit of combined therapy is not limited to patients with shock.

Still, it is unclear why combined therapy is superior to monotherapy. Possible reasons include coverage of atypical pathogens, greater probability of covering multiresistant microorganisms, synergies, and antiinflammatory and immunomodulatory effects of some antimicrobials. In the present study, as all cases were caused by S pneumoniae, it is reasonable to assume that factors other than covering atypical pathogens or covering multiresistant microorganisms were related to decreased mortality.

Interestingly, epidemiology of invasive pneumococcal disease changed significantly in Spain after the introduction of the 7-valent pneumococcal conjugate vaccine, where a shift in pneumococcal serotypes has been documented (serotypes not covered by the vaccine). This has been associated with more empyema and different rates of shock or respiratory failure.4749 Substantial reduction in hospitalization for pneumonia among adults has been reported after introduction of the 7-valent pneumococcal conjugate vaccine.50

A significant decrease in mortality was observed in the whole population as well as in the subgroups of patients with shock and receiving mechanical ventilation (Fig 2), even when stratified according to combined antibiotic therapy vs monotherapy (Fig 3) and early antibiotic treatment vs non-early antibiotic administration (Fig 4). This observation is not only of academic interest: In view of these results, all patients with pneumococcal SCAP requiring ICU admission should receive early treatment and combined antibiotic therapy.

Significant differences in antibiotic regimens administered to the study groups were seen (Table 5), the most important being that azithromycin was not administered to the control group, because it was not available in IV formulation in Spain at the time of the CAPUCI I study. Also, more broad-spectrum antibiotic combinations were administered in the control group than in the case group; in the case group, 80.0% of patients received a combination of cephalosporin plus a macrolide or fluoroquinolone compared with 47.6% of control subjects, suggesting a higher compliance to guidelines in the case group. No differences in mortality were found between different antibiotic regimens.

Interestingly, our study population comes from a large, prospective, multicenter database and is homogeneous, since all the patients were admitted to the ICU. To our knowledge, this is the first study to compare the clinical characteristics of the subset of critically ill patients in the ICU with pneumococcal CAP. Moreover, whereas most prior studies evaluating antibiotic treatment in SCAP have been limited to subgroups with shock, our results showed a lower mortality rate in different populations, stressing the clinical implications of our findings.

The major limitation of the present study is its design, where prescription of antibiotics and hemodynamic resuscitation were not standardized. On the other hand, there were no significant differences between the two cohorts (Tables 1, 2).

Another important limitation is that several improvements have been introduced in the management of critical patients, including management of septic shock and mechanical ventilation. Even though major determinants of mortality for SCAP were included in our analysis, it was not possible to record all of these changes. Severity of illness was recorded with different scores; therefore, univariate and multivariate analysis adjusted severity for the “estimated risk of death” rather than a score. We acknowledge that the use of matching criteria for respiratory failure other than mechanical ventilation, such as Pao2/Fio2, may be associated with different outcomes, but this may also be influenced by other supporting measures like positive end-expiratory pressure level or other ventilator settings. Bacteremia alone is not a good tool to predict outcome in pneumococcal pneumonia51; for this reason, this variable was not used to match cohorts. Although reports4749 have correlated variation in serotypes with outcomes and complications, data regarding vaccination or serotypes were not recorded in our study. Finally, a selection bias may limit the generalization of findings.

In summary, incidence, mortality, and management of severe pneumococcal pneumonia has significantly changed in the last decade. Improved ICU survival was associated with earlier antibiotic prescription and increased use of combined antibiotic therapy.

Author contributions: S. G. served as principal author, had full access to all of the data in the study, and takes responsibility for the integrity of the data and the accuracy of the data analysis. S. G. and J. R. contributed to the study concept and design; B. B., J. S.-V., J. V., L. V., R. Z., and A. T. contributed to data interpretation; S. G. and J. R. contributed to drafting of the manuscript; B. B., J. S.-V., J. V., L. V., R. Z., and A. T. contributed to critical revision of the manuscript; and B. B., J. S.-V., J. V., L. V., R. Z., and A. T. contributed to approval of the final version.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Drs Rello and Zaragoza serve on the speaker’s bureau and advisory boards for Pfizer Inc. The remaining authors have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Role of sponsors: The sponsors had no role in the design of the study, the collection and analysis of the data, or the preparation of the manuscript.

Other contributions: CAPUCI II is a European Critical Care Research Network endorsed project by the European Society of Intensive Care Medicine. We are indebted to Elsa Afonso, BSN, research nurse, for supervising the databases and coordinating the sites participating in the CAPUCI II project and to Michael Maudsley, BS, for editing the language in the final manuscript. Thanks also to Marta Garcia Alfaro, MD: Your patience, understanding, and your precious advice were ultimate for the realization of the present manuscript.

Additional information: The e-Appendixes can be found in the Supplemental Materials section of the online article.

