The Relationship Between Monocyte Distribution Width (MDW) and Blood Culture Result in Adult Patients Admitted for Sepsis in the Emergency Department of a Tertiary Hospital

Background of the Study

With the advent of the surviving sepsis campaign, particularly in the emergency setting, sepsis remains a leading cause of mortality and is a heavy financial burden in healthcare worldwide.1 Survival during septic episodes is significantly improved when sepsis is recognized early and organ dysfunction is prevented by prompt antimicrobial and supportive treatment. However, early sepsis diagnosis remains challenging, especially for emergency and critical care physicians. Despite the development of helpful clinical tools such as the Systemic Inflammatory Response Syndrome (SIRS) criteria and quick Sepsis Related Organ Failure Assessment (qSOFA) score , delays in detection and uncertainties leading to misdiagnosis are still inevitable, leading to adverse outcomes and higher healthcare burden.2 To improve diagnostic accuracy, laboratory measurement of sepsis biomarkers has become commonplace in current practice.

A routine hematologic screen such as the complete blood count with differential (CBC) remains a simple, low--cost tool in the workup of many conditions. In recent years, monocyte distribution width (MDW) is a new hematologic parameter that is part of the complete blood count with differential available in select hematology analyzers. Recent studies have shown this parameter to be a novel marker for early sepsis detection, which is particularly important in the emergency setting.3 Several studies compared its performance against commonly used sepsis biomarkers such as C-reactive protein and procalcitonin and found that the inability to accurately distinguish sepsis from other commonly encountered conditions in the emergency setting limits the discriminatory power of these existing markers.4,5 The premise of using monocyte distribution width as a biomarker for early sepsis detection lies in the fact that WBCs increase in size during the progression of infection with clinical signs of escalation from systemic inflammatory response syndrome (SIRS) to sepsis.6 In particular, monocytes are involved in the early response to bacterial invasion in the bloodstream, acting as the first to intercept the invading bacteria by means of phagocytosis and immune processing. A study showed that of the changes relating to the size of white blood cells, acute changes in monocyte size (MDW) best discriminated sepsis from other acute conditions in the emergency department.7 During innate immune activation, monocyte morphology shifts into the activated form, allowing cells to migrate from the peripheral blood to the site of infection. During bacteremia, activated monocytes have increased cell size with ameboid cell differentiation, volume, and increased antigen expression of functional markers, particularly CD16. This makes an accurate measurement of monocyte size a good determinant of the degree of monocytic immune activation in septic patients. This infection-related variation in size may be monitored by measuring the spread of monocytes in coulter chambers.

Monitoring monocytes provides a window into the systemic inflammation, which aids in determining the severity and progression of infection.8 Through the proprietary Volume, Conductivity, and Scatter (VCS) technology of the UniCel DxH900, which can detect morphologic changes in immature and reactive cells similar to a peripheral blood smear, signals obtained by the bioelectrical impedance analysis of cell volumes, conductivity, and light scatter signals are used to evaluate morphological changes in leukocytes, particularly in monocytes. This uses three independent energy sources all at once: direct current impedance to measure cell volume of all cell types, radiofrequency opacity to characterize conductivity for the internal composition of each cell, and a laser beam to measure light scatter for cytoplasmic granularity and nuclear structure.2,4 Therefore, the value of MDW represents the width of a set of monocyte volume values as a standard deviation.6 Hence, MDW gives a clinical picture of the monocyte population’s volume in the peripheral blood. Since MDW has the advantage of being measured routinely as part of the CBC with differential, it can potentially be a cost-effective biomarker for early sepsis diagnosis.3

