Contents
pdf Download PDF
pdf Download XML
33 Views
15 Downloads
Share this article
Original Article | Volume 12 Issue 8 (AUGUST, 2026) | Pages 184 - 191
Correlation of Defined Daily Dose, Days of Therapy and Antimicrobial Resistance among patients with positive blood culture in the Intensive Care Unit (ICU)
 ,
 ,
 ,
 ,
1
Post graduate student, Department of Microbiology, SRM Medical College Hospital and Research Centre, Faculty of Medicine and Health Science, SRMIST, Kattankulathur, Tamil Nadu, India
2
Professor, Department of Microbiology, SRM Medical College Hospital and Research Centre, Faculty of Medicine and Health Science, SRMIST, Kattankulathur, Tamil Nadu, India
3
Professor and Head, Department of Microbiology, SRM Medical College Hospital and Research Centre, Faculty of Medicine and Health Science, SRMIST, Kattankulathur, Tamil Nadu, India
4
Head I/C, Department of CCTR, SRM Medical College Hospital and Research Centre, Faculty of Medicine and Health Science, SRMIST, Kattankulathur, Tamil Nadu, India
5
Professor and Head, Department of Critical Care Medicine, SRM Medical College Hospital and Research Centre, Faculty of Medicine and Health Science, SRMIST, Kattankulathur, Tamil Nadu, India
Under a Creative Commons license
Open Access
Received
March 10, 2026
Revised
June 18, 2026
Accepted
July 27, 2026
Published
July 7, 2026
Abstract
Background: Globally, antimicrobial resistance (AMR) presents a significant threat to human health driven largely by irrational antimicrobial usage, which often leads to prolonged hospital stay, increased morbidity and mortality. Antimicrobial stewardship (AMS) emphasizes appropriate antibiotic use through strict implementation of antimicrobial policy guidelines. Hence, this study aims to correlate Defined Daily Dose (DDD), Days of Therapy (DOT) and Antimicrobial Resistance in Intensive Care Unit (ICU) patients with bacteremia.Materials and Methods:A prospective cross-sectional study was conducted over three months in the SRM Medical College Hospital and Research Centre, including patients over 18 years old receiving antimicrobials with positive blood cultures. Antimicrobial usage was assessed using WHO-recommended metrics such as DDD per 100 patient bed days and DOT per 1000 patient bed days. Resistance data were obtained from microbiology surveillance records.Results:Among 50 culture-positive ICU patients, 36% were aged 51-70 years and 34% were 31-50 years, with 56% of males. Among the pathogens isolated, Klebsiella pneumoniae (28%), Escherichia coli (22%), and Acinetobacter baumannii (22%) were the predominant organisms, followed by Pseudomonas, Enterococcus and Staphylococcus species. Stewardship interventions resulted in de-escalation in 54% of cases, escalation in 20%, and no change in 26%. Mean empirical DDD and DOT were 4.95 and 3.7 days, respectively, while the mean definitive DDD and DOT were 4.05 and 4.3 days. Wide variation reflects individuals' therapy adjustments. Higher mortality was observed in patients infected with multidrug-resistant (MDR) and extensively drug-resistant (XDR) organisms than in drug-sensitive cases. Conclusion:In conclusion, structured stewardship prescribing practices decrease unnecessary antimicrobial use and result in better clinical outcomes, highlighting the value of continuous AMS monitoring and feedback in combating AMR. Clinical significance:This study is clinically significant for the optimization of antibiotic usage and improve patients outcomes by formulation targerted antimicrobial stewardship strategies
Keywords
INTRODUCTION
Bacteremia plays a vital role in illness and death among critically ill patients in Intensive Care Units (ICU). Factors like invasive procedures, long hospital stays, weak immune systems, and mechanical ventilation elevate the risk of bloodstream infections and the use of broad-spectrum antibiotics in ICUs. This practice contributes to the growth of multidrug-resistant (MDR) pathogens. Antimicrobial resistance (AMR) has become a global health issue. The World Health Organization (WHO) has emphasized the great demand for systematic monitoring of antimicrobial use [1]. Measures such as Defined Daily Dose (DDD) and Days of Therapy (DOT) are commonly used to evaluate antibiotic consumption. DDD shows the strength of antibiotic exposure, while DOT indicates how long treatment lasts, regardless of dosage [2,3]. It is necessary to understand the correlation between consumption metrics and patterns of antimicrobial resistance. This knowledge will help create a targeted antimicrobial stewardship program (AMSP). AMSP initiatives aim to improve antibiotic usage, reduce toxicity, lower costs and address AMR. De-escalation based on culture and sensitivity results stands out as one of the most effective stewardship strategies [4,5]. This study looks at patterns of antibiotic use through DDD and DOT metrics and connects them with AMR trends in ICU patients diagnosed with bacteremia. Aims and objectives: To evaluate the number of patients with positive blood cultures in ICU and measure antibiotic consumption using DDD and DOT metrics. To examine antimicrobial use, microbiological findings and stewardship interventions, including culture-guided de-escalation practices among critically ill adults with bloodstream infections