CAP

community-acquired pneumonia

IQR

interquartile range

SCAP

severe community-acquired pneumonia

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Esquinas Rodriguez AM, Papadakos PJ, Carron M, Cosentini R, Chiumello D. Clinical review: helmet and non-invasive mechanical ventilation in critically ill patients. Crit Care. 2013;17(2):223. [CrossRef] [PubMed]
 
Gaieski DF, Mikkelsen ME, Band RA, et al. Impact of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department. Crit Care Med. 2010;38(4):1045-1053. [CrossRef] [PubMed]
 
Nobre V, Sarasin FP, Pugin J. Prompt antibiotic administration and goal-directed hemodynamic support in patients with severe sepsis and septic shock. Curr Opin Crit Care. 2007;13(5):586-591. [CrossRef] [PubMed]
 
Kumar A, Roberts D, Wood KE, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006;34(6):1589-1596. [CrossRef] [PubMed]
 
Waterer GW, Kessler LA, Wunderink RG. Delayed administration of antibiotics and atypical presentation in community-acquired pneumonia. Chest. 2006;130(1):11-15. [CrossRef] [PubMed]
 
Bordon J, Aliberti S, Duvvuri P, et al. Early administration of the first antimicrobials should be considered a marker of optimal care of patients with community-acquired pneumonia rather than a predictor of outcomes. Int J Infect Dis. 2013;17(5):e293-e298. [CrossRef] [PubMed]
 
Waterer GW, Somes GW, Wunderink RG. Monotherapy may be suboptimal for severe bacteremic pneumococcal pneumonia. Arch Intern Med. 2001;161(15):1837-1842. [CrossRef] [PubMed]
 
Baddour LM, Yu VL, Klugman KP, et al; International Pneumococcal Study Group. Combination antibiotic therapy lowers mortality among severely ill patients with pneumococcal bacteremia. Am J Respir Crit Care Med. 2004;170(4):440-444. [CrossRef] [PubMed]
 
Luján M, Gallego M, Rello J. Optimal therapy for severe pneumococcal community-acquired pneumonia. Intensive Care Med. 2006;32(7):971-980. [CrossRef] [PubMed]
 
Naucler P, Darenberg J, Morfeldt E, Ortqvist A, Henriques Normark B. Contribution of host, bacterial factors and antibiotic treatment to mortality in adult patients with bacteraemic pneumococcal pneumonia. Thorax. 2013;68(6):571-579. [CrossRef] [PubMed]
 
Burgos J, Luján M, Larrosa MN, et al. Risk factors for respiratory failure in pneumococcal pneumonia: the importance of pneumococcal serotypes. Eur Respir J. 2014;43(2):545-553. [CrossRef] [PubMed]
 
Burgos J, Lujan M, Falcó V, et al. The spectrum of pneumococcal empyema in adults in the early 21st century. Clin Infect Dis. 2011;53(3):254-261. [CrossRef] [PubMed]
 
Luján M, Gallego M, Belmonte Y, et al. Influence of pneumococcal serotype group on outcome in adults with bacteraemic pneumonia. Eur Respir J. 2010;36(5):1073-1079. [CrossRef] [PubMed]
 
Griffin MR, Zhu Y, Moore MRUS, Whitney CG, Grijalva CG. U.S. hospitalizations for pneumonia after a decade of pneumococcal vaccination. N Engl J Med. 2013;369(2):155-163. [CrossRef] [PubMed]
 
Rello J, Lisboa T, Lujan M, et al; DNA-Neumococo Study Group. Severity of pneumococcal pneumonia associated with genomic bacterial load. Chest. 2009;136(3):832-840. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1  Flow diagram of patient selection and mortality in the different subgroups. CAPUCI = Community-Acquired Pneumonia en la Unidad de Cuidados Intensivos.Grahic Jump Location
Figure Jump LinkFigure 2  ICU mortality in the whole population and in different subgroups of patients. IMV = invasive mechanical ventilation.Grahic Jump Location
Figure Jump LinkFigure 3  Kaplan-Meier survival curve stratified for monotherapy vs combined therapy. A, The whole population. B, Patients with shock. C, Patients receiving mechanical ventilation.Grahic Jump Location
Figure Jump LinkFigure 4  Kaplan-Meier survival curve stratified for early vs nonearly antibiotic treatment. A, The whole population. B, Patients with shock. C, Patients receiving mechanical ventilation.Grahic Jump Location

Tables

Table Graphic Jump Location
TABLE 1  ] Description of Matched Variables

Data are given as No. (%).

Table Graphic Jump Location
TABLE 2  ] Other Demographics Data and Clinical Presentations

Data given as No. (%) unless otherwise indicated. IQR = interquartile range.

Table Graphic Jump Location
TABLE 3  ] Comparison Between Bacteremic and Nonbacteremic Patients

Data given as No. (%) unless otherwise indicated. AB = antibiotic. See Table 2 legend for expansion of other abbreviation.

Table Graphic Jump Location
TABLE 4  ] Characteristics of Antibiotic Treatment

Data given as No. (%) unless otherwise indicated. IDSA/ATS = Infectious Diseases Society of America/American Thoracic Society. See Table 3 for expansion of other abbreviation.