Several validation studies were conducted which sought to establish reference ranges and cutoff values of <13.98 (low), 13.98-21.28 (moderate), and >21.28 (high) for sepsis.10, 11 Others compared the performance of MDW to other current sepsis biomarkers such as procalcitonin and C-reactive protein. Although procalcitonin (PCT) was increasingly recognized as the best tool to evaluate ensuing sepsis in at-risk patients, since its increase is generally regarded as a precedent for septic shock in bacteremic patients, the major limitations of PCT monitoring are brought about by costs related to repeat assaying, and false negative results in patients with invasive fungal infections.4,5,7 More recent papers analyzed MDW in subjects with Severe Acute Respiratory Sydrome-Coronavirus-2 (SARS-CoV-2) infection to explore whether its elevation reflects the degree of infection.12,13,14 Other studies used similar parameters but focused on patients in intensive care units.9,15,16,17 However, laboratory-based studies investigating MDW, sepsis, and blood culture results are lacking in the local setting. In the current Philippine hematology laboratory practice, including cell population data does not yet see widespread adoption for us to have a deeper understanding and practical application of these additional data from the current hematology analyzers. With the trend of shifting towards laboratory automation as the demand for faster turnaround times and increasing volumes of laboratory tests requested, it is hoped that this study would help in the decision to procure more capable and efficient analyzers to better serve the population with timely and accurate test results.

General Objective

This study aimed to determine the relationship between monocyte distribution width and blood culture growth in patients with sepsis admitted to the emergency department of a tertiary hospital.

Specific Objectives

Specifically, this study aimed:

1. To describe the distribution of baseline monocyte distribution width value of adult patients admitted at the emergency department with a clinical consideration of sepsis when grouped according to age and sex.

2. To determine if there is significant relationship between monocyte distribution width and subsequent blood culture results.

3. To determine the likelihood of blood culture positivity when stratified according to low, moderate and high monocyte distribution width values.

Significance of the Study

Determining the baselineMDW for emergency department patientsadmitted for sepsis helps establish cut-off values for the local population served.

Having baseline MDW data of emergency department patients suspected of having sepsis may help risk stratification according to MDW values. This simplifies the triaging of patients according to MDW values, which could impact the creation and/or modification of patient care management algorithms and facilitate the inclusion of MDW as a reportable hematologic parameter.

Knowing how the values of the monocyte distribution width of the patient population correlate with the concurrent blood culture status may support the utility of MDW as a reportable hematologic parameter, hopefully leading to broader adoption of MDW as an important hematologic parameter and as a new sepsis biomarker. Policymakers and stakeholders in infectious diseases and emergency care settings may find the study useful in drafting institutional sepsis clinical pathways.

Conceptual Framework

Scope and Limitation

This study described the monocyte distribution width of adult patients (age 18-89) who presented to the emergency department of the Philippine General Hospital with CBC- differential and blood culture included in the initial evaluation. This study was limited to examining the hematologic parameters and blood culture results of the initial laboratory work-up in the emergency department. The Beckman Coulter DxH 900 analyzer was used to analyze samples for MDW measurement. The samples did not include follow-up specimens for CBC with differential and blood culture extracted after admission to the ward/room.

METHODS

Study Design

This was a triple-blind cross sectional study.

Study Setting

This study was done in coordination with the Division of Hematology and the Division of Microbiology in the Department of Laboratories, Philippine General Hospital.

Study Period

Conceptualization, review of related literature, protocol drafting, technical review and preliminary preparation for ethics review were done from March to August 2023. Determination of eligible samples and data gathering was conducted in September, 2023. Statistical analysis of results and final manuscript completion was done from September to October 2023.

Study Population

Inclusion Criteria

Eligible patients include adults (age 18-89) in the emergency department of the Philippine General Hospital with an admitting impression of sepsis and initial laboratory work up. These include simultaneous CBC with differential and blood culture for a period of one year from January 1, 2022, to December 31, 2022. The samples submitted must have successfully fulfilled the acceptance criteria of the Department of Laboratories and whose official results have been finalized and released as part of the patient’s medical record.

Exclusion Criteria

Patients with underlying conditions potentially associated with the deregulation of the immune system, including but not limited to Acquired Immunodeficiency Syndrome (AIDS), organ or bone marrow transplantation, and hematologic diseases, and those with ongoing or recent antimicrobial therapeutic regimens have been excluded from the sample.

