Do diabetes and poor control of acute stress-related hyperglycemia increase the risk of ICU-acquired infections? A retrospective assessment in patients with septic shock

Annals of Intensive Care volume 15, Article number: 168 (2025) Published: 22 October 2025

Background

Patients with septic shock who survive the early resuscitation phase are prone to ICU-acquired infections. Although hyperglycemia harbors potent immunomodulatory properties, the impact of preexisting diabetes and the control of acute stress-induced hyperglycemia on the risk of further infections remains unclear.

Materials and methods

We conducted a retrospective (2008–2023) single-center study in patients with septic shock who remained alive in the ICU after 72 h. Glycemic control was assessed during the first 72 h. Mild and severe hyperglycemia were defined by blood glucose levels > 8 mmol/L and > 10 mmol/L, respectively. Poor glycemic control was defined when blood glucose levels were above 8 mmol/L for more than 20% of time. The primary outcome was ICU-acquired infections.

Results

The study involved 901 patients, with preexisting diabetes present in 22% of them. Most patients (71%) experienced hyperglycemic episodes > 8 mmol/L, prompting fast-acting insulin treatment. ICU-acquired infections developed in 243 patients (26.9%), with median time from ICU admission to diagnosis of 9 days, interquartile range [6–13]. There was no association between preexisting diabetes and ICU-acquired infections. Patients with further ICU-acquired infections displayed poorer control of stress-induced hyperglycemia, with longer exposure to hyperglycemia (78% with mild or severe hyperglycemia for more than 20% of time compared to 68% of patients without subsequent infections (p = 0.005)). Poor glycemic control was independently associated with the development of ICU-acquired infections.

Conclusion

72-hour poor glycemic control, but not preexisting diabetes, was independently associated with an increased risk of ICU-acquired infections in septic shock patients and may therefore contribute to the post-aggressive immunosuppressive response. This argues for effective glycemic management to improve outcomes in this setting.

 

ICU patients with infectious complications after abdominopelvic surgery: Is thoracic CT in addition to abdominal CT helpful?

 

by Heiner Nebelung, Natalie Wotschel, Hanns-Christoph Held, Johanna Kirchberg, Jürgen Weitz, Christoph Georg Radosa, Michael Laniado, Ralf-Thorsten Hoffmann and Verena Plodeck 

 

Annals of Intensive Care volume 13, Article number: 6 (2023) 

 

Background

The aim of this study was to assess the usefulness of adding thoracic CT to abdominal CT in intensive care unit (ICU) patients with signs of infection after abdominopelvic surgery.

Methods

143 thoracoabdominal CTs of ICU patients with signs of infection after abdominopelvic surgery were retrospectively reviewed for thoracic pathologies. It was determined if pathologic findings were visible only on thoracic CT above the diaphragmatic dome or also on abdominal CT up to the diaphragmatic dome. All thoracic pathologies visible only above the diaphragmatic dome were retrospectively analyzed by an ICU physician in terms of clinical relevance. Diagnostic and therapeutic efficacy of thoracic CT were assessed with regard to an infectious focus and to other pathologic findings.

Results

297 pathologic thoracic findings were recorded. 26 of the 297 findings could only be detected on images obtained above the diaphragmatic dome (in 23 of 143 CTs). A change in patient management was initiated due to only one of the 26 supradiaphragmatic findings. Diagnostic efficacy of thoracic CT in addition to abdominal CT to identify an infectious focus was 3.5% (95%-CI: 0.5–6.5%) and therapeutic efficacy was 0.7% (95%-CI: 0–2.1%). With regard to all pathologic thoracic findings, diagnostic efficacy was 16.1% (95%-CI: 10.1–22.1%) and therapeutic efficacy remained at 0.7%.

Conclusions

Additional thoracic CT to detect an infectious focus in ICU patients after abdominopelvic surgery leads to identification of the focus in only 3.5% and to changes in patient management in only 0.7%. Other relevant findings are more common (16.1%), but very rarely affect patient management.

