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PubMed2025

CAUSAL ASSOCIATION BETWEEN SEPSIS AND FIBROBLAST GROWTH FACTORS AS WELL AS THEIR RECEPTORS LEVELS: A TWO-SAMPLE MENDELIAN RANDOMIZATION STUDY.

Objective: The potential association between sepsis risk and circulating levels of fibroblast growth factors (FGFs) and their receptors (FGFRs) has been a focus of research; however, the causal relationship between them remains to be elucidated. We hypothesize a causal association between genetically predicted FGFs, FGFRs, and sepsis risk, and we conduct a Mendelian randomization (MR) study to validate this hypothesis. Methods: We utilized a two-sample MR design to assess the effect of genetic variants associated with various FGFs (FGF1, FGF2, FGF7, FGF16, FGF19, FGF21, FGF23, FGF5) and FGFRs (FGFR1, FGFR2, FGFR3, α-Klotho) on sepsis risk, using genome-wide association study summary statistics. Our MR analyses employed the inverse-variance weighted (IVW) method, along with weighted median, weighted mode, and MR-Egger regression, supplemented by sensitivity analyses to ensure robustness. Results: The MR analysis identified an unequal number of instrumental variables ranging from 2 to 17 for FGFs and FGFRs when sepsis was the outcome. No significant correlation was found between genetically determined FGF levels and sepsis risk by IVW analysis (all P > 0.05). Correspondingly, similar nonsignificant associations were observed for FGFRs (all P > 0.05). Other MR methods corroborated the IVW findings. Sensitivity analyses, including Cochran's Q test, MR-Egger, and MR pleiotropy residual sum and outlier, indicated no significant heterogeneity or pleiotropy in the relationships, with the exception of a nonsignificant correlation between FGFR1 and sepsis that persisted after the exclusion of an outlier (odds ratio, 0.84; P = 0.34). Conclusion: The analysis found no significant causal associations between FGFs, their receptors, and sepsis risk, indicating a need for further research on their complex interactions.

Humans↗

PubMed2026

ATF4-histone 2-hydroxyisobutyrylation feedback loop drives sepsis-induced inflammation.

BACKGROUND AND PURPOSE: The role and mechanisms of lysine 2-hydroxyisobutyrylation (Khib) in the acute inflammatory phase of sepsis remain unclear. We investigated the function and underlying mechanisms of histone H4 lysine 5 2-hydroxyisobutyrylation (H4K5-hib) in sepsis-induced inflammation in vivo and in vitro. EXPERIMENTAL APPROACH: Acute sepsis was induced by caecal ligation and puncture (CLP) in mice, and inflammatory responses were modelled in lipopolysaccharide (LPS)-stimulated macrophages. CUT&Tag-seq was used to identify genomic targets associated with H4K5-hib and activating transcription factor 4 (ATF4). Immunofluorescence, Western blotting, qPCR, dual-luciferase assays, and ELISA were performed to investigate the underlying mechanisms. KEY RESULTS: H4K5-hib levels were increased in macrophages during the acute inflammatory phase of sepsis. LPS stimulation enhanced H4K5-hib enrichment at the ATF4 promoter, thereby promoting ATF4 transcription. Inhibition of EP300-mediated 2-hydroxyisobutyrylation or mutation of H4K5 abolished ATF4 activation. Increased H4K5-hib activated the ATF4/NLRP3 signalling axis, promoting inflammasome assembly and amplifying inflammatory responses. ATF4 directly bound to the EP300 promoter and enhanced its transcription, forming a positive feedback loop that further increased H4K5-hib levels. In CLP-induced sepsis, pharmacological inhibition of EP300 or ATF4 reduced H4K5-hib levels and suppressed NLRP3 inflammasome activation. CONCLUSION AND IMPLICATIONS: These findings reveal a previously unrecognized epigenetic mechanism underlying sepsis-induced inflammation and identify the EP300/ATF4/H4K5-hib positive feedback loop as a potential therapeutic target for sepsis.

Animals↗

PubMed2025

Rapid and accurate sepsis diagnostics via a novel probe-based multiplex real-time PCR system.

