P724 Serum levels of IL-6, IL-8 and IL-10 at fever onset in neutropenic patients: a rapid test for the prediction of Gram-negative bacteraemia?Results of an EORTC Infectious Disease Group multicentre study

Triglyceride-rich lipoproteins bind and inactive bacterial endotoxin in vitro and prevent death when given before a lethal dose of endotoxin in animals. However, lipoproteins have not yet been demonstrated to improve survival in polymicrobial gram-negative sepsis. We therefore tested the ability of triglyceride-rich lipoproteins to prevent death after cecal ligation and puncture (CLP) in rats. Animals were given bolus infusions of either chylomicrons (1 g triglyceride/kg per 4 h) or an equal volume of saline for 28 h after CLP. Chylomicron infusions significantly improved survival (measured at 96 h) compared with saline controls (80 vs 27%, P < or = 0.03). Chylomicron infusions also reduced serum levels of endotoxin, measured 90 min (26 +/- 3 vs 136 +/- 51 pg/ml, mean +/- SEM, P < or = 0.03) and 6 h (121 +/- 54 vs 1,026 +/- 459 pg/ml, P < or = 0.05) after CLP. The reduction in serum endotoxin correlated with a reduction in serum tumor necrosis factor, measured 6 h after CLP (0 +/- 0 vs 58 +/- 24 pg/ml, P < or = 0.03), suggesting that chylomicrons improve survival in this model by limiting macrophage exposure to endotoxin and thereby reducing secretion of inflammatory cytokines. Infusions of a synthetic triglyceride-rich lipid emulsion (Intralipid; KabiVitrum, Inc., Alameda, CA) (1 g triglyceride/kg) also significantly improved survival compared with saline controls (71 vs 27%, P < or = 0.03). These data demonstrate that triglyceride-rich lipoproteins can protect animals from lethal polymicrobial gram-negative sepsis.

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In Vivo Pharmacodynamics of Ceftobiprole against Multiple Bacterial Pathogens in Murine Thigh and Lung Infection Models

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01273-07 ◽

2008 ◽

Vol 52 (10) ◽

pp. 3492-3496 ◽

Cited By ~ 57

Author(s):

W. A. Craig ◽

D. R. Andes

Keyword(s):

Serum Levels ◽

Lung Infection ◽

Lung Model ◽

Dose Fractionation ◽

Time Curve ◽

Gram Negative ◽

Infection Models ◽

Bactericidal Activities

ABSTRACT Ceftobiprole medocaril is the parenteral prodrug of ceftobiprole, a novel pyrrolidinone broad-spectrum cephalosporin with in vitro and in vivo bactericidal activities against methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae (PRSP). We have used murine thigh and lung infection models in neutropenic and normal mice to characterize the in vivo pharmacokinetic (PK)-pharmacodynamic (PD) activities of ceftobiprole against multiple strains of S. aureus (including MRSA), S. pneumoniae (including PRSP), and gram-negative bacilli. Serum levels of ceftobiprole following the administration of multiple doses were determined by a microbiological assay. In vivo bactericidal activities and postantibiotic effects (PAEs) of ceftobiprole against MRSA and PRSP strains were determined from serial CFU/thigh values following single doses of ceftobiprole (40 and 160 mg/kg of body weight). Dose fractionation studies were used to determine which PK-PD index correlated best with activity. Magnitudes of the PK-PD indices were calculated from MICs and PK parameters. A sigmoid dose-response model was used to estimate the dose (mg/kg/24 h) required to achieve a static and 2-log10 kill effects over 24 h. PK results showed area under the concentration-time curve/dose values of 1.8 to 2.8 and half-lives of 0.29 to 0.51 h. MICs ranged from 0.015 to 2 μg/ml. Ceftobiprole demonstrated time-dependent killing; its in vivo PAEs varied from 3.8 h to 4.8 h for MRSA and from 0 to 0.8 h for PRSP. The time above MIC (T > MIC) correlated best with efficacy for both MRSA and PRSP. The T > MIC values required for the static doses were significantly longer (P < 0.001) for Enterobacteriaceae (36 to 45%) than for S. aureus (14 to 28%) and S. pneumoniae (15 to 22%). The drug showed activities in the lung model similar to those in the thigh model. The presence of neutrophils significantly enhanced the activity of ceftobiprole against S. pneumoniae but only slightly against Klebsiella pneumoniae. Based on its PD profile, ceftobiprole is a promising new β-lactam agent with activity against gram-negative and gram-positive organisms including MRSA and PRSP.

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Impact of empirical antibiotic regimens on mortality in neutropenic patients with bloodstream infection presenting with septic shock

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01744-21 ◽

2021 ◽

Author(s):

Mariana Chumbita ◽

Pedro Puerta-Alcalde ◽

Carlota Gudiol ◽

Nicole Garcia-Pouton ◽

Júlia Laporte-Amargós ◽

...