In-hospital mortality associated with the misdiagnosis or unidentified site of infection at admission

In-hospital mortality associated with the misdiagnosis or unidentified site of infection at admission

by Toshikazu Abe, et al.

Background

Rapid detection, early resuscitation, and appropriate antibiotic use are crucial for sepsis care. Accurate identification of the site of infection may facilitate a timely provision of appropriate care. We aimed to investigate the relationship between misdiagnosis of the site of infection at initial examination and in-hospital mortality.

Methods

This was a secondary-multicenter prospective cohort study involving 37 emergency departments. Consecutive adult patients with infection from December 2017 to February 2018 were included. Misdiagnosis of the site of infection was defined as a discrepancy between the suspected site of infection at initial examination and that at final diagnosis, including those infections remaining unidentified during hospital admission, whereas correct diagnosis was defined as site concordance. In-hospital mortality was compared between those misdiagnosed and those correctly diagnosed.

Results

Of 974 patients included in the analysis, 11.6% were misdiagnosed. Patients diagnosed with lung, intra-abdominal, urinary, soft tissue, and CNS infection at the initial examination, 4.2%, 3.8%, 13.6%, 10.9%, and 58.3% respectively, turned out to have an infection at a different site. In-hospital mortality occurred in 15%. In both generalized estimating equation (GEE) and propensity score-matched models, misdiagnosed patients exhibited higher mortality despite adjustment for patient background, site infection, and severity. The adjusted odds ratios (misdiagnosis vs. correct diagnosis) for in-hospital mortality were 2.66 (95% CI, 1.45–4.89) in the GEE model and 3.03 (95% CI, 1.24–7.38) in the propensity score-matched model. The difference in the absolute risk in the GEE model was 0.11 (0.04–0.18).

Conclusions

Among patients with infection, misdiagnosed site of infection is associated with a > 10% increase in in-hospital mortality.

Prompt Administration of Antibiotics and Fluids in the Treatment of Sepsis: A Murine Trial*

Prompt Administration of Antibiotics and Fluids in the Treatment of Sepsis: A Murine Trial*

by Lewis, Anthony J.; Griepentrog, John E.; Zhang, Xianghong; Angus, Derek C.; Seymour, Christopher W.; Rosengart, Matthew R.

Critical Care Medicine: May 2018 - Volume 46 - Issue 5 - p e426–e434

Objectives: Sepsis, the acute organ dysfunction caused by a dysregulated host response to infection, poses a serious public health burden. Current management includes early detection, initiation of antibiotics and fluids, and source control as necessary. Although observational data suggest that delays of even a few hours in the initiation of antibiotics or IV fluids is associated with survival, these findings are controversial. There are no randomized data in humans, and prior animal studies studied time from experimental manipulation, not from the onset of clinical features of sepsis. Using a recently developed murine cecal ligation and puncture model that precisely monitors physiologic deterioration, we hypothesize that incremental hourly delays in the first dose of antibiotics, in the first bolus of fluid resuscitation, or a combination of the two at a clinically relevant point of physiologic deterioration during polymicrobial sepsis will shorten survival. Design: Randomized laboratory animal experimental trial. Setting: University basic science laboratory. Subjects: Male C57BL/6J, female C57BL/6J, aged (40–50 wk old) male C57BL/6J, and BALB/C mice. Interventions: Mice (n = 200) underwent biotelemetry-enhanced cecal ligation and puncture and were randomized after meeting validated criteria for acute physiologic deterioration. Treatment groups consisted of a single dose of imipenem/cilastatin, a single bolus of 30 mL/kg fluid resuscitation, or a combination of the two. Mice were allocated to receive treatment at the time of meeting deterioration criteria, after a 2-hour delay or after a 4-hour delay. Measurements and Main Results: Hourly delays in the initiation of antibiotic therapy led to progressively shortened survival in our model (p < 0.001). The addition of fluid resuscitation was unable to rescue animals, which received treatment 4 hours after meeting enrollment criteria. Systemic inflammation was increased, and host physiology was increasingly deranged with hourly delays to antibiotics. Conclusions: We conclude that antibiotic therapy is highly time sensitive, and efforts should be made to deliver this critical therapy as early as possible in sepsis, perhaps extending into the first point of medical contact outside the hospital.