Sepsis is a critical clinical emergency that requires prompt diagnosis and intervention. Its prevalence has increased due to the aging population and increased antibiotic resistance. Early identification and the use of innovative technologies are crucial for improving patient outcomes. Modern methodologies are needed to minimize the turnaround time for diagnosis and improve outcomes. Rapid diagnostic tests and multiplex PCR are effective but have limitations in identifying a range of pathogens and target genes. Our study evaluated two novel probe-based multiplex real-time PCR systems: the SEPSI ID and SEPSI DR panels. These systems can quickly identify bacterial and fungal pathogens, alongside antibiotic resistance genes. The assays cover 29 microorganisms (gram-negative bacteria, gram-positive bacteria, yeast, and mold species), alongside 23 resistance genes and four virulence factors. A streamlined workflow uses 2 µL of broth from positive blood cultures (BCs) without nucleic acid extraction and provides results in approximately 1 h. We present the results from an evaluation of 228 BCs and 22 isolates previously characterized by whole-genome sequencing. In comparison to the reference methods, the SEPSI ID panel demonstrated a sensitivity of 96.88%, a specificity of 100%, and a PPV of 100%, whereas the SEPSI DR panel showed a sensitivity of 97.8%, a PPV of 89.7%, and a specificity of 96.7%. Both panels also identified additional pathogens and resistance-related targets not detected by conventional methods. This assay shows promise for rapidly and accurately diagnosing sepsis. Future studies should validate its performance in various clinical settings to enhance sepsis management and improve patient outcomes.IMPORTANCEWe present a new diagnostic method that enables the quick and precise identification of pathogens and resistance genes from positive blood cultures, eliminating the need for nucleic acid extraction. This technique can also be used on fresh pathogen cultures. It has the potential to greatly improve treatment protocols, leading to better patient outcomes, more responsible antibiotic use, and more efficient management of healthcare resources.

Humans↗

PubMed1979

Reduction of deep sepsis after total hip arthroplasty.

The role of the operating room environment in the development of deep sepsis after total hip arthroplasty was studied at four centers. The incidence of deep sepsis after 5,865 total hip arthroplasties performed in the four centers varied from 0.5% to 2.3%. Procedures performed in a conventional operating room were associated with the highest incidence of deep sepsis (1.3%). The use of a vertical, unidrectional airflow system with a helmet aspirator suite was associated with the lowest incidence of deep sepsis (0.6%). Although patients with previous hip surgery had an increased incidence of deep sepsis regardless of the operating room environment, those procedures performed in a vertical, unidrectional facility had a lower incidence of deep sepsis. Newer techniques designed for the reduction of airborne contamination of the operative wound seem to reduce the incidence of deep-wound sepsis after total hip arthroplasty, especially in patients with previous hip surgery.

Arthroplasty↗

PubMed1979

Effect of sepsis on tissue adenine nucleotide levels.

Tissue adenine nucleotides were measured in rats to determine if there is depletion of energy stores associated with sepsis. Peritonitis was produced by cecal ligation and cecal puncture. At 16 to 24 hours after ligation, rats which were lethargic but still normotensive (late sepsis) and showed clinical and laboratory confirmation of peritonitis-sepsis were stunned by a blow on the head, and small pieces of tissue were removed and frozen. Adenine nucleotides were measured enzymatically. In late sepsis adenosine triphosphate (ATP) levels in liver and kidney decreased significantly; however, no significant decreases were observed in the diaphragm or gastrocnemius muscle. Hydrogen polarograph measurements of hepatic blood flow indicated that flow was decreased markedly at this stage of peritonitis. A second group of rats was prepared in the same manner, except they were studied 10 hours after ligation (early sepsis). Most rats at this stage of sepsis appeared to be only mildly ill; however, blood cultures obtained from six rats so prepared all were positive. These rats did not show any decrease in either hepatic blood flow or tissue adenine nucleotides. Thus the changes in adenine nucleotides observed in late sepsis (lpw-flow septic rats) are similar to those seen during early hemorrhagic shock and suggest inadequate perfusion associated with peritonitis as the cause.