Sampling Procedure

This study utilized simple random sampling using a fishbowl method from a list of eligible patients. These patients must be admitted from January 1, 2022, to December 31, 2022 in the emergency department with a clinical consideration of sepsis with samples sent for complete blood count and blood culture until a sample size of 335 was reached. Laboratory data was collected and reviewed for an initial sepsis work-up upon first contact in the emergency department, which include a complete blood count with differential and a blood culture. The duly accomplished official laboratory request form, machine-extracted logs, division worksheets, and logbooks were utilized in gathering data. Matching of the samples for demographic data such as age and sex was not performed.

Sample Size and Power Calculations

To arrive at the desired number of samples to be included in the study, the following formula for cross-sectional study was used to calculate the sample size:

Where:

Z= Z value

p= percentage

c= confidence interval

Following statistical consultation regarding sample size, the researchers determined a total of 335 samples would need to be reviewed to derive a 95% confidence interval with a power of 80% and a margin of error of 5%.

Operational Definition of Terms

Monocyte Distribution Width

In this study, monocyte distribution width (MDW) refers to an in-vitro hematological parameter used as a biomarker for sepsis where values more than 20 are indicative of sepsis.8 This value is part of the cell population data research parameters and is obtained from blood samples of adult patients admitted at the emergency department of the Philippine General Hospital, collected in EDTA-K3 tube and analyzed using the Beckman Coulter UniCel DxH900 analyzer (Beckman Coulter, Inc.) within two hours of collection, as per manufacturer recommendation.

Blood Culture

Blood culture is a laboratory test used to detect the presence of and identify bacteria in the peripheral blood.

In this study, blood culture was done by incubating blood culture bottles containing blood samples of adequate volume (10 mL for adults and 4 mL for pediatric patients) in an automated blood culture system (BACTEC Continuous Monitoring System, BD Diagnostics) to check for growth and subsequent identification of organism using the Vitek MS.

Sepsis

Sepsis is defined by the Third International Consensus Definitions for Sepsis and Septic

Shock (2016) as a life-threatening organ dysfunction caused by a dysregulated host response to infection. The Center for Disease Control (CDC) defines sepsis as the body’s extreme response to an infection.20 It is a life-threatening medical emergency which happens when an infection triggers multisystemic chain reactions throughout the body.22 If left untreated, sepsis can have fatal outcomes of tissue damage, organ failure, and death.

In this study, definitive diagnosis of sepsis was achieved by demonstrating microbial growth by means of a blood culture.

Differential Leukocyte Count

A differential leukocyte count provides a relative percentage of each type of white blood cell and helps reveal abnormal white blood cell populations such as blasts, immature granulocytes, and circulating lymphoma cells in the peripheral blood.20

In this study, all blood samples will be analyzed using UniCel DxH900 (Beckman Coulter, Inc.) with version 2 software within 6 hours of collection. This instrument measures specific cell volume parameters and the distribution of cell volumes within a group of cells. The official results, verified and released into the patient’s medical record, were utilized for this study.

Randomization Procedure

Randomization procedures consisted of simple random sampling using the fishbowl method. Upon determining the study population that fulfills the inclusion criteria, a list of eligible samples was created, from which fishbowl method was done until the sample size of 335 was reached.

Blinding

A triple blind procedure was utilized to reduce bias from researchers during the data gathering procedure and statistician involved in data processing and analysis. Anonymity of the samples was ensured by numerical coding in the data collection forms.

Data Collection Methods and Tools

Maneuvers

Case finding, Sample Identification, and Data Collection

Blood specimens for culture and hematology counts were collected following standard laboratory protocols and acceptance criteria. Blood samples were collected in appropriate blood culture bottles and adequate volume (10 mL for adults and 4 mL for pediatric patients). Blood culture bottles containing blood samples were incubated in BACTEC Automated Blood Culture System and plated for identification and susceptibility testing if flagged as positive.

Specimens for hematology counts were assessed for volume adequacy and the presence of clots. These were subsequently loaded into the Beckman Coulter DxH900 analyzer for cell counting. Results were verified and documented in worksheets, backed up electronically, and/or retained in respective logbooks before final release into the medical record.