Danger Signals in the ICU

Danger Signals in the ICU

by Schenck, Edward J.; Ma, Kevin C.; Murthy, Santosh B.; Choi, Augustine M. K.  

Critical Care Medicine: May 2018 - Volume 46 - Issue 5 - p 791–798

Objectives: Sterile and infectious critical illnesses often result in vasoplegic shock and a robust systemic inflammatory response that are similar in presentation. The innate immune system is at the center of the response to both infectious and traumatic insults. Damage-associated molecular patterns are small molecules that are released from stressed or dying cells. Damage-associated molecular patterns activate pattern recognition receptors and coordinate the leading edge of the innate immune response. This review introduces the concept of damage-associated molecular patterns and how they activate a systemic inflammatory response, specifically in trauma, neurologic injury, and infection. It also explores how, when carried to extremes, damage-associated molecular patterns may even perpetuate multisystem organ failure. Data Sources: Basic and clinical studies were obtained from a PubMed search through August 2017. Study Selection: Articles considered include original articles, review articles, and conference proceedings. Data Extraction: An analysis of scientific, peer-reviewed data was performed. High quality preclinical and clinical studies adjudicated by the authors were included and summarized. Data Synthesis: Pattern recognition receptors respond to damage-associated molecular patterns and then activate inflammatory pathways. Damage-associated molecular patterns have been linked to the recruitment of sentinel leukocytes and the initiation of the inflammatory cascade. Damage-associated molecular patterns have been linked to many conditions in critical care illnesses. Preclinical models have added insight into how they may mediate distant organ dysfunction. Conclusions: Damage-associated molecular pattern activation and release is an important research for intensive care practitioners. It will add to our understanding of the phase and state of the innate immune response to an insult. Early work is encouraging. However, only with improved understanding of damage-associated molecular pattern activation and function, we can perhaps hope to target damage-associated molecular patterns as diagnostic and/or therapeutic modalities in the future.

Quick Sequential Organ Failure Assessment and Systemic Inflammatory Response Syndrome Criteria as Predictors of Critical Care Intervention Among Patients With Suspected Infection

Quick Sequential Organ Failure Assessment and Systemic Inflammatory Response Syndrome Criteria as Predictors of Critical Care Intervention Among Patients With Suspected Infection

Moskowitz, A et al
Critical Care Medicine: November 2017 - Volume 45 - Issue 11 - p 1813–1819