Adenine Nucleotides↗

PubMed2026

Parallel single-cell host immune profiling and pathogen genomic characterization in Klebsiella-associated sepsis: a pilot study.

OBJECTIVES: Sepsis is a life-threatening syndrome characterized by profound immune dysregulation and substantial biological heterogeneity. Here, we conducted a pilot study to explore host immune remodeling in Klebsiella-associated sepsis by combining single-cell RNA sequencing of peripheral blood mononuclear cells with whole-genome sequencing of the corresponding bloodstream isolates. METHODS: In this prospective observational pilot study, we analyzed peripheral blood mononuclear cells (PBMCs) from two patients with Klebsiella-associated sepsis and two healthy controls (HC) using single-cell RNA sequencing. PBMC composition, differential transcriptional responses, and pathway analysis were assessed across immune subsets. The corresponding bloodstream isolates were characterized by phenotypic antimicrobial susceptibility testing and whole-genome sequencing. RESULTS: Compared to HC, septic patients showed expansion of the myeloid compartment and contraction of the NK/T compartment. High-resolution analysis suggested shifts within lymphoid populations. At the transcriptional level, sepsis was associated with compartment-specific enrichment of interferon-related and host-defence pathways, as well as oxidative phosphorylation, ATP synthesis, and mitochondrial electron transport signatures across multiple PBMC subsets. Classical monocytes exhibited a coordinated decrease in MHC class II-related transcripts. The sepsis-associated isolates were identified as Klebsiella pneumoniae and Klebsiella variicola and were notable for overall antimicrobial susceptibility, limited resistomes, and absence of canonical hypervirulence determinants. CONCLUSION: Our data provide a preliminary description of immune remodeling during Klebsiella-associated sepsis and suggest that severe clinical disease may be associated with isolates lacking classical multidrug-resistance or hypervirulence features. These findings should be interpreted as preliminary and hypothesis-generating and require validation in larger cohorts with detailed clinical severity assessment.

Female↗

PubMed2026

A murine model of sepsis induces age- and sex-specific chromatin remodeling in myeloid-derived suppressor cells.

INTRODUCTION: Sepsis survivors frequently develop long-term immune dysfunction, but the epigenetic mechanisms underlying persistent myeloid suppression remain unclear. Myeloid-derived suppressor cells (MDSCs), whose function is shaped by host age and sex, are key contributors to post-sepsis immune dysregulation. METHODS: Here, we present a high-resolution epigenetic map targeting gene promoters of MDSCs after sepsis and daily chronic stress using MAPit-FENGC, a single-molecule assay that simultaneously profiles DNA methylation and chromatin accessibility. In a clinically relevant murine model, including young and older adult male and female mice, splenic MDSCs were isolated for MAPit-FENGC and single-cell RNA sequencing. RESULTS: Unsupervised clustering identified nine promoter classes reflecting chromatin dynamics: age- and sex-dependent sepsis-induced opening (Classes 1-4), persistent closure with varying levels of DNA methylation (Classes 5-7), and constitutive openness post-sepsis (Classes 8, 9). Transcriptomic profiling corroborated these promoter states, linking accessibility with gene expression. CONCLUSIONS: These findings define promoter-level epigenetic classes across a targeted locus panel in splenic CD11b+Gr1+ cells within this murine sepsis model and generate mechanistic hypotheses regarding age- and sex-associated chromatin states.

Animals↗

PubMed2026

Proteomics Analysis of Plasma for Risk of Sepsis: Findings from the Atherosclerosis Risk in Communities Study.