Loadlist of both the division of microbiology and hematology were examined to identify adult patients (18-89 years old) in the emergency department with complete blood count with differential and blood culture requested for an admitting impression of sepsis. These patients had blood specimens simultaneously submitted to both divisions on the same date and whose official results have already been released.

These patients were assigned an alphanumeric code for de-identification and coding purposes. Their results were extracted in a data collection form devoid of patient identifiers to ensure confidentiality.

MDW data were extracted from the research parameters of the UniCel DxH900 automated hematology analyzer, whereas blood culture results were extracted from the microbiology worksheets.

Data Processing and Analysis

Data were processed and analyzed using the SPSS Statistical Software v.17.0 (Released 2019. IBM SPSS Statistics for Windows, Version 26.0. Armonk, NY: IBM Corp.). Frequency and percentage were used to describe the distribution of MDW when grouped according to age and sex. Correlation was used to determine if there is a significant relationship between MDW and subsequent blood culture results. Chi-square and likelihood ratio determined the likelihood of blood culture positivity when stratified according to low, normal, and high MDW values.

Data Protection Plan

Sample anonymity was secured by designating unique alphanumeric codes during case identification and data gathering before processing. Another layer of protection was added using a triple-blind procedure, which helped minimize bias in the data gathering and processing steps. Access to data was made exclusive to the investigators, while the statistician was provided access to data that had undergone coding and blinding procedures. Data will be stored for a maximum of 10 years after completion of the study. Data collection forms and other physical records will be disposed of through incineration. Electronic data will subsequently be permanently deleted. Collected data was only used for research purposes. Furthermore, the study's investigators performed data gathering, processing, and analysis.

Storage of Archival Data

The Division of Microbiology will retain full custody of the physical logbooks and worksheets for blood culture tests. Similarly, the Division of Hematology will retain jurisdiction over the backup files for long-term storage in an external hard drive as per department policy for records retention. Data gathered from these sources was transferred to their respective data collection forms, which underwent appropriate coding and blinding procedures before an analysis.

Ethical Considerations

The study posed no known risks to individual patients. Patient identifiers, sensitive demographic data, and other confidential clinical information in the medical record were not gathered. All gathered data were held in utmost confidentiality, and access was only limited to the investigators and statistician directly involved in data analysis. Retention of blood samples followed the individual division protocols for biohazardous waste disposal.

The study was submitted to the UP Manila Research Ethics Board for review and approval before implementation.

Informed Consent and Confidentiality

In accordance with the National Ethical Guidelines for Health and Health-Related Research in 2017, a waiver of consent was obtained from the research ethics committee for this study which posed no more than minimal risk to patients. The rights and welfare of the participants were not adversely affected by the waiver. Patient identifiers were de-identified, coded, and anonymized. No personal data such as name, address, and contact information were collected from the medical record, request forms, and officially released reports.

Risks of the Study

The study posed no more than minimal risk to patients. No additional sample collection or invasive procedures were performed during data gathering. Data privacy measures were strictly implemented to remove identifiers. Data collection was limited to the investigators who exercised the utmost care in handling, processing, and storing data. In the event of a data privacy breach, the matter will be forwarded to the PGH Data Privacy Officer for proper handling and investigation.

Benefits of the Study

This study will primarily benefit patients who present in the emergency department with vague signs and symptoms of early sepsis. No monetary compensation, special privileges, additional testing, or tokens in kind were provided to the patients whose samples were selected for inclusion.

Declaration of Conflict of Interest

This study was investigator-funded and was not sponsored by any third party. There was no subsidy or funding from Beckman Coulter, Inc., the propriety owner of UniCel DxH900 whereby the outcome of the study could influence compensation for the investigators. The investigators did not have significant financial interests, such as receiving services and/or equity payments. Finally, the investigators had no significant personal interest, family interest, sponsorships, or interest in the study results.