MATERIALS AND METHODS
A prospective cross-sectional study was conducted over three months period (January 2025 to March 2025) in the ICU of SRM Medical College Hospital and Research Centre, Kattankulathur, Chengalpattu District, Tamil Nadu. The study was approved by institutional ethics committee, ethical number is SRMIEC-ST1124-1895. Before enrollment of patients, written informed consent was obtained from all eligible patients or their legal guardians. Inclusion criteria: Adult patients aged 18 and above who were admitted to the ICU with microbiologically confirmed positive blood cultures and patients receiving antimicrobial therapy for at least one day were included in the study. Exclusion criteria: The patients below 18 years of age or receiving antimicrobial treatment outside ICU or disinterested patients were excluded from the study. Detailed demographic information, clinical characteristics, blood culture results, antimicrobial regimens, and patient outcomes were systematically collected using a structured form. This method ensured consistency and completeness of the clinical and microbiological data recorded for each participant. Antimicrobial use was assessed using standardized WHO method [6]. In detail, the DDD was calculated by dividing the total administered antimicrobial dose by the WHO assigned standard DDD for each agent. DOT was recorded as the total number of days a patient received a specific antimicrobial, regardless of dosage changes. The antimicrobial resistance profiles of the isolates were classified into multidrug-resistant (MDR) and extensively drug-resistant (XDR) categories based on widely accepted criteria [7]. Stewardship interventions were noted and categorized into three groups: de-escalation, escalation, and no change, depending on how antimicrobial regimens were adjusted after culture results and clinical assessment [8].
RESULTS
The study included 50 bloodstream infection positive patients, of which 36% (18 patients) were between 51 and 70 years of age, with a slightly higher proportion of males. The predominant pathogens were gram-negative organisms such as Klebsiella pneumoniae (28%), Acinetobacter baumannii (22%) and Escherichia coli (22%). Gram-positive isolates such as Staphylococcus aureus and Enterococcus faecalis formed a smaller proportion of the cases (Table 1). Category Prevalance (%) Age Group (years) 18-30 14 31-50 34 51-70 36 71-90 16 Gender Female 44 Male 56 Organism Klebsiella pneumoniae 28 Acinetobacter baumannii 22 Escherichia coli 22 Staphylococcus aureus 12 Pseudomonas aeruginosa 12 Enterococcus faecalis 4 Table 1. Age-wise and gender-wise distribution of patients and organisms isolated from blood cultures.14 patients in 18-30 years,34 patients in 31-50 years,36 patients in 51-70 and 16 patients in 71-90 years.Male[56] patients are more than female[44] patients.Klebsiella pneumoniae is the predominant organism which was isolated in 28 patients followed by Acinetobacter baumannii and Escherichia coli in 22 patients each,Pseudomonas aeruginosa in 12 patients and least being Enterococcus faecalis isolated in blood from 4 patients. Antibiotics were dde-escalated in 27 case s,escalated in 10 cases and did not change in 13 cases(Figure 1).Antimicrobial were When antimicrobial usage patterns were evaluated, empirical therapy showed a mean DDD of 4.95 and an average DOT of 3.9 days, reflecting the use of broader initial coverage (Fig 2 and 3). Once culture and susceptibility data were available, definitive therapy demonstrated a reduction in DDD to 4.05 and a slight increase in DOT to 4.3 days, indicating dose adjustments and treatment refinement (Fig 2 and 3). Stewardship interventions played a significant role, with de-escalation occurring in over half of the patients, while smaller proportions required escalation or had no change in therapy. Importantly, patients infected with MDR or XDR organisms experienced notably higher mortality (1%), underscoring the clinical impact of resistant pathogens in the ICU setting.
