Underlying Disorders and Their Impact on the Host Response to Infection

Dhainaut, Jean-François; Claessens, Yann-Érick; Janes, Jonathan; Nelson, David R.

doi:10.1086/432001

Cited by 88 publications

(67 citation statements)

References 67 publications

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“…There is a strong genetic influence on the outcome of sepsis, with polymorphisms in genes coding for TNF-␣, TNF-␤, IL-1Ra, IL-6, IL-10, heat shock protein, Toll-like receptor 2, and Toll-like receptor 4 being linked to increased susceptibility to sepsis (22). In addition, underlying disorders like cancer or major surgery may increase the likelihood of sepsis in individuals (17).…”

Section: Discussionmentioning

confidence: 99%

Presymptomatic Prediction of Sepsis in Intensive Care Unit Patients

Lukaszewski

Yates

Jackson

et al. 2008

Clin Vaccine Immunol

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Postoperative or posttraumatic sepsis remains one of the leading causes of morbidity and mortality in hospital populations, especially in populations in intensive care units (ICUs). Central to the successful control of sepsis-associated infections is the ability to rapidly diagnose and treat disease. The ability to identify sepsis patients before they show any symptoms would have major benefits for the health care of ICU patients. For this study, 92 ICU patients who had undergone procedures that increased the risk of developing sepsis were recruited upon admission. Blood samples were taken daily until either a clinical diagnosis of sepsis was made or until the patient was discharged from the ICU. In addition to standard clinical and laboratory parameter testing, the levels of expression of interleukin-1␤ (IL-1␤), IL-6, IL-8, and IL-10, tumor necrosis factor-␣, FasL, and CCL2 mRNA were also measured by real-time reverse transcriptase PCR. The results of the analysis of the data using a nonlinear technique (neural network analysis) demonstrated discernible differences prior to the onset of overt sepsis. Neural networks using cytokine and chemokine data were able to correctly predict patient outcomes in an average of 83.09% of patient cases between 4 and 1 days before clinical diagnosis with high sensitivity and selectivity (91.43% and 80.20%, respectively). The neural network also had a predictive accuracy of 94.55% when data from 22 healthy volunteers was analyzed in conjunction with the ICU patient data. Our observations from this pilot study indicate that it may be possible to predict the onset of sepsis in a mixed patient population by using a panel of just seven biomarkers.

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Section: Discussionmentioning

confidence: 99%

Presymptomatic Prediction of Sepsis in Intensive Care Unit Patients

Lukaszewski

Yates

Jackson

et al. 2008

Clin Vaccine Immunol

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“…These underlying disorders may alter the overall immune response, even though the coagulation and inflammatory response to infection is not altered 11 . Clinical trials on antisepsis agents often exclude the very elderly, HIV-positive individuals and patients with malignancies because they are at higher risk of death and less likely to respond to treatment.…”

Section: Discussionmentioning

confidence: 99%

Comparative study of survivor and nonsurvivor sepsis patients in a university hospital

Oliveira

Barata

Murta

et al. 2008

Rev. Soc. Bras. Med. Trop.

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To determine parameters associated with the evolution of sepsis, a five-year retrospective study was conducted in a university hospital. One hundred and four consecutive sepsis patients were evaluated, of whom 55.8% were men. The mortality was 68.3% and was associated with older age (p<0.05). Chronic comorbidities and infection site were not associated with prognosis. Gram-positive bacteria were more frequently identified in survivors (p<0.05), while non-detection of the germ was associated with mortality (p<0.01). Appropriate use of antibiotics (germ sensitive to at least one drug administered) was associated with survival (p<0.0001) while inappropriate use (p<0.05) or empirical use (p<0.01) were more frequent in nonsurvivors. Leukocytosis was the main abnormality (54.8%) detected on diagnosis, from the leukocyte count. During the evolution, normal leukocyte count was associated with survival (p<0.01) and leukocytosis with mortality (p<0.05). In conclusion, mortality was associated with nondetection of the pathogen, leukocytosis during the evolution of the sepsis and inappropriate or empirical use of antimicrobials. Evidence-based treatment that is directed towards modifiable risk factors might improve the prognosis for sepsis patients.Key-words: Sepsis. Prognosis. Antimicrobials. Risk factors. RESUMOPara determinar parâmetros associados à evolução da sepse, foi realizado estudo retrospectivo de 5 anos em um hospital universitário. Foram avaliados 104 pacientes consecutivos com sepse, sendo 55,8% homens. A mortalidade foi de 68,3%, associada à idade elevada (p<0,05). Doenças crônicas associadas e sítio de infecção não relacionados ao prognóstico. Identificação de bactérias Gram-positivos foi mais frequente em sobreviventes (p<0,05) e não detecção do germe foi associada à mortalidade (p<0,01). O uso apropriado de antibióticos (germe sensível a pelo menos uma droga administrada) foi associado à sobrevida (p<0,0001) enquanto uso inapropriado (p<0,05) ou empírico (p<0,01) foi mais freqüente em não sobreviventes. No diagnóstico, leucocitose foi a principal (54,8%) alteração no leucograma. Na evolução, leucograma normal foi associado à sobrevida (p<0,01) e leucocitose à mortalidade (p<0,05). Em conclusão, a mortalidade foi associada à ausência de detecção do germe, leucocitose na evolução da sepse e uso inapropriado ou empírico de antibióticos. O tratamento baseado em evidências e direcionado para fatores de risco que podem ser modificados deve melhorar o prognóstico do paciente com sepse.Palavras-chaves: Sepse. Prognóstico. Antimicrobianos. Fatores de risco.Fatores de risco.