Keyword(s):

Risk Factors ◽

Septic Shock ◽

Kidney Injury ◽

Bloodstream Infections ◽

Gram Positive ◽

Gram Negative ◽

Neutropenic Patients ◽

Prospective Cohorts ◽

Independent Risk Factors ◽

The Impact

Objectives: We analyzed risk factors for mortality in febrile neutropenic patients with bloodstream infections (BSI) presenting with septic shock and assessed the impact of empirical antibiotic regimens. Methods: Multicenter retrospective study (2010-2019) of two prospective cohorts comparing BSI episodes in patients with or without septic shock. Multivariate analysis was performed to identify independent risk factors for mortality in episodes with septic shock. Results: Of 1563 patients with BSI, 257 (16%) presented with septic shock. Those patients with septic shock had higher mortality than those without septic shock (55% vs 15%, p<0.001). Gram-negative bacilli caused 81% of episodes with septic shock; gram-positive cocci, 22%; and Candida species 5%. Inappropriate empirical antibiotic treatment (IEAT) was administered in 17.5% of septic shock episodes. Empirical β-lactam combined with other active antibiotics was associated with the lowest mortality observed. When amikacin was the only active antibiotic, mortality was 90%. Addition of empirical specific gram-positive coverage had no impact on mortality. Mortality was higher when IEAT was administered (76% vs 51%, p=0.002). Age >70 years (OR 2.3, 95% CI 1.2-4.7), IEAT for Candida spp. or gram-negative bacilli (OR 3.8, 1.3-11.1), acute kidney injury (OR 2.6, 1.4-4.9) and amikacin as the only active antibiotic (OR 15.2, 1.7-134.5) were independent risk factors for mortality, while combination of β-lactam and amikacin was protective (OR 0.32, 0.18-0.57). Conclusions: Septic shock in febrile neutropenic patients with BSI is associated with extremely high mortality, especially when IEAT is administered. Combination therapy including an active β-lactam and amikacin results in the best outcomes.

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Anti-ceramide antibodies in leprosy: marker for nerve damage?

The Journal of Infection in Developing Countries ◽

10.3855/jidc.513 ◽

2010 ◽

Vol 4 (06) ◽

pp. 378-381 ◽

Cited By ~ 3

Author(s):

Kalpana Singh ◽

Bhawna Singh ◽

Prakash Ray

Keyword(s):

Infectious Disease ◽

Serum Levels ◽

Serum Marker ◽

Nerve Damage ◽

Healthy Controls ◽

Chi Square ◽

Leprosy Patients ◽

Chi Square Test ◽

Multibacillary Leprosy

Background: Leprosy is a chronic infectious disease primarily affecting the peripheral nervous system and skin. Multibacillary leprosy is associated with nerve damage which could contribute to myelin alteration. As ceramide is a constituent of myelin sheath, the present study aimed to compare anti-ceramide antibody titre in paucibacillary and multibacillary leprosy patients with controls. Methodology: Serum levels of anti-ceramide antibody were measured using enzyme-linked immunosorbent assays (ELISA) in 50 leprosy patients (25 paucibacillary and 25 multibacillary) and 25 healthy controls. Results were reported in OD units as mean ± SD and analyzed by Chi square test (significance at p < 0.05). Results: Patients suffering from multibacillary leprosy had significantly higher anti-ceramide antibody serum levels compared to paucibacillary leprosy patients and healthy controls (p < 0.005). Conclusions: Since nerve damage is the most debilitating effect of leprosy, the search for a serum marker for assessing nerve damage is required in countries where leprosy is still widespread. In multibacillary leprosy patients, the role of anti-ceramide antibody as a marker for nerve damage should be explored.

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Influence of Selective Bowel Decontamination on the Organisms Recovered During Bacteremia in Neutropenic Patients

Infection Control and Hospital Epidemiology ◽

10.1086/502463 ◽

2004 ◽

Vol 25 (8) ◽

pp. 685-689 ◽

Cited By ~ 4

Author(s):

Florian Daxboeck ◽

Werner Rabitsch ◽

Alexander Blacky ◽

Maria Stadler ◽

Paul A. Kyrle ◽

...

Keyword(s):