DISCUSSION
This study evaluates the use of antimicrobials and resistance patterns among culture-positive patients admitted to a tertiary care intensive care unit. Critically ill patients are especially vulnerable due to the initiation of antimicrobial therapy without prior confirmation of infection. However, this approach significantly increases selective pressure, leading to the growth and spread of resistant organisms in ICUs. The age distribution in this study showed that most patients were middle-aged or elderly. This trend indicates a strong correlation between long-term health issues, weakened immune systems, and frequent healthcare visits among older adults. These factors make them more susceptible to bloodstream infections [9]. This result corroborates with the reports of Lat et al. (2021) that higher prevalence of male patients may be due to differences in underlying health conditions and how they seek care[10]. In the present study, the major causes of bacteremia are gram-negative organisms such as Klebsiella pneumoniae (28%), Acinetobacter baumannii (22%), and Escherichia coli (22%). This microbiological profile finding is similar to patterns seen in ICUs globally, where gram-negative bacilli lead bloodstream infections because of their high survival rate and resistance in hospital settings [11,12]. The ongoing presence of Acinetobacter spp. and Klebsiella spp. is concerning, as these pathogens often cause outbreaks and are resistant to many antimicrobial classes [13]. The assessment of antimicrobial use showed higher DDD values during the empirical phase than during definitive therapy. This indicates great clinical demand to initiate broad-spectrum antimicrobial regimens in critically ill patients suspected of having sepsis, where delays in effective treatment can lead to higher mortality. Once culture and susceptibility results were available, the decrease in definitive DDD suggests better dose optimization and narrowing of the antimicrobial spectrum. Stewardship-driven ICU studies have observed similar reductions following microbiological confirmation [14]. Conversely, DOT values were slightly higher during definitive treatment. DOT measures how long patients receive antimicrobials regardless of dose, and its increase during the definitive phase likely means that clinicians completed an appropriate treatment course after identifying the cause of the infection [15]. This pattern shows that doctors maintained suitable treatment durations while avoiding unnecessary dose increases, highlighting how DDD and DOT work together as indicators for stewardship. The correlation analysis revealed a strong interlink between empirical and definitive DDD and a moderate to strong link between empirical and definitive DOT. These findings suggest that patients needing more antimicrobial exposure at the start often continue to require prolonged therapy. This likely reflects greater illness severity, delayed source control, or infections with resistant organisms. ICU surveillance studies of Huttner et al. (2019) have observed similar connections between antimicrobial use and clinical severity[16]. Importantly, these correlations imply inappropriate continuation of therapy and highlight the need for personalized treatment decisions based on patient responses and lab results. This study reveals that Antimicrobial Resistance (AMR) significantly impacts patient clinical outcomes, particularly in patients with MDR and XDR, leading to worse outcomes and increased mortality. This finding aligns with global evidence showing that resistant infections lead to delayed effective treatment, longer ICU stays, worsening organ issues, and higher healthcare costs [17,18]. The existence of resistant Klebsiella pneumoniae and Acinetobacter baumannii in ICU highlights the critical necessity for continuous resistance surveillance and stringent infection control protocols [19,20]. Overall, this study emphasizes the importance of systematic monitoring of antimicrobial use in ICUs. Using both DDD and DOT provides a detailed understanding of the intensity and duration of therapy. When combined with microbiological data and stewardship oversight, these metrics can help guide safe prescribing, reduce unnecessary antimicrobial use, and limit the spread of resistance. Ongoing evaluation of antimicrobial use trends, along with timely microbiological feedback, is crucial for improving outcomes in critically ill patients with bloodstream infections..
CONCLUSION
In conclusion, this study highlights the importance of antimicrobial consumption indicators like DDD and DOT, which provide useful information about prescribing habits in ICU patients with bacteremia. The difference between empirical and definitive therapy clarifies the essentiality of culture-based optimization. High rates of MDR and XDR necessitate strong antimicrobial stewardship and regular surveillance. Improving AMS programs, encouraging timely de-escalation, and tracking antimicrobial usage are crucial for lowering AMR burden and enhancing patient outcomes. Clinical significance: The relationship between antimicrobial consumption and antimicrobial resistance in studied using the primary outcome indicators Defined Daily Dose and Days of Therapy. Our study provides and evidence that this can help in the selection of appropriate antibiotic therapy in critically ill patients reducing inappropriate antimicrobial use also limiting the spread of resistant pathogen.
