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Predictors of severe sepsis among patients hospitalized for community-acquired pneumonia.

With an incidence of three to five cases per 1,000 adults per year, Community-acquired pneumonia (CAP), is a frequent cause of death worldwide. (1-3) Severe sepsis, the syndrome of infection complicated by systemic inflammation and organ dysfunction, is a complication of CAP. Severe sepsis is a worldwide health problem, and a significant one in the United States, with an incidence of 343 cases per 100,000 inhabitants in the U.S. At least one-third of CAP patients present to the hospital with severe sepsis. (4-5)

Initial identification of the severity of sepsis is important in order to institute different management and monitoring measures. (6) Clinicians often do not recognize the presence of severe sepsis in CAP patients, even when organ dysfunction is present. Studies aimed at identifying the CAP population at risk of developing severe sepsis in the community before arriving at the hospital are lacking.

The aim of our study was to determine the risk factors for presentation at the hospital with severe sepsis in patients with CAP.

Patients and data collection

A prospective, multi-center, observational cohort study was carried out in 13 hospitals belonging to the Spanish National Health System (CAP Quality Group); a complete, detailed description has been reported in a prior publication. (7) Briefly, the inclusion criterion was a diagnosis of CAP, defined as acute symptoms or signs with a new compatible radiographic lung infiltrate. Exclusion criteria were nursing-home patients, transplant or oncologic patients, leukopenia or neutropenia (unless attributable to pneumonia), Human immunodeficiency virus-positive (HIV) patients with severe immunosuppression (CD4 <100), treatment with corticosteroids (>20 mg/day) or other immunosuppressive drugs, and patients with DNR (do not resuscitate) orders or in whom CAP was considered a terminal event. The study was approved by the ethics committee (ISS Hospital La Fe 2004/15 July, Assent 2004/0101), and I the patients provided written informed consent.

We recorded data on age, gender, prior antibiotic treatment for the current episode, comorbid conditions (chronic obstructive pulmonary disease [COPD], heart, liver, neurological or renal diseases, and diabetes mellitus), clinical, analytical and radiological results, and the prognostic scales Pneumonia Severity Index (PSI) (8) and CURB65 risk class. (9)

Comorbidities were assessed based on clinical history along with prior discharge diagnoses and clinical records, review of medications, and results of analyses. (8) Sepsis and severe sepsis were evaluated at CAP diagnosis on hospital admission, following previously accepted criteria. (4,7,10) Sepsis was defined as the presence of pneumonia and systemic inflammatory response syndrome (SIRS). Severe sepsis was considered if criteria for sepsis were met and acute failure of at least one organ was present: arterial hypoxemia (PaO2/FiO2 <300), creatinine >2 mg/dL, acute confusion, or hypotension (systolic arterial tension [ST] <90 mmHg). While organ dysfunction has also been defined in terms of hepatic or hematologic failure, information on these organ systems was not available in the data set.

Microbiological analysis and diagnostic criteria

Microbiological studies comprised the following: 2,550 (62.7%) blood cultures; 3,636 (89.3%) urinary antigens for Legionella pneumophila and 3,654 (89.8%) for Streptococcus pneumonia; 1,760 (43.2%) sputum cultures, 1,902 (46.7%) paired serological studies for Chlamydophila pneumoniae, Mycoplasma pneumoniae, Coxiella burnetii, and Legionella pneumophila; nasopharyngeal swabs to detect viral nucleic acids; and invasive samples obtained by bronchoscopy (285 [7%] bronchial aspirate [BAS] and 118 [2.9%] bronchoalveolar lavage [BAL]), and 276 (6.8%) pleural fluid cultures.

Microbiologic diagnostic criteria were the following: 1) positive urinary antigens for S pneumoniae and Legionella pneumophila; 2) isolation of microorganisms in BAL ([greater than or equal to]104 UFC/mL), BAS ([greater than or equal to]105 UFC/mL) or in pleural fluid; 3) isolation of one predominant microorganism in sputum or L pneumophila in buffered charcoal yeast extract (BCYE) agar; 4) microorganisms in blood culture; 5) seroconversion or a four-fold antibody increase in titers of IgG for C pneumoniae ([greater than or equal to] 1:512), M pneumoniae and C burnetii, ([greater than or equal to] 1:160) or IgM [greater than or equal to] 1:32 for C pneumoniae, and [greater than or equal to] 1:80 for M pneumoniae and C burnetii; 6) positive detection of viral nucleic acids in nasopharyngeal swab.