Intensive Care Unit ◽

Staphylococcus Aureus ◽

Bone Marrow ◽

Anaerobic Bacteria ◽

Blood Cultures ◽

University Teaching ◽

Coagulase Negative Staphylococci ◽

Gram Negative ◽

Neutropenic Patients ◽

Care Ward

AbstractObjective:To assess the influence of prophylactic selective bowel decontamination (SBD) on the spectrum of microbes causing bloodstream infection (BSI).Design:The microbes causing BSI in neutropenic patients of a hematologic ward (HW) and a bone marrow transplantation unit (BMTU), respectively, were compared by retrospective analysis of blood culture results from January 1996 to June 2003.Setting:A 30-bed HW (no SBD) and a BMTU including a 7-bed normal care ward and an 8-bed intensive care unit (SBD used) of a 2,200-bed university teaching hospital.Results:The overall incidences of bacteremia in the HW and the BMTU were similar (72.6 vs 70.6 episodes per 1,000 admissions; P = .8). Two hundred twenty episodes of BSI were recorded in 164 neutropenic patients of the HW and 153 episodes in 127 neutropenic patients of the BMTU. Enterobacteriaceae (OR, 3.14; CI95, 1.67–5.97; P = .0002) and Streptococcus species (OR, 2.04; CI95, 1.14–3.70; P = .015) were observed more frequently in HW patients and coagulase-negative staphylococci more frequently in BMTU patients (OR, 0.15; CI95, 0.09–0.26; P< .00001). No statistically significant differences were found for gram-negative nonfermentative bacilli (P = .53), Staphylococcus aureus (P = .21), Enterococcus species (P = .48), anaerobic bacteria (P = .1), or fungi (P = .50).Conclusions:SBD did not lead to a significant reduction in the incidence of bacteremia, but significant changes in microbes recovered from blood cultures were observed. SBD should be considered when empiric antimicrobial therapy is prescribed for suspected BSI.

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Serum biomarkers to differentiate Gram-negative, Gram-positive and fungal infection in febrile patients

Journal of Medical Microbiology ◽

10.1099/jmm.0.001360 ◽

2021 ◽

Vol 70 (7) ◽

Author(s):

Dongguang Niu ◽

Qian Huang ◽

Fan Yang ◽

Weiliang Tian ◽

Chen Li ◽

...

Keyword(s):

Bloodstream Infection ◽

Bacterial Infections ◽

Fungal Infections ◽

Serum Levels ◽

Serum Biomarker ◽

Diagnostic Efficiency ◽

Gram Positive ◽

Gram Negative ◽

Neutrophil Lymphocyte Ratio ◽

Bacteria And Fungi

Introduction. Contamination of specimens and overuse of broad spectrum antibiotics contribute to false positives and false negatives, respectively. Therefore, useful and applicable biomarkers of bacteremia are still required. Hypothesis/Gap Statement. IL-6 can be used as a serum biomarker to discriminate among bacterial infections and fungal infections in febrile patients with a bloodstream infection. Aim. We aimed to evaluate the diagnostic efficiency of neutrophil/lymphocyte ratio (NLR), procalcitonin (PCT) and interleukin-6 (IL-6) in discriminating Gram-negative (G−) bacteria from Gram-positive (G+) bacteria and fungi in febrile patients. Methodology. A total of 567 patients with fever were evaluated. Serum levels of IL-6, PCT, NLR and CRP were compared among a G− group (n=188), a G+ group (n=168), a fungal group (n=38) and a culture negative group (n=173). Sensitivity, specificity, Yuden’s index and area under the Receiver operating characteristic (ROC) curve (AUC) were obtained to analyse the diagnostic abilities of these biomarkers in discriminating bloodstream infection caused by different pathogens. Results. Serum IL-6 and PCT in the G− group increased significantly when compared with both the G+ group and fungal group (P <0.05). AUC of IL-6 (0.767, 95 % CI:0.725–0.805) is higher than AUC of PCT (0.751, 95 % CI:0.708–0.796) in discriminating the G− group from G+ group. When discriminating the G− group from fungal group, the AUC of IL-6 (0.695, 95 % CI:0.651–0.747) with a cut-off value of 464.3 pg ml−1 was also higher than the AUC of PCT (0.630, 95 % CI:0.585–0.688) with a cut-off value of 0.68 ng ml−1. Additionally, AUC of NLR (0.685, 95 % CI:0.646–0.727) in discriminating the fungal group from G+ group at the cut-off value of 9.03, was higher than AUC of IL-6, PCT and CRP. Conclusion. This study suggests that IL-6 could be used as a serum biomarker to discriminate among bacterial infections and fungal infections in febrile patients with a bloodstream infection. In addition, NLR is valuable to discriminate fungal infections from Gram-positive infections in febrile patients with a bloodstream infection.

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A forensic evaluation of plague – a re-emerging infectious disease with biowarfare potential

Medicine Science and the Law ◽

10.1177/0025802420908483 ◽

2020 ◽

Vol 60 (3) ◽

pp. 200-205

Author(s):

Roger W. Byard

Keyword(s):

Infectious Disease ◽

Antibiotic Resistance ◽

Urban Areas ◽

Forensic Evaluation ◽

Gram Negative ◽

Acute Infectious Disease ◽

Recent Occurrence ◽

Splenic Necrosis ◽

Potential Use ◽

Significant Mortality

Plague is an acute infectious disease caused by the gram-negative cocco-bacillus Yersinia pestis. It has been responsible for 200 million deaths throughout history with three major pandemics. There are three forms: bubonic, septicaemic and pneumonic, each carrying a significant mortality rate. The usual transmission is from fleas carried by rodents. Recently, it has been listed as one of the reemerging infectious diseases globally, with a potential use in bioterrorism. At autopsy there may be lymphadenopathy, fulminant pneumonia or diffuse interstitial pneumonitis. However any organ may be affected with myocarditis, meningitis, pharyngitis and hepatic and splenic necrosis. The lethality of plague with the resurgence in numbers of cases, development of antibiotic resistance, recent occurrence in urban areas and the lack of a vaccine make it a disease not to be missed in the mortuary.

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