Dissemination/Data Sharing Plan

Collected data were used only for research purposes and were not utilized for marketing. Only the principal investigator and co-investigators were granted full access to the anonymized data. Results of the study will be disseminated through oral and/or poster presentation through the following channels: 1) Annual Research Forum of the Department of Laboratories; 2) Possible publication either in local or international pathology journals; 3) Presentation in oral and/or poster formats in professional gatherings including but not limited to conventions hosted by the Philippine Society of Pathologists and conventions hosted by other medical societies.

RESULTS

Age

Table 1 shows the MDW values distributed according to age. The majority comprised

samples from adult patients aged 26 to 35 (n=80, 23.8%). The remaining age groups have the following distributions: ages 36-45 (n=73, 21.79%), ages 66-75 (n=49, 14.6%), 46-55 (n=42,

12.5%), ages 76-85 (n=40, 11.9%), ages 56-65 (n=36, 10.74%), ages 86-89 (n=9, 2.68%), whereas

the age group of 18 to 25 years old have the least number of samples (n=6, 1.79%).

Table 1. Monocyte Distribution Width Distribution According to Age.

Sex

Table 2 shows the MDW values distributed according to sex. Majority of the samples are

from males (n=178, 53.13%) while the rest are females (n=157, 46.86%).

Table 2. Monocyte Distribution Width Distribution According to Sex.

Test of Significance

Table 3 shows the correlation between MDW and blood culture results. Pearson correlation showed a very strong correlation, r(1,335)=0.880, p<0.001, between the two variables, MDW and blood culture result.

Table 3. Correlation Between MDW and Blood Culture Result.

** Correlation is significant at the 0.001 level (2-tailed).

Likelihood of Blood Culture Positivity

Table 4 shows the likelihood of blood culture results when stratified according to MDW values. Samples with moderate MDW values ranging from 13.98 to 21.28 had a 100% likelihood of negative blood culture result (n=99, 100%); no samples from this group had positive blood culture results. Samples with high MDW values above 21.28 have a 54.33% likelihood of a positive blood culture result (n=182, 54.33%) and a 45.67% likelihood of a negative blood culture result (n=153, 45.67%). No samples with a low MDW of <13.98 among the cases included in the sample size.

Table 4. Likelihood of Blood Culture Result When Stratified According to MDW Values.

Chi-Square Tests

A chi-square test was done to determine the likelihood of blood culture positivity when stratified according to low, normal, and monocyte distribution values. Results show (see Table 5) that MDW will likely determine whether the blood culture is positive or negative X2 (1, 334)

= 167.17, p<0.001.

Table 5. Chi-Square Tests for MDW and Blood Culture Result.

a.     0 cells (0.0%) have expected count less than 5. The minimum expected count is 45.21.

b.     Computed only for a 2x2 table.

DISCUSSION

Although clinically difficult to define, sepsis has been reported as a major cause of increased morbidity, length of stay, and mortality among hospitalized patients.23 Despite this, sepsis diagnosis remains a challenge both to the clinical team and the laboratory. The risk for developing sepsis is often associated with preexisting chronic medical conditions such as diabetes, chronic inflammatory or immune disorder, obesity, cancer, and heart diseases.24 The survival of patients is heavily impacted by early diagnosis, as well as early commencement of appropriate medical intervention.25 Early recognition of sepsis is often hampered by ambiguous clinical features and by low sensitivity and specificity of current laboratory biomarkers. In an effort to decrease mortality, strengthening the management of sepsis patients can be paramount to improve quality of care and outcomes in the emergency care setting. Currently, there is no single laboratory test or a standalone biomarker that has sufficient sensitivity and specificity which allows for diagnosis of sepsis in a timely and accurate manner. To date, most clinicians utilize both CRP and PCT to predict sepsis in the emergency department. Although microbiologic studies are considered the “gold standard”, up to 30-50% of sepsis presentations are culture negative.32 With these in mind, exploring new avenues for routine use of MDW for early sepsis identification to achieve efficient and timely sepsis diagnosis is no small challenge to laboratory medicine.