Mixed etiology was defined as pneumonia due to more than one pathogen (virus or bacteria). (11)

The evaluated outcome was mortality during hospitalization and at 30-day and 90-day follow-up. Length of stay (LOS) was defined as the number of days from hospital admission to discharge.

Data analysis was performed using the SPSS statistical software package, version 15.0. Categorical variable results were expressed as count (percentage) and were compared using the [chi square] test. Continuous variables were expressed as median with interquartile range (IQR) and were analyzed using nonparametric tests. PSI and CURB65 scales were categorized as low risk (PSI [less than or equal to] III/ CURB65 [less than or equal to] 2) and high risk (PSI >III/ CURB65 [greater than or equal to] 3). Severe sepsis was dichotomized as yes (severe-sepsis criteria at hospital admission) and no (non-severe-sepsis criteria, the reference group).

Two multivariable statistical studies to predict risk factors for severe-sepsis CAP, the dependent variable, were performed using stepwise logistic regression analyses. In the first model, the included independent variables were those related to characteristics of patients. In the second model, the independent variables were those related to etiology (causal microorganisms). In both models, the independent variables were those found to be significant in the univariate analyses. The Hosmer and Lemeshow goodness-of-fit test was performed to evaluate the adequacy of the models. (12)

The cohort comprised 4,374 patients presenting to the emergency department with CAP and admitted to the hospital. We studied 4,070 patients after excluding 237 nursing-home and 66 DNR patients: 1,529 (37.6%) had severe sepsis (Table 1).

Mortality for the whole cohort was 3.3% and the median length of stay was 7 (IQR 4-10) days. Mortality was significantly higher in severe-sepsis CAP (Table 2).

Characteristics related to severe-sepsis CAP compared to the reference group are shown in Table 1. Severe-sepsis CAP was more frequent in men, patients older than 65 years, and those with COPD and renal disease, whereas diabetes mellitus was more frequent in those without sepsis. Severe-sepsis CAP also presented with higher PSI and CURB65 scores and more multilobar infiltrates. Patients who received prior antibiotic treatment had lower rates of severe sepsis.

Etiological diagnosis in the whole cohort was reached in 1,506 (37%) patients: 859 (57%) S pneumoniae, 104 (6.9%) L pneumophila, 44 (2.9%) C pneumoniae, 50 (3.3%) C burnetii, 50 (3.3%) M pneumoniae, 45 (3%) Pseudomonas aeruginosa, 43 (2.9%) Haemophilus influenzae, 18 (1.2%) viruses, 15 (1%) E. coli and 121 (8%) mixed etiology.

Severe-sepsis CAP patients had the highest percentage of identified causal microorganisms and more bacteremic episodes. S pneumoniae was the most frequent microorganism found, with a higher percentage in severe sepsis. Atypical microorganisms were more frequent in patients with non-severe sepsis, whereas mixed etiology appeared more often in severe-sepsis CAP. Mixed etiology was caused mainly by S pneumoniae (29.3% with virus or atypical pathogens, 13.8% with Pseudomonas aeruginosa and 5.1% with S aureus) (Table 3).

Four independent risk factors related to patients' characteristics were associated with severe-sepsis CAP: age >65 years, alcohol abuse, renal disease, and COPD, whereas prior antibiotic treatment and diabetes were protective factors. With regard to causal microorganisms, S pneumoniae, mixed etiology, and bacteremia were found to be risk factors (Table 4).

Discussion

The most important findings of our study were: 1) 37.6% of hospitalized CAP patients had developed community-onset severe sepsis already at admission; 2) elderly patients, alcohol abusers, patients with renal disease, and COPD patients were more likely to develop community-onset severe sepsis, whereas prior antibiotic treatment was a protective factor; 3) S pneumoniae and mixed etiology are the main causal microorganisms of severe sepsis.

Severe-sepsis CAP is not well characterized in terms of the most susceptible population even though it can appear in over one-third of the patients. We have identified the aforementioned characteristics, two of them related to comorbid conditions. However, diabetes was more frequent in those without severe sepsis, probably reflecting more lenient hospitalization criteria in diabetic patients.