BACKGROUND: Sepsis is a life-threatening complication of infection with high mortality. A high-throughput analysis of circulating blood proteins may provide mechanistic insight and potent therapeutic targets for the prevention of sepsis. METHODS: We used multivariable Cox regression analysis to examine the association of 4955 plasma proteins, measured by SomaScan, with the risk of incident sepsis among 11 065 participants of the Atherosclerosis Risk in Communities (ARIC) Study (visit 3 in 1993 to 1995; mean age, 60.1 years, 54.4% female, 21.0% Black). Proteins (false discovery rate [FDR] of P < 0.05) discovered at visit 3 were replicated using data at visit 5 (n = 4869 in 2011 to 2013: mean age, 75.5 years) and in the Cardiovascular Health Study (CHS) (n = 3512 in 1992 to 1993; mean age, 74.5 years). Canonical pathways were identified by enrichment analyses. RESULTS: At ARIC visit three, 669 proteins were associated with the risk of sepsis; 175 were replicated at visit 5. Of these, 90 were validated in the CHS. The top 20 proteins ranked by P value were relevant to acute inflammatory signaling in innate immunity. Pathway analyses implicated activation of pro-inflammatory pathways (e.g., cytokine storm signaling) as well as inhibition of anti-inflammatory pathways (e.g., liver X receptor/retinoid X receptor [LXR/RXR] activation), which also play relevant roles in lipid metabolism. CONCLUSIONS: In this analysis, levels of acute inflammatory proteins measured during routine visits were associated with the subsequent incidence of sepsis. An increased risk of sepsis associated with the inhibition of anti-inflammatory pathways, such as LXR/RXR warrants further mechanistic investigation.

Humans↗

PubMed1977

[Pathologic anatomy of sepsis in children with acute leukemia].

Autopsies of 252 cases of acute leukosis in children dying of sepsis were examined. Except 2, all the children had been in the state of exacerbation of the leukemic process and received current intensive therapy. Sepsis was the immediate cause of death in 68 (26.9%) cases. Most prevalent were such forms of sepsis as sepsis with embolic foci of necrosis in organs (44 cases), septicemia (18), septicopyemia (6). In 40 cases considerable leukemic infiltration of the bone marrow and internal organs, in 18 cases moderate and in 10 poor was observed. The criterian of sepsis in children with acute leukosis is the presence of embolic foci of necrosis, less frequently of metastatic abscesses. All the other signs may be associated both with leukemic and septic processes. The causative agent of sepsis in the majority of cases was hemolytic coagulaso-positive staphylococcus.

Acute Disease↗

PubMed2025

Dual RNA isolation from blood: an optimized protocol for host and bacterial RNA purification for dual RNA-sequencing analysis in whole blood sepsis samples.

Dual RNA-sequencing (dual RNA-seq) holds significant promise for deciphering bacterial virulence mechanisms during systemic infections. However, its application in sepsis research is hindered by technical challenges, including a low bacterial burden in blood and limited sample volumes and RNA yield from vulnerable populations, such as neonates. We developed an optimized protocol [dual RNA isolation from blood (DRIB)] for simultaneous stabilization, isolation and purification of high-quality host leukocyte and bacterial RNA from low-volume whole blood samples (0.5 ml). This protocol is compatible with clinical sample collection workflows and high-throughput RNA sequencing. The feasibility of DRIB for dual RNA-seq was validated using a pilot cohort of clinical adult sepsis samples, enabling the investigation of host-bacterial gene expression during sepsis. The DRIB protocol yielded 2.10-6.91 µg of total RNA per clinical sample in our pilot cohort. Dual-species ribosomal RNA (rRNA) depletion and RNA-seq generated 16.6-24.8 million filtered reads per sample, with 63±7% of reads uniquely mapped to host or bacterial sequences. Host genes accounted for 51-68% (8.4-10.9 million) reads, while 0.5-6.7% (79,496-789,808 reads) mapped to bacterial genomes. Bioinformatic analysis revealed that both shared and individual transcriptional patterns were identified in host and bacterial responses, including pathways related to immune metabolism and metal-ion binding. Our optimized DRIB protocol and RNA-seq pipeline effectively captured both host and bacterial RNA transcription in clinical sepsis samples. Expanding this approach to larger cohorts and varying disease timepoints will provide crucial new insights into host-bacterial gene co-expression dynamics in sepsis progression and outcomes.

Humans↗

PubMed2026

Enterocutaneous Fistula-Associated Sepsis and Mortality: Development and Validation of a Multimodal Artificial Intelligence Prediction Model.