The present investigation examined results obtained during initial emergency department consult. Patients in this setting may be affected by systemic inflammation and bacterial colonization at a single or even multiple sites independently from sepsis.29 

Under such circumstances, the timeliness of intervention with empiric antimicrobials is critical. However, definite diagnosis and streamlined therapy relies upon the availability of results of microbiologic studies, primarily blood culture, which may take hours to days to be finalized and reported under standard protocols. These delays may be life threatening in unstable patients.30 Readily available as part of CBC and differential in select analyzers, this study focused on MDW as an early sepsis biomarker being a relatively simple proxy of innate monocyte response to bacterial or fungal bloodstream infection. Recent studies showed that changes in the volume of monocytes may be due to monocyte activation upon bloodstream infection as part of the innate immune response.26 The study by Crouser et al. showed that MDW can discriminate sepsis from SIRS and that the magnitude of MDW elevations correlate with infection severity and organ dysfunction, with MDW values rising in parallel with the severity of ensuing sepsis.26 In addition, the results of study supports that of Polili et al. which concluded that MDW in the initial evaluation of patients admitted to the Emergency Department may increase the odds of early sepsis detection 6-fold using Sepsis-2 and 4-fold using Sepsis-3 assessments.27 In terms of comparability, an additional prospective study demonstrated the ability of MDW to predict sepsis in a cohort of 260 patients showing that MDW and procalcitonin have comparable performance in predicting sepsis.27 The study by Piva et al.32 showed that in septic patients, MDW had high values not only in gram positive and negative bacteria, but also when causative agents are viral or fungal infections. Our study confirmed the previously reported data by Piva et al. regarding their best cut-point for MDW associated with sepsis of 24.63 which is relatively higher compared to values reported by other studies. The MDW cut-off values should be discussed, and evaluation should be considered taking into account the clinical setting in which studies have been performed. In the emergency setting, severity of patient characteristics and admitting impression can justify the need for a specific cut-off.

Several recent studies indicated that MDW can be used to assist sepsis diagnosis in the Emergency Department in association with other clinical criteria for sepsis. Agnello et al.29 found that patients with sepsis at entry had higher values of MDW, compared with patients without sepsis. In addition, patients who developed sepsis during their hospital stay showed higher values of MDW at the onset. In this setting, the early administration of antibiotics and other evidence-based measures are mandatory to decrease infection-related mortality.30 Therefore, the diagnostic challenge of early recognition remains the most important in terms of management. The study by Piva et al.33 evaluated the diagnostic accuracy of MDW among ICU patients. They found that MDW when measured at the onset of symptoms, has an AUC comparable with that of procalcitonin. The study by Polili et al.28 found that using MDW alone with a cut-off of 20.0 achieved the highest levels of sensitivity of 95.9% and negative predictive value (NPV) of 86.4%. These parameters indicated that MDW can be used to rule out sepsis when the patient does not exceed a level of 20.0. In addition, their study found that all patients with MDW ≤ 20 had consistently negative blood cultures. The study by Li et al.36 found that the accuracy MDW alone or MDW and CBC plus SIRS were both better than procalcitonin. They reported their best cut-off value at 19.26 which is similar to other studies and concluded that MDW had a better performance for early sepsis screening and patient outcome prediction than procalcitonin.36

As part of the first-line responders of the adaptive and innate immune response together with macrophages and dendritic cells, monocytes are activated by microorganisms by means of pattern recognition receptors. MDW measures and reflects the size and shape change of monocyte during activation and differentiation process which makes it advantageous compared to current protein-based biomarkers.26 Protein production from transcription to translation usually takes hours to complete whereas the differentiation of monocytes in the bloodstream begins earlier in the sepsis cascade which may be one reason for the enhanced sensitivity and unique position of MDW in the sepsis diagnosis.

In the context of the Philippines’ healthcare system, MDW is relatively inexpensive than procalcitonin and C-reactive protein. These biomarker assays may not be widely available and using these for sepsis screening may be quite expensive. In this regard, MDW, which is part of the CBC with differential count report in modern hematology analyzers, may play the role of an economical but accurate screening tool in the emergency department setting. Other biomarker assays may be used as second-line in ambiguous or doubtful cases.