Table Graphic Jump Location
TABLE 5  ] Most Frequent Patterns of Antibiotic Treatment

Data given as No. (%) unless otherwise indicated.

a 

P value calculated between case group and control group.

Table Graphic Jump Location
TABLE 6  ] Univariate Analysis to Assess Risk Factors for ICU Mortality Due to Pneumococcal SCAP

Data given as No. (%) unless otherwise indicated. SCAP = severe community-acquired pneumonia. See Table 2 and 3 legends for expansion of other abbreviations.

Table Graphic Jump Location
TABLE 7  ] Multivariate Analysis to Assess Risk Factors for ICU Mortality Due to SCAP

See Table 3 and 6 legends for expansion of abbreviations.

References

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Vallés J, Palomar M, Alvárez-Lerma F, et al; GTEI/SEMICYUC Working Group on Bacteremia. Evolution over a 15-year period of clinical characteristics and outcomes of critically ill patients with community-acquired bacteremia. Crit Care Med. 2013;41(1):76-83. [CrossRef] [PubMed]
 
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Menéndez R, Torres A, Reyes S, et al. Initial management of pneumonia and sepsis: factors associated with improved outcome. Eur Respir J. 2012;39(1):156-162. [CrossRef] [PubMed]
 
Dellinger RP, Levy MM, Rhodes A, et al; Surviving Sepsis Campaign Guidelines Committee including The Pediatric Subgroup. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39(2):165-228. [CrossRef] [PubMed]
 
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Esquinas Rodriguez AM, Papadakos PJ, Carron M, Cosentini R, Chiumello D. Clinical review: helmet and non-invasive mechanical ventilation in critically ill patients. Crit Care. 2013;17(2):223. [CrossRef] [PubMed]
 
Gaieski DF, Mikkelsen ME, Band RA, et al. Impact of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department. Crit Care Med. 2010;38(4):1045-1053. [CrossRef] [PubMed]
 
Nobre V, Sarasin FP, Pugin J. Prompt antibiotic administration and goal-directed hemodynamic support in patients with severe sepsis and septic shock. Curr Opin Crit Care. 2007;13(5):586-591. [CrossRef] [PubMed]
 
Kumar A, Roberts D, Wood KE, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006;34(6):1589-1596. [CrossRef] [PubMed]
 
Waterer GW, Kessler LA, Wunderink RG. Delayed administration of antibiotics and atypical presentation in community-acquired pneumonia. Chest. 2006;130(1):11-15. [CrossRef] [PubMed]
 
Bordon J, Aliberti S, Duvvuri P, et al. Early administration of the first antimicrobials should be considered a marker of optimal care of patients with community-acquired pneumonia rather than a predictor of outcomes. Int J Infect Dis. 2013;17(5):e293-e298. [CrossRef] [PubMed]
 
Waterer GW, Somes GW, Wunderink RG. Monotherapy may be suboptimal for severe bacteremic pneumococcal pneumonia. Arch Intern Med. 2001;161(15):1837-1842. [CrossRef] [PubMed]
 
Baddour LM, Yu VL, Klugman KP, et al; International Pneumococcal Study Group. Combination antibiotic therapy lowers mortality among severely ill patients with pneumococcal bacteremia. Am J Respir Crit Care Med. 2004;170(4):440-444. [CrossRef] [PubMed]
 
Luján M, Gallego M, Rello J. Optimal therapy for severe pneumococcal community-acquired pneumonia. Intensive Care Med. 2006;32(7):971-980. [CrossRef] [PubMed]
 
Naucler P, Darenberg J, Morfeldt E, Ortqvist A, Henriques Normark B. Contribution of host, bacterial factors and antibiotic treatment to mortality in adult patients with bacteraemic pneumococcal pneumonia. Thorax. 2013;68(6):571-579. [CrossRef] [PubMed]
 
Burgos J, Luján M, Larrosa MN, et al. Risk factors for respiratory failure in pneumococcal pneumonia: the importance of pneumococcal serotypes. Eur Respir J. 2014;43(2):545-553. [CrossRef] [PubMed]
 
Burgos J, Lujan M, Falcó V, et al. The spectrum of pneumococcal empyema in adults in the early 21st century. Clin Infect Dis. 2011;53(3):254-261. [CrossRef] [PubMed]
 
Luján M, Gallego M, Belmonte Y, et al. Influence of pneumococcal serotype group on outcome in adults with bacteraemic pneumonia. Eur Respir J. 2010;36(5):1073-1079. [CrossRef] [PubMed]
 
Griffin MR, Zhu Y, Moore MRUS, Whitney CG, Grijalva CG. U.S. hospitalizations for pneumonia after a decade of pneumococcal vaccination. N Engl J Med. 2013;369(2):155-163. [CrossRef] [PubMed]
 
Rello J, Lisboa T, Lujan M, et al; DNA-Neumococo Study Group. Severity of pneumococcal pneumonia associated with genomic bacterial load. Chest. 2009;136(3):832-840. [CrossRef] [PubMed]
 
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