BACKGROUND: Predicting enterocutaneous fistula (ECF)-associated sepsis and mortality poses significant challenges in digital health care due to the disease's complexity and heterogeneous clinical manifestations. Current approaches that rely on single-modal data or traditional scoring systems often fail to capture the intricate immune-inflammatory dynamics and multisystem involvement in patients with ECF. OBJECTIVE: This study aims to develop an artificial intelligence (AI)-driven multimodal fusion model integrating clinical, imaging, and transcriptomic data for early prediction of ECF-associated sepsis and 28-day mortality, addressing the limitations of conventional single-dimensional models. METHODS: This study leveraged publicly available datasets (Medical Information Mart for Intensive Care III [MIMIC-III], electronic Intensive Care Unit [eICU], and The Cancer Genome Atlas) to construct a multimodal framework. Clinical parameters were processed using Extreme Gradient Boosting, abdominal imaging features were extracted via convolutional neural networks, and transcriptomic profiles were analyzed with variational autoencoders. A Transformer-based fusion network was employed for joint prediction and validated through cross-validation and external testing. Key features were identified using Shapley Additive Explanations and Local Interpretable Model-Agnostic Explanations interpretability algorithms, while immune regulatory mechanisms were explored via weighted gene co-expression network analysis. RESULTS: The multimodal model achieved an area under the curve (AUC) of 0.89 for predicting sepsis and 28-day mortality, outperforming unimodal models (clinical-only model, AUC 0.72, and imaging-only model, AUC 0.78). Critical predictors included Sequential Organ Failure Assessment score, lactate levels, intra-abdominal free fluid on imaging, and immunoregulatory genes (programmed death-ligand 1 [PD-L1] and indoleamine 2,3-dioxygenase 1 [IDO1]). Mechanistic analysis revealed distinct immune reprogramming in patients with sepsis, characterized by increased regulatory T cells and M2 macrophages, along with downregulated cluster of differentiation 8+ (CD8+) T cells. CONCLUSIONS: This multimodal AI model offers an innovative digital solution in medical informatics, enabling precise early risk stratification for ECF-associated sepsis. By integrating multisource data and providing interpretable insights into immune-inflammatory pathways, the model enhances health care quality for patients with ECF and paves the way for personalized intervention strategies.

Humans↗

PubMedDate not supplied

The effect of PEEP on oxygenating capacity in acute respiratory failure with sepsis.

We report an evaluation of the effect of postive-end-expiratory-pressure (PEEP) on improving pulmonary oxygenating capacity in the adult respiratory distress syndrome (ARDS), when the latter is associated with generalized gram-negative sepsis. Fifty-seven cases treated in our RICU with PEEP ventilation (April 1972 to January 1975) were retrospectively reviewed. Oxygenating capacity improvement was evaluated in terms of the changes in PaO2/FIO2 and AaDO2 (FIO2 = 1.0). Both the short term (2-3 hours from the initiation of PEEP) and the overall effects of PEEP were evaluated. A mean PEEP of 5.6 cm H2O initially increased PaO2/FIO2 by a mean of 94 torr and decreased AaDO2 (FIO2 = 1.0) by 105 torr in the 28 nonseptic patients. In the 29 septic patients, 5.1 cm H2O PEEP initially increased PaO2/FIO2 by 32 torr and decreased AsDO2 (FIO2 = 1.0) by 38 torr. The differences between the septic and nonseptic patients were statistically significant (P less than 0.001). Likewise, the long-term effect of similar levels of PEEP was in increasing PaO2/FIO2 by 142 torr and by 75 torr in the nonseptic and septic patients, respectively. The final reduction in AaDO2 (FIO2 = 1.0) was 163 torr and 87 torr in the nonseptic and septic patients, respectively. These differences between patient groups were also statistically significant (P less than 0.02). Mortality during PEEP was 15/29 and 3/28 in the septic and nonseptic patients, respectively. Overall mortality in the septic and nonseptic groups was 18/29 and 5/28, respectively. We conclude that ARDS with sepsis constitutes a more severe pulmonary insult than ARDS without sepsis, and/or that generalized sepsis creates a more prolonged pulmonary insult that makes it less amenable to PEEP. Thus, high levels of PEEP may be needed to treat ARDS associated with sepsis.