Using MDW can afford great convenience as it can be measured routinely through a hematological analyzer with cell population data functionality which should be readily available to provide results for blood cell counts that can be delivered within minutes during emergency department consult or ICU stay. These findings suggest that MDW can be significantly helpful in identifying sepsis among critically ill patients in clinical practice, with further benefit for repeated measurement according to clinical judgment. Notwithstanding, providing this new parameter to clinicians, laboratorians should interpret MDW with care and should take into account the clinical context, which is required for the correct diagnosis, and should understand its limitations in some patients, such as those with hematologic diseases. Proper materials for quality control, both internal and external, are a must so that compliance with established performance specifications may be assessed, particularly for MDW values that are near cut-off. Since more advanced hematology analyzers suited for a center with high volume load typically feature cell population data, integration of MDW information with other indices may yield more useful laboratory data which may aid the diagnosis. Recent studies feature the prognostic value of red blood cell distribution width (RDW) in particular, which may be a useful predictor of mortality.35

Overall, given our practice setting, exploring the role of MDW as a low-cost alternative to other sepsis biomarkers currently available in the Philippine setting (procalcitonin and C- reactive protein) may help screen for early sepsis and expedite treatment planning even as the patient presents to the emergency department as the initial point of contact. MDW has several compelling reasons to be included sepsis clinical pathways: first, it is measured as part of a routine CBC with differential and should be readily available as part of the initial laboratory workup requested; second, there are no special patient preparations needed and no added tube is required for specimen collection thereby decreasing potential iatrogenic blood loss from performing additional blood draws for different assays; finally, no additional equipment is needed to be procured to measure this parameter as it comes packaged as part of cell population data with most modern high-throughput hematology analyzers.

CONCLUSION

Sepsis represents a life-threatening condition with ambiguous clinical signs and symptoms for which early detection for timely and appropriate medical care is critical for survival especially in patients initially presenting for consult in the emergency setting. In addition to current sepsis biomarkers for early diagnosis, MDW is an appealing, reliable, easily available, fast, low-cost, and time saving routine hematologic parameter to expedite clinical decision making and treatment planning. As CBC is one of the most frequently ordered laboratory tests in the emergency department, addition of MDW constitutes a promising tool in evaluating for sepsis. This study showed a significant relationship with strong correlation between MDW and blood culture result. High MDW values above 21.28 have a high likelihood of blood culture positivity whereas samples with MDW values from below 13.98 and between

13.98 to 21.28 have high likelihood of a negative blood culture result.

RECOMMENDATIONS

Focusing the study on other practice settings, such as the intensive care units (ICU) and outpatient settings, may be considered to determine differences among patients presenting in different care settings. Studying MDW values during and after sepsis may help explore its role as a prognostic tool for follow-up.

Other demographic and clinical factors may be considered for analysis: comorbidities, qSOFA score, previous surgery, other sepsis biomarkers, sepsis strata, and subsequent microbiologic isolates, particularly various multi-drug resistant organisms.

Multi-centric investigations to further understand the role of MDW in sepsis diagnostic algorithms are warranted. Further prospective studies are warranted to confirm the results of this investigation, which further support the role of MDW as a valid diagnostic tool for identifying sepsis, with more precise estimates preferably from a larger population, possibly into a broader array of inflammation parameters and biomarkers. In addition, retrospective studies may be done on longer time horizons and larger samples to better characterize test sensitivity, specificity, positive and negative predictive values as stand-alone and/or in relation to other sepsis biomarkers.

Specific exclusion criteria in our study should be considered, particularly diseases involving immune system deregulation. These may be associated with volumetric variations of monocytes during bloodstream infections. The lack of these characteristics may limit the overall generalizability of the results.

Further investigation on the impact of antimicrobial therapy before the initial consult on MDW values may be looked into. Understanding the effect of previous antimicrobial therapy on MDW may help adjust cut-offs and reference ranges.

Recently published systematic review by Hu et al.35 highlight the prognostic value of red cell distribution width (RDW) that predicts mortality. In addition, MDW readings will soon be integrated into routine blood counts with current blood cell analyzers.

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APPENDIX

A. BUDGET