Objectives: Objectives:The Sepsis III clinical criteria for the diagnosis of sepsis rely on scores derived to predict inhospital mortality. In this study, we introduce the novel outcome of “received critical care intervention” and investigate the related predictive performance of both the quick Sequential Organ Failure Assessment and the Systemic Inflammatory Response Syndrome criteria.
Design:This was a single-center, retrospective analysis of electronic health records. Setting: Setting:Tertiary care hospital in the United States. Patients: Patients:Patients with suspected infection who presented to the emergency department and were admitted to the hospital between January 2010 and December 2014. Interventions: Interventions:Systemic Inflammatory Response Syndrome and quick Sequential Organ Failure Assessment scores were calculated, and their relationships to the receipt of critical care intervention and inhospital mortality were determined. 
Measurement and Main Results:A total of 24,164 patients were included of whom 6,693 (27.7%) were admitted to an ICU within 48 hours; 4,453 (66.5%) patients admitted to the ICU received a critical care intervention. Among those with quick Sequential Organ Failure Assessment less than 2, 13.4% received a critical care intervention and 3.5% died compared with 48.2% and 13.4%, respectively, for quick Sequential Organ Failure Assessment greater than or equal to 2. The area under the receiver operating characteristic was similar whether quick Sequential Organ Failure Assessment was used to predict receipt of critical care intervention or inhospital mortality (0.74 [95% CI, 0.73–0.74] vs 0.71 [0.69–0.72]). The area under the receiver operating characteristic of Systemic Inflammatory Response Syndrome for critical care intervention (0.69) and mortality (0.66) was lower than that for quick Sequential Organ Failure Assessment (p < 0.001 for both outcomes). The sensitivity of quick Sequential Organ Failure Assessment for predicting critical care intervention was 38%. 
Conclusions: Emergency department patients with suspected infection and low quick Sequential Organ Failure Assessment scores frequently receive critical care interventions. The misclassification of these patients as “low risk,” in combination with the low sensitivity of quick Sequential Organ Failure Assessment greater than or equal to 2, may diminish the clinical utility of the quick Sequential Organ Failure Assessment score for patients with suspected infection in the emergency department.

Preventing central venous line related bloodstream infections in adult ICUs: Start from the basics and bundle

Preventing central venous line related bloodstream infections in adult ICUs: Start from the basics and bundle

Arvaniti K
Intensive and Critical Care Nursing Article in Press

In the Intensive Care Unit (ICU), central venous line associated bloodstream infections (CLABSIs) represent an important component of healthcare-associated infections and are linked to increased morbidity, mortality and overall hospital-associated cost (Warren et al., 2006; Stevens et al., 2014). CLABSIs are considered a preventable cause of healthcare-associated patient’s adverse events. Despite major scientific advances in pathogenesis, surveillance methods and treatment approach, the most appropriate interventions to prevent and control CLABSIs remain debatable.

Arterial Catheter Use in the ICU: A National Survey of Antiseptic Technique and Perceived Infectious Risk

Arterial Catheter Use in the ICU: A National Survey of Antiseptic Technique and Perceived Infectious Risk


Critical Care Medicine: November 2015 - Volume 43 - Issue 11 - p 2346–2353


Cohen, David M. et al


Objectives: Recent studies have shown that the occurrence rate of bloodstream infections associated with arterial catheters is 0.9–3.4/1,000 catheter-days, which is comparable to that of central venous catheters. In 2011, the Centers for Disease Control and Prevention published new guidelines recommending the use of limited barrier precautions during arterial catheter insertion, consisting of sterile gloves, a surgical cap, a surgical mask, and a small sterile drape. The goal of this study was to assess the attitudes and current infection prevention practices used by clinicians during insertion of arterial catheters in ICUs in the United States. Design: An anonymous, 22-question web-based survey of infection prevention practices during arterial catheter insertion. Setting: Clinician members of the Society of Critical Care Medicine. Subjects: Eleven thousand three hundred sixty-one physicians, nurse practitioners, physician assistants, respiratory therapists, and registered nurses who elect to receive e-mails from the Society of Critical Care Medicine. Interventions: None. Measurements and Main Results: There were 1,265 responses (11% response rate), with 1,029 eligible participants after exclusions were applied. Only 44% of participants reported using the Centers for Disease Control and Prevention–recommended barrier precautions during arterial catheter insertion, and only 15% reported using full barrier precautions. The mean and median estimates of the incidence density of bloodstream infections associated with arterial catheters were 0.3/1,000 catheter-days and 0.1/1,000 catheter-days, respectively. Thirty-nine percent of participants reported that they would support mandatory use of full barrier precautions during arterial catheter insertion. Conclusions: Barrier precautions are used inconsistently by critical care clinicians during arterial catheter insertion in the ICU setting. Less than half of clinicians surveyed were in compliance with current Centers for Disease Control and Prevention guidelines. Clinicians significantly underestimated the infectious risk posed by arterial catheters, and support for mandatory use of full barrier precautions was low. Further studies are warranted to determine the optimal preventive strategies for reducing bloodstream infections associated with arterial catheters.