At hospital admission, patients with severe-sepsis CAP had higher PSI and CURB65 scores, although more than half of these patients had a CURB65 score [less than or equal to]2, pointing out the limitations of scales for severity assessment. Patients who had initiated outpatient antibiotic treatment presented a lower frequency of severe-sepsis CAP at hospital arrival. Prior studies have reported the protective effect on mortality when antibiotic therapy was rapidly initiated between four and six hours after arrival at the hospital. (7,13) Prompt antibiotic administration may rapidly reduce the bacterial load, down-regulating the initial inflammatory cascade and thus decreasing the risk of sepsis. (14,15) On initial severity assessment of CAP, severe-sepsis criteria should be taken into account for the decision-making process, including allocation, monitoring, and management. (6)

The multivariable statistical analyses results confirm that alcohol abuse and two comorbid conditions (COPD and renal disease) were independent host risk factors for developing severe-sepsis CAP in the community The impact of alcohol on developing severe CAP has been linked to an abnormal immune response. (15-18) Curiously, despite the increased risk for severe CAP in COPD patients, mortality is not higher, probably due to the use of previous antibiotics and corticosteroids that reduce inflammatory response. (19-20) Our results suggest that patients with alcohol abuse, COPD, and renal diseases should be specifically targeted for preventive strategies when in contact with health systems, that is, at discharge or during scheduled outpatient visits. Moreover, if treated as outpatients for CAP, they should be closely monitored and receive instructions to rapidly recognize the signs of sepsis.

Bacteremia and etiological microorganisms are more frequently identified when CAP presents with severe sepsis, most likely due to a higher burden of pathogens in most severe episodes. (2,21) S pneumoniae was the most frequently isolated microorganism in severe CAP (1,22,23) and, specifically, some serotypes have been independently associated with septic shock. (24) Mixed etiology was the second-most common etiology in severe-sepsis CAP, underscoring the impact of associated microorganisms on severity. Patients presenting with severe sepsis should benefit from optimizing microbiological tests to rule out bacteremia and mixed etiology, immediately before initiating a combination antibiotic therapy.

This study has some limitations. We have excluded the nursing-home population and patients with CAP considered a terminal event in order to avoid a different population with different characteristics, more frequent nosocomial infections, and/ or multidrug resistant microorganisms and limited therapeutic efforts; therefore, our findings are not applicable to that subset of population. Second, microbiological diagnosis with regard to viruses was incomplete in a considerable subset of patients, the percentage of blood cultures was suboptimal (62.7%), and determination of S pneumoniae serotypes was not performed. The indications of microbiological tests in our study relied on the attending physicians. Third, the information regarding septic shock was not recorded. Nevertheless, our strengths are the large sample size and the prospective study design.

Conclusions

Elderly patients, alcohol abuse, and some comorbidities such as COPD and renal disease are predisposing conditions for progressing to severe-sepsis CAP in the community, mainly due to S pneumoniae and mixed etiologies. Those findings may have clinical implications for patients and physicians in primary care and emergency rooms. Preventive CAP strategies such as vaccination--influenza and S pneumoniae--and health measures recommended in guidelines should be reinforced in the most susceptible patients. Recognition of severe-sepsis CAP signals should be encouraged for patients and for physicians in primary care and/or emergency rooms. Initial severity CAP assessment could be improved by evaluation of severe-sepsis criteria at diagnosis in order to optimize microbiological and analytical tests, to provide closer monitoring and a rapid antibiotic treatment. Efforts should be directed to encouraging actions to reduce the burden of severe-sepsis CAP episodes and facilitate its prompt recognition. 6

REFERENCES

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(2.) Rello J. Demographics, guidelines, and clinical experience in severe community-acquired pneumonia. Critical Care. 2008;12 Suppl 6:S2. doi: 10.1186/cc7025. pmid:19105795

(3.) Welte T, Kohnlein T. Global and local epidemiology of community-acquired pneumonia: the experience of the CAPNETZ Network. Semin Respir Crit Care Med. 2009;30: 127-135. doi: 10.1055/S-0029-1202941. pmid:19296412

(4.) Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al. 2001 SCCM/ ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Intensive Care Med. 2003; 29:530-538. pmid:12664219 doi: 10.1007/S00134-003-1662-x