Adolescent↗

PubMed2025

INCREASED CIRCULATORY KREBS CYCLE METABOLITES IN SEPSIS IS ASSOCIATED WITH INCREASED INTERLEUKIN-6 RELEASE AND WORSE SURVIVAL.

Objective : Recent studies have proposed that Krebs cycle metabolites may serve as potential biomarkers for prognosis in sepsis. However, whether these metabolites are associated with disease severity and can be applied to improve the effectiveness of current prognosis assessment in sepsis remains unclear and is explored in this study. Methods : This prospective multicenter cohort study was conducted in medical intensive care units (ICUs). From December 2019 to September 2022, consecutive patients admitted to medical ICUs for sepsis were screened and recruited. Plasma samples were obtained for measurements of cytokines and Krebs cycle metabolites, including citrate/isocitrate, cis-aconitate, alpha-ketoglutarate, succinate, fumarate, and malate. Results : In total, 97 patients admitted for sepsis were enrolled in the study. The 28-day mortality rate was 17.5%, and nonsurvivors exhibited significantly increased plasma lactate levels and Sequential Organ Failure Assessment (SOFA) scores. Plasma levels of Krebs cycle metabolites were significantly correlated with both plasma lactate and interleukin-6 levels. Except for citrate/isocitrate, all Krebs cycle metabolites were significantly elevated in patients with acute kidney injury. Multivariate Cox proportional hazard models, adjusted for plasma lactate levels and SOFA scores, revealed that plasma levels of alpha-ketoglutarate (adjusted hazard ratio [HR]: 2.404, P = 0.002), fumarate (adjusted HR: 1.904, P = 0.001) and malate (adjusted HR: 1.327, P = 0.019) were associated with increased risk of 28-day mortality. Conclusions : Study findings indicate that Krebs cycle metabolites, particularly alpha-ketoglutarate, fumarate, and malate, when applied with SOFA score, might enhance prognostic assessment in patients with sepsis.

Humans↗

PubMed2026

Rare genetic variant risks in patients with sepsis-associated acute respiratory distress syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a complex, heterogeneous, and deadly condition often resulting from pulmonary lesions due to sepsis, among other causes. There is a lack of targeted therapies to specifically treat the patients. Common genetic factors in the population (frequency > 1%) have been associated with ARDS susceptibility, but systematic genetic screens of the role of rare genetic variants are lacking. We used the network of known molecular interactions to identify ARDS risks from clusters of biologically related genes containing qualifying variants (QVs) with frequency < 1% likely affecting function. METHODS: We conducted whole-exome sequencing in sepsis patients from the GEN-SEP cohort (n = 822, of which 272 developed ARDS). A network-based heterogeneity clustering algorithm was used to discover significant gene clusters (p < 1 × 10–5). Gene-set enrichment analysis and logistic regression models aggregating QVs were used for cross-verification to confirm consistency and deepen understanding of the effect sizes of gene clusters. RESULTS: We identified 19 significant clusters (plowest = 3.29 × 10–10), each containing an average of 102 genes (11.6% mean similarity). QVs in nine gene clusters were associated with sepsis-associated ARDS (plowest = 1 × 10–5) but were not associated with 28-day survival. Clusters were enriched in several biological pathways, notably the Toll-like receptor cascades. CONCLUSIONS: These results support a marked genetic heterogeneity underlying ARDS susceptibility and the presence of rare risk variants involving multiple biological processes that are associated with sepsis outcomes. Particularly, they underscore the importance of rare variants in genes of the Toll-like receptor cascades in the risk for sepsis-associated ARDS.

Humans↗

PubMed1979

A ten-year retrospective study of sepsis in severely burned patients treated with or without silver sulfadiazinate.