Rapid Diagnosis of Infection in the Critically Ill, a Multicenter Study of Molecular Detection in Bloodstream Infections, Pneumonia, and Sterile Site Infections

Rapid Diagnosis of Infection in the Critically Ill, a Multicenter Study of Molecular Detection in Bloodstream Infections, Pneumonia, and Sterile Site Infections

Critical Care Medicine: November 2015 - Volume 43 - Issue 11 - p 2283–2291

Vincent, Jean-Louis et al.



Objective: Early identification of causative microorganism(s) in patients with severe infection is crucial to optimize antimicrobial use and patient survival. However, current culture-based pathogen identification is slow and unreliable such that broad-spectrum antibiotics are often used to insure coverage of all potential organisms, carrying risks of overtreatment, toxicity, and selection of multidrug-resistant bacteria. We compared the results obtained using a novel, culture-independent polymerase chain reaction/electrospray ionization-mass spectrometry technology with those obtained by standard microbiological testing and evaluated the potential clinical implications of this technique. 
Design: Observational study. Setting: Nine ICUs in six European countries. Patients: Patients admitted between October 2013 and June 2014 with suspected or proven bloodstream infection, pneumonia, or sterile fluid and tissue infection were considered for inclusion. Interventions: None. 
Measurements and Main Results: We tested 616 bloodstream infection, 185 pneumonia, and 110 sterile fluid and tissue specimens from 529 patients. From the 616 bloodstream infection samples, polymerase chain reaction/electrospray ionization-mass spectrometry identified a pathogen in 228 cases (37%) and culture in just 68 (11%). Culture was positive and polymerase chain reaction/electrospray ionization-mass spectrometry negative in 13 cases, and both were negative in 384 cases, giving polymerase chain reaction/electrospray ionization-mass spectrometry a sensitivity of 81%, specificity of 69%, and negative predictive value of 97% at 6 hours from sample acquisition. The distribution of organisms was similar with both techniques. Similar observations were made for pneumonia and sterile fluid and tissue specimens. Independent clinical analysis of results suggested that polymerase chain reaction/electrospray ionization-mass spectrometry technology could potentially have resulted in altered treatment in up to 57% of patients. 
Conclusions: Polymerase chain reaction/electrospray ionization-mass spectrometry provides rapid pathogen identification in critically ill patients. The ability to rule out infection within 6 hours has potential clinical and economic benefits.

Likelihood of infection in patients with presumed sepsis at the time of intensive care unit admission: a cohort study

Likelihood of infection in patients with presumed sepsis at the time of intensive careunit admission: a cohort study

Critical Care 2015, 19:319

Klein Klouwenberg, PMC et al

Introduction: A clinical suspicion of infection is mandatory for diagnosing sepsis in patients with a systemic inflammatory response syndrome. Yet, the accuracy of categorizing critically ill patients presenting to the intensive care unit (ICU) as being infected or not is unknown. We therefore assessed the likelihood of infection in patients who were treated for sepsis upon admission to the ICU, and quantified the association between plausibility of infection and mortality.
Methods: We studied a cohort of critically ill patients admitted with clinically suspected sepsis to two tertiary ICUs in the Netherlands between January 2011 and December 2013. The likelihood of infection was categorized as none, possible, probable or definite by post-hoc assessment. We used multivariable competing risks survival analyses to determine the association of the plausibility of infection with mortality.
Results: Among 2579 patients treated for sepsis, 13% had a post-hoc infection likelihood of “none”, and an additional 30% of only “possible”. These percentages were largely similar for different suspected sites of infection. In crude analyses, the likelihood of infection was associated with increased length of stay and complications. In multivariable analysis, patients with an unlikely infection had a higher mortality rate compared to patients with a definite infection (subdistribution hazard ratio 1.23; 95% confidence interval 1.03-1.49).
Conclusions: This study is the first prospective analysis to show that the clinical diagnosis of sepsis upon ICU admission corresponds poorly with the presence of infection on post-hoc assessment. A higher likelihood of infection does not adversely influence outcome in this population.