(5.) Blanco J, Muriel-Bombin A, Sagredo V, et al. Incidence, organ dysfunction and mortality in severe sepsis: a Spanish multicentre study. Crit Care. 2008;12: R158. doi: 10.1186/cc7157. pmid:19091069

(6.) Ewig S, Ruiz M, Mensa J, et al. Severe Community-acquired Pneumonia. Assessment of Severity Criteria. AMJ Respir Crit Care Med. 1998;158:1102-1108. pmid:9769267 doi: 10.1164/ajrccm.158.4.9803114

(7.) Menendez R, Torres A, Reyes S, et al. Initial management of pneumonia and sepsis: factors associated with improved outcome. Eur Respir J. 2012;39:156-162. doi: 10.1183/09031936.00188710. pmid:21828033

(8.) Fine MJ, Auble TE, Yealy DM, et al. A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med. 1997;336:243-250. pmid:8995086 doi: 10.1056/nejm199701233360402

(9.) Lim WS, van der Eerden MM, Laing R, et al. Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. Thorax. 2003;58:377-382. pmid:12728155 doi: 10.1136/thorax.58.5.377

(10.) Dremsizov T, Clermont G, Kellum JA, Kalassian KG, Fine MJ, Angus DC. Severe sepsis in community-acquired pneumonia: when does it happen, and do systemic inflammatory response syndrome criteria help predict course? Chest. 2006;129:968-978. pmid:16608946 doi: 10.1378/c h est.129.4.968

(11.) Cilloniz C, Ewig S, Ferrer M, et al. Community-acquired polymicrobial pneumonia in the intensive care unit: aetiology and prognosis. Crit Care. 2011 ;15: R209. doi: 10.1186/ cc 10444. pmid:21914220

(12.) Hosmer D, Lemeshow S. Applied logistic regression. New York: John Wiley & Sons, 1989. Inc ed.

(13.) Restrepo MI, Mortensen EM, Velez JA, Frei C, Anzueto A. A comparative study of community-acquired pneumonia patients admitted to the ward and the ICU. Chest. 2008;133:610-617. pmid:17989157 doi: 10.1378/chest.07-1456

(14.) Schaaf BM, Boehmke F, Esnaashari H, et al. Pneumococcal septic shock is associated with the interleukin-10-1082 gene promoter polymorphism. Am J Respir Crit Care Med. 2003;168:476-480. pmid:12746253 doi: 10.1164/rccm.200210-1164oc

(15.) Ruiz M, Ewig S, Torres A, et al. Severe community-acquired pneumonia. Risk factors and follow-up epidemiology Am J Respir Crit Care Med. 1999;160:923-929. pmid:10471620 doi: 10.1164/ajrccm. 160.3.9901107

(16.) Mehta AJ, Guidot DM. Alcohol abuse, the alveolar macrophage and pneumonia. AmJMedSci. 2012;343:244-247. doi: 10.1097/MAJ.0b013e31823ede77. pmid:22173040

(17.) Bertran MJ, Trilla A, Codina C, CarneX, Ribas J, Asenjo MA. Analysis of the cost-effectiveness relationship in the empirical treatment in patients with infections of the lower respiratory tract acquired in the community. Enferm Infecc Microbiol Clin. 2000;18:445-451. pmid:11149168

(18.) de Wit M, Jones DG, Sessler CN, Zilberberg MD, Weaver MF. Alcohol-use disorders in the critically ill patient. Chest 2010;138:994-1003. doi: 10.1378/chest.09-1425. pmid:20923804

(19.) Liapikou A, Polverino E, Ewig S, et al. Severity and outcomes of hospitalised community-acquired pneumonia in COPD patients. Eur Respir J. 2012;39:855-861. doi: 10.1183/09031936.00067111. pmid:21920895

(20.) Almirall J, Bolibar I, Serra-Prat M, et al. Relationship between the use of inhaled steroids for chronic respiratory diseases and early outcomes in community-acquired pneumonia. PLoSOne. 2013; 8: e73271. doi: 10.1371 /journal.pone.0073271. pmid:24039899

(21.) Menendez R, Sahuquillo-Arce JM, Reyes S, et al. Cytokine activation patterns and biomarkers are influenced by microorganisms in community-acquired pneumonia. Chest, doi: 10.1378/chest.l 1-1446.

