Characteristics and outcomes of culture-negative versus culture-positive severe sepsis

Phua, Jason; Ngerng, Wang Jee; See, Kay Choong; Tay, Cho Jui; Kiong, Timothy; Lim, Hui Fang; Chew, Mei Ying; Yip, Hwee Seng; Tan, Adeline; Khalizah, Haji Jamil; Capistrano, Rolando; Lee, Kang Hoe; Mukhopadhyay, Amartya

doi:10.1186/cc12896

Cited by 281 publications

(304 citation statements)

References 35 publications

(66 reference statements)

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“…However, we found an independent association with lower mortality for patients with viral infection regardless of bacterial co-infection. While our data do not explain this finding, we note that a previous study by our group found lower mortality for culture-negative versus culture-positive sepsis [43]. Meanwhile, the impact of viral co-infection on outcomes remains unclear [44].…”

Section: Discussioncontrasting

confidence: 54%

The Use of Polymerase Chain Reaction Amplification for the Detection of Viruses and Bacteria in Severe Community-Acquired Pneumonia

Siow

Koay²,

Lee³

et al. 2016

Respiration

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Background: Pathogens are often not identified in severe community-acquired pneumonia (CAP), and the few studies using polymerase chain reaction (PCR) techniques for virus detection are from temperate countries. Objective: This study assesses if PCR amplification improves virus and bacteria detection, and if viral infection contributes to mortality in severe CAP in a tropical setting, where respiratory pathogens have less well-defined seasonality. Methods: In this cohort study of patients with severe CAP in an intensive care unit, endotracheal aspirates for intubated patients and nasopharyngeal swabs for non-intubated patients were sent for PCR amplification for respiratory viruses. Blood, endotracheal aspirates for intubated patients, and sputum for non-intubated patients were analysed using a multiplex PCR system for bacteria. Results: Out of 100 patients, using predominantly cultures, bacteria were identified in 42 patients; PCR amplification increased this number to 55 patients. PCR amplification identified viruses in 32 patients. In total, only bacteria, only viruses, and both bacteria and viruses were found in 37, 14, and 18 patients, respectively. The commonest viruses were influenza A H1N1/2009 and rhinovirus; the commonest bacterium was Streptococcus pneumoniae. Hospital mortality rates for patients with no pathogens, bacterial infection, viral infection, and bacterial-viral co-infection were 16.1, 24.3, 0, and 5.6%, respectively (p = 0.10). On multivariable analysis, virus detection was associated with lower mortality (adjusted odds ratio 0.12, 95% confidence interval 0.2-0.99; p = 0.049). Conclusions: Viruses and bacteria were detected in 7 of 10 patients with severe CAP with the aid of PCR amplification. Viral infection appears to be independently associated with lower mortality.

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Section: Discussioncontrasting

confidence: 54%

The Use of Polymerase Chain Reaction Amplification for the Detection of Viruses and Bacteria in Severe Community-Acquired Pneumonia

Siow

Koay²,

Lee³

et al. 2016

Respiration

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“…Thus, this supports our finding that SIDS appears to have a causal relationship to the initial fulmination of a prodromal ARI that may cause neuronal death in the physiologically susceptible infants [8]. We note that many U.S. medical examiners do not culture lung exudate of potential SIDS cases because "of a perceived lack of testing utility" [15], and that in many cases the cultures are negative in spite of other evidence of severe sepsis [16]. Figure 5 shows the same relationship for ARI to LBO as SIDS and SUID.…”

Section: The Infection Vector For Sidssupporting

confidence: 82%

The Role of Respiratory Infection in Sudden Infant Death Syndrome (SIDS)