Zero risk for central line-associated bloodstream infection. Are we there yet?

Zero risk for central line-associated bloodstream infection. Are we there yet? Critical care medicine, Feb 2012, Vol. 40(2), p. 388-393.

McLaws, M-L. and Burrell, A.R.

http://journals.lww.com/ccmjournal/Abstract/2012/02000/Zero_risk_for_central_line_associated_bloodstream.3.aspx

Objective: Identify the longest period a central line remains free from central line-associated bloodstream infection during an 18-month insertion-bundle project.

Reduction of catheter related bloodstream infections in intensive care: one for all, all for one?

Nursing in Critical Care Volume14, Issue3,2009.
Onno K Helder, Jos M Latour
Abstract
Published Online: 1 Apr 2009DOI 10.1111/j.1478-5153.2009.00340.x

EfCCNa survey: European intensive care nurses' attitudes and beliefs towards end-of-life care
Jos M Latour, Paul Fulbrook, John W Albarran
Abstract
Published Online: 1 Apr 2009DOI 10.1111/j.1478-5153.2008.00328.x

Methicillin-resistant Staphylococcus aureus central line-associated bloodstream infections in US intensive care units, 1997-2007.

Methicillin-resistant Staphylococcus aureus central line-associated bloodstream infections in US intensive care units, 1997-2007.
Burton DC, Edwards JR, Horan TC, Jernigan JA, Fridkin SK.JAMA. 2009
Feb 18;301(7):727-36. PMID: 19224749
[PubMed - indexed for MEDLINE]
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The electronic medical record as a tool for infection surveillance: Successful automation of device-days.

Am J Infect Control. 2009 Mar 6. [Epub ahead of print] LinkOut

The electronic medical record as a tool for infection surveillance: Successful automation of device-days.
Wright MO, Fisher A, John M, Reynolds K, Peterson LR, Robicsek A.
Department of Infection Control, NorthShore University HealthSystem, Evanston, IL.

BACKGROUND: Manual collection of central venous catheter, ventilator, and indwelling urinary catheter device-days is time-consuming, often restricted to intensive care units (ICU) and prone to error.

METHODS: We describe the use of an electronic medical record to extract existing clinical documentation of invasive devices. This allowed automated device-days calculations for device-associated infection surveillance in an acute care setting.

RESULTS: The automated system had high sensitivity, specificity, and positive and negative predictive values (>0.90) compared with chart review. The system is not restricted to ICUs and reduces surveillance efforts by a conservative estimate of over 3.5 work-weeks per year in our setting. Eighty percent of urinary catheter days and 50% of central venous catheter-days occurred outside the ICU.

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Diabetes mellitus is an independent risk factor for ICU-acquired bloodstream infections.

Intensive Care Medicine

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Johnson, D.; Lineweaver, L.; Maze, L.M.
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The clinical effectiveness of central venous catheters treated with anti-infective agents in preventing catheter-related bloodstream infections

Critical Care Medicine Feb 2009

Section: Review Articles
Pages: 702-712
The clinical effectiveness of central venous catheters treated with anti-infective agents in preventing catheter-related bloodstream infections: A systematic review

Authors: Juliet C. Hockenhull, MSc; Kerry M. Dwan, MSc; Godfrey W. Smith, MD;
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Risk factors and prognosis of catheter-related bloodstream infection in critically ill patients: a multicenter study.

pp. 2185-2193
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http://zetoc.mimas.ac.uk/wzgw?db=etoc&terms=RN240539030&field=zid