(22.) Schaaf B, Kruse J, Rupp J, et al. Sepsis severity predicts outcome in community-acquired pneumococcal pneumonia. Eur Respir J. 2007;30:517-524. pmid:17537775 doi: 10.1183/09031936.00021007

(23.) de Roux A, Ewig S, Garcia E, et al. Mixed community-acquired pneumonia in hospitalised patients. Eur Respir J. 2006;27:795-800. pmid:16585087 doi: 10.1183/09031936.06.00058605

(24.) Garcia-Vidal C, Ardanuy C, Tubau F, et al. Pneumococcal pneumonia presenting with septic shock: host- and pathogen-related factors and outcomes. Thorax. 2010;65:77-81. doi: 10.1136/thx.2009.123612. pmid:19996337

Beatriz Montull, MR Rosario Menendez, MD, PhD, and Raul Mendez, MP, are members of the Pneumology Department, ISS/Hospital Universitario y Politecnico La Fe, CIBER Enfermedades Respiratorias (CIBERES), Valencia, Spain. AntoniTorrez, MD, PhD, is a member of the Pneumology Department, Hospital Clinico y Provincial, IDIBAPS, CIBER Enfermedades Respiratorias (CIBERES), Barcelona, Spain. Complete information about all contributing authors can be found at http://www.plosone.org/article/authors/ info%3Adoi%2F10.1371 %2Fjournal.pone.0145929

doi:10.1371/journal.pone.0145929. http://journals.plos.org/ plosone/article?id=10.1371/journal.pone.0145929. The manuscript was lightly edited for style.

TEST QUESTIONS

1. What is the U.S. incidence rate of community-acquired pneumonia (CAP), per 100,000 habitants?

a. 1,167 cases

b. 512 cases

c. 343 cases

d. 150 cases

2. A syndrome defined by infection, complicated by systemic inflammation and organ dysfunction, is known as

a. severe sepsis.

b. metabolic syndrome.

c. sepsis.

d. none of the above

3. Which is a concerning health complication associated with CAP?

a. depression

b. deafness

c. severe sepsis

d. diabetes

4. What were the researchers seeking to identify in the patients that presented to clinicians with CAP and severe sepsis?

a. risk factors associated with severe sepsis

b. causative microorganisms associated with severe sepsis

c. both a and b

d. neither a nor b

5. What primary diagnosis was used for inclusion criteria of the patients in the study?

a. diabetes

b. coronary artery disease

c. multiple sclerosis

d. CAP

6. Patients who were excluded from the research study included nursing-home patients, transplant/oncologic patients, immunosuppressive HIV patients, patients undergoing treatment with corticosteroids or other immunosuppressive drugs, DNR patients, and patients in which CAP was a terminal event.

a. True

b. False

7. According to the study, what health outcome was measured during hospitalization, and at 30-day and 90-day follow-up?

a. hospital readmission rate

b. mortality

c. both a and b

d. neither a nor b

8. Of the study population that presented to the emergency room with CAP, what percentage had severe sepsis upon admission?

a. 52.6 percent

b. 11.8 percent

c. 49.2 percent

d. 37.6 percent

9. Which two factors were found to be protective with regard to the patient characteristic findings?

a. alcohol abuse and prior antibiotic treatment

b. elderly patients and renal disease

c. renal disease and diabetes

d. diabetes and prior antibiotic treatment

10. Which risk factors were more likely to be developed in community-onset severe-sepsis patients?

a. elderly, diabetes, and COPD patients

b. elderly, alcohol abusers, renal disease patients, and COPD patients

c. elderly, coronary artery disease, alcohol abusers, and diabetes

d. none of the above

11. Which were identified as being causal of severe sepsis?

a. S. pneumoniae and mixed etiology

b. H. influenzae and mixed etiology

c. M. pneumoniae and H. influenzae

d. S. pneumoniae and M. pneumoniae

12. When assessing a CAP patient upon admission, a main limitation found in the study was the scales that are currently in use for determining the severity.

a. True

b. False

13. Why was the nursing-home population excluded from the study?

a. This population exhibits different health characteristics.

b. This population exhibits more frequent nosocomial infections.

c. This population exhibits more multidrug resistant microorganisms.

d. all of the above

14. While the study had some apparent limitations, what factor(s) did the researchers believe were the strengths of the study?

a. large sample size and prospective study design

b. inclusion of all patient populations across healthcare settings

c. microbiological testing that included identification of bacteria and viruses

d. all of the above

15. The concluding recommendations on the care of CAP patients include the development of preventive CAP strategies in susceptible patients and the early recognition of severe sepsis in patients presenting with CAR

a. True

b. False

Continuing Education

To earn CEUs, see test on page 14 or online at www.mlo-online.com under the CE Tests tab.