Mage¹,

Latorre²,

Jeník³

et al. 2016

Scandinavian Journal of Forensic Science

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Abstract:Introduction: The Sudden Infant Death Syndrome (SIDS) is not likely to be explained by a currently measureable presence in all cases and absence in controls, as otherwise it would have been solved already. Indeed, any proposed physiological model for SIDS causation must explain the constant mathematical and statistical properties of SIDS age and gender. We have shown previously that SIDS are characterized by a common 4-parameter lognormal age distribution sparing neonatal infants, by a nominal 50% male excess, and by a higher rate in winter than summer. We test now whether SIDS is closely related to a fulminating prodromal Acute Respiratory Infection (ARI) by a common increasing rate with the infants increasing Live Birth Order (LBO), all remaining the same, independent of the change in preferred sleeping positions of the infants, prone or supine. Methods: We use U.S. published infant mortality data from wonder.cdc.gov and other countries (Colombia, U.K., Europe, Australasia) to make comparisons between the two causes of death (ARI and SIDS) to evaluate how closely ARI resembles the characteristics of SIDS. Results: Gender: SIDS male excess 50%, ARI male excess 50%; Ages: SIDS 90% post-neonatal, ARI 96% post-neonatal; Seasonality: SIDS and ARI are higher in winter than summer; Live birth order: SIDS and ARI rates increase with increasing LBO with similar mathematical relationship. Conclusion: Our results show that all SIDS are very likely relatable to a single cause tied to a fulminating prodromal ARI in a physiologically anemic infant who is genetically (X-link recessive) susceptible to cerebral anoxia. An alternative cause of all SIDS death by a collection of subsets of different causes, such as brainstem-related respiratory abnormalities and cardiac QT abnormalities, is not supported because they cannot all have the same age-gender-seasonal-familial-distributions of SIDS, required by Cramér's Theorem.

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“…Future work should include comprehensive pathogen phenotyping, such as by using metagenomic sequencing, given the recognized high proportion of culturenegative patients with sepsis (36,37). Comparison of patients with FP with specific control subjects, such as a group of patients undergoing laparotomy for noninfectious indications, would control for the effects of damage-associated molecular pattern-mediated signaling due to the surgical procedure as well as any modulating influences on the transcriptome due to general anesthesia, whereas inclusion …”

Section: Discussionmentioning

confidence: 99%

Shared and Distinct Aspects of the Sepsis Transcriptomic Response to Fecal Peritonitis and Pneumonia

Burnham

Davenport

Radhakrishnan

et al. 2017

Am J Respir Crit Care Med

172

206

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Rationale: Heterogeneity in the septic response has hindered efforts to understand pathophysiology and develop targeted therapies. Source of infection, with different causative organisms and temporal changes, might influence this heterogeneity.Objectives: To investigate individual and temporal variations in the transcriptomic response to sepsis due to fecal peritonitis, and to compare these with the same parameters in community-acquired pneumonia.Methods: We performed genome-wide gene expression profiling in peripheral blood leukocytes of adult patients admitted to intensive care with sepsis due to fecal peritonitis (n = 117) or community-acquired pneumonia (n = 126), and of control subjects without sepsis (n = 10). Measurements and Main Results:A substantial portion of the transcribed genome (18%) was differentially expressed compared with that of control subjects, independent of source of infection, with eukaryotic initiation factor 2 signaling being the most enriched canonical pathway. We identified two sepsis response signature (SRS) subgroups in fecal peritonitis associated with early mortality (P = 0.01; hazard ratio, 4.78). We defined gene sets predictive of SRS group, and serial sampling demonstrated that subgroup membership is dynamic during intensive care unit admission. We found that SRS is the major predictor of transcriptomic variation; a small number of genes (n = 263) were differentially regulated according to the source of infection, enriched for IFN signaling and antigen presentation. We define temporal changes in gene expression from disease onset involving phagosome formation as well as natural killer cell and IL-3 signaling.Conclusions: The majority of the sepsis transcriptomic response is independent of the source of infection and includes signatures reflecting immune response state and prognosis. A modest number of genes show evidence of specificity. Our findings highlight opportunities for patient stratification and precision medicine in sepsis.

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Characteristics and outcomes of culture-negative versus culture-positive severe sepsis

Cited by 281 publications

References 35 publications

The Use of Polymerase Chain Reaction Amplification for the Detection of Viruses and Bacteria in Severe Community-Acquired Pneumonia

The Use of Polymerase Chain Reaction Amplification for the Detection of Viruses and Bacteria in Severe Community-Acquired Pneumonia

The Role of Respiratory Infection in Sudden Infant Death Syndrome (SIDS)

Shared and Distinct Aspects of the Sepsis Transcriptomic Response to Fecal Peritonitis and Pneumonia

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