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“…The host susceptibility and underlying disorders that chronically (e.g., cancers and hematologic malignancies) and acutely (e.g., major surgery and multiple trauma) impair host responses to infection contribute to the severity of the infections, thereby resulting in a worse outcome (39). The clinical signs and symptoms of an invasive fungal infection (IFI) can be absent until the infection is at an advanced stage due to the reduction or absence of a systemic inflammatory response in patients with profound neutropenia or receiving steroids (40,41).…”

Section: Figmentioning

confidence: 99%

In Vivo Efficacy of Liposomal Amphotericin B against Wild-Type and Azole-Resistant Aspergillus fumigatus Isolates in Two Different Immunosuppression Models of Invasive Aspergillosis

Seyedmousavi

Mouton

Melchers

et al. 2017

Antimicrob Agents Chemother

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Using an immunocompetent murine model of invasive aspergillosis (IA), we previously reported that the efficacy of liposomal amphotericin B (L-AmB) (Ambisome) is not hampered by the presence of azole resistance mutations in Aspergillus fumigatus (S. Seyedmousavi, W. J. G. Melchers, J. W. Mouton, and P. E. Verweij, Antimicrob Agents Chemother 57:1866 -1871, 2013, https://doi.org/10.1128/AAC.02226 -12). We here investigated the role of immune suppression, i.e., neutropenia and steroid treatment, in L-AmB efficacy in mice infected with wild-type (WT) A. fumigatus and with azole-resistant A. fumigatus harboring a TR 34 /L98H mutation in the cyp-51A gene. Survival of treated animals at day 14 in both immunosuppressed models was significantly better than that of nontreated controls. A dose-response relationship was observed that was independent of the azole-resistant mechanism and the immunosuppression method used. In the neutropenic model, 100% survival was reached at an L-AmB dose of 16 mg/kg of body weight for the WT strain and the TR 34 /L98H isolate. In the steroid-treated group, 90.9% survival and 100% survival were achieved for the WT isolate and the TR 34 /L98H isolate with an L-AmB dose of 16 mg/kg, respectively. The 50% effective dose (ED 50 ) was 1.40 mg/kg (95% confidence interval [CI], 0.66 to 3.00 mg/kg) for the WT isolate and 1.92 mg/kg (95% CI, 0.60 to 6.17 mg/kg) for the TR 34 /L98H isolate in the neutropenic model and was 2.40 mg/kg (95% CI, 1.93 to 2.97 mg/kg) for the WT isolate and 2.56 mg/kg (95% CI, 1.43 to 4.56 mg/kg) for the TR 34 /L98H isolate in the steroid-treated group. Overall, there were no significant differences between the two different immunosuppressed conditions in the efficacy of L-AmB against the wild-type and azole-resistant isolates (P Ͼ 0.9). However, the required L-AmB exposure was significantly higher than that seen in the immunocompetent model.

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Underlying Disorders and Their Impact on the Host Response to Infection

Cited by 88 publications

References 67 publications

Presymptomatic Prediction of Sepsis in Intensive Care Unit Patients

Presymptomatic Prediction of Sepsis in Intensive Care Unit Patients

Comparative study of survivor and nonsurvivor sepsis patients in a university hospital

In Vivo Efficacy of Liposomal Amphotericin B against Wild-Type and Azole-Resistant Aspergillus fumigatus Isolates in Two Different Immunosuppression Models of Invasive Aspergillosis

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