REFERENCES
1. WHO Methodology for Point Prevalence Survey on Antibiotic Use in Hospitals. (n.d.). In www.who.int. Retrieved August 1, 2025, from https://www.who.int/publications/i/item/WHO-EMP-IAU-2018.01 2. Trivedi, K., Seo, S., Samore, M., Ohl, C., Newland, J., Neuhauser, M., Moran, G., May, L., Malani, P., Lipsett, P., Jenkins, T., Hamilton, C., Fishman, N., Falck-Ytter, Y., Dellit, T., Srinivasan, A., Septimus, E., Schuetz, A., MacDougall, C., … Barlam, T. (2016). Implementing an Antibiotic Stewardship Program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clinical Infectious Diseases, 62(10), e51-e77. https://doi.org/10.1093/cid/ciw118 3. Polk, R. E., Fox, C., Mahoney, A., Letcavage, J., & MacDougall, C. (2007). Measurement of adult antibacterial drug use in 130 US hospitals: comparison of defined daily dose and days of therapy. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 44(5), 664–670. https://doi.org/10.1086/511640 4. Baur, D., Gladstone, B. P., Burkert, F., Carrara, E., Foschi, F., Döbele, S., & Tacconelli, E. (2017). Effect of antibiotic stewardship on the incidence of infection and colonisation with antibiotic-resistant bacteria and Clostridium difficile infection: a systematic review and meta-analysis. The Lancet. Infectious diseases, 17(9), 990–1001. https://doi.org/10.1016/S1473-3099(17)30325-0 5. Leone, M., Bechis, C., Baumstarck, K. et al. De-escalation versus continuation of empirical antimicrobial treatment in severe sepsis: a multicenter non-blinded randomized noninferiority trial. Intensive Care Med 40, 1399–1408 (2014). https://doi.org/10.1007/s00134-014-3411-8 6. Indicator Metadata Registry Details. (2015). In Who.int. https://www.who.int/data/gho/indicator-metadata-registry/imr-details/5766 7. Magiorakos, A. P., Srinivasan, A., Carey, R. B., Carmeli, Y., Falagas, M. E., Giske, C. G., Harbarth, S., Hindler, J. F., Kahlmeter, G., Olsson-Liljequist, B., Paterson, D. L., Rice, L. B., Stelling, J., Struelens, M. J., Vatopoulos, A., Weber, J. T., & Monnet, D. L. (2012). Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 18(3), 268–281. https://doi.org/10.1111/j.1469-0691.2011.03570.x 8. Ghanshani, Rajesh & Gupta, Rajeev & Gupta, BhagwanSwarup & Kalra, Sushil & Khedar, RaghubirSingh & Sood, Smita. (2015). Epidemiological study of prevalence, determinants, and outcomes of infections in medical ICU at a tertiary care hospital in India. Lung India. 32. 441. 10.4103/0970-2113.164155. 9. Prince, M. J., Wu, F., Guo, Y., Gutierrez Robledo, L. M., O'Donnell, M., Sullivan, R., & Yusuf, S. (2015). The burden of disease in older people and implications for health policy and practice. The Lancet, 385(9967), 549–562. https://doi.org/10.1016/S0140-6736(14)61347-7 10. Lat, Tasnim & McGraw, Meghan & White, Heath. (2021). Gender Differences in Critical Illness and Critical Care Research. Clinics in chest medicine. 42. 543-555. 10.1016/j.ccm.2021.04.012. 11. Peleg, A. Y., & Hooper, D. C. (2010). Hospital-acquired infections due to gram-negative bacteria. New England Journal of Medicine, 362(19), 1804-1813. https://doi.org/10.1056/NEJMra0904124\ 12. Tacconelli, E., Carrara, E., Savoldi, A., Harbarth, S., Mendelson, M., Monnet, D. L., Pulcini, C., Kahlmeter, G., Kluytmans, J., Carmeli, Y., Ouellette, M., Outterson, K., Patel, J., Cavaleri, M., Cox, E. M., Houchens, C. R., Grayson, M. L., Hansen, P., Singh, N., Theuretzbacher, U., … WHO Pathogens Priority List Working Group (2018). Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. The Lancet. Infectious diseases, 18(3), 318–327. https://doi.org/10.1016/S1473-3099(17)30753-3 13. Karaiskos, I., & Giamarellou, H. (2014). Multidrug-resistant and extensively drug-resistant Gram-negative pathogens: current and emerging therapeutic approaches. Expert Opinion on Pharmacotherapy, 15(10), 1351–1370. https://doi.org/10.1517/14656566.2014.914172 14. Davey, P., Marwick, C. A., Scott, C. L., Charani, E., McNeil, K., Brown, E., Gould, I. M., Ramsay, C. R., & Michie, S. (2017). Interventions to improve antibiotic prescribing practices for hospital inpatients. The Cochrane database of systematic reviews, 2(2), CD003543. https://doi.org/10.1002/14651858.CD003543.pub4 15. Morris, A. M., Brener, S., Dresser, L., Daneman, N., Dellit, T. H., Avdic, E., Cosgrove, S. E., Hamilton, K. W., Schwartz, B. S., & Fishman, N. O. (2014). Use of antimicrobial stewardship metrics in the intensive care unit. Intensive Care Medicine, 40(9), 1259-1267. https://doi.org/10.1007/s00134-014-3369-3 16. Huttner, B. D., Catho, G., Pano-Pardo, J. R., Pulcini, C., & Schouten, J. (2020). COVID-19: don't neglect antimicrobial stewardship principles!. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 26(7), 808–810. https://doi.org/10.1016/j.cmi.2020.04.024 17. Cosgrove, Sara. (2006). The Relationship between Antimicrobial Resistance and Patient Outcomes: Mortality, Length of Hospital Stay, and Health Care Costs. Clinical Infectious Diseases. 42. S82-S89. 10.1086/499406. 18. Cassini, A., Högberg, L. D., Plachouras, D., Quattrocchi, A., Hoxha, A., Simonsen, G. S., Colomb-Cotinat, M., Kretzschmar, M. E., Devleesschauwer, B., Cecchini, M., Ouakrim, D. A., Oliveira, T. C., Struelens, M. J., Suetens, C., Monnet, D. L., & Burden of AMR Collaborative Group (2019). Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis. The Lancet. Infectious diseases, 19(1), 56–66. https://doi.org/10.1016/S1473-3099(18)30605-4 19. Peleg, A. Y., & Hooper, D. C. (2010). Hospital-acquired infections due to gram-negative bacteria. New England Journal of Medicine, 362(19), 1804-1813. https://doi.org/10.1056/NEJMra0904124\ 20. Leone, M., Bechis, C., Baumstarck, K. et al. De-escalation versus continuation of empirical antimicrobial treatment in severe sepsis: a multicenter non-blinded randomized noninferiority trial. Intensive Care Med 40, 1399–1408 (2014). https://doi.org/10.1007/s00134-014-3411-8.
Recommended Articles
Original Article
Combination Anesthetic Hematoma Block Vs. Standard Lidocaine In Distal Radius Fractures: A Prospective, Randomized Clinico-Radiological Study.
...
Published: 08/08/2026
Original Article
EFFICACY OF SALICYLIC ACID–MANDELIC ACID PEEL VERSUS ACETIC ACID PEEL IN THE TREATMENT OF ACNE VULGARIS: A SPLIT-FACE COMPARATIVE STUDY.
...
Published: 24/03/2026
Original Article
ETIOLOGICAL, CLINICO-BIOCHEMICAL PROFILE AND OUTCOME OF PATIENTS WITH METABOLIC ACIDOSIS ADMITTED TO A TERTIARY CARE CENTRE.
...
Published: 23/06/2025
Original Article
AN ASSESSMENT OF SERUM SODIUM LEVELS IN DECOMPENSATED AND COMPENSATED CHRONIC LIVER DISEASE AND ITS CLINICAL OUTCOME
...
Published: 26/10/2024
Chat on WhatsApp
© Copyright Journal of Contemporary Clinical Practice