Three groups of extensive burn patients of the surgical intensive care unit (ICU) have been compared: Group I: twenty patients, who were treated locally without silver sulfadiazinate (1968-1970); Group II: the twenty first patients topically treated with silver sulfadiazinate (1970-1972); Group III: twenty similarly treated patients, with silver sulfadiazinate, six years later (1976-1977). The groups are statistically comparable. All bacteriological samples were computerized; the chi-square method was used for statistical analysis of the data. The main conclusions are: (A) Silver sulfadiazinate treatment reduced Pseudomonas aeruginosa and Proteus sepsis. No change in Coliform bacilli sepsis was observed. After six years, a rise in Klebsiella sepsis and Candida sepsis was noted. (B) A quantitative estimate of infections in each group was made by measuring the percentage of positive samples, taking into account the five above-mentioned strains. In the beginning, silver sulfadiazinate reduced quantitative sepsis, but this benefit decreased after six years; the same evolution was demonstrated for positive blood bacteriology; severe septicaemia showed a parallel pattern.

Burns↗

PubMed1977

Neonatal sepsis at The Johns Hopkins Hospital, 1969-1975: bacterial isolates and clinical correlates.

The experience with neonatal sepsis at The Johns Hopkins Hospital during 1969-1975 was reviewed. Major pathogens included Escherichia coli, group B streptococcus, other streptococci, and Klebsiella. Nineteen percent of coliform isolates were kanamycin-resistant. The frequency of recovery of E. coli was increased in early-onset sepsis, and the frequency of recovery of Klebsiella was increased in late-onset sepsis. The mortality rate was 23%. The frequency of recovery of E. coli was increased in fatal cases, and mortality was highly correlated with the presence of gastrointestinal catastrophe. Ampicillin and gentamicin are the initial antibiotics of choice for neonatal sepsis at this institution; a penicillinase-resistant penicillin should be added when Staphylococcus aureus involvement is likely, and addition of chloramphenicol or clindamycin should be considered for infants at increased risk for Bacteroides fragilis sepsis.

Escherichia coli Infections↗

PubMed1976

Tobramycin and cephalothin for treatment of suspected sepsis in neutropenic children with cancer.

The safety and efficacy of tobramycin and cephalothin in treatment of suspected sepsis were studied in neutropenic children with various malignancies. Twenty episodes of suspected sepsis in 19 febrile children with cancer were treated with parenteral tobramycin and cephalothin; the duration of therapy ranged from one to 80 days. In 14 of the 20 episodes of suspected sepsis, a favorable clinical response was achieved within five days after initiation of antibiotic therapy. These episodes included a urinary tract infection with Proteus mirabilis and sepsis due to Escherichia coli. In four of the additional six episodes, clinical deterioration was though to be caused by the underlying malignancies. Two episodes included a case of E. coli spesis that ended fatally and a nosocomial infection with Eikenella corrodens. Results of this study suggest that combination therapy with tobramycin and cephalothin is safe and efficacious in treatment of suspected sepsis in febrile children with malignancies and neutropenia.

Agranulocytosis↗

PubMed1976

The changing pattern of bacterial sepsis since the introduction of antibiotic therapy.

During the six-year period, 1968-1973, sepsis developed in 1 of every 80 patients admitted to the Presbyterian Hospital, New York. In 1 of 133 patients the sepsis was due to Gram-positive organisms, and in 1 of 188 patients to Gram-negative organisms. The mortality rate for Gram-positive cases was 4.4 percent, for Gram-negative cases 19.1 percent, and for urologic cases 15.3 percent (versus 56.25 percent in 1959-1964). Data are presented on the relative incidences of involved pathogens in 1740 cases of Gram-positive sepsis /78 deaths), and in 1236 cases of Gram-negative sepsis (205 deaths). The lowering of the sepsis mortality rate has been the result of preventative measures, early diagnosis, and vigorous treatment. Treatment includes the correction of acidosis and anoxia, early administration of bactericidal antibiotics, and restoration of the microcirculation by administration of corticosteroids, beta-adrenergic drugs, and appropriate diuretics.

Adrenergic beta-Antagonists↗