LEARNING OBJECTIVES

Upon completion of this article, the reader will be able to:

1. Discuss the health indications that led to the development of this particular study.

2. Identify inclusion and exclusion criteria in regard to the design of the study.

3. Discuss results, findings, and limitations of the study.

4. Discuss the concluding recommendations regarding patients with severe-sepsis CAR

By Beatriz Montull, MP, Rosario Menendez, MD, PhD, Antoni Torres, MD, PhD, and Raul Mendez, MP
Table 1. Characteristics of CAP with severe sepsis.

Characteristics                                  Severe Sepsis

                                                   No, n (%)

Total No.                                          n = 2,541

Demographic                 Age *                  69 (50-78)
data
               Age [greater than or equal to]    1473 (58.1)
                          65 years

                         Male gender             1635 (64.3)

                       Current smoker             574 (22.6)

                      Alcohol abuse (a)           273 (10.7)

                    Prior corticosteroid           95 (3.8)
                        treatment (b)

                      Prior antibiotic            651 (25.6)

Comorbid              Diabetes Mellitus           566 (22.3)
condition
                        Liver disease             102 (4)

                        Heart disease             346 (13.6)

                        Renal disease             136 (5.4)

                   Neurological disorders         245 (9.7)

                            COPD                  494 (19.8)

Radiographic       Multilobar infiltrates         501 (19.7)
findings
                      Pleural Effusion            391 (15.4)

Prognostic               PSI (IV-V)               866 (34.1)
scales
                  CURB65 ([greater than or
                        equal to] 3)

Characteristics                                      Severe Sepsis

                                                  Yes, n (%)

Total No.                                         n = 1,529     p (c)

Demographic                 Age *                  73 (60-81)   <0.001
data
               Age [greater than or equal to]    1024 (67.1)    <0.001
                          65 years

                         Male gender             1065 (69.7)     0.001

                       Current smoker             343 (22.5)     0.937

                      Alcohol abuse (a)           200 (13.1)     0.024

                    Prior corticosteroid           74 (4.9)      0.083
                        treatment (b)

                      Prior antibiotic            261 (17.1)    <0.001

Comorbid              Diabetes Mellitus           294 (19.2)     0.020
condition
                        Liver disease              70 (4.6)      0.378

                        Heart disease             227 (14.8)     0.277

                        Renal disease             132 (8.6)     <0.001

                   Neurological disorders         157 (10.3)     0.531

                            COPD                  477 (32.0)    <0.001

Radiographic       Multilobar infiltrates         427 (27.9)    <0.001
findings
                      Pleural Effusion            248 (16.3)     0.469

Prognostic               PSI (IV-V)               971 (63.5)    <0.001
scales
                  CURB65 ([greater than or        663 (43.3)    <0.001
                        equal to] 3)

Data are presented as number (percentage) unless otherwise indicated.

* Data are presented as median (interquartile range).

(a) Alcohol abuse: more than 80 g/day.

(b) Previous corticosteroid treatment: less than 20 mg/day
prednisone or equivalent.

(c) p value: the [chi square] test was performed for categorical data
and the Mann-Whitney U test was performed for continuous data.

Table 2. Length of stay and mortality in CAP with regard to
severe sepsis.

                                     Severe Sepsis

                         No. n (%)   Yes, n (%)   p value (b)

Total No.                n = 2,541   n = 1,529

LOS (a)                   6 (4-9)    8 (5-12)       <0.001

Mortality   At 30 days    75 (3)     104 (6.9)      <0.001

            At 90 days   102 (4.2)   127 (8.8)      <0.001

                            Severe Sepsis

                         0R (c)   95% CI (d)

Total No.

LOS (a)

Mortality   At 30 days   2.404    1.773-3.258

            At 90 days   2.194    1.676-2.872

Data are presented as number (percentage) unless otherwise indicated.

(a) LOS: Length of stay (days). Data are presented as median
(interquartile range).

(b) p value: the 82 test was performed for categorical data and the
Mann-Whitney U test was performed for continuous data.

(c) OR: Odds ratio

(d) CI: Confidence interval

Table 3. Etiology of CAP in relation to severe sepsis.

Etiology                                           Severe Sepsis

Groups                                               No, n (%)

Total No.                   Total No. (%)            n = 2,541

Known etiology                                      860 (33.8)
n = 1,507

Gram-positive                                       466 (18.3)
n = 866

                            S. pneumoniae           463 (18.2)
                           n = 859 (21.1)

                          MRSA n = 7 (0.2)            3 (0.1)

Gram-negative                                       123 (4.8)
n = 207

                           L. pneumophila            60 (2.4)
                            n = 104 (2.6)

                      H. influenza n = 43 (1.1)      25 (1.0)

                     P. aeruginosa n = 45 (1.1)      30 (1.2)

                         E. colin = 15 (0.4)          8 (0.3)

Atypical pathogens                                  102 (4.0)
n = 144

                     C. pneumoniae n = 44 (1.1)      26 (1)

                      C. burnetii n = 50 (1.2)       37 (1.5)

                     M. pneumoniae n = 50 (1.2)      39 (1.5)

Viruses n = 18                                       11 (0.4)

Mixed etiology                                       63 (2.5)
(b) n = 121

Bacteremia                                          137 (9.0)
n = 284

Etiology                                              Severe Sepsis

Groups                                             Yes, n (%)

Total No.                   Total No. (%)          n = 1,529    p (a)

Known etiology                                     646 (42.2)   <0.001
n = 1,507

Gram-positive                                      400 (26.2)   <0.001
n = 866

                            S. pneumoniae          396 (25.9)   <0.001
                           n = 859 (21.1)

                          MRSA n = 7 (0.2)           4 (0.3)     0.284

Gram-negative                                       84 (5.5)     0.358
n = 207

                           L. pneumophila           44 (2.9)     0.312
                            n = 104 (2.6)

                      H. influenza n = 43 (1.1)     18 (1.2)     0.559

                     P. aeruginosa n = 45 (1.1)     15 (1.0)     0.555

                         E. colin = 15 (0.4)         7 (0.5)     0.466

Atypical pathogens                                  42 (2.7)     0.034
n = 144

                     C. pneumoniae n = 44 (1.1)     18 (1.2)     0.645

                      C. burnetii n = 50 (1.2)      13 (0.9)     0.089

                     M. pneumoniae n = 50 (1.2)     11 (0.7)     0.022

Viruses n = 18                                       7 (0.5)     0.908

Mixed etiology                                      58 (3.8)     0.017
(b) n = 121

Bacteremia                                         147 (14.5)   <0.001
n = 284

Data are presented as number (percentage) unless otherwise indicated.

(a) p value: the %2 test was performed for categorical data.

(b) Mixed etiology is defined as pneumonia due to more than one
pathogen (virus or bacteria).

Table 4. Multivariable analysis results of severe sepsis related to
host factors (first model) and microorganisms (second model).

                                         Severe Sepsis n = 1,529

                                       OR (a)   95% CI (b)     p

First model: Host factors

Demographic data      Age ([greater     1.34    1.15-1.55    <0.001
and habits            than or equal
                      to] 65 years)

                      Alcohol abuse     1.31    1.07-1.61     0.010

Comorbid condition       Diabetes       0.74    0.63-0.88    <0.001
                         Mellitus

                      Renal disease     1.57    1.22-2.03     0.001

                           COPD         1.75    1.50-2.04    <0.001

Prior antibiotic                        0.62    0.52-0.73    <0.001
treatment

Second model: Microorganisms

Etiology              S. pneumoniae     1.59    1.31-1.95    <0.001

                      L. pneumophila    1.81    1.14-2.86     0.012

                      Mixed etiology    1.65    1.10-2.49     0.017

                        Bacteremia      1.37    1.05-1.79     0.021

(a) OR: Odds ratio

(b) CI: Confidence interval
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Author:Montull, Beatriz; Menendez, Rosario; Torres, Antoni; Mendez, Raul
Publication:Medical Laboratory Observer
Geographic Code:1USA
Date:Mar 1, 2016